@article {pmid34101373, year = {2021}, author = {Icht, M and Zukerman, G and Ben-Itzchak, E and Ben-David, BM}, title = {Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta-analysis study.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {14}, number = {9}, pages = {1948-1964}, doi = {10.1002/aur.2551}, pmid = {34101373}, issn = {1939-3806}, mesh = {*Autism Spectrum Disorder/complications ; Emotions ; Humans ; *Intellectual Disability/complications ; Language ; }, abstract = {Daily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) experience difficulties in identification of spoken emotions. We conducted a meta-analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer-reviewed journal articles) comparing individuals with ASD-without-ID (N = 614) and typically-developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF-ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD-without-ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new-look on emotion processing in ASD-without-ID. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions and target improved performance with complex emotions. LAY SUMMARY: Individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta-analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions.}, }
@article {pmid33335279, year = {2021}, author = {Zeng, Y and Gao, W and Chen, X and Shen, K}, title = {Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component.}, journal = {British journal of cancer}, volume = {124}, number = {5}, pages = {975-981}, pmid = {33335279}, issn = {1532-1827}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.<br><br>METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.<br><br>RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.<br><br>CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.}, }
@article {pmid34557972, year = {2021}, author = {Han, J and Harrison, L and Patzelt, L and Wu, M and Junker, D and Herzig, S and Berriel Diaz, M and Karampinos, DC}, title = {Imaging modalities for diagnosis and monitoring of cancer cachexia.}, journal = {EJNMMI research}, volume = {11}, number = {1}, pages = {94}, pmid = {34557972}, issn = {2191-219X}, support = {SFB824/A9//deutsche forschungsgemeinschaft/ ; }, abstract = {Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-D-glucose (18FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.}, }
@article {pmid33704190, year = {2020}, author = {Bondy, S and Tajzler, C and Hotte, SJ and Kapoor, A and Zbuk, K and Lalani, AA}, title = {Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report.}, journal = {Current oncology (Toronto, Ont.)}, volume = {28}, number = {1}, pages = {226-232}, pmid = {33704190}, issn = {1718-7729}, mesh = {*Adrenal Cortex Neoplasms/genetics ; *Adrenocortical Carcinoma/diagnosis/genetics ; Adult ; *Breast Neoplasms ; Female ; Genomics ; Humans ; *Li-Fraumeni Syndrome/genetics ; Mastectomy ; Neoplasm Recurrence, Local ; }, abstract = {Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina® HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.}, }
@article {pmid34555180, year = {2021}, author = {Giroud, M and Jodeleit, H and Prentice, KJ and Bartelt, A}, title = {Adipocyte function and the development of cardiometabolic disease.}, journal = {The Journal of physiology}, volume = {}, number = {}, pages = {}, doi = {10.1113/JP281979}, pmid = {34555180}, issn = {1469-7793}, abstract = {KEY POINTS: Obesity and the associated adipocyte pathology are risk factors for cardiovascular disease Translational research is possible but strongly depends on the mouse model used White adipose tissue inflammation contributes to metabolic and vascular dysfunction Brown adipose tissue thermogenesis supports metabolic and vascular function ABSTRACT: Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications, and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance, and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology, and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which makes temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators, and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease. Abstract figure legend While cardiometabolic health is associated with adipose tissue browning and beneficial adipokine profiles, obesity leads to adipose tissue whitening, inflammation, and atherosclerosis. This article is protected by copyright. All rights reserved.}, }
@article {pmid34528573, year = {2021}, author = {Trontzas, IP and Syrigos, NK and Kotteas, EA}, title = {A case of trastuzumab-induced dermatomyositis.}, journal = {Journal of cancer research and therapeutics}, volume = {17}, number = {4}, pages = {1112-1114}, doi = {10.4103/jcrt.JCRT_209_19}, pmid = {34528573}, issn = {1998-4138}, abstract = {Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention.}, }
@article {pmid33915261, year = {2021}, author = {López-Salazar, V and Tapia, MS and Tobón-Cornejo, S and Díaz, D and Alemán-Escondrillas, G and Granados-Portillo, O and Noriega, L and Tovar, AR and Torres, N}, title = {Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil.}, journal = {The Journal of nutritional biochemistry}, volume = {94}, number = {}, pages = {108751}, doi = {10.1016/j.jnutbio.2021.108751}, pmid = {33915261}, issn = {1873-4847}, mesh = {Animals ; Bacteria/classification/genetics ; Cells, Cultured ; Coconut Oil/*pharmacology ; Computational Biology ; DNA, Bacterial/genetics ; Feces/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Regulation/drug effects ; Genotype ; Glucose Intolerance ; Hepatocytes/drug effects ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/genetics/metabolism ; Non-alcoholic Fatty Liver Disease/*prevention &amp; control ; Olive Oil/*pharmacology ; Oxygen Consumption/drug effects ; PPAR alpha/genetics/*metabolism ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S ; Random Allocation ; Soybean Oil/*pharmacology ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {Diets rich in mono or polyunsaturated fats have been associated with a healthy phenotype, but there is controversial evidence about coconut oil (CO), which is rich in saturated medium-chain fatty acids. Therefore, the purpose of the present work was to study whether different types of oils rich in polyunsaturated (soybean oil, SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO) can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial function in wild type and PPARα KO mice. The group that received SO showed the highest microbial diversity, increase in Akkermansia muciniphila, high insulin sensitivity and low grade inflammation, The OO group showed similar insulin sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in fatty acid oxidation and low grade inflammation. The CO consumption led to the lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-cholesterol concentration and the lowest respiratory capacity and fatty acid oxidation in the mitochondria. The absence of PPARα decreased alpha diversity and increased LPS concentration particularly in the CO group, and increased insulin sensitivity in the groups fed SO or OO. These results indicate that consuming mono or polyunsaturated fatty acids produced health benefits at the recommended intake but a high concentration of oils (three times the recommended oil intake in rodents) significantly decreased the microbial alpha-diversity independent of the type of oil.}, }
@article {pmid32957504, year = {2020}, author = {Griffin, N and Marsland, M and Roselli, S and Oldmeadow, C and Attia, J and Walker, MM and Hondermarck, H and Faulkner, S}, title = {The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer.}, journal = {Biomolecules}, volume = {10}, number = {9}, pages = {}, pmid = {32957504}, issn = {2218-273X}, support = {G1101013//Faculty of Health and Medicine, University of Newcastle Australia/International ; }, mesh = {Biomarkers, Tumor/antagonists &amp; inhibitors/*biosynthesis/genetics ; Breast Neoplasms/drug therapy/genetics/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/genetics/metabolism ; Carcinoma, Lobular/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Targeted Therapy/methods ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Receptor, ErbB-2/*metabolism ; Receptor, trkA/antagonists &amp; inhibitors/*biosynthesis/genetics ; Survival Analysis ; }, abstract = {The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.}, }
@article {pmid34466203, year = {2021}, author = {Zingue, S and Atenguena, EO and Zingue, LL and Tueche, AB and Njamen, D and Nkoum, AB and Ndom, P}, title = {Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.}, journal = {The Pan African medical journal}, volume = {39}, number = {}, pages = {182}, pmid = {34466203}, issn = {1937-8688}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Cameroon/epidemiology ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/pathology ; Early Detection of Cancer/methods ; Female ; Hospitals, General ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult ; }, abstract = {Introduction: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon).<br><br>Methods: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaoundé General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05.<br><br>Results: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 ± 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 ± 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011).<br><br>Conclusion: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.}, }
@article {pmid33513952, year = {2021}, author = {O'Rourke, JA and Graham, MA}, title = {Gene Expression Responses to Sequential Nutrient Deficiency Stresses in Soybean.}, journal = {International journal of molecular sciences}, volume = {22}, number = {3}, pages = {}, pmid = {33513952}, issn = {1422-0067}, support = {Project 5030-21220-006-00D//United States Department of Agriculture, Agricultural Research Service/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant/genetics ; Iron/metabolism ; Nutrients/*metabolism ; Phosphates/metabolism ; Plant Roots/genetics/growth &amp; development ; Soybeans/*genetics/growth &amp; development/metabolism ; Stress, Physiological/*genetics ; Transcriptome/*genetics ; }, abstract = {Throughout the growing season, crops experience a multitude of short periods of various abiotic stresses. These stress events have long-term impacts on plant performance and yield. It is imperative to improve our understanding of the genes and biological processes underlying plant stress tolerance to mitigate end of season yield loss. The majority of studies examining transcriptional changes induced by stress focus on single stress events. Few studies have been performed in model or crop species to examine transcriptional responses of plants exposed to repeated or sequential stress exposure, which better reflect field conditions. In this study, we examine the transcriptional profile of soybean plants exposed to iron deficiency stress followed by phosphate deficiency stress (-Fe-Pi). Comparing this response to previous studies, we identified a core suite of genes conserved across all repeated stress exposures (-Fe-Pi, -Fe-Fe, -Pi-Pi). Additionally, we determined transcriptional response to sequential stress exposure (-Fe-Pi) involves genes usually associated with reproduction, not stress responses. These findings highlight the plasticity of the plant transcriptome and the complexity of unraveling stress response pathways.}, }
@article {pmid33593316, year = {2021}, author = {Liu, J and Zheng, X and Han, Z and Lin, S and Han, H and Xu, C}, title = {Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {168}, pmid = {33593316}, issn = {1471-2407}, mesh = {Adenocarcinoma/*mortality/pathology/therapy ; Aged ; Breast Neoplasms/*mortality/pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program/*statistics &amp; numerical data ; Survival Rate ; }, abstract = {BACKGROUND: The prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.<br><br>METHODS: We retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient's 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).<br><br>RESULTS: Comparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.<br><br>CONCLUSIONS: The prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.}, }
@article {pmid34198053, year = {2021}, author = {Sela, Y and Bar-Or, RL and Kor, A and Lev-Ran, S}, title = {The Internet addiction test: Psychometric properties, socio-demographic risk factors and addictive co-morbidities in a large adult sample.}, journal = {Addictive behaviors}, volume = {122}, number = {}, pages = {107023}, doi = {10.1016/j.addbeh.2021.107023}, pmid = {34198053}, issn = {1873-6327}, mesh = {Adult ; *Behavior, Addictive/epidemiology ; Cross-Sectional Studies ; Humans ; Internet ; *Internet Addiction Disorder ; Prevalence ; Psychometrics ; Reproducibility of Results ; Risk Factors ; Surveys and Questionnaires ; }, abstract = {The Internet Addiction Test (IAT) (Young, 1998) is one of the most utilized diagnostic instruments to evaluate internet addiction. Despite the wide use of IAT in research and clinical settings, there is lack of an empirical validation of this scale among a largescale adult population. The present study aimed to: (1) investigate the psychometric properties of a Hebrew version of the IAT among large-scale Israeli adult sample. (2) Assess the socio-demographic characteristics of individuals who suffer from IA. (3) Assess the co-morbidity of IA in relation to substance and behavioral addictions. A cross sectional study was conducted, by constructing a representative sample (N = 4035) of the Jewish adult (18-70 y/o, M = 40.5, SD = 14.5) population in Israel. Participants responded an online survey, that measured IAT, socio-demographic characteristics, substance and behavioral addictions. Results showed that two-factor model (Emotional and Cognitive Preoccupation with the Internet and Loss of Control and Interference with Daily Life) has good psychometric properties and fits the data well. Young age, not being married (Risk Ratio [RR] = 1.98, 95% CI [1.51-2.63]), and having a low socio-economic status (RR = 1.41, 95% CI [1.05-1.90]) were found to be associated with IA. Drug (RR = 4.50, 95% CI [2.89-7.01]) and alcohol (RR = 3.54, 95% CI [1.50-5.42]) use disorders were associated with IA. High co-morbidity between behavioral addictions and IA was also found (RR = 15.24, 95% CI [11.17-20.78]). Overall, results show that the Hebrew version of the IAT is a valid and reliable instrument, and provide a comprehensive picture of IA prevalence and profile in adult Israeli sample.}, }
@article {pmid33759307, year = {2021}, author = {Zhang, J and Zhou, B and Sun, J and Chen, H and Yang, Z}, title = {Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.}, journal = {Journal of biochemical and molecular toxicology}, volume = {35}, number = {7}, pages = {e22779}, doi = {10.1002/jbt.22779}, pmid = {33759307}, issn = {1099-0461}, mesh = {9,10-Dimethyl-1,2-benzanthracene/*toxicity ; Animals ; Female ; MAP Kinase Signaling System/*drug effects ; Mammary Neoplasms, Animal/chemically induced/drug therapy/*metabolism/pathology ; NF-E2-Related Factor 2/*metabolism ; Neoplasm Proteins/*metabolism ; Rats ; Receptors, Aryl Hydrocarbon/*metabolism ; Triterpenes/*pharmacology ; }, abstract = {The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.}, }
@article {pmid34417460, year = {2021}, author = {Gonzalez-Rellan, MJ and Fondevila, MF and Fernandez, U and Rodríguez, A and Varela-Rey, M and Veyrat-Durebex, C and Seoane, S and Bernardo, G and Lopitz-Otsoa, F and Fernández-Ramos, D and Bilbao, J and Iglesias, C and Novoa, E and Ameneiro, C and Senra, A and Beiroa, D and Cuñarro, J and Dp Chantada-Vazquez, M and Garcia-Vence, M and Bravo, SB and Da Silva Lima, N and Porteiro, B and Carneiro, C and Vidal, A and Tovar, S and Müller, TD and Ferno, J and Guallar, D and Fidalgo, M and Sabio, G and Herzig, S and Yang, WH and Cho, JW and Martinez-Chantar, ML and Perez-Fernandez, R and López, M and Dieguez, C and Mato, JM and Millet, O and Coppari, R and Woodhoo, A and Fruhbeck, G and Nogueiras, R}, title = {O-GlcNAcylated p53 in the liver modulates hepatic glucose production.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {5068}, pmid = {34417460}, issn = {2041-1723}, mesh = {Acetylglucosamine/*metabolism ; Animals ; Base Sequence ; Caloric Restriction ; Cell Line ; Colforsin/pharmacology ; Diabetes Mellitus, Type 2/complications/metabolism ; Epinephrine/metabolism ; Glucagon/metabolism ; Glucocorticoids/metabolism ; Gluconeogenesis/drug effects ; Glucose/*metabolism ; Glycosylation ; Hepatocytes/drug effects/metabolism ; Humans ; Hydrocortisone/metabolism ; Hyperglycemia/complications/metabolism ; Insulin Resistance ; Intracellular Signaling Peptides and Proteins/metabolism ; Liver/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications/metabolism ; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Protein Stability/drug effects ; Pyruvic Acid/metabolism ; RNA, Messenger/genetics/metabolism ; Transcription, Genetic/drug effects ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.}, }
@article {pmid33478862, year = {2021}, author = {Zhang, H and Ge, XY and Qiao, HQ}, title = {Analysis of prognostic risk factors in 3427 patients with invasive ductal carcinoma of breast: Results based on the SEER database.}, journal = {Asian journal of surgery}, volume = {44}, number = {3}, pages = {577-579}, doi = {10.1016/j.asjsur.2020.12.014}, pmid = {33478862}, issn = {0219-3108}, mesh = {Breast/pathology ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Neoplasm Staging ; Prognosis ; Risk Factors ; }, }
@article {pmid33785437, year = {2021}, author = {Garcia, AM and Bishop, EL and Li, D and Jeffery, LE and Garten, A and Thakker, A and Certo, M and Mauro, C and Tennant, DA and Dimeloe, S and Evelo, CT and Coort, SL and Hewison, M}, title = {Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {211}, number = {}, pages = {105891}, pmid = {33785437}, issn = {1879-1220}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Adipogenesis ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/drug effects/immunology/*metabolism ; Fatty Acids/*biosynthesis ; Glycolysis ; Humans ; *Immune Tolerance ; Vitamin D/*analogs &amp; derivatives/pharmacology ; }, abstract = {The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of immune function, promoting anti-inflammatory, tolerogenic T cell responses by modulating antigen presentation by dendritic cells (DC). Transcriptomic analyses indicate that DC responses to 1,25D involve changes in glycolysis, oxidative phosphorylation, electron transport and the TCA cycle. To determine the functional impact of 1,25D-mediated metabolic remodelling, human monocyte-derived DC were differentiated to immature (+vehicle, iDC), mature (+LPS, mDC), and immature tolerogenic DC (+1,25D, itolDC) and characterised for metabolic function. In contrast to mDC which showed no change in respiration, itolDC showed increased basal and ATP-linked respiration relative to iDC. Tracer metabolite analyses using 13C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of 13C-glucose revealed significant incorporation of label in palmitate and palmitoleate, indicating that 1,25D promotes metabolic fatty acid synthesis in itolDC. Inhibition of fatty acid synthesis in itolDC altered itolDC morphology and suppressed expression of CD14 and IL-10 by these cells. These data indicate that the ability of 1,25D to induce tolerogenic DC involves metabolic remodelling leading to synthesis of fatty acids.}, }
@article {pmid34452576, year = {2021}, author = {Ameli, F and Ghafourina Nassab, F and Masir, N and Kahtib, F}, title = {Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {22}, number = {8}, pages = {2603-2609}, doi = {10.31557/APJCP.2021.22.8.2603}, pmid = {34452576}, issn = {2476-762X}, abstract = {INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).<br><br>MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.<br><br>RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.<br><br>CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.}, }
@article {pmid34449311, year = {2021}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {142}, number = {}, pages = {111991}, doi = {10.1016/j.biopha.2021.111991}, pmid = {34449311}, issn = {1950-6007}, abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.<br><br>PATIENTS AND METHODS: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46-0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 2-3, and Her-2 positivity were 1.87 (1.03-3.42), 2.31 (1.20-4.44), 1.67 (1.09-2.56), 2.43 (1.18-4.97), 1.17 (1.03-1.19), 1.28 (1.13-2.24), 1.20 (1.05-2.22), and 1.59 (1.01-2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38-0.97) compared with that for no adjuvant radiotherapy.<br><br>CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.}, }
@article {pmid34448091, year = {2021}, author = {Jimbo, H and Horimoto, Y and Okazaki, M and Ishizuka, Y and Kido, H and Saito, M}, title = {Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {197}, pmid = {34448091}, issn = {2198-7793}, abstract = {BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.<br><br>CASE PRESENTATION: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.<br><br>CONCLUSIONS: The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.}, }
@article {pmid34437555, year = {2021}, author = {Shulman, D and Shnitzer-Akuka, M and Reifen-Tagar, M}, title = {The cost of attributing moral blame: Defensiveness and resistance to change when raising awareness to animal suffering in factory farming.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0254375}, doi = {10.1371/journal.pone.0254375}, pmid = {34437555}, issn = {1932-6203}, abstract = {Social change campaigns often entail raising awareness of harm caused by people's behavior. For example, campaigns to reduce meat eating frequently highlight the suffering endured by animals. Such messages may simultaneously attribute moral blame to individuals for causing the harm described. Given people's motivation to protect their moral self-image, we expected that information about the suffering of animals in the meat industry presented with a blaming (versus absolving) frame would generate greater defensiveness and correspondingly resistance to change in support of veg*nism (veganism/vegetarianism). We ran three studies to test this expectation. In two studies, we found that raising awareness of animal suffering using a blaming frame increased defensiveness, leading to lower veg*n-supporting attitudes and behavioral intentions. In one study, our hypothesis was not supported, however, a mini-meta analysis across the three studies suggests the overall pattern is robust. This work expands our understanding of the role of moral self-image preservation in defensiveness and resistance to change, and has applied relevance for the development of effective communication strategies in social and moral campaigns.}, }
@article {pmid32404955, year = {2020}, author = {Tille, JC and Vieira, AF and Saint-Martin, C and Djerroudi, L and Furhmann, L and Bidard, FC and Kirova, Y and Tardivon, A and Reyal, F and Carton, M and Vincent-Salomon, A}, title = {Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {11}, pages = {2198-2207}, pmid = {32404955}, issn = {1530-0285}, mesh = {Age Factors ; Breast Neoplasms/immunology/metabolism/mortality/*pathology ; Carcinoma, Lobular/immunology/metabolism/mortality/*pathology ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology/*pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi2 tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.}, }
@article {pmid32738354, year = {2021}, author = {Camacho Londoño, JE and Kuryshev, V and Zorn, M and Saar, K and Tian, Q and Hübner, N and Nawroth, P and Dietrich, A and Birnbaumer, L and Lipp, P and Dieterich, C and Freichel, M}, title = {Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca2+ entry after pressure-overload induced cardiac remodelling.}, journal = {Progress in biophysics and molecular biology}, volume = {159}, number = {}, pages = {86-104}, doi = {10.1016/j.pbiomolbio.2020.07.006}, pmid = {32738354}, issn = {1873-1732}, support = {Z01 ES101684/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena/physiology ; Calcium/*metabolism ; Calcium Signaling ; Cardiomegaly/metabolism ; Gene Expression Regulation ; Humans ; Ion Channels/genetics/metabolism ; Male ; Mice ; Mice, Knockout ; Myocytes, Cardiac/*metabolism ; TRPC Cation Channels/*metabolism ; Transcriptional Activation/physiology ; Ventricular Remodeling/*physiology ; }, abstract = {AIMS: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca2+ entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling.<br><br>METHODS AND RESULTS: Mn2+-quench analysis in cardiomyocytes from several Trpc-deficient mice revealed that both TRPC1 and TRPC4 are required for BGCE. Electrically-evoked cell shortening of cardiomyocytes from TRPC1/C4-DKO mice was reduced, whereas parameters of cardiac contractility and relaxation assessed in vivo were unaltered. As pathological cardiac remodelling in mice depends on their genetic background, and the development of cardiac remodelling was found to be reduced in TRPC1/C4-DKO mice on a mixed genetic background, we studied TRPC1/C4-DKO mice on a C57BL6/N genetic background. Cardiac hypertrophy was reduced in those mice after chronic isoproterenol infusion (-51.4%) or after one week of transverse aortic constriction (TAC; -73.0%). This last manoeuvre was preceded by changes in the pressure overload induced transcriptional program as analysed by RNA sequencing. Genes encoding specific collagens, the Mef2 target myomaxin and the gene encoding the mechanosensitive channel Piezo2 were up-regulated after TAC in wild type but not in TRPC1/C4-DKO hearts.<br><br>CONCLUSIONS: Deletion of the TRPC1 and TRPC4 channel proteins protects against development of pathological cardiac hypertrophy independently of the genetic background. To determine if the TRPC1/C4-dependent changes in the pressure overload induced alterations in the transcriptional program causally contribute to cardio-protection needs to be elaborated in future studies.}, }
@article {pmid34413744, year = {2021}, author = {Moghimi, M and Khodadadi, K}, title = {Dermatomyositis following Biosimilar Trastuzumab in a Breast Cancer Patient: A Case Report.}, journal = {Case reports in oncology}, volume = {14}, number = {2}, pages = {1134-1138}, doi = {10.1159/000517819}, pmid = {34413744}, issn = {1662-6575}, abstract = {Trastuzumab, as a recombinant IgG1 kappa, is a humanized monoclonal antibody against human epidermal growth factor receptor 2. Accordingly, it is widely used in breast cancers at early and advanced stages. Dermatomyositis is a rare adverse event of trastuzumab therapy, which is not well documented yet. In this study, a patient was treated for invasive ductal carcinoma with some symptoms of rash and generalized fatigue. These symptoms started after the fifth cycle of trastuzumab, which were gradually deteriorating. This patient's medical and family histories were unremarkable. The progression of the disease was ruled out as a possible cause of dermatomyositis, and the laboratory evaluation revealed a moderate increase in serum muscle protein (CPK). So, trastuzumab treatment was discontinued, and by passing 1 month from the start of prednisolone and hydroxychloroquine, the patient had no symptoms.}, }
@article {pmid34409828, year = {2021}, author = {Shabanov, GA and Rybchenko, AA and Lugovaya, EA and Vdovenko, SI}, title = {[Biological age estimation based on the spectral analysis of the human brain bioelectric activity.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {34}, number = {3}, pages = {466-471}, pmid = {34409828}, issn = {1561-9125}, mesh = {*Aging ; *Brain ; Cell Differentiation ; Humans ; Risk Factors ; }, abstract = {For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients' cancer G1-G4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G1-G4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients' medical treatment.}, }
@article {pmid34330920, year = {2021}, author = {Thomson-Luque, R and Votborg-Novél, L and Ndovie, W and Andrade, CM and Niangaly, M and Attipa, C and Lima, NF and Coulibaly, D and Doumtabe, D and Guindo, B and Tangara, B and Maiga, F and Kone, AK and Traore, K and Kayentao, K and Ongoiba, A and Doumbo, S and Thera, MA and Traoré, B and Seydel, K and Osório, NS and Portugal, S}, title = {Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4711}, pmid = {34330920}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI099628/AI/NIAID NIH HHS/United States ; }, mesh = {Blood Circulation Time ; Erythrocytes/parasitology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Bacterial ; Gene Ontology ; Genes, Bacterial/genetics ; Humans ; Malaria, Falciparum/*blood/parasitology/physiopathology ; Parasitemia/*blood/parasitology/physiopathology ; Plasmodium falciparum/*genetics/physiology ; }, abstract = {Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum's tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.}, }
@article {pmid33348399, year = {2020}, author = {Reis, APAM and Teixeira, CMS and Medeiros, ARL and Chaves, KZC and Albuquerque, CR and Melo, MR}, title = {Sociodemographic and Clinical-pathological Study of Molecular Subtitles of Breast Carcinoma in a Reference Unit of Maranhão.}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {42}, number = {12}, pages = {820-828}, doi = {10.1055/s-0040-1719147}, pmid = {33348399}, issn = {1806-9339}, mesh = {Brazil/epidemiology ; Breast Neoplasms/*epidemiology/etiology/pathology ; Cross-Sectional Studies ; Demography ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Medical Records ; Middle Aged ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Social Class ; }, abstract = {OBJECTIVE: To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry.<br><br>METHODS: A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranhão, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive.<br><br>RESULTS: A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level < 9 years (40%), staging > IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5 cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others.<br><br>CONCLUSION: It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.}, }
@article {pmid33554951, year = {2020}, author = {Şahin, S and Cakir, A and Gonul, II and Seckin, S and Uluoglu, O}, title = {Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.}, journal = {Annali italiani di chirurgia}, volume = {91}, number = {}, pages = {583-591}, pmid = {33554951}, issn = {2239-253X}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, IGF Type 1/*genetics ; }, abstract = {OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer.<br><br>MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically.<br><br>RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025).<br><br>CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis.<br><br>KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.}, }
@article {pmid32776387, year = {2020}, author = {Takahara, T and Satou, A and Sugie, M and Watanabe, M and Kanao, K and Sumitomo, M and Tsuzuki, T}, title = {Prognostic significance of p16 expression in high-grade prostate adenocarcinoma.}, journal = {Pathology international}, volume = {70}, number = {10}, pages = {743-751}, doi = {10.1111/pin.12997}, pmid = {32776387}, issn = {1440-1827}, mesh = {Adenocarcinoma/*diagnosis/drug therapy/metabolism/pathology ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/*diagnosis/drug therapy/metabolism/pathology ; }, abstract = {Management of advanced hormone-naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52-87) years. The median follow-up was 62 months (range 2-98). Fourteen patients had p16-positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16-positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC-P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis-targeted therapy.}, }
@article {pmid33608011, year = {2021}, author = {O'Donnell, AJ and Reece, SE}, title = {Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms.}, journal = {Malaria journal}, volume = {20}, number = {1}, pages = {105}, pmid = {33608011}, issn = {1475-2875}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; UF110155//The Royal Society/ ; NF140517//The Royal Society/ ; RGP0046/2013//Human Frontier Science Program/ ; }, mesh = {Animals ; Anopheles/parasitology/*physiology ; *Circadian Rhythm ; Erythrocytes/parasitology ; Female ; Mosquito Vectors/parasitology/*physiology ; Plasmodium berghei/growth &amp; development/*physiology ; *Reproduction, Asexual ; }, abstract = {BACKGROUND: Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species of Plasmodium appear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for example Plasmodium chabaudi, is governed by host rhythms, yet seems completely independent of host rhythms in Plasmodium berghei, another rodent malaria species, is mysterious.<br><br>METHODS: This study reports a series of five experiments probing the relationships between the asynchronous IDC schedule of P. berghei and the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms.<br><br>RESULTS: The results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs on P. berghei; (ii) the IDC schedule of P. berghei is impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes.<br><br>CONCLUSIONS: Overall, host rhythms do not affect the performance of P. berghei and its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.}, }
@article {pmid32789812, year = {2021}, author = {Wakefield, B and Diko, S and Gilmer, R and Connell, KA and DeWitt, PE and Hurt, KJ}, title = {Accuracy of obstetric laceration diagnoses in the electronic medical record.}, journal = {International urogynecology journal}, volume = {32}, number = {7}, pages = {1907-1915}, pmid = {32789812}, issn = {1433-3023}, mesh = {Anal Canal/injuries ; Delivery, Obstetric ; Electronic Health Records ; Female ; Humans ; *Lacerations/diagnosis/epidemiology ; Perineum/injuries ; Pregnancy ; Retrospective Studies ; Risk Factors ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Patient safety data including rates of obstetric anal sphincter injury (OASI) are often derived from hospital discharge codes. With the transition to electronic medical records (EMRs), we hypothesized that electronic provider-entered delivery data would more accurately document obstetric perineal injury than traditional billing/diagnostic codes.<br><br>METHODS: We evaluated the accuracy of perineal laceration diagnoses after singleton vaginal deliveries during one calendar year at an American tertiary academic medical center. We reviewed the entire hospital chart to determine the most likely laceration diagnosis and compared that expert review diagnosis (ExpRD) with documentation in the EMR delivery summary (EDS) and ICD-9 diagnostic codes (IDCs).<br><br>RESULTS: We retrospectively selected 354 total delivery records. OASI complicated 56 of those. 303 records (86%) were coded identically by the EDS and IDCs. Diagnoses from the IDCs and the EDS were mostly correct compared with ExpRD (sensitivity = 96%, specificity = 100%). There was no systematic over- or under-diagnosis of OASI for either the EDS (p = 0.070) or the IDCs (p = 0.447). When considering all laceration types the EDS was correct for 21 (5.9%) lacerations that were incorrect according to the IDCs. Overall, the EDS was more accurate (p < 0.05) owing to errors in IDC minor laceration diagnoses.<br><br>CONCLUSIONS: Electronic medical record delivery summary data and EMR-derived diagnostic codes similarly characterize OASI. The EDS does not improve OASI reporting, but may be more accurate when considering all perineal lacerations. This assumes that providers have correctly identified and categorized the lacerations that they record in the EMR.}, }
@article {pmid34379693, year = {2021}, author = {He, X and Anthony, DC and Catoni, Z and Cao, W}, title = {Pulmonary tumor embolism: A retrospective study over a 30-year period.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0255917}, doi = {10.1371/journal.pone.0255917}, pmid = {34379693}, issn = {1932-6203}, abstract = {BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.<br><br>METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.<br><br>RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4±2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).<br><br>CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.}, }
@article {pmid23406456, year = {2013}, author = {Erro, R and Barone, P and Moccia, M and Amboni, M and Vitale, C}, title = {Abnormal eating behaviors in progressive supranuclear palsy.}, journal = {European journal of neurology}, volume = {20}, number = {3}, pages = {e47-e48}, doi = {10.1111/ene.12077}, pmid = {23406456}, issn = {1468-1331}, mesh = {Aged ; *Feeding Behavior ; Feeding and Eating Disorders/*etiology ; Humans ; Middle Aged ; Supranuclear Palsy, Progressive/*complications ; }, }
@article {pmid34359556, year = {2021}, author = {Zhang, JQ and Cheng, TM and Lin, WC and Chiu, KC and Wu, SY}, title = {Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.}, journal = {Cancers}, volume = {13}, number = {15}, pages = {}, doi = {10.3390/cancers13153654}, pmid = {34359556}, issn = {2072-6694}, abstract = {PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments.<br><br>METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group).<br><br>RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE.<br><br>CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.}, }
@article {pmid33494912, year = {2021}, author = {Días, R and Mendes, ÂB and Lages, N and Machado, H}, title = {Ultrasound-guided fascial plane blocks as unique anesthetic technique for total mastectomy in a covid-19 era: a case report.}, journal = {Revista espanola de anestesiologia y reanimacion}, volume = {68}, number = {7}, pages = {408-413}, doi = {10.1016/j.redar.2020.09.010}, pmid = {33494912}, issn = {2340-3284}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Breast Neoplasms/complications/drug therapy/*surgery ; COVID-19/*prevention &amp; control ; Carcinoma, Ductal, Breast/complications/drug therapy/*surgery ; Combined Modality Therapy ; Cross Infection/*prevention &amp; control ; Fascia ; Female ; Heart Failure/chemically induced/complications ; Humans ; Hypertension/complications ; Hypertension, Pulmonary/complications ; Infection Control/*methods ; Intercostal Nerves ; *Mastectomy, Simple ; Middle Aged ; Neoadjuvant Therapy/adverse effects ; Neoplasm Recurrence, Local/*surgery ; Nerve Block/*methods ; Pain Management/methods ; *SARS-CoV-2 ; Thoracic Nerves ; Thoracic Wall/innervation ; Ultrasonography, Interventional/methods ; }, abstract = {INTRODUCTION: Regional anesthesia techniques were recently introduced to provide analgesia for breast surgery. These techniques are rarely used as the primary anesthesia due to the complexity of breast innervation, with numerous structures that can potentially be disrupted during breast surgery.<br><br>CASE REPORT: A female patient in her sixties diagnosed with invasive ductal carcinoma on her left breast was scheduled for a simple mastectomy. After anesthetic evaluation, identification of high risk perioperative cardiovascular complications, it was proposed to perform the surgery only with regional anesthesia. A combination of pectoral nerve block (Pecs II), pecto-intercostal fascial block (PIFB) and supraclavicular nerve block ultrasound-guided were successfully performed.<br><br>CONCLUSION: This is the first case reporting a novel approach in a patient with severe cardiopulmonary disease who underwent breast surgery in a COVID-19 era.}, }
@article {pmid33795819, year = {2021}, author = {Nagasawa, S and Kuze, Y and Maeda, I and Kojima, Y and Motoyoshi, A and Onishi, T and Iwatani, T and Yokoe, T and Koike, J and Chosokabe, M and Kubota, M and Seino, H and Suzuki, A and Seki, M and Tsuchihara, K and Inoue, E and Tsugawa, K and Ohta, T and Suzuki, Y}, title = {Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {438}, pmid = {33795819}, issn = {2399-3642}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Female ; GATA3 Transcription Factor/genetics/metabolism ; *Gene Amplification ; Gene Expression Profiling ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/genetics/metabolism ; Young Adult ; }, abstract = {In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.}, }
@article {pmid33039708, year = {2020}, author = {Bitencourt, AGV and Gibbs, P and Rossi Saccarelli, C and Daimiel, I and Lo Gullo, R and Fox, MJ and Thakur, S and Pinker, K and Morris, EA and Morrow, M and Jochelson, MS}, title = {MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103042}, pmid = {33039708}, issn = {2352-3964}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Biomarkers ; Breast Neoplasms/*diagnostic imaging/*genetics/therapy ; Female ; *Gene Expression ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; *Machine Learning ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Neoadjuvant Therapy ; ROC Curve ; Receptor, ErbB-2/*genetics/metabolism ; Young Adult ; }, abstract = {BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC).<br><br>METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20).<br><br>FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test).<br><br>INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients.<br><br>FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.}, }
@article {pmid31710002, year = {2020}, author = {Zhu, S and Zhao, JG and Chen, JR and Liu, ZH and Sun, GX and Wang, ZP and Ni, YC and Dai, JD and Shen, PF and Zeng, H}, title = {Intraductal carcinoma of the prostate in prostate biopsy samples: correlation with aggressive pathological features after radical prostatectomy and prognostic value in high-risk prostate cancer.}, journal = {Asian journal of andrology}, volume = {22}, number = {5}, pages = {519-525}, pmid = {31710002}, issn = {1745-7262}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/*pathology/surgery ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Nomograms ; Prognosis ; Proportional Hazards Models ; Prostate/pathology ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/blood/*pathology/surgery ; Risk Factors ; Seminal Vesicles/pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive pathological pattern of prostate cancer (PCa). We investigated the association of IDC-P in prostate biopsy (PBx) with several pathological features after radical prostatectomy (RP) and its prognostic value in high-risk PCa. A total of 418 patients with high-risk PCa after RP were included in this study. IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification. Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features. Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P. IDC-P was identified in PBx in 36/418 (8.6%) patients. Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP, including Gleason score 8-10 (P < 0.001), seminal vesicular invasion (P < 0.001), and pathological T (pT) 3a (P = 0.043). Patients with IDC-P in PBx manifested poorer biochemical-free survival (BFS) than those without IDC-P (37.47 months vs not reached, P < 0.001). The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools. We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa. In addition, IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.}, }
@article {pmid31907974, year = {2020}, author = {DeVaux, RS and Ropri, AS and Grimm, SL and Hall, PA and Herrera, EO and Chittur, SV and Smith, WP and Coarfa, C and Behbod, F and Herschkowitz, JI}, title = {Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling.}, journal = {Journal of cellular biochemistry}, volume = {121}, number = {7}, pages = {3465-3478}, pmid = {31907974}, issn = {1097-4644}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Interleukin-6/*genetics ; Neoplasm Invasiveness ; RNA, Antisense/*genetics ; RNA, Long Noncoding/*genetics ; STAT3 Transcription Factor/*metabolism ; Signal Transduction ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment.}, }
@article {pmid34320711, year = {2021}, author = {Fan, T and Wang, CQ and Li, XT and Yang, H and Zhou, J and Song, YJ}, title = {MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {31}, number = {8}, pages = {937-940}, doi = {10.29271/jcpsp.2021.08.937}, pmid = {34320711}, issn = {1681-7168}, mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *MicroRNAs/genetics ; RNA-Binding Proteins/genetics ; Transcription Factors/genetics ; }, abstract = {OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.<br><br>STUDY DESIGN: An experimental study.<br><br>PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.<br><br>METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT⁃PCR.<br><br>RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para⁃carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2) is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.<br><br>CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.}, }
@article {pmid34293926, year = {2021}, author = {Chen, X and Li, X and Wang, J and Zhao, L and Peng, X and Zhang, C and Liu, K and Huang, G and Lai, Y}, title = {Breast invasive ductal carcinoma diagnosis with a three-miRNA panel in serum.}, journal = {Biomarkers in medicine}, volume = {}, number = {}, pages = {}, doi = {10.2217/bmm-2020-0785}, pmid = {34293926}, issn = {1752-0371}, support = {SZLY2018023//Clinical Research Project of Shenzhen Health Commission,/ ; JCYJ20180507183102747//Science and Technology Development Fund Project of Shenzhen,/ ; //Shenzhen High-level Hospital Construction Fund/ ; JCYJ2017001, JCYJ2017004, JCYJ2017005, JCYJ2017006//Basic Research Project of Peking University Shenzhen Hospital,/ ; LCYJ2017001//Clinical Research Project of Peking University Shenzhen Hospital,/ ; }, abstract = {Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials &amp; methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.}, }
@article {pmid34297787, year = {2021}, author = {Ahmed, F and Adnan, M and Malik, A and Tariq, S and Kamal, F and Ijaz, B}, title = {Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0255243}, doi = {10.1371/journal.pone.0255243}, pmid = {34297787}, issn = {1932-6203}, abstract = {Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient's data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients' biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.}, }
@article {pmid33433431, year = {2021}, author = {Xia, Y and Liu, X and Li, W and Zhu, Y}, title = {Potential role of significant GATA3 mutation in male breast cancer responding to endocrine therapy: A case report.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {1}, pages = {161-164}, doi = {10.4103/IJPM.IJPM_160_19}, pmid = {33433431}, issn = {0974-5130}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast/pathology ; Breast Neoplasms, Male/diagnostic imaging/*drug therapy/*genetics/secondary ; Endocrine System/drug effects ; GATA3 Transcription Factor/*genetics ; Humans ; Male ; Middle Aged ; *Mutation ; Positron Emission Tomography Computed Tomography ; }, abstract = {A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.}, }
@article {pmid33433407, year = {2021}, author = {Farrag, MS and Anter, AH and Farrag, NS and Ibrahiem, AT}, title = {"Switch of E-Cadherin to N-Cadherin expression in different molecular subtypes of breast invasive duct carcinomas and its correlation with clinicopathological features".}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {1}, pages = {38-46}, doi = {10.4103/IJPM.IJPM_924_19}, pmid = {33433407}, issn = {0974-5130}, mesh = {Antigens, CD/*genetics ; Biomarkers, Tumor ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/classification/*genetics/*pathology/secondary ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paraffin Embedding ; Prognosis ; Young Adult ; }, abstract = {Background: In breast cancer, metastasis and recurrence is the main culprit in treatment failure. This study aimed to explore the role of E-cadherin/N-cadherin Switch in progression, spread and metastasis in breast invasive duct carcinoma.<br><br>Materials and Methods: A cross-sectional study on 118 formalinfixed paraffinembedded mastectomy specimens of invasive breast duct carcinoma. Primary antibodies for E-cadherin (monoclonal, clone HECD-1; Zymed Laboratories; dilution 1:600) and N-cadherin (monoclonal, clone 3B9; Zymed Laboratories, Inc., Montrouge, France; dilution 1:200) were applied for all cases. The study revealed that E-cadherin high expression was significantly associated with advanced TNM clinical stage (P = 0.021), and nodal metastasis (P < 0.001). High expression of N-cadherin was significantly positively correlated with tumor sizes (P < 0.00), advanced clinical stage (P < 0.00), and nodal metastasis (P < 0.008). Mean OS was 39.99 months in cases with negative expression versus 41.8 months in cases with positive expression. Mean DFS in cases with positive E. cadh expression was 41.89 months was higher than mean DFS in cases with negative E. cadh expression which was 40.52 months, but it showed no statistical significance (P = 0.57).<br><br>Conclusions/Significance: This study demonstrated that loss of E-cadherin and gain of N-cadherin promotes invasion, migration, and metastasis in invasive ductal carcinoma cells. Importantly, these findings may exploit new cancer therapies using N-cadherin antagonists.}, }
@article {pmid32408395, year = {2020}, author = {Solagna, F and Nogara, L and Dyar, KA and Greulich, F and Mir, AA and Türk, C and Bock, T and Geremia, A and Baraldo, M and Sartori, R and Farup, J and Uhlenhaut, H and Vissing, K and Krüger, M and Blaauw, B}, title = {Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling.}, journal = {Acta physiologica (Oxford, England)}, volume = {230}, number = {1}, pages = {e13496}, pmid = {32408395}, issn = {1748-1716}, mesh = {Animals ; Chromatin/*chemistry ; Exercise ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*metabolism ; *Physical Conditioning, Animal ; Protein Biosynthesis ; *Serum Response Factor/genetics/metabolism ; *Signal Transduction ; Transcription Factors/*metabolism ; }, abstract = {AIM: Resistance exercise increases muscle mass over time. However, the early signalling events leading to muscle growth are not yet well-defined. Here, we aim to identify new signalling pathways important for muscle remodelling after exercise.<br><br>METHODS: We performed a phosphoproteomics screen after a single bout of exercise in mice. As an exercise model we used unilateral electrical stimulation in vivo and treadmill running. We analysed muscle biopsies from human subjects to verify if our findings in murine muscle also translate to exercise in humans.<br><br>RESULTS: We identified a new phosphorylation site on Myocardin-Related Transcription Factor B (MRTF-B), a co-activator of serum response factor (SRF). Phosphorylation of MRTF-B is required for its nuclear translocation after exercise and is accompanied by the transcription of the SRF target gene Fos. In addition, high-intensity exercise also remodels chromatin at specific SRF target gene loci through the phosphorylation of histone 3 on serine 10 in myonuclei of both mice and humans. Ablation of the MAP kinase member MSK1/2 is sufficient to prevent this histone phosphorylation, reduce induction of SRF-target genes, and prevent increases in protein synthesis after exercise.<br><br>CONCLUSION: Our results identify a new exercise signalling fingerprint in vivo, instrumental for exercise-induced protein synthesis and potentially muscle growth.}, }
@article {pmid34293708, year = {2021}, author = {Okcu, O and Öztürk, Ç and Şen, B and Arpa, M and Bedir, R}, title = {Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters.}, journal = {Annals of diagnostic pathology}, volume = {54}, number = {}, pages = {151792}, doi = {10.1016/j.anndiagpath.2021.151792}, pmid = {34293708}, issn = {1532-8198}, abstract = {BACKGROUND AND OBJECTIVE: Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases.<br><br>MATERIALS AND METHODS: 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&amp;E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed.<br><br>RESULTS: We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis.<br><br>CONCLUSION: Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.}, }
@article {pmid32740271, year = {2020}, author = {Granek, L and Nakash, O}, title = {Prevalence and risk factors for suicidality in cancer patients and oncology healthcare professionals strategies in identifying suicide risk in cancer patients.}, journal = {Current opinion in supportive and palliative care}, volume = {14}, number = {3}, pages = {239-246}, pmid = {32740271}, issn = {1751-4266}, mesh = {Age Factors ; Cancer Care Facilities/organization &amp; administration ; Health Personnel/education/*organization &amp; administration ; Humans ; Inservice Training ; Mass Screening/organization &amp; administration ; Neoplasms/pathology/*psychology ; Prevalence ; Risk Factors ; Sex Factors ; Socioeconomic Factors ; Suicide/*statistics &amp; numerical data ; }, abstract = {PURPOSE OF REVIEW: The aim of this study was to summarize the literature on prevalence and risk factors for suicidality in cancer patients and to document the research on oncology healthcare professionals' strategies in identifying this risk.<br><br>RECENT FINDINGS: Cancer patients exhibit increased risk of suicidality compared with the general population. Various risk factors have been identified including sociodemographic factors such as poverty, being male and elderly as well as disease-related attributes such as cancer type and stage. The literature on how healthcare professionals identify suicide risk is sparse. Ten articles were found that focused on two main themes. These included information on systematic strategies in identifying suicide risk and factors that affect healthcare professionals' ability to identify risk in their patients.<br><br>SUMMARY: Although there is an immense amount of literature documenting the problem of suicidality among patients, the research on how healthcare professionals identify and respond to these indications in patients is nearly nonexistent. Cancer centres should implement standardized and systematic screening of cancer patients for suicidality and research on this patient population should collect and report these data. Ongoing training and education for healthcare professionals who work in the oncology setting on how to identify and respond to suicide risk among cancer patients is urgently needed.}, }
@article {pmid33888263, year = {2021}, author = {Schaub, JR and Tang, SC}, title = {Delayed Gemcitabine-Induced Posterior Reversible Encephalopathy Syndrome.}, journal = {The American journal of the medical sciences}, volume = {361}, number = {6}, pages = {795-798}, doi = {10.1016/j.amjms.2020.10.030}, pmid = {33888263}, issn = {1538-2990}, mesh = {Antimetabolites, Antineoplastic/*adverse effects ; Deoxycytidine/adverse effects/*analogs &amp; derivatives ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Posterior Leukoencephalopathy Syndrome/*chemically induced/*diagnostic imaging ; Time Factors ; }, abstract = {INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiographic syndrome that has been expanding rapidly in the world of clinical medical oncology and hematology. In this article, we provide a unique patient case of delayed gemcitabine-induced PRES.<br><br>BRIEF CASE REPORT: A 60-year-old African American female with significant past medical history of ER+/PR+/HER2- invasive ductal carcinoma of the left breast is seen in the medical oncology clinic with vague, mild complaints of lightheadedness. She had progressed on multiple lines of chemotherapy and was ultimately switched to gemcitabine. One month after her third dose of gemcitabine, she developed acute vision loss and soon developed generalized tonic-clonic seizure. Extensive workup was unrevealing other than PRES and she slowly improved with supportive care and withdrawal of the medication.<br><br>DISCUSSION: Multiple case reports have described PRES in the context of combination chemotherapy with gemcitabine and a platinum agent in the treatment of gastrointestinal malignancies. With growing evidence, this case is consistent with the hypothesis that gemcitabine as monotherapy has a direct association with PRES. This case highlights a unique aspect in that PRES can occur at a delayed time interval, much further than the expected hours to days after the previous treatment.}, }
@article {pmid33154304, year = {2020}, author = {Oral, O and Unverdi, H and Kumcu, E and Turkbey, D and Dogan, S and Hucumenoglu, S}, title = {Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {4}, pages = {551-558}, doi = {10.4103/IJPM.IJPM_637_18}, pmid = {33154304}, issn = {0974-5130}, mesh = {Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mucin 5AC/*genetics ; Mucin-1/*genetics ; Mucin-2/*genetics ; Mucin-6/*genetics ; Prognosis ; }, abstract = {Aims: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters.<br><br>Materials and Methods: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas.<br><br>Results: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion.<br><br>Conclusions: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.}, }
@article {pmid34279157, year = {2021}, author = {Ren, X and Ju, Y and Wang, C and Wei, R and Sun, H and Zhang, Q}, title = {MARCKS on Tumor-Associated Macrophages is Correlated with Immune Infiltrates and Poor Prognosis in Hepatocellular Carcinoma.}, journal = {Cancer investigation}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/07357907.2021.1950757}, pmid = {34279157}, issn = {1532-4192}, abstract = {BACKGROUND: Hepatocellular carcinoma is the fourth most common cause of cancer-related death. However, the cross-talk between tumor immune microenvironment and hepatocellular carcinoma (HCC) remains unclear.<br><br>MATERIAL AND METHODS: We analyzed the expression of miR-143-3p in exosomes from different HCC cell lines. Differentially expressed genes (DEGs) in Tumor-associated macrophages (TAMs) co-cultured with HCC cell lines were overlapped with miR-143-3p target genes. We used the Oncomine, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) databases to assess Myristoylated alanine-rich C-kinase substrate (MARCKS) expression in various types of cancers. The relationship between patient clinicopathological characteristics and MARCKS expression level was identified using the Kaplan-Meier plotter database. Last, we analyzed how MARCKS expression correlated with immune infiltration makers using the TCGA database, Tumor IMmune Estimation Resource (TIMER), and Gene Expression Profiling Interactive Analysis (GEPIA).<br><br>RESULTS: Exosomal miR-143-3p was elevated after IL-6 treatment in the HCC cell line. MARCKS, a target gene of miR-143-3p, was up-regulated in Tumor-associated macrophages co-cultured with high-metastatic-potential HCC cell line. MARCKS expression was identified as significantly correlated with outcome in multiple types of cancer, especially in HCC. High MARCKS expression level was associated with poorer overall survival (OS), Progress-free survival (PFS), and also with patient gender, race, hepatitis virus background, stage, grade, AJCC_T, and vascular invasion. MARCKS was positively associated with levels of T follicular helper cells (TFH) (R = .48, p < .001), T helper type 2 (Th2) cells (R = .47, p < .001), macrophages (R = .41, p ≤ .001), T helper cells (R = .40, p < .001), T helper type 1 (Th1) cells (R = .38, p < .001), T cells (R = .34, p < .001), NK CD56bright cells (R = .34, p < .001) and immature DC (iDC) (R = .33, p < .001), and negatively associated with levels of T helper 17 (Th17) cells. Also, MARCKS may influence the M2 polarization and immune escape.<br><br>CONCLUSION: The present study suggests that MARCKS on TAMs is associated with poor prognosis and immune cell infiltration in HCC.}, }
@article {pmid34278746, year = {2021}, author = {Qi, H and Schmöhl, F and Li, X and Qian, X and Tabler, CT and Bennewitz, K and Sticht, C and Morgenstern, J and Fleming, T and Volk, N and Hausser, I and Heidenreich, E and Hell, R and Nawroth, PP and Kroll, J}, title = {Reduced Acrolein Detoxification in akr1a1a Zebrafish Mutants Causes Impaired Insulin Receptor Signaling and Microvascular Alterations.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2101281}, doi = {10.1002/advs.202101281}, pmid = {34278746}, issn = {2198-3844}, support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; IRTG1874/2 DIAMICOM//Deutsche Forschungsgemeinschaft/ ; CSC 201806230275//China Scholarship Council/ ; 81800390//National Natural Science Foundation of China/ ; }, abstract = {Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a-/- zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a-/- larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. Akr1a1a-/- larvae display impaired glucose homeostasis and angiogenic retina hyaloid vasculature, which are caused by reduced acrolein detoxification ability and increased internal ACR concentration. The effects of acrolein on hyaloid vasculature can be reversed by acrolein-scavenger l-carnosine treatment. In adult akr1a1a-/- mutants, impaired glucose tolerance accompanied by angiogenic retina vessels and glomerular basement membrane thickening, consistent with an early pathological appearance in diabetic retinopathy and nephropathy, are observed. Thus, the data strongly suggest impaired ACR detoxification and elevated ACR concentration as biomarkers and inducers for diabetes and diabetic complications.}, }
@article {pmid33835493, year = {2021}, author = {Nash, Y and Ganoth, A and Borenstein-Auerbach, N and Levy-Barazany, H and Goldsmith, G and Kopelevich, A and Pozyuchenko, K and Sakhneny, L and Lazdon, E and Blanga-Kanfi, S and Alhadeff, R and Benromano, T and Landsman, L and Tsfadia, Y and Frenkel, D}, title = {From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {5}, pages = {e21374}, doi = {10.1096/fj.201901945R}, pmid = {33835493}, issn = {1530-6860}, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Diabetes Mellitus, Experimental/etiology/pathology/*therapy ; Diabetes Mellitus, Type 1/etiology/pathology/*therapy ; Diabetes Mellitus, Type 2/etiology/pathology/*therapy ; Enzyme Inhibitors/administration &amp; dosage ; Female ; Herpesvirus 3, Human/physiology ; Insulin/*metabolism ; Insulysin/*antagonists &amp; inhibitors/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Peptide Fragments/*administration &amp; dosage ; Viral Envelope Proteins/*metabolism ; }, abstract = {Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin-related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro-inflammatory profile of CD4+ T-cells toward insulin. Together, we propose a potential role of a designed VZV-derived peptide to serve as a selectively-targeted and as an efficient diabetes therapy.}, }
@article {pmid33336932, year = {2021}, author = {Liang, RB and Yu, K and Wu, JL and Liu, JX and Lin, Q and Li, B and Zhang, YQ and Ge, QM and Li, QY and Shu, HY and Shao, Y}, title = {Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma.}, journal = {Cancer medicine}, volume = {10}, number = {3}, pages = {824-832}, pmid = {33336932}, issn = {2045-7634}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/metabolism/*pathology/surgery ; Case-Control Studies ; Eye Neoplasms/epidemiology/metabolism/*secondary/surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p < 0.001, p < 0.001, p = 0.038, respectively). In the single risk factor ROC analysis, cutoff values of CA153, ApoA1, and Hb were 43.3 u/mL (CI: 0.966-0.984, p < 0.001), 1.11 g/L (CI: 0.923-0.951, p < 0.001), and 112 g/L (CI: 0.815-0.857, p < 0.001), respectively. Among the ROC curves of combined risk factors, CA153+ApoA1+Hb had the best accuracy, with the sensitivity and specificity of 89.47% and 99.32%, respectively (CI: 0.964-0.983, p < 0.001). CA153, ApoA1, and Hb are risk factors for OM in IDC. In clinical practice, the three parameters could be used as predictive factors for the early detection of OM.}, }
@article {pmid33605547, year = {2021}, author = {Xu, F and Gao, Y and Diao, X and Li, J and Jiang, H and Zhao, H}, title = {Diagnostic value of sialyl-Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge.}, journal = {Cancer medicine}, volume = {10}, number = {5}, pages = {1783-1790}, pmid = {33605547}, issn = {2045-7634}, mesh = {Adult ; Antigens, Tumor-Associated, Carbohydrate/*analysis ; Biomarkers, Tumor/analysis ; Biopsy ; Breast/immunology/pathology ; Breast Neoplasms/complications/*immunology/pathology ; Carcinoma, Ductal, Breast/complications/*immunology/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*immunology/pathology ; Confidence Intervals ; Female ; Humans ; Hyperplasia/immunology/pathology ; Immunohistochemistry ; Logistic Models ; Nipple Discharge/*immunology ; Odds Ratio ; Papilloma, Intraductal/complications/*immunology/pathology ; Receptor, ErbB-2/analysis ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Mucin-associated sialyl-Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease.<br><br>METHODS: PND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions.<br><br>RESULTS: PND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2-positive IDC (p = 0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p = 0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p = 0.037) were statistically significant independent risk factors for malignant PND.<br><br>CONCLUSIONS: Mucin-associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.}, }
@article {pmid34204158, year = {2021}, author = {Itani, MM and Nassar, FJ and Tfayli, AH and Talhouk, RS and Chamandi, GK and Itani, ARS and Makoukji, J and Boustany, RN and Hou, L and Zgheib, NK and Nasr, RR}, title = {A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer.}, journal = {International journal of molecular sciences}, volume = {22}, number = {11}, pages = {}, pmid = {34204158}, issn = {1422-0067}, support = {R. NASR Grant//Lebanese National Council for Scientific Research (CNRS-L)/ ; R NASR proposal//Medical Practice Plan, AUB/ ; R Nasr proposal//Northwestern University Kiphart award/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood/*genetics ; Breast Neoplasms/*blood/*diagnosis/genetics/pathology ; Circulating MicroRNA/*blood/*genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Statistics, Nonparametric ; Young Adult ; }, abstract = {Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.}, }
@article {pmid32920553, year = {2020}, author = {Bartlett, H and Elghobashy, M and Deshmukh, N and Rao, R and Shaaban, AM}, title = {Radiation-Associated Primary Osteosarcoma of the Breast.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {87}, number = {5}, pages = {322-326}, doi = {10.1159/000509580}, pmid = {32920553}, issn = {1423-0291}, mesh = {Aged ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/*etiology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Osteosarcoma/*diagnostic imaging/*etiology/surgery ; Radiation Injuries/complications ; Radiotherapy/*adverse effects ; }, abstract = {INTRODUCTION: Non-epithelial primary mammary osteosarcomas are extremely rare. The differentials include metaplastic carcinoma and malignant phyllodes tumour. This is the first published case of primary breast osteosarcoma arising after local radiotherapy.<br><br>CASE PRESENTATION: A 73-year-old female presented with a right-sided breast lump. The same breast had been irradiated 11 years previously for invasive ductal carcinoma. Diagnostic excision revealed a highly cellular, malignant spindle-cell lesion merged with an osteoid matrix and foci of calcification and bone formation. Immunohistochemistry and molecular studies showed no lines of differentiation. Due to the lack of epithelial/glandular differentiation, in situ carcinoma or leaf-like pattern, the diagnosis of post-irradiation osteosarcoma was made. She underwent mastectomy and is disease-free at 8 months of follow-up.<br><br>CONCLUSION: Post-irradiation osteosarcoma should be considered in the differential diagnosis of breast lesions showing malignant osteoid. Extensive sampling and careful search for epithelial differentiation is required to guide management. Complete surgical excision is recommended.}, }
@article {pmid34243714, year = {2021}, author = {Chiong, F and Wasef, MS and Liew, KC and Cowan, R and Tsai, D and Lee, YP and Croft, L and Harris, O and Gwini, SM and Athan, E}, title = {The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.}, journal = {BMC infectious diseases}, volume = {21}, number = {1}, pages = {671}, pmid = {34243714}, issn = {1471-2334}, abstract = {BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB.<br><br>METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality.<br><br>RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups.<br><br>CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.}, }
@article {pmid32662684, year = {2020}, author = {Shan, Z and Liu, L and Shen, J and Hao, H and Zhang, H and Lei, L and Liu, F and Wang, Z}, title = {Enhanced UV Resistance Role of Death Domain-Associated Protein in Human MDA-MB-231 Breast Cancer Cells by Regulation of G2 DNA Damage Checkpoint.}, journal = {Cell transplantation}, volume = {29}, number = {}, pages = {963689720920277}, pmid = {32662684}, issn = {1555-3892}, mesh = {Adult ; Breast Neoplasms/*genetics ; Cell Proliferation ; DNA Damage/*genetics ; Death Domain/*genetics ; Female ; G2 Phase Cell Cycle Checkpoints ; Humans ; Immunohistochemistry/*methods ; Middle Aged ; }, abstract = {PURPOSE: Death domain-associated protein (DAXX) is a multifunctional nuclear protein involved in apoptosis, transcription, deoxyribonucleic acid damage response, and tumorigenesis. However, the role of DAXX in breast cancer development and progression remains elusive. In this study, we examined the expression patterns and function of DAXX in human breast cancer samples and cell lines.<br><br>METHODS: Immunohistochemistry was used to analyze the expression and localization patterns of DAXX. Additionally, we investigated whether DAXX played an intrinsic role in the cellular response to damage induced by ultraviolet (UV) irradiation in MDA-MB-231 breast cancer cells (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma).<br><br>RESULTS: Our results showed that nucleus size, chromatin organization, and DAXX localization were altered in breast cancer tissues compared with those in control tissues. Compared with cytoplasmic and nuclear expression in benign breast tissues, DAXX was colocalized with promyelocytic leukemia in nuclei with a granular distribution. Endogenous DAXX messenger ribonucleic acid levels were upregulated upon UV radiation in MDA-MB-231 cells. DAXX-deficient cells tended to be more sensitive to irradiation than control cells. Conversely, DAXX-overexpressing cells exhibited reduced phosphorylated histone H2AX (γ-H2AX) accumulation, increased cell survival, and resistance to UV-induced damage. The protective effects of DAXX may be related to the activation of the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (ATM-CHK2)-cell division cycle 25c (CDC25c) signaling pathways in Gap2/Mitosis (G2/M) checkpoint and ultimately cell cycle arrest at G2/M phase.<br><br>CONCLUSIONS: Taken together, these results suggested that DAXX may be an essential component in breast cancer initiation, malignant progression, and radioresistance.}, }
@article {pmid34188137, year = {2021}, author = {Mayopoulos, GA and Ein-Dor, T and Li, KG and Chan, SJ and Dekel, S}, title = {COVID-19 positivity associated with traumatic stress response to childbirth and no visitors and infant separation in the hospital.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13535}, pmid = {34188137}, issn = {2045-2322}, support = {R21 HD100817/HD/NICHD NIH HHS/United States ; R21HD100817//National Institute of Child Health and Human Development/ ; }, mesh = {Adult ; Anxiety/diagnosis ; Birth Weight ; COVID-19/diagnosis/*psychology/virology ; Female ; Hospitals ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Pain/pathology ; Parturition/*psychology ; Patient Admission/statistics &amp; numerical data ; Pregnancy ; Pregnant Women/*psychology ; SARS-CoV-2/isolation &amp; purification ; Stress Disorders, Post-Traumatic/*diagnosis ; Stress, Psychological ; Surveys and Questionnaires ; }, abstract = {As the novel coronavirus (COVID-19) has spread globally, a significant portion of pregnant and delivering women were infected with COVID-19. While emerging studies examined birth outcomes in COVID-19 positive women, knowledge of the psychological experience of childbirth and maternal wellness remains lacking. This matched-control survey-based study included a sample of women recruited during the first wave of the pandemic in the US who gave birth in the previous six months. Women reporting confirmed/suspected COVID-19 (n = 68) during pregnancy or childbirth were matched on background factors with women reporting COVID-19 negativity (n = 2,276). We found nearly 50% of COVID positive women endorsed acute traumatic stress symptoms at a clinical level in response to childbirth. This group was more than twice as likely to endorse acute stress and to have no visitors during maternity hospitalization than COVID negative women; they were also less likely to room-in with newborns. The COVID positive group reported higher levels of pain in delivery, lower newborn weights, and more infant admission to neonatal intensive care units. Our findings suggest COVID-19 affected populations are at increased risk for traumatic childbirth and associated risk for psychiatric morbidity. Attention to delivering women's wellbeing is warranted during the pandemic.}, }
@article {pmid34142156, year = {2021}, author = {Nakamura, T and Okabe, K and Hirayama, S and Chirifu, M and Ikemizu, S and Morioka, H and Nakabeppu, Y and Yamagata, Y}, title = {Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkab492}, pmid = {34142156}, issn = {1362-4962}, abstract = {Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.}, }
@article {pmid34096509, year = {2021}, author = {Badak, B and Aykanat, NEB and Kacar, S and Sahinturk, V and Arik, D and Canaz, F}, title = {Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.}, journal = {Annali italiani di chirurgia}, volume = {10}, number = {}, pages = {}, pmid = {34096509}, issn = {2239-253X}, abstract = {BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell.<br><br>MATERIAL METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method.<br><br>RESULT: 250 μM astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients.<br><br>CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results.<br><br>KEY WORDS: Breast, cancer, metastasis.}, }
@article {pmid34031394, year = {2021}, author = {Amit, I and Iancu, O and Levy-Jurgenson, A and Kurgan, G and McNeill, MS and Rettig, GR and Allen, D and Breier, D and Ben Haim, N and Wang, Y and Anavy, L and Hendel, A and Yakhini, Z}, title = {CRISPECTOR provides accurate estimation of genome editing translocation and off-target activity from comparative NGS data.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3042}, pmid = {34031394}, issn = {2041-1723}, mesh = {Algorithms ; *CRISPR-Cas Systems ; Computational Biology/*methods ; DNA-Binding Proteins/genetics ; Gene Editing/*methods ; HEK293 Cells ; Homeodomain Proteins/genetics ; Humans ; Nuclear Proteins/genetics ; Software ; Transcription Factors/genetics ; }, abstract = {Controlling off-target editing activity is one of the central challenges in making CRISPR technology accurate and applicable in medical practice. Current algorithms for analyzing off-target activity do not provide statistical quantification, are not sufficiently sensitive in separating signal from noise in experiments with low editing rates, and do not address the detection of translocations. Here we present CRISPECTOR, a software tool that supports the detection and quantification of on- and off-target genome-editing activity from NGS data using paired treatment/control CRISPR experiments. In particular, CRISPECTOR facilitates the statistical analysis of NGS data from multiplex-PCR comparative experiments to detect and quantify adverse translocation events. We validate the observed results and show independent evidence of the occurrence of translocations in human cell lines, after genome editing. Our methodology is based on a statistical model comparison approach leading to better false-negative rates in sites with weak yet significant off-target activity.}, }
@article {pmid34016966, year = {2021}, author = {Georgiadi, A and Lopez-Salazar, V and Merahbi, RE and Karikari, RA and Ma, X and Mourão, A and Klepac, K and Bühler, L and Alfaro, AJ and Kaczmarek, I and Linford, A and Bosma, M and Shilkova, O and Ritvos, O and Nakamura, N and Hirose, S and Lassi, M and Teperino, R and Machado, J and Scheideler, M and Dietrich, A and Geerlof, A and Feuchtinger, A and Blutke, A and Fischer, K and Müller, TD and Kessler, K and Schöneberg, T and Thor, D and Hornemann, S and Kruse, M and Nawroth, P and Pivovarova-Ramich, O and Pfeiffer, AFH and Sattler, M and Blüher, M and Herzig, S}, title = {Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2999}, pmid = {34016966}, issn = {2041-1723}, mesh = {3T3-L1 Cells ; Adipocytes/metabolism ; Adipose Tissue, White/cytology/*metabolism ; Adolescent ; Adult ; Aged ; Animals ; CHO Cells ; Cohort Studies ; Cricetulus ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood/metabolism/prevention &amp; control ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Female ; Gene Knockdown Techniques ; Glucose/metabolism ; HEK293 Cells ; Hep G2 Cells ; Humans ; Insulin/metabolism ; Insulin Resistance ; Islets of Langerhans/metabolism ; Liver/metabolism ; Male ; Membrane Proteins/administration &amp; dosage/blood/genetics/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; NIH 3T3 Cells ; Prediabetic State/blood/drug therapy/etiology/*metabolism ; Primary Cell Culture ; Proteins/analysis/*metabolism ; Receptors, G-Protein-Coupled/blood/genetics/*metabolism ; Recombinant Fusion Proteins/administration &amp; dosage/genetics/isolation &amp; purification ; Young Adult ; }, abstract = {The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.}, }
@article {pmid34002584, year = {2021}, author = {Lei, S and Zheng, R and Zhang, S and Chen, R and Wang, S and Sun, K and Zeng, H and Wei, W and He, J}, title = {Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030.}, journal = {Cancer biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.20892/j.issn.2095-3941.2020.0523}, pmid = {34002584}, issn = {2095-3941}, support = {2018-I2M-3-003//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2018YFC1315305//National Key Research and Development Program of China/ ; }, abstract = {OBJECTIVE: Breast cancer was the most common cancer and the fifth cause of cancer deaths among women in China in 2015. The evaluation of the long-term incidence and mortality trends and the prediction of the future burden of breast cancer could provide valuable information for developing prevention and control strategies.<br><br>METHODS: The burden of breast cancer in China in 2015 was estimated by using qualified data from 368 cancer registries from the National Central Cancer Registry. Incident cases and deaths in 22 cancer registries were used to assess the time trends from 2000 to 2015. A Bayesian age-period-cohort model was used to project the burden of breast cancer to 2030.<br><br>RESULTS: Approximately 303,600 new cases of breast cancer (205,100 from urban areas and 98,500 from rural areas) and 70,400 breast cancer deaths (45,100 from urban areas and 24,500 from rural areas) occurred in China in 2015. Urban regions of China had the highest incidence and mortality rates. The most common histological subtype of breast cancer was invasive ductal carcinoma, followed by invasive lobular carcinoma. The age-standardized incidence and mortality rates increased by 3.3% and 1.0% per year during 2000-2015, and were projected to increase by more than 11% until 2030. Changes in risk and demographic factors between 2015 and 2030 in cases are predicted to increase by approximately 13.3% and 22.9%, whereas deaths are predicted to increase by 13.1% and 40.9%, respectively.<br><br>CONCLUSIONS: The incidence and mortality of breast cancer continue to increase in China. There are no signs that this trend will stop by 2030, particularly in rural areas. Effective breast cancer prevention strategies are therefore urgently needed in China.}, }
@article {pmid34001921, year = {2021}, author = {Hosio, M and Urpilainen, E and Hautakoski, A and Marttila, M and Arffman, M and Sund, R and Ahtikoski, A and Puistola, U and Läärä, E and Karihtala, P and Jukkola, A}, title = {Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {10445}, pmid = {34001921}, issn = {2045-2322}, abstract = {We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.}, }
@article {pmid33930678, year = {2021}, author = {Solomon, Z and Ginzburg, K and Ohry, A and Mikulincer, M}, title = {Overwhelmed by the news: A longitudinal study of prior trauma, posttraumatic stress disorder trajectories, and news watching during the COVID-19 pandemic.}, journal = {Social science &amp; medicine (1982)}, volume = {278}, number = {}, pages = {113956}, doi = {10.1016/j.socscimed.2021.113956}, pmid = {33930678}, issn = {1873-5347}, mesh = {*COVID-19 ; Humans ; Israel/epidemiology ; Longitudinal Studies ; Pandemics ; *Prisoners of War ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic/epidemiology/etiology ; *Veterans ; }, abstract = {RATIONALE: It has been recognized that exposure to mass trauma tends to increase the time spent watching television (TV) news. Yet, research on the effects of this tendency on individuals' well-being yielded inconclusive findings.<br><br>OBJECTIVE: The aim of this longitudinal study is to examine the effects of prior trauma and posttraumatic stress disorder (PTSD) on changes in the amount of TV news watching and its effect on subsequent PTSD. More specifically, we examined the interrelations of prior exposure to war captivity, long-term PTSD trajectories, and amount of change TV news watching with PTSD severity during the COVID-19 pandemic, among aging Israeli combat veterans.<br><br>METHODS: One-hundred-and-twenty Israeli ex-prisoners of war (ex-POWs) from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) were followed up at five points of time: 1991 (T1), 2003 (T2), 2008 (T3), 2015 (T4), and in April-May 2020 (T5), during the outbreak of the COVID-19 pandemic.<br><br>RESULTS: Ex-POWs had higher odds of COVID-19 related increase in TV news watching, which, in turn, contributed to PTSD severity at T5. In addition, delayed PTSD trajectory was associated with COVID-19 related increase in TV news watching, which, in turn, contributed to more severe PTSD at T5.<br><br>CONCLUSIONS: These findings highlight the negative implications of TV news watching during a mass trauma for traumatized individuals. More specifically, they demonstrate its potential pathogenic role in exacerbating prior PTSD among trauma survivors.}, }
@article {pmid33927073, year = {2021}, author = {Huang, X and Cai, S and Wu, P and Huang, S and Yao, M}, title = {Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer.}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {46}, number = {3}, pages = {263-271}, doi = {10.11817/j.issn.1672-7347.2021.190371}, pmid = {33927073}, issn = {1672-7347}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnostic imaging/genetics ; Female ; Humans ; Receptor, ErbB-2/genetics ; Receptors, Estrogen ; Receptors, Progesterone ; X-Rays ; }, abstract = {OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer.<br><br>METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed.<br><br>RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67≥20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively).<br><br>CONCLUSIONS: Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.}, }
@article {pmid33921735, year = {2021}, author = {Oprean, CM and Badau, LM and Segarceanu, NA and Ciocoiu, AD and Rivis, IA and Vornicu, VN and Hoinoiu, T and Grujic, D and Bredicean, C and Dema, A}, title = {Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {33921735}, issn = {2075-4418}, abstract = {The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.}, }
@article {pmid33907159, year = {2021}, author = {He, Q and Xue, S and Wa, Q and He, M and Feng, S and Chen, Z and Chen, W and Luo, X}, title = {Mining immune-related genes with prognostic value in the tumor microenvironment of breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {100}, number = {17}, pages = {e25715}, doi = {10.1097/MD.0000000000025715}, pmid = {33907159}, issn = {1536-5964}, support = {No. 81572769, No. 81372238//National Natural Science Foundation of China/ ; 2016ZDXM006//Natural Science Foundation of Chongqing (CN)/ ; No. 20PJ198//Scientific Research Foundation of Health Commission of Sichuan Provinc/ ; }, mesh = {Biomarkers, Tumor/*genetics ; *Breast Neoplasms/genetics/immunology/pathology ; *Carcinoma, Ductal/genetics/immunology/pathology ; Databases, Genetic ; Female ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humans ; Kaplan-Meier Estimate ; Molecular Targeted Therapy/methods ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; *Tumor Microenvironment/genetics/immunology ; }, abstract = {ABSTRACT: The tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable.Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis.Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer.We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.}, }
@article {pmid33863525, year = {2021}, author = {D'Iorio, A and Esposito, M and Maggi, G and Amboni, M and Vitale, C and Santangelo, G}, title = {Neuropsychological correlates of prospective memory: A comparison between tremor-dominant Parkinson's disease and cervical dystonia.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {87}, number = {}, pages = {156-161}, doi = {10.1016/j.jocn.2021.03.006}, pmid = {33863525}, issn = {1532-2653}, mesh = {Aged ; Cognitive Dysfunction/diagnosis/etiology/*psychology ; Executive Function/physiology ; Female ; Humans ; Male ; Memory Disorders/diagnosis/etiology/psychology ; *Memory, Episodic ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/complications/diagnosis/*psychology ; Retrospective Studies ; Torticollis/complications/diagnosis/*psychology ; Tremor/complications/diagnosis/*psychology ; }, abstract = {Cervical Dystonia (CD) and Parkinson's disease, particularly tremor-dominant motor phenotype (TD-PD), showed a selective deficit of time-based prospective memory (TBPM). The two movement disorders are mainly characterized by dysfunctions of basal-ganglia and prefrontal cortex but it is reported that cerebellum also plays a key role in their pathogenesis. These cerebral structures are specifically involved in TBPM rather than in event-based PM (EBPM), but until now no study directly compared these two components of PM between CD and TD-PD patients. Therefore, the present study aimed at investigating if differences in PM functioning between CD and TD-PD patients might exist and if the type of movement disorder moderated the relationship between deficit of PM and deficit of executive functions and retrospective memory. Thirty TD-PD, 27CD patients and 29 healthy subjects (HCs), matched for demographic features, underwent neuropsychological tests for PM, executive functions, retrospective memory and self-rated questionnaires. The three groups did not differ on neuropsychological variables except for TBPM where TD-PD and CD patients performed worse than HCs; moreover, TD-PD performed worse than CD patients. Moderation analysis indicated that the type of movement disorder moderated the relationship between executive dysfunction and TBPM, but not EBPM. In conclusion, selective deficit of TBPM characterizes both CD and TD-PD but it is associated with executive dysfunction only in TD-PD. It might be possible to speculate that the involvement of the cerebellum, responsible for internal timing processes, could explain the impairment of TBPM in both movement disorders. This issue deserves to be explored in future neuroimaging studies.}, }
@article {pmid33850160, year = {2021}, author = {Fayad, R and Rojas, MV and Partisani, M and Finetti, P and Dib, S and Abelanet, S and Virolle, V and Farina, A and Cabaud, O and Lopez, M and Birnbaum, D and Bertucci, F and Franco, M and Luton, F}, title = {EFA6B regulates a stop signal for collective invasion in breast cancer.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2198}, pmid = {33850160}, issn = {2041-1723}, mesh = {Animals ; Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Guanine Nucleotide Exchange Factors/*genetics/*metabolism ; Humans ; Mice ; Mice, Nude ; Transcriptome ; cdc42 GTP-Binding Protein ; }, abstract = {Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.}, }
@article {pmid33824828, year = {2021}, author = {Khanam, R and Fanous, IS and Fadhel, EN and Hyder, T and Brufsky, A}, title = {Voltage-Gated Calcium Channel Antibody-Induced Oropharyngeal Dysphagia Presenting as a Paraneoplastic Neurological Complication in Breast Cancer.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e13677}, pmid = {33824828}, issn = {2168-8184}, abstract = {Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.}, }
@article {pmid33824344, year = {2021}, author = {Kricheli-Katz, T and Regev, T}, title = {The effect of language on performance: do gendered languages fail women in maths?.}, journal = {NPJ science of learning}, volume = {6}, number = {1}, pages = {9}, pmid = {33824344}, issn = {2056-7936}, abstract = {Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.}, }
@article {pmid33818021, year = {2021}, author = {Alyami, H and Yoo, TK and Cheun, JH and Lee, HB and Jung, SM and Ryu, JM and Bae, SJ and Jeong, J and Yoon, CI and Ahn, J and Paik, PS and Cho, MK and Park, WC}, title = {Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.}, journal = {Journal of breast cancer}, volume = {24}, number = {2}, pages = {175-182}, pmid = {33818021}, issn = {1738-6756}, abstract = {PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.<br><br>METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.<br><br>RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.<br><br>CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.}, }
@article {pmid33776732, year = {2021}, author = {Sugimoto, H and Oda, G and Yokoyama, M and Hayashi, K and Yoshino, M and Ogawa, A and Hosoya, T and Nakagawa, T and Uetake, H}, title = {Hydronephrosis Caused by Metastatic Breast Cancer.}, journal = {Case reports in oncology}, volume = {14}, number = {1}, pages = {378-385}, pmid = {33776732}, issn = {1662-6575}, abstract = {Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.}, }
@article {pmid33735776, year = {2021}, author = {Levin, Y and Lev Bar-Or, R and Forer, R and Vaserman, M and Kor, A and Lev-Ran, S}, title = {The association between type of trauma, level of exposure and addiction.}, journal = {Addictive behaviors}, volume = {118}, number = {}, pages = {106889}, doi = {10.1016/j.addbeh.2021.106889}, pmid = {33735776}, issn = {1873-6327}, mesh = {*Alcoholism ; *Behavior, Addictive/epidemiology ; Checklist ; Humans ; Risk Factors ; *Substance-Related Disorders/epidemiology ; }, abstract = {Exposure to trauma is considered a risk factor for the development of addictive disorders. Currently, there is a knowledge gap concerning specific links between types and levels of exposure to traumatic events and addiction.In this study we explored the associations between interpersonal trauma and risk of addictive behaviors, stratified by type of trauma (physical, weapon, sexual assault, and combat) and level of exposure (direct/indirect), focusing on a wide range of substances and behaviors. Data from an online representative sample of 4025 respondents were collected, including the Life Events Checklist (LEC-5), substance use disorders and behavioral addictions metrics, and sociodemographic data. Substantial differences were found between specific types of trauma and risk of addiction. Among those exposed to sexual assault, the risk of alcohol use disorder was found to 15.4%, 95%CI[14.4-16.4%], compared to 12.1%,95%CI[11.3-12.8] among those exposed to combat-related trauma. Both direct and indirect exposure to trauma were found to be significantly related with risk of addiction. While direct exposure was most highly associated with addictions across several types of trauma, in the case of combat-related trauma, indirect exposure was more highly associated with alcohol and pornography addiction (14.5%,95%CI[13.2-15.8%] and 10.0%, 95%CI[6.3-15.0%], respectively) compared to direct exposure (10.7%,95%CI[9.9-11.6%] and 7.4%, 95%CI[4.7-11.6%], respectively). Our findings emphasize the strong association between all types of trauma and the risk of several specific substance and behavioral addictions. Specifically, the role of indirect exposure to trauma is highlighted.}, }
@article {pmid33730716, year = {2021}, author = {Bar-Or, RL and Kor, A and Jaljuli, I and Lev-Ran, S}, title = {The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.}, journal = {European addiction research}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000513776}, pmid = {33730716}, issn = {1421-9891}, abstract = {INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.<br><br>METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.<br><br>RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).<br><br>CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.}, }
@article {pmid33725931, year = {2021}, author = {Oh, BH and Woo, CG and Lee, YJ and Park, YS}, title = {Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.}, journal = {Medicine}, volume = {100}, number = {11}, pages = {e24373}, doi = {10.1097/MD.0000000000024373}, pmid = {33725931}, issn = {1536-5964}, support = {NRF-2019R1A2C1085809//Chungbuk National University Korea National University Development Project (2020)/ ; }, mesh = {Brain Neoplasms/metabolism/*secondary ; Breast Neoplasms, Male/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.<br><br>PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).<br><br>DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).<br><br>INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions).<br><br>OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.<br><br>LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.}, }
@article {pmid33710293, year = {2021}, author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY}, title = {Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity.}, journal = {JAMA network open}, volume = {4}, number = {3}, pages = {e211785}, pmid = {33710293}, issn = {2574-3805}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*drug therapy/*mortality/pathology ; Carcinoma, Ductal/chemistry/*drug therapy/*mortality/pathology ; Cause of Death ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Young Adult ; }, abstract = {Importance: Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer.<br><br>Objective: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.<br><br>This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020.<br><br>Exposures: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.<br><br>Main Outcomes and Measures: The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments.<br><br>Results: A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001).<br><br>Conclusions and Relevance: The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.}, }
@article {pmid33676449, year = {2021}, author = {Ji, L and Cheng, L and Zhu, X and Gao, Y and Fan, L and Wang, Z}, title = {Risk and prognostic factors of breast cancer with liver metastases.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {238}, pmid = {33676449}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/secondary/therapy ; Chemoradiotherapy, Adjuvant/methods ; Datasets as Topic ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Liver/diagnostic imaging/pathology ; Liver Neoplasms/*epidemiology/secondary/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Prognosis ; Receptor, ErbB-2/analysis/antagonists &amp; inhibitors/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/mortality/*pathology/therapy ; Young Adult ; }, abstract = {BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).<br><br>METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.<br><br>RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001).<br><br>CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.}, }
@article {pmid33663447, year = {2021}, author = {Mills, MN and Walker, C and Thawani, C and Naz, A and Figura, NB and Kushchayev, S and Etame, A and Yu, HM and Robinson, TJ and Liu, J and Vogelbaum, MA and Forsyth, PA and Czerniecki, BJ and Soliman, HH and Han, HS and Ahmed, KA}, title = {Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {223}, pmid = {33663447}, issn = {1471-2407}, mesh = {Ado-Trastuzumab Emtansine/adverse effects/*therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Brain/pathology ; Brain Neoplasms/*secondary ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Necrosis ; *Radiosurgery/adverse effects ; Radiotherapy Dosage ; Receptor, ErbB-2/*analysis ; }, abstract = {BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation.<br><br>METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging.<br><br>RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis.<br><br>CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.}, }
@article {pmid33645934, year = {2021}, author = {Da Costa, I and Belnou, P and Soulier, A and Lapidus, N and Tsai, ES and Bourcier, E and Moisi, L and Sautet, A and Bonnet, F and Lescot, T and Verdonk, F}, title = {Impact of delayed patient flow on surgical outcomes after hip fracture: An observational study.}, journal = {European journal of anaesthesiology}, volume = {38 Suppl 1}, number = {}, pages = {S67-S68}, doi = {10.1097/EJA.0000000000001271}, pmid = {33645934}, issn = {1365-2346}, mesh = {Aged ; Aged, 80 and over ; Female ; France/epidemiology ; Hemorrhage/*epidemiology/etiology ; Hip Fractures/complications/*surgery ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Postoperative Complications/epidemiology ; Recovery of Function/*physiology ; Time Factors ; Time-to-Treatment/*statistics &amp; numerical data ; Treatment Outcome ; }, }
@article {pmid33641217, year = {2021}, author = {Pramod, N and Nigam, A and Basree, M and Mawalkar, R and Mehra, S and Shinde, N and Tozbikian, G and Williams, N and Majumder, S and Ramaswamy, B}, title = {Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.}, journal = {The oncologist}, volume = {26}, number = {6}, pages = {e943-e953}, pmid = {33641217}, issn = {1549-490X}, mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular/genetics/therapy ; Female ; Humans ; Mastectomy, Segmental ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.}, }
@article {pmid33628571, year = {2021}, author = {Sarawagi, A and Maxwell, J}, title = {Chyle Leak after Right Axillary Lymph Node Dissection in a Patient with Breast Cancer.}, journal = {Case reports in surgery}, volume = {2021}, number = {}, pages = {8812315}, pmid = {33628571}, issn = {2090-6900}, abstract = {Background: A female patient was diagnosed with a right-sided chyle leak following right skin sparing mastectomy, axillary lymph node dissection, and immediate tissue expander placement in the setting of invasive ductal carcinoma status post neoadjuvant chemotherapy. Summary. Our patient underwent a level I and II right axillary lymph node dissection followed by an axillary drain placement. On the first postoperative day, a change from serosanguinous to milky fluid in this drain was noted. The patient was diagnosed with a chyle leak based on the milky appearance and elevated triglyceride levels in the fluid. While chyle leaks are rare after an axillary dissection and even rarer to present on the right side, it is a complication of which breast surgeons should be aware. The cause of this complication is thought to be due to injury of the main thoracic duct, its branches, the subclavian duct, or its tributaries. Management is usually conservative; however, awareness of this potential complication even on the right side is of the utmost importance.<br><br>Conclusion: Chyle leaks are an uncommon complication of axillary node dissections and even rarer for them to present on the right side. It can be diagnosed by monitoring the drainage for changes in appearance and volume and by conducting supporting laboratory tests. Conservative management is generally suggested.}, }
@article {pmid33625616, year = {2021}, author = {Chandrika, M and Chua, PJ and Muniasamy, U and Huang, RYJ and Thike, AA and Ng, CT and Tan, PH and Yip, GW and Bay, BH}, title = {Prognostic significance of phosphoglycerate dehydrogenase in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {186}, number = {3}, pages = {655-665}, pmid = {33625616}, issn = {1573-7217}, support = {NMRC/CIRG/1370/2013//National Medical Research Council/ ; }, mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; *Phosphoglycerate Dehydrogenase/genetics ; Prognosis ; Serine ; }, abstract = {PURPOSE: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation.<br><br>METHODS: Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay.<br><br>RESULTS: Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced.<br><br>CONCLUSION: The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.}, }
@article {pmid33621744, year = {2021}, author = {Gupta, V and Agarwal, P and Deshpande, P}, title = {Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer.}, journal = {Annals of diagnostic pathology}, volume = {52}, number = {}, pages = {151722}, doi = {10.1016/j.anndiagpath.2021.151722}, pmid = {33621744}, issn = {1532-8198}, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.<br><br>MATERIALS AND METHODS: A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.<br><br>RESULTS: Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.<br><br>CONCLUSION: A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.<br><br>MICRO ABSTRACT: The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.}, }
@article {pmid33611829, year = {2021}, author = {Huang, D and Zhou, B and Luo, ZZ and Yu, SC and Tang, B}, title = {Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th-17/Treg imbalance via the c-Jun/allograft inflammatory factor 1 axis.}, journal = {The Kaohsiung journal of medical sciences}, volume = {37}, number = {7}, pages = {594-603}, doi = {10.1002/kjm2.12367}, pmid = {33611829}, issn = {2410-8650}, support = {//The Science and Technology Plan of Jiangxi Province Health Committee, Grant/Award Number: 20204366/ ; //The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee, Grant/Award Number: 20181001/ ; 20204366//The Science and Technology Plan of Jiangxi Province Health Committee/ ; 20181001//The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee/ ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder. Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4+ T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.}, }
@article {pmid33581714, year = {2021}, author = {Saeed, U and Uppal, SR and Piracha, ZZ and Rasheed, A and Aftab, Z and Zaheer, H and Uppal, R}, title = {Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy.}, journal = {Virology journal}, volume = {18}, number = {1}, pages = {34}, pmid = {33581714}, issn = {1743-422X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Viral/immunology/*isolation &amp; purification ; COVID-19/*diagnosis/epidemiology/immunology/virology ; COVID-19 Serological Testing/*methods ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; SARS-CoV-2/genetics/immunology/*isolation &amp; purification ; Young Adult ; }, abstract = {Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.}, }
@article {pmid33530236, year = {2021}, author = {Liu, N and Li, S and Jia, J and Qiao, Y and Li, Y}, title = {Advanced breast cancer with cachexia: A case report.}, journal = {Medicine}, volume = {100}, number = {4}, pages = {e24397}, doi = {10.1097/MD.0000000000024397}, pmid = {33530236}, issn = {1536-5964}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*complications/therapy ; Cachexia/etiology/*therapy ; Fatal Outcome ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; }, abstract = {RATIONALE: Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients.<br><br>PATIENT CONCERNS: In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache.<br><br>DIAGNOSES: Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area.<br><br>INTERVENTIONS: The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions.<br><br>OUTCOMES: She became extremely thin, weighing only 50 kg at admission on July 23, 2018. This eventually led to multiple organ failure and death.<br><br>LESSONS: We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.}, }
@article {pmid33495219, year = {2021}, author = {Tewari, SG and Rajaram, K and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Metabolic Survival Adaptations of Plasmodium falciparum Exposed to Sublethal Doses of Fosmidomycin.}, journal = {Antimicrobial agents and chemotherapy}, volume = {65}, number = {4}, pages = {}, pmid = {33495219}, issn = {1098-6596}, support = {R01 AI065853/AI/NIAID NIH HHS/United States ; R01 AI125534/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; }, mesh = {*Antimalarials/therapeutic use ; *Apicoplasts ; *Fosfomycin/analogs &amp; derivatives/pharmacology/therapeutic use ; Humans ; *Malaria, Falciparum/drug therapy ; Plasmodium falciparum/genetics ; }, abstract = {The malaria parasite Plasmodium falciparum contains the apicoplast organelle that synthesizes isoprenoids, which are metabolites necessary for posttranslational modification of Plasmodium proteins. We used fosmidomycin, an antibiotic that inhibits isoprenoid biosynthesis, to identify mechanisms that underlie the development of the parasite's adaptation to the drug at sublethal concentrations. We first determined a concentration of fosmidomycin that reduced parasite growth by ∼50% over one intraerythrocytic developmental cycle (IDC). At this dose, we maintained synchronous parasite cultures for one full IDC and collected metabolomic and transcriptomic data at multiple time points to capture global and stage-specific alterations. We integrated the data with a genome-scale metabolic model of P. falciparum to characterize the metabolic adaptations of the parasite in response to fosmidomycin treatment. Our simulations showed that, in treated parasites, the synthesis of purine-based nucleotides increased, whereas the synthesis of phosphatidylcholine during the trophozoite and schizont stages decreased. Specifically, the increased polyamine synthesis led to increased nucleotide synthesis, while the reduced methyl-group cycling led to reduced phospholipid synthesis and methyltransferase activities. These results indicate that fosmidomycin-treated parasites compensate for the loss of prenylation modifications by directly altering processes that affect nucleotide synthesis and ribosomal biogenesis to control the rate of RNA translation during the IDC. This also suggests that combination therapies with antibiotics that target the compensatory response of the parasite, such as nucleotide synthesis or ribosomal biogenesis, may be more effective than treating the parasite with fosmidomycin alone.}, }
@article {pmid33484951, year = {2021}, author = {Lemmer, IL and Willemsen, N and Hilal, N and Bartelt, A}, title = {A guide to understanding endoplasmic reticulum stress in metabolic disorders.}, journal = {Molecular metabolism}, volume = {47}, number = {}, pages = {101169}, doi = {10.1016/j.molmet.2021.101169}, pmid = {33484951}, issn = {2212-8778}, abstract = {BACKGROUND: The global rise of metabolic disorders, such as obesity, type 2 diabetes, and cardiovascular disease, demands a thorough molecular understanding of the cellular mechanisms that govern health or disease. The endoplasmic reticulum (ER) is a key organelle for cellular function and metabolic adaptation and, therefore disturbed ER function, known as "ER stress," is a key feature of metabolic disorders.<br><br>SCOPE OF REVIEW: As ER stress remains a poorly defined phenomenon, this review provides a general guide to understanding the nature, etiology, and consequences of ER stress in metabolic disorders. We define ER stress by its type of stressor, which is driven by proteotoxicity, lipotoxicity, and/or glucotoxicity. We discuss the implications of ER stress in metabolic disorders by reviewing evidence implicating ER phenotypes and organelle communication, protein quality control, calcium homeostasis, lipid and carbohydrate metabolism, and inflammation as key mechanisms in the development of ER stress and metabolic dysfunction.<br><br>MAJOR CONCLUSIONS: In mammalian biology, ER is a phenotypically and functionally diverse platform for nutrient sensing, which is critical for cell type-specific metabolic control by hepatocytes, adipocytes, muscle cells, and neurons. In these cells, ER stress is a distinct, transient state of functional imbalance, which is usually resolved by the activation of adaptive programs such as the unfolded protein response (UPR), ER-associated protein degradation (ERAD), or autophagy. However, challenges to proteostasis also impact lipid and glucose metabolism and vice versa. In the ER, sensing and adaptive measures are integrated and failure of the ER to adapt leads to aberrant metabolism, organelle dysfunction, insulin resistance, and inflammation. In conclusion, the ER is intricately linked to a wide spectrum of cellular functions and is a critical component in maintaining and restoring metabolic health.}, }
@article {pmid33468810, year = {2020}, author = {Ishihara, S and Kashiwagi, S and Asano, Y and Kawano, Y and Kouhashi, R and Yabumoto, A and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {13}, pages = {2089-2091}, pmid = {33468810}, issn = {0385-0684}, mesh = {Aged ; Axilla ; *Breast Neoplasms/drug therapy ; *Dermatitis/drug therapy/etiology ; Female ; Humans ; Metronidazole ; Trastuzumab/adverse effects ; }, abstract = {Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.}, }
@article {pmid33462507, year = {2021}, author = {Gao, R and Bai, S and Henderson, YC and Lin, Y and Schalck, A and Yan, Y and Kumar, T and Hu, M and Sei, E and Davis, A and Wang, F and Shaitelman, SF and Wang, JR and Chen, K and Moulder, S and Lai, SY and Navin, NE}, title = {Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes.}, journal = {Nature biotechnology}, volume = {39}, number = {5}, pages = {599-608}, pmid = {33462507}, issn = {1546-1696}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA240526/CA/NCI NIH HHS/United States ; T32 CA217789/CA/NCI NIH HHS/United States ; R01 CA236864/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Pancreatic Ductal/*genetics/pathology ; *Clonal Evolution ; DNA Copy Number Variations/*genetics ; Gene Expression Regulation, Neoplastic ; Genomics/trends ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation/genetics ; Single-Cell Analysis ; Transcriptome/*genetics ; Tumor Microenvironment/genetics ; }, abstract = {Single-cell transcriptomic analysis is widely used to study human tumors. However, it remains challenging to distinguish normal cell types in the tumor microenvironment from malignant cells and to resolve clonal substructure within the tumor. To address these challenges, we developed an integrative Bayesian segmentation approach called copy number karyotyping of aneuploid tumors (CopyKAT) to estimate genomic copy number profiles at an average genomic resolution of 5 Mb from read depth in high-throughput single-cell RNA sequencing (scRNA-seq) data. We applied CopyKAT to analyze 46,501 single cells from 21 tumors, including triple-negative breast cancer, pancreatic ductal adenocarcinoma, anaplastic thyroid cancer, invasive ductal carcinoma and glioblastoma, to accurately (98%) distinguish cancer cells from normal cell types. In three breast tumors, CopyKAT resolved clonal subpopulations that differed in the expression of cancer genes, such as KRAS, and signatures, including epithelial-to-mesenchymal transition, DNA repair, apoptosis and hypoxia. These data show that CopyKAT can aid in the analysis of scRNA-seq data in a variety of solid human tumors.}, }
@article {pmid33462216, year = {2021}, author = {Deshpande, D and Agarwal, N and Fleming, T and Gaveriaux-Ruff, C and Klose, CSN and Tappe-Theodor, A and Kuner, R and Nawroth, P}, title = {Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {426}, pmid = {33462216}, issn = {2041-1723}, mesh = {Aged ; Aged, 80 and over ; Animals ; Diabetes Mellitus, Experimental/chemically induced/*complications ; Diabetic Neuropathies/etiology/*pathology ; Female ; Ganglia, Spinal/cytology/pathology ; Humans ; Lysosomes ; Male ; Mice ; Mice, Knockout ; Nociception/*physiology ; Pro-Opiomelanocortin/*deficiency/genetics ; Proteolysis ; Receptors, Opioid, mu/genetics/metabolism ; Sensory Receptor Cells/*pathology ; Streptozocin/toxicity ; }, abstract = {Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) is an endogenous opioid precursor peptide, which plays a protective role against pain. Here, we report dysfunctional POMC-mediated antinociception in sensory neurons in diabetes. In streptozotocin-induced diabetic mice the Pomc promoter is repressed due to increased binding of NF-kB p50 subunit, leading to a loss in basal POMC level in peripheral nerves. Decreased POMC levels are also observed in peripheral nervous system tissue from diabetic patients. The antinociceptive pathway mediated by POMC is further impaired due to lysosomal degradation of μ-opioid receptor (MOR). Importantly, the neuropathic phenotype of the diabetic mice is rescued upon viral overexpression of POMC and MOR in the sensory ganglia. This study identifies an antinociceptive mechanism in the sensory ganglia that paves a way for a potential therapy for diabetic neuropathic pain.}, }
@article {pmid33445940, year = {2020}, author = {Bartovská, Z and Andrle, F and Beran, O and Zlámal, M and Řezáč, D and Murinova, I and Holub, M}, title = {Data from the first wave of Covid-19 from the Central Military Hospital, Prague, Czech Republic.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {69}, number = {4}, pages = {164-171}, pmid = {33445940}, issn = {1210-7913}, mesh = {COVID-19/diagnosis/*epidemiology/therapy ; Czech Republic/epidemiology ; Female ; Hospitals, Military ; Humans ; Male ; Middle Aged ; Retrospective Studies ; United States ; }, abstract = {AIMS: To process data from the first wave of Covid-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected in the Infectious Diseases Clinic (IDC) of the First Faculty of Medicine and Central Military Hospital, Prague. To analyse some clinical, diagnostic and therapeutic aspects of Covid-19 in the context of the Czech Republic and to compare them with the data from the most recent literature.<br><br>PATIENTS AND METHODS: This retrospective study analysed data on patients admitted to the IDC between 12 March 2020 and 5 May 2020. The study cohort included 53 patients with Covid-19, 25 females and 28 males, with an average age of 57 years. The parameters analysed were clinical symptoms, average length of hospital stay, complications, and death. Additional data concerned the age, weight, smoking habits, history of comorbidities, and selected laboratory results. These data were compared between groups of patients differing in severity of the course of Covid-19. Finally, imaging findings, serology results, and therapy outcomes were studied. Statistical analysis was performed using the SigmaStat software.<br><br>RESULTS: Eleven (20.8%) patients had a mild course of the disease, 16 (30.2%) patients had a moderate course, 22 (41.5%) patients had a severe course, and four (7.5%) patients had a critical course. The study patients presented with the following clinical symptoms: fever in 88.5% of cases, cough in 84.6% of cases, difficulty breathing in 77.4% of cases, diarrhoea in 23.1% of cases, chest pain in 17.3% of cases, and anosmia in 11.5% of cases. The average length of hospital stay was eight days. The most common complication was a bacterial superinfection, reported in 17 (32.1%) study patients. The overall case fatality rate for Covid-19 in our study was 5.7%. The average age of the study cohort was 57 years, and patients with a severe course of the disease were of older average age than those with a less severe course of the disease (p < 0.05). The predominant comorbidities were hypertension and diabetes mellitus. The analysis of the baseline laboratory data showed significant differences between the groups of patients differing in severity of the course of Covid-19 in CRP, procalcitonin, and d-dimers but not in lymphocyte count. High resolution computed tomography (HRCT) scan of the lungs was performed in 22 patients, and 21 of them had typical findings for Covid-19. The average MuLBSTA score for Covid-19 pneumonia severity in our study cohort was 11.5 points and was not associated with the severity of the course of the disease. Serology tests were performed in 43 study patients, with 29 (67.4%) of them turning out positive in the first test and other five (11.6%) testing positive when retested. Hydroxychloroquine (HCQ) was given experimentally as monotherapy or in combination with azithromycin (AZI) to 24 (45.3%) patients. Two patients on HCQ therapy also received inosinum pranobexum (isoprinosine) for severe lymphopenia, one patient received convalescent plasma, six patients were given AZI alone, and one patient was treated with inosinum pranobexum alone. Altogether 37.7% of study patients were prescribed other antibiotics for confirmed or suspected bacterial superinfection. Standard clinical and pharmaceutical care was provided to patients with particular focus on the safety of off-label drug use. HCQ was with drawn in three patients due to a prolonged corrected QT interval (QTc).<br><br>CONCLUSIONS: In the first wave of the SARS-CoV-2 epidemic, our study patients showed comorbidities and risk factors which are consistent with the international literature, but the course of the disease was mostly moderate to severe, with a low proportion of critically ill patients and fatal outcomes. As soon as new information became available, new diagnostic and therapeutic options were introduced into routine practice. Based on our experience, we are well prepared for a possible second wave of SARS-CoV-2 in terms of the diagnostics, but the therapeutic options still remain very limited.}, }
@article {pmid33429799, year = {2021}, author = {Karatas, M and Zengel, B and Durusoy, R and Tasli, F and Adibelli, Z and Simsek, C and Uslu, A}, title = {Clinicopathologic features of single bone metastasis in breast cancer.}, journal = {Medicine}, volume = {100}, number = {1}, pages = {e24164}, doi = {10.1097/MD.0000000000024164}, pmid = {33429799}, issn = {1536-5964}, mesh = {Adult ; Aged ; Bone Neoplasms/*classification/pathology ; Bone and Bones/*pathology/physiopathology ; Breast Neoplasms/*complications ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis/*physiopathology ; }, abstract = {ABSTRACT: The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.}, }
@article {pmid33402291, year = {2021}, author = {Mnejja, M and Kallel, S and Thabet, W and Regaieg, M and Kallel, R and Boudawara, T and Daoud, J and Hammami, B and Charfeddine, I}, title = {[Ductal carcinomas of the parotid gland].}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {25}, number = {2}, pages = {155-160}, doi = {10.1016/j.canrad.2020.06.034}, pmid = {33402291}, issn = {1769-6658}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery ; Carcinoma, Ductal, Breast/pathology/secondary ; Facial Nerve/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neck Dissection/statistics &amp; numerical data ; Neoplasm Invasiveness ; Parotid Gland/diagnostic imaging/surgery ; Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery ; Prognosis ; Retrospective Studies ; Skin Neoplasms/pathology ; }, abstract = {PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland.<br><br>MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed.<br><br>RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression.<br><br>CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.}, }
@article {pmid33391657, year = {2020}, author = {De Pauw, V and Navez, J and Holbrechts, S and Lemaitre, J}, title = {Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {12}, pages = {rjaa535}, pmid = {33391657}, issn = {2042-8812}, abstract = {Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.}, }
@article {pmid33371069, year = {2020}, author = {Yue, L and Wentao, L and Xin, Z and Jingjing, H and Xiaoyan, Z and Na, F and Tonghui, M and Dalin, L}, title = {Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.}, journal = {Medicine}, volume = {99}, number = {51}, pages = {e23406}, doi = {10.1097/MD.0000000000023406}, pmid = {33371069}, issn = {1536-5964}, mesh = {Acrylamides/administration &amp; dosage/*therapeutic use ; Adult ; Aminoquinolines/administration &amp; dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; ErbB Receptors/*genetics/*metabolism ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, ErbB-2/antagonists &amp; inhibitors/metabolism ; }, abstract = {INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs.<br><br>PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2.<br><br>DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed.<br><br>INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy.<br><br>OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months.<br><br>CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.}, }
@article {pmid33356097, year = {2021}, author = {Zhong, S and Wong, HC and Low, HY and Zhao, R}, title = {Phototriggerable Transient Electronics via Fullerene-Mediated Degradation of Polymer:Fullerene Encapsulation Layer.}, journal = {ACS applied materials &amp; interfaces}, volume = {13}, number = {1}, pages = {904-911}, doi = {10.1021/acsami.0c18795}, pmid = {33356097}, issn = {1944-8252}, abstract = {Transient electronics is an emerging class of electronics that has attracted a lot of attention because of its potential as an environmental-friendly alternative to the existing end-of-life product disposal or treatments. However, the controlled degradation of transient electronics under environmentally benign conditions remains a challenge. In this work, the tunable degradation of transient electronics including passive resistor devices and active memory devices was realized by photodegradable thin polymer films comprising fullerene derivatives, [6,6]-phenyl-C61-butyric acid methyl esters (PCBM). The photodegradation of polymer:PCBM under an aqueous environment is triggered by ultraviolet (UV) light. Experimental results demonstrate that the addition of PCBM in commodity polymers, including but not limited to polystyrene, results in a catalytic effect on polymer photodegradation when triggered by UV light. The degradation mechanism of transient electronics is ascribed to the photodegradation of polymer:PCBM encapsulation layers caused by the synergistic effect between UV and water exposure. The polymer:PCBM encapsulation system presented herein offers a simple way to achieve the realization of light-triggered device degradation for bioapplication and expands the material options for tailorable degradation of transient electronics.}, }
@article {pmid33342987, year = {2020}, author = {Shinseki, K and Takahashi, M and Kushima, A and Nakamoto, T and Wakata, M and Nakajima, T and Toda, T and Ito, K and Fujibayashi, M}, title = {[One Case of Accessory Breast Cancer Complicated by Contralateral Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {12}, pages = {1703-1705}, pmid = {33342987}, issn = {0385-0684}, mesh = {Axilla ; *Breast Diseases ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/complications/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.}, }
@article {pmid33331427, year = {2020}, author = {Bertoldi, AS and Guetter, CR and Coltro, GA and Vosgerau, LM and Brighenti, LMV and Fauat, NI and Kubrusly, FB and Marques, CAM and Kubrusly, LF}, title = {CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.}, journal = {Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery}, volume = {33}, number = {3}, pages = {e1525}, pmid = {33331427}, issn = {2317-6326}, mesh = {Adrenergic beta-Antagonists/*administration &amp; dosage ; Animals ; Antihypertensive Agents/*administration &amp; dosage ; Carvedilol/*administration &amp; dosage ; Esophageal and Gastric Varices/complications/prevention &amp; control ; Gastrointestinal Hemorrhage/etiology/*prevention &amp; control ; Hypertension, Portal/*complications ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy.<br><br>AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model.<br><br>METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days.<br><br>RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups.<br><br>CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.}, }
@article {pmid33329538, year = {2020}, author = {Niespolo, C and Johnston, JM and Deshmukh, SR and Satam, S and Shologu, Z and Villacanas, O and Sudbery, IM and Wilson, HL and Kiss-Toth, E}, title = {Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {574046}, pmid = {33329538}, issn = {1664-3224}, support = {PG/16/44/32146/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {3' Untranslated Regions ; Animals ; Binding Sites ; Cell Line, Tumor ; Cytokines/*metabolism ; Gene Expression Regulation ; Humans ; Inflammation ; Interleukin-8/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology ; Macrophages/*metabolism ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Phenotype ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Protein-Serine-Threonine Kinases/*antagonists &amp; inhibitors/genetics/metabolism/physiology ; RNA, Messenger/genetics/metabolism ; }, abstract = {The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate TRIB1 itself remain elusive. Here, we show that the long and conserved 3'untranslated region (3'UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple "high confidence" miRNAs potentially binding to the 3'UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3'UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.}, }
@article {pmid33328559, year = {2020}, author = {Wu, SG and Yang, SP and Zhang, WW and Wang, J and Lian, CL and Chen, YX and He, ZY}, title = {The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {22070}, pmid = {33328559}, issn = {2045-2322}, mesh = {Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; Survival Rate ; }, abstract = {The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.}, }
@article {pmid33316685, year = {2021}, author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY}, title = {Pathologic response rates for breast cancer stages as a predictor of outcomes in patients receiving neoadjuvant chemotherapy followed by breast-conserving surgery.}, journal = {Surgical oncology}, volume = {36}, number = {}, pages = {91-98}, doi = {10.1016/j.suronc.2020.11.015}, pmid = {33316685}, issn = {1879-3320}, abstract = {PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.<br><br>PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients' PRRs; other independent predictors were controlled for or stratified in the analysis.<br><br>RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13-0.56), 0.36 (0.15-0.85), and 0.15 (0.08-0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35-0.89), 0.91 (0.62-0.96), and 0.63 (0.43-0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06-2.24), 1.08 (1.03-1.82), and 1.19 (1.07-2.01) for all-cause mortality, LRR, and DM, respectively.<br><br>CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.}, }
@article {pmid33302909, year = {2020}, author = {Desa, DE and Strawderman, RL and Wu, W and Hill, RL and Smid, M and Martens, JWM and Turner, BM and Brown, EB}, title = {Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {1217}, pmid = {33302909}, issn = {1471-2407}, support = {R21 CA208921/CA/NCI NIH HHS/United States ; W81XWH-15-1-0040//U.S. Department of Defense/ ; W81XWH-17-1-0011//U.S. Department of Defense/ ; R21CA208921//Foundation for the National Institutes of Health/ ; }, mesh = {Breast Neoplasms/chemistry/*ultrastructure ; Carcinoma, Ductal, Breast/chemistry/secondary/*ultrastructure ; *Estrogens ; Female ; Fibrillar Collagens/*ultrastructure ; Humans ; Image Processing, Computer-Assisted ; *Neoplasm Metastasis ; Neoplasm Proteins/*ultrastructure ; Neoplasms, Hormone-Dependent/chemistry/*ultrastructure ; Prognosis ; Risk ; *Second Harmonic Generation Microscopy ; Single-Blind Method ; Stromal Cells/chemistry/ultrastructure ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Metastases are the leading cause of breast cancer-related deaths. The tumor microenvironment impacts cancer progression and metastatic ability. Fibrillar collagen, a major extracellular matrix component, can be studied using the light scattering phenomenon known as second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time (MFS). Here we assess the effects of heterogeneity in the tumor matrix on the possible use of F/B as a prognostic tool.<br><br>METHODS: SHG imaging was performed on sectioned primary tumor excisions from 95 untreated, estrogen receptor-positive, lymph node negative invasive ductal carcinoma patients. We identified two distinct regions whose collagen displayed different average F/B values, indicative of spatial heterogeneity: the cellular tumor bulk and surrounding tumor-stroma interface. To evaluate the impact of heterogeneity on F/B's prognostic ability, we performed SHG imaging in the tumor bulk and tumor-stroma interface, calculated a 21-gene recurrence score (surrogate for OncotypeDX®, or S-ODX) for each patient and evaluated their combined prognostic ability.<br><br>RESULTS: We found that F/B measured in tumor-stroma interface, but not tumor bulk, is prognostic of MFS using three methods to select pixels for analysis: an intensity threshold selected by a blinded observer, a histogram-based thresholding method, and an adaptive thresholding method. Using both regression trees and Random Survival Forests for MFS outcome, we obtained data-driven prediction rules that show F/B from tumor-stroma interface, but not tumor bulk, and S-ODX both contribute to predicting MFS in this patient cohort. We also separated patients into low-intermediate (S-ODX < 26) and high risk (S-ODX ≥26) groups. In the low-intermediate risk group, comprised of patients not typically recommended for adjuvant chemotherapy, we find that F/B from the tumor-stroma interface is prognostic of MFS and can identify a patient cohort with poor outcomes.<br><br>CONCLUSIONS: These data demonstrate that intratumoral heterogeneity in F/B values can play an important role in its possible use as a prognostic marker, and that F/B from tumor-stroma interface of primary tumor excisions may provide useful information to stratify patients by metastatic risk.}, }
@article {pmid33278619, year = {2021}, author = {Hadano, Y and Kakuma, T and Matsumoto, T and Ishibashi, K and Isoda, M and Yasunaga, H}, title = {Reduction of 30-day death rates from Staphylococcus aureus bacteremia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {103}, number = {}, pages = {308-315}, doi = {10.1016/j.ijid.2020.11.199}, pmid = {33278619}, issn = {1878-3511}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/microbiology/mortality ; Case Management ; Female ; Hospitals ; Humans ; Japan ; Male ; Middle Aged ; *Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Specialization ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/*drug effects ; Treatment Outcome ; }, abstract = {OBJECTIVES: Most Japanese hospitals need to keep to higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximize the effect of these QCIs with only a small number of infectious disease specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious disease consultations (IDCs).<br><br>METHODS: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalized structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB.<br><br>RESULTS: A total of 114 patients with SAB were analyzed. The 30-day all-cause mortality differed significantly between the two periods (17.3% vs. 4.8%, P = 0.02). Age, three-QCI point ≥ 1, and Pitt bacteremia score ≥ 3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs.<br><br>CONCLUSION: Mandatory IDCs for SAB improved 30-day mortality and adherence to QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.}, }
@article {pmid33251496, year = {2020}, author = {Li, X and Schmöhl, F and Qi, H and Bennewitz, K and Tabler, CT and Poschet, G and Hell, R and Volk, N and Poth, T and Hausser, I and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J}, title = {Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish.}, journal = {iScience}, volume = {23}, number = {12}, pages = {101763}, pmid = {33251496}, issn = {2589-0042}, abstract = {Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b -/- mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b -/- embryos. Akr1a1b -/- mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b -/- mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis.}, }
@article {pmid33247280, year = {2020}, author = {Puzis, R and Farbiash, D and Brodt, O and Elovici, Y and Greenbaum, D}, title = {Increased cyber-biosecurity for DNA synthesis.}, journal = {Nature biotechnology}, volume = {38}, number = {12}, pages = {1379-1381}, pmid = {33247280}, issn = {1546-1696}, mesh = {*Computer Security ; DNA/*biosynthesis ; Genetic Engineering ; Plasmids/genetics ; }, }
@article {pmid33243732, year = {2020}, author = {Xu, X and Wang, J and Yan, C and Men, Y and Jiang, H and Fang, H and Xu, X and Yang, J}, title = {[Association of JMJD3, MMP-2 and VEGF expressions with clinicopathological features of invasive ductal breast carcinoma].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {40}, number = {11}, pages = {1593-1600}, pmid = {33243732}, issn = {1673-4254}, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A ; }, abstract = {OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.<br><br>METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.<br><br>RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue (P < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes (P < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients (P < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (r=-0.569, P < 0.05) and VEGF (r=-0.533, P < 0.05) and a positive correlation between MMP2 and VEGF (r=0.923, P < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.<br><br>CONCLUSIONS: The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.}, }
@article {pmid33239449, year = {2021}, author = {Chen, J and Fleming, T and Katz, S and Dewenter, M and Hofmann, K and Saadatmand, A and Kronlage, M and Werner, MP and Pokrandt, B and Schreiter, F and Lin, J and Katz, D and Morgenstern, J and Elwakiel, A and Sinn, P and Gröne, HJ and Hammes, HP and Nawroth, PP and Isermann, B and Sticht, C and Brügger, B and Katus, HA and Hagenmueller, M and Backs, J}, title = {CaM Kinase II-δ Is Required for Diabetic Hyperglycemia and Retinopathy but Not Nephropathy.}, journal = {Diabetes}, volume = {70}, number = {2}, pages = {616-626}, doi = {10.2337/db19-0659}, pmid = {33239449}, issn = {1939-327X}, mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Diabetes Mellitus, Type 2/genetics/*metabolism ; Diabetic Nephropathies/genetics/*metabolism ; Diabetic Retinopathy/genetics/*metabolism ; Gene Expression ; Hyperglycemia/genetics/*metabolism ; Mice ; Mice, Knockout ; Receptors, Leptin/genetics/metabolism ; }, abstract = {Type 2 diabetes has become a pandemic and leads to late diabetic complications of organs, including kidney and eye. Lowering hyperglycemia is the typical therapeutic goal in clinical medicine. However, hyperglycemia may only be a symptom of diabetes but not the sole cause of late diabetic complications; instead, other diabetes-related alterations could be causative. Here, we studied the role of CaM kinase II-δ (CaMKIIδ), which is known to be activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor-mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we provide evidence for improved insulin sensing with increased glucose transport into skeletal muscle and also reduced hepatic glucose production. Despite normoglycemia, CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy, but diabetic retinopathy was prevented. We also unmasked a retina-specific gene expression signature that might contribute to CaMKII-dependent retinal diabetic complications. These data challenge the clinical concept of normalizing hyperglycemia in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolic signals in different diabetic organs.}, }
@article {pmid33238981, year = {2020}, author = {Huang, Z and Hu, C and Liu, K and Yuan, L and Li, Y and Zhao, C and Hu, C}, title = {Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {1145}, pmid = {33238981}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*secondary/therapy ; Brain Neoplasms/*secondary/therapy ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary/therapy ; Male ; Middle Aged ; *Nomograms ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients.<br><br>METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University.<br><br>RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally.<br><br>CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.}, }
@article {pmid33209168, year = {2020}, author = {Fouhi, ME and Benider, A and Gaëtan, KZA and Mesfioui, A}, title = {[Epidemiological and anatomopathological profile of breast cancer at the Ibn Rochd University Hospital, Casablanca].}, journal = {The Pan African medical journal}, volume = {37}, number = {}, pages = {41}, pmid = {33209168}, issn = {1937-8688}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Delayed Diagnosis ; Female ; Hospitals, University ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {The present study aims to determine the various epidemiological characteristics among newly diagnosed patients with breast cancer in Casablanca during 2018. During that period, 668 cases were collected, the average age was 51.6 years, the female was the most represented with 662 cases (99.1%) and men with 6 cases (0.9%), a sex ratio (M/F) of 0.009. The average age of menopause was 49.8 years and the average age of menarche was 13.5 years, 31.7% had a history of cancer (breast 14.1%, stomach and 9% liver 7%). The average diagnosis delay was 10 months, the thyroid disease was the most represented pathology, the left breast was diagnosed in 50.2% and the right breast in 44.7% and 1.3% in the bilateral location. The most common histological type was invasive ductal carcinoma (73.2%). The vascular and lymphatic invasion was observed in 42.2%, axillary nodes were affected in 71.1% of cases. The histological prognosis (SBR) revealed a predominance of grade II in 55.9% of cases. The Luminal B continues to be the most common phenotype (46%) followed by Triple Negative (15.3%) and Luminal A (14.2%) and HER2 (7.4%). The immediate prognosis is a cause for concern because of delayed diagnosis. It seems urgent to develop the health information policy and education.}, }
@article {pmid33204409, year = {2020}, author = {Missori, G and Serra, F and Prestigiacomo, G and Ricciardolo, AA and Brugioni, L and Gelmini, R}, title = {Case Report: Metastatic breast cancer to the gallbladder.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {343}, pmid = {33204409}, issn = {2046-1402}, mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; *Cholecystitis, Acute/etiology/surgery ; Female ; *Gallbladder Neoplasms/secondary/surgery ; Humans ; }, abstract = {Cholecystitis is one of the leading causes of emergency surgical interventions; the occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. Metastatic breast cancer to the gallbladder is even less frequent; in fact, breast cancer usually metastasizes to bone, lung, lymph nodes, liver and brain. We report the case of an 83-year-old female patient with a previous history of breast surgery with axillary dissection in 1997, followed by adjuvant chemotherapy due to invasive ductal carcinoma of the left breast. The patient was admitted at the emergency department for sepsis and an episode of acute kidney failure, anuria and fever. Right-upper quadrant abdominal pain triggered by food intake and abdominal tenderness was also present, placing the diagnostic suspicion of biliary sepsis due to acute cholecystitis. The histological examination of the surgical specimen highlighted the presence of metastasis from an infiltrating ductal breast carcinoma with positive hormone receptors. We also report here the results of a review of the literature looking at articles describing cases of gallbladder metastasis from breast cancer.}, }
@article {pmid33163280, year = {2020}, author = {Zhang, J and Sun, M and Chang, E and Lu, CY and Chen, HM and Wu, SY}, title = {Pathologic response as predictor of recurrence, metastasis, and survival in breast cancer patients receiving neoadjuvant chemotherapy and total mastectomy.}, journal = {American journal of cancer research}, volume = {10}, number = {10}, pages = {3415-3427}, pmid = {33163280}, issn = {2156-6976}, abstract = {To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the pathologic response (PR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of PR; other independent predictors were controlled for or stratified in the analysis. We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13-0.34), 0.19 (0.08-0.48), and 0.33 (0.23-0.47), respectively, for pCR; 0.56 (0.48-0.65), 0.67 (0.51-0.89), and 0.61 (0.52-0.70), respectively, for AJCC downstaging; and 1.85 (1.56-2.18), 1.17 (0.84-1.62), and 1.61 (1.36-1.90), respectively, for AJCC upstaging. The PR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment.}, }
@article {pmid33148662, year = {2021}, author = {Chen, F and Ding, K and Priedigkeit, N and Elangovan, A and Levine, KM and Carleton, N and Savariau, L and Atkinson, JM and Oesterreich, S and Lee, AV}, title = {Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells.}, journal = {Cancer research}, volume = {81}, number = {2}, pages = {268-281}, doi = {10.1158/0008-5472.CAN-20-0696}, pmid = {33148662}, issn = {1538-7445}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD/genetics/metabolism ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Cadherins/antagonists &amp; inhibitors/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Prognosis ; Single-Cell Analysis/*methods ; *Transcriptome ; Tumor Cells, Cultured ; }, abstract = {Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. SIGNIFICANCE: This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.}, }
@article {pmid33140128, year = {2021}, author = {Chen, XY and Thike, AA and Koh, VCY and Nasir, NDM and Bay, BH and Tan, PH}, title = {Breast ductal Carcinoma in situ associated with microinvasion induces immunological response and predicts ipsilateral invasive recurrence.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {478}, number = {4}, pages = {679-686}, pmid = {33140128}, issn = {1432-2307}, support = {SHF/FG668S/2015//SingHealth Foundation/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention &amp; control ; Prognosis ; Proportional Hazards Models ; }, abstract = {Although microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and established invasive ductal carcinoma, survival outcomes and biological behaviour of DCIS-Mi are still poorly understood. This study investigated the potential influence of Mi on disease-free survival (DFS) and assessed its correlations with clinicopathological parameters, prognosis, molecular, and immune markers. CD4, CD8, forkhead box P3 (FOXP3), CD68, CD163, programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression in pure DCIS and DCIS-Mi, from a cohort of 198 patients, were determined by immunohistochemistry. DFS, clinicopathological parameters, immune markers, and biomarker expression were correlated with presence of Mi. Twelve out of 198 DCIS cases were associated with Mi. DCIS-Mi was significantly linked with ipsilateral invasive recurrence (p = 0.032). Kaplan-Meier analysis revealed that DCIS-Mi had worse DFS for ipsilateral invasive recurrence (p = 0.011) and this was affirmed by multivariate Cox regression analysis (95% CI 1.181-9.010, HR = 3.262, p = 0.023). DCIS-Mi was associated with higher densities of immune infiltrates positive for CD4 (p = 0.037), FOXP3 (p = 0.037), CD163 (p = 0.01), and PD-L1 (p = 0.015). This study demonstrated that DCIS-Mi was correlated with high densities of immune infiltrates and predicted ipsilateral invasive recurrence.}, }
@article {pmid33130707, year = {2020}, author = {Kosaka, Y and Kikuchi, M and Nishimiya, H and Katoh, H and Kawaguchi, R and Araki, N and Shimazu, M and Tsumura, H and Waraya, M and Takada, F and Sengoku, N and Sangai, T}, title = {[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {9}, pages = {1387-1389}, pmid = {33130707}, issn = {0385-0684}, mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Child ; Female ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery ; Humans ; Mastectomy ; }, abstract = {A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy(CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.}, }
@article {pmid33126344, year = {2020}, author = {Liu, C and Wang, C and Du, Z and Xue, H and Liu, Z}, title = {Clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia.}, journal = {Medicine}, volume = {99}, number = {44}, pages = {e22904}, doi = {10.1097/MD.0000000000022904}, pmid = {33126344}, issn = {1536-5964}, mesh = {Age Factors ; Anticarcinogenic Agents/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; China/epidemiology ; Female ; Humans ; Imatinib Mesylate/*therapeutic use ; Incidence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology ; Male ; Middle Aged ; *Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Time Factors ; }, abstract = {This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.}, }
@article {pmid33106505, year = {2020}, author = {Tsai, HT and Huang, CS and Tu, CC and Liu, CY and Huang, CJ and Ho, YS and Tu, SH and Tseng, LM and Huang, CC}, title = {Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18276}, pmid = {33106505}, issn = {2045-2322}, mesh = {Bayes Theorem ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Calcinosis/*diagnosis/genetics ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Taiwan ; Whole Exome Sequencing ; }, abstract = {Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.}, }
@article {pmid33097605, year = {2021}, author = {Kurley, SJ and Tischler, V and Bierie, B and Novitskiy, SV and Noske, A and Varga, Z and Zürrer-Härdi, U and Brandt, S and Carnahan, RH and Cook, RS and Muller, WJ and Richmond, A and Reynolds, AB}, title = {A requirement for p120-catenin in the metastasis of invasive ductal breast cancer.}, journal = {Journal of cell science}, volume = {134}, number = {6}, pages = {}, pmid = {33097605}, issn = {1477-9137}, support = {R01 CA200681/CA/NCI NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P30 HD015052/HD/NICHD NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R01 CA055724/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; R01 CA111947/CA/NCI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; }, abstract = {We report here the effects of targeted p120-catenin (encoded by CTNND1; hereafter denoted p120) knockout (KO) in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment, ultimately leading to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.}, }
@article {pmid33086236, year = {2021}, author = {Bishop, JA and Rooper, LM and Sangoi, AR and Gagan, J and Thompson, LDR and Inagaki, H}, title = {The Myoepithelial Cells of Salivary Intercalated Duct-type Intraductal Carcinoma Are Neoplastic: A Study Using Combined Whole-slide Imaging, Immunofluorescence, and RET Fluorescence In Situ Hybridization.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {4}, pages = {507-515}, doi = {10.1097/PAS.0000000000001605}, pmid = {33086236}, issn = {1532-0979}, mesh = {Aged ; Automation, Laboratory ; *Biomarkers, Tumor/analysis/genetics ; Calcium-Binding Proteins/*analysis ; *Carcinoma, Ductal/chemistry/genetics/pathology ; Female ; *Fluorescent Antibody Technique ; Gene Fusion ; Humans ; Image Interpretation, Computer-Assisted ; *In Situ Hybridization, Fluorescence ; Male ; Microfilament Proteins/*analysis ; Middle Aged ; Predictive Value of Tests ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/chemistry/genetics/pathology ; }, abstract = {Intraductal carcinoma (IDC) is a salivary gland tumor currently believed to be analogous to breast ductal carcinoma in situ, consisting of a complex neoplastic epithelial proliferation surrounded by a continuous layer of myoepithelial cells presumed to be native and non-neoplastic. Recent molecular insights have shown that there are at least 3 different types of IDC: (1) intercalated duct-like, with frequent NCOA4-RET fusions; (2) apocrine, with multiple mutations similar to salivary duct carcinoma; and (3) mixed intercalated duct-like and apocrine with frequent RET fusions, especially TRIM27-RET. Recent observations (eg, IDC occurring in lymph nodes) have challenged the notion that the myoepithelial cells of IDC are non-neoplastic. Five IDCs with known RET fusions by RNA sequencing were retrieved from the authors' archives, including 4 intercalated duct-like IDCs with NCOA4-RET, and 1 mixed intercalated duct-like/apocrine IDC with TRIM27-RET. A panel of immunohistochemistry antibodies (S100 protein, p63 or p40, mammaglobin, smooth muscle actin, calponin, androgen receptor) was tested. To precisely localize RET split-positive cells, each case was subjected to sequential retrieval of whole-slide imaging data of hematoxylin and eosin (HE) staining, immunofluorescence staining for calponin, and fluorescence in situ hybridization (FISH) for RET. Because NCOA4-RET is an inversion difficult to visualize on conventional RET FISH, a novel 3-color FISH technique was utilized to demonstrate it clearly. In all 5 cases, the proliferative ducts were completely surrounded by a layer of myoepithelial cells that were positive for p63 or p40, smooth muscle actin, and calponin. Using combined HE, calponin immunofluorescence, and RET FISH imaging, the positive signals were unmistakably identified in both calponin-negative ductal cells and peripheral, calponin-positive myoepithelial cells in all 5 cases. Utilizing combined HE, calponin immunofluorescence, and RET FISH imaging, we demonstrated that IDCs with RET fusions harbored this alteration in both the ductal and myoepithelial cells. This is compelling evidence that the myoepithelial cells of IDC are not mere bystanders, but are rather a component of the neoplasm itself, similar to other biphasic salivary gland neoplasms like pleomorphic adenoma and epithelial-myoepithelial carcinoma. This finding raises questions about the appropriate terminology, classification, and staging of IDC.}, }
@article {pmid33049657, year = {2020}, author = {Zhang, J and Lu, CY and Qin, L and Chen, HM and Wu, SY}, title = {Breast-conserving surgery with or without irradiation in women with invasive ductal carcinoma of the breast receiving preoperative systemic therapy: A cohort study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {139-147}, pmid = {33049657}, issn = {1532-3080}, abstract = {PURPOSE: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival.<br><br>PATIENTS AND METHODS: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs).<br><br>RESULTS: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2-4) or nodal (ypN2-3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03-0.81), 0.32 (0.16-0.64), 0.43 (0.23-0.79), 0.23 (0.13-0.42), 0.52 (0.20-1.33), and 0.34 (0.13-0.87) in the ypT0, ypT1, ypT2-4, ypN0, ypN1, and ypN2-3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00-4.07), 0.46 (0.26-0.83), 0.18 (0.06-0.51), 0.28 (0.06-1.34), 0.25 (0.10-0.63), 0.47 (0.23-0.88), and 0.32 in the cT0-1, cT2, cT3, cT4, cN0, cN1, and cN2-3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST.<br><br>CONCLUSION: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.}, }
@article {pmid33047834, year = {2021}, author = {Nishimoto, A and Kuwahara, H and Ohashi, R and Ansai, SI}, title = {Multicentric endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report.}, journal = {Journal of cutaneous pathology}, volume = {48}, number = {1}, pages = {165-170}, doi = {10.1111/cup.13896}, pmid = {33047834}, issn = {1600-0560}, abstract = {Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71-year-old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.}, }
@article {pmid33027710, year = {2021}, author = {Thongpiya, J and Sa-Nguanraksa, D and Samarnthai, N and Sarasombath, PT}, title = {Filariasis of the breast caused by Brugia pahangi: A concomitant finding with invasive ductal carcinoma.}, journal = {Parasitology international}, volume = {80}, number = {}, pages = {102203}, pmid = {33027710}, issn = {1873-0329}, mesh = {Animals ; Breast Diseases/*diagnosis/parasitology ; Breast Neoplasms/*pathology ; Brugia pahangi/classification/*isolation &amp; purification ; Carcinoma, Ductal, Breast/*pathology ; DNA, Ribosomal Spacer/analysis ; Female ; Filariasis/*diagnosis/parasitology ; Humans ; Middle Aged ; RNA, Helminth/analysis ; RNA, Ribosomal/analysis ; Thailand ; }, abstract = {Extralymphatic filariasis is an uncommon phenomenon that can be caused by several lymphatic filarial species, including zoonotic filaria of animal origins. In this study, we report a case of a 64-year-old Thai woman who presented with a lump in her left breast that was diagnosed with invasive ductal carcinoma. At the same time, a small nodule was found in her right breast, via imaging study, without any abnormal symptoms. A core needle biopsy of the right breast nodule revealed a filarial-like nematode compatible with the adult stage of Brugia sp. A molecular identification of the nematode partial mt 12rRNA gene and ITS1 suggested the causative species as closely related to Brugia pahangi, a zoonotic lymphatic filaria of animals such as cats and dogs. The sequence of the partial mt 12rRNA and ITS1 gene in this patient was 94% and 99% identical to the previously reported sequence of mt 12rRNA and ITS1 genes of B. pahangi. The sequence of ITS1 gene is 99% similar to B. pahangi microfilaria from infected dogs in Bangkok, which was highly suspected of having a zoonotic origin. As far as we know, this is the first case report of B. pahangi filariasis presented with a breast mass concomitantly found in a patient with invasive ductal carcinoma. This raised serious concern regarding the zoonotic transmission of filariasis from natural animal reservoirs.}, }
@article {pmid33027370, year = {2020}, author = {Gewehr, DM and Salgueiro, GR and Noronha, L and Kubrusly, FB and Kubrusly, LF and Coltro, GA and Preto, PC and Bertoldi, AS and Vieira, HI}, title = {Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.}, journal = {Arquivos brasileiros de cardiologia}, volume = {115}, number = {3}, pages = {480-490}, doi = {10.36660/abc.20190306}, pmid = {33027370}, issn = {1678-4170}, mesh = {Animals ; Humans ; *Hypertension, Pulmonary/chemically induced ; Hypertrophy, Right Ventricular/chemically induced ; Male ; Monocrotaline/toxicity ; *Pulmonary Arterial Hypertension ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.<br><br>OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.<br><br>METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.<br><br>RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).<br><br>CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).}, }
@article {pmid33023170, year = {2020}, author = {Petre, AR and Craciunescu, R and Fratu, O}, title = {Design, Implementation and Simulation of a Fringing Field Capacitive Humidity Sensor.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {19}, pages = {}, pmid = {33023170}, issn = {1424-8220}, support = {51675/09.07.2019, SMIS code 125125//Operational Programme Human Capital of the Ministry of European Funds through the Financial Agreement/ ; 33PCCDI/2018//Ministry of Innovation and Research, UEFISCDI, MultiMonD2 within PNCDI III/ ; }, abstract = {The world population is growing in an accelerated way urging the need for a more efficient and sustainable agricultural industry. Initially developed for smart cities which face the same challenges caused by an increasing population, Internet of Things (IoT) technologies have evolved rapidly over the last few years and are now moving successfully to agriculture. Wireless Sensor Networks (WSNs) have been reported to be used in the agri-food sector and could answer the call for a more optimized agricultural management. This paper investigates a PCB-made interdigited capacitive (IDC) soil humidity sensor as a low-price alternative to the existing ones on the market. An in-depth comparative study is performed on 30 design variations, part of them also manufactured for further investigations. By measurements and simulations, the influence of the aspect ratio and dielectric thickness on the sensitivity and capacitance of the sensor are studied. In the end, a Humidity and Temperature Measurement Wireless Equipment (HTMWE) for IoT agriculture applications is implemented with this type of sensor.}, }
@article {pmid33016589, year = {2019}, author = {Merry, R and Butenhoff, K and Campbell, BW and Michno, JM and Wang, D and Orf, JH and Lorenz, AJ and Stupar, RM}, title = {Identification and Fine-Mapping of a Soybean Quantitative Trait Locus on Chromosome 5 Conferring Tolerance to Iron Deficiency Chlorosis.}, journal = {The plant genome}, volume = {12}, number = {3}, pages = {1-13}, doi = {10.3835/plantgenome2019.01.0007}, pmid = {33016589}, issn = {1940-3372}, mesh = {Genome-Wide Association Study ; Iron/*deficiency ; *Plant Diseases ; Quantitative Trait Loci ; Soybeans/*genetics ; }, abstract = {CORE IDEAS: 'Fiskeby III' harbors a combination of abiotic stress traits, including iron deficiency chlorosis (IDC) tolerance. An IDC quantitative trait locus on chromosome Gm05 was identified in genome-wide association studies and biparental populations. Fine-mapping resolved a 137-kb interval containing strong candidate genes. Iron deficiency chlorosis (IDC) is an important nutrient stress for soybean [Glycine max (L.) Merr.] grown in high-pH soils. Despite numerous agronomic attempts to alleviate IDC, genetic tolerance remains the most effective preventative measure against symptoms. In this study, two association mapping populations and a biparental mapping population were used for genetic mapping of IDC tolerance. Quantitative trait loci (QTLs) were identified on chromosomes Gm03, Gm05, and Gm06. Heterogenous inbred families were developed to fine-map the Gm05 QTL, which was uniquely supported in all three mapping populations. Fine-mapping resulted in a QTL with an interval size of 137 kb on the end of the short arm of Gm05, which produced up to a 1.5-point reduction in IDC severity on a 1 to 9 scale in near isogenic lines.}, }
@article {pmid33011829, year = {2021}, author = {Sadeghalvad, M and Mohammadi-Motlagh, HR and Rezaei, N}, title = {Immune microenvironment in different molecular subtypes of ductal breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {185}, number = {2}, pages = {261-279}, pmid = {33011829}, issn = {1573-7217}, support = {41086//Tehran University of Medical Sciences/ ; }, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/immunology ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; *Immunity, Cellular ; Prognosis ; *Tumor Microenvironment ; }, abstract = {PURPOSE: Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.<br><br>RESULTS: The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR- T cells, and Tγδ cells is related to more immunosuppressive microenvironment, especially in ER- and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER+ BC, although in other subtypes such as TN or HER2+ are associated with a favorable prognosis.<br><br>CONCLUSION: Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.}, }
@article {pmid32995936, year = {2021}, author = {Doello, K and Conde, V and Perez, MC and Mendoza, I and Mesas, C and Prados, J}, title = {Unusual long survival in a case of heterotaxy and polysplenia.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {43}, number = {4}, pages = {607-611}, pmid = {32995936}, issn = {1279-8517}, abstract = {Heterotaxy syndrome with polysplenia is an extremely rare congenital disorder caused by a disruption in the embryonic development that results in an abnormal arrangement of the abdominal and thoracic organs. We present the case of a 59-year-old female patient with invasive ductal carcinoma of the right breast (luminal A type) and CT findings of heterotaxy syndrome with polysplenia. The most remarkable anomalies identified were a left inferior vena cava draining into the hemiazygos vein, absent inferior vena cava at the thoracic level, and hepatic veins directly draining into the right atrium. Moreover, an atrial septal defect was identified, explaining the pulmonary hypertension of unknown cause previously detected in the patient. The relevance of this case lies in the unusual anatomical abnormalities found and the large patient survival, having in to account the great rate of heterotaxy syndrome mortality in the first years of life.}, }
@article {pmid32988889, year = {2020}, author = {Yildirim, E and Bektas, S and Gundogar, O and Findik, D and Alcicek, S and Erdogan, KO and Yildiz, M}, title = {The Relationship of GATA3 and Ki-67 With Histopathological Prognostic Parameters, Locoregional Recurrence and Disease-free Survival in Invasive Ductal Carcinoma of the Breast.}, journal = {Anticancer research}, volume = {40}, number = {10}, pages = {5649-5657}, doi = {10.21873/anticanres.14578}, pmid = {32988889}, issn = {1791-7530}, mesh = {Adult ; Biomarkers, Tumor ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Disease-Free Survival ; Estrogens/genetics ; Female ; GATA3 Transcription Factor/*genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/*genetics ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*genetics/pathology ; Progesterone/genetics ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: In recent years, GATA-binding protein 3 (GATA3) has been indicated as a marker showing good prognosis in breast cancer. In luminal breast cancer, which has good a prognosis, it shows more significant elevation in small-sized and low-grade tumors. In contrast, Ki-67 is defined as a poor prognostic factor. The aim of this study was to emphasise the prognostic importance of GATA3 and the inverse relationship with Ki-67.<br><br>MATERIALS AND METHODS: In our study, 90 patients with invasive ductal breast cancer were immunohistochemically evaluated for Ki-67 and GATA3 expression. The relationship between GATA3 and Ki-67 expression was examined. In addition, the relationship between these two factors with estrogen, progesterone, human epidermal growth factor 2 receptor antibodies and other prognostic parameters such as disease-free survival and local recurrence was investigated. We accepted the level of ≥5% nüclear reaction as positive for GATA 3. A Ki-67 cut-off value of 20% was accepted as positive.<br><br>RESULTS: In GATA3 positive breast cancers, good prognostic parameters were seen including high estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, small tumor size and low histological grade as well as low Ki-67 expression. In breast cancers showing high Ki-67 expression, ER, PR, and GATA3 positivity were lower and there was higher human epidermal growth factor receptor 2 (HER2) positivity and high histological grade while the tumor size was larger.<br><br>CONCLUSION: Our study has revealed that GATA3 has an inverse relationship with Ki-67, whereas it has a positive releationship with good prognostic factors.}, }
@article {pmid32980661, year = {2020}, author = {Lou, B and Boger, M and Bennewitz, K and Sticht, C and Kopf, S and Morgenstern, J and Fleming, T and Hell, R and Yuan, Z and Nawroth, PP and Kroll, J}, title = {Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans.}, journal = {Redox biology}, volume = {37}, number = {}, pages = {101723}, pmid = {32980661}, issn = {2213-2317}, mesh = {*Aldehyde Dehydrogenase/genetics ; Aldehydes ; Animals ; *Diabetes Mellitus ; Gene Knockout Techniques ; Humans ; *Hyperglycemia/genetics ; *Zebrafish/genetics ; }, abstract = {Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1-/- zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1-/- zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l-Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.}, }
@article {pmid32975612, year = {2020}, author = {Yoshida, Y and Matsumoto, I and Tanaka, T and Yamao, K and Hayashi, A and Kamei, K and Satoi, S and Takebe, A and Nakai, T and Takenaka, M and Takeyama, Y}, title = {Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {222}, pmid = {32975612}, issn = {2198-7793}, abstract = {BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.<br><br>CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.<br><br>CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.}, }
@article {pmid32947148, year = {2020}, author = {Zhang, J and Lu, CY and Chen, CH and Chen, HM and Wu, SY}, title = {Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {70-78}, pmid = {32947148}, issn = {1532-3080}, abstract = {PURPOSE: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).<br><br>PATIENTS AND METHODS: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.<br><br>RESULTS: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52-0.81, P < 0.0001) and 0.58 (0.47-0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2-4 (ypT3-4) and postchemotherapy pathologic nodal stages N2-3 (ypN2-3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38-0.69, P < 0.0001), 0.60 (0.40-0.88, P = 0.0096), and 0.64 (0.48-0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0-4, ypN0-3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.<br><br>CONCLUSION: For patients with breast cancer ypT3-4, ypN2-3, or pathologic stages IIIA-IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.}, }
@article {pmid32877689, year = {2020}, author = {Rohm, M and Herzig, S}, title = {An Antibody Attack against Body Wasting in Cancer.}, journal = {Cell metabolism}, volume = {32}, number = {3}, pages = {331-333}, doi = {10.1016/j.cmet.2020.08.003}, pmid = {32877689}, issn = {1932-7420}, mesh = {Adipose Tissue ; Animals ; *Cachexia/etiology ; Growth Differentiation Factor 15 ; Humans ; Mice ; *Neoplasms/complications ; }, abstract = {Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.}, }
@article {pmid32876204, year = {2020}, author = {Salim, TR and Andrade, TM and Klein, CH and Oliveira, GMM}, title = {Inequalities in Mortality Rates from Malformations of Circulatory System Between Brazilian Macroregions in Individuals Younger Than 20 Years.}, journal = {Arquivos brasileiros de cardiologia}, volume = {115}, number = {6}, pages = {1164-1173}, pmid = {32876204}, issn = {1678-4170}, mesh = {Brazil/epidemiology ; *Cardiovascular Diseases ; *Cardiovascular System ; Cause of Death ; Female ; *Heart Defects, Congenital ; Humans ; Male ; Mortality ; }, abstract = {BACKGROUND: Deaths from malformations of the circulatory system (MCS) have a major impact on mortality reduction. given that most cases are avoidable with correct diagnosis and treatment.<br><br>OBJECTIVES: To describe the distribution of mortality from MCS by sex. age. and macroregion in Brazil. in individuals under the age of 20. between 2000 and 2015.<br><br>METHODS: A descriptive study of mortality rates and proportional mortality (PM) from MCS. other congenital malformations (OCM). circulatory system disease (CSD). ill-defined causes (IDC). and external causes (EC) in Brazil.<br><br>RESULTS: There were 1.367.355 deaths from all causes in individuals younger than 20. 55.0% under 1 year of age. A total of 144.057 deaths were caused by congenital malformations. 39% of them by MCS. In both sexes. the annual mortality from MCS was 5.3/100.000. PM from MCS was 4.2%. CSD 2.2%. IDC 6.2% and EC 24.9%. Unspecified MCS showed the highest PM rates in both sexes and age groups. especially in the north and northeast regions (60%). Deaths from malformations occurred 5.7 times more frequently during the first year of life than in other ages (MCS: 5.0; OCM: 6.4).<br><br>CONCLUSIONS: MCS was the leading cause of death among all malformations. being twice as important as CSD. mainly under 1 year of age. The frequency of misdiagnosis of MCS as cause of death was high in all ages and both sexes. especially in the north and northeast regions. These findings highlight the need for the development of public health strategies focused on correct diagnosis and early treatment of congenital cardiopathies. leading to a reduction in mortality. (Arq Bras Cardiol. 2020; 115(6):1164-1173).}, }
@article {pmid32868877, year = {2020}, author = {Murray, AS and Hyland, TE and Sala-Hamrick, KE and Mackinder, JR and Martin, CE and Tanabe, LM and Varela, FA and List, K}, title = {The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy.}, journal = {Oncogene}, volume = {39}, number = {41}, pages = {6421-6436}, pmid = {32868877}, issn = {1476-5594}, support = {R25 GM058905/GM/NIGMS NIH HHS/United States ; F31 CA217148/CA/NCI NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; R01 CA160565/CA/NCI NIH HHS/United States ; R01 CA222359/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use ; Apoptosis/drug effects/genetics ; Breast/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Cell Line, Tumor ; Cell Survival/genetics ; Datasets as Topic ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/drug therapy/genetics/*pathology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Serine Endopeptidases/genetics/*metabolism ; Triple Negative Breast Neoplasms/drug therapy/genetics/*pathology ; }, abstract = {Breast cancer progression is accompanied by increased expression of extracellular and cell-surface proteases capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. The type II transmembrane serine proteases (TTSPs) are a family of cell-surface proteases that play critical roles in numerous types of cancers. Therefore, the aim of this study was to identify novel and uncharacterized TTSPs with differential expression in breast cancer and to determine their potential roles in progression. Systematic in silico data analysis followed by immunohistochemical validation identified increased expression of the TTSP family member, TMPRSS13 (transmembrane protease, serine 13), in invasive ductal carcinoma patient tissue samples compared to normal breast tissue. To test whether loss of TMPRSS13 impacts tumor progression, TMPRSS13 was genetically ablated in the oncogene-induced transgenic MMTV-PymT tumor model. TMPRSS13 deficiency resulted in a significant decrease in overall tumor burden and growth rate, as well as a delayed formation of detectable mammary tumors, thus suggesting a causal relationship between TMPRSS13 expression and the progression of breast cancer. Complementary studies using human breast cancer cell culture models revealed that siRNA-mediated silencing of TMPRSS13 expression decreases proliferation, induces apoptosis, and attenuates invasion. Importantly, targeting TMPRSS13 expression renders aggressive triple-negative breast cancer cell lines highly responsive to chemotherapy. At the molecular level, knockdown of TMPRSS13 in breast cancer cells led to increased protein levels of the tumor-suppressive protease prostasin. TMPRSS13/prostasin co-immunoprecipitation and prostasin zymogen activation experiments identified prostasin as a potential novel target for TMPRSS13. Regulation of prostasin levels may be a mechanism that contributes to the pro-oncogenic properties of TMPRSS13 in breast cancer. TMPRSS13 represents a novel candidate for targeted therapy in combination with standard of care chemotherapy agents in patients with hormone receptor-negative breast cancer or in patients with tumors refractory to endocrine therapy.}, }
@article {pmid32856854, year = {2020}, author = {Chowdhury, SS and Khatun, M and Khan, TH and Laila, AB}, title = {Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {8}, pages = {2265-2270}, pmid = {32856854}, issn = {2476-762X}, mesh = {Adult ; BRCA1 Protein/*genetics ; Bangladesh/epidemiology ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/genetics/*pathology ; Cross-Sectional Studies ; *Exons ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Tertiary Care Centers ; }, abstract = {BACKGROUND: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.<br><br>METHODS: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.<br><br>RESULTS: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.<br><br>CONCLUSIONS: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.}, }
@article {pmid32853021, year = {2021}, author = {Bakhtari, N and Mozdarani, H and Salimi, M and Omranipour, R}, title = {Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients.}, journal = {Neoplasma}, volume = {68}, number = {1}, pages = {190-199}, doi = {10.4149/neo_2020_200225N185}, pmid = {32853021}, issn = {0028-2685}, mesh = {Adult ; Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/blood/genetics/radiotherapy ; Female ; Humans ; Leukocytes, Mononuclear/metabolism ; *MicroRNAs/biosynthesis/blood ; Middle Aged ; ROC Curve ; Radiation Tolerance ; }, abstract = {Identifying patient's cellular radiosensitivity before radiotherapy (RT) in breast cancer (BC) patients allows proper alternations in routinely used treatment programs and reduces the adverse side effects in exposed patients. This study was conducted on blood samples taken from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC (mean age: 47±9.93) and 30 healthy women (mean age: 44.43±6.7). The standard G2 assay was performed to predict cellular radiosensitivity. To investigate miR-22 and miR-335 expression levels in peripheral blood mononuclear cells (PBMCs), qPCR was performed. The sensitivity and specificity of the mentioned miRNAs were assessed by plotting the Receiver Operating Characteristic (ROC) curve. Binary logistic regression was performed to identify the miRNA involvement in BC and cellular radiosensitivity (CR) of BC patients. The frequency of spontaneous and radiation-induced chromatid breaks (CBs) was significantly different between control and patient groups (p<0.05). A cut-off value was determined to differentiate the patients with and without cellular radiosensitivity. miR-22 and miR-335 were significantly downregulated in BC patients. miRNAs expression levels were directly associated with CR. ROC curve assessment identified that both miRNAs had acceptable specificity and sensitivity in the prediction of BC and CR of BC patients. Binary logistic regression showed that both miRNAs could also predict BC successfully. Although only miR-22 was shown potent to predict CR of BC patients, both miR-22 and miR-335 might act as tumor suppressor miRNAs in BC. miR-22 and miR-335 may be promising potential biomarkers in BC prediction along with other important biomarkers. Moreover, mirR-22 might be a potential biomarker for the prediction of CR in BC patients.}, }
@article {pmid32846803, year = {2020}, author = {Li, G and Yao, J and Wu, T and Chen, Y and Wang, Z and Wang, Y and Wang, F and Zhong, R and Yang, S}, title = {Triple metachronous primary cancer of uterus, colon, and breast cancer: A case report and review of the literature.}, journal = {Medicine}, volume = {99}, number = {34}, pages = {e21764}, doi = {10.1097/MD.0000000000021764}, pmid = {32846803}, issn = {1536-5964}, mesh = {Aged ; Breast Neoplasms/*complications/pathology/therapy ; Colonic Neoplasms/*complications ; Female ; Humans ; Mammography ; Mastectomy ; Sentinel Lymph Node Biopsy ; Uterine Neoplasms/*complications ; }, abstract = {RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019.<br><br>PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy.<br><br>DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases.<br><br>OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively.<br><br>LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.}, }
@article {pmid32811533, year = {2020}, author = {Chao, X and Liu, L and Sun, P and Yang, X and Li, M and Luo, R and Huang, Y and He, J and Yun, J}, title = {Immune parameters associated with survival in metaplastic breast cancer.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {92}, pmid = {32811533}, issn = {1465-542X}, mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*immunology/metabolism ; Biomarkers, Tumor/*immunology/metabolism ; Breast Neoplasms/*immunology/*mortality/pathology/therapy ; CD8-Positive T-Lymphocytes/*immunology ; Carcinoma, Squamous Cell/immunology/mortality/pathology/therapy ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Programmed Cell Death 1 Receptor/*immunology/metabolism ; Survival Rate ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.<br><br>METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.<br><br>RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm2, 20%), CD4+ TILs (> 250/mm2), and CD8+ TILs (> 70/mm2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.<br><br>CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.}, }
@article {pmid32783993, year = {2020}, author = {Domínguez-de-la-Cruz, E and Muñoz, ML and Pérez-Muñoz, A and García-Hernández, N and Moctezuma-Meza, C and Hinojosa-Cruz, JC}, title = {Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.}, journal = {Gene}, volume = {761}, number = {}, pages = {145047}, doi = {10.1016/j.gene.2020.145047}, pmid = {32783993}, issn = {1879-0038}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism ; Case-Control Studies ; DNA Copy Number Variations/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes/genetics ; Humans ; Mexico/epidemiology ; Middle Aged ; Mitochondria/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.}, }
@article {pmid32782013, year = {2020}, author = {Kurozumi, S and Alsaleem, M and Monteiro, CJ and Bhardwaj, K and Joosten, SEP and Fujii, T and Shirabe, K and Green, AR and Ellis, IO and Rakha, EA and Mongan, NP and Heery, DM and Zwart, W and Oesterreich, S and Johnston, SJ}, title = {Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {85}, pmid = {32782013}, issn = {1465-542X}, support = {AAM127669/WT_/Wellcome Trust/United Kingdom ; SAC160073/KOMEN/Susan G. Komen/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Computer Simulation ; Databases, Genetic/statistics &amp; numerical data ; Female ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.<br><br>METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.<br><br>RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2-11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04-5.05; p = 0.040).<br><br>CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.}, }
@article {pmid32781417, year = {2020}, author = {Lu, K and Wang, X and Zhang, W and Ye, H and Lao, L and Zhou, X and Yao, S and Lv, F}, title = {Clinicopathological and genomic features of breast mucinous carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {53}, number = {}, pages = {130-137}, pmid = {32781417}, issn = {1532-3080}, mesh = {Adenocarcinoma, Mucinous/*genetics/*pathology ; Adult ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Female ; Gene Expression Profiling ; Genome ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prospective Studies ; SEER Program ; Young Adult ; }, abstract = {INTRODUCTION: Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood.<br><br>MATERIALS AND METHODS: 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis.<br><br>RESULTS: MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P < 0.001). However, after adjusting for clinicopathological factors, survival advantage of MC disappeared. In terms of genomic features of MC, representative upregulated genes of MC in transcriptomic level were MUC2, TFF1 and CARTPT. Upregulated pathways of MC included neurotransmitter-related pathways. Moreover, MC was featured by the amplification of 6p25.2, 6q12 and 11q12.3.<br><br>CONCLUSION: MC is a distinct histological subtype compared with IDC in terms of clinicopathological characteristics and genomic features. Further investigation need to be conducted to explore the formation of this specific histological subtype.}, }
@article {pmid32758491, year = {2020}, author = {Sechrist, H and Glasgow, A and Bomeisl, P and Gilmore, H and Harbhajanka, A}, title = {Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.}, journal = {Human pathology}, volume = {104}, number = {}, pages = {54-65}, doi = {10.1016/j.humpath.2020.07.022}, pmid = {32758491}, issn = {1532-8392}, mesh = {Aged ; *Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology/therapy ; Clinical Decision-Making ; Female ; *Gene Expression Profiling ; Humans ; *Immunohistochemistry ; *In Situ Hybridization ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Receptor, ErbB-2/analysis/genetics ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Retrospective Studies ; *Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; Transcriptome ; Treatment Outcome ; }, abstract = {Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&amp;E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.}, }
@article {pmid32748295, year = {2020}, author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Naito, Y and Tochigi, K and Sano, T and Ishida, S and Funahashi, Y and Fujita, T and Matsukawa, Y and Hattori, R and Tsuzuki, T}, title = {Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.}, journal = {International journal of clinical oncology}, volume = {25}, number = {12}, pages = {2130-2137}, doi = {10.1007/s10147-020-01756-0}, pmid = {32748295}, issn = {1437-7772}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Bone Neoplasms/secondary ; Carcinoma, Ductal/mortality/*pathology ; Hormones ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/mortality/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC).<br><br>METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates.<br><br>RESULTS: For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively).<br><br>CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.}, }
@article {pmid32745951, year = {2020}, author = {Altinoz, A and Al Ameri, M and Qureshi, W and Boush, N and Nair, SC and Abdel-Aziz, A}, title = {Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates.}, journal = {Breast (Edinburgh, Scotland)}, volume = {53}, number = {}, pages = {119-124}, pmid = {32745951}, issn = {1532-3080}, mesh = {Adult ; Arabs/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Predisposition to Disease/*epidemiology/ethnology/genetics ; Genetic Testing/statistics &amp; numerical data ; Hereditary Breast and Ovarian Cancer Syndrome/ethnology/*genetics/pathology ; Humans ; Middle Aged ; Prevalence ; Retrospective Studies ; United Arab Emirates/epidemiology ; }, abstract = {INTRODUCTION: Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE.<br><br>MATERIAL &amp; METHODS: A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation.<br><br>RESULTS: 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (±9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%).<br><br>CONCLUSIONS: This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.}, }
@article {pmid32719289, year = {2020}, author = {Dhia, SB and Belaid, I and Stita, W and Hochlaf, M and Ezzairi, F and Ahmed, SB}, title = {Bilateral parotid gland metastasis from a breast invasive ductal carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {16}, number = {3}, pages = {672-674}, doi = {10.4103/jcrt.JCRT_1047_17}, pmid = {32719289}, issn = {1998-4138}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/therapy ; Palliative Care ; Parotid Neoplasms/*secondary/therapy ; }, abstract = {Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.}, }
@article {pmid32710711, year = {2020}, author = {Jones, B and Thomas, G and Sprenger, J and Nofech-Mozes, S and Khorasani, M and Vitkin, A}, title = {Peri-tumoural stroma collagen organization of invasive ductal carcinoma assessed by polarized light microscopy differs between OncotypeDX risk group.}, journal = {Journal of biophotonics}, volume = {13}, number = {11}, pages = {e202000188}, doi = {10.1002/jbio.202000188}, pmid = {32710711}, issn = {1864-0648}, support = {PJT-156110//CIHR/Canada ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/genetics ; Collagen ; Female ; Humans ; Microscopy, Polarization ; Risk Factors ; }, abstract = {A commercially available genomic test, OncotypeDX has emerged as a useful postsurgical treatment guide for early stage breast cancer. Despite widespread clinical adoption, there remain logistical issues with its implementation. Collagenous stromal architecture has been shown to hold prognostic value that may complement OncotypeDX. Polarimetric analysis of breast cancer surgical samples allows for the quantification of collagenous stroma abundance and organization. We examine intratumoural collagen abundance and alignment along the tumor-host interface for 45 human samples of invasive ductal carcinoma categorized as low or higher risk by OncotypeDX. Furthermore, we probe the separatory power of collagen alignment patterns to classify unlabeled samples as low or higher OncotypeDX risk group using a linear discriminant (LD) model. No significant difference in mean collagen abundance was found between the two risk groups. However, collagen alignment along the tumor boundary was found to be significantly lower in higher risk samples. The LD model achieved a 71% total accuracy and 81% sensitivity to higher risk samples. Prognostic information extracted from the stromal morphology has potential to complement OncotypeDX as an easy-to-implement prescreening methodology.}, }
@article {pmid32700071, year = {2020}, author = {Richards, D and Ayala, AA and Wu, Y and Middleton, LP}, title = {Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.}, journal = {Oncology and therapy}, volume = {8}, number = {1}, pages = {81-89}, pmid = {32700071}, issn = {2366-1089}, abstract = {INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.<br><br>METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained.<br><br>RESULTS: Thirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&amp;E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3 years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA.<br><br>CONCLUSIONS: In our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.}, }
@article {pmid32694843, year = {2019}, author = {Seitz, S and Kwon, Y and Hartleben, G and Jülg, J and Sekar, R and Krahmer, N and Najafi, B and Loft, A and Gancheva, S and Stemmer, K and Feuchtinger, A and Hrabe de Angelis, M and Müller, TD and Mann, M and Blüher, M and Roden, M and Berriel Diaz, M and Behrends, C and Gilleron, J and Herzig, S and Zeigerer, A}, title = {Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.}, journal = {Nature metabolism}, volume = {1}, number = {10}, pages = {1009-1026}, pmid = {32694843}, issn = {2522-5812}, mesh = {Adiposity ; Adult ; Animals ; Autophagy ; Blood Glucose/*metabolism ; Cholesterol/blood ; Female ; Homeostasis ; Humans ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria, Liver/*metabolism ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/metabolism ; Up-Regulation ; rab GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis. RAB24 is highly upregulated in the livers of obese patients with NAFLD and positively correlates with increased body fat in humans. Liver-selective inhibition of Rab24 increases autophagic flux and mitochondrial connectivity, leading to a strong improvement in hepatic steatosis and a reduction in serum glucose and cholesterol levels in obese mice. Our study highlights a potential therapeutic application of trafficking regulators, such as RAB24, for NAFLD and establishes a conceptual functional connection between intracellular transport and systemic metabolic dysfunction.}, }
@article {pmid32665190, year = {2020}, author = {Escott, CE and Zaenger, D and Switchencko, JM and Lin, JY and Abugideiri, M and Arciero, CA and Pfister, NT and Xu, KM and Meisel, JL and Subhedar, P and Torres, M and Curran, WJ and Patel, PR}, title = {The Influence of Histologic Grade on Outcomes of Elderly Women With Early Stage Breast Cancer Treated With Breast Conserving Surgery With or Without Radiotherapy.}, journal = {Clinical breast cancer}, volume = {20}, number = {6}, pages = {e701-e710}, doi = {10.1016/j.clbc.2020.05.007}, pmid = {32665190}, issn = {1938-0666}, abstract = {BACKGROUND: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy.<br><br>MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup.<br><br>RESULTS: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043).<br><br>CONCLUSION: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.}, }
@article {pmid32661241, year = {2020}, author = {Tasdemir, N and Ding, K and Savariau, L and Levine, KM and Du, T and Elangovan, A and Bossart, EA and Lee, AV and Davidson, NE and Oesterreich, S}, title = {Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {11487}, pmid = {32661241}, issn = {2045-2322}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; 5F30CA203154/NH/NIH HHS/United States ; K99CA237736/NH/NIH HHS/United States ; 1F31CA203055-01/NH/NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA203055/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; }, mesh = {Autoantigens/genetics ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Differentiation/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Inhibitor of Differentiation Protein 1/genetics ; Inhibitor of Differentiation Proteins/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/genetics ; Phosphatidylinositol 3-Kinases/genetics ; *Proteomics ; Proto-Oncogene Proteins c-akt/genetics ; Ribosomal Protein S6 Kinases, 90-kDa/genetics ; Signal Transduction/genetics ; Transcriptome/*genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.}, }
@article {pmid32637252, year = {2020}, author = {Jones, B and Thomas, G and Westreich, J and Nofech-Mozes, S and Vitkin, A and Khorasani, M}, title = {Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.}, journal = {Biomedical optics express}, volume = {11}, number = {6}, pages = {3246-3262}, pmid = {32637252}, issn = {2156-7085}, abstract = {As a leading cause of death in women, breast cancer is a global health concern for which personalized therapy remains largely unrealized, resulting in over- or under-treatment. Recently, tumor stroma has been shown to carry important prognostic information, both in its relative abundance and morphology, but its current assessment methods are few and suboptimal. Herein, we present a novel stromal architecture signature (SAS) methodology based on polarized light imaging that quantifies patterns of tumor connective tissue. We demonstrate its ability to differentiate between myxoid and sclerotic stroma, two pathology-derived categories associated with significantly different patient outcomes. The results demonstrate a 97% sensitivity and 88% specificity for myxoid stroma identification in a pilot study of 102 regions of interest from human invasive ductal carcinoma breast cancer surgical specimens (20 patients). Additionally, the SAS numerical score is indicative of the wide range of stromal characteristics within these binary classes and highlights ambiguous mixed-morphology regions prone to misclassification. The enabling polarized light microscopy technique is inexpensive, fast, fully automatable, applicable to fresh or embedded tissue without the need for staining and thus potentially translatable into research and/or clinical settings. The SAS metric yields quantifiable and objective stromal characterization with promise for prognosis in many types of cancers beyond breast carcinoma, enabling researchers and clinicians to further investigate the emerging and important role of stromal architectural patterns in solid tumors.}, }
@article {pmid32636849, year = {2020}, author = {Siegers, GM and Dutta, I and Kang, EY and Huang, J and Köbel, M and Postovit, LM}, title = {Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1287}, pmid = {32636849}, issn = {1664-3224}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Intraepithelial Lymphocytes/*immunology ; Middle Aged ; Nodal Protein/*immunology/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Triple Negative Breast Neoplasms/*immunology/metabolism ; Tumor Escape/*immunology ; Tumor Microenvironment/*immunology ; }, abstract = {Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short- nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.}, }
@article {pmid32619221, year = {2020}, author = {Escoter-Torres, L and Greulich, F and Quagliarini, F and Wierer, M and Uhlenhaut, NH}, title = {Anti-inflammatory functions of the glucocorticoid receptor require DNA binding.}, journal = {Nucleic acids research}, volume = {48}, number = {15}, pages = {8393-8407}, pmid = {32619221}, issn = {1362-4962}, mesh = {Animals ; DNA/*genetics/metabolism ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation/genetics ; Glucocorticoids/genetics/metabolism ; Humans ; Inflammation/*genetics/pathology ; Mice ; Protein Interaction Domains and Motifs/genetics ; RNA-Seq ; Receptors, Glucocorticoid/*genetics ; Transcriptional Activation/genetics ; }, abstract = {The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR's anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to pro-inflammatory transcription factors is thought to repress transcription. Using mice with a point mutation in GR's zinc finger, that still tether via protein-protein interactions while being unable to recognize DNA, we demonstrate that DNA binding is essential for both transcriptional activation and repression. Performing ChIP-Seq, RNA-Seq and proteomics under inflammatory conditions, we show that DNA recognition is required for the assembly of a functional co-regulator complex to mediate glucocorticoid responses. Our findings may contribute to the development of safer immunomodulators with fewer side effects.}, }
@article {pmid32618211, year = {2020}, author = {Bhattad, PB and Jain, V}, title = {Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {8}, number = {}, pages = {2324709620938942}, pmid = {32618211}, issn = {2324-7096}, mesh = {Biopsy ; Breast Neoplasms/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung/*pathology ; Lymph Nodes/*pathology ; Lymphoma/*pathology ; Magnetic Resonance Imaging ; Mediastinum/*pathology ; Middle Aged ; Neoplasm Metastasis/diagnosis ; Positron Emission Tomography Computed Tomography ; Sarcoidosis/complications/*diagnosis ; }, abstract = {Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography-computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.}, }
@article {pmid32617838, year = {2021}, author = {Hashinokuchi, A and Akamine, T and Kometani, T and Shikada, Y and Nozoe, T and Kato, S}, title = {Spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer: a case report and literature review.}, journal = {General thoracic and cardiovascular surgery}, volume = {69}, number = {1}, pages = {137-141}, pmid = {32617838}, issn = {1863-6713}, mesh = {Aged ; *Breast Neoplasms ; Female ; Humans ; Neoplasm Recurrence, Local ; Pleurodesis ; *Pneumothorax/etiology/therapy ; Quality of Life ; Recurrence ; Thoracic Surgery, Video-Assisted ; }, abstract = {We report a 69-year-old woman with spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer. She was treated for right breast cancer (invasive ductal carcinoma, ypT4bN1M0, stage IIIB) 2 years earlier, and was admitted for right pneumothorax and chest computed tomography, which showed multiple small cavitating lesions in bilateral lungs. The pneumothorax was treated conservatively with chest drainage, but subsequently recurred ipsilaterally. During video-assisted thoracic surgery, we detected small white nodules with visceral pleural rupture; therefore, we performed partial lung resection. The pathological findings revealed metastatic breast cancer with pleural invasion. Forty days later, ipsilateral pneumothorax recurred, and chemical pleurodesis was performed, which resolved the pneumothorax and prevented subsequent recurrence. Early diagnosis and definitive treatment, including pleurodesis, should be considered to prevent recurrence of spontaneous pneumothorax and improve patients' quality of life, even in patients with advanced malignancy.}, }
@article {pmid32609836, year = {2020}, author = {Sreekumar, S and Levine, KM and Sikora, MJ and Chen, J and Tasdemir, N and Carter, D and Dabbs, DJ and Meier, C and Basudan, A and Boone, D and McAuliffe, PF and Jankowitz, RC and Lee, AV and Atkinson, JM and Oesterreich, S}, title = {Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.}, journal = {Endocrinology}, volume = {161}, number = {9}, pages = {}, pmid = {32609836}, issn = {1945-7170}, support = {R00 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Line, Tumor ; Estradiol/pharmacology ; Estrogen Receptor alpha/*genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Invasiveness ; Protein Processing, Post-Translational/drug effects ; Proteolysis/drug effects ; Ubiquitination/drug effects ; }, abstract = {Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.}, }
@article {pmid32599083, year = {2020}, author = {Grabenstetter, A and Mohanty, AS and Rana, S and Zehir, A and Brannon, AR and D'Alfonso, TM and DeLair, DF and Tan, LK and Ross, DS}, title = {E-cadherin immunohistochemical expression in invasive lobular carcinoma of the breast: correlation with morphology and CDH1 somatic alterations.}, journal = {Human pathology}, volume = {102}, number = {}, pages = {44-53}, pmid = {32599083}, issn = {1532-8392}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD/biosynthesis/*genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Cadherins/biosynthesis/*genetics ; Carcinoma, Lobular/diagnosis/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Mutation ; }, abstract = {E-cadherin (ECAD) immunohistochemical (IHC) expression is lost in ∼90% of invasive lobular carcinomas (ILCs) owing to genomic alterations of CDH1. We examined morphologic features and ECAD IHC expression in invasive breast carcinomas (BCs) with known CDH1 alterations. Between January 2014 and May 2018, 202 cases of BC with a CDH1 somatic alteration were identified. ECAD expression was lost in 77% (155/202) of cases and was retained in 23% (47/202) cases. Most (90%, 139/155) ECAD-negative cases were morphologically classified as ILC, while the remaining (10%, 16/155) were invasive mammary carcinoma with mixed ductal and lobular features (IMC). Of 47 cases with ECAD staining, 62% (29/47) were classified as ILC, 23% (11/47) were classified as IMC, and 15% (7/47) were classified as invasive ductal carcinoma (IDC). Of note, 51% (24/47) of ECAD-positive cases were initially diagnosed as IDC or IMC based on ECAD expression alone. For ECAD-negative BCs, 98% (152/155) of CDH1 alterations were truncating, and 2% (3/155) were variants of unknown significance (VUS). Truncating CDH1 alterations were identified in the majority of ECAD-positive BCs (72%, 34/47); however, VUS-type CDH1 alterations were more prevalent (28%, 13/47) in ECAD-positive BCs than in ECAD-negative BCs. Although 90% of ECAD-negative tumors were compatible with ILC in this study, 17% (29/168) of ILC cases were ECAD positive. In addition, CDH1 truncating alterations were seen in ECAD-positive ILC, supporting the notion of aberrant ECAD staining. Therefore, ECAD IHC expression must be interpreted in conjunction with morphology, and BC with classic histologic features of ILC should not be reclassified as IDC/IMC based solely on the status of ECAD IHC expression.}, }
@article {pmid32589068, year = {2021}, author = {Epstein, JI and Amin, MB and Fine, SW and Algaba, F and Aron, M and Baydar, DE and Beltran, AL and Brimo, F and Cheville, JC and Colecchia, M and Comperat, E and da Cunha, IW and Delprado, W and DeMarzo, AM and Giannico, GA and Gordetsky, JB and Guo, CC and Hansel, DE and Hirsch, MS and Huang, J and Humphrey, PA and Jimenez, RE and Khani, F and Kong, Q and Kryvenko, ON and Kunju, LP and Lal, P and Latour, M and Lotan, T and Maclean, F and Magi-Galluzzi, C and Mehra, R and Menon, S and Miyamoto, H and Montironi, R and Netto, GJ and Nguyen, JK and Osunkoya, AO and Parwani, A and Robinson, BD and Rubin, MA and Shah, RB and So, JS and Takahashi, H and Tavora, F and Tretiakova, MS and True, L and Wobker, SE and Yang, XJ and Zhou, M and Zynger, DL and Trpkov, K}, title = {The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {145}, number = {4}, pages = {461-493}, doi = {10.5858/arpa.2020-0015-RA}, pmid = {32589068}, issn = {1543-2165}, mesh = {Biomarkers, Tumor/analysis/genetics ; Biopsy, Needle/standards ; Consensus ; Humans ; Image-Guided Biopsy/standards ; Immunohistochemistry/standards ; Magnetic Resonance Imaging/standards ; Male ; Molecular Diagnostic Techniques/standards ; Neoplasm Grading/*standards ; Pathology/*standards ; Predictive Value of Tests ; Prostatic Neoplasms/chemistry/genetics/*pathology ; }, abstract = {CONTEXT.&#x2014;: Controversies and uncertainty persist in prostate cancer grading.<br><br>OBJECTIVE.&#x2014;: To update grading recommendations.<br><br>DATA SOURCES.&#x2014;: Critical review of the literature along with pathology and clinician surveys.<br><br>CONCLUSIONS.&#x2014;: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.}, }
@article {pmid32586354, year = {2020}, author = {Blohmer, M and Zhu, L and Atkinson, JM and Beriwal, S and Rodríguez-López, JL and Rosenzweig, M and Brufsky, AM and Tseng, G and Lucas, PC and Lee, AV and Oesterreich, S and Jankowitz, RC}, title = {Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {70}, pmid = {32586354}, issn = {1465-542X}, support = {SAC160073/KOMEN/Susan G. Komen/United States ; CCR14300865/KOMEN/Susan G. Komen/United States ; SAC150021/KOMEN/Susan G. Komen/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; U24 CA180921/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology/*radiotherapy ; Carcinoma, Ductal, Breast/metabolism/pathology/radiotherapy ; Carcinoma, Lobular/metabolism/*mortality/pathology/radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Orbital Neoplasms/metabolism/radiotherapy/*secondary ; Prognosis ; Radiotherapy, Intensity-Modulated ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.<br><br>METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.<br><br>RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.<br><br>CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.}, }
@article {pmid32585364, year = {2020}, author = {Erener, S}, title = {Diabetes, infection risk and COVID-19.}, journal = {Molecular metabolism}, volume = {39}, number = {}, pages = {101044}, pmid = {32585364}, issn = {2212-8778}, mesh = {Adult ; Aged ; Animals ; *Betacoronavirus ; COVID-19 ; Child ; Comorbidity ; Coronavirus Infections/*epidemiology/immunology/pathology/virology ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/*epidemiology/immunology ; Diabetes Mellitus, Type 2/*epidemiology/immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Incidence ; Male ; Mice ; Middle Aged ; Pandemics ; Pneumonia, Viral/*epidemiology/immunology/pathology/virology ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19.<br><br>SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided.<br><br>MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.}, }
@article {pmid32581209, year = {2020}, author = {Lan, T and Lu, Y and Luo, H and He, J and He, J and Hu, Z and Xu, H}, title = {Effects of Marital Status on Prognosis in Women with Infiltrating Ductal Carcinoma of the Breast: A Real-World 1: 1 Propensity-Matched Study.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e923630}, pmid = {32581209}, issn = {1643-3750}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal/mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Marital Status/*statistics &amp; numerical data ; Middle Aged ; Multivariate Analysis ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; SEER Program ; United States/epidemiology ; }, abstract = {BACKGROUND The effects of marital status on infiltrating ductal carcinoma of breast cancer (IDC) have not been studied in detail. This study investigated the impact of marital status on IDC patients. MATERIAL AND METHODS SEER databases were searched from 2010 to 2015 for subjects who were married, divorced, single, and widowed. The influence of marital status on breast cancer-specific survival (BCSS) and overall survival (OS) of IDC patients was investigated through multivariate Cox regression analysis and Kaplan-Meier analysis. To prevent bias, propensity score matching (PSM) analysis was performed. RESULTS The 5-year OS was 89.6%in married patients, 84.9% in divorced patients, 83.5% in single patients, and 71.3% in widowed patients (p<0.001). The 5-year BCSS were 92.9%, 90.2%, 87.6%, and 86.4%, respectively (p<0.001). Multivariate Cox regression analysis revealed that marriage was a protective factor for patients with IDC in terms of OS (divorced: HR, 1.27; 95% CI, 1.21-1.32; p<0.001; single: HR, 1.36; 95% CI, 1.31-1.42; p<0.001; widowed: HR, 1.42; 95% CI, 1.36-1.48; p<0.001) and BCSS (divorced: HR, 1.15; 95% CI, 1.09-1.21; p<0.001; single: HR, 1.27; 95% CI, 1.21-1.33; p<0.001; widowed: HR, 1.32; 95% CI, 1.25-1.40; p<0.001). Following subgroup and PSM analysis, married patients were shown to have better OS and BCSS as opposed to divorced, single, or widowed patients. CONCLUSIONS We identify marital status as a predictor of survival in those with IDC. Widowed patients showed the highest mortality risk.}, }
@article {pmid32580398, year = {2020}, author = {Kim, HM and Koo, JS}, title = {Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32580398}, issn = {1422-0067}, support = {2016 (6-2016-0163)//faculty research grant from Yonsei University College of Medicine/ ; }, mesh = {Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/metabolism/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Forkhead Transcription Factors/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating/*classification/*immunology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; STAT6 Transcription Factor/metabolism ; Survival Rate ; }, abstract = {The clinical significance of immune cell subtypes in breast cancer remains poorly understood. To identify tumor-infiltrating immune cell subtypes in breast cancer and investigate their implications, tissue microarrays were constructed using 334 cases of invasive ductal carcinoma (luminal A type: 162 (48.5%), luminal B type: 96 (28.7%), HER-2 type: 21 (6.3%), and triple negative breast cancer: 55 (16.5%)). Hormone receptors (ER, PR, and HER-2), Ki-67, and immune cell subtype-related proteins (STAT4, STAT6, FOXP3, CD8, CD68, and CD163) were assessed immunohistochemically. The proportion of highly expressed STAT6, FOXP3, CD8, CD68, and CD163 proteins was found to be lowest in luminal A type but highest in the HER-2 type. Additionally, high-level STAT6, FOXP3, CD68, and CD163 protein expression was associated with higher histologic grade. ER negativity was associated with high STAT6, FOXP3, and CD163 expression levels, whereas PR negativity and high Ki-67 labeling index were associated with high CD163 expression. Univariate (p = 0.003) and multivariate Cox (hazard ratio: 2.435, 95% CI: 1.110-5.344, p = 0.049) analyses showed that high CD8 expression is an independent factor associated with shorter disease-free survival. Immune cell subtype-related protein expression is dependent on breast cancer molecular subtypes, and CD8 expression is associated with patient prognosis.}, }
@article {pmid32563094, year = {2020}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {Local recurrence of breast cancer caused by core needle biopsy: Case report and review of the literature.}, journal = {International journal of surgery case reports}, volume = {72}, number = {}, pages = {318-321}, pmid = {32563094}, issn = {2210-2612}, abstract = {INTRODUCTION: Needle tract seeding is the implantation of tumor cells at the site of needle passage during needle biopsy. Histopathological examination of resected specimens after biopsy shows an incidence of 22%-50%. However, reports of actual local recurrence are extremely rare. Here we report such a case.<br><br>PRESENTATION OF CASE: A 67-year-old woman was diagnosed with ductal carcinoma by histopathology and underwent right mastectomy and sentinel lymph node biopsy. Histopathological examination revealed non-invasive ductal carcinoma. One year after the first operation, a mass was found at the site of the core needle biopsy (CNB) scar near the previous surgical wound on the right chest. Histological examination revealed the tumor as adenocarcinoma, and a skin lesion resection was performed. After surgery, radiation therapy and endocrine therapy were performed. She remains relapse-free as of this writing, 9 months after resection.<br><br>DISCUSSION: Reports of local recurrence due to needle tract seeding are extremely rare. We found nine cases of mastectomy and seven cases of partial resection performed for the first surgery; six patients received radiation therapy and 10 did not. Histological diagnosis at the time of the first operation was invasive carcinoma in all cases.<br><br>CONCLUSION: The risk of seeding is high with multiple punctures in CNB, in cases with a short period until surgery, and in mucinous carcinoma. Considering these factors, CNB puncture should preferably be at a site that is included in the resection area during surgery. If not resected, close follow-up is necessary considering the possibility of local recurrence.}, }
@article {pmid32548206, year = {2020}, author = {Arensman, K and Dela-Pena, J and Miller, JL and LaChance, E and Beganovic, M and Anderson, M and Rivelli, A and Wieczorkiewicz, SM}, title = {Impact of Mandatory Infectious Diseases Consultation and Real-time Antimicrobial Stewardship Pharmacist Intervention on Staphylococcus aureus Bacteremia Bundle Adherence.}, journal = {Open forum infectious diseases}, volume = {7}, number = {6}, pages = {ofaa184}, pmid = {32548206}, issn = {2328-8957}, abstract = {Background: The purpose of this study was to evaluate the impact of infectious diseases consultation (IDC) and a real-time antimicrobial stewardship (AMS) review on the management of Staphylococcus aureus bacteremia (SAB).<br><br>Methods: This retrospective study included adult inpatients with SAB from January 2016 to December 2018 at 7 hospitals. Outcomes were compared between 3 time periods: before mandatory IDC and AMS review (period 1), after mandatory IDC and before AMS review (period 2), and after mandatory IDC and AMS review (period 3). The primary outcome was bundle adherence, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary end points included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related readmission, and in-hospital all-cause mortality.<br><br>Results: A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n = 241/371), 54% in period 2 (n = 47/87), and 76% in period 3 (n = 92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.93; P = .02) and period 2 (OR, 0.37; 95% CI, 0.20-0.67; P = .0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P < .001), source control (34% vs 45% vs 45%; P = .04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P = .01). No differences were noted for readmission or mortality.<br><br>Conclusions: The addition of AMS pharmacist review to mandatory IDC was associated with significantly improved quality care bundle adherence.}, }
@article {pmid32544183, year = {2020}, author = {Moon, HR and Ospina-Muñoz, N and Noe-Kim, V and Yang, Y and Elzey, BD and Konieczny, SF and Han, B}, title = {Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform.}, journal = {PloS one}, volume = {15}, number = {6}, pages = {e0234012}, pmid = {32544183}, issn = {1932-6203}, support = {HHSN261201400021C/CA/NCI NIH HHS/United States ; UL1 TR000006/TR/NCATS NIH HHS/United States ; P30 CA023168/CA/NCI NIH HHS/United States ; }, mesh = {CD24 Antigen/metabolism ; Carcinoma, Ductal, Breast/classification/genetics/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Humans ; Microfluidics/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Triple Negative Breast Neoplasms/classification/genetics/*pathology ; *Tumor Microenvironment ; }, abstract = {Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.}, }
@article {pmid32509097, year = {2020}, author = {Lv, X and Ye, J and Jiang, G and Wang, Y and Lv, J and Wang, Y}, title = {Simultaneous multiple primary cancers with concomitant inflammatory myofibroblastic tumor: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {13}, number = {5}, pages = {1212-1215}, pmid = {32509097}, issn = {1936-2625}, abstract = {Multiple primary cancers are of rare occurrence. Most multiple primary cancers are metachronous multiple primary cancers, while simultaneous multiple primary cancers are rare. Inflammatory myofibroblastic tumors are rare. Inflammatory myofibroblastic tumor occurs most frequently in children and young adults. Herein, we report a rare case of simultaneous multiple primary cancers and inflammatory myofibroblastic tumor. A 44-year-old woman was admitted for a breast mass evaluation. The patient was positive for antinuclear, anti-mitochondrial, and anti-RO52 antibodies. Breast magnetic resonance imaging revealed a right breast mass. After neoadjuvant chemotherapy, modified radical mastectomy was performed. Postoperative histopathology revealed an invasive ductal carcinoma. Two months later, computed tomography revealed a nodule in the right upper lobe and ground-glass opacity in the lower lobe of the lungs. Lobectomy and lobe biopsy were performed. Postoperative histopathology revealed that the mass in the right upper lobe was an inflammatory myofibroblastic tumor and the right lower lobe lesion was an invasive adenocarcinoma. Immunohistochemistry of the inflammatory myofibroblastic tumor revealed negativity for anaplastic lymphoma kinase. At the 4-month follow-up, the patient showed good recovery. The etiology of multiple primary cancers and inflammatory myofibroblastic tumors is still unknown; in this case, we believe that autoimmune factors are the main cause of multiple primary cancers with concomitant inflammatory myofibroblastic tumor. Tissue biopsy is needed to ensure correct diagnosis of multiple primary cancers and inflammatory myofibroblastic tumor. Surgery-based comprehensive therapy is recommended. The prognosis is favorable and regular follow-up is necessary.}, }
@article {pmid32488076, year = {2020}, author = {Subudhi, AK and O'Donnell, AJ and Ramaprasad, A and Abkallo, HM and Kaushik, A and Ansari, HR and Abdel-Haleem, AM and Ben Rached, F and Kaneko, O and Culleton, R and Reece, SE and Pain, A}, title = {Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2763}, pmid = {32488076}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans Proteins ; Circadian Rhythm/*physiology ; Disease Models, Animal ; Erythropoiesis/*physiology ; Female ; Gene Expression ; Host-Parasite Interactions/genetics/*physiology ; Humans ; Malaria/*metabolism/parasitology ; Mice ; Mice, Knockout ; Plasmodium chabaudi/genetics/growth &amp; development ; Plasmodium falciparum/genetics/growth &amp; development ; Protozoan Proteins/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Rodentia ; Secologanin Tryptamine Alkaloids/*metabolism ; Transcriptome ; }, abstract = {Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.}, }
@article {pmid32480118, year = {2020}, author = {Chan, SJ and Ein-Dor, T and Mayopoulos, PA and Mesa, MM and Sunda, RM and McCarthy, BF and Kaimal, AJ and Dekel, S}, title = {Risk factors for developing posttraumatic stress disorder following childbirth.}, journal = {Psychiatry research}, volume = {290}, number = {}, pages = {113090}, doi = {10.1016/j.psychres.2020.113090}, pmid = {32480118}, issn = {1872-7123}, mesh = {Adult ; Delivery, Obstetric/*psychology/statistics &amp; numerical data ; Female ; Humans ; Labor, Obstetric/*psychology ; Mental Health ; Parturition/*psychology ; Postpartum Period/*psychology ; Pregnancy ; Pregnancy Complications/*epidemiology ; Pregnancy Outcome/epidemiology/psychology ; Prevalence ; Risk Factors ; Stress Disorders, Post-Traumatic/*epidemiology ; Surveys and Questionnaires ; }, abstract = {Women can develop childbirth-related posttraumatic stress disorder (CB-PTSD) in at-term delivery with healthy baby outcome as well as following pre-term delivery and neonatal complications, a potential added stressor. No study compares risk factors of CB-PTSD associated with different infant outcomes. We investigated CB-PTSD risk factors by comparing women with or without neonatal complications. Analysis reveals the importance of antepartum and birth-related risk factors in CB-PTSD above and beyond child outcomes, suggesting childbirth is an independent stressor capable of evoking CB-PTSD.}, }
@article {pmid32439746, year = {2020}, author = {Bacorn, C and Kim, E and Borowsky, AD and Lin, LK}, title = {Previously undiagnosed neuroendocrine tumour mimicking breast cancer metastasis to the orbit.}, journal = {BMJ case reports}, volume = {13}, number = {5}, pages = {}, doi = {10.1136/bcr-2020-234629}, pmid = {32439746}, issn = {1757-790X}, mesh = {Adenocarcinoma/*pathology/therapy ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*secondary/therapy ; Diplopia ; Female ; Humans ; Intestinal Neoplasms/*pathology/therapy ; Neuroendocrine Tumors/*pathology/therapy ; Octreotide/therapeutic use ; Orbit ; Orbital Neoplasms/*secondary/therapy ; Pancreatic Neoplasms/*pathology/therapy ; Stomach Neoplasms/*pathology/therapy ; }, abstract = {Metastatic neuroendocrine neoplasms to the breast are rare and histopathologic overlap with mammary carcinomas has led to misdiagnosis. We present a case of a middle-aged woman with diplopia and a right medial rectus mass. Metastatic breast cancer was initially suspected based on a history of invasive ductal carcinoma. Detailed immunohistochemistry of the orbital biopsy, gallium-68 dotatate positron emission tomography-CT, and reevaluation of her prior breast specimen, demonstrated that her initial breast carcinoma diagnosis was in error and she was ultimately diagnosed with a previously unknown gastrointestinal neuroendocrine tumour metastatic to both the orbit and breast. This case highlights the challenges of differentiating between metastatic neuroendocrine tumours and invasive mammary carcinomas with neuroendocrine differentiation both in the breast and in the orbit. It is important to recognise the overlap so that a primary neuroendocrine neoplasm is not missed, or treatment significantly delayed.}, }
@article {pmid32438745, year = {2020}, author = {Moran Lauter, AN and Rutter, L and Cook, D and O'Rourke, JA and Graham, MA}, title = {Examining Short-Term Responses to a Long-Term Problem: RNA-Seq Analyses of Iron Deficiency Chlorosis Tolerant Soybean.}, journal = {International journal of molecular sciences}, volume = {21}, number = {10}, pages = {}, pmid = {32438745}, issn = {1422-0067}, support = {Project 5030-21220-006-00D//Agricultural Research Service/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; Iron/*deficiency ; Plant Leaves/genetics ; Plant Necrosis and Chlorosis/*genetics ; Plant Roots/genetics ; *RNA-Seq ; Signal Transduction ; Soybeans/*genetics ; Stress, Physiological/genetics ; Transcription Factors/metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) is a global crop production problem, significantly impacting yield. However, most IDC studies have focused on model species, not agronomically important crops. Soybean is the second largest crop grown in the United States, yet the calcareous soils across most of the upper U.S. Midwest limit soybean growth and profitability. To understand early soybean iron stress responses, we conducted whole genome expression analyses (RNA-sequencing) of leaf and root tissue from the iron efficient soybean (Glycine max) cultivar Clark, at 30, 60 and 120 min after transfer to iron stress conditions. We identified over 10,000 differentially expressed genes (DEGs), with the number of DEGs increasing over time in leaves, but decreasing over time in roots. To investigate these responses, we clustered our expression data across time to identify suites of genes, their biological functions, and the transcription factors (TFs) that regulate their expression. These analyses reveal the hallmarks of the soybean iron stress response (iron uptake and homeostasis, defense, and DNA replication and methylation) can be detected within 30 min. Furthermore, they suggest root to shoot signaling initiates early iron stress responses representing a novel paradigm for crop stress adaptations.}, }
@article {pmid32424149, year = {2020}, author = {Cheung, SM and Husain, E and Masannat, Y and Miller, ID and Wahle, K and Heys, SD and He, J}, title = {Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy.}, journal = {British journal of cancer}, volume = {123}, number = {2}, pages = {261-267}, pmid = {32424149}, issn = {1532-1827}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Female ; Glycolysis/genetics ; Humans ; Lactate Dehydrogenase 5/genetics/metabolism ; Lactic Acid/isolation &amp; purification/*metabolism ; Magnetic Resonance Spectroscopy ; Middle Aged ; *Prognosis ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {BACKGROUND: Precision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.<br><br>METHODS: Thirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.<br><br>RESULTS: There was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = -0.3734, p = 0.0421).<br><br>CONCLUSION: Our results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.}, }
@article {pmid32423910, year = {2020}, author = {O'Connor, P and Bhadbhade, P and Khan, Q and Williamson, S}, title = {Acral vascular syndrome during an immune checkpoint inhibitor.}, journal = {BMJ case reports}, volume = {13}, number = {5}, pages = {}, doi = {10.1136/bcr-2019-233463}, pmid = {32423910}, issn = {1757-790X}, mesh = {African Americans ; Diagnosis, Differential ; Female ; Fingers/blood supply/pathology ; Gangrene/chemically induced/*diagnostic imaging/*pathology/surgery ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Middle Aged ; Raynaud Disease/chemically induced/*diagnostic imaging/*pathology/surgery ; Thrombosis ; Vasculitis ; }, abstract = {Immune checkpoint inhibitors, including antiprogrammed death cell protein 1 (anti-PD-1) and anti cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), have been associated with a range of autoimmune-related side effects since their introduction in cancer treatment. Small vessel digital necrosis, referred to as the acral vascular syndrome, is a rare but serious complication that can result in loss of digits. Here we present a case report of acral vascular syndrome and review possible aetiologies. A 45- year-old woman with invasive ductal carcinoma of the left breast presented to the emergency department during neoadjuvant treatment with carboplatin, docetaxel and pembrolizumab with complaints of severe pain in her right third digit. She had physical findings consistent with ischaemic necrosis and gangrene of the distal phalanx. Angiography demonstrated Raynaud's phenomenon in the distal portion of the digits. Laboratory testing showed a weakly positive RNA polymerase III antibody level. Her case resulted in surgical amputation of her affected digit after partial resolution of symptoms with prednisone, vasodilators and antibiotics.}, }
@article {pmid32408270, year = {2020}, author = {Pedro, J and Cunha, FM and Neto, V and Hespanhol, V and Martins, DF and Guimarães, S and Varela, A and Carvalho, D}, title = {Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?.}, journal = {Endocrinology, diabetes &amp; metabolism case reports}, volume = {2020}, number = {}, pages = {}, pmid = {32408270}, issn = {2052-0573}, abstract = {Summary: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up.<br><br>Learning points: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.}, }
@article {pmid32381867, year = {2020}, author = {Tamaoki, M and Nio, Y and Tamaoki, M and Sakamoto, M and Uesugi, K and Sakamoto, T and Imai, S and Maruyama, R}, title = {[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {47}, number = {1}, pages = {77-81}, pmid = {32381867}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/radiotherapy ; Female ; *Hemangiosarcoma/etiology ; Humans ; Japan ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; *Neoplasms, Radiation-Induced ; *Skin Neoplasms ; }, abstract = {We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.}, }
@article {pmid32380439, year = {2020}, author = {Rodriguez-Ibarria, NG and Pinar, MB and García, L and Cabezón, MA and Lloret, M and Rey-Baltar, MD and Rdguez-Melcón, JI and Lara, PC}, title = {Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {52}, number = {}, pages = {45-49}, pmid = {32380439}, issn = {1532-3080}, mesh = {Aged ; Brachytherapy/*methods ; Breast Neoplasms/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*radiotherapy ; Radiotherapy Dosage ; }, abstract = {Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.}, }
@article {pmid32371885, year = {2020}, author = {Schwarz, D and Hidmark, AS and Sturm, V and Fischer, M and Milford, D and Hausser, I and Sahm, F and Breckwoldt, MO and Agarwal, N and Kuner, R and Bendszus, M and Nawroth, PP and Heiland, S and Fleming, T}, title = {Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {7593}, pmid = {32371885}, issn = {2045-2322}, mesh = {Animals ; Biopsy ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1/complications ; Diabetic Neuropathies/*diagnostic imaging/etiology/*pathology ; Disease Models, Animal ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging/methods/standards ; Mice ; Microscopy ; Microscopy, Electron ; }, abstract = {In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves' fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.}, }
@article {pmid32365829, year = {2020}, author = {Cortes-Urrea, C and Bueno-Gutiérrez, F and Solarte, M and Guevara-Burbano, M and Tobar-Tosse, F and Vélez-Varela, PE and Bonilla, JC and Barreto, G and Velasco-Medina, J and Moreno, PA and Rivas, JL}, title = {Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.}, journal = {Biomolecules}, volume = {10}, number = {5}, pages = {}, pmid = {32365829}, issn = {2218-273X}, support = {PI18/00591//Instituto de Salud Carlos III/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; *Exome ; Female ; Humans ; Middle Aged ; *Mutation ; Oncogenes ; }, abstract = {Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.}, }
@article {pmid32354932, year = {2020}, author = {Fujii, T and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Shirabe, K}, title = {Relationship Between FDG Uptake and the Platelet/lymphocyte Ratio in Patients With Breast Invasive Ductal Cancer.}, journal = {In vivo (Athens, Greece)}, volume = {34}, number = {3}, pages = {1365-1369}, pmid = {32354932}, issn = {1791-7549}, mesh = {Aged ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/etiology/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Leukocyte Count ; *Lymphocyte Count ; Middle Aged ; Neutrophils ; *Platelet Count ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Tumor Microenvironment ; }, abstract = {BACKGROUND/AIM: We investigated the relationship between F18-fluorodeoxyglucose (FDG) uptake and the platelet/lymphocyte ratio (PLR), as both represent inflammation.<br><br>PATIENTS AND METHODS: We retrospectively analyzed the cases of 143 consecutive invasive ductal carcinoma patients who had undergone preoperative FDG-PET and surgery. We divided the patients into groups based on their maximum standardized uptake value (SUVmax) values: low (<2.5) and high (≥2.5) and based on their PLRs: low (<130) and high (≥130). We determined the relationships between the SUVmax or PLR and clinicopathological features.<br><br>RESULTS: Seventy-three patients (51.0%) had a high SUVmax in their primary tumor. There were significant associations between SUVmax and the PLR. A multivariate analysis revealed that high PLR, but not NLR, was independent factor associated with a high SUVmax. Seventy-four patients (51.7%) had a high PLR; The factors significantly associated with high PLR were large tumor size, presence of node metastasis, presence of vascular invasion, high NLR, and high SUVmax.<br><br>CONCLUSION: In breast cancer patients, the PLR is independently associated with the SUVmax, but not with recurrent disease. In breast cancer patients with a high SUVmax and/or PLR, these values may reflect the tumor microenvironment.}, }
@article {pmid32338774, year = {2020}, author = {Kumar, V and Agrawal, R and Pandey, A and Kopf, S and Hoeffgen, M and Kaymak, S and Bandapalli, OR and Gorbunova, V and Seluanov, A and Mall, MA and Herzig, S and Nawroth, PP}, title = {Compromised DNA repair is responsible for diabetes-associated fibrosis.}, journal = {The EMBO journal}, volume = {39}, number = {11}, pages = {e103477}, pmid = {32338774}, issn = {1460-2075}, support = {R37 AG046320/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; //Helmholtz Cross Program Topic Metabolic Dysfunction/ ; //Foundation for Diabetes Research/ ; GRK 1874-DIAMICOM//Deutsche Forschungsgemeinschaft (DFG)/ ; R01 AG027237/AG/NIA NIH HHS/United States ; SFB1118//Deutsche Forschungsgemeinschaft (DFG)/ ; }, mesh = {A549 Cells ; *DNA End-Joining Repair ; Diabetes Mellitus, Type 1/genetics/*metabolism/pathology ; Diabetes Mellitus, Type 2/genetics/*metabolism/pathology ; Fibrosis ; HEK293 Cells ; Humans ; }, abstract = {Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD+ /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes.}, }
@article {pmid32317515, year = {2020}, author = {Pyla, RD and Potekar, RM and Patil, VS and Reddy, AK and Sathyashree, KV}, title = {Quantitative mast cell analysis and hormone receptor study (ER, PR and HER2/neu) in invasive carcinoma of breast.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {2}, pages = {200-204}, doi = {10.4103/IJPM.IJPM_155_19}, pmid = {32317515}, issn = {0974-5130}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Mast Cells/immunology/*pathology ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tumor Microenvironment/*immunology ; }, abstract = {Context: Breast cancer constitutes nearly one third of cancers among women. Immune responses caused by neoplastic cells lead to the accumulation of inflammatory cells like mast cells (MCs), macrophages, lymphocytes, and plasma cells around the tumor tissue forming the tumor microenvironment.<br><br>Aim: The study aims at quantifying the role of MCs in different grades of invasive carcinoma of breast with respect to estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2/neu).<br><br>Materials and Methods: This study included 60 cases of invasive carcinoma of breast. Toluidine blue staining was used for quantitative MC analysis and correlated with immunohistochemistry analysis for hormonal markers' positivity-ER, PR and HER2/neu.<br><br>Results: The mean age was 52 years (range: 25-75 years). The average number of MCs in Grade I, II, and III were 24.05, 18.4, and 7.9, respectively, with a significant P value. ER, PR, and HER2/neu positivity was found in 60%, 55%, and 32% of the cases, respectively. ER positivity with mean MC count of 23.55 was found in 36 cases, and 33 cases were positive for PR with a mean MC count of 24.18 and a significant P value. HER2 positive cases were 28 with a mean MC count of 20.82.<br><br>Conclusion: The presence of MCs in breast cancer is inversely proportional to the grade of tumor, i.e., a maximum number of MCs were seen in low grade tumors. In addition, there is a positive correlation between ER and PR receptor positivity with the presence of MCs in the stroma of breast cancer.}, }
@article {pmid32310154, year = {2020}, author = {Suhani, S and Kazi, M and Parshad, R and Seenu, V and Verma, E and Mathur, S and Gupta, SD and Haresh, KP}, title = {An audit of over 1000 breast cancer patients from a tertiary care center of Northern India.}, journal = {Breast disease}, volume = {39}, number = {2}, pages = {91-99}, doi = {10.3233/BD-190435}, pmid = {32310154}, issn = {1558-1551}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/physiopathology ; Breast Neoplasms, Male/*epidemiology/physiopathology ; Female ; Humans ; India/epidemiology ; Male ; *Medical Audit ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers/*statistics &amp; numerical data ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the commonest cancer among women. India along with United States and China collectively account for one third of the global burden. The present study reports the clinico-epidemiological data of our patient population. This may help in better understanding of the disease in our population and also form ground for conducting further breast cancer research in India.<br><br>METHODS: The study was conducted at an apex teaching and medical research institution in India from September 2013 to April 2015 as a retrospective review of prospectively collected data of breast cancer patients. The socio-demographic characteristics, reproductive risk factors, clinical presentation, TNM staging and histopathological characteristics for breast cancer in these patients were recorded. The data was recorded on an Xcel spreadsheet and analyzed using IBM SPSS 21.<br><br>RESULTS: The study comprised of 1310 breast cancer patients with males comprising 1.1%. The median age of presentation was 47 years, and menarche 14 years. Most of women were married and multiparous. More than half of the women were postmenopausal at presentation. All patients were symptomatic at presentation with median duration of symptom of 5 months and median lump size of 5 cm. Most common stage at presentation was Stage II and most common histopathology was Invasive ductal carcinoma. 61.9% tumors were hormone receptor positive. Triple negative cancers formed one third of all tumors.<br><br>CONCLUSION: Breast cancer in the Indian scenario is a disease of younger woman who lack the characteristic reproductive and demographic risk factors. This calls for a need to study the clinico-demographic risk factors and characteristics of our own population.}, }
@article {pmid32279596, year = {2020}, author = {Duman, B and Kuşman, A and Çolak, B and Şenler, FÇ and Kumbasar, H}, title = {Tamoxifen-induced acute mania: A case report.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {26}, number = {8}, pages = {2025-2027}, doi = {10.1177/1078155220915959}, pmid = {32279596}, issn = {1477-092X}, mesh = {Acute Disease ; Antineoplastic Agents, Hormonal/*adverse effects ; Breast Neoplasms/*drug therapy ; Female ; Humans ; Mania/*chemically induced ; Middle Aged ; Tamoxifen/*adverse effects ; }, abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication.<br><br>CASE REPORT: A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21 days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania.<br><br>MANAGEMENT AND OUTCOME: The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24 h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then.<br><br>DISCUSSION: To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen's nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.}, }
@article {pmid32272928, year = {2020}, author = {Sutham, K and Khuwuthyakorn, P and Thinnukool, O}, title = {Thailand medical mobile application for patients triage base on criteria based dispatch protocol.}, journal = {BMC medical informatics and decision making}, volume = {20}, number = {1}, pages = {66}, pmid = {32272928}, issn = {1472-6947}, mesh = {*Emergency Medical Services ; Humans ; *Mobile Applications ; Patients ; Reproducibility of Results ; Retrospective Studies ; Thailand ; Triage ; }, abstract = {BACKGROUND: Before patients are admitted into the emergency department, it is important to undertake a pre-hospital process, both in terms of treatment performance and a request for resources from an emergency unit. The existing system to triage patients in Thailand is not functioning to its full capacity in either the primary medical system or pre-hospital treatment with shortcomings in the areas of speed, features, and appropriate systems. There is a high possibility of issuing a false Initial Dispatch Code (IDC), which will cause the over or underutilisation of emergency resources, such as rescue teams, community hospitals and emergency medical volunteers.<br><br>METHODS: A usability system design, together with a reliability test, was applied to develop an application to optimise the pre-hospital process, specifically to sort patients, using an IDC to improve the request for emergency resources. The triage mobile application was developed on both iOS and Android operating systems to support patient triage based on Criteria Based Dispatch (CBD). The 25 main symptom categories covered by CBD were used to design and develop the application, and 12 emergency medical staff, including doctors and nurses, were asked to test the system in the aspects of triage protocol correction, triage reliability, usability and user satisfaction.<br><br>RESULTS: The results of testing the proposed triage application were compared with the time used to triage by experienced staff and it was found that, in non-trauma cases, it was faster and more effective to use the application for emergency operations and to correct the IDC code representation.<br><br>CONCLUSIONS: The triage application will be utilised to support the pre-hospital process and to classify patients' conditions before they are admitted to the Emergency Department (ED). The application is suitable for users who are not medical emergency staff. Patients with non-trauma symptoms may be a suitable group to use the application in terms of time used to identify IDC for their own symptoms. The use of the application can be beneficial for those who wish to self-identify their symptoms before requesting medical services.}, }
@article {pmid32269189, year = {2020}, author = {Lee, YH and Kwon, MJ and Park, JH and Jeong, SJ and Kim, TH and Jeong, HW and Lee, SH}, title = {Neurofibromatosis Type 1 with the Development of Pheochromocytoma and Breast Cancer.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {59}, number = {13}, pages = {1665-1669}, pmid = {32269189}, issn = {1349-7235}, mesh = {Adrenal Gland Neoplasms/*complications/surgery ; Adrenalectomy ; Adult ; Biopsy ; Breast Neoplasms/*complications/therapy ; Cafe-au-Lait Spots/pathology ; Female ; Humans ; Incidental Findings ; Neurofibromatosis 1/*complications ; Pheochromocytoma/*complications ; Skin Neoplasms/pathology ; }, abstract = {A 40-year-old woman presented with a left adrenal incidentaloma. Based on the presence of café-au-lait spots, cutaneous neurofibroma, and family history, she was diagnosed with neurofibromatosis type 1 (NF1). Adrenal incidentaloma screening showed an elevated normetanephrine level; the left adrenal mass showed the uptake of I-123 meta-iodobenzylguanidine. She underwent left adrenalectomy, and pheochromocytoma was diagnosed. One year later, the results of a biopsy of a palpable mass in the left breast suggested invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy followed by left breast-conserving surgery. We herein report a rare case of an NF1 patient who developed both pheochromocytoma and breast cancer.}, }
@article {pmid32266446, year = {2020}, author = {Zong, L and Mo, S and Yu, S and Zhou, Y and Zhang, M and Chen, J and Xiang, Y}, title = {Expression of the immune checkpoint VISTA in breast cancer.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {69}, number = {8}, pages = {1437-1446}, doi = {10.1007/s00262-020-02554-3}, pmid = {32266446}, issn = {1432-0851}, support = {81672648//National Natural Science Foundation of China/International ; 81971475//National Natural Science Foundation of China/International ; CAMS-2017-I2M-1-002//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; CAMS-2016-I2M-1-001//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; B7 Antigens/*metabolism ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*metabolism ; Survival Rate ; }, abstract = {V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as well as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast [corrected]. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.}, }
@article {pmid32246378, year = {2020}, author = {Le, AN and Harton, J and Desai, H and Powers, J and Zelley, K and Bradbury, AR and Nathanson, KL and Shah, PD and Doucette, A and Freedman, GM and Gabriel, P and Domchek, SM and MacFarland, SP and Maxwell, KN}, title = {Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome.}, journal = {Breast cancer research and treatment}, volume = {181}, number = {1}, pages = {181-188}, pmid = {32246378}, issn = {1573-7217}, support = {K08 CA215312/CA/NCI NIH HHS/United States ; K08CA21531//National Cancer Institute (US)/ ; ITMAT MHB//University of Pennsylvania/ ; 1017184//Burroughs Wellcome Fund/ ; }, mesh = {Adolescent ; Adult ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Female ; Follow-Up Studies ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/*complications ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasms, Radiation-Induced/*etiology/pathology ; Prognosis ; Radiotherapy, Adjuvant/*adverse effects ; Retrospective Studies ; Survival Rate ; Tumor Suppressor Protein p53/genetics ; Young Adult ; }, abstract = {PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy.<br><br>METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses.<br><br>RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort.<br><br>CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.}, }
@article {pmid32236595, year = {2020}, author = {Gao, X and Bao, H and Liu, L and Zhu, W and Zhang, L and Yue, L}, title = {Systematic analysis of lysine acetylome and succinylome reveals the correlation between modification of H2A.X complexes and DNA damage response in breast cancer.}, journal = {Oncology reports}, volume = {43}, number = {6}, pages = {1819-1830}, pmid = {32236595}, issn = {1791-2431}, mesh = {Acetylation ; Adult ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Case-Control Studies ; Cell Line, Tumor ; Cell Survival ; *DNA Damage ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*metabolism ; Humans ; Lysine/*chemistry ; MCF-7 Cells ; Middle Aged ; Nuclear Proteins/metabolism ; Proteomics/*methods ; Succinic Acid/chemistry ; Up-Regulation ; }, abstract = {Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para‑carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.}, }
@article {pmid32212794, year = {2020}, author = {Rasmy, A and Sorour, Y}, title = {Effect of Obesity on Neoadjuvant Systemic Therapy Outcomes in Patients with Early Breast Cancer: A Retrospective Institutional Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {3}, pages = {683-691}, pmid = {32212794}, issn = {2476-762X}, mesh = {Adult ; Aged ; Body Mass Index ; Breast Neoplasms/complications/*therapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Obesity/*complications ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Obesity and overweight are usually considered as poor prognostic factors in early breast cancer. Body mass index (BMI) is a significant predictive factor for lower pathologic complete response (pCR) rates after neo-adjuvant systemic therapy (NST). The relationship between obesity and breast cancer prognosis varies according to patient and tumor characteristics such as menopausal status and tumor subtype, respectively.<br><br>PATIENTS AND METHODS: Between March 2010 and October 2013, 80 patients with early breast cancer who had received standard NST from KFSH Saudi Arabia were included in this study. For statistical analysis, the study participants were categorized into two groups based on their BMI, as normal (BMI < 25 kg/m2) and obese groups (BMI ≥ 25 kg/m2). pCR was defined as non-invasive cancer in the breast/axillary tissue.<br><br>RESULTS: The median age of our patients was 48 (range, 38-68) years. Invasive ductal carcinoma (IDC) subtype was identified in 93.8% of the cases. Additionally, 26 (32.5%) and 33 (41.25%) patients were diagnosed with stage II and stage IIIA breast cancer, respectively. Lymphovascular invasion was detected in 32.5%, whereas intermediate and high-grade malignancy were found in 61.25% and 32.5% of the patients, respectively. Forty-four patients (55%) were obese. pCR was achieved in 56 patients (70%), and the comparison between patients with and without pCR revealed that those in the former group had significantly lower tumor grades. Significantly, lower relapse and mortality rates were distinguished in patients who achieved pCR than in those who did not. Additionally, comparison between normal and obese patients revealed that a high number of patients in both groups were post-menopausal (p = 0.001). However, survival analysis indicated the absence of significant differences in disease-free survival between the two groups based on BMI (p = 0.19). Conversely, patients with normal BMI had significantly better overall survival than obese patients (p = 0.029), with a higher mortality rate noted in the obese group (16.7% vs 2.3%, p = 0.037).<br><br>CONCLUSIONS: In the present study, 58.3% of patients that failed to achieve pCR had BMI above the normal level; they moreover had higher relapse rates and lower survival compared with normal BMI patients. This finding needs to be verified through further prospective studies to determine if BMI is a risk factor for breast cancer.}, }
@article {pmid32209879, year = {2020}, author = {Liu, Q and Zhang, J and Kulkarni, HR and Baum, RP}, title = {177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {5}, pages = {e232-e235}, doi = {10.1097/RLU.0000000000003005}, pmid = {32209879}, issn = {1536-0229}, mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology/*radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Neuroendocrine Tumors/diagnostic imaging/metabolism/pathology/*radiotherapy ; Octreotide/*analogs &amp; derivatives/therapeutic use ; Positron Emission Tomography Computed Tomography ; Receptors, Somatostatin/*metabolism ; Treatment Outcome ; }, abstract = {Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.}, }
@article {pmid32202536, year = {2020}, author = {Szentirmai, E and Giannico, GA}, title = {Intraductal carcinoma of the prostate.}, journal = {Pathologica}, volume = {112}, number = {1}, pages = {17-24}, doi = {10.32074/1591-951X-5-20}, pmid = {32202536}, issn = {1591-951X}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Prostatectomy/trends ; Prostatic Neoplasms/*diagnosis/*genetics/therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.}, }
@article {pmid32190711, year = {2020}, author = {Lee, RA and Vo, DT and Zurko, JC and Griffin, RL and Rodriguez, JM and Camins, BC}, title = {Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.}, journal = {Open forum infectious diseases}, volume = {7}, number = {3}, pages = {ofaa064}, pmid = {32190711}, issn = {2328-8957}, abstract = {Background: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown.<br><br>Methods: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture.<br><br>Results: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P < .001), echocardiography (79% vs 45%; P < .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P < .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P < .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76).<br><br>Conclusions: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.}, }
@article {pmid32161717, year = {2020}, author = {Guo, T and Chen, Z and Xu, J and Zhang, Y}, title = {Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {32}, pmid = {32161717}, issn = {2234-943X}, abstract = {Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.}, }
@article {pmid32157060, year = {2019}, author = {Egawa, C and Yanai, A and Yanagawa, T and Takatsuka, Y and Takeno, A and Masuzawa, T and Hata, T and Kagawa, Y and Ohmura, Y and Katsura, Y and Murakami, K and Sakamoto, T and Kawai, K and Takeda, Y and Murata, K}, title = {[Long-Term Survival in a Case of Breast Cancer with Brain Metastases and No Other Distant Metastases Treated by Surgical Removal and Gamma Knife Radiosurgery].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2063-2065}, pmid = {32157060}, issn = {0385-0684}, mesh = {Adult ; *Brain Neoplasms/radiotherapy/secondary ; *Breast Neoplasms/radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; *Radiosurgery ; }, abstract = {A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.}, }
@article {pmid32156965, year = {2019}, author = {Kinoshita, H and Teraoka, H and Mori, T and Hasegawa, T and Noda, E and Takashima, T and Hirakawa, K and Ohira, M}, title = {[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2461-2463}, pmid = {32156965}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; Female ; Humans ; *Jaundice/etiology ; *Liver Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel ; }, abstract = {A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.}, }
@article {pmid32156942, year = {2019}, author = {Morisaki, T and Takashima, T and Asano, Y and Kashiwagi, S and Noda, S and Onoda, N and Ohira, M}, title = {[Two Cases of Orbital Metastasis from Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2392-2394}, pmid = {32156942}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms ; Eye Neoplasms/*secondary ; Female ; Humans ; *Liver Neoplasms ; Magnetic Resonance Imaging ; }, abstract = {Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.}, }
@article {pmid32156914, year = {2019}, author = {Nakama, Y and Maruyama, Y and Hisaka, T and Yasumoto, M and Okabe, Y and Naito, Y and Yamaguchi, M and Tanaka, M and Tanaka, H and Akagi, Y and Okuda, K}, title = {[A Vesected Case of Pancreatic Metastasis from Breast Cancer Which Recurred Six Years after Breast Surgery].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {13}, pages = {2309-2311}, pmid = {32156914}, issn = {0385-0684}, mesh = {*Adenocarcinoma/secondary/surgery ; Adult ; *Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/secondary ; }, abstract = {A 43-year-old woman who underwent surgical resection of invasive ductal carcinoma in the left breast at the age of 37 years old presented at our hospital for evaluation of pancreatic tumor. The original tumor was estrogen receptor(ER)progesterone receptor(PgR)and HER2 positive. At that time, she underwent radical mastectomy with no evident nodal disease. Postoperatively, the patient was placed on adjuvant tamoxifen therapy for several years. Six years following the original diagnosis of breast cancer, she was referred to the hospital for routine check-up while asymptomatic. Follow-up examination showed a solitary hypodense mass approximately 0.9 cm in size in the pancreas body on dynamic CT scan. The patient underwent a standard distal pancreatectomy with standard regional lymphadenectomy. Histopathological examination and immunohistochemical features revealed that the tumor was compatible with metastatic pancreatic adenocarcinoma from breast cancer.}, }
@article {pmid32139710, year = {2020}, author = {Roy, S and Kumar, R and Mittal, V and Gupta, D}, title = {Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {4113}, pmid = {32139710}, issn = {2045-2322}, support = {SRF//Council of Scientific and Industrial Research (CSIR)/International ; SRF//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/PR6963/BID/7/427/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/BI/25/066/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; }, mesh = {Algorithms ; Breast Neoplasms/*classification/genetics ; Carcinoma, Ductal, Breast/*classification/genetics ; Databases, Genetic ; Datasets as Topic ; Early Detection of Cancer ; Female ; Gene Ontology ; Humans ; Machine Learning ; Microarray Analysis ; Models, Biological ; Neoplasm Staging ; Protein Interaction Maps ; RNA, Neoplasm ; RNA-Seq ; Reproducibility of Results ; *Supervised Machine Learning ; *Transcriptome ; }, abstract = {Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.}, }
@article {pmid32138738, year = {2020}, author = {Sun, T and Yang, W and Toprani, SM and Guo, W and He, L and DeLeo, AB and Ferrone, S and Zhang, G and Wang, E and Lin, Z and Hu, P and Wang, X}, title = {Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.}, journal = {Cell communication and signaling : CCS}, volume = {18}, number = {1}, pages = {36}, pmid = {32138738}, issn = {1478-811X}, support = {R01 CA226981/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.<br><br>METHODS: High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24-/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.<br><br>CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.}, }
@article {pmid32119669, year = {2020}, author = {Rangel, GW and Clark, MA and Kanjee, U and Goldberg, JM and MacInnis, B and José Menezes, M and Ferreira, MU and Duraisingh, MT}, title = {Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle.}, journal = {PLoS neglected tropical diseases}, volume = {14}, number = {3}, pages = {e0008104}, pmid = {32119669}, issn = {1935-2735}, support = {R01 AI140751/AI/NIAID NIH HHS/United States ; R01 HL139337/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Culture Media/chemistry ; Erythrocytes/*parasitology ; Female ; *Gene Expression Profiling ; *Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Malaria, Vivax/*parasitology ; Male ; Parasitology/methods ; Plasmodium vivax/genetics/*growth &amp; development ; Sequence Analysis, RNA ; }, abstract = {Approximately one-third of the global population is at risk of Plasmodium vivax infection, and an estimated 7.51 million cases were reported in 2017. Although, P. vivax research is currently limited by the lack of a robust continuous in vitro culture system for this parasite, recent work optimizing short-term ex vivo culture of P. vivax from cryopreserved isolates has facilitated quantitative assays on synchronous parasites. Pairing this improved culture system with low-input Smart-seq2 RNAseq library preparation, we sought to determine whether transcriptional profiling of P. vivax would provide insight into the differential survival of parasites in different culture media. To this end we probed the transcriptional signature of three different ex vivo P. vivax samples in four different culture media using only 1000 cells for each time point taken during the course of the intraerythrocytic development cycle (IDC). Using this strategy, we achieved similar quality transcriptional data to previously reported P. vivax transcriptomes. We found little effect with varying culture media on parasite transcriptional signatures, identified many novel gametocyte-specific genes from transcriptomes of FACS-isolated gametocytes, and determined invasion ligand expression in schizonts in biological isolates and across the IDC. In total, these data demonstrate the feasibility and utility of P. vivax RNAseq-based transcriptomic studies using minimal biomass input to maximize experimental capacity.}, }
@article {pmid32103749, year = {2020}, author = {Tewari, SG and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.}, journal = {Malaria journal}, volume = {19}, number = {1}, pages = {94}, pmid = {32103749}, issn = {1475-2875}, support = {R01 AI125534/AI/NIAID NIH HHS/United States ; R01 AI065853/NH/NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command/ ; }, mesh = {Erythrocytes/*metabolism/parasitology ; Malaria, Falciparum/*metabolism/parasitology ; Parasitemia/*metabolism/parasitology ; Plasmodium falciparum/*growth &amp; development ; }, abstract = {BACKGROUND: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development.<br><br>METHODS: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures.<br><br>RESULTS: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures.<br><br>CONCLUSIONS: The current study revealed a number of heretofore unidentified metabolic components of the host-parasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.}, }
@article {pmid32088208, year = {2020}, author = {Guillet, C and Rechsteiner, M and Bellini, E and Choschzick, M and Moskovszky, L and Dedes, K and Papassotiropoulos, B and Varga, Z}, title = {Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.}, journal = {Human pathology}, volume = {98}, number = {}, pages = {64-73}, doi = {10.1016/j.humpath.2020.02.002}, pmid = {32088208}, issn = {1532-8392}, mesh = {Adult ; Age of Onset ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Heredity ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; *Mutation ; Papilloma/*genetics/pathology/surgery ; Pedigree ; Phenotype ; Proto-Oncogene Proteins c-akt/*genetics ; }, abstract = {Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancer needs to be analyzed in further studies.}, }
@article {pmid32086991, year = {2020}, author = {Luo, Y and Kishi, S and Sasaki, T and Ohmori, H and Fujiwara-Tani, R and Mori, S and Goto, K and Nishiguchi, Y and Mori, T and Kawahara, I and Kondoh, M and Kuniyasu, H}, title = {Targeting claudin-4 enhances chemosensitivity in breast cancer.}, journal = {Cancer science}, volume = {111}, number = {5}, pages = {1840-1850}, pmid = {32086991}, issn = {1349-7006}, support = {17KJB320010//Natural Science Foundation of Jiangsu Education Department Project/ ; 16H05164//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19923//Ministry of Education, Culture, Sports, Science and Technology/ ; 81702723//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Antibodies/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Claudin-1 ; Claudin-4/chemistry/genetics/*immunology ; Drug Synergism ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Paclitaxel/pharmacology/therapeutic use ; Tamoxifen/pharmacology/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy/metabolism/pathology ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.}, }
@article {pmid32079470, year = {2020}, author = {Yin, S and Fan, Y and He, X and Wei, G and Wen, Y and Zhao, Y and Shi, M and Wei, J and Chen, H and Han, J and Jiang, L and Zhang, Q}, title = {The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.}, journal = {RNA biology}, volume = {17}, number = {6}, pages = {828-842}, pmid = {32079470}, issn = {1555-8584}, mesh = {Computational Biology/methods ; Erythrocytes/parasitology ; Exosome Multienzyme Ribonuclease Complex ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Ontology ; Humans ; Life Cycle Stages ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/*genetics/*growth &amp; development ; *RNA Splicing ; RNA Stability ; RNA, Messenger/genetics ; RNA, Protozoan/*genetics ; RNA, Untranslated/genetics ; }, abstract = {The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.}, }
@article {pmid32063604, year = {2020}, author = {Granados, K and Hüser, L and Federico, A and Sachindra, S and Wolff, G and Hielscher, T and Novak, D and Madrigal-Gamboa, V and Sun, Q and Vierthaler, M and Larribère, L and Umansky, V and Utikal, J}, title = {T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.}, journal = {British journal of cancer}, volume = {122}, number = {7}, pages = {1023-1036}, pmid = {32063604}, issn = {1532-1827}, support = {OAICE-CAB-09-133-2015//Universidad de Costa Rica (University of Costa Rica)/International ; PED-054-2015-2//Ministerio de Ciencia Tecnología y Telecomunicaciones (Ministerio de Ciencia Tecnología y Telecomunicaciones de Costa Rica)/International ; 259332240 / RTG 2099//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; }, mesh = {Animals ; Calcium Channels, T-Type/*genetics ; Disease Models, Animal ; Female ; Humans ; Melanoma/*drug therapy/pathology ; Mice ; Protein Kinase Inhibitors/pharmacology/*therapeutic use ; }, abstract = {BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).<br><br>METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.<br><br>RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.<br><br>CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.}, }
@article {pmid32062352, year = {2020}, author = {Kanwar, N and Carmine-Simmen, K and Nair, R and Wang, C and Moghadas-Jafari, S and Blaser, H and Tran-Thanh, D and Wang, D and Wang, P and Wang, J and Pasculescu, A and Datti, A and Mak, T and Lewis, JD and Done, SJ}, title = {Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis.}, journal = {EBioMedicine}, volume = {52}, number = {}, pages = {102646}, pmid = {32062352}, issn = {2352-3964}, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Calcium/metabolism ; Calcium Channels/chemistry/*genetics/metabolism ; Calcium Signaling ; Cell Line ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Progression ; Female ; *Gene Amplification ; Gene Expression ; Humans ; Immunohistochemistry ; Mice ; Models, Biological ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Domains and Motifs ; }, abstract = {BACKGROUND: Previously, we found that amplification of chromosome 17q24.1-24.2 is associated with lymph node metastasis, tumour size, and lymphovascular invasion in invasive ductal carcinoma. A gene within this amplicon, CACNG4, an L-type voltage-gated calcium channel gamma subunit, is elevated in breast cancers with poor prognosis. Calcium homeostasis is achieved by maintaining low intracellular calcium levels. Altering calcium influx/efflux mechanisms allows tumour cells to maintain homeostasis despite high serum calcium levels often associated with advanced cancer (hypercalcemia) and aberrant calcium signaling.<br><br>METHODS: In vitro 2-D and 3-D assays, and intracellular calcium influx assays were utilized to measure tumourigenic activity in response to altered CANCG4 levels and calcium channel blockers. A chick-CAM model and mouse model for metastasis confirmed these results in vivo.<br><br>FINDINGS: CACNG4 alters cell motility in vitro, induces malignant transformation in 3-dimensional culture, and increases lung-specific metastasis in vivo. CACNG4 functions by closing the channel pore, inhibiting calcium influx, and altering calcium signaling events involving key survival and metastatic pathway genes (AKT2, HDAC3, RASA1 and PKCζ).<br><br>INTERPRETATION: CACNG4 may promote homeostasis, thus increasing the survival and metastatic ability of tumour cells in breast cancer. Our findings suggest an underlying pathway for tumour growth and dissemination regulated by CACNG4 that is significant with respect to developing treatments that target these channels in tumours with aberrant calcium signaling.<br><br>FUNDING: Canadian Breast Cancer Foundation, Ontario; Canadian Institutes of Health Research.}, }
@article {pmid32051475, year = {2020}, author = {Beetch, M and Harandi-Zadeh, S and Yang, T and Boycott, C and Chen, Y and Stefanska, B and Mohammed, SI}, title = {DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {2415}, pmid = {32051475}, issn = {2045-2322}, mesh = {Animals ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*veterinary ; *DNA Methylation ; Disease Progression ; Dog Diseases/*genetics/pathology ; Dogs/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/*veterinary ; }, abstract = {Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.}, }
@article {pmid32050925, year = {2020}, author = {Dettogni, RS and Stur, E and Laus, AC and da Costa Vieira, RA and Marques, MMC and Santana, IVV and Pulido, JZ and Ribeiro, LF and de Jesus Parmanhani, N and Agostini, LP and Dos Reis, RS and de Vargas Wolfgramm Dos Santos, E and Alves, LNR and Garcia, FM and Santos, JA and do Prado Ventorim, D and Reis, RM and Louro, ID}, title = {Potential biomarkers of ductal carcinoma in situ progression.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {119}, pmid = {32050925}, issn = {1471-2407}, support = {0468/2015//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 66141494/2014//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 66271126/2014//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 0698/2015//Fundação de Amparo à Pesquisa do Espirito Santo-Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (FAPES-CAPES)/ ; }, mesh = {Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics/metabolism ; Computational Biology ; Disease Progression ; Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; Transcriptome ; }, abstract = {BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.<br><br>METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.<br><br>RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.<br><br>CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.}, }
@article {pmid32050826, year = {2020}, author = {Mostyka, M and Jessurun, J and Matrai, C}, title = {Sarcoid-Like Granulomatosis in a Patient With Breast Cancer Mimicking Refractory Metastatic Disease.}, journal = {International journal of surgical pathology}, volume = {28}, number = {6}, pages = {668-671}, doi = {10.1177/1066896920905887}, pmid = {32050826}, issn = {1940-2465}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Granuloma, Respiratory Tract/chemically induced/*pathology ; Humans ; Lung/pathology ; Pulmonary Fibrosis/chemically induced/pathology ; }, abstract = {Sarcoid-like granulomatosis is a known but rare adverse reaction to immune checkpoint inhibitors and chemotherapy in the treatment of advanced solid tumors. We present a case of a 29-year-old female with a pathologically confirmed poorly differentiated invasive ductal carcinoma of the breast with presumed metastases to the lungs, hilar lymph nodes, liver, and spleen. Despite appropriate chemotherapy, the patient developed pulmonary lesions that were interpreted on imaging studies as progression of malignancy. Autopsy revealed disseminated sarcoid-like granulomatosis with multiple noncaseating granulomata with associated fibrosis in the lungs, liver, and spleen. No residual invasive carcinoma or metastatic disease was identified. This case illustrates the difficulty in differentiating this nonneoplastic process from progressive disease in the clinical setting.}, }
@article {pmid32043593, year = {2020}, author = {Shahir, M and Mahmoud Hashemi, S and Asadirad, A and Varahram, M and Kazempour-Dizaji, M and Folkerts, G and Garssen, J and Adcock, I and Mortaz, E}, title = {Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells.}, journal = {Journal of cellular physiology}, volume = {235}, number = {10}, pages = {7043-7055}, pmid = {32043593}, issn = {1097-4652}, mesh = {Animals ; Biomarkers/metabolism ; Cell Communication/immunology ; Cell Proliferation/physiology ; Cells, Cultured ; Cytokines/immunology/metabolism ; Dendritic Cells/*immunology/metabolism ; Exosomes/*immunology/metabolism ; Female ; Immune Tolerance/*immunology ; Immunity/immunology ; Inflammation/immunology/metabolism ; Lymphocytes/immunology/metabolism ; Mesenchymal Stem Cells/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; }, abstract = {Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-β (TGF-β) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.}, }
@article {pmid32031117, year = {2020}, author = {Söyleyici, NA and Aslan, F and Avcýkurt, AS and Akgün, GA}, title = {Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {1}, pages = {19-24}, doi = {10.4103/IJPM.IJPM_658_19}, pmid = {32031117}, issn = {0974-5130}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/surgery ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; Prognosis ; Trans-Activators/*genetics ; Vascular Endothelial Growth Factor A/genetics ; }, abstract = {Background: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated.<br><br>Methods: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated.<br><br>Results: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF.<br><br>Conclusion: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.}, }
@article {pmid32031116, year = {2020}, author = {Varma, K and Chauhan, A and Bhargava, M and Misra, V and Srivastava, S}, title = {Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {1}, pages = {13-18}, doi = {10.4103/IJPM.IJPM_419_19}, pmid = {32031116}, issn = {0974-5130}, mesh = {Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; beta Catenin/*genetics ; }, abstract = {Background: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet.<br><br>Materials and Methods: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association.<br><br>Results: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns.<br><br>Conclusion: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.}, }
@article {pmid32029638, year = {2020}, author = {Aminian, A and Zajichek, A and Arterburn, DE and Wolski, KE and Brethauer, SA and Schauer, PR and Nissen, SE and Kattan, MW}, title = {Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach.}, journal = {Diabetes care}, volume = {43}, number = {4}, pages = {852-859}, pmid = {32029638}, issn = {1935-5548}, support = {R01 DK105960/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Bariatric Surgery/statistics &amp; numerical data ; Computer Simulation ; Diabetes Complications/*diagnosis/epidemiology/pathology ; Diabetes Mellitus, Type 2/*complications/*diagnosis/epidemiology/*surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; *Machine Learning ; Male ; Middle Aged ; Organs at Risk/pathology ; Prognosis ; Retrospective Studies ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.<br><br>RESEARCH DESIGN AND METHODS: A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m2 and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.<br><br>RESULTS: The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient's data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.<br><br>CONCLUSIONS: The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.}, }
@article {pmid32019280, year = {2020}, author = {Wu, J and Ding, S and Lin, L and Fei, X and Lin, C and Andriani, L and Goh, C and Huang, J and Hong, J and Gao, W and Zhu, S and Wang, H and Huang, O and Chen, X and He, J and Li, Y and Shen, K and Chen, W and Zhu, L}, title = {Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.}, journal = {Cancer research and treatment}, volume = {52}, number = {3}, pages = {671-679}, pmid = {32019280}, issn = {2005-9256}, support = {81572581//National Natural Science Foundation of China/ ; 81772797//National Natural Science Foundation of China/ ; 14411950200//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 14411950201//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 16411966- 900//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 201840323//Grant of Shanghai municipal commission of health and family planning/ ; }, mesh = {Adenocarcinoma, Mucinous/metabolism/pathology/*therapy ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/metabolism/pathology/*therapy ; Carcinoma, Ductal, Breast/metabolism/pathology/*therapy ; China/epidemiology ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/epidemiology/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; *Transcriptome ; }, abstract = {PURPOSE: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).<br><br>Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.<br><br>RESULTS: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).<br><br>CONCLUSION: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.}, }
@article {pmid32007118, year = {2019}, author = {Komaei, I and Guccione, F and Sarra, F and Palmeri, E and Ieni, A and Cardia, R and Currò, G and Navarra, G and Palmeri, R}, title = {Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.}, journal = {Il Giornale di chirurgia}, volume = {40}, number = {6}, pages = {544-550}, pmid = {32007118}, issn = {1971-145X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*etiology/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage ; Diagnosis, Differential ; Epirubicin/administration &amp; dosage ; Female ; Humans ; Letrozole/administration &amp; dosage ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology/therapy ; Photons ; Radiotherapy, High-Energy/*adverse effects ; Sarcoma/diagnosis/*etiology/pathology/therapy ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation.<br><br>CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast.<br><br>CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.}, }
@article {pmid31992198, year = {2020}, author = {Assefa, T and Zhang, J and Chowda-Reddy, RV and Moran Lauter, AN and Singh, A and O'Rourke, JA and Graham, MA and Singh, AK}, title = {Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches.}, journal = {BMC plant biology}, volume = {20}, number = {1}, pages = {42}, pmid = {31992198}, issn = {1471-2229}, support = {NA//Iowa Soybean Association/ ; NA//Iowa State University/ ; NA//North Central Soybean Research Program (US)/ ; NA//Agricultural Research Service/ ; NA//National Institute of Food and Agriculture/ ; }, mesh = {Epistasis, Genetic ; Gene Expression Profiling ; Genes, Plant ; Genome, Plant ; *Genome-Wide Association Study ; Iron/*metabolism ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Seed Bank ; Soybeans/*genetics ; Stress, Physiological/*genetics ; }, abstract = {BACKGROUND: Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.<br><br>RESULTS: A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.<br><br>CONCLUSIONS: This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.}, }
@article {pmid31992119, year = {2020}, author = {Billena, C and Padia, S and O'Brien, B and Knoble, J and Gokhale, A and Rajagopalan, M}, title = {Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.}, journal = {Immunotherapy}, volume = {12}, number = {2}, pages = {123-130}, doi = {10.2217/imt-2019-0020}, pmid = {31992119}, issn = {1750-7448}, mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*drug therapy/*radiotherapy ; Female ; Humans ; Nivolumab/*therapeutic use ; Radiodermatitis/complications/*etiology ; Radiotherapy, Adjuvant ; }, abstract = {Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.}, }
@article {pmid31980982, year = {2020}, author = {Zhao, Y and Wang, Y and Zhu, F and Zhang, J and Ma, X and Zhang, D}, title = {Gene expression profiling revealed MCM3 to be a better marker than Ki67 in prognosis of invasive ductal breast carcinoma patients.}, journal = {Clinical and experimental medicine}, volume = {20}, number = {2}, pages = {249-259}, pmid = {31980982}, issn = {1591-9528}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/therapy ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*genetics ; Middle Aged ; Minichromosome Maintenance Complex Component 3/*genetics ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; }, abstract = {Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.}, }
@article {pmid31941968, year = {2020}, author = {Elmetwali, T and Salman, A and Wei, W and Hussain, SA and Young, LS and Palmer, DH}, title = {CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {342}, pmid = {31941968}, issn = {2045-2322}, mesh = {Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; Apoptosis/drug effects ; CD40 Antigens/metabolism ; CD40 Ligand/genetics/*metabolism/pharmacology ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Line, Tumor ; Cell Membrane/*metabolism ; Cell Proliferation ; Dendritic Cells/cytology/immunology/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Genetic Vectors/genetics/metabolism ; Humans ; Immunoglobulins/metabolism ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Membrane Glycoproteins/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Urinary Bladder Neoplasms/immunology/metabolism/pathology ; }, abstract = {In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.}, }
@article {pmid31937300, year = {2020}, author = {Westwood, ML and O'Donnell, AJ and Schneider, P and Albery, GF and Prior, KF and Reece, SE}, title = {Testing possible causes of gametocyte reduction in temporally out-of-synch malaria infections.}, journal = {Malaria journal}, volume = {19}, number = {1}, pages = {17}, pmid = {31937300}, issn = {1475-2875}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; UF110155//Royal Society/ ; }, mesh = {Animals ; *Circadian Rhythm/immunology ; Erythrocytes/*parasitology ; Female ; Flow Cytometry ; Gametogenesis/physiology ; Linear Models ; Malaria/blood/immunology/*parasitology ; Male ; Merozoites/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Plasmodium chabaudi/genetics/growth &amp; development/immunology/*physiology ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Tumor Necrosis Factor-alpha/*administration &amp; dosage/blood/immunology ; }, abstract = {BACKGROUND: The intraerythrocytic development cycle (IDC) of the rodent malaria Plasmodium chabaudi is coordinated with host circadian rhythms. When this coordination is disrupted, parasites suffer a 50% reduction in both asexual stages and sexual stage gametocytes over the acute phase of infection. Reduced gametocyte density may not simply follow from a loss of asexuals because investment into gametocytes ("conversion rate") is a plastic trait; furthermore, the densities of both asexuals and gametocytes are highly dynamic during infection. Hence, the reasons for the reduction of gametocytes in infections that are out-of-synch with host circadian rhythms remain unclear. Here, two explanations are tested: first, whether out-of-synch parasites reduce their conversion rate to prioritize asexual replication via reproductive restraint; second, whether out-of-synch gametocytes experience elevated clearance by the host's circadian immune responses.<br><br>METHODS: First, conversion rate data were analysed from a previous experiment comparing infections of P. chabaudi that were in-synch or 12 h out-of-synch with host circadian rhythms. Second, three new experiments examined whether the inflammatory cytokine TNF varies in its gametocytocidal efficacy according to host time-of-day and gametocyte age.<br><br>RESULTS: There was no evidence that parasites reduce conversion or that their gametocytes become more vulnerable to TNF when out-of-synch with host circadian rhythms.<br><br>CONCLUSIONS: The factors causing the reduction of gametocytes in out-of-synch infections remain mysterious. Candidates for future investigation include alternative rhythmic factors involved in innate immune responses and the rhythmicity in essential resources required for gametocyte development. Explaining why it matters for gametocytes to be synchronized to host circadian rhythms might suggest novel approaches to blocking transmission.}, }
@article {pmid31932496, year = {2020}, author = {Jelacic, TM and Ribot, WJ and Chua, J and Boyer, AE and Woolfitt, AR and Barr, JR and Friedlander, AM}, title = {Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {204}, number = {5}, pages = {1263-1273}, pmid = {31932496}, issn = {1550-6606}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Bacillus anthracis/*immunology ; Bacillus licheniformis/*immunology ; Bacillus subtilis/*immunology ; Cytokines/immunology ; Dendritic Cells/*immunology ; Female ; Humans ; *Immunity, Innate ; Macrophages/*immunology ; Male ; Monocytes/*immunology ; Polyglutamic Acid/*immunology ; }, abstract = {The poly-γ-glutamic acid (PGA) capsule produced by Bacillus anthracis is composed entirely of d-isomer glutamic acid, whereas nonpathogenic Bacillus species produce mixed d-, l-isomer PGAs. To determine if B. anthracis PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to B. anthracis PGA and PGAs from nonpathogenic B. subtilis subsp. chungkookjang and B. licheniformis Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with B. anthracis PGA being least stimulatory and B. licheniformis PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but B. subtilis PGA also elicited IL-10 and TNF-α, whereas B. licheniformis PGA elicited all those plus IL-1β. Similarly, all three PGAs elicited IL-8 from iDCs, but B. subtilis PGA also elicited IL-6, and B. licheniformis PGA elicited those plus IL-12p70, IL-10, IL-1β, and TNF-α. Only B. licheniformis PGA induced dendritic cell maturation. TLR assays also yielded differential results. B. subtilis PGA and B. licheniformis PGA both elicited more TLR2 signal than B. anthracis PGA, but only responses to B. subtilis PGA were affected by a TLR6 neutralizing Ab. B. licheniformis PGA elicited more TLR4 signal than B. anthracis PGA, whereas B. subtilis PGA elicited none. B. anthracis PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of B. anthracis PGA reduced monocytes' cytokine responses. We conclude that B. anthracis PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic Bacillus species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.}, }
@article {pmid31931856, year = {2020}, author = {Yoosuf, N and Navarro, JF and Salmén, F and Ståhl, PL and Daub, CO}, title = {Identification and transfer of spatial transcriptomics signatures for cancer diagnosis.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {6}, pmid = {31931856}, issn = {1465-542X}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/*diagnosis/genetics ; Carcinoma, Ductal, Breast/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Female ; Humans ; *Machine Learning ; Molecular Typing/*methods ; ROC Curve ; Spatial Analysis ; *Transcriptome ; }, abstract = {BACKGROUND: Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types.<br><br>METHODS: We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles.<br><br>RESULTS: We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC.<br><br>CONCLUSIONS: This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.}, }
@article {pmid31929965, year = {2019}, author = {Lin, L and Wang, X and Tang, C and Liang, J}, title = {Clinical Characteristics and Prognosis of Gastrointestinal Metastases in Solid Tumor Patients: A Retrospective Study and Review of Literatures.}, journal = {Analytical cellular pathology (Amsterdam)}, volume = {2019}, number = {}, pages = {4508756}, pmid = {31929965}, issn = {2210-7185}, mesh = {Adenocarcinoma/mortality/pathology/*secondary ; Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal/mortality/pathology/*secondary ; Female ; Gastrointestinal Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms/mortality/*pathology ; }, abstract = {Background: According to the literature and our experience, patients with gastrointestinal metastases are relatively rare. Numerous case reports and literature reviews have been reported. We present one of the larger case series of gastrointestinal metastases.<br><br>Objectives: To explore the clinical characteristics and prognosis of patients with gastrointestinal tract metastases, which are rare metastatic sites.<br><br>Methods: Patients with gastrointestinal metastases in the setting of stage IV primary carcinomas treated at Beijing Ditan Hospital and Peking University International Hospital from November 1992 to August 2017 were included in this study. The diagnosis of gastrointestinal tract metastases was based on histopathology.<br><br>Results: 30 patients (median age 56 years, 56.7% female) were included. The most common primary carcinomas associated with gastrointestinal metastases were breast (11 patients, 36.7%), stomach (9 patients, 30.0%), and lung (4 patients, 13.3%) cancer. The major pathological types were adenocarcinoma (16 patients, 53.3%) and ductal carcinoma (9 patients, 30.0%). Ten patients (33.3%) underwent local gastrointestinal treatment, and 20 patients (66.7%) underwent nonlocal treatment (involving chemotherapy alone or best supportive care). For breast cancer patients and gastric cancer patients who underwent local therapy, a significant survival advantage was observed (p = 0.001 and p = 0.012, respectively). The presence of other common metastases was identified as an independent poor prognostic factor through multivariate analysis with a HR (hazard ratio) of survival of 0.182 (95% confidence interval (CI) 0.11-0.523, p = 0.031).<br><br>Conclusion: Gastrointestinal metastases are most frequently from breast invasive ductal carcinoma. The presentation of other common metastases with gastrointestinal metastasis indicates poor prognosis, and selected patients may benefit from surgical intervention.}, }
@article {pmid31929443, year = {2020}, author = {Eckert, L and Mattia, L and Patel, S and Okumura, R and Reynolds, P and Stuiver, I}, title = {Reducing the Risk of Indwelling Catheter-Associated Urinary Tract Infection in Female Patients by Implementing an Alternative Female External Urinary Collection Device: A Quality Improvement Project.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {47}, number = {1}, pages = {50-53}, doi = {10.1097/WON.0000000000000601}, pmid = {31929443}, issn = {1528-3976}, mesh = {Adult ; California ; Catheter-Related Infections/prevention &amp; control ; Catheters, Indwelling/*adverse effects/microbiology ; Female ; Humans ; Quality Improvement ; Urinary Tract Infections/*prevention &amp; control ; Urine Specimen Collection/methods/*standards/statistics &amp; numerical data ; }, abstract = {PURPOSE: The purpose of this quality improvement project was to reduce catheter-associated urinary tract infection (CAUTI) risk for female patients by implementing a female external urinary collection (FEUC) device with suction as an alternative to indwelling catheter (IDC).<br><br>PARTICIPANTS AND SETTING: Participants were female patients admitted to our 386-bed community hospital in Southern California and who required urinary management.<br><br>APPROACH: We implemented a comprehensive CAUTI prevention program in 2014 that was in place for 1.5 years before this project was started. The CAUTI prevention program was based on the US Center for Disease Control and Prevention's CAUTI prevention recommendations. To supplement our CAUTI prevention efforts in our female patients, we implemented the FEUC device in our intensive care, telemetry, medical-surgical, orthopedic, and acute rehabilitations inpatient care units. Indwelling catheter use and CAUTI cases were identified by our Infection Prevention department.<br><br>OUTCOMES: Prior to introduction of the FEUC device, in 2015, the baseline female IDC utilization rate was 31.7% (7181 IDC device-days/22,656 patient-days) and the female CAUTI rate was 1.11 (8 cases/7181 IDC device-days) per 1000 days. Following introduction of the device, both rates declined. In 2016, the IDC utilization rate was 29.7% (P = .000) and the CAUTI rate was 0% (P =.005). We continued to observe a reduction in 2017 IDC utilization rates of 26% (P = .000); the 2017 CAUTI rate of 0.90 was not significantly different to our prior year rate (P = .726).<br><br>IMPLICATIONS FOR PRACTICE: We found that the introduction of the FEUC device reduced the risk for CAUTI. We will continue to prioritize the use of external devices for urinary management to help reduce the risk of our patients developing CAUTI.}, }
@article {pmid31927471, year = {2020}, author = {Mema, E and Schnabel, F and Chun, J and Kaplowitz, E and Price, A and Goodgal, J and Moy, L}, title = {The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer.}, journal = {European journal of radiology}, volume = {124}, number = {}, pages = {108813}, doi = {10.1016/j.ejrad.2020.108813}, pmid = {31927471}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Density/*physiology ; Cohort Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/*diagnostic imaging ; Young Adult ; }, abstract = {PURPOSE: To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC).<br><br>METHODS: The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression.<br><br>RESULTS: Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts.<br><br>CONCLUSIONS: The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.}, }
@article {pmid31902979, year = {2019}, author = {Sultan, G and Zubair, S and Tayubi, IA and Dahms, HU and Madar, IH}, title = {Towards the early detection of ductal carcinoma (a common type of breast cancer) using biomarkers linked to the PPAR(γ) signaling pathway.}, journal = {Bioinformation}, volume = {15}, number = {11}, pages = {799-805}, pmid = {31902979}, issn = {0973-2063}, abstract = {Breast cancer is a leading cause of morbidity and mortality among women comprising about 12% females worldwide. The underlying alteration in the gene expression, molecular mechanism and metabolic pathways responsible for incidence and progression of breast tumorigenesis are yet not completely understood. In the present study, potential biomarker genes involved in the early progression for early diagnosis of breast cancer has been detailed. Regulation and Gene profiling of Ductal Carcinoma In-situ (DCIS), Invasive Ductal Carcinoma (IDC) and healthy samples have been analyzed to follow their expression pattern employing normalization, statistical calculation, DEGs annotation and Protein-Protein Interaction (PPI) network. We have performed a comparative study on differentially expressed genes among Healthy vs DCIS, Healthy vsIDC and DCIS vs IDC. We found MCM102 and SLC12A8as consistently over-expressed and LEP, SORBS1, SFRP1, PLIN1, FABP4, RBP4, CD300LG, ID4, CRYAB, ECRG4, G0S2, FMO2, ADAMTS5, CAV1, CAV2, ABCA8, MAMDC2, IGFBP6, CLDN11, TGFBR3as under-expressed genes in all the 3 conditions categorized for pre-invasive and invasive ductal breast carcinoma. These genes were further studied for the active pathways where PPAR(γ) signaling pathway was found to be significantly involved. The gene expression profile database can be a potential tool in the early diagnosis of breast cancer.}, }
@article {pmid31902119, year = {2020}, author = {Acun, T and Senses, KM}, title = {Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {27}, number = {3}, pages = {483-489}, pmid = {31902119}, issn = {1880-4233}, support = {2017-50737594-02//Bülent Ecevit Üniversitesi/ ; 217S251//Türkiye Bilimsel ve Teknolojik Araştirma Kurumu/ ; }, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*mortality/pathology ; DNA Copy Number Variations ; *DNA Methylation ; Down-Regulation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/genetics/*metabolism ; Humans ; *Mutation ; Prognosis ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Survival Rate ; }, abstract = {BACKGROUND: DNAJC10 (ERDJ5), a member of HSP40 family, was considered as an anti-oncogenic gene in neuroblastoma, prostate and colon cancers. But, the role and importance of DNAJC10 gene in breast cancer is currently unknown. In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer.<br><br>METHODS: Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively.<br><br>RESULTS: DNAJC10 mRNA expression was significantly reduced in 3 out of 4 breast cancer cell lines compared to the nontumorigenic mammary epithelial cell line (MCF 10A). DNAJC10 protein expression was significantly less frequent in invasive ductal carcinoma samples (n = 121) compared with adjacent normal breast tissues (n = 32) (p < 0.0001). Downregulation of DNAJC10 mRNA was associated with poor overall survival (OS) (n = 626) (p = 0.0096) and relapse-free survival (n = 1764) (p = 5.3e-12). According to the COSMIC and cBioPortal databases, point mutations and copy number variations of DNAJC10 were very rare in breast cancer samples. Besides, no genetic alterations on the experimentally validated promoter regions were found in breast cell lines. CpG island located in the promoter regions of DNAJC10 gene was found to be frequently hypomethylated in breast cell lines.<br><br>CONCLUSIONS: In the light of previous knowledge regarding the role of DNAJC10 in carcinogenesis, findings of this study suggest that DNAJC10 is a potential diagnostic/prognostic biomarker and tumor suppressor candidate for breast cancer. Epigenetic factors other than promoter methylation could contribute to the downregulation of DNAJC10 expression.}, }
@article {pmid31894281, year = {2020}, author = {Zhao, C and Zheng, S and Yan, Z and Deng, Z and Wang, R and Zhang, B}, title = {CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.}, journal = {Oncology reports}, volume = {43}, number = {2}, pages = {571-580}, doi = {10.3892/or.2019.7426}, pmid = {31894281}, issn = {1791-2431}, mesh = {Adult ; Aged ; Animals ; Annexin A2/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Chemokines, CC/*metabolism ; Disease Progression ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism/*pathology/*secondary ; MCF-7 Cells ; Mice ; Middle Aged ; Neoplasm Transplantation ; Tumor Burden ; }, abstract = {Chemokine (C‑C motif) ligand 18 (CCL18) is derived from breast tumor‑associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N‑terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial‑mesenchymal transition (EMT) via the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F‑actin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular F‑actin measurement assay showed that reduction of AnxA2 suppressed CCL18‑induced F‑actin polymerization though phosphorylation of integrin β1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18‑induced EMT via the PI3K/Akt/GSK3β/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential anti‑invasion/metastasis target for therapeutic intervention in breast cancer.}, }
@article {pmid31876826, year = {2020}, author = {Phan Sy, O and Rouchy, RC and De Leiris, N and Nika, E and Djaileb, L}, title = {FDG PET/CT of a Supraclavicular Silicone Granuloma at Follow-up of a Breast Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {3}, pages = {e169-e170}, doi = {10.1097/RLU.0000000000002894}, pmid = {31876826}, issn = {1536-0229}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/complications/*surgery ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Granuloma/*diagnostic imaging/*etiology/pathology ; Humans ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Silicones/*adverse effects ; }, abstract = {We report herein the case of a 33-year-old woman who was referred for FDG PET/CT staging prior to pregnancy after a 4-year lost to follow-up for a breast invasive ductal carcinoma (pT2N1 SBRII). FDG PET/CT revealed right supraclavicular lymphadenopathy potentially caused by breast carcinoma recurrence. No additional site was involved. Supraclavicular ultrasonography showed typical "snowstorm" appearance. MRI revealed signs of breast implant intracapsular rupture and signal intensity of silicone within a supraclavicular node. Fine-needle aspiration and microbiopsy of adenopathy finally confirmed silicone granuloma and ruled out breast cancer recurrence.}, }
@article {pmid31871301, year = {2020}, author = {Chen, G and Ding, XF and Pressley, K and Bouamar, H and Wang, B and Zheng, G and Broome, LE and Nazarullah, A and Brenner, AJ and Kaklamani, V and Jatoi, I and Sun, LZ}, title = {Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {6}, pages = {1486-1496}, doi = {10.1158/1078-0432.CCR-19-2478}, pmid = {31871301}, issn = {1557-3265}, support = {R01 CA192564/CA/NCI NIH HHS/United States ; P30 CA054174/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Down-Regulation ; Everolimus/*pharmacology ; Female ; Humans ; Matrix Metalloproteinase 9/chemistry/*metabolism ; Mice ; Mice, Nude ; Mice, Transgenic ; Receptor, ErbB-2/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression.<br><br>EXPERIMENTAL DESIGN: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells.<br><br>RESULTS: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell-formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo.<br><br>CONCLUSIONS: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.}, }
@article {pmid31856858, year = {2019}, author = {Wan, L and Liu, T and Hong, Z and Pan, Y and Sizemore, ST and Zhang, J and Ma, Z}, title = {NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {148}, pmid = {31856858}, issn = {1465-542X}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Nedd4 Ubiquitin Protein Ligases/*genetics/metabolism ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Receptor, IGF Type 1/metabolism ; Young Adult ; }, abstract = {BACKGROUND: A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4.<br><br>METHODS: The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method.<br><br>RESULTS: NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively).<br><br>CONCLUSIONS: NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.}, }
@article {pmid31856344, year = {2020}, author = {Giles, M and Graham, L and Ball, J and King, J and Watts, W and Harris, A and Oldmeadow, C and Ling, R and Paul, M and O'Brien, A and Parker, V and Wiggers, J and Foureur, M}, title = {Implementation of a multifaceted nurse-led intervention to reduce indwelling urinary catheter use in four Australian hospitals: A pre- and postintervention study.}, journal = {Journal of clinical nursing}, volume = {29}, number = {5-6}, pages = {872-886}, doi = {10.1111/jocn.15142}, pmid = {31856344}, issn = {1365-2702}, support = {//NSW Ministry of Health Translational Research Grants Scheme/ ; }, mesh = {Adult ; Catheter-Related Infections/etiology/*prevention &amp; control ; Catheters, Indwelling/*adverse effects ; Controlled Before-After Studies ; Female ; Humans ; Male ; New South Wales ; Patient Care Bundles/*nursing ; Practice Patterns, Nurses' ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/etiology/*prevention &amp; control ; }, abstract = {AIMS AND OBJECTIVES: This study aimed to reduce indwelling urinary catheter (IDC) use and duration through implementation of a multifaceted "bundled" care intervention.<br><br>BACKGROUND: Indwelling urinary catheters present a risk for patients through the potential development of catheter-associated urinary tract infection (CAUTI), with duration of IDC a key risk factor. Catheter-associated urinary tract infection is considered preventable yet accounts for over a third of all hospital-acquired infections. The most effective CAUTI reduction strategy is to avoid IDC use where ever possible and to remove the IDC as early as appropriate.<br><br>DESIGN: A cluster-controlled pre- and poststudy at a facility level with a phased intervention implementation approach.<br><br>METHODS: A multifaceted intervention involving a "No CAUTI" catheter care bundle was implemented, in 4 acute-care hospitals, 2 in metropolitan and 2 in rural locations, in New South Wales, Australia. Indwelling urinary catheter point prevalence and duration data were collected at the bedside on 1,630 adult inpatients at preintervention and 1,677 and 1,551 at 4 and 9 months postintervention. This study is presented in line with the StaRI checklist (see Appendix S1).<br><br>RESULTS: A nonsignificant trend towards reduction in IDC prevalence was identified, from 12% preintervention to 10% of all inpatients at 4 and 9 months. Variability in preintervention IDC prevalence existed across hospitals (8%-16%). Variability in reduction was evident across hospitals at 4 months (between -2% and 4%) and 9 months (between 0%-8%). Hospitals with higher preintervention prevalence showed larger decreases, up to 50% when preintervention prevalence was 16%. Indwelling urinary catheter duration increased as more of the short-term IDC placements were avoided.<br><br>CONCLUSIONS: Implementation of a multifaceted intervention resulted in reduced IDC use in four acute-care hospitals in Australia. This result was not statistically significant but did reflect a positive trend of reduction. There was a significant reduction in short-term IDC use at 9 months postintervention.<br><br>Clinical nurse leaders can effectively implement change strategies that influence patient outcomes. Implementation of the evidence-based "No CAUTI" bundle increased awareness of appropriate indications and provided nurses with the tools to inform decision-making related to insertion and removal of IDCs in acute inpatient settings. Working in partnership with inpatients and the multidisciplinary team is essential in minimising acute-care IDC use.}, }
@article {pmid31856180, year = {2019}, author = {Walzer, KA and Fradin, H and Emerson, LY and Corcoran, DL and Chi, JT}, title = {Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging.}, journal = {PLoS genetics}, volume = {15}, number = {12}, pages = {e1008506}, pmid = {31856180}, issn = {1553-7404}, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization, Fluorescence/*methods ; Life Cycle Stages ; Microfluidic Analytical Techniques ; Multigene Family ; Plasmodium falciparum/genetics/*growth &amp; development ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; }, abstract = {Malaria parasites follow a complex life cycle that consists of multiple stages that span from the human host to the mosquito vector. Among the species causing malaria, Plasmodium falciparum is the most lethal, with clinical symptoms manifesting during the intraerythrocytic developmental cycle (IDC). During the IDC, P. falciparum progresses through a synchronous and continuous cascade of transcriptional programming previously established using population analyses. While individual parasites are known to exhibit transcriptional variations to evade the host immune system or commit to a sexual fate, such rare expression heterogeneity is largely undetectable on a population level. Therefore, we combined single-cell RNA-sequencing (scRNA-seq) on a microfluidic platform and fluorescence imaging to delineate the transcriptional variations among individual parasites during late asexual and sexual stages. The comparison between asexual and sexual parasites uncovered a set of previously undefined sex-specific genes. Asexual parasites were segregated into three distinct clusters based on the differential expression of genes encoding SERAs, rhoptry proteins, and EXP2 plus transporters. Multiple pseudotime analyses revealed that these stage-specific transitions are distinct. RNA fluorescent in situ hybridization of cluster-specific genes validated distinct stage-specific expression and transitions during the IDC and defined the highly variable transcriptional pattern of EXP2. Additionally, these analyses indicated huge variations in the stage-specific transcript levels among parasites. Overall, scRNA-seq and RNA-FISH of P. falciparum revealed distinct stage transitions and unexpected degrees of heterogeneity with potential impact on transcriptional regulation during the IDC and adaptive responses to the host.}, }
@article {pmid31849934, year = {2019}, author = {Alexia, C and Cren, M and Louis-Plence, P and Vo, DN and El Ahmadi, Y and Dufourcq-Lopez, E and Lu, ZY and Hernandez, J and Shamilov, F and Chernysheva, O and Vasilieva, M and Vorotnikov, I and Vishnevskay, Y and Tupitsyn, N and Rossi, JF and Villalba, M}, title = {Polyoxidonium® Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2693}, pmid = {31849934}, issn = {1664-3224}, mesh = {Adenocarcinoma/*drug therapy/immunology ; Adjuvants, Immunologic/*therapeutic use ; Adult ; Aged ; Breast Neoplasms/*drug therapy/immunology ; Cell Differentiation/drug effects/immunology ; Chemotherapy, Adjuvant/methods ; Dendritic Cells/*drug effects/immunology ; Female ; Humans ; Killer Cells, Natural/drug effects/immunology ; Lymphocyte Activation/drug effects/immunology ; Lymphocytes, Tumor-Infiltrating/drug effects/immunology ; Middle Aged ; Neoadjuvant Therapy/methods ; Piperazines/*therapeutic use ; Polymers/*therapeutic use ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; }, abstract = {Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4+ T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.}, }
@article {pmid31849088, year = {2020}, author = {Arispe Angulo, KR and Jawa, Z and Visotcky, A and Majidi, SS and Chitambar, CR and Jorns, JM}, title = {A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.}, journal = {Histopathology}, volume = {76}, number = {5}, pages = {661-670}, doi = {10.1111/his.14049}, pmid = {31849088}, issn = {1365-2559}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Humans ; Middle Aged ; Mitotic Index ; Neoadjuvant Therapy/methods ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIMS: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC.<br><br>METHODS AND RESULTS: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and ≥15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P = 0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P < 0.001), and a higher percentage of tumour-infiltrating lymphocytes (P = 0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n = 32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively.<br><br>CONCLUSIONS: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.}, }
@article {pmid31844635, year = {2019}, author = {Redell, M and Sierra-Hoffman, M and Assi, M and Bochan, M and Chansolme, D and Gandhi, A and Sheridan, K and Soosaipillai, I and Walsh, T and Massey, J}, title = {The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.}, journal = {Open forum infectious diseases}, volume = {6}, number = {11}, pages = {ofz479}, pmid = {31844635}, issn = {2328-8957}, abstract = {Background: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens.<br><br>Methods: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections.<br><br>Results: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%.<br><br>Conclusions: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.}, }
@article {pmid31844357, year = {2019}, author = {Amadi, OF and Okeke, IB and Ndu, IK and Ekwochi, U and Nduagubam, OC and Ezenwosu, OU and Asinobi, IN and Osuorah, CD}, title = {Cancer Mortality in the Niger Delta Region of Nigeria: A Case Study of the University of Port Harcourt Teaching Hospital.}, journal = {Nigerian medical journal : journal of the Nigeria Medical Association}, volume = {60}, number = {5}, pages = {262-267}, pmid = {31844357}, issn = {0300-1652}, abstract = {Aim: The aim of this study is to determine the pattern of cancer mortality (CM) seen in the University of Port Harcourt Teaching Hospital (UPTH) which is a cancer reference center in the Niger Delta Region.<br><br>Methodology: This is a 6-year retrospective study of cancer-related deaths in UPTH using patients' admission registers in all the wards and emergency units. Furthermore, the death certificates of cases were reviewed.<br><br>Results: Three hundred and sixteen cases of cancer-related deaths occurred, involving 174 females and 142 males, in a female-to-male sex ratio of 1.2:1. All age groups were affected, with age group 40-49 years accounting for the majority (20.6%). CM was seen in all the systems, except the central nervous system. Cancers of the gastrointestinal tract and its accessory organs (liver and gall bladder) caused most mortality (27.9%), in a female-to-male ratio of 0.8:1. The single most involved organ in CM is the female breast (20.6%), distantly followed by mortality due to prostate cancers and hematolymphoid cancers which accounted for 9.2% each. Colorectal cancers accounted for 7.3% of cancer deaths and ranked 4th. Cancers of both cervix and stomach each accounted for 5.7% of mortality. The major histologic diagnoses were carcinomas (adenocarcinoma; 36.7%, invasive ductal carcinoma; 20.3%, squamous cell carcinomas; 8.2% and hepatocellular carcinomas; 4.4%). Leukemias and lymphomas accounted for 9.2% of cases, whereas sarcomas accounted for 5.1% of cases.<br><br>Conclusion: Infection-related and noninfection-related cancers cause most mortality in UPTH. The 5th decade was the most commonly affected, while female breast was the single most involved organ. Breast, prostate and hematolymphoid malignancies are common causes of CM with death from breast occurring earliest. Majority of the deceased were educated, working-class urban dwellers. More advocacies on public acceptance of cancer screening and cancer preventive lifestyles as well as governments' improvement on workforce training and treatment infrastructure will improve the current CM profile in Port Harcourt.}, }
@article {pmid31814295, year = {2020}, author = {Li, Y and Su, P and Wang, Y and Zhang, H and Liang, Y and Zhang, N and Song, X and Li, X and Li, J and Yang, Q}, title = {Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.}, journal = {Cancer medicine}, volume = {9}, number = {3}, pages = {872-881}, pmid = {31814295}, issn = {2045-7634}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*epidemiology/secondary ; Brain Neoplasms/*epidemiology/secondary ; Breast/pathology ; Carcinoma, Ductal, Breast/*epidemiology/secondary ; Carcinoma, Lobular/*epidemiology/secondary ; Female ; Humans ; Liver Neoplasms/*epidemiology/secondary ; Lung Neoplasms/*epidemiology/secondary ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; SEER Program/statistics &amp; numerical data ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; }, abstract = {BACKGROUND: The distant metastasis was the most predictive characters of poor prognosis for triple-negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis.<br><br>METHODS: Using the 2010-2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi-squared test. Logistic regression was used for identification of predictive factors. The log-rank testing was utilized with disease-specific survival (DSS) and overall survival (OS) as the primary outcomes.<br><br>RESULTS: A total of 23 270 patients with TNBC were involved, including 1544 patients with distant metastatic cancer. Bone metastasis was diagnosed in 559 cases, brain metastasis in 124 cases, liver metastasis found in 369 cases and lung metastasis in 492 cases. Histologic subtypes including metaplastic breast carcinoma and invasive lobular carcinoma showed significant differences in preferential DMS compared with invasive ductal carcinoma. Furthermore, we found different histologic subtypes with specific DMS showed various prognosis. We also evaluated different DMS of specific histologic subtypes showed different prognosis.<br><br>CONCLUSION: Certain histologic subtypes of breast cancer are associated with preferential DMS and prognosis; this knowledge may help to further understand the mechanism of breast cancer metastasis and to monitor the prognosis of patients with TNBC.}, }
@article {pmid31809502, year = {2019}, author = {Pick, FC and Fish, KE and Biggs, CA and Moses, JP and Moore, G and Boxall, JB}, title = {Application of enhanced assimilable organic carbon method across operational drinking water systems.}, journal = {PloS one}, volume = {14}, number = {12}, pages = {e0225477}, pmid = {31809502}, issn = {1932-6203}, mesh = {Carbon/*analysis/metabolism ; Drinking Water/chemistry/microbiology/*standards ; Flow Cytometry/methods ; Organic Chemicals/*analysis/metabolism ; Pseudomonas fluorescens/metabolism ; Reproducibility of Results ; Spirillum/metabolism ; Water Microbiology/*standards ; Water Purification ; Water Quality/*standards ; }, abstract = {Assimilable organic carbon (AOC) is known to correlate with microbial growth, which can consequently degrade drinking water quality. Despite this, there is no standardised AOC test that can be applied to drinking water distribution systems (DWDS). Herein we report the development of a quick, robust AOC that incorporates known strains Pseudomonas fluorescens strain P-17 and Spirillum strain NOX, a higher inoculum volume and enumeration using flow cytometry to generate a quicker (total test time reduced from 14 to 8 days), robust method. We apply the developed AOC test to twenty drinking water treatment works (WTW) to validate the method reproducibility and resolution across a wide range of AOC concentrations. Subsequently, AOC was quantified at 32 sample points, over four DWDS, for a year in order to identify sinks and sources of AOC in operative networks. Application of the developed AOC protocol provided a previously unavailable insight and novel evidence of pipes and service reservoirs exhibiting different AOC and regrowth behaviour. Observed correlations between AOC and microbial growth highlight the importance of monitoring AOC as an integral part of managing drinking water quality at the consumers tap.}, }
@article {pmid31791269, year = {2019}, author = {Lee, CH and Hsieh, JC and Wu, TM and Yeh, TS and Wang, HM and Lin, YC and Chen, JS and Lee, CL and Huang, WK and Hung, TM and Yen, TT and Chan, SC and Chou, WC and Kuan, FC and Hu, CC and Chang, PH}, title = {Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1167}, pmid = {31791269}, issn = {1471-2407}, support = {CMRPG2D0171, CMRPG2D0172, CMRPG2G0681, CMRPG2G0682//Chang Gung Memorial Hospital/ ; CMRPG2D0173//Chang Gung Memorial Hospital/ ; PMRPG3G0791, CMRPG3G0771, CORPG3F0731, CMRPG3E1631-33//Chang Gung Memorial Hospital/ ; CMRPG3G1131-1133, CMRPG3H0871-73//Chang Gung Memorial Hospital/ ; MOST-108-2628-B-182A-001//Ministry of Science and Technology, Taiwan/ ; MOST-107-2314-B-182-053, MOST-104-2314-B-182-031-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {AC133 Antigen/immunology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/*mortality/pathology ; Cell Count ; Female ; Humans ; Liquid Biopsy ; Middle Aged ; Neoplastic Cells, Circulating/immunology/*pathology ; Neoplastic Stem Cells/immunology/*pathology ; Prognosis ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy.<br><br>METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses.<br><br>RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS.<br><br>CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.}, }
@article {pmid31789065, year = {2020}, author = {Tijani, S and Sharma, K and Yuen, H and Shaaban, A}, title = {Metastatic "Ductal Carcinoma In Situ-Like" Lobular Carcinoma in a Lymph Node: A Case Report and Review of the Literature.}, journal = {International journal of surgical pathology}, volume = {28}, number = {4}, pages = {436-439}, doi = {10.1177/1066896919888744}, pmid = {31789065}, issn = {1940-2465}, mesh = {Axilla ; Biomarkers, Tumor/analysis/metabolism ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Diagnosis, Differential ; Diagnostic Errors/prevention &amp; control ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy ; Middle Aged ; }, abstract = {Metastatic breast cancer resembling ductal carcinoma in situ (DCIS) is a rare phenomenon. In this article, we present a unique case of metastatic lobular carcinoma with DCIS-like morphology in the left axillary lymph nodes of a 52-year-old female. She presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm tumor in the upper outer quadrant. Microscopic assessment revealed a pleomorphic lobular carcinoma in the lower outer quadrant and a grade 2 invasive ductal carcinoma in the upper outer quadrant. Sixteen of the 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features. Immunohistochemical analysis of the primary and metastatic lobular carcinoma showed no expression of E-cadherin and p63 antibodies. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported. The case suggests that lobular carcinoma can morphologically recreate a primary microenvironment at a distant site and simulate in situ growth. Recognition of this pattern is important to avoid misdiagnosis.}, }
@article {pmid31779581, year = {2019}, author = {Luo, K and Wang, S and Fu, Y and Zhou, P and Huang, X and Gu, Q and Li, W and Wang, Y and Hu, F and Liu, S}, title = {Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂).}, journal = {BMC genetics}, volume = {20}, number = {1}, pages = {87}, pmid = {31779581}, issn = {1471-2156}, mesh = {Animals ; Carps/genetics/*physiology ; Evolution, Molecular ; Female ; Fish Proteins/genetics ; *Genetic Variation ; Goldfish/genetics/*physiology ; Homeodomain Proteins/*genetics ; Hybridization, Genetic ; Male ; Multigene Family ; Sequence Analysis, DNA/veterinary ; }, abstract = {BACKGROUND: Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.<br><br>RESULT: In this study, we investigated the genetic variation of 12 Hox genes in the two types of improved carp lineages derived from common carp (♀) × blunt snout bream (♂). Hox gene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations in Hox genes in the first generation of IDMC, and almost all the Hox gene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters of Hox genes in both improved carp lineages, and partially recombinant clusters of Hox genes were stably inherited from the first generation to the second generation in both types of improved carp lineages. On the other hand, some Hox genes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.<br><br>CONCLUSIONS: Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.}, }
@article {pmid31765735, year = {2020}, author = {Morimoto, M and Horikoshi, Y and Nakaso, K and Kurashiki, T and Kitagawa, Y and Hanaki, T and Sakamoto, T and Honjo, S and Umekita, Y and Fujiwara, Y and Matsura, T}, title = {Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer.}, journal = {Cancer letters}, volume = {470}, number = {}, pages = {149-160}, doi = {10.1016/j.canlet.2019.11.028}, pmid = {31765735}, issn = {1872-7980}, mesh = {Aged ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MAP Kinase Signaling System ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Pancreas/pathology ; Pancreatic Neoplasms/mortality/*pathology ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {The expression and functions of TYRO3, a member of the TAM receptor tyrosine kinase family, in pancreatic cancer (PC) have not been specifically elucidated. In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9) using Western blotting. TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival. Our study demonstrates the critical role of TYRO3 in PC progression through Akt and ERK activation and suggests TYRO3 as a novel promising target for therapeutic strategies against PC.}, }
@article {pmid31748977, year = {2020}, author = {Petry, V and Bonadio, RC and Cagnacci, AQC and Senna, LAL and Campos, RDNG and Cotti, GC and Hoff, PM and Fragoso, MCBV and Estevez-Diz, MDP}, title = {Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome).}, journal = {Familial cancer}, volume = {19}, number = {1}, pages = {47-53}, pmid = {31748977}, issn = {1573-7292}, mesh = {Adult ; Brazil/epidemiology ; Breast Neoplasms/genetics/*radiotherapy ; Female ; Fibrosarcoma/epidemiology ; Follow-Up Studies ; *Genes, p53 ; *Germ-Line Mutation ; Humans ; Leiomyosarcoma/epidemiology ; Li-Fraumeni Syndrome/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Retrospective Studies ; Young Adult ; }, abstract = {The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.}, }
@article {pmid31744918, year = {2019}, author = {Xie, M and Leroy, H and Mascarau, R and Woottum, M and Dupont, M and Ciccone, C and Schmitt, A and Raynaud-Messina, B and Vérollet, C and Bouchet, J and Bracq, L and Benichou, S}, title = {Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction.}, journal = {mBio}, volume = {10}, number = {6}, pages = {}, pmid = {31744918}, issn = {2150-7511}, mesh = {CD4-Positive T-Lymphocytes/metabolism/virology ; Dendritic Cells/metabolism/virology ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Humans ; Macrophages/metabolism/virology ; Myeloid Cells/metabolism/virology ; SAM Domain and HD Domain-Containing Protein 1/*metabolism ; *Viral Tropism ; *Virus Replication ; }, abstract = {Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients.IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.}, }
@article {pmid31737920, year = {2020}, author = {Taylor, AS and Morgan, TM and Wallington, DG and Chinnaiyan, AM and Spratt, DE and Mehra, R}, title = {Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.}, journal = {The Prostate}, volume = {80}, number = {2}, pages = {146-152}, pmid = {31737920}, issn = {1097-0045}, support = {P50 CA069568/CA/NCI NIH HHS/United States ; P50 CA186786/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*genetics/*pathology ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal/*genetics/*pathology ; Cell Growth Processes/genetics ; Cohort Studies ; Genetic Predisposition to Disease ; Genomics/methods ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/*pathology ; RNA, Neoplasm/*genetics ; }, abstract = {BACKGROUND: The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay.<br><br>DESIGN: Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high).<br><br>RESULTS: The presence of CF/IDC was significantly associated with Decipher risk score (P = .007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR] 1.04 per percent increase [95% confidence interval [CI], 1.02-1.06]; P = .0004) and CF predominant (OR, 9.60 [95%CI, 1.48-62.16]; P = .02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92 [95%CI, 0.65-5.67]; P = .24).<br><br>CONCLUSIONS: Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are relative to genomic assessment on long-term outcomes.}, }
@article {pmid31734782, year = {2020}, author = {Kim, K and Kim, IJ and Pak, K and Kim, SJ and Choi, SJ and Park, H and Kang, T and Kong, IJ and Shin, YB and Kim, H and Yoon, JA}, title = {The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {47}, number = {5}, pages = {1094-1102}, pmid = {31734782}, issn = {1619-7089}, mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging/surgery ; Feasibility Studies ; Humans ; Lymph Node Excision ; *Lymphedema/diagnostic imaging/etiology ; Lymphoscintigraphy ; Mastectomy ; }, abstract = {PURPOSE: We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy.<br><br>METHODS: We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides.<br><br>RESULTS: The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm.<br><br>CONCLUSIONS: The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.}, }
@article {pmid31711023, year = {2019}, author = {Zhou, J and Tan, H and Bai, Y and Li, J and Lu, Q and Chen, R and Zhang, M and Feng, Q and Wang, M}, title = {Evaluating the HER-2 status of breast cancer using mammography radiomics features.}, journal = {European journal of radiology}, volume = {121}, number = {}, pages = {108718}, doi = {10.1016/j.ejrad.2019.108718}, pmid = {31711023}, issn = {1872-7727}, mesh = {Area Under Curve ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/*genetics ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics ; China ; Female ; Genes, erbB-2/*genetics ; Humans ; Mammography/*methods ; Middle Aged ; Preoperative Care ; ROC Curve ; Sensitivity and Specificity ; Support Vector Machine ; }, abstract = {PURPOSE: The aim of our study was to evaluate the HER-2 status in breast cancer patients using mammography (MG) radiomics features.<br><br>METHODS: A total of 306 Chinese female patients with invasive ductal carcinoma of no special type (IDC-NST) enrolled from January 2013 to July 2018 were divided into a training set (n = 244) and a testing set (n = 62). One hundred and eighty-six radiomics features were extracted from digital MG images based on the training set. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal predictive features for HER-2 status from the training set. Both support vector machine (SVM) and logistic regression models were employed based on the selected features. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training set and testing set were used to evaluate the predictive performance of the models.<br><br>RESULTS: Compared with the SVM model, the performance of the logistic regression model using a combination of cranial caudal (CC) and mediolateral oblique (MLO) MG views was optimal. In the training set, the sensitivity, specificity, accuracy and area under the curve (AUC) values of the logistic regression model for evaluating HER-2 status based on quantitative radiomics features were 87.29%, 58.73%, 80.00% and 0.846 (95% confidence interval (CI), 0.800-0.887), respectively, and in the testing set, the values were 73.91%, 68.75%, 77.00% and 0.787 (95% CI, 0.673-0.885), respectively.<br><br>CONCLUSIONS: Radiomics features could be an efficient tool for the preoperative evaluation of HER-2 status in patients with breast cancer.}, }
@article {pmid31706703, year = {2019}, author = {Quagliarini, F and Mir, AA and Balazs, K and Wierer, M and Dyar, KA and Jouffe, C and Makris, K and Hawe, J and Heinig, M and Filipp, FV and Barish, GD and Uhlenhaut, NH}, title = {Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet.}, journal = {Molecular cell}, volume = {76}, number = {4}, pages = {531-545.e5}, pmid = {31706703}, issn = {1097-4164}, support = {K99 CA154887/CA/NCI NIH HHS/United States ; R00 CA154887/CA/NCI NIH HHS/United States ; R01 DK108987/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Blood Glucose/metabolism ; Chromatin/*metabolism ; *Circadian Clocks/genetics ; *Circadian Rhythm/genetics ; *Diet, High-Fat ; Dietary Fats/administration &amp; dosage/blood/*metabolism ; Disease Models, Animal ; *Energy Metabolism/genetics ; Fasting/metabolism ; Gene Expression Regulation ; Glucocorticoids/metabolism ; Gluconeogenesis ; Ligands ; Liver/*metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/blood/genetics/*metabolism ; PPAR alpha/genetics/metabolism ; Postprandial Period ; Receptors, Glucocorticoid/deficiency/genetics/*metabolism ; STAT5 Transcription Factor/genetics/metabolism ; Secretory Pathway ; Signal Transduction ; Time Factors ; Transcription, Genetic ; Triglycerides/blood ; }, abstract = {The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.}, }
@article {pmid31677352, year = {2020}, author = {Chen, HH and Chen, DY and Huang, LG and Chen, YM and Hsieh, CW and Hung, WT and Tang, KT and Chen, G}, title = {Association between periodontitis and the risk of inadequate disease control in patients with rheumatoid arthritis under biological treatment.}, journal = {Journal of clinical periodontology}, volume = {47}, number = {2}, pages = {148-159}, doi = {10.1111/jcpe.13213}, pmid = {31677352}, issn = {1600-051X}, mesh = {Arthritis, Rheumatoid/*complications/*drug therapy/*epidemiology ; Humans ; Periodontitis/*complications/*epidemiology/*therapy ; Prospective Studies ; }, abstract = {AIM: To assess the association between periodontitis (PD) and inadequate disease control (IDC) in patients with rheumatoid arthritis (RA) receiving biological therapy.<br><br>MATERIALS AND METHODS: In total, 111 RA patients receiving biological therapy for at least 3 months were assessed for periodontal disease at baseline. RA disease activity was assessed at baseline and at 3 months of follow-up. A multivariable logistic regression analysis was used to estimate the association between PD and IDC, adjusting for age, sex, smoking, diabetes, and baseline RA disease activity. An additional exploratory model further controlled for disease characteristics and other medications.<br><br>RESULTS: Among 111 patients, 84 (75.7%) had PD, of whom 37 (44.0%) received periodontal treatment. Thirty-four (40.5%) of PD patients had IDC; 12 (32.4%) of treated PD patients and 22 (46.8%) of untreated patients had IDC, respectively. The ORs (95% CIs) for IDC were 1.45 (0.50-4.23) in PD patients and 1.84 (0.59-5.76) in untreated PD patients. In the exploratory model, the ORs (95% CIs) for IDC were 5.00 (1.19-21.03) in PD patients and 6.26 (1.34-29.34) in untreated PD patients.<br><br>CONCLUSION: This single-centre, prospective study failed to demonstrate a consistently positive correlation between PD and IDC in RA patients receiving biological treatment.}, }
@article {pmid31673038, year = {2019}, author = {Golberg, A and Sheviryov, J and Solomon, O and Anavy, L and Yakhini, Z}, title = {Molecular harvesting with electroporation for tissue profiling.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {15750}, pmid = {31673038}, issn = {2045-2322}, mesh = {Animals ; Electroporation/*methods ; Female ; Gene Ontology ; Genomics ; Hep G2 Cells ; Humans ; Kidney/*metabolism/pathology ; Liver/*metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Proteins/metabolism ; Neoplasms/genetics/metabolism/pathology ; Proteomics ; RNA, Neoplasm/metabolism ; Transplantation, Heterologous ; }, abstract = {Recent developments in personalized medicine are based on molecular measurement steps that guide personally adjusted medical decisions. A central approach to molecular profiling consists of measuring DNA, RNA, and/or proteins in tissue samples, most notably in and around tumors. This measurement yields molecular biomarkers that are potentially predictive of response and of tumor type. Current methods in cancer therapy mostly use tissue biopsy as the starting point of molecular profiling. Tissue biopsies involve a physical resection of a small tissue sample, leading to localized tissue injury, bleeding, inflammation and stress, as well as to an increased risk of metastasis. Here we developed a technology for harvesting biomolecules from tissues using electroporation. We show that tissue electroporation, achieved using a combination of high-voltage short pulses, 50 pulses 500 V cm-1, 30 µs, 1 Hz, with low-voltage long pulses 50 pulses 50 V cm-1, 10 ms, delivered at 1 Hz, allows for tissue-specific extraction of RNA and proteins. We specifically tested RNA and protein extraction from excised kidney and liver samples and from excised HepG2 tumors in mice. Further in vivo development of extraction methods based on electroporation can drive novel approaches to the molecular profiling of tumors and of tumor environment and to related diagnosis practices.}, }
@article {pmid31672492, year = {2020}, author = {Kim, JE and Kim, BG and Jang, Y and Kang, S and Lee, JH and Cho, NH}, title = {The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer.}, journal = {Cancer letters}, volume = {469}, number = {}, pages = {256-265}, doi = {10.1016/j.canlet.2019.10.039}, pmid = {31672492}, issn = {1872-7980}, mesh = {Antineoplastic Agents/pharmacology ; Cancer-Associated Fibroblasts/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/drug effects/genetics ; Disease Progression ; Exosome Multienzyme Ribonuclease Complex/genetics ; Exosomes/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/*genetics ; Proto-Oncogene Proteins c-fos/*genetics ; Stromal Cells/metabolism/pathology ; Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology ; }, abstract = {Stroma-derived exosomal microRNA (exomiR) contributes to tumor progression, however, which remains poorly understood. In our study, we analyzed exomiRs from the cancer-associated fibroblast (CAF) and normal fibroblast (NF) isolated from an invasive ductal carcinoma (IDC) patient and found that the level of microRNA (miR)-4516 was approximately 5-fold lower in CAF-derived exosomes than NF-derived ones. In gene annotation analysis, miR-4516 target genes were mainly associated with the regulation of proliferation. miR-4516 overexpression or mimic treatment suppressed the proliferation of breast cancer cells, especially triple negative breast cancer (TNBC) cells. Among miR-4516 targets, FOSL1 was overexpressed in TNBC cells compared to non-TNBC cells and promoted tumor proliferation. The expression of miR-4516 and FOSL1 was reversely correlated in breast cancer patient tissues. Particularly, TNBC patients with high FOSL1 expression showed a significant poorer survival than those with low FOSL1 expression. Our results show that the loss of miR-4516 from CAF-derived exosomes is associated with FOSL1-dependent TNBC progression and suggest that miR-4516 can be used as an anti-cancer drug for TNBC.}, }
@article {pmid31666416, year = {2019}, author = {Autenshlyus, AI and Davletova, KI and Studenikina, AA and Mikhaylova, ES and Varaksin, NA and Zhurakovsky, IP and Proskura, AV and Sidorov, SV and Lyakhovich, VV}, title = {[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type].}, journal = {Biomeditsinskaia khimiia}, volume = {65}, number = {5}, pages = {424-431}, doi = {10.18097/PBMC20196505424}, pmid = {31666416}, issn = {2310-6972}, mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal/*immunology ; Cytokines/*immunology ; *Extracellular Matrix ; Female ; Humans ; Lymphatic Metastasis ; *Tumor Microenvironment ; }, abstract = {The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.}, }
@article {pmid31661032, year = {2019}, author = {Klomek, AB}, title = {Prevention of postpartum suicidality in Israel.}, journal = {Israel journal of health policy research}, volume = {8}, number = {1}, pages = {77}, pmid = {31661032}, issn = {2045-4015}, mesh = {Child ; Female ; Humans ; Israel ; Postpartum Period ; Pregnancy ; Risk Factors ; *Suicide ; USSR ; }, abstract = {Postpartum suicidality in Israel had not been systematically studied until the recent important investigation by Glasser and colleagues. The authors review rates, trends, and characteristics of postpartum women who considered, attempted, or completed suicide in Israel. This commentary argues that, although postpartum suicidality is relatively rare, it is extremely tragic-not just for the women, but for the entire family and community. The main aim of this commentary is to emphasize that preventive efforts should continue and expand, especially among at-risk groups. At-risk groups include the youngest age group, postpartum Arab women, and postpartum former Soviet Union immigrants. Identification of women at risk or suffering from postpartum depression (PPD) is mandated in Israel. Efforts should include broader screening for various types of suicide ideation and behavior. Assessments should specifically include passive suicide ideation, active suicide ideation with method, intent, and plan, as well as various types of suicide attempts and preparatory behaviors. In addition, specific interventions formulated on evidence-based psychotherapies should be provided in family practice, obstetric, and pediatric settings. These settings are less stigmatized in comparison to mental health settings. Potential therapies can be (among others) Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), which are effective in preventing perinatal depression.}, }
@article {pmid31660917, year = {2019}, author = {Peng, Z and Klomek, AB and Li, L and Su, X and Sillanmäki, L and Chudal, R and Sourander, A}, title = {Associations between Chinese adolescents subjected to traditional and cyber bullying and suicidal ideation, self-harm and suicide attempts.}, journal = {BMC psychiatry}, volume = {19}, number = {1}, pages = {324}, pmid = {31660917}, issn = {1471-244X}, mesh = {Adolescent ; Adolescent Behavior ; Bullying/*statistics &amp; numerical data ; Child ; China/epidemiology ; Crime Victims/*statistics &amp; numerical data ; Cyberbullying/statistics &amp; numerical data ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; Self-Injurious Behavior/*epidemiology/etiology ; Students/statistics &amp; numerical data ; *Suicidal Ideation ; Suicide, Attempted/*statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The incidence of bullying is high among adolescents. Adolescents who were victims of bullying have a higher risk of self-harm and suicidal behavior than adolescents who were non-victims. However, research on suicide and both traditional and cyber bullying was limited in China. Therefore, this study examined the associations between Chinese adolescents who were the victims of traditional and cyber bullying and the prevalence of suicidal ideation, self-harm and suicide attempts.<br><br>METHODS: This was a population-based study of 2647 students (51.2% girls) with a mean age of 13.6 ± 1.1 years from 10 junior high schools in Shantou, China. Information on bullying victimization, suicidal ideation, self-harm and suicide attempts were collected using a self-administered questionnaire and the psychopathology of the students was assessed using the Strengths and Difficulties Questionnaire (SDQ). The associations were examined with multinomial logistic regression, adjusted for covariates.<br><br>RESULTS: Traditional bullying victimization was reported by 16.7% of the adolescents, cyber bullying victimization by 9.0% and both by 3.5%. The prevalence of suicidal ideation was 23.5%, self-harm was 6.2% and suicide attempts was 4.2%. Psychopathology symptoms were risk factors for suicide ideation only, ideation plus self-harm, self-harm only and suicide attempts. Victims of both traditional and cyber bullying had the highest risk of suicidal ideation only, ideation plus self-harm and suicide attempts, compared to those reporting one form of bullying. Victims of cyber bullying only had the second highest risk of suicidal ideation only and suicidal ideation plus self-harm compared to non-victims.<br><br>CONCLUSIONS: Adolescents who were victims of both traditional and cyber bullying had greater risks of adverse outcomes of suicidal ideation only, suicidal ideation plus self-harm and suicide attempts. The results of the current study suggest that those exposed to both forms of bullying should be routinely screened for suicidal risk. In addition, school-based anti-bully interventions should also target cyber bullying.}, }
@article {pmid31656498, year = {2019}, author = {Mohammedi, L and Doula, FD and Mesli, F and Senhadji, R}, title = {Cyclin D1 overexpression in Algerian breast cancer women: correlation with CCND1 amplification and clinicopathological parameters.}, journal = {African health sciences}, volume = {19}, number = {2}, pages = {2140-2146}, pmid = {31656498}, issn = {1729-0503}, mesh = {Adult ; Aged ; Algeria ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cyclin D1/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prognosis ; }, abstract = {Background: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas.<br><br>Objectives: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters.<br><br>Materials and methods: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138).<br><br>Results: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression.<br><br>Conclusion: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis.}, }
@article {pmid31647159, year = {2020}, author = {Seckin, ZI and Brumble, LM and Libertin, CR}, title = {Serologic screening and infectious disease consultation (IDC): Indicated in heart, lung, liver (HLL) solid organ transplants (SOT) for measles, mumps, rubella, and varicella.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {1}, pages = {e13202}, doi = {10.1111/tid.13202}, pmid = {31647159}, issn = {1399-3062}, mesh = {Adult ; Antibodies, Viral/*blood ; Chickenpox/etiology/immunology/prevention &amp; control ; Communicable Disease Control/*methods ; Communicable Diseases/*etiology/immunology ; Humans ; Measles/etiology/immunology/prevention &amp; control ; Mumps/etiology/immunology/prevention &amp; control ; *Organ Transplantation ; *Referral and Consultation ; Retrospective Studies ; Rubella/etiology/immunology/prevention &amp; control ; *Serologic Tests ; Vaccination ; }, abstract = {BACKGROUND: Solid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre-transplant infectious disease consultation (IDC) improves vaccination rates.<br><br>METHODS: This study was an institution-based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC).<br><br>RESULTS: One hundred and eighty-seven (77%) of a total 242 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients, vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre-transplant IDC patients and only in 9 (16.7%) NIDC patients (P < .001).<br><br>CONCLUSIONS: Despite the relatively high IDC rate, patients' screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol-driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.}, }
@article {pmid31617074, year = {2020}, author = {Sethy, C and Goutam, K and Nayak, D and Pradhan, R and Molla, S and Chatterjee, S and Rout, N and Wyatt, MD and Narayan, S and Kundu, CN}, title = {Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.}, journal = {Journal of cancer research and clinical oncology}, volume = {146}, number = {1}, pages = {245-259}, pmid = {31617074}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*genetics/metabolism ; Cell Adhesion Molecules/biosynthesis/*genetics/metabolism ; Female ; Humans ; Middle Aged ; NF-kappa B/metabolism ; Neovascularization, Pathologic/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; }, abstract = {PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs).<br><br>METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens.<br><br>RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors.<br><br>CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.}, }
@article {pmid31612916, year = {2019}, author = {Shimmura, H and Kuramochi, H and Jibiki, N and Katagiri, S and Nishino, T and Araida, T}, title = {Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {11}, pages = {1049-1054}, doi = {10.1093/jjco/hyz141}, pmid = {31612916}, issn = {1465-3621}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; BRCA2 Protein/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Carcinoma, Pancreatic Ductal/*drug therapy ; Female ; Fluorouracil/therapeutic use ; Genetic Testing ; Germ Cells ; Germ-Line Mutation ; Humans ; Irinotecan/therapeutic use ; Leucovorin/therapeutic use ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Middle Aged ; Mutation ; Oxaliplatin/therapeutic use ; Pancreatic Neoplasms/*drug therapy ; Pancreaticoduodenectomy ; }, abstract = {Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history-her mother died of pancreatic adenocarcinoma at age 48-we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.}, }
@article {pmid31594782, year = {2019}, author = {Jakharia-Shah, A and Wheatley, H and Beesley, M}, title = {Reminder of an important clinical lesson: breast cancer metastasis to the parotid gland.}, journal = {BMJ case reports}, volume = {12}, number = {10}, pages = {}, doi = {10.1136/bcr-2018-226494}, pmid = {31594782}, issn = {1757-790X}, mesh = {Biopsy, Fine-Needle/methods ; Breast Neoplasms/complications/diagnostic imaging/pathology/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Parotid Gland/*pathology/surgery ; Parotid Neoplasms/pathology/*secondary/surgery ; Positron Emission Tomography Computed Tomography/methods ; Receptor, ErbB-2/metabolism ; Treatment Outcome ; }, abstract = {A 59-year-old woman presented to an otolaryngology clinic with an 8-week history of a painless lump over her left parotid gland. Her medical history included an invasive ductal carcinoma (33 mm) and a ductal carcinoma in situ (70 mm) of the right breast, for which she had a mastectomy and various adjuvant therapies. The primary tumour presented 8 years prior to the metachronous metastasis. This patient was a non-smoker and had no significant family history. Post-superficial parotidectomy pathology revealed the parotid gland tumour to be oestrogen receptor-positive and HER2 receptor-positive, thus ruling out the initial differential diagnosis of a pleomorphic adenoma. A consequential total parotidectomy with a posterolateral neck dissection was performed with sparing of the facial nerve. The patient recovered well having only encountered a self-resolving salivary fistula. She portrayed no signs of facial nerve palsy and subsequent imaging scans showed no abnormalities.}, }
@article {pmid31584185, year = {2020}, author = {Xu, Q and Rangaswamy, US and Wang, W and Robbins, SH and Harper, J and Jin, H and Cheng, X}, title = {Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo.}, journal = {International journal of cancer}, volume = {146}, number = {2}, pages = {531-541}, doi = {10.1002/ijc.32694}, pmid = {31584185}, issn = {1097-0215}, mesh = {Animals ; Chlorocebus aethiops ; Coculture Techniques ; *Cross-Priming ; Dendritic Cells/*immunology/metabolism ; Female ; HeLa Cells ; Humans ; Immunotherapy/*methods ; Interferon Type I/immunology/metabolism ; Neoplasms/immunology/*therapy ; Newcastle disease virus/genetics/immunology ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/genetics/immunology ; RNA/administration &amp; dosage/genetics ; RNA, Viral/administration &amp; dosage/genetics ; T-Lymphocytes/immunology ; Vero Cells ; }, abstract = {We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.}, }
@article {pmid31578784, year = {2020}, author = {Patel, DP and Herrick, JS and Stoffel, JT and Elliott, SP and Lenherr, SM and Presson, AP and Welk, B and Jha, A and Myers, JB and , }, title = {Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.}, journal = {Neurourology and urodynamics}, volume = {39}, number = {1}, pages = {211-219}, doi = {10.1002/nau.24172}, pmid = {31578784}, issn = {1520-6777}, mesh = {Adult ; Female ; Health Behavior ; Humans ; Intermittent Urethral Catheterization/*adverse effects ; Male ; Middle Aged ; Patient Compliance ; Patient Satisfaction ; *Quality of Life ; Registries ; Spinal Cord Injuries/*complications ; Urinary Bladder, Neurogenic/*etiology ; Urinary Tract Infections/*etiology ; }, abstract = {INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation.<br><br>METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL.<br><br>RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties).<br><br>CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.}, }
@article {pmid31576258, year = {2019}, author = {Marsili, C and Wilson, CM and Gura, N}, title = {Prospective Surveillance Screenings to Identify Physical Therapy Needs During Breast Cancer Diagnosis and Surviviorship: A Case Report.}, journal = {Cureus}, volume = {11}, number = {7}, pages = {e5265}, pmid = {31576258}, issn = {2168-8184}, abstract = {Breast cancer and its treatments can cause detrimental effects to function and quality of life (QoL). These patients do not conventionally receive physical therapy services until impairments and functional limitations have become extensive. Emerging treatment models advocate for early rehabilitation screenings and proactive interventions, which are termed prospective surveillance. The purpose of this case report was to describe two prospective surveillance screenings at initial diagnosis and survivorship and subsequent physical therapy episodes of care for a patient with breast cancer. A 39-year-old female was diagnosed with invasive ductal carcinoma of the right breast. Approximately three months after the initial diagnosis, the patient had a right nipple-sparing mastectomy and immediate reconstruction with an expander. In addition, one lymph node was removed and underwent a biopsy, which was negative for metastases. The patient was screened by a physical therapist after her initial cancer diagnosis at the breast multidisciplinary clinic. This was after her mastectomy with an expander; the therapist recommended an episode of outpatient physical therapy due to impairments in pain, fatigue, loss of range of motion, weakness, and limitations in performance of her activities of daily living. The patient was seen initially for five visits. She underwent her final reconstructive surgery one month after discharge from physical therapy. Six months after her final reconstructive surgery, she was screened by the same physical therapist in the cancer survivorship clinic. Once again, therapy was recommended due to pain as well as deficits to her range of motion, strength, and functional status. The second episode of care lasted 14 visits and the patient showed improvements in pain, range of motion, shoulder strength and gains in the patient-specific functional scale and upper extremity functional index. This case reflects the importance of prospective surveillance screenings to overall patient outcomes. This patient may not have otherwise received physical therapy and its associated benefits without the prospective screenings by the physical therapist.}, }
@article {pmid34191158, year = {2019}, author = {Aarstad, EM and Nordhaug, P and Naghavi-Behzad, M and Larsen, LB and Gerke, O and Hildebrandt, MG}, title = {Prevalence of focal incidental breast uptake on FDG-PET/CT and risk of malignancy: a systematic review and meta-analysis.}, journal = {European journal of hybrid imaging}, volume = {3}, number = {1}, pages = {16}, pmid = {34191158}, issn = {2510-3636}, support = {//Danmarks Frie Forskningsfond/ ; //Syddansk Universitet/ ; }, abstract = {BACKGROUND: FDG-PET/CT is increasingly used for oncologic and inflammatory diseases. Focal incidental FDG uptake occurs rarely in breast tissue but has often significant consequences. This study aimed to systematically review literature regarding focal incidental breast uptake (FIBU) on FDG-PET/CT in order to yield an update on the prevalence and risk of malignancy for FIBU.<br><br>METHODS: A systematic search for relevant articles published between 2012 and 2018 was performed through MEDLINE, Embase, and Cochrane databases. Studies addressing the detection of FIBU in patients without a previous history of breast malignancy were included. The QUADAS-2 was used for quality assessment, and eligible data were pooled using a fixed-effects model. I2 was calculated for the heterogeneity between studies.<br><br>RESULTS: Eight studies containing 180,002 scans were included in the systematic review. The median prevalence of FIBU for both genders was 0.52% (range 0.18-22.5%). Prevalence for women was mentioned separately in five studies and varied from 0.51 to 23.5%. One study reporting a high prevalence was based on patients being staged for known malignancy, and the word "breast" was used in the search, which may have caused selection bias. Data from four studies were eligible for meta-analysis. A high degree of heterogeneity was observed for prevalence data (I2 of 97.5%), while moderate heterogeneity was observed for data on malignancy risk assessment (I2 of 62.8%). The pooled prevalence of FIBU in women was 0.61% (range 0.56-0.66%), and the pooled prevalence of malignancy of FIBUs was 38.7% (range 34.4-43.0%). The most commonly detected malignancy was invasive ductal carcinoma.<br><br>CONCLUSION: FIBU occurs rarely on FDG-PET/CT for female patients but yields a high risk of malignancy according to the results of published papers. Therefore, it should be considered relevant to further elucidate patients with incidentally detected FDG uptake in breast in clinical practice.}, }
@article {pmid31539353, year = {2019}, author = {Gonzalez, SM and Aguilar-Jimenez, W and Alvarez, N and Rugeles, MT}, title = {Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells.}, journal = {Hormone molecular biology and clinical investigation}, volume = {40}, number = {1}, pages = {}, doi = {10.1515/hmbci-2019-0003}, pmid = {31539353}, issn = {1868-1891}, mesh = {CD4-Positive T-Lymphocytes/*drug effects/immunology/virology ; Cells, Cultured ; Cholecalciferol/*pharmacology ; Dendritic Cells/*drug effects/immunology/virology ; HIV Infections/*immunology/prevention &amp; control/transmission/virology ; HIV-1/*drug effects/immunology/physiology ; Humans ; Immunologic Factors/pharmacology ; Monocytes/drug effects/immunology/virology ; Virus Internalization/drug effects ; Vitamins/*pharmacology ; }, abstract = {Background Dendritic cells (DCs) play a crucial role during HIV-1 transmission due to their ability to transfer virions to susceptible CD4+ T cells, particularly in the lymph nodes during antigen presentation which favors the establishment of systemic infection. As mature dendritic cells (mDCs) exhibit a greater ability to transfer virions, compared to immature DCs (iDCs), maintenance of an iDC phenotype could decrease viral transmission. The immunomodulatory vitamin D (VitD) has been shown to reduce activation and maturation of DCs; hence, we hypothesized that it would reduce viral transference by DCs. Materials and methods We evaluated the effect of in vitro treatment with a precursor of VitD, cholecalciferol, on the activation/maturation phenotype of differentiated monocyte-derived DCs and their ability to transfer HIV-1 to autologous CD4+ T cells. Results Our findings show that although cholecalciferol decreases the activation of iDCs, it did not impact the maturation phenotype after LPS treatment nor iDCs' ability to transfer viral particles to target cells. Conclusion These findings suggest that despite cholecalciferol potentially modulates the phenotype of mucosal iDCs in vivo, such modulation might not impact the ability of these cells to transfer HIV-1 to target CD4+ T cells.}, }
@article {pmid31538688, year = {2020}, author = {Haynes, HR and Rose, DSC}, title = {Synchronous small lymphocytic lymphoma and metastatic breast carcinoma in axillary lymph nodes: Preservation of follicular architecture only in the portions of affected lymph nodes involved by metastatic carcinoma.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {245-246}, doi = {10.1111/tbj.13538}, pmid = {31538688}, issn = {1524-4741}, mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {We present a case of metastatic ductal carcinoma of breast with the incidental discovery of small lymphocytic lymphoma (SLL) in regional axillary nodes. The co-occurence of metastatic carcinoma and low-grade lymphoma in lymph nodes is rare but well recognized. However, in this case, in the lymph nodes in which sizeable metastatic carcinoma deposits were present, the follicular structures between the sinusoidal carcinomatous infiltrates were preserved, whereas the uninvolved portions of the nodes were overrun by SLL. This is the first description of this phenomenon. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.}, }
@article {pmid31529566, year = {2019}, author = {van Kooten, XF and Petrini, LFT and Kashyap, A and Voith von Voithenberg, L and Bercovici, M and Kaigala, GV}, title = {Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {58}, number = {43}, pages = {15259-15262}, doi = {10.1002/anie.201907150}, pmid = {31529566}, issn = {1521-3773}, support = {607322//FP7 People: Marie-Curie Actions/International ; 727761//H2020 European Research Council/International ; }, mesh = {Breast Neoplasms/*genetics/pathology ; DNA, Neoplasm/analysis/metabolism ; Female ; Formaldehyde/chemistry ; Genotype ; Humans ; MCF-7 Cells ; Microscopy, Confocal ; Paraffin Embedding ; Point Mutation ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.}, }
@article {pmid31512354, year = {2020}, author = {Ali Mlees, M}, title = {Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {139-143}, doi = {10.1111/tbj.13493}, pmid = {31512354}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology ; Dilatation, Pathologic/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Image-Guided Biopsy ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Papilloma/*diagnosis/pathology ; Ultrasonography, Interventional ; }, abstract = {Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.}, }
@article {pmid31508769, year = {2019}, author = {Couto, MSA and Firme, VAC and Guerra, MR and Bustamante-Teixeira, MT}, title = {The effect of redistribution of ill-defined causes of death on the mortality rate of breast cancer in Brazil.}, journal = {Ciencia &amp; saude coletiva}, volume = {24}, number = {9}, pages = {3517-3528}, doi = {10.1590/1413-81232018249.31402017}, pmid = {31508769}, issn = {1678-4561}, mesh = {Brazil/epidemiology ; Breast Neoplasms/*mortality ; Cause of Death/*trends ; Cities/statistics &amp; numerical data ; Female ; Humans ; Mortality/*trends ; }, abstract = {The relevance of breast cancer for women has driven research about mortality of this disease. However, these studies are affected by problems generated by deaths due to ill-defined causes (IDC). To highlight distortions caused by IDC in studies that evaluate mortality, we calculated the age-standardized mortality rates of breast cancer, with and without adjustment for IDC for the years 1990, 2000, and 2010. Then, panel data regression models were estimated and enabled us to identify that the adjustment for IDC: has elevated breast cancer mortality rate of Brazilian municipalities by 9% in the period considered; has drawn mortality rates of the South, Southeast, Northeast and North regions closer; has reduced the increasing trend of mortality by almost 60%, mainly in the Southeast and South regions; has increased, more sharply, the mortality in cities with less than 5 thousand inhabitants; has curbed the significance of most factors associated with breast cancer; has revealed that the effect of longevity and the public health expenditure may be overestimated. These results highlight the importance of adjustment for IDC in producing reliable mortality indicators.}, }
@article {pmid31488082, year = {2019}, author = {McQuerry, JA and Jenkins, DF and Yost, SE and Zhang, Y and Schmolze, D and Johnson, WE and Yuan, Y and Bild, AH}, title = {Pathway activity profiling of growth factor receptor network and stemness pathways differentiates metaplastic breast cancer histological subtypes.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {881}, pmid = {31488082}, issn = {1471-2407}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; U54 CA209978/CA/NCI NIH HHS/United States ; U54CA209978/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bcl-2-Like Protein 11/metabolism ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Osteonectin/genetics ; Phenotype ; Prognosis ; RNA-Seq/methods ; Receptors, Growth Factor/*metabolism ; Signal Transduction/*genetics ; Snail Family Transcription Factors/metabolism ; Transcriptome/*genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; }, abstract = {BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC).<br><br>METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes.<br><br>RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression.<br><br>CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.}, }
@article {pmid31486035, year = {2020}, author = {Delaunay, T and Achard, C and Grégoire, M and Tangy, F and Boisgerault, N and Fonteneau, JF}, title = {A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2058}, number = {}, pages = {127-132}, doi = {10.1007/978-1-4939-9794-7_8}, pmid = {31486035}, issn = {1940-6029}, mesh = {Animals ; Antigen-Presenting Cells/immunology/metabolism ; Cell Death/immunology ; Dendritic Cells/immunology/metabolism ; Genetic Therapy/methods ; Genetic Vectors/*genetics ; Humans ; *Immunomodulation ; Immunophenotyping ; Monocytes/immunology/metabolism ; Neoplasms/*immunology/metabolism/pathology/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/*genetics/immunology ; }, abstract = {Oncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC).}, }
@article {pmid31467444, year = {2020}, author = {Sarhan, MS and Mourad, EF and Nemr, RA and Abdelfadeel, MR and Daanaa, HA and Youssef, HH and Goda, HA and Hamza, MA and Fayez, M and Eichler-Löbermann, B and Ruppel, S and Hegazi, NA}, title = {An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria.}, journal = {The Journal of antibiotics}, volume = {73}, number = {1}, pages = {66-71}, pmid = {31467444}, issn = {1881-1469}, mesh = {Actinobacteria/*chemistry ; Bacteriological Techniques ; Colony Count, Microbial ; Culture Media ; Endophytes/*chemistry ; *Microbiota ; Plant Roots/microbiology ; Plant Shoots/microbiology ; Plants/microbiology ; }, abstract = {The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce "the inoculum-dependent culturing strategy, IDC". The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.}, }
@article {pmid31440248, year = {2019}, author = {Escoter-Torres, L and Caratti, G and Mechtidou, A and Tuckermann, J and Uhlenhaut, NH and Vettorazzi, S}, title = {Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1859}, pmid = {31440248}, issn = {1664-3224}, mesh = {Animals ; Gene Expression Regulation/*drug effects/*immunology ; Glucocorticoids/*immunology/pharmacology ; Humans ; Immunosuppressive Agents/*immunology/pharmacology ; Receptors, Glucocorticoid/*immunology ; }, abstract = {For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles.}, }
@article {pmid31437176, year = {2019}, author = {Santos Junior, OR and da Costa Rocha, MO and Rodrigues de Almeida, F and Sales da Cunha, PF and Souza, SCS and Saad, GP and Santos, TADQ and Ferreira, AM and Tan, TC and Nunes, MCP}, title = {Speckle tracking echocardiographic deformation indices in Chagas and idiopathic dilated cardiomyopathy: Incremental prognostic value of longitudinal strain.}, journal = {PloS one}, volume = {14}, number = {8}, pages = {e0221028}, pmid = {31437176}, issn = {1932-6203}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*diagnostic imaging/mortality/physiopathology ; Chagas Cardiomyopathy/complications/*diagnostic imaging/mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/*diagnostic imaging/etiology/mortality/physiopathology ; Heart Transplantation/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Prognosis ; Stroke Volume/physiology ; Survival Analysis ; Ventricular Function, Left/physiology ; }, abstract = {BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis.<br><br>OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients.<br><br>METHODS: We enrolled 112 patients, age of 56.7 ± 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation.<br><br>RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035).<br><br>CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.}, }
@article {pmid31427562, year = {2019}, author = {Sun, Y and Lei, B and Huang, Q}, title = {SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {25}, number = {}, pages = {6244-6254}, pmid = {31427562}, issn = {1643-3750}, mesh = {Adenylate Kinase/*metabolism ; Apoptosis/physiology ; Carcinoma, Hepatocellular/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Cell Survival/physiology ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms/genetics/*metabolism/*pathology ; Neoplasm Invasiveness ; SOXF Transcription Factors/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.}, }
@article {pmid31424026, year = {2020}, author = {Chen, JR and Zhao, JG and Zhu, S and Zhang, MN and Chen, N and Liu, JD and Sun, GX and Shen, PF and Zeng, H}, title = {Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.}, journal = {Asian journal of andrology}, volume = {22}, number = {4}, pages = {427-431}, pmid = {31424026}, issn = {1745-7262}, mesh = {Abiraterone Acetate/therapeutic use ; Adenocarcinoma/metabolism/*secondary/therapy ; Aged ; Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Biopsy, Large-Core Needle ; Bone Neoplasms/metabolism/*secondary/therapy ; Docetaxel/therapeutic use ; Functional Status ; Humans ; Kaplan-Meier Estimate ; Male ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neuroendocrine Tumors ; Orchiectomy ; Prognosis ; Progression-Free Survival ; Proportional Hazards Models ; Prostate-Specific Antigen/metabolism ; Prostatectomy ; Prostatic Neoplasms/metabolism/*pathology/therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism/pathology/therapy ; Retrospective Studies ; Survival Rate ; }, abstract = {This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml-1, had worse prognoses if EPE was detected. In patients with PSA <50 ng ml-1, EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.}, }
@article {pmid31391072, year = {2019}, author = {Tan, X and Li, Z and Ren, S and Rezaei, K and Pan, Q and Goldstein, AT and Macri, CJ and Cao, D and Brem, RF and Fu, SW}, title = {Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {89}, pmid = {31391072}, issn = {1465-542X}, mesh = {3' Untranslated Regions ; Breast Neoplasms/*genetics/*pathology/therapy ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; DNA Damage ; Disease Progression ; Drug Resistance, Neoplasm/*genetics ; Epithelial-Mesenchymal Transition/genetics ; Female ; Forkhead Box Protein M1/genetics ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; MicroRNAs/*genetics ; Models, Biological ; RNA Interference ; Radiation Tolerance/*genetics ; }, abstract = {BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.<br><br>METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.<br><br>RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.<br><br>CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.}, }
@article {pmid31390230, year = {2019}, author = {Ortega, A and Olea-Herrero, N and Arenas, MI and Vélez-Vélez, E and Moreno-Gómez-Toledano, R and Muñoz-Moreno, C and Lázaro, A and Esbrit, P and Tejedor, A and Bosch, RJ}, title = {Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.}, journal = {American journal of physiology. Renal physiology}, volume = {317}, number = {4}, pages = {F874-F880}, doi = {10.1152/ajprenal.00091.2019}, pmid = {31390230}, issn = {1522-1466}, mesh = {Acute Kidney Injury/*chemically induced/pathology/*urine ; Animals ; Antineoplastic Agents/*toxicity ; Biomarkers/urine ; Cisplatin/*toxicity ; Creatinine/urine ; Kidney/pathology ; Kidney Function Tests ; Male ; Parathyroid Hormone-Related Protein/*urine ; Rats ; Rats, Wistar ; }, abstract = {Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.}, }
@article {pmid31388122, year = {2020}, author = {Goodes, LM and King, GK and Rea, A and Murray, K and Boan, P and Watts, A and Bardsley, J and Hartshorn, C and Thavaseelan, J and Rawlins, M and Brock, JA and Dunlop, SA}, title = {Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.}, journal = {Spinal cord}, volume = {58}, number = {1}, pages = {25-34}, pmid = {31388122}, issn = {1476-5624}, mesh = {Adult ; Catheters, Indwelling/statistics &amp; numerical data ; Humans ; Incidence ; Inpatients/statistics &amp; numerical data ; Length of Stay/*statistics &amp; numerical data ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries/complications/*epidemiology ; Time Factors ; Urinary Catheterization/adverse effects/*statistics &amp; numerical data ; Urinary Tract Infections/*epidemiology/etiology ; Western Australia/epidemiology ; }, abstract = {STUDY DESIGN: Retrospective audit.<br><br>OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).<br><br>SETTING: Western Australian Hospitals managing SCI patients.<br><br>METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.<br><br>RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively).<br><br>CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.<br><br>SPONSORSHIP: None.}, }
@article {pmid31357083, year = {2019}, author = {Arabpour, M and Rasolmali, R and Talei, AR and Mehdipour, F and Ghaderi, A}, title = {Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.}, journal = {Molecular immunology}, volume = {114}, number = {}, pages = {172-178}, doi = {10.1016/j.molimm.2019.07.019}, pmid = {31357083}, issn = {1872-9142}, mesh = {Adult ; Aged ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD40 Ligand/immunology ; Carcinoma, Ductal/immunology ; Female ; Granzymes/*immunology ; Humans ; Interleukins/immunology ; Lymph Nodes/*immunology ; Lymphocyte Activation/*immunology ; Middle Aged ; Perforin/immunology ; }, abstract = {B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB+ B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB+ B cells were perforin-negative. Both naïve (CD24lowCD27-) and active/memory (CD24hiCD27+) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB+ B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB+ B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB+ B cells in breast tumor immunity.}, }
@article {pmid31354196, year = {2019}, author = {Ogunleye, AJ and Olanrewaju, AJ and Arowosegbe, M and Omotuyi, OI}, title = {Molecular docking based screening analysis of GSK3B.}, journal = {Bioinformation}, volume = {15}, number = {3}, pages = {201-208}, pmid = {31354196}, issn = {0973-2063}, abstract = {GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.}, }
@article {pmid31352554, year = {2019}, author = {Zacharioudakis, K and Kontoulis, T and Vella, JX and Zhao, J and Ramakrishnan, R and Cunningham, DA and Mufti, RA and Leff, DR and Thiruchelvam, P and Hogben, K and Hadjiminas, DJ}, title = {Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.}, journal = {Breast cancer research and treatment}, volume = {178}, number = {1}, pages = {115-120}, pmid = {31352554}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Preoperative Period ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound.<br><br>METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy.<br><br>RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%.<br><br>CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients with PND.}, }
@article {pmid31351155, year = {2019}, author = {Ding, Q and Chen, H and Lim, B and Damodaran, S and Chen, W and Tripathy, D and Piha-Paul, S and Luthra, R and Meric-Bernstam, F and Sahin, AA}, title = {HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {32-38}, doi = {10.1016/j.humpath.2019.07.006}, pmid = {31351155}, issn = {1532-8392}, mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Receptor, ErbB-2/*genetics/metabolism ; Retrospective Studies ; }, abstract = {HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n = 14) and extracellular (n = 4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor positive; the 4 cases with extracellular domain mutations were exclusively estrogen receptor negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of nonclassic ILC.}, }
@article {pmid31350286, year = {2019}, author = {Lourenco, C and Kalkat, M and Houlahan, KE and De Melo, J and Longo, J and Done, SJ and Boutros, PC and Penn, LZ}, title = {Modelling the MYC-driven normal-to-tumour switch in breast cancer.}, journal = {Disease models &amp; mechanisms}, volume = {12}, number = {7}, pages = {}, pmid = {31350286}, issn = {1754-8411}, support = {//CIHR/Canada ; }, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Regulation, Neoplastic ; *Genes, myc ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; }, abstract = {The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CAH1047R) led to the development of organised acinar structures in mice. Expressing both PIK3CAH1047R and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay in vivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.}, }
@article {pmid31331321, year = {2019}, author = {Nkinda, L and Patel, K and Njuguna, B and Ngangali, JP and Memiah, P and Bwire, GM and Majigo, MV and Mizinduko, M and Pastakia, SD and Lyamuya, E}, title = {C - reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania.}, journal = {BMC endocrine disorders}, volume = {19}, number = {1}, pages = {77}, pmid = {31331321}, issn = {1472-6823}, support = {-//Intra-ACP academic mobility scholarship/ ; }, mesh = {Biomarkers/*blood ; Blood Glucose/*analysis ; C-Reactive Protein/*analysis ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Glucose Intolerance/*blood/epidemiology/virology ; HIV/*isolation &amp; purification ; HIV Infections/*complications/virology ; Humans ; Incidence ; Interleukin-6/*blood ; Male ; Middle Aged ; Prognosis ; Tanzania/epidemiology ; }, abstract = {BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania.<br><br>METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75 g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant.<br><br>RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (> 25 kg/m2), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p = 0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p = 0.03).We did not find a significant association between IL-6 and dysglycemia.<br><br>CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.}, }
@article {pmid31319513, year = {2019}, author = {Fang, A and Dong, J and Zhang, R}, title = {Simulation of Heavy Metals Migration in Soil-Wheat System of Mining Area.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, pmid = {31319513}, issn = {1660-4601}, mesh = {China ; Edible Grain/chemistry ; Environmental Monitoring ; Metals, Heavy/analysis/*metabolism ; Mining ; Regression Analysis ; Soil ; Soil Pollutants/analysis/*metabolism ; Triticum/*metabolism ; }, abstract = {Heavy metals in the soil of mining areas have become a primary source of pollution, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. A long-term field experiment under natural conditions was carried out to explore the distribution characteristic and migration law of heavy metals in a soil-wheat system of a mining area in Xuzhou. According to the second level standard of environmental quality standards for soils of China (GB 15618-1995), 30.8 g of CrCl3·6H2O, 8.3 g of Pb(CH3COO)2·3H2O, and 16.5 g of ZnSO4·7H2O were added into the soil of three experimental sites, respectively. The other experimental site with no additional compounds was used as the control site. The Cr, Pb, and Zn concentrations in the soil-wheat system were counted and their corresponding migration models were constructed. From 2014 to 2017, the mean concentrations of Cr (49.09 mg·kg-1), Pb (20.08 mg·kg-1), and Zn (39.11 mg·kg-1) in the soil of the addition sites were higher than that of the control site. The mean concentrations of Cr, Pb, and Zn in wheat of the addition sites were greater than that of the control site with the values of 3.29, 0.06, and 29 mg·kg-1. In comparison, the Cr, Pb, and Zn concentrations in the soil of all experimental sites were lower than the second level standard of environmental quality standards for soils of China (GB 15618-1995), whereas the Cr concentration exceeded its corresponding soil background value of Xuzhou in 2017. The Pb concentration in soil of the addition site was greater than its corresponding background value from 2014 to 2016. The Pb and Zn concentrations in wheat of all experimental sites were lower than the national hygienic standard for grains of China (GB2715-2005) and the national guidelines for cereals of China (NY 861-2004), but the Cr concentration significantly exceeded the national guidelines for cereals of China (NY 861-2004). By constructing the Identical-Discrepant-Contrary (IDC) gray connection models, the result showed that there was a non-linear relationship of Cr, Pb, and Zn concentrations in the soil-wheat system, and the absolute values of most correlation coefficients r were lower than 0.5 and the values of greyness f G (r) were more than 0.5. The curvilinear regression models could not reflect the relationship of Cr, Pb, and Zn concentrations in the soil-wheat system with the regression coefficient r 2 values far less than 1. Due to the values of regression coefficient r 2 being close to 1, this study suggested that the allocation estimation models could be used for simulating the Cr, Pb, and Zn migration in the soil-wheat system of a mining area in Xuzhou.}, }
@article {pmid31312338, year = {2019}, author = {Traoré, B and Koulibaly, M and Diallo, A and Bah, M}, title = {Molecular profile of breast cancers in Guinean oncological settings.}, journal = {The Pan African medical journal}, volume = {33}, number = {}, pages = {22}, pmid = {31312338}, issn = {1937-8688}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/genetics/*pathology ; Breast Neoplasms, Male/epidemiology/genetics/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Guinea/epidemiology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/epidemiology/*pathology ; }, abstract = {Breast cancer is a complex disease characterized by the accumulation of multiple molecular alterations giving each tumor phenotype and an own evolutionary potential. This study aimed to describe the distribution of the profile and molecular subtypes of breast cancers followed at Surgical Oncology Unit of Donka National Hospital. This was retrospective and descriptive study on cases of breast cancer in which the hormone receptor status and expression of the Her2 oncogene have been performed from 2007 to 2016. We recorded 58 cases including 56 (96.6%) women and 2 (3.4%) men. The average age was 48.2 ± 10.9. Invasive ductal carcinoma accounted for 50 (86.2%) cases. The SBR grade was II in 31(53.4%) cases, III in 21 (36.2%) cases and I in 6 (10.3%) cases. The tumor was classified as T4 in 36 (62.1%) cases; it was metastatic in 11(19.0%) cases. Estrogen receptors were positive in 29 (50.0%) cases, progesterone receptors positive in 25 (43.1%) cases, the Her2 oncogene was positive in 22 (39.3%) cases. The distribution of molecular sub-types was: 20 (34.5%) luminal A, 15 (25.9%) triple negative, 13 (22.4%) Her2 overexpressed, 8 (13.8%) luminal B and 2 (3.2%) undetermined. This preliminary study showed the poor accessibility of immunohistochemistry for the molecular diagnosis of breast cancer in our country. Luminal A subtypes and triple negatives were more common. The determination of molecular subtypes is a rational basis for hormone therapy and targeted therapy, thus personalizing the treatment of breast cancer.}, }
@article {pmid31308566, year = {2019}, author = {Malik, SS and Baig, M and Khan, MB and Masood, N}, title = {Survival analysis of breast cancer patients with different treatments: a multicentric clinicopathological study.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {69}, number = {7}, pages = {976-980}, pmid = {31308566}, issn = {0030-9982}, mesh = {Adult ; Age Factors ; Antineoplastic Agents/*therapeutic use ; Body Mass Index ; Breast Neoplasms/epidemiology/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/pathology/*therapy ; Cohort Studies ; Combined Modality Therapy ; Consanguinity ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy/*methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Obesity/epidemiology ; Overweight/epidemiology ; Pakistan/epidemiology ; Prospective Studies ; Radiotherapy/*methods ; Risk Factors ; Survival Analysis ; Survival Rate ; }, abstract = {OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups.<br><br>Methods: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24.<br><br>RESULTS: There were 347 subjects with a mean age of 44.3±12.2 years and body mass index of 27.9±4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options.<br><br>CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.}, }
@article {pmid31299411, year = {2019}, author = {Molina, J and Noguer, M and Lepe, JA and Pérez-Moreno, MA and Aguilar-Guisado, M and Lasso de la Vega, R and Peñalva, G and Crespo-Rivas, JC and Gil-Navarro, MV and Salvador, J and Cisneros, JM}, title = {Clinical impact of an educational antimicrobial stewardship program associated with infectious diseases consultation targeting patients with cancer: Results of a 9-year quasi-experimental study with an interrupted time-series analysis.}, journal = {The Journal of infection}, volume = {79}, number = {3}, pages = {206-211}, doi = {10.1016/j.jinf.2019.07.002}, pmid = {31299411}, issn = {1532-2742}, mesh = {*Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; Communicable Diseases/drug therapy/*epidemiology/etiology ; Drug Utilization/statistics &amp; numerical data ; Female ; Health Plan Implementation ; Humans ; Male ; Neoplasms/complications/*epidemiology ; *Referral and Consultation ; Time Factors ; }, abstract = {OBJECTIVES: Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.<br><br>METHODS: An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.<br><br>RESULTS: Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p < 0.01; -8.1% annual reduction for 30-day mortality, p = 0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p = 0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p = 0.71; change in slope -1.98 DDD per quarter, p < 0.01). The decreasing trend for mortality before the ASP also continued after its implementation.<br><br>CONCLUSIONS: The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.}, }
@article {pmid31291711, year = {2020}, author = {Xu, Q and Shao, Y and Zhang, J and Zhang, H and Zhao, Y and Liu, X and Guo, Z and Chong, W and Gu, F and Ma, Y}, title = {Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.}, journal = {Cancer research and treatment}, volume = {52}, number = {1}, pages = {218-245}, pmid = {31291711}, issn = {2005-9256}, support = {81572851//National Scientific Foundation of China/ ; 81672636//National Scientific Foundation of China/ ; }, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*drug therapy/*etiology/mortality ; Carrier Proteins/*genetics ; Cell Transformation, Neoplastic/*genetics ; *Disease Susceptibility ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Proteins/*genetics ; Prognosis ; Recurrence ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.<br><br>Materials and Methods: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.<br><br>RESULTS: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.<br><br>CONCLUSION: AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.}, }
@article {pmid31288210, year = {2019}, author = {Shelef, L and Klomek, AB and Fruchter, E and Kedem, R and Mann, JJ and Zalsman, G}, title = {Suicide ideation severity is associated with severe suicide attempts in a military setting.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {61}, number = {}, pages = {49-55}, doi = {10.1016/j.eurpsy.2019.06.005}, pmid = {31288210}, issn = {1778-3585}, mesh = {Adult ; Female ; Humans ; Intention ; Male ; Middle Aged ; Military Personnel/*psychology ; Risk Factors ; Self Report ; Self-Control/*psychology ; *Severity of Illness Index ; *Suicidal Ideation ; Suicide, Attempted/psychology ; Veterans/*psychology ; Young Adult ; }, abstract = {BACKGROUND: There is an ongoing debate on the effectiveness of suicidal behavior prevention measures in the military. The association of three widely used tools with severe suicide attempts was assessed in this setting.<br><br>METHODS: Thirty-nine Israeli soldiers (59% males), mean age 19 yrs., who attempted suicide during military service were divided into two groups: severe (n = 14; 35.9%) and moderate suicide attempts, and were assessed using the Scale for Suicide Ideation (SSI), Suicide Intent Scale (SIS) and the Columbia Suicide Severity Rating Scale (C-SSRS).<br><br>RESULTS: Seven items from the SSI (p = 0.008), two items from SIS and one item from C-SSRS were associated with severe suicide attempts. Kendall's tau-b correlation with bootstrap demonstrated stability of these correlations.<br><br>CONCLUSION: Greater severity of suicidal ideation was associated with more severe suicide attempts. The combination of male gender, available firearms and current severe suicide ideation is high-risk danger sign in a military setting, even when reported intent to die is low.}, }
@article {pmid31284267, year = {2019}, author = {Liu, S and Wei, H and Li, Y and Diao, L and Lian, R and Zhang, X and Zeng, Y}, title = {Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure.}, journal = {Reproduction (Cambridge, England)}, volume = {158}, number = {3}, pages = {247-255}, doi = {10.1530/REP-19-0172}, pmid = {31284267}, issn = {1741-7899}, mesh = {Abortion, Habitual/*immunology/metabolism ; Adult ; Cell Differentiation ; Dendritic Cells/immunology/*metabolism ; Embryo Implantation/*immunology ; Female ; Humans ; Interleukin-10/*metabolism ; Interleukin-6/metabolism ; Pregnancy ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.}, }
@article {pmid31275451, year = {2019}, author = {Simeunovic, D and Odanovic, N and Pljesa-Ercegovac, M and Radic, T and Radovanovic, S and Coric, V and Milinkovic, I and Matic, M and Djukic, T and Ristic, A and Risimic, D and Seferovic, P and Simic, T and Simic, D and Savic-Radojevic, A}, title = {Glutathione Transferase P1 Polymorphism Might Be a Risk Determinant in Heart Failure.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {6984845}, pmid = {31275451}, issn = {1875-8630}, mesh = {Aged ; Cardiomyopathy, Dilated/complications/*genetics ; Coronary Artery Disease/complications/*genetics ; Female ; Glutathione S-Transferase pi/*genetics ; Heart Failure/etiology/*genetics ; Humans ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; }, abstract = {Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.}, }
@article {pmid31256281, year = {2019}, author = {D'Iorio, A and Maggi, G and Vitale, C and Amboni, M and Di Meglio, D and Trojano, L and Santangelo, G}, title = {Prospective memory in Parkinson's disease: the role of the motor subtypes.}, journal = {Journal of neurology}, volume = {266}, number = {10}, pages = {2505-2511}, pmid = {31256281}, issn = {1432-1459}, mesh = {Aged ; Cognitive Dysfunction/etiology/*physiopathology ; Executive Function/physiology ; Female ; Humans ; Hypokinesia/etiology/*physiopathology ; Male ; *Memory, Episodic ; Middle Aged ; Muscle Rigidity/etiology/*physiopathology ; Parkinson Disease/classification/complications/*physiopathology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson's disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM.<br><br>METHODS: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances.<br><br>RESULTS: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD.<br><br>CONCLUSION: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.}, }
@article {pmid31244288, year = {2019}, author = {Ghaderi, F and Mehdipour, F and Hosseini, A and Talei, A and Ghaderi, A}, title = {Establishment and Characterization of a New Triple Negative Breast Cancer Cell Line from an Iranian Breast Cancer Tissue.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {6}, pages = {1683-1689}, pmid = {31244288}, issn = {2476-762X}, mesh = {Adult ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Culture Techniques ; Cell Line, Tumor ; *Cell Movement ; *Cell Proliferation ; *Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Triple Negative Breast Neoplasms/metabolism/*pathology ; }, abstract = {Breast cancer is the most common malignancy and the leading cause of cancer-related death among women worldwide. The underlying mechanisms for breast cancer development, especially in young women, are not completely understood. Although there are several experimental models to understand the biology of breast cancer such as immortalized cell lines, many of these cell lines have been in culture for decades and most of them have been derived from Caucasians or African-Americans. So, it is required to establish a new cell line derived from primary tumors and Asian women. In this study Pari-Institute for Cancer Research (Pari-ICR) was derived from the primary breast tumor of a 36-years old patient with invasive ductal carcinoma. We characterized the cell line by examining morphology, expression of different markers, and functional profile. Immunocytochemistry showed that this cell line does not express estrogen and progesterone receptors as well as human epidermal growth factor receptor 2 (HER2). Pari-ICR cell line expresses high levels of Vimentin, Ezrin, and S100 but does not express EpCAM, Cytokeratin19, Pan-cytokeratin, Nestin, and Desmin. Its doubling time of Pari-ICR was about 22h and was able to grow as colonies in soft agar. It displayed a higher ability of migration and invasion in comparison with MCF-7 cell line. This breast cancer cell line can serve as a model for understanding the molecular mechanisms of breast carcinogenesis. Moreover, it can be used as an appropriate resource to find novel biomarkers or assess new drugs.}, }
@article {pmid31243309, year = {2019}, author = {Zwarts, I and van Zutphen, T and Kruit, JK and Liu, W and Oosterveer, MH and Verkade, HJ and Uhlenhaut, NH and Jonker, JW}, title = {Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {9299}, pmid = {31243309}, issn = {2045-2322}, mesh = {Adipose Tissue/metabolism ; Animals ; Diet ; Duodenum/metabolism ; Fructose/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Glucose Transporter Type 5/*metabolism ; HEK293 Cells ; Haplorhini ; Humans ; Hydrocarbons, Fluorinated/pharmacology ; Ligands ; Liver X Receptors/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Response Elements ; Sulfonamides/pharmacology ; Transcription, Genetic ; }, abstract = {Fructose has become a major constituent of our modern diet and is implicated as an underlying cause in the development of metabolic diseases. The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human GLUT5 promoter we identified a strong and specific regulation by liver X receptor α (LXRα, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human GLUT5 promoter, located at -385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the in vivo relevance of its regulation by LXR. Together, our findings show that LXRα regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXRα might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.}, }
@article {pmid31240968, year = {2021}, author = {Shenkman, G and Pardo Aviv, L and Hain, D and Goren, O and Shapira, S and Nakash, O and Brunstein Klomek, A and Berant, E}, title = {The moderation of attachment in the association between depressive symptoms and self-harm among a clinical sample.}, journal = {Journal of mental health (Abingdon, England)}, volume = {30}, number = {1}, pages = {58-65}, doi = {10.1080/09638237.2019.1630723}, pmid = {31240968}, issn = {1360-0567}, abstract = {BACKGROUND: Self-harm is a severe health problem worldwide and in particular in clinical settings. The association of depression and self-harm has been extensively studied alongside various variables that have been examined as moderating this association. However, no previous study has examined the moderating role of attachment in this association.<br><br>AIM: We explored the role of attachment orientation in moderating the association between depressive symptoms and self-harm among a sample of patients in a community mental health clinic.<br><br>METHOD: This study was a de-identified archival study of patients' medical charts, and used a convenience sample of 199 patients, which completed self-report measures following the initial intake appointment as part of clinic procedures.<br><br>RESULTS: Findings showed that both attachment anxiety and avoidance moderated the association between depressive symptoms and self-harm, such that depressive symptoms were positively associated with self-harm only when attachment anxiety scores were high, and attachment avoidance scores were high or average.<br><br>CONCLUSIONS: Attachment anxiety and avoidance should be assessed in the initial intake of patients as it has a contribution to understanding self-harm vulnerability among new patients. Future studies should explore this moderation longitudinally so causality could be inferred.}, }
@article {pmid31238731, year = {2019}, author = {Farsang, A and Bódi, I and Fölker, O and Minkó, K and Benyeda, Z and Bálint, Á and Oláh, I}, title = {Avian coronavirus infection induces mannose-binding lectin production in dendritic cell precursors of chicken lymphoid organs.}, journal = {Acta veterinaria Hungarica}, volume = {67}, number = {2}, pages = {183-196}, doi = {10.1556/004.2019.020}, pmid = {31238731}, issn = {0236-6290}, mesh = {Animals ; Avian Proteins/metabolism ; Cecum/*immunology ; *Chickens ; Coronavirus Infections/metabolism/*veterinary ; Dendritic Cells/*metabolism ; Gammacoronavirus/physiology ; Mannose-Binding Lectins/*metabolism ; Poultry Diseases/*metabolism ; Specific Pathogen-Free Organisms ; Spleen/*immunology ; }, abstract = {The aim of this immunocytochemical study was to compare mannose-binding lectin (MBL) production induced by avian coronavirus in the spleen and caecal tonsil (CT). One-day-old specific-pathogen-free (SPF) chickens were experimentally infected with six QX field isolates and the H120 vaccine strain. In the negative control birds, the spleen was MBL negative, while the CT showed scattered MBL-positive cells in close proximity and within the surface epithelium and germinal centre (GC)-like cell clusters. MBL was detectable in the ellipsoid-associated cells (EACs) and cell clusters in the periarterial lymphoid sheath (PALS) by 7 days post infection (dpi). In both organs, the MBL-positive cells occupy antigen-exposed areas, indicating that GC formation depends on resident precursors of dendritic cells. The majority of MBL-positive EACs express the CD83 antigen, providing evidence that coronavirus infection facilitated the maturation of dendritic cell precursors. Surprisingly, co-localisation of MBL and CD83 was not detectable in the CT. In the spleen (associated with circulation), the EACs producing MBL and expressing CD83 are a common precursor of both follicular (FDC) and interdigitating dendritic cells (IDC). In the CT (gut-associated lymphoid tissue, GALT) the precursors of FDC and IDC are MBL-producing cells and CD83-positive cells, respectively. In the CT the two separate precursors of lymphoid dendritic cells provide some 'autonomy' for the GALT.}, }
@article {pmid31229512, year = {2019}, author = {Cao, L and Basudan, A and Sikora, MJ and Bahreini, A and Tasdemir, N and Levine, KM and Jankowitz, RC and McAuliffe, PF and Dabbs, D and Haupt, S and Haupt, Y and Lucas, PC and Lee, AV and Oesterreich, S and Atkinson, JM}, title = {Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.}, journal = {Cancer letters}, volume = {461}, number = {}, pages = {21-30}, pmid = {31229512}, issn = {1872-7980}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis ; Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Cell Cycle Checkpoints ; Cell Cycle Proteins/*genetics/metabolism ; Cell Proliferation ; DNA Copy Number Variations ; Estrogen Receptor alpha/*genetics ; Female ; Follow-Up Studies ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics/metabolism/*pathology ; Prognosis ; Proto-Oncogene Proteins/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Survival Rate ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). To identify potential genetic drivers of ILC progression, we used NanoString nCounter technology to investigate the DNA copy number (CN) in 70 well-curated primary ILC samples. We confirmed prior observations of frequent amplification of CCND1 (33%), and MYC (17%) in ILC, but additionally identified a substantial subset of ILCs with ESR1 and ERBB2 (19%) amplifications. Of interest, tumors with ESR1 CN gains (14%) and amplification (10%) were more likely to recur compared to those with normal CN. Finally, we observed that MDM4 (MDMX) was amplified in 17% of ILC samples. MDM4 knockdown in TP53 wild-type ILC cell lines caused increased apoptosis, decreased proliferation associated with cell cycle arrest, and concomitant activation of TP53 target genes. Similar effects were seen in TP53 mutant cells, indicting a TP53-independent role for MDM4 in ILC. To conclude, amplification of ESR1 and MDM4 are potential genetic drivers of ILC. These amplifications may represent actionable, targetable tumor dependencies, and thus have potential clinical implications and warrant further study.}, }
@article {pmid31217350, year = {2019}, author = {Lodd, E and Wiggenhauser, LM and Morgenstern, J and Fleming, TH and Poschet, G and Büttner, M and Tabler, CT and Wohlfart, DP and Nawroth, PP and Kroll, J}, title = {The combination of loss of glyoxalase1 and obesity results in hyperglycemia.}, journal = {JCI insight}, volume = {4}, number = {12}, pages = {}, pmid = {31217350}, issn = {2379-3708}, mesh = {Animals ; CRISPR-Cas Systems ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/genetics ; Diet ; Disease Models, Animal ; Gene Knockout Techniques ; Genetic Predisposition to Disease ; Glucose/metabolism ; Hyperglycemia/*etiology/genetics ; Insulin Resistance ; Lactoylglutathione Lyase/genetics/*physiology ; Liver/metabolism ; Male ; Obesity/*complications ; Pyruvaldehyde/metabolism ; Retina/pathology ; Zebrafish/growth &amp; development ; }, abstract = {The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.}, }
@article {pmid31203172, year = {2019}, author = {Raetz, AG and David, SS}, title = {When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer.}, journal = {DNA repair}, volume = {80}, number = {}, pages = {16-25}, pmid = {31203172}, issn = {1568-7856}, support = {R01 CA067985/CA/NCI NIH HHS/United States ; R29 CA067985/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA/metabolism ; *DNA Damage ; DNA Glycosylases/*metabolism ; *DNA Repair ; Guanine/analogs &amp; derivatives/metabolism ; Humans ; Neoplasms/genetics/*metabolism ; *Signal Transduction ; }, abstract = {MUTYH is a base-excision repair glycosylase that removes adenine opposite 8-oxoguanine (OG). Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), which progresses to cancer with very high penetrance. Whole genome and whole exome sequencing studies have found MUTYH deficiencies in an increasing number of cancer types. While the canonical OG:A repair activity of MUTYH is well characterized and similar to bacterial MutY, here we review more recent evidence that MUTYH has activities independent of OG:A repair and appear centered on the interdomain connector (IDC) region of MUTYH. We summarize evidence that MUTYH is involved in rapid DNA damage response (DDR) signaling, including PARP activation, 9-1-1 and ATR signaling, and SIRT6 activity. MUTYH alters survival and DDR to a wide variety of DNA damaging agents in a time course that is not consistent with the formation of OG:A mispairs. Studies that suggest MUTYH inhibits the repair of alkyl-DNA damage and cyclopyrimidine dimers (CPDs) is reviewed, and evidence of a synthetic lethal interaction with mismatch repair (MMR) is summarized. Based on these studies we suggest that MUTYH has evolved from an OG:A mispair glycosylase to a multifunctional scaffold for DNA damage response signaling.}, }
@article {pmid31200836, year = {2019}, author = {Jeyapala, R and Savio, AJ and Olkhov-Mitsel, E and Kamdar, S and Zhao, F and Cuizon, C and Liu, RSC and Zlotta, A and Fleshner, N and van der Kwast, T and Bapat, B}, title = {GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.}, journal = {European urology oncology}, volume = {2}, number = {3}, pages = {231-238}, doi = {10.1016/j.euo.2018.08.003}, pmid = {31200836}, issn = {2588-9311}, mesh = {Biomarkers, Tumor/genetics ; Carcinoma, Intraductal, Noninfiltrating/blood/genetics/mortality/pathology ; Cell Line, Tumor ; DNA Methylation ; DNA-Binding Proteins/genetics ; Epigenesis, Genetic ; Homeodomain Proteins/*genetics ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/*pathology/surgery ; Proto-Oncogene Proteins/genetics ; Recurrence ; Survival Analysis ; }, abstract = {BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.<br><br>OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.<br><br>Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.<br><br>The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.<br><br>RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.<br><br>CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.<br><br>PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.}, }
@article {pmid31192864, year = {2019}, author = {Horimoto, Y and Terao, T and Tsutsumi, Y and Tanabe, M and Mogushi, K and Hlaing, MT and Sasaki, R and Saeki, H and Okazaki, M and Sonoue, H and Arakawa, A and Saito, M}, title = {Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.}, journal = {The American journal of surgical pathology}, volume = {43}, number = {9}, pages = {1221-1228}, doi = {10.1097/PAS.0000000000001300}, pmid = {31192864}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Female ; Gene Amplification ; Genes, erbB-2 ; Humans ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/metabolism ; }, abstract = {Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC). However, the reasons for this difference are poorly understood. On the basis of the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type overexpresses HER2 protein without gene amplification and retrospectively investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period, employing fluorescence in situ hybridization (FISH). To compare HER2 protein expressions between in situ and invasive components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ disease were also examined. Furthermore, for comparison of FISH status between in situ and coexisting invasive components, another patient cohort, 78 FISH-positive IDC cases, were employed. To elucidate biological differences among DCIS with various combinations of ER and HER2 protein expressions, we also analyzed public microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and HER2 protein-overexpressing specimens, significantly lower than the 94% in ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 protein expression was decreased in the invasive component as compared with coexisting in situ portions in 40% of individual tumors, whereas the FISH status of these 2 components was well preserved. Moreover, ER(+) and HER2 protein-overexpressing DCIS showed significantly higher hypoxia-inducible factor-1α protein expression than the ER(+) and HER2 protein-nonoverexpressing tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors, frequently overexpress HER2 protein without gene amplification. Our data may provide novel insights for understanding the biology of DCIS.}, }
@article {pmid31192530, year = {2019}, author = {Zhang, J and Zhao, B and Jin, F}, title = {The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database.}, journal = {The breast journal}, volume = {25}, number = {5}, pages = {838-847}, doi = {10.1111/tbj.13347}, pmid = {31192530}, issn = {1524-4741}, mesh = {Breast Neoplasms/*classification/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Female ; Humans ; Middle Aged ; Neoplasm Staging/*standards/statistics &amp; numerical data ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; SEER Program ; United States ; }, abstract = {The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (Her-2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(-), PR(-), and Her-2(-) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.}, }
@article {pmid31182966, year = {2019}, author = {Bao, Y and Wang, L and Shi, L and Yun, F and Liu, X and Chen, Y and Chen, C and Ren, Y and Jia, Y}, title = {Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.}, journal = {Cellular &amp; molecular biology letters}, volume = {24}, number = {}, pages = {38}, pmid = {31182966}, issn = {1689-1392}, mesh = {Breast Neoplasms/*genetics ; Down-Regulation/genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Receptors, Cell Surface/*metabolism ; Reproducibility of Results ; Sequence Analysis, RNA ; Signal Transduction/*genetics ; Transcriptome/genetics ; Up-Regulation/genetics ; }, abstract = {Background: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.<br><br>Methods: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.<br><br>Results: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.<br><br>Conclusion: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.}, }
@article {pmid31182685, year = {2019}, author = {Arabpour, M and Ghods, A and Shariat, M and Talei, AR and Mehdipour, F and Ghaderi, A}, title = {Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer.}, journal = {Iranian journal of immunology : IJI}, volume = {16}, number = {2}, pages = {108-116}, doi = {10.22034/IJI.2019.80254}, pmid = {31182685}, issn = {1735-367X}, mesh = {4-1BB Ligand/*metabolism ; Adult ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Female ; Flow Cytometry ; Humans ; Lymphocyte Activation ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node/*metabolism ; }, abstract = {BACKGROUND: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity.<br><br>OBJECTIVE: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters.<br><br>METHODS: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry.<br><br>RESULTS: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage.<br><br>CONCLUSIONS: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.}, }
@article {pmid31177561, year = {2019}, author = {Downes, MR and Xu, B and van der Kwast, TH}, title = {Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome.}, journal = {Histopathology}, volume = {75}, number = {5}, pages = {715-722}, doi = {10.1111/his.13938}, pmid = {31177561}, issn = {1365-2559}, mesh = {Aged ; Aged, 80 and over ; Humans ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; *Neoplasm Grading ; Pelvic Neoplasms/*pathology/secondary ; Prognosis ; Prostate/pathology ; Prostatectomy ; Prostatic Neoplasms/*pathology ; Retrospective Studies ; }, abstract = {AIMS: Lymph node metastases at the time of prostatectomy are an infrequent finding. The correlation of the pattern of nodal metastases with patient outcome has yet to be explored.<br><br>METHODS AND RESULTS: Lymph node-positive prostatectomies were retrospectively reviewed. The presence of cribriform carcinoma (CC), intraductal carcinoma (IDC) and ISUP grade (G) were documented. The largest nodal metastasis was assessed for the morphological patterns present. G was assigned to the metastasis based on percentage morphological patterns present. Statistical analysis used spss to assess disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS). One hundred and ten cases were identified: G5 (n = 52), G4 (n = 8), G3 (n = 34), G2 (n = 10) and no G (n = 6; treatment effect). IDC or CC was present in 103 (94%) specimens. More than one positive node correlated with worse DFS [P = 0.012, hazard ratio (HR) = 1.951, 95% confidence interval (CI) = 1.142-3.331] and DMFS (P = 0.009, HR = 2.647, 95% CI = 1.239-5.651). G in the prostate and nodal metastasis were poorly correlated (kappa = 0.073, P = 0.195). The presence of pattern 5 was seen in 33 nodes (30%) and correlated with DFS (P = 0.020, HR = 1.903, 95% CI = 1.091-3.320), DSS (P = 0.021, HR = 5.937, 95% CI = 1.084-32.533) and DMFS (P = 0.007, HR = 2.695, 95% CI = 1.269-5.726). Nodal cribriform pattern showed no prognostic correlation and pattern 3 metastasis showed a significant trend towards better outcome (DMFS P = 0.033, HR = 0.431, 95% CI = 0.194-0.958).<br><br>CONCLUSIONS: IDC or CC is identified in 94% of node-positive prostate cancers. Although G in the largest nodal metastasis has prognostic significance, its G does not reflect that of the primary prostatic adenocarcinoma.}, }
@article {pmid31172621, year = {2019}, author = {Hamzah, JL and Ong, KW and Tan, BY}, title = {Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.}, journal = {The breast journal}, volume = {25}, number = {4}, pages = {706-708}, doi = {10.1111/tbj.13308}, pmid = {31172621}, issn = {1524-4741}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Nipples/*pathology ; Paget's Disease, Mammary/pathology ; Ultrasonography, Mammary ; }, abstract = {Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.}, }
@article {pmid31171819, year = {2019}, author = {Chavez, DE and Gronau, I and Hains, T and Kliver, S and Koepfli, KP and Wayne, RK}, title = {Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8329}, pmid = {31171819}, issn = {2045-2322}, mesh = {*Adaptation, Physiological ; Animals ; Animals, Wild/genetics ; *Biological Evolution ; Body Patterning ; Canidae/*genetics ; Computational Biology ; DNA/analysis ; Diet ; Female ; *Genomics ; Genotype ; Hedgehog Proteins/genetics ; Molar ; Monte Carlo Method ; Pigmentation ; Predatory Behavior ; }, abstract = {Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.}, }
@article {pmid31171772, year = {2019}, author = {Haythorne, E and Rohm, M and van de Bunt, M and Brereton, MF and Tarasov, AI and Blacker, TS and Sachse, G and Silva Dos Santos, M and Terron Exposito, R and Davis, S and Baba, O and Fischer, R and Duchen, MR and Rorsman, P and MacRae, JI and Ashcroft, FM}, title = {Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2474}, pmid = {31171772}, issn = {2041-1723}, support = {BB/L020874/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; 090532/Z/09/Z//Wellcome Trust (Wellcome)/International ; 095531//Wellcome Trust (Wellcome)/International ; BB/P018726/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; 884655//Wellcome Trust (Wellcome)/International ; FC001999//RCUK | MRC | Medical Research Foundation/International ; FC001999//Cancer Research UK (CRUK)/International ; 322620//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/International ; //Wellcome Trust/United Kingdom ; FC001999//Wellcome Trust (Wellcome)/International ; }, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Diabetes Mellitus, Experimental/*genetics/metabolism ; Diabetes Mellitus, Type 2/*genetics/metabolism ; Gene Expression Profiling ; Gluconeogenesis ; Glucose/*metabolism ; Glycolysis ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism ; Metabolomics ; Mice ; Mice, Transgenic ; Mitochondria/*metabolism ; NAD/metabolism ; Oxidative Phosphorylation ; Oxygen Consumption ; Potassium Channels, Inwardly Rectifying/genetics ; Proteomics ; }, abstract = {Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.}, }
@article {pmid31171763, year = {2019}, author = {Kim, SJ and Kim, JY}, title = {An Unusual Cutaneous Recurrence of Carcinoma in the Mastectomy Bed and Its Imaging Features: A Case Report.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {800-805}, pmid = {31171763}, issn = {1941-5923}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/methods ; Mastectomy/*methods ; Neoplasm Recurrence, Local/*diagnostic imaging/surgery ; Rare Diseases ; Risk Assessment ; Skin Neoplasms/*secondary/surgery ; Ultrasonography, Doppler, Color/methods ; }, abstract = {BACKGROUND Chest wall recurrences of carcinoma after mastectomy usually involve subcutaneous tissue or the deep muscular layer. Recurrences arising in the skin are rare, and there are few reports of the associated radiologic features. This report presents an unusual case of cutaneous recurrence in the mastectomy bed and demonstrates its radiologic features using sonography and magnetic resonance imaging (MRI). CASE REPORT A 44-year-old woman presented with a palpable lump in the inferomedial area of the right chest wall. Six years ago, she had undergone total mastectomy for ductal carcinoma in situ in her right breast. Sonography showed an indistinct, oval, heterogeneous echoic mass measuring 0.9 cm, confined within the skin layer, corresponding to the palpable lump. A color Doppler sonogram showed minimal, spotted vascularity in and around the mass. Sonography-guided fine-needle aspiration biopsy was performed, revealing multiple clusters of atypical cells, suggestive of ductal carcinoma. On subsequent breast MRI, the mass, measuring 1.3 cm, was again localized to the skin; dynamic contrast-enhanced scans showed a circumscribed margin, oval shape, and rim enhancement (morphology) and slow initial enhancement and persistent delayed enhancement (kinetics). The mass was surgically excised and the pathological examination confirmed the diagnosis as recurrent invasive ductal carcinoma in the dermis. CONCLUSIONS Cutaneous recurrence in the mastectomy bed can manifest as a mass with suspicious radiologic features: indistinct margin on the sonogram and rim enhancement on the MRI. Awareness of such radiologic features may aid in differentiating between the various cutaneous manifestations encountered after mastectomy.}, }
@article {pmid31169985, year = {2019}, author = {Yamashita, H and Kurita, A and Azuma, S and Kudo, Y and Matsuzaki, N and Yazumi, S}, title = {Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer.}, journal = {Diagnostic cytopathology}, volume = {47}, number = {10}, pages = {1037-1041}, doi = {10.1002/dc.24249}, pmid = {31169985}, issn = {1097-0339}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Diagnosis, Differential ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Middle Aged ; Mucin 5AC/genetics/*metabolism ; Pancreatic Neoplasms/metabolism/*pathology/secondary ; }, abstract = {Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51-year-old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound-fine-needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.}, }
@article {pmid31146042, year = {2019}, author = {Zhu, J and Sun, K and Xu, X and Sun, J and Kong, Q and Wang, S and Shi, J}, title = {A Preliminary Attempt of Nonintervention in the Treatment of Patients with Intervertebral Disc Calcification Combined with Ossification of the Posterior Longitudinal Ligament.}, journal = {World neurosurgery}, volume = {129}, number = {}, pages = {181-185}, doi = {10.1016/j.wneu.2019.05.169}, pmid = {31146042}, issn = {1878-8769}, mesh = {Child ; Female ; Humans ; Intervertebral Disc/*pathology ; Ossification of Posterior Longitudinal Ligament/*complications/pathology ; Ossification, Heterotopic/*complications/pathology ; Remission, Spontaneous ; *Watchful Waiting ; }, abstract = {BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, controversy remains in terms of the best way to treat this condition.<br><br>CASE DESCRIPTION: An 8-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurologic dysfunction. Computed tomography and magnetic resonance imaging revealed the calcified intervertebral disc and OPLL at the C5-C6 level and spinal cord compression. We performed a noninterventional strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and computed tomography revealed the complete resorption of ossified lesion. Magnetic resonance imaging also showed no sign of compression on the spinal cord and nerve root at the involved segment.<br><br>CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and sex-specific, further research is necessary. Treatment for IDC combined with OPLL needs to follow the treatment principles as described in the text.}, }
@article {pmid31142066, year = {2019}, author = {Zhao, JG and Nie, L and Chen, XQ and Chen, N and Zeng, H}, title = {[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {57}, number = {6}, pages = {422-427}, doi = {10.3760/cma.j.issn.0529-5815.2019.06.006}, pmid = {31142066}, issn = {0529-5815}, support = {81402110, 81672547//National Natural Science Foundation of China/ ; }, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/mortality/*pathology/secondary ; Retrospective Studies ; }, abstract = {Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.}, }
@article {pmid31134761, year = {2019}, author = {Chen, S and Chen, H and Yi, Y and Jiang, X and Lei, H and Luo, X and Chen, Y and Liu, S and Yuan, D and Jia, X and Li, J}, title = {Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.}, journal = {Cancer medicine}, volume = {8}, number = {8}, pages = {4043-4054}, pmid = {31134761}, issn = {2045-7634}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Paget's Disease, Mammary/*epidemiology/etiology/mortality/pathology ; Population Surveillance ; Prognosis ; SEER Program ; }, abstract = {BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.<br><br>METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.<br><br>RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.<br><br>CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.}, }
@article {pmid31120568, year = {2019}, author = {Henry, NL and Cannon-Albright, LA}, title = {Breast cancer histologic subtypes show excess familial clustering.}, journal = {Cancer}, volume = {125}, number = {18}, pages = {3131-3138}, pmid = {31120568}, issn = {1097-0142}, support = {NU58DP0063200-01/CC/CDC HHS/United States ; HHSN261201800016I/CA/NCI NIH HHS/United States ; //University of Utah/ ; P30 CA42014//Huntsman Cancer Institute/ ; HHSN261201800016C/CA/NCI NIH HHS/United States ; //Utah Cancer Registry/ ; //Huntsman Cancer Foundation/ ; P30 CA042014/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/epidemiology/*genetics/pathology ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Lobular/epidemiology/*genetics/pathology ; Family ; Female ; Genetic Predisposition to Disease ; Humans ; Inflammatory Breast Neoplasms/epidemiology/*genetics/pathology ; Middle Aged ; Pedigree ; SEER Program ; Utah/epidemiology ; }, abstract = {BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype.<br><br>METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives.<br><br>RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes.<br><br>CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.}, }
@article {pmid31111513, year = {2019}, author = {Shah, RB and Shore, KT and Yoon, J and Mendrinos, S and McKenney, JK and Tian, W}, title = {PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma).}, journal = {The Prostate}, volume = {79}, number = {11}, pages = {1267-1273}, doi = {10.1002/pros.23831}, pmid = {31111513}, issn = {1097-0045}, mesh = {Adenocarcinoma/*genetics/metabolism/pathology ; Alleles ; Biomarkers, Tumor ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Humans ; Male ; Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/*genetics/metabolism ; Prostatic Neoplasms/*genetics/metabolism/pathology ; }, abstract = {BACKGROUND: The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high-risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features.<br><br>METHODS: Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma.<br><br>RESULTS: Eight-eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P < 0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC-P had the highest relative risk (4.993, 95% confidence interval, 3.451-7.223, P < 0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present.<br><br>CONCLUSIONS: PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC-P. This is the first study showing the association of PTEN loss with stromogenic PCa.}, }
@article {pmid31109373, year = {2019}, author = {Tan, W and Tao, L and Zhou, Z and Yin, W and Chen, Y}, title = {Tumor-to-tumor metastasis: a rare case of breast carcinoma metastasizing to a pheochromocytoma, and a literature review.}, journal = {Diagnostic pathology}, volume = {14}, number = {1}, pages = {46}, pmid = {31109373}, issn = {1746-1596}, support = {NO. JCYJ201710//the Science and Research Foundation of Peking University, Shenzhen Hospital/ ; NO. SZSM201812088//the "San-ming" Project of Medicine in Shenzhen/ ; }, mesh = {Adrenal Gland Neoplasms/*diagnostic imaging/secondary ; Adrenal Glands/diagnostic imaging/pathology ; Adult ; Breast/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Pheochromocytoma/*diagnostic imaging/secondary ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Tumor-to-tumor metastasis is a well-recognized but uncommon entity. Breast carcinoma is one of the most common metastatic donors. Breast carcinoma metastasizes commonly to adrenal glands. However, the co-existence of a metastatic lesion with an existing adrenal tumor is a rare finding.<br><br>CASE PRESENTATION: A 35-year-old woman was diagnosed with pheochromocytoma using computed tomography and ultrasound examinations. The tumor was surgically removed. Histological and immunohistochemical staining suggested that there were two components in the tumor: pheochromocytoma and metastatic cancer.<br><br>CONCLUSION: This is the second published case of pheochromocytoma with tumor-to-tumor metastasis from an invasive ductal carcinoma of the breast. Furthermore, we highlight the importance of awareness of tumor-to-tumor metastasis in pathological diagnosis.}, }
@article {pmid31107526, year = {2019}, author = {Nasir, A and Lehrke, HD and Mounajjed, T and Said, S and Zhang, L and Yasir, S and Shah, SS and Chandan, VS and Smyrk, TC and Moreira, RK and Boland Froemming, JM and Herrera Hernandez, LP and Wu, TT and Graham, RP}, title = {Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites.}, journal = {American journal of clinical pathology}, volume = {152}, number = {2}, pages = {190-199}, doi = {10.1093/ajcp/aqz032}, pmid = {31107526}, issn = {1943-7722}, mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Albumins/genetics/*metabolism ; Bile Duct Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Hepatocellular/genetics/*metabolism/pathology ; Cholangiocarcinoma/genetics/*metabolism/pathology ; Gallbladder Neoplasms/genetics/*metabolism/pathology ; Humans ; In Situ Hybridization ; Liver Neoplasms/genetics/*metabolism/pathology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized.<br><br>METHODS: Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays.<br><br>RESULTS: Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases.<br><br>CONCLUSIONS: Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.}, }
@article {pmid31100224, year = {2018}, author = {Montironi, R and Zhou, M and Magi-Galluzzi, C and Epstein, JI}, title = {Features and Prognostic Significance of Intraductal Carcinoma of the Prostate.}, journal = {European urology oncology}, volume = {1}, number = {1}, pages = {21-28}, doi = {10.1016/j.euo.2018.03.013}, pmid = {31100224}, issn = {2588-9311}, mesh = {Biopsy ; Carcinoma, Ductal/*diagnosis/genetics ; Diagnosis, Differential ; Disease Management ; *Genomic Instability ; Humans ; Male ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/*diagnosis/genetics ; Tumor Burden ; }, abstract = {CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is an intraglandular/ductal neoplastic growth of glandular epithelial cells characterized by marked abnormality of the glandular architecture and/or cytological atypia that exceeds what is typically seen in high-grade prostatic intraepithelial neoplasia (HPGIN). It has been shown that IDC-P is a strong independent indicator of poor prognosis for prostate carcinoma (PCa).<br><br>OBJECTIVE: To review the pathological and genetic features, diagnostic criteria and differential diagnosis, and clinical significance of IDC-P.<br><br>EVIDENCE ACQUISITION: PubMed was searched using keywords including prostate carcinoma, intraductal carcinoma, IDC, histology, diagnostic criteria, and prognosis. The references in relevant articles were also reviewed.<br><br>EVIDENCE SYNTHESIS: IDC-P is a distinct entity with characteristic morphological and genetic features. It is strongly associated with aggressive PCa with high Gleason score/grade groups and large tumor volume, and portends unfavorable clinical outcomes. Morphological diagnostic criteria have been established to distinguish it from other lesions with similar histological features. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant PCa. However, patients with isolated IDC-P in biopsy specimens are recommended to have either definitive treatment or immediate repeat biopsy.<br><br>CONCLUSIONS: It is critical to recognize and report IDC-P, especially in prostate biopsies, where the clinical impact of such a diagnosis is greatest.<br><br>PATIENT SUMMARY: Intraductal carcinoma is a unique form of aggressive prostate cancer. In this report, we review its pathological and genetic features and poor prognostic significance. It is critical for pathologists to recognize and report this lesion in prostate specimens, especially in prostate biopsies for patient management.}, }
@article {pmid31092426, year = {2019}, author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Wojnar, A and Dziegiel, P}, title = {Correlation of Expression of CHI3L1 and Nogo-A and their Role in Angiogenesis in Invasive Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {39}, number = {5}, pages = {2341-2350}, doi = {10.21873/anticanres.13351}, pmid = {31092426}, issn = {1791-7530}, mesh = {Aged ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chitinase-3-Like Protein 1/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Neovascularization, Pathologic/*genetics ; Nogo Proteins/*genetics ; Receptors, Cell Surface/genetics ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor C/*genetics ; Vascular Endothelial Growth Factor D/genetics ; }, abstract = {BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC).<br><br>MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data.<br><br>RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found.<br><br>CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.}, }
@article {pmid31087408, year = {2019}, author = {Baydoun, S and Gonzalez, P and Whitman, GJ and Dryden, M and Xi, Y and Dogan, B}, title = {Is Ductography Still Warranted in the 21st century?.}, journal = {The breast journal}, volume = {25}, number = {4}, pages = {654-662}, doi = {10.1111/tbj.13302}, pmid = {31087408}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Contrast Media ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging/methods ; Mammography/*methods/statistics &amp; numerical data ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVE: To determine the utility of ductography in conjunction with mammography and ultrasound in patients with pathologic nipple discharge, and the incremental role of MRI after triple-modality evaluation.<br><br>MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had presented with pathologic nipple discharge and had undergone mammography and/or ultrasound and ductography between January 1, 2005, and October 31, 2010. We tested the diagnostic sensitivity, specificity and accuracy of combined triple-modality evaluation as well as of MRI performed in addition to these imaging techniques. We used the gold standard of image-guided biopsies, surgical excision, or long-term clinical and imaging follow-up.<br><br>RESULTS: Among 94 study patients, benign papillomas were identified in 42 (44.7%), abscess in one (1%), duct ectasia in four (4.3%), and malignancy (invasive ductal carcinoma or ductal carcinoma in situ) or high-risk lesion (atypical ductal hyperplasia) in 10 (10.6%). Forty-six patients (49%) underwent surgical excision; 89.1% of which had presurgical planning with ductography. In 35 (37.2%) with negative imaging, resolution of nipple discharge was confirmed on median clinical and imaging follow-up of 36 months. Two patients with negative imaging were lost to follow-up. Sensitivity, specificity, PPV, and NPV for accurately demonstrating the etiology of pathologic nipple discharge were 13%, 97%, 89%, and 37% respectively for mammography; 73%, 97%, 98%, and 64% respectively for ultrasound; 76%, 72%, 84%, and 61% respectively for ductography; 86%, 70%, 85%, and 72% respectively for combined ultrasound and ductography; and 75%, 100%, 100% and 67% respectively for DCE-MRI.<br><br>CONCLUSION: The combination of mammography, ultrasound and ductography is highly accurate for identifying the etiology of pathologic nipple discharge. DCE-MRI can be used as an alternate to ductography if necessary.}, }
@article {pmid31063527, year = {2019}, author = {Ciurea, AI and Boca, I and Rogojan, L and Ciule, LD and Ciortea, CA}, title = {Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.}, journal = {Medical ultrasonography}, volume = {21}, number = {2}, pages = {200-203}, doi = {10.11152/mu-1769}, pmid = {31063527}, issn = {2066-8643}, mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Fatal Outcome ; Female ; Humans ; Muscle Neoplasms/*diagnostic imaging/*secondary ; Neoplasm Recurrence, Local/*diagnostic imaging ; Pectoralis Muscles/*diagnostic imaging ; Ultrasonography, Mammary/*methods ; }, abstract = {Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.}, }
@article {pmid31060593, year = {2019}, author = {Petridis, C and Arora, I and Shah, V and Megalios, A and Moss, C and Mera, A and Clifford, A and Gillett, C and Pinder, SE and Tomlinson, I and Roylance, R and Simpson, MA and Sawyer, EJ}, title = {Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {58}, pmid = {31060593}, issn = {1465-542X}, support = {MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; 8873/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Age Factors ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/epidemiology/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/*genetics ; Case-Control Studies ; Checkpoint Kinase 2/genetics ; Computational Biology ; DNA Copy Number Variations ; Female ; *Gene Frequency ; Genotype ; *Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Neoplasm Grading ; Tumor Suppressor Protein p53/genetics ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal breast cancer, and approximately 20% of screen-detected tumours are pure DCIS. Most risk factors for breast cancer have similar associations with DCIS and IDC; however, there is limited data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in DCIS and which women with DCIS should be referred for genetic screening. The aim of this study was to assess the frequency of germline variants in BRCA2, BRCA1, CHEK2, PALB2 and TP53 in DCIS in women aged less than 50 years of age.<br><br>METHODS: After DNA extraction from the peripheral blood, Access Array technology (Fluidigm) was used to amplify all exons of these five known breast cancer predisposition genes using a custom made targeted sequencing panel in 655 cases of pure DCIS presenting in women under the age of 50 years together with 1611 controls.<br><br>RESULTS: Case-control analysis revealed an excess of pathogenic variants in BRCA2 (OR = 27.96, 95%CI 6.56-119.26, P = 2.0 × 10-10) and CHEK2 (OR = 8.04, 95%CI 2.93-22.05, P = 9.0 × 10-6), with weaker associations with PALB2 (P = 0.003), BRCA1 (P = 0.007) and TP53 (P = 0.02). For oestrogen receptor (ER)-positive DCIS the frequency of pathogenic variants was 9% under the age of 50 (14% with a family history of breast cancer) and 29% under the age of 40 (42% with a family history of breast cancer). For ER-negative DCIS, the frequency was 9% (16% with a family history of breast cancer) and 8% (11% with a family history of breast cancer) under the ages of 50 and 40, respectively.<br><br>CONCLUSIONS: This study has shown that breast tumourigenesis in women with pathogenic variants in BRCA2, CHEK2, PALB2, BRCA1 and TP53 can involve a DCIS precursor stage and that the focus of genetic testing in DCIS should be on women under the age of 40 with ER-positive DCIS.}, }
@article {pmid31057361, year = {2019}, author = {Aplin, FP and Fridman, GY}, title = {Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.}, journal = {Frontiers in neuroscience}, volume = {13}, number = {}, pages = {379}, pmid = {31057361}, issn = {1662-4548}, support = {R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, abstract = {Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.}, }
@article {pmid31049740, year = {2019}, author = {Sanderink, WBG and Laarhuis, BI and Strobbe, LJA and Sechopoulos, I and Bult, P and Karssemeijer, N and Mann, RM}, title = {A systematic review on the use of the breast lesion excision system in breast disease.}, journal = {Insights into imaging}, volume = {10}, number = {1}, pages = {49}, pmid = {31049740}, issn = {1869-4101}, abstract = {PURPOSE: To outline the current status of and provide insight into possible future research on the breast lesion excision system (BLES) as a diagnostic and therapeutic device.<br><br>METHODS: A systematic search of the literature was performed using PubMed, Embase, and the Cochrane databases to identify relevant studies published between January 2002 and April 2018. Studies were considered eligible for inclusion if they evaluated the diagnostic or therapeutic accuracy or safety of BLES.<br><br>RESULTS: Ultimately, 17 articles were included. The reported underestimation rates of atypical ductal hyperplasia and ductal carcinoma in situ (DCIS) ranged from 0 to 14.3% and from 0 to 22.2%, respectively. Complete excision rates for invasive ductal carcinoma and DCIS ranged from 5.3 to 76.3%. Bleeding was the most frequently reported complication (0-11.8%). Device-related complications may arise, with an empty basket being the most common (0.6-3.6%). Thermal damage of the specimen, caused by the use of a radiofrequency cutting wire, was reported in eight of the included studies. Most thermal artifacts were reported as superficial and small (0.1-1.9 mm).<br><br>CONCLUSIONS: The BLES, an automated, image-guided, single-pass biopsy system for breast lesions using radiofrequency is designed to excise and retrieve an intact tissue specimen. It is an efficient and safe breast biopsy method with acceptable complication rates, which may be used as an alternative to vacuum-assisted biopsies. The variable rate of complete excision raises questions about the possibility to use BLES as a therapeutic device for the excision of small lesions. Further research should focus on this aspect of BLES.}, }
@article {pmid31046734, year = {2019}, author = {Aras, S and Maroun, MC and Song, Y and Bandyopadhyay, S and Stark, A and Yang, ZQ and Long, MP and Grossman, LI and Fernández-Madrid, F}, title = {Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {411}, pmid = {31046734}, issn = {1471-2407}, support = {R01 CA122277/CA/NCI NIH HHS/United States ; R01 CA122277//National Institutes of Health/ ; W81XWH-16-1-0516//U.S. Department of Defense/ ; }, mesh = {Autoantigens/metabolism ; Autoimmunity ; Breast Neoplasms/*diagnosis/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Neoplasm Invasiveness ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Prospective Studies ; Protein Array Analysis ; Rapamycin-Insensitive Companion of mTOR Protein/genetics ; Transcription Factors/*genetics/*metabolism ; Up-Regulation ; }, abstract = {BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.<br><br>METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype.<br><br>RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis.<br><br>CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.}, }
@article {pmid31045815, year = {2019}, author = {Li, JP and Zhang, XM and Zhang, Z and Zheng, LH and Jindal, S and Liu, YJ}, title = {Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {98}, number = {18}, pages = {e15449}, doi = {10.1097/MD.0000000000015449}, pmid = {31045815}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Ductal/*mortality/*pathology ; Disease-Free Survival ; Female ; Genes, p53/*physiology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Triple Negative Breast Neoplasms/*mortality/*pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.}, }
@article {pmid31040709, year = {2019}, author = {Hinnen, D and Kruger, DF}, title = {Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {12}, number = {}, pages = {447-455}, pmid = {31040709}, issn = {1178-7007}, abstract = {Background: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases.<br><br>Purpose: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D.<br><br>Conclusion: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions.}, }
@article {pmid31023035, year = {2019}, author = {Albayrak, M and Senol, O and Demirkaya-Miloglu, F and Calik, M and Kadioglu, Y}, title = {Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.}, journal = {Bratislavske lekarske listy}, volume = {120}, number = {3}, pages = {184-187}, doi = {10.4149/BLL_2019_031}, pmid = {31023035}, issn = {0006-9248}, mesh = {Adult ; *Breast Neoplasms/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; Female ; Humans ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; }, abstract = {OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples.<br><br>METHODS: Samples were deparaffinized and 20‑micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model.<br><br>RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones.<br><br>CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).}, }
@article {pmid31016756, year = {2019}, author = {Zenan, H and Zixiong, L and Zhicheng, Y and Mei, H and Xiongbin, Y and Tiantian, W and Min, D and Renbin, L and Changchang, J}, title = {Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer.}, journal = {Journal of cellular physiology}, volume = {234}, number = {11}, pages = {20584-20602}, doi = {10.1002/jcp.28662}, pmid = {31016756}, issn = {1097-4652}, mesh = {Aging ; Biomarkers, Tumor ; Blood Platelets/classification/physiology ; Breast Neoplasms/*classification/*genetics/pathology ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Leukocytes/*classification/*physiology ; Logistic Models ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; }, abstract = {To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.}, }
@article {pmid31004170, year = {2019}, author = {Harbertson, J and Scott, PT and Lemus, H and Michael, NL and Hale, BR}, title = {Cross-Sectional Study of Sexual Behavior, Alcohol Use, and Mental Health Conditions Associated With Sexually Transmitted Infections Among Deploying Shipboard US Military Personnel.}, journal = {Military medicine}, volume = {184}, number = {11-12}, pages = {e693-e700}, doi = {10.1093/milmed/usz070}, pmid = {31004170}, issn = {1930-613X}, mesh = {Adult ; Alcohol Drinking/adverse effects/epidemiology/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Mental Disorders/*diagnosis/epidemiology/psychology ; Middle Aged ; Military Personnel/psychology/*statistics &amp; numerical data ; Risk Factors ; Risk-Taking ; Sexual Behavior/*psychology ; Sexually Transmitted Diseases/*diagnosis/epidemiology/psychology ; Ships/statistics &amp; numerical data ; United States/epidemiology ; }, abstract = {INTRODUCTION: Limited comprehensive data exist on risk behavior associated with sexually transmitted infections (STI) among ship-assigned US military personnel during the predeployment time period (PDT). This study examined whether sexual risk behaviors, alcohol use, involuntary drug consumption (IDC), posttraumatic stress disorder (PTSD), and depression during the 12 months prior to deployment were associated with provider-diagnosed STIs in this population.<br><br>MATERIALS AND METHODS: Using cross-sectional data collected during 2012-2014 among sexually active personnel, multivariable regression assessed factors associated with STIs among all men (n = 1,831). Stratified analyses were conducted among men who have sex with women (MSW, n = 1,530), men who have sex with men or men and women (MSM, n = 83), and excluded those not reporting sexual partner gender (n = 218).<br><br>RESULTS: Among MSW, transactional sex (AOR 3.8, 95% CI 1.5-9.4) meeting sexual partners at work (AOR 4.3, 95% CI 2.0-9.2), IDC (AOR 6.6, 95% CI 3.0-14.5), and incomplete mental health assessments (AOR 4.4, 95% CI 1.6-12.0) were significantly associated with STIs after adjustment. Among all men, those who identified as MSM (AOR 4.6, 95% CI 1.9-11.2) and drug screen positive (AOR 3.3, 95% CI 1.3-8.6) were significantly more likely to report an STI.<br><br>CONCLUSIONS: Previously unreported factors significantly associated with STIs at the PDT among MSW in the adjusted analysis were meeting sexual partners at work and IDC. IDC during the PDT warrants further exploration. These results can inform tailored STI reduction interventions among shipboard personnel and similarly aged civilians undergoing similar transition/travel experiences.}, }
@article {pmid30995855, year = {2019}, author = {Mikudova, V and Rejlekova, K and Gyarfas, J and Oravcova, I and Chovanec, M and Mardiak, J and Mego, M}, title = {Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy - a Case Report.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {2}, pages = {139-142}, doi = {10.14735/amko2018139}, pmid = {30995855}, issn = {1802-5307}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Injections, Spinal ; Meningeal Neoplasms/*drug therapy/secondary ; Prognosis ; }, abstract = {BACKGROUND: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months.<br><br>METHODS: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival.<br><br>RESULTS: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM.<br><br>CONCLUSION: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.}, }
@article {pmid30993692, year = {2019}, author = {Khani, F and Wobker, SE and Hicks, JL and Robinson, BD and Barbieri, CE and De Marzo, AM and Epstein, JI and Pritchard, CC and Lotan, TL}, title = {Intraductal carcinoma of the prostate in the absence of high-grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations.}, journal = {The Journal of pathology}, volume = {249}, number = {1}, pages = {79-89}, doi = {10.1002/path.5283}, pmid = {30993692}, issn = {1096-9896}, mesh = {Aged ; Biomarkers, Tumor/*genetics ; Carcinoma in Situ/classification/*genetics/pathology ; Carcinoma, Ductal/classification/*genetics/pathology ; DNA Copy Number Variations ; Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mitogen-Activated Protein Kinases/genetics ; *Mutation ; Neoplasm Grading ; Neoplasm Invasiveness ; *Oncogenes ; PTEN Phosphohydrolase/genetics ; Phenotype ; Phosphatidylinositol 3-Kinase/genetics ; Prostatic Neoplasms/classification/*genetics/pathology ; Transcriptional Regulator ERG/genetics ; Transcriptome ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) most often appears associated with high-grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC-P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low-grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC-P (iIDC-P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC-P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC-P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC-P alterations were similar to those previously described in high-grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC-P (BRCA2, CHEK2, CDK12) and other known PCa-associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC-P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC-P and the low-grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC-P in four. Despite a CNA profile similar to conventional PCa, iIDC-P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC-P is not likely a precursor to the associated low-grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.}, }
@article {pmid30989460, year = {2019}, author = {Lee, J and Kim, HE and Song, YS and Cho, EY and Lee, A}, title = {miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway.}, journal = {Breast cancer research and treatment}, volume = {176}, number = {1}, pages = {119-130}, pmid = {30989460}, issn = {1573-7217}, support = {NRF-2017R1D1A1B03034165//National Research Foundation of Korea/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; RNA Interference ; Signal Transduction ; Transcriptome ; Transforming Growth Factor beta/*metabolism ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence.<br><br>METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-β downstream pathway.<br><br>RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFβRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFβRII, especially in cells transfected with both miRNAs.<br><br>CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-β activity, leading to early breast cancer carcinogenesis.}, }
@article {pmid30985953, year = {2019}, author = {Erro, R and Picillo, M and Amboni, M and Savastano, R and Scannapieco, S and Cuoco, S and Santangelo, G and Vitale, C and Pellecchia, MT and Barone, P}, title = {Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.}, journal = {European journal of neurology}, volume = {26}, number = {9}, pages = {1212-1218}, doi = {10.1111/ene.13968}, pmid = {30985953}, issn = {1468-1331}, mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Hypokinesia/etiology/*physiopathology ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years.<br><br>METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4 years.<br><br>RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up.<br><br>CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.}, }
@article {pmid30982780, year = {2019}, author = {Ren, W and Guan, W and Zhang, J and Wang, F and Xu, G}, title = {Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development.}, journal = {Aging}, volume = {11}, number = {7}, pages = {2151-2176}, pmid = {30982780}, issn = {1945-4589}, mesh = {Adult ; Aged ; Binding, Competitive ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; MicroRNAs/genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Pyridoxaminephosphate Oxidase/antagonists &amp; inhibitors/genetics/*metabolism ; RNA, Long Noncoding/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Tumor Stem Cell Assay ; }, abstract = {Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.}, }
@article {pmid30959550, year = {2019}, author = {Deva Magendhra Rao, AK and Patel, K and Korivi Jyothiraj, S and Meenakumari, B and Sundersingh, S and Sridevi, V and Rajkumar, T and Pandey, A and Chatterjee, A and Gowda, H and Mani, S}, title = {Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.}, journal = {Molecular oncology}, volume = {13}, number = {6}, pages = {1342-1355}, pmid = {30959550}, issn = {1878-0261}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Gene Regulatory Networks/genetics ; Humans ; Prognosis ; RNA, Long Noncoding/genetics/*metabolism ; Sequence Analysis, RNA ; }, abstract = {Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (~ 58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was performed in n = 52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3, and FAM83H-AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and report that overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.}, }
@article {pmid30943919, year = {2019}, author = {Campbell, EJ and Dachs, GU and Morrin, HR and Davey, VC and Robinson, BA and Vissers, MCM}, title = {Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {307}, pmid = {30943919}, issn = {1471-2407}, support = {R1512//Canterbury Medical Research Foundation/ ; R1512//New Zealand Breast Cancer Foundation/ ; }, mesh = {Antigens, Neoplasm/genetics/*metabolism ; Ascorbic Acid/*metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carbonic Anhydrase IX/genetics/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics/*metabolism ; Retrospective Studies ; Survival Analysis ; Up-Regulation ; Vascular Endothelial Growth Factor A/genetics/*metabolism ; }, abstract = {BACKGROUND: The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.<br><br>METHODS: In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.<br><br>RESULTS: HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.<br><br>CONCLUSIONS: Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.}, }
@article {pmid30916846, year = {2019}, author = {Leshem, R and van Lieshout, PHHM and Ben-David, S and Ben-David, BM}, title = {Does emotion matter? The role of alexithymia in violent recidivism: A systematic literature review.}, journal = {Criminal behaviour and mental health : CBMH}, volume = {29}, number = {2}, pages = {94-110}, doi = {10.1002/cbm.2110}, pmid = {30916846}, issn = {1471-2857}, mesh = {*Affective Symptoms ; Aggression/psychology ; Crime/*statistics &amp; numerical data ; Criminals/*psychology ; *Emotions ; Humans ; Male ; *Recidivism ; Recurrence ; Risk Assessment ; Risk Factors ; Violence/*psychology/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Several variables have been evidenced for their association with violent reoffending. Resultant interventions have been suggested, yet the rate of recidivism remains high. Alexithymia, characterised by deficits in emotion processing and verbal expression, might interact with these other risk factors to affect outcomes.<br><br>AIM: Our goal was to examine the role of alexithymia as a possible moderator of risk factors for violent offender recidivism. Our hypothesis was that, albeit with other risk factors, alexithymia increases the risk of violent reoffending.<br><br>METHOD: We conducted a systematic literature review, using terms for alexithymia and violent offending and their intersection.<br><br>RESULTS: (a) No study that directly tests the role of alexithymia in conjunction with other potential risk factors for recidivism and actual violent recidivism was uncovered. (b) Primarily alexithymia researchers and primarily researchers into violence have separately found several clinical features in common between aspects of alexithymia and violence, such as impulsivity (total n = 24 studies). (c) Other researchers have established a relationship between alexithymia and both dynamic and static risk factors for violent recidivism (n = 16 studies).<br><br>CONCLUSION: Alexithymia may be a possible moderator of risk of violent offence recidivism. Supplementing offenders' rehabilitation efforts with assessments of alexithymia may assist in designing individually tailored interventions to promote desistance among violent offenders.}, }
@article {pmid30914612, year = {2019}, author = {Oki, T and Sugimoto, T and Ogawa, M and Dabanaka, K and Hanazaki, K}, title = {[A Case of Early-Onset Breast Cancer for Which the Operative Indication for Breast Conservation Was Based on BRCA Genetic Testing].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {3}, pages = {555-557}, pmid = {30914612}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms/genetics/surgery ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Testing ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; *Neoplasm Recurrence, Local ; }, abstract = {We report a case of a patient with early-onset breast cancer who decided to undergo adaptation for breast-conserving surgery based on the results of genetic testing. A 25-year-old woman became aware of a lump in her left breast and visited a nearby hospital, where she was diagnosed with breast cancer. She has no personal history. Her paternal grandfather was diagnosed with rectal cancer at age 60. Ultrasonography revealed an irregularly-shaped hypoechoic mass measuring 3.8 cm in the C area of her left breast and an enlarged lymph node 2.0 cm in diameter in the left axillary area. The breast tumor was pathologically diagnosed as invasive ductal carcinoma by core needle biopsy and was immunohistochemically characterized as ER(-), PgR(-), and HER2(-), s o-called triple negative. Moreover, lymph node metastasis was confirmed by fine needle aspiration cytology. She underwent neoadjuvant chemotherapy and achieved a clinical complete response. A woman with early-onset triple negative breast cancer has a high probability of hereditary breast and ovarian cancer, with a high risk of ipsilateral second breast cancer after conserving surgery. Thus, BRCA genetic testing may be necessary before surgery. As no pathogenic mutation wasfound in BRCA 1/2 in this case, the patient underwent breast-conserving surgery followed by radiation therapy for the conserved breast. The patient remained healthy and without any recurrence 4 years and 2 months after surgery.}, }
@article {pmid30914564, year = {2019}, author = {Takizawa, K and Sakata, J and Ando, T and Yuza, K and Toge, K and Hirose, Y and Nakano, T and Ishikawa, H and Katada, T and Miura, K and Nagahashi, M and Shimada, Y and Kameyama, H and Kobayashi, T and Wakai, T}, title = {[A Case of Peritoneal Recurrence of Invasive Ductal Carcinoma Derived from Intraductal Papillary Mucinous Neoplasm after Surgery Treated with Palliative Radiation Therapy and Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {2}, pages = {372-374}, pmid = {30914564}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Mucinous ; Aged, 80 and over ; *Carcinoma, Pancreatic Ductal/pathology/therapy ; Combined Modality Therapy ; Humans ; Male ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology/therapy ; *Peritoneal Neoplasms/secondary/therapy ; }, abstract = {An 82-year-old man with a diagnosis ofintraductal papillary mucinous carcinoma(IPMC)underwent pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1. Six months after surgery, he had upper abdominal pain, and CT demonstrated a recurrent intraabdominal tumor located at the surgical incision scar. It was diagnosed as a solitary peritoneal recurrence, and palliative radiation therapy at a dose of 30 Gy was performed for the relief of abdominal pain after administration ofoxycodone. He was free ofpain without pharmacological therapy and received subsequent chemotherapy with nabpaclitaxel plus gemcitabine(GnP). He remains free ofpain and alive without progression ofthe disease 24 months after recurrence. Hypofractionated-accelerated radiotherapy is feasible and results in pain relief for local recurrence of IPMC.}, }
@article {pmid30914555, year = {2019}, author = {Monden, K and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R}, title = {[The Diagnostic Problem of Automated Breast Volume Scanner(ABUS)for a Breast Cancer Patient with Dementia-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {2}, pages = {345-347}, pmid = {30914555}, issn = {0385-0684}, mesh = {Aged, 80 and over ; *Breast Neoplasms/complications/diagnosis ; *Dementia/complications ; Female ; Humans ; Mammography ; Mastectomy ; *Sentinel Lymph Node Biopsy ; }, abstract = {The patient was an 84-year-old woman.She had presented with a mass on her right breast.Mammography revealed an illdefined mass.Handheld ultrasonography(HHUS)revealed a low echoic mass, 25mm in diameter, on the AC area of her right breast.An automated breast volume scanner(ABUS)was not useful for detecting the lesion because the patient had dementia and restless body movements.A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma, which was positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.We examined her whole body and made a diagnosis of T2N0M0, StageⅡA.She underwent a muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma, positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.The surgical margins were negative for malignancy, and no metastasis was observed in the sentinel lymph node.She was given endocrine as adjuvant therapies.Three years after the surgery, she was well without metastases.Patients with dementia could not use ABUS.HHUS will be useful for these patients.}, }
@article {pmid30913871, year = {2019}, author = {Chen, WR and Deng, JP and Wang, J and Sun, JY and He, ZY and Wu, SG}, title = {Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.}, journal = {Cancer research and treatment}, volume = {51}, number = {4}, pages = {1437-1448}, pmid = {30913871}, issn = {2005-9256}, support = {81872459//National Natural Science Foundation of China/ ; 81803050//National Natural Science Foundation of China/ ; 2016J01635//Natural Science Foundation of Fujian Province/ ; 2018A030313666//Guangdong Academy of Sciences/ ; }, mesh = {Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant ; Clinical Decision-Making/*methods ; Female ; Gene Expression Profiling/methods ; Humans ; Multivariate Analysis ; Neoplasm Micrometastasis/drug therapy/*genetics ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; SEER Program ; Treatment Outcome ; }, abstract = {PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.<br><br>RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.<br><br>CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.}, }
@article {pmid30912402, year = {2019}, author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Zargar, MA}, title = {Association of Protein Expression and Methylation of DAPK1 with Clinicopathological Features in Invasive Ductal Carcinoma Patients from Kashmir.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {3}, pages = {839-848}, pmid = {30912402}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; *DNA Methylation ; Death-Associated Protein Kinases/*genetics/*metabolism ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; }, abstract = {Aims: Death-associated protein kinase-1 (DAPK1) is a pro-apoptotic Ser/Thr kinase that participates in cell apoptosis and tumor suppression. DAPK1 is frequently lost in many different tumor types including breast cancer. The aim of this study was to evaluate the promoter methylation status of DAPK1 and a possible correlation with the expression of DAPK1 and standard clinicopathological features in invasive ductal breast carcinoma patients (IDC). Methods: Methylation Specific PCR (MSP) was carried out to investigate the promoter methylation status of DAPK1 from 128 breast cancer patients. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry (n=128) and western blotting (n=56). Results: We found significant difference in DAPK1 promoter methylation frequency among breast tumors when compared with the corresponding normal tissues. Hypermethylation of DAPK1 is significantly correlated with the loss of DAPK1 protein expression (P < .001, rs= -0.361). The loss of DAPK1 protein was significantly associated with estrogen receptor (ER) negativity (p= 0.003), triple negative breast cancer (TNB) (p= 0.024) and advanced tumor stages (P = 0.001). Moreover, age at diagnosis (p= 0.041), tumor stage (p= 0.034), ER negativity (p= 0.004) and TNB cancers (p=0.003) correlated significantly with the hypermethylation of the DAPK1 promoter. Coclusion: This study indicates that DAPK1 is methylated in IDC and promoter hypermethylation could be attributed to silencing of DAPK1 gene expression in breast cancer. Thus, we consider DAPK1 inactivation by promoter hypermethylation likely plays a role in the development and progression of breast cancer.}, }
@article {pmid30905927, year = {2019}, author = {Koc-Günel, S and Tekeli, N and Smaczny, C and Vogl, T and Rohde, G}, title = {A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {390-393}, pmid = {30905927}, issn = {1941-5923}, mesh = {Breast Neoplasms/*complications ; Female ; Humans ; Lung Neoplasms/*complications/*diagnosis ; Lymphangioleiomyomatosis/*complications/*diagnosis ; Middle Aged ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare progressive cystic and nodular disease of the lung characterized by smooth muscle cell proliferation. LAM predominantly affects young premenopausal women. This report is of a case of LAM presenting in a 47-year-old woman with a past history of breast cancer and discusses the possibility of an association between the two conditions. CASE REPORT A 47-year-old woman presented as an emergency with an exacerbation of a four-month history of shortness of breath and dry cough. Her symptoms began following the start of anti-hormonal treatment with letrozole and goserelin acetate for a moderately differentiated (grade 2) invasive ductal carcinoma of the breast (pT2, pN0, M0) which was positive for expression of estrogen receptor (ER+), progesterone receptor (PR+), and human epidermal growth factor receptor 2 (HER2+). Until the previous four months, she had breast-conserving treatment with radiotherapy and tamoxifen therapy. Following hospital admission, she was found to be in type I respiratory failure. Chest X-ray, lung computed tomography (CT), and positron-emission tomography (PET) showed diffuse cystic and nodular lung lesions, consistent with a diagnosis of LAM, and antihormonal therapy was discontinued. She developed pericarditis that was treated with the anti-inflammatory agent, colchicine. Treatment with letrozole and sirolimus improved her respiratory symptoms. CONCLUSIONS A rare case of LAM is presented in a woman with a recent history of breast cancer. Because both tumors were hormone-dependent, this may support common underlying gene associations and signaling pathways between the two types of tumor.}, }
@article {pmid30900303, year = {2019}, author = {Nie, L and Pan, X and Zhang, M and Yin, X and Gong, J and Chen, X and Xu, M and Zhou, Q and Chen, N}, title = {The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center.}, journal = {The Prostate}, volume = {79}, number = {8}, pages = {819-825}, doi = {10.1002/pros.23785}, pmid = {30900303}, issn = {1097-0045}, mesh = {Biopsy, Large-Core Needle/methods ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Cohort Studies ; Gene Expression ; Gene Rearrangement ; Genetic Heterogeneity ; Humans ; Image-Guided Biopsy/methods ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics/*metabolism/pathology ; Serine Endopeptidases/genetics/metabolism ; Transcriptional Regulator ERG/biosynthesis/genetics ; Tumor Burden ; }, abstract = {BACKGROUND: Overexpression of ERG protein resulting from TMPRSS2:ERG rearrangement is highly specific for prostate cancer (PCa). However, the biological function of this fusion protein and its relationship with clinicopathological features still remain controversial.<br><br>METHOD: In this study, we evaluated ERG protein expression/gene rearrangement and heterogeneity by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in a cohort of 633 consecutive PCa initially diagnosed by core-needle biopsy in the West China Hospital.<br><br>RESULT: Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P = 0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%, P = 0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC-P) (10.0% vs 18.6%, P = 0.012). Follow-up analysis found that patients who progressed to castration-resistant prostate cancer (CRPC) have a lower frequency of ERG protein expression at initial biopsies compared to androgen deprivation therapy (ADT)-sensitive cases (14.1% vs 23.5%, P = 0.042), but Kaplan-Meier curve showed that ERG protein expression was not an independent prognostic marker. Of all the 106 ERG-positive cases, eight cases (7.5%) exhibited heterogeneous expression of ERG protein, in which ERG was only positive in tumors with Gleason pattern 3, but negative in Gleason pattern 4. The FISH analysis was consistent with IHC in six of these cases. In the other two cases, ERG rearrangement was detected in tumors with both Gleason pattern 3 and 4 by FISH, despite the negative protein expression in Gleason pattern 4. In case 1, a repeated biopsy was performed when the disease progressed to CRPC, and no ERG-positive cells were identified neither by IHC nor FISH.<br><br>CONCLUSION: This was by far the largest series of ERG expression and heterogeneity analysis in Chinese PCa. The ERG rearrangement seemed to be frequently expressed in patients with relatively younger age and lower Gleason score and infrequently expressed in PCa with the IDC-P. PCa with positive ERG were less frequently to progress to CRPC, but there was no prognostic significance of ERG expression. In heterogeneous cases, ERG protein was detectable only in tumors with Gleason pattern 3 but not in pattern 4. Tumor cells with positive ERG expression/rearrangement seemed easily response to ADT.}, }
@article {pmid30897334, year = {2019}, author = {Wang, YF and Han, J}, title = {OTOR in breast carcinoma as a potent prognostic predictor correlates with cell proliferation, migration, and invasiveness.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {97}, number = {6}, pages = {750-757}, doi = {10.1139/bcb-2018-0305}, pmid = {30897334}, issn = {1208-6002}, mesh = {Biomarkers, Tumor/antagonists &amp; inhibitors/*genetics/metabolism ; Breast Neoplasms/diagnosis/*genetics/metabolism/*pathology ; *Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Prognosis ; Proteins/antagonists &amp; inhibitors/*genetics/metabolism ; RNA, Small Interfering/pharmacology ; }, abstract = {Otoraplin (OTOR), recognized as an important cochlear gene, has a predicted secretory signal peptide sequence and harbors a high degree of cross-species conservation. However, its role in tumor progression is relatively unclear, especially in breast carcinoma (BC). This study investigated the clinicopathological significance of OTOR in breast infiltrating ductal carcinoma (IDC) with high metastasis to uncover its biological function in BC. OTOR was highly overexpressed in BC tissues and cells compared with normal samples. OTOR overexpression was associated with certain clinicopathological characteristics and poorer prognosis (overall survival; OS) of patients with breast IDC. As determined using CCK-8, colony formation, wound-healing, and Transwell assays, silencing OTOR using siRNA impeded BC-cell proliferation, migration, and invasiveness, which may have resulted from inactivating the mitogen-activated protein kinase - extracellular-signal-regulated kinase pathway. These results indicate that OTOR plays a crucial role in the progression of and prognosis for BC, which could help to identify future therapeutic targets for treating BC patients.}, }
@article {pmid30890538, year = {2019}, author = {Rohm, M and Zeigerer, A and Machado, J and Herzig, S}, title = {Energy metabolism in cachexia.}, journal = {EMBO reports}, volume = {20}, number = {4}, pages = {}, pmid = {30890538}, issn = {1469-3178}, mesh = {Adipose Tissue/metabolism ; Animals ; Cachexia/etiology/*metabolism ; *Energy Metabolism ; Gastrointestinal Absorption ; Humans ; Liver/metabolism ; Muscle, Skeletal/metabolism ; Neoplasms/complications/metabolism ; Organ Specificity ; }, abstract = {Cachexia is a wasting disorder that accompanies many chronic diseases including cancer and results from an imbalance of energy requirements and energy uptake. In cancer cachexia, tumor-secreted factors and/or tumor-host interactions cause this imbalance, leading to loss of adipose tissue and skeletal and cardiac muscle, which weakens the body. In this review, we discuss how energy enters the body and is utilized by the different organs, including the gut, liver, adipose tissue, and muscle, and how these organs contribute to the energy wasting observed in cachexia. We also discuss futile cycles both between the organs and within the cells, which are often used to fine-tune energy supply under physiologic conditions. Ultimately, understanding the complex interplay of pathologic energy-wasting circuits in cachexia can bring us closer to identifying effective treatment strategies for this devastating wasting disease.}, }
@article {pmid30890151, year = {2019}, author = {Tewari, SG and Rajaram, K and Schyman, P and Swift, R and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Short-term metabolic adjustments in Plasmodium falciparum counter hypoxanthine deprivation at the expense of long-term viability.}, journal = {Malaria journal}, volume = {18}, number = {1}, pages = {86}, pmid = {30890151}, issn = {1475-2875}, support = {R01 AI125534/AI/NIAID NIH HHS/United States ; AI125534//National Institute of Allergy and Infectious Diseases/ ; W81XWH-15-C-0061//Medical Research and Materiel Command/ ; }, mesh = {*Adaptation, Physiological ; Animals ; Gene Expression Profiling ; Hypoxanthine/*metabolism ; Metabolic Networks and Pathways ; Metabolomics ; Plasmodium falciparum/growth &amp; development/metabolism/*physiology ; Survival ; Time Factors ; }, abstract = {BACKGROUND: The malarial parasite Plasmodium falciparum is an auxotroph for purines, which are required for nucleic acid synthesis during the intra-erythrocytic developmental cycle (IDC) of the parasite. The capabilities of the parasite and extent to which it can use compensatory mechanisms to adapt to purine deprivation were studied by examining changes in its metabolism under sub-optimal concentrations of hypoxanthine, the primary precursor utilized by the parasite for purine-based nucleic acid synthesis.<br><br>METHODS: The concentration of hypoxanthine that caused a moderate growth defect over the course of one IDC was determined. At this concentration of hypoxanthine (0.5 μM), transcriptomic and metabolomic data were collected during one IDC at multiple time points. These data were integrated with a metabolic network model of the parasite embedded in a red blood cell (RBC) to interpret the metabolic adaptation of P. falciparum to hypoxanthine deprivation.<br><br>RESULTS: At a hypoxanthine concentration of 0.5 μM, vacuole-like structures in the cytosol of many P. falciparum parasites were observed after the 24-h midpoint of the IDC. Parasites grown under these conditions experienced a slowdown in the progression of the IDC. After 72 h of deprivation, the parasite growth could not be recovered despite supplementation with 90 µM hypoxanthine. Simulations of P. falciparum metabolism suggested that alterations in ubiquinone, isoprenoid, shikimate, and mitochondrial metabolism occurred before the appearance of these vacuole-like structures. Alterations were found in metabolic reactions associated with fatty acid synthesis, the pentose phosphate pathway, methionine metabolism, and coenzyme A synthesis in the latter half of the IDC. Furthermore, gene set enrichment analysis revealed that P. falciparum activated genes associated with rosette formation, Maurer's cleft and protein export under two different nutrient-deprivation conditions (hypoxanthine and isoleucine).<br><br>CONCLUSIONS: The metabolic network analysis presented here suggests that P. falciparum invokes specific purine-recycling pathways to compensate for hypoxanthine deprivation and maintains a hypoxanthine pool for purine-based nucleic acid synthesis. However, this compensatory mechanism is not sufficient to maintain long-term viability of the parasite. Although P. falciparum can complete a full IDC in low hypoxanthine conditions, subsequent cycles are disrupted.}, }
@article {pmid30888194, year = {2019}, author = {Yang, M and Xu, Z and Zhang, QZ and Wang, K and Ji, XY and Xu, J and Zhang, JY and Niu, G}, title = {A breast one-patient panel of heterogeneous genomes reveals genetic alterations driving DCIS into invasive lesions.}, journal = {Future oncology (London, England)}, volume = {15}, number = {14}, pages = {1565-1576}, doi = {10.2217/fon-2018-0555}, pmid = {30888194}, issn = {1744-8301}, mesh = {Actinin/genetics ; Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/metabolism/mortality ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/metabolism ; DNA Copy Number Variations ; Female ; *Genetic Heterogeneity ; *Genetic Variation ; *Genomics/methods ; Humans ; Mammography/methods ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Precision Medicine ; Prognosis ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; Whole Exome Sequencing ; }, abstract = {Aim: Utilize breast cancer samples in the same patient to indicate breast cancer development. Patients &amp; methods: We performed whole-exome analysis of spatially independent ductal carcinoma in situ (DCIS) and invasive ductal carcinoma samples from the same breast. Results: In VEGF pathway, we observed two genes disrupted in DCIS, while another four (including ACTN2) mutated in invasive ductal carcinoma. When looked up TCGA database, we identified seven breast cancer patients with ACTN2 somatic mutations and observed a dramatic decrease in the overall survival time in ACTN2 mutant patients (p = 0.0182). A further finding in the TCGA database shows that breast cancer patients with ≥2 mutated genes in VEGF pathways showed worse prognosis (p = 0.0013). Conclusion: TCGA database and special case could inform each other to reveal DCIS developmental rules.}, }
@article {pmid30879795, year = {2019}, author = {Sheaffer, WW and Gray, RJ and Wasif, N and Stucky, CC and Cronin, PA and Kosiorek, HE and Basu, A and Pizzitola, VJ and Patel, B and Giurescu, ME and Lorans, R and McCullough, AE and Ocal, IT and Pockaj, BA}, title = {Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.}, journal = {American journal of surgery}, volume = {217}, number = {6}, pages = {1025-1029}, doi = {10.1016/j.amjsurg.2018.12.069}, pmid = {30879795}, issn = {1879-1883}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology/surgery ; Female ; Humans ; *Mastectomy, Radical ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention.<br><br>METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging.<br><br>RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging.<br><br>CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.}, }
@article {pmid30872758, year = {2019}, author = {Roth, JD and Pariser, JJ and Stoffel, JT and Lenherr, SM and Myers, JB and Welk, B and Elliott, SP}, title = {Patient subjective assessment of urinary tract infection frequency and severity is associated with bladder management method in spinal cord injury.}, journal = {Spinal cord}, volume = {57}, number = {8}, pages = {700-707}, pmid = {30872758}, issn = {1476-5624}, support = {CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; }, mesh = {Adult ; Catheters, Indwelling/adverse effects/*trends ; Cross-Sectional Studies ; *Diagnostic Self Evaluation ; Female ; Humans ; Intermittent Urethral Catheterization/adverse effects/*trends ; Male ; Middle Aged ; Prospective Studies ; Registries ; Severity of Illness Index ; Spinal Cord Injuries/*complications/diagnosis/*therapy ; Urinary Tract Infections/diagnosis/*etiology ; }, abstract = {STUDY DESIGN: The Neurogenic Bladder Research Group (NBRG) registry is a multicenter prospective observational study. This manuscript is retrospective based on a cross-sectional survey.<br><br>OBJECTIVES: To assess patient subjective assessment of urinary tract infection (UTI) frequency and severity are associated with the degree of use of catheters or incontinence products.<br><br>SETTING: Multiple hospitals across the United States.<br><br>METHODS: Eligibility included: age > 18 years and acquired SCI. Over 1.5 years, 1479 eligible participants were enrolled. We excluded those with surgical reconstruction or diversion of the bladder. In total, 1282 participants were grouped by bladder management: (1) indwelling catheter (IDC), (2) clean intermittent catheterization (CIC), (3) external devices (pads/condom), and (4) volitional voiding (Void). UTI frequency was classified as 0, 1-3, 4-6, or > 6 over the prior year. UTI severity was determined by hospitalization for UTI in the prior year. Multivariate regression compared these factors across groups.<br><br>RESULTS: UTIs were least frequent in Void followed by pads/condom, CIC, and IDC (all p ≤ 0.001). UTI severity followed a similar pattern. Controlling for covariates, the adjusted odds of UTI frequency (Void = reference) were 2.28 (1.38-3.76) for pads/condom, 3.42 (2.25-5.18) for CIC, and 4.3 (2.59-6.70) for IDC (all p ≤ 0.001).<br><br>CONCLUSIONS: Patient subjective assessment of UTI frequency is highest with IDC, followed by CIC, pads/condom, and lowest with spontaneous voiding. The odds of hospitalization for UTI were three times higher for IDC than spontaneous voiding. UTI risk should be considered when counseling patients about bladder management options. These associations do not imply causation but warrant further investigation in a prospective manner.<br><br>SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) Award (CER14092138).}, }
@article {pmid30872384, year = {2019}, author = {Li, Y and Zhang, N and Zhang, H and Yang, Q}, title = {Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma.}, journal = {Journal of clinical pathology}, volume = {72}, number = {6}, pages = {418-424}, doi = {10.1136/jclinpath-2018-205544}, pmid = {30872384}, issn = {1472-4146}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/ethnology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/ethnology/mortality/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/ethnology/mortality/*pathology/therapy ; United States/epidemiology ; Young Adult ; }, abstract = {AIMS: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors.<br><br>METHODS: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19 383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the χ2 test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot.<br><br>RESULTS: A total of 586 patients with TN-MBC and 18 797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS.<br><br>CONCLUSION: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer.}, }
@article {pmid30864836, year = {2019}, author = {Dong, Y and Zhang, WW and Wang, J and Sun, JY and He, ZY and Wu, SG}, title = {The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.}, journal = {Future oncology (London, England)}, volume = {15}, number = {14}, pages = {1629-1639}, doi = {10.2217/fon-2018-0967}, pmid = {30864836}, issn = {1744-8301}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/*genetics/mortality/*therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Postoperative Care ; Prognosis ; Radiotherapy, Adjuvant ; Recurrence ; SEER Program ; }, abstract = {Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p = 0.029) and after (p = 0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.}, }
@article {pmid30843776, year = {2018}, author = {Menichetti, F and Bertolino, G and Sozio, E and Carmignani, C and Rosselli Del Turco, E and Tagliaferri, E and Sbrana, F and Ripoli, A and Barnini, S and Desideri, I and Dal Canto, L and Tascini, C and , }, title = {Impact of infectious diseases consultation as a part of an antifungal stewardship programme on candidemia outcome in an Italian tertiary-care, University hospital.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {30}, number = {5}, pages = {304-309}, doi = {10.1080/1120009X.2018.1507086}, pmid = {30843776}, issn = {1973-9478}, mesh = {Aged ; Antifungal Agents/*therapeutic use ; Antimicrobial Stewardship/methods ; Candida/drug effects ; Candidemia/*drug therapy ; Communicable Diseases/*drug therapy ; Female ; Fluconazole/therapeutic use ; Hospitals, University ; Humans ; Italy ; Male ; Referral and Consultation ; Retrospective Studies ; }, abstract = {Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.}, }
@article {pmid30843116, year = {2019}, author = {Goodfellow, J and Gorrie, G and Leach, V and Patel, S and Mackay, G}, title = {Cancer and motor neuron disease-causal or coincidental? Two contrasting cases.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {7}, pages = {1461-1463}, pmid = {30843116}, issn = {1590-3478}, mesh = {Breast Neoplasms/*complications/immunology/pathology ; Carcinoma, Ductal, Breast/*complications/immunology/pathology ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*complications/immunology/pathology/therapy ; Middle Aged ; Motor Neuron Disease/*complications/etiology/immunology ; *Paraneoplastic Syndromes, Nervous System/immunology ; Small Cell Lung Carcinoma/*complications/immunology/pathology/therapy ; }, abstract = {INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission.<br><br>CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.}, }
@article {pmid30842485, year = {2019}, author = {Rossi, A and Dupaty, L and Aillot, L and Zhang, L and Gallien, C and Hallek, M and Odenthal, M and Adriouch, S and Salvetti, A and Büning, H}, title = {Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {3631}, pmid = {30842485}, issn = {2045-2322}, mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology/virology ; Capsid/*immunology ; Capsid Proteins/*immunology ; Dendritic Cells/*immunology/virology ; Dependovirus/genetics/*immunology ; Genetic Vectors/*administration &amp; dosage/*immunology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; *Transduction, Genetic ; }, abstract = {AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV's intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV's in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8+ T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform.}, }
@article {pmid30825809, year = {2019}, author = {Owen, WA and Brazeal, HA and Shaw, HL and Lee, MV and Appleton, CM and Holley, SO}, title = {Focal breast pain: imaging evaluation and outcomes.}, journal = {Clinical imaging}, volume = {55}, number = {}, pages = {148-155}, doi = {10.1016/j.clinimag.2019.02.008}, pmid = {30825809}, issn = {1873-4499}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Cancer Pain/diagnostic imaging/etiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Follow-Up Studies ; Humans ; Incidental Findings ; Mammography/methods ; Mastodynia/*diagnostic imaging/etiology ; Middle Aged ; Prognosis ; Retrospective Studies ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVES: To determine the number and characteristics of cancers detected and the optimal imaging evaluation in women presenting with focal breast pain (FBP).<br><br>MATERIALS AND METHODS: We performed a retrospective review of 4720 women who underwent imaging for FBP from 2001 to 2013. Women 18 and over with one or two foci of breast pain and no concurrent breast symptoms were included. 944 patients met criteria. We recorded the imaging work-up, presence and type of finding at the site of pain, BI-RADS® assessment, and pathological outcomes. Subsequent imaging and clinical follow up was recorded.<br><br>RESULTS: Imaging evaluation consisted of sonogram alone in 286 women, mammogram alone in 231 women, and both in 427 women. 113 women had an imaging finding at the site of pain; 103 were designated benign or probably benign. 12 biopsies of corresponding findings were performed: 9 benign, 1 invasive lobular carcinoma, 1 invasive ductal carcinoma, 1 ductal carcinoma in situ. All three malignancies were seen mammographically; 2 had an ultrasound correlate. At initial evaluation, 4 incidental breast cancers were diagnosed remote from the site of FBP. All were seen on mammogram and 2 of 4 had an ultrasound correlate. On follow up evaluation, 9 cancers were diagnosed at the site of pain and 13 incidental cancers were diagnosed.<br><br>CONCLUSION: FBP is rarely associated with malignancy. Targeted ultrasound may be deferred in women 40 and older with FBP, no other clinical findings, and a negative mammogram.}, }
@article {pmid30820924, year = {2019}, author = {Murakami, W and Tozaki, M and Nakamura, S and Ide, Y and Inuzuka, M and Hirota, Y and Murakami, K and Takahama, N and Ohgiya, Y and Gokan, T}, title = {The clinical impact of MRI screening for BRCA mutation carriers: the first report in Japan.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {26}, number = {5}, pages = {552-561}, pmid = {30820924}, issn = {1880-4233}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/*genetics/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics/pathology ; Female ; Follow-Up Studies ; *Genes, BRCA1 ; *Genes, BRCA2 ; Humans ; Japan ; *Magnetic Resonance Imaging ; Mammography ; Mass Screening/methods ; Middle Aged ; *Mutation ; Public Health Surveillance/methods ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: There is no consensus on the appropriate surveillance for high-risk women with breast cancer in Japan. We investigated their imaging features and pathological characteristics to build a proper surveillance system for asymptomatic high-risk individuals in the future.<br><br>METHODS: We retrospectively reviewed 93 female (median age 43 years) BRCA1 and BRCA2 mutation carriers from our institutional clinical database from 2011 to 2017. The study population was composed of 112 breast cancers. Mammography and MRI were reviewed by examiners blinded to patients' clinical history. Final surgical or biopsy histopathology served as the reference standard in all the patients.<br><br>RESULTS: Fifty-nine breast cancers met selection criteria; of these, 30 were BRCA1-associated tumors, and 29 were BRCA2-associated tumors. Invasive ductal carcinoma was the most prevalent type in both BRCA1 and BRCA2. There were statistically significant differences in phenotype, nuclear grade, and Ki-67 labeling index between BRCA1 and BRCA2 mutation carriers. Additionally, imaging findings on mammography and MRI were statistically different. Tumors in BRCA2 carriers demonstrated mammographic calcifications more frequently, while those in BRCA1 carriers demonstrated a mass or architectural distortion (P < 0.001). Enhancement pattern on MRI also significantly differed between the two subgroups (P = 0.006). The size of MRI-detected lesions was statistically smaller than the size of those detected by other modalities (P = 0.004).<br><br>CONCLUSIONS: The imaging and histological characteristics of BRCA1/2 mutation carriers were consistent with other countries' studies. MRI-detected lesions were significantly smaller than lesions detected by non-MRI modality. All lesions in BRCA1 mutation carriers could be detected by MRI.}, }
@article {pmid30813596, year = {2019}, author = {Myers, MB and McKim, KL and Banda, M and George, NI and Parsons, BL}, title = {Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology.}, journal = {International journal of molecular sciences}, volume = {20}, number = {5}, pages = {}, pmid = {30813596}, issn = {1422-0067}, mesh = {Alleles ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fluorescein/metabolism ; Humans ; Middle Aged ; Mutation/genetics ; *Mutation Rate ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/genetics ; Polymerase Chain Reaction ; *Precision Medicine ; Proto-Oncogene Proteins B-raf/genetics ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10-5, the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.}, }
@article {pmid30807826, year = {2019}, author = {Griggs, RB and Santos, DF and Laird, DE and Doolen, S and Donahue, RR and Wessel, CR and Fu, W and Sinha, GP and Wang, P and Zhou, J and Brings, S and Fleming, T and Nawroth, PP and Susuki, K and Taylor, BK}, title = {Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.}, journal = {Neurobiology of disease}, volume = {127}, number = {}, pages = {76-86}, pmid = {30807826}, issn = {1095-953X}, support = {R01 DA037621/DA/NIDA NIH HHS/United States ; F31 NS083292/NS/NINDS NIH HHS/United States ; R56 NS107398/NS/NINDS NIH HHS/United States ; R01 NS062306/NS/NINDS NIH HHS/United States ; R01 NS045954/NS/NINDS NIH HHS/United States ; T32 NS077889/NS/NINDS NIH HHS/United States ; }, mesh = {Adenylyl Cyclases/*metabolism ; Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/physiology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Diabetes Mellitus, Type 2/complications/*metabolism ; Diabetic Neuropathies/*metabolism ; Guanine Nucleotide Exchange Factors/*metabolism ; Male ; Mice ; Pain Measurement ; Posterior Horn Cells/drug effects/metabolism ; Pyruvaldehyde/*metabolism/pharmacology ; Signal Transduction/drug effects/physiology ; TRPA1 Cation Channel/*metabolism ; }, abstract = {Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca2+ mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes.}, }
@article {pmid30798329, year = {2019}, author = {Sawai, H and Kurimoto, M and Koide, S and Kiriyama, Y and Haba, S and Matsuo, Y and Morimoto, M and Koide, H and Kamiya, A and Yamao, K}, title = {Invasive Ductal Carcinoma Arising in Mucinous Cystic Neoplasm of Pancreas: A Case Report.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {242-247}, pmid = {30798329}, issn = {1941-5923}, mesh = {Adult ; Carcinoma, Pancreatic Ductal/*pathology ; Cystadenoma, Mucinous/*pathology ; Female ; Humans ; Mutation ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology ; Pancreatic Neoplasms/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; }, abstract = {BACKGROUND Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. CASE REPORT A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. CONCLUSIONS We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.}, }
@article {pmid30789657, year = {2019}, author = {Nguyen, B and Veys, I and Leduc, S and Bareche, Y and Majjaj, S and Brown, DN and Boeckx, B and Lambrechts, D and Sotiriou, C and Larsimont, D and Desmedt, C}, title = {Genomic, Transcriptomic, Epigenetic, and Immune Profiling of Mucinous Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {111}, number = {7}, pages = {742-746}, doi = {10.1093/jnci/djz023}, pmid = {30789657}, issn = {1460-2105}, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Methylation/genetics ; Epigenomics/methods ; Female ; Genomic Instability/genetics ; Genomics/methods ; Humans ; Lymphatic Metastasis ; Mucin-2/*genetics ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcriptome/genetics ; }, abstract = {Although invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC are distinguished by tumor cells floating in extracellular mucin. MuBC patients are generally older and associated with a favorable prognosis. To unravel the molecular architecture of MuBC, we applied low-pass whole-genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium and The Cancer Genome Atlas. Genomic data (n = 26 MuBC, n = 535 estrogen receptor [ER] positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC), and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low tumor infiltrating lymphocyte levels (median = 0.0%, average = 3.4%, 95% confidence interval = 1.9% to 4.9%). Compared with IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test) and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs 6.7% in MuBC, P = .01 in the International Cancer Genomics Consortium; and 34.8% vs 0.0%, P = .02 in The Cancer Genome Atlas, two-sided Fisher's exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC.}, }
@article {pmid30786684, year = {2018}, author = {Hybiak, J and Domagala, P and Domagala, W}, title = {BRCA1 and PARP1 mRNA expression during progression from normal breast to ductal carcinoma in situ and invasive breast cancer: a laser microdissection study.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {69}, number = {4}, pages = {347-355}, doi = {10.5114/pjp.2018.81694}, pmid = {30786684}, issn = {1233-9687}, mesh = {BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Humans ; Laser Capture Microdissection ; Poly (ADP-Ribose) Polymerase-1/*genetics ; RNA, Messenger ; }, abstract = {The contribution of DNA damage repair mechanisms to the progression of normal breast to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma is largely unknown. The purpose of this report was to assess the mRNA expression levels of two important genes associated with DNA repair, BRCA1 and PARP1, in normal breast tissue, DCIS G1, G2 and G3, and co-existing adjacent invasive ductal carcinoma. BRCA1 and PARP1 mRNA expression was assessed in 32 ductal carcinomas in situ of the breast using a laser microdissection and pressure catapulting system and quantitative real-time PCR. The relative expression of BRCA1 mRNA was significantly increased in DCIS G2 and DCIS G3 relative to normal breast tissue (p = 0.02, p = 0.001, respectively). Significant differences in BRCA1 expression were observed between DCIS G1 and G2 (p = 0.02) and between DCIS G1 and G3 (p = 0.0007). No significant differences in BRCA1 expression were observed between normal breast tissue and DCIS G1 and between DCIS component and adjacent invasive ductal carcinoma. No significant differences in the relative expression of PARP1 mRNA were observed between groups. Increased BRCA1 mRNA expression (but not PARP1 mRNA) occurs early in the development of breast cancer, i.e. at the noninvasive (DCIS) stage, suggesting a demand for increased activity of a DNA double-strand break repair by homologous recombination. DCIS G1 and normal breast tissue share highly similar BRCA1 and PARP1 expression level. This finding supports the idea that DCIS G1 belongs to a separate family of precursor lesions with low malignant potential.}, }
@article {pmid30772465, year = {2019}, author = {Ducommun, S and Deak, M and Zeigerer, A and Göransson, O and Seitz, S and Collodet, C and Madsen, AB and Jensen, TE and Viollet, B and Foretz, M and Gut, P and Sumpton, D and Sakamoto, K}, title = {Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates.}, journal = {Cellular signalling}, volume = {57}, number = {}, pages = {45-57}, doi = {10.1016/j.cellsig.2019.02.001}, pmid = {30772465}, issn = {1873-3913}, mesh = {AMP-Activated Protein Kinases/*metabolism ; Animals ; Guanine Nucleotide Exchange Factors/*metabolism ; Hepatocytes/metabolism ; Homeostasis/genetics/physiology ; Lipid Metabolism/genetics ; Liver/*metabolism ; Mass Spectrometry/methods ; Membrane Proteins/*metabolism ; Mice, Knockout ; Muscle Proteins/*metabolism ; Phosphorylation ; Substrate Specificity ; }, abstract = {AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.}, }
@article {pmid30771577, year = {2019}, author = {Liao, W and Li, C and Tang, Y and Huang, F and Kuang, H and Liang, S and Yang, Y}, title = {Aquaporin-4 antibody positive short transverse myelitis associated with breast cancer.}, journal = {Multiple sclerosis and related disorders}, volume = {30}, number = {}, pages = {119-122}, doi = {10.1016/j.msard.2019.02.011}, pmid = {30771577}, issn = {2211-0356}, mesh = {Adult ; Antibodies/*cerebrospinal fluid ; Aquaporin 4/*immunology ; Breast Neoplasms/*cerebrospinal fluid/complications/diagnostic imaging ; Carcinoma/*cerebrospinal fluid/complications/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Myelitis, Transverse/*blood/complications/diagnostic imaging ; Spinal Cord/diagnostic imaging ; }, abstract = {Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). A typical finding on spinal magnetic resonance imaging (MRI) of NMOSD is longitudinally extensive transverse myelitis (LETM). However, patients with NMOSD presenting with short-segment transverse myelitis (STM) during myelitis attacks associated with breast cancer are uncommon. We report a case of a 35-year-old woman with STM and left eye optic neuritis. The patient was positive for serum aquaporin-4 antibodies (AQP4-IgG), and a biopsy of the left breast showed invasive ductal carcinoma. The patient was diagnosed with NMOSD and breast malignancy. This is the first report of a patient with NMOSD whose spinal MRI showed STM and serum test showed that the patient's AQP4-IgG was positive and complicated by breast cancer. This case improves our understanding of the association between NMOSD and cancer and raises the question of whether it was a coincidental occurrence. It is important to search for extensive malignancies in patients presenting with atypical MRI or no reaction to traditional therapies.}, }
@article {pmid30771195, year = {2019}, author = {Miyake, M and Yamada, A and Miyake, K and Endo, I}, title = {Esophageal metastasis of breast cancer during endocrine therapy for pleural dissemination 21 years after breast surgery: a case report.}, journal = {Surgical case reports}, volume = {5}, number = {1}, pages = {22}, pmid = {30771195}, issn = {2198-7793}, abstract = {BACKGROUND: The esophageal metastasis of breast cancer is rare. Moreover, it is extremely unusual for patients to experience the symptoms of esophageal metastasis during their lifetimes. We present a case of dysphagia caused by esophageal metastasis after a long interval following a primary mastectomy.<br><br>CASE PRESENTATION: A 77-year-old woman with a history of heterochronous bilateral breast cancer and under treatment for pleural dissemination recurrence originating from right breast cancer complained of dysphagia. At the age of 56, she had undergone a right radical mastectomy for right breast cancer. The histopathological findings revealed invasive ductal carcinoma, pT3N1M0, which was estrogen receptor (ER)- and progesterone receptor (PgR)-positive. At the age of 73, she underwent a second operation, a left modified radical mastectomy. The histopathological examination revealed invasive ductal carcinoma, pT1N0M0, which was negative for ER, PgR, and human epidermal growth factor receptor 2 (HER2). Four years after completion of adjuvant therapy for the left breast cancer, pleural effusion on her left side was observed and histopathological examination of a sample revealed pleural dissemination resulting from the right breast cancer. After initiation of therapy for recurrence, she developed dysphagia and, therefore, underwent an upper gastrointestinal tract endoscopic examination. The examination revealed whole circumferential stenosis and a band unstained by Lugol's solution located 30 cm from her incisors. Examination of a biopsy specimen revealed a subepithelial luminal structure and dysplastic cells. Immunostaining was positive for CK7 and negative for CK20; furthermore, the sample was ER and PgR-positive. Considering the pathological findings, the patient was diagnosed with esophageal metastasis of her right breast cancer.<br><br>CONCLUSIONS: Metastatic lesions in the esophagus are often located in the submucosa; therefore, they may not be definitively diagnosed by histopathological examination of mucosal biopsy specimens. Esophageal metastasis originating from breast cancer often occurs as a part of multiple organ metastases; however, esophageal metastasis is usually not considered a prognostic factor for patients. Therefore, treatment should be determined according to the severity of the other metastatic sites and the degree of esophageal stenosis.}, }
@article {pmid30770989, year = {2019}, author = {Yan, Z and Ohuchida, K and Zheng, B and Okumura, T and Takesue, S and Nakayama, H and Iwamoto, C and Shindo, K and Moriyama, T and Nakata, K and Miyasaka, Y and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M}, title = {CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.}, journal = {Journal of cancer research and clinical oncology}, volume = {145}, number = {5}, pages = {1147-1164}, pmid = {30770989}, issn = {1432-1335}, mesh = {Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor ; Carcinoma, Pancreatic Ductal/genetics/metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Survival ; Disease Models, Animal ; Disease Progression ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/secondary ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/genetics/*metabolism/mortality/*pathology ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; Receptors, Thrombopoietin/genetics/*metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.<br><br>METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.<br><br>RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.<br><br>CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.}, }
@article {pmid30769363, year = {2019}, author = {Guillamat-Prats, R and Rami, M and Herzig, S and Steffens, S}, title = {Endocannabinoid Signalling in Atherosclerosis and Related Metabolic Complications.}, journal = {Thrombosis and haemostasis}, volume = {119}, number = {4}, pages = {567-575}, doi = {10.1055/s-0039-1678738}, pmid = {30769363}, issn = {2567-689X}, mesh = {Adipose Tissue/metabolism ; Animals ; Arachidonic Acid/chemistry ; Atherosclerosis/*metabolism ; Bile Acids and Salts/chemistry ; Blood Glucose/metabolism ; Cardiovascular System/metabolism ; Cytokines/metabolism ; Endocannabinoids/*metabolism ; Humans ; Inflammation ; Insulin Resistance ; Ligands ; Lipid Metabolism ; Lipids/chemistry ; Liver/metabolism ; Mice ; Mice, Knockout ; Obesity, Abdominal/metabolism ; Pancreas/metabolism ; Receptor, Cannabinoid, CB2/*metabolism ; Receptors, Cannabinoid/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Risk Factors ; *Signal Transduction ; }, abstract = {Endocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signalling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism and consequently atherosclerotic plaque stability. In addition, recent findings in various metabolic disease models highlight the relevance of peripheral CB1 cannabinoid receptors in adipose tissue, liver and pancreas, which crucially regulate lipid and glucose metabolism as well as macrophage properties in these organs. This suggests that targeting the endocannabinoid system in the vasculature and peripheral organs might have a therapeutic potential for atherosclerosis by inhibiting vascular inflammation and improving metabolic risk factors. This review will provide a brief update on the effects of endocannabinoid signalling in atherosclerosis and related metabolic complications.}, }
@article {pmid30762822, year = {2019}, author = {Louarn, N and Dauta, A and Lechapt-Zalcman, E and Kauv, P and Itti, E}, title = {Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap: A Case Resolved by 18F-DOPA PET/MRI.}, journal = {Clinical nuclear medicine}, volume = {44}, number = {4}, pages = {e315-e317}, doi = {10.1097/RLU.0000000000002492}, pmid = {30762822}, issn = {1536-0229}, mesh = {Breast Neoplasms/pathology ; *Dihydroxyphenylalanine ; Female ; *Fluorine Radioisotopes ; Humans ; *Magnetic Resonance Imaging ; Meningeal Neoplasms/*diagnostic imaging/*secondary ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Recurrence ; Skull/diagnostic imaging/metabolism ; }, abstract = {A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.}, }
@article {pmid30761666, year = {2019}, author = {Yilmaz, R and Akpinar, Y and Ozyavuz, I and Önder, S and Tukenmez, M and Dursun, M}, title = {Synchronous metastatic leiomyosarcoma and primer invasive ductal carcinoma tumors in the same breast: Mammography, ultrasonography, and magnetic resonance imaging findings.}, journal = {The breast journal}, volume = {25}, number = {2}, pages = {310-311}, doi = {10.1111/tbj.13211}, pmid = {30761666}, issn = {1524-4741}, mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Leiomyosarcoma/*diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mammography ; Ultrasonography, Mammary ; Unilateral Breast Neoplasms/*diagnostic imaging/pathology/secondary ; }, }
@article {pmid30760857, year = {2019}, author = {Alsaleem, M and Toss, MS and Joseph, C and Aleskandarany, M and Kurozumi, S and Alshankyty, I and Ogden, A and Rida, PCG and Ellis, IO and Aneja, R and Green, AR and Mongan, NP and Rakha, EA}, title = {The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {32}, number = {7}, pages = {967-976}, doi = {10.1038/s41379-019-0209-9}, pmid = {30760857}, issn = {1530-0285}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Genomic Instability/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Middle Aged ; Tissue Array Analysis ; Young Adult ; }, abstract = {E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6.0 arrays, and next-generation sequencing for differential gene expression. Our results showed 27% of high-grade invasive ductal carcinoma showed reduced/loss of E-cadherin membranous expression. CDH1 copy number loss was in 21% of invasive ductal carcinoma, which also showed low CDH1 mRNA expression (p = 0.003). CDH1 copy number was associated with copy number loss of TP53, ATM, BRCA1, and BRCA2 (p < 0.001). Seventy-nine percent of invasive ductal carcinoma with reduced CDH1 mRNA expression showed elevated expression of E-cadherin transcription suppressors TWIST2, ZEB2, NFKB1, LLGL2, CTNNB1 (p < 0.01). Reduced/loss E-cadherin expression was associated with differential expression of 2143 genes including those regulating Wnt (FZD2, GNG5, HLTF, WNT2, and CER1) and PIK3-AKT (FGFR2, GNF5, GNGT1, IFNA17, and IGF1) signaling pathways. Interestingly, key genes differentially expressed between invasive lobular carcinoma and invasive ductal tumors did not show association with E-cadherin loss in invasive ductal carcinoma. We conclude that E-cadherin loss in invasive ductal carcinoma is likely a consequence of genomic instability occurring during carcinogenesis. Potential novel regulators controlling E-cadherin expression in invasive ductal carcinoma warrant further investigation.}, }
@article {pmid30728399, year = {2019}, author = {Kaur, P and Porras, TB and Ring, A and Carpten, JD and Lang, JE}, title = {Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {1482}, pmid = {30728399}, issn = {2045-2322}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Computer Simulation ; DNA Copy Number Variations/genetics ; Databases, Genetic/*standards/*trends ; Exome/genetics ; Female ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Mutation/genetics ; Precision Medicine/methods ; }, abstract = {Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor.}, }
@article {pmid30725231, year = {2019}, author = {Liu, Y and Pandey, PR and Sharma, S and Xing, F and Wu, K and Chittiboyina, A and Wu, SY and Tyagi, A and Watabe, K}, title = {ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness.}, journal = {Breast cancer research and treatment}, volume = {175}, number = {1}, pages = {77-90}, pmid = {30725231}, issn = {1573-7217}, support = {R01CA205067//National Cancer Institute (US)/ ; F31 CA200286/CA/NCI NIH HHS/United States ; F31CA200286//National Cancer Institute/ ; R01CA173499//National Cancer Institute/ ; R01 CA173499/CA/NCI NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; R01CA185650//National Cancer Institute/ ; R01 CA205067/CA/NCI NIH HHS/United States ; R01 CA185650/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Proliferation ; Chalcone/analogs &amp; derivatives/chemistry/pharmacology ; Connexins/*genetics ; Disease Models, Animal ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Inhibitor of Differentiation Protein 2/*genetics ; Mice ; Neoplasm Staging ; Neoplastic Stem Cells/*metabolism ; Prognosis ; *Promoter Regions, Genetic ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer which could progress to or recur as invasive breast cancer. The underlying molecular mechanism of DCIS progression is yet poorly understood, and appropriate biomarkers to distinguish benign form of DCIS from potentially invasive tumor are urgently needed.<br><br>METHODS: To identify the key regulators of DCIS progression, we performed gene-expression analysis of syngeneic breast cancer cell lines MCF10A, DCIS.com, and MCF10CA and cross-referenced the targets with patient cohort data.<br><br>RESULTS: We identified ID2 as a critical gene for DCIS initiation and found that ID2 promoted DCIS formation by enhancing cancer stemness of pre-malignant cells. ID2 also plays a pivotal role in survival of the aggressive cancer cells. In addition, we identified INHBA and GJB2 as key regulators for the transition of benign DCIS to aggressive phenotype. These two genes regulate migration, colonization, and stemness of invasive cancer cells. Upregulation of ID2 and GJB2 predicts poor prognosis after breast-conserving surgery. Finally, we found a natural compound Helichrysetin as ID2 inhibitor which suppresses DCIS formation in vitro and in vivo.<br><br>CONCLUSION: Our results indicate that ID2 is a key driver of DCIS formation and therefore is considered to be a potential target for prevention of DCIS, while INHBA and GJB2 play vital roles in progression of DCIS to IDC and they may serve as potential prognosis markers.}, }
@article {pmid30719718, year = {2019}, author = {Dianatinasab, M and Fararouei, M and Daneshi, N and Rezaian, S and Mohammadianpanah, M and Chaman, R and Ghiasvand, R}, title = {Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study.}, journal = {International journal of cancer}, volume = {145}, number = {11}, pages = {2917-2925}, doi = {10.1002/ijc.32182}, pmid = {30719718}, issn = {1097-0215}, mesh = {Abortion, Spontaneous/epidemiology ; Adult ; Breast Feeding/statistics &amp; numerical data ; Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Humans ; Iran ; Middle Aged ; Risk Factors ; }, abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.}, }
@article {pmid30712460, year = {2020}, author = {Song, G and He, L and Yang, X and Yang, Y and Cai, X and Liu, K and Feng, G}, title = {Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.}, journal = {The Journal of international medical research}, volume = {48}, number = {1}, pages = {300060518815364}, pmid = {30712460}, issn = {1473-2300}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cluster Analysis ; Databases, Genetic ; *Disease Progression ; Down-Regulation/genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Reproducibility of Results ; Signal Transduction/genetics ; Up-Regulation/genetics ; }, }
@article {pmid30692436, year = {2018}, author = {Kodera, A and Inoue, H and Ogura, K and Sakaguchi, S and Yukawa, H and Matsuoka, A and Tanaka, N and Kinoshita, J and Yoshimatsu, K and Naritaka, Y and Hirano, A}, title = {[Bevacizumab plus Paclitaxel Therapy Was Effective for Metastatic Breast Cancer with Dysphagia Due to Mediastinal Lymph Node Metastasis-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {13}, pages = {2276-2278}, pmid = {30692436}, issn = {0385-0684}, mesh = {Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration &amp; dosage ; *Breast Neoplasms/complications/drug therapy ; *Deglutition Disorders/drug therapy/etiology ; Female ; Humans ; Lymph Nodes ; Paclitaxel/administration &amp; dosage ; Quality of Life ; }, abstract = {A 69-year-old woman noticed a tumor of the right breast, and presented to our hospital with dysphagia. A tumor of size 10 cm exposed to the skin and swollen axillary lymph node were observed. She was diagnosed with invasive ductal carcinoma, luminal-B by core-needle biopsy. CT scan revealed primary breast cancer with lung, bone, and lymph node metastasis. Endoscopic and fluoroscopic findings of the esophagus showed severe stenosis by extrinsic compression. In order to improve the quality of life(QOL)immediately, bevacizumab plus paclitaxel therapy was initiated. After the first course, the dysphagia improved, and she was able to take normal meals after 2 courses of treatment. Primary tumor and metastatic lesions had remarkably shrunk on CT scan. After 4 courses of treatment, we changed to endocrine therapy and continued outcome treatment. Bevacizumab was effective for immediate improvement of QOL in such as an oncologic emergent case of metastatic breast cancer.}, }
@article {pmid30689164, year = {2019}, author = {da Silva Filho, AF and Vieira-de-Mello, GS and Dos Santos, PB and de Melo Rêgo, MJB and Ribeiro-Silva, A and Beltrão, EIC}, title = {N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.}, journal = {Pathology oncology research : POR}, volume = {25}, number = {2}, pages = {759-768}, pmid = {30689164}, issn = {1532-2807}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/enzymology/*pathology ; Female ; Humans ; Middle Aged ; N-Acetylglucosaminyltransferases/analysis/*metabolism ; }, abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.}, }
@article {pmid30675210, year = {2019}, author = {Smalley, T and Islam, SMA and Apostolatos, C and Apostolatos, A and Acevedo-Duncan, M}, title = {Analysis of PKC-ζ protein levels in normal and malignant breast tissue subtypes.}, journal = {Oncology letters}, volume = {17}, number = {2}, pages = {1537-1546}, pmid = {30675210}, issn = {1792-1074}, abstract = {It is estimated that breast cancer will be the second leading cause of cancer-associated mortality in women in 2018. Previous research has demonstrated that the atypical protein kinase C-ζ (PKC-ζ) is a component of numerous dysregulated pathways in breast cancer, including cellular proliferation, survival, and cell cycle upregulation. The present study investigated the PKC-ζ protein in breast tissue to evaluate its potential as a biomarker for breast cancer invasion, and demonstrated that an overexpression of PKC-ζ protein can be indicative of carcinogenesis. The present study analyzed the expression of PKC-ζ in individuals with no tumor complications and malignant female human breast tissue samples (lobular carcinoma in situ, invasive lobular carcinoma, ductal carcinoma in situ and invasive ductal carcinoma) with the use of western blot analysis, immunohistochemistry and statistical analysis (83 samples). The present study also evaluated the invasive behavior of MDA-MB-231 breast cancer cells following the knockdown of PKC-ζ with a Transwell invasion assay and an immunofluorescent probe for filamentous actin (F-actin) organization. The data demonstrated that PKC-ζ expression was identified to be higher in invading tissues when compared with non-invading tissues. The results also suggest that PKC-ζ is more abundant in ductal tissues when compared with lobular tissues. In addition, the protein studies also suggest that PKC-ζ is a component for invasive behavior through the Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) pathway, and PKC-ζ is required for the F-actin reorganization in invasive cells. Therefore, PKC-ζ should be considered to be a biomarker in the development of breast cancer as well as an indicator of invading tumor cells.}, }
@article {pmid30659022, year = {2019}, author = {Guo, Q and Li, VZ and Nichol, JN and Huang, F and Yang, W and Preston, SEJ and Talat, Z and Lefrère, H and Yu, H and Zhang, G and Basik, M and Gonçalves, C and Zhan, Y and Plourde, D and Su, J and Torres, J and Marques, M and Habyan, SA and Bijian, K and Amant, F and Witcher, M and Behbod, F and McCaffrey, L and Alaoui-Jamali, M and Giannakopoulos, NV and Brackstone, M and Postovit, LM and Del Rincón, SV and Miller, WH}, title = {MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ.}, journal = {Cancer research}, volume = {79}, number = {7}, pages = {1646-1657}, pmid = {30659022}, issn = {1538-7445}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; R21 CA226567/CA/NCI NIH HHS/United States ; PJT-156269//CIHR/Canada ; MOP-142281//CIHR/Canada ; }, mesh = {Animals ; Breast Carcinoma In Situ/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; CRISPR-Cas Systems ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Heterografts ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; Nodal Protein/*metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; *Signal Transduction ; }, abstract = {The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A-derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. SIGNIFICANCE: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.}, }
@article {pmid30652428, year = {2019}, author = {Liu, Y and Ide, Y and Inuzuka, M and Tazawa, S and Kanada, Y and Matsunaga, Y and Kuwayama, T and Sawada, T and Akashi-Tanaka, S and Nakamura, S}, title = {BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.}, journal = {Molecular genetics &amp; genomic medicine}, volume = {7}, number = {3}, pages = {e493}, pmid = {30652428}, issn = {2324-9269}, mesh = {Adult ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Genetic Testing/standards ; Humans ; Incidence ; Japan ; *Mutation ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations.<br><br>METHODS: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR).<br><br>RESULTS: (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023-0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR.<br><br>CONCLUSION: DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.}, }
@article {pmid30621656, year = {2019}, author = {Framarino-Dei-Malatesta, M and Chiarito, A and Bianciardi, F and Fiorelli, M and Ligato, A and Naso, G and Pecorella, I}, title = {Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {36}, pmid = {30621656}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*diagnosis/diagnostic imaging/drug therapy/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Muscle Neoplasms/*diagnosis/diagnostic imaging/pathology/secondary ; Neoplasm Metastasis ; Piperazines/therapeutic use ; Pyridines/therapeutic use ; }, abstract = {BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer.<br><br>CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months.<br><br>CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.}, }
@article {pmid30608397, year = {2019}, author = {Bertozzi, S and Cedolini, C and Londero, AP and Baita, B and Giacomuzzi, F and Capobianco, D and Tortelli, M and Uzzau, A and Mariuzzi, L and Risaliti, A}, title = {Sentinel lymph node biopsy in patients affected by breast ductal carcinoma in situ with and without microinvasion: Retrospective observational study.}, journal = {Medicine}, volume = {98}, number = {1}, pages = {e13831}, pmid = {30608397}, issn = {1536-5964}, mesh = {Aged ; Breast/pathology ; Breast Carcinoma In Situ/mortality/pathology/*surgery ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Micrometastasis ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy/*mortality ; }, abstract = {With the introduction of an organized mammographic screening, the incidence of ductal carcinoma in situ (DCIS) has experienced an important increase. Our experience with sentinel lymph node biopsy (SLNB) among patients with DCIS is reviewed.We collected retrospective data on patients operated on their breasts for DCIS (pTis), DCIS with microinvasion (DCISM) (pT1mi) and invasive ductal carcinoma (IDC) sized ≤2 cm (pT1) between January 2002 and June 2016, focusing on the result of SLNB.543 DCIS, 84 DCISM, and 2111 IDC were included. In cases of DCIS and DCISM, SLNB resulted micrometastatic respectively in 1.7% and 6.0% of cases and macrometastatic respectively in 0.9% and 3.6% of cases. 5-year disease-free survival and overall survival in DCISM and IDC were similar, while significantly longer in DCIS. 5-year local recurrence rate of DCIS and DCISM were respectively 2.5% and 7.9%, and their 5-year distant recurrence rate respectively 0% and 4%. IDC, tumor grading ≥2 and lymph node (LN) macrometastasis were significant predictors for decreased overall survival. Significant predictors for distant metastases were DCISM, IDC, macroscopic nodal metastasis, and tumor grading ≥2. Predictors for the microinvasive component in DCIS were tumor multifocality/multicentricity, grading ≥2, ITCs and micrometastases.Our study suggests that despite its rarity, sentinel node metastasis may also occur in case of DCIS, which in most cases are micrometastases. Even in the absence of an evident invasive component, microinvasion should always be suspected in these cases, and their management should be the same as for IDC.}, }
@article {pmid30607556, year = {2019}, author = {Wang, G and Zhou, C and Conklin, C and Hayes, MM and Villamil, CF and Ostry, A and Jones, EC}, title = {Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {474}, number = {3}, pages = {333-339}, pmid = {30607556}, issn = {1432-2307}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Carcinoma, Squamous Cell/chemistry/mortality/*pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Time Factors ; Urinary Bladder Neoplasms/chemistry/mortality/*secondary/therapy ; }, abstract = {Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.}, }
@article {pmid30594914, year = {2019}, author = {Khorshidi, H and Azari, I and Oskooei, VK and Taheri, M and Ghafouri-Fard, S}, title = {DSCAM-AS1 up-regulation in invasive ductal carcinoma of breast and assessment of its potential as a diagnostic biomarker.}, journal = {Breast disease}, volume = {38}, number = {1}, pages = {25-30}, doi = {10.3233/BD-180351}, pmid = {30594914}, issn = {1558-1551}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Carcinoma, Ductal, Breast/*diagnosis/*genetics ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Association Studies ; Humans ; Middle Aged ; RNA, Long Noncoding/*genetics ; Real-Time Polymerase Chain Reaction ; Tamoxifen/therapeutic use ; Up-Regulation ; }, abstract = {BACKGROUND: The long non-coding RNA (lncRNA) DSCAM-AS1 has been demonstrated to participate in the pathogenesis of breast cancer and tamoxifen resistance.<br><br>OBJECTIVE: To evaluate expression profile of DSCAM-AS1 in invasive ductal carcinoma of breast and its suitability as a biomarker for diagnosis of breast cancer.<br><br>METHODS: We evaluated expression of DSCAM-AS1 in 108 breast tissues including tumoral and adjacent non-cancerous tissues (ANCTs) by means of quantitative real time PCR.<br><br>RESULTS: DSCAM-AS1 was up-regulated in tumoral tissues compared with ANCTs (Fold change = 2.86, P = 0.011). Its expression was significantly higher in patients aged less than 55 compared with older patients (P = 0.02). However, its expression levels had not a good performance as a diagnostic biomarker for breast cancer.<br><br>CONCLUSIONS: The significant up-regulation of DSCAM-AS1 in tumoral tissues compared with ANCTs provides further evidences for participation of this lncRNA in the pathogenesis of breast cancer.}, }
@article {pmid30587740, year = {2018}, author = {Yano, Y and Kuga, T and Harada, T and Sano, F and Inokuchi, T and Fujii, Y}, title = {[A Case of Suspected Therapy-Related Leukemia after Chemotherapy for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {45}, number = {12}, pages = {1775-1777}, pmid = {30587740}, issn = {0385-0684}, mesh = {*Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; *Leukemia/chemically induced ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasms, Second Primary ; Sentinel Lymph Node Biopsy ; }, abstract = {Therapy-related leukemia(TRL)is a distinctive clinical syndrome that occurs after exposure to chemotherapy or radiotherapy. We report a case of suspected TRLafter chemotherapy in a patient with breast cancer. A 61-year-old woman underwent total mastectomy and sentinel lymph node biopsy(negative)for her breast cancer. Histopathologic analysis showed invasive ductal carcinoma, pStage I. Her subtype histology was Luminal B-type, and postoperative adjuvant chemotherapy and endocrine therapy were administered. Four years after chemotherapy, a blood examination showed pancytopenia. Bone marrow examination showed acute promyelocytic leukemia. She was treated with chemotherapy and achieved complete remission. Breast cancer provides long-term survival after treatment. Attention should be paid to the occurrence of TRLin breast cancer surveillance.}, }
@article {pmid30582225, year = {2019}, author = {Bertagnolo, V and Grassilli, S and Volinia, S and Al-Qassab, Y and Brugnoli, F and Vezzali, F and Lambertini, E and Palomba, M and Piubello, Q and Orvieto, E and Natali, C and Piva, R and Croce, CM and Capitani, S}, title = {Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {5}, pages = {708-721}, pmid = {30582225}, issn = {1098-2744}, support = {FIRB RBAP10Z7FS_002//Italian MIUR/International ; IG 170631//Associazione Italiana per la Ricerca sul Cancro/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Proliferation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Stem Cells/metabolism/*pathology ; Phospholipase C beta/genetics/*metabolism ; Prognosis ; Tumor Cells, Cultured ; }, abstract = {Cells in non-invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide-dependent phospholipase C (PLC-β2), known to counteract the effects of hypoxia in low-invasive breast tumor-derived cells. Here, we studied the correlation between PLC-β2 levels and the propensity of non-invasive breast tumor cells to acquire malignant features. Using archival FFPE samples and DCIS-derived cells, we demonstrate that PLC-β2 is up-regulated in DCIS and that its forced down-modulation induces an epithelial-to-mesenchymal shift, expression of the cancer stem cell marker CD133, and the acquisition of invasive properties. The ectopic expression of PLC-β2 in non-transformed and DCIS-derived cells is, to some extent, dependent on the de-regulation of miR-146a, a tumor suppressor miRNA in invasive breast cancer. Interestingly, an inverse relationship between the two molecules, indicative of a role of miR-146a in targeting PLC-β2, was not detected in primary DCIS from patients who developed a second invasive breast neoplasia. This suggests that alterations of the PLC-β2/miR-146a relationship in DCIS may constitute a molecular risk factor for the appearance of new breast lesions. Since neither traditional classification systems nor molecular characterizations are able to predict the malignant potential of DCIS, as is possible for invasive ductal carcinoma (IDC), we propose that the assessment of the PLC-β2/miR-146a levels at diagnosis could be beneficial for identifying whether DCIS patients may have either a low or high propensity for invasive recurrence.}, }
@article {pmid30577784, year = {2018}, author = {Ssemmanda, S and Katagirya, E and Bukirwa, P and Alele, D and Lukande, R and Kalungi, S}, title = {Breast diseases histologically diagnosed at a tertiary facility in Uganda (2005-2014).}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1285}, pmid = {30577784}, issn = {1471-2407}, mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Female ; Fibroadenoma/diagnosis/*epidemiology/pathology ; Humans ; Male ; Risk Factors ; Uganda/epidemiology ; }, abstract = {BACKGROUND: The prevalence and distribution of histologically diagnosed breast disease are not well documented in low income countries, Uganda inclusive. Although the greater majority of breast lesions globally are benign, breast cancer is the most frequently diagnosed cancer all over the world. We aimed at documenting the prevalence of different breast diseases histologically diagnosed at the histopathology laboratory of the Department of Pathology of the Makerere University College of Health Sciences (MakCHS Lab) over a decade (2005-2014). We also describe the demographic characteristics of the patients in Uganda diagnosed with breast disease at the MakCHS Lab during the same period.<br><br>METHODS: This was a 10 year retrospective study of histologically diagnosed breast disease between 2005 and 2014 inclusive at the MakCHS Lab. We extracted information from hard copies of all 2510 histopathology reports retrieved from archives of the Department of Pathology at the MakCHS Lab. 640 records that were either damaged beyond recognition of key details, were duplicated, were implausible or had no conclusive diagnosis made were excluded. Information to be analyzed was then entered into Epidata (version 3.1) on a password protected laptop. Data analysis was done using SPSS software (v16 for Windows × 64).<br><br>RESULTS: From the 1870 patients' records eventually analyzed, breast disease was most diagnosed in female patients (97.1%). The overall mean age for breast disease diagnosis was 33 years (S.D ± 16.46) and median age 26 years (IQR: 20-43). Fibroadenoma (40.1%) was the most diagnosed breast disease overall. We noticed steadily increasing frequency of diagnosis of cancerous breast diseases over the last half of the study period. Invasive ductal carcinoma was the most diagnosed breast cancer (326 cases, 55.6%). A high female to male breast cancer ratio of 48:1 was observed. The highest regional breast cancer proportion was from the Western region of the Country.<br><br>CONCLUSIONS: There is need for more research into the picture of breast disease in the country, covering various demographic characteristics of the country's population for all regions and informing about its incidence rates and prevalence and also the breast cancer risk estimate for benign breast disease.}, }
@article {pmid30570854, year = {2018}, author = {Sunar, V and T Dogan, H and Sarici, F and Ates, O and Akin, S and Baspinar, B and Aksoy, S and Altundag, K}, title = {Association between androgen receptor status and prognosis in triple negative breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {23}, number = {5}, pages = {1325-1330}, pmid = {30570854}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Ductal, Breast/metabolism/*secondary/therapy ; Carcinoma, Lobular/metabolism/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Androgen/*metabolism ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/metabolism/*pathology/therapy ; }, abstract = {PURPOSE: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients.<br><br>METHODS: A total of 84 TNBC patients treated between 2000 - 2015 in Hacettepe University Cancer Institute were included and their medical records were analyzed retrospectively. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with ≥1% nuclear staining were considered AR-positive, while the ones with <1% staining were considered AR-negative. We analyzed the association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC.<br><br>RESULTS: Of the 84 TNBC patients, 25 (29.8%) were AR-positive. The frequency of grade 3 tumors was lower among AR-positive TNBC tumors compared to AR-negative tumors (40 vs 86.4%, p<0.001). In the AR-positive group, invasive ductal carcinoma (IDC) was less prevalent compared to AR-negative group (56 vs 86.4%, p<0.002). However, there were not statistically significant differences between AR positive and negative groups in terms of overall survival (OS) and disease free survival (DFS) (p=0.449, p=0.733, respectively). We found that grade 3 tumors were less frequent in AR-positive TNBC in our study. Nonetheless, we did not detect statistically significant difference in terms of overall survival and disease free survival between AR positive and negative TNBC.<br><br>CONCLUSION: Routine evaluation of AR could contribute to further studies that may enlighten the role of AR targeting therapies in TNBC.}, }
@article {pmid30562218, year = {2019}, author = {Alkhasawneh, A and Nassri, A and John, I}, title = {Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.}, journal = {The American Journal of dermatopathology}, volume = {41}, number = {7}, pages = {502-504}, doi = {10.1097/DAD.0000000000001322}, pmid = {30562218}, issn = {1533-0311}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Dedifferentiation ; Female ; GATA3 Transcription Factor/metabolism ; Humans ; Keratins/metabolism ; Lymphatic Metastasis ; Melanoma/metabolism/*secondary ; Middle Aged ; Neoplasms, Second Primary/metabolism/*pathology ; Skin Neoplasms/metabolism/*pathology/secondary ; }, abstract = {Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.}, }
@article {pmid30558571, year = {2018}, author = {Semango, GP and Charles, RM and Swai, CI and Mremi, A and Amsi, P and Sonda, T and Shao, ER and Mavura, DR and Joosten, LAB and Sauli, E and Nyindo, M}, title = {Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1258}, pmid = {30558571}, issn = {1471-2407}, support = {001//Tanzania Commission for Science and Technology/ ; }, mesh = {Adolescent ; Adult ; Age Factors ; CD4 Lymphocyte Count ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; HIV Infections/*complications/immunology ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; Sarcoma, Kaposi/*epidemiology ; Sex Factors ; Tanzania ; Young Adult ; }, abstract = {BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015.<br><br>METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values ≤10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value ≤5%. All patients' notes were kept confidential as per the Helsinki declaration.<br><br>RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/μl). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p < 0.009). Increased age, above 35 years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p < 0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p < 0.010).<br><br>CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.}, }
@article {pmid30557036, year = {2019}, author = {Dabarian, AL and Mady, C and Barbosa-Ferreira, JM and Ianni, BM and Hotta, VT and Ramires, FJA and Lopes, HF and Buck, PC and Pessoa, FG and Fonseca, KCB and Nogueira, AR and Fernandes, F}, title = {Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels.}, journal = {Canadian journal of physiology and pharmacology}, volume = {97}, number = {2}, pages = {140-145}, doi = {10.1139/cjpp-2018-0349}, pmid = {30557036}, issn = {1205-7541}, mesh = {Adipokines/*blood/metabolism ; Adult ; Autonomic Nervous System/physiopathology ; Cardiomyopathy, Dilated/blood/diagnosis/*metabolism/physiopathology ; Chagas Cardiomyopathy/blood/diagnosis/*metabolism/physiopathology ; Echocardiography, Doppler ; Electrocardiography ; Female ; Heart ; Heart Rate/physiology ; Humans ; Insulin/*blood/metabolism ; Male ; Middle Aged ; }, abstract = {Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 μU/mL) when compared with control (8.0 ± 4.9 μU/mL) and IDC (9.9 ± 5.0 μU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 μg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.}, }
@article {pmid30544169, year = {2019}, author = {Martínez Nicolás, I and Lê Cook, B and Flores, M and Del Olmo Rodriguez, M and Hernández Rodríguez, C and Llamas Sillero, P and Baca-Garcia, E}, title = {The impact of a comprehensive electronic patient portal on the health service use: an interrupted time-series analysis.}, journal = {European journal of public health}, volume = {29}, number = {3}, pages = {413-418}, doi = {10.1093/eurpub/cky257}, pmid = {30544169}, issn = {1464-360X}, mesh = {Ambulatory Care/statistics &amp; numerical data ; Chronic Disease ; Emergency Service, Hospital/statistics &amp; numerical data ; Health Services Research ; Hospitalization/statistics &amp; numerical data ; Humans ; Interrupted Time Series Analysis ; *Patient Portals ; Patient Readmission/statistics &amp; numerical data ; Spain ; *Utilization Review ; }, abstract = {BACKGROUND: There is little empirical research on the potential benefit that electronic patient portals (EPP) can have on the care quality and health outcomes of diverse multi-ethnic international populations. The purpose of this study is to determine the extent to which an EPP was associated with improvements in health service use.<br><br>METHODS: Using a quasi-experimental interrupted time-series approach, we assessed health service use before (April 2012-September 2015) and after (October 2015-December 2016) the implementation of a comprehensive EPP at four hospitals in Madrid, Spain. Primary outcomes were number of outpatient visits, any hospital admission, any 30-day all-cause readmission and any emergency department visit.<br><br>RESULTS: Implementation of the EPP was associated with a significant decline in readmissions. Among patients with chronic heart failure, EPP implementation was associated with a significant decline for all outcome measures, and among patients with COPD, a decline in all outcomes except readmissions. Among patients diagnosed with malignant hematological diseases, no significant changes were identified.<br><br>CONCLUSIONS: EPPs hold promise for reducing hospital readmissions. Certain patient populations with chronic conditions may differentially benefit from portal use depending on their needs for communication with their providers.}, }
@article {pmid30542725, year = {2018}, author = {Shettar, A and Damineni, S and Mukherjee, G and Kondaiah, P}, title = {Gap junction β‑2 expression is negatively associated with the estrogen receptor status in breast cancer tissues and is a regulator of breast tumorigenesis.}, journal = {Oncology reports}, volume = {40}, number = {6}, pages = {3645-3653}, doi = {10.3892/or.2018.6764}, pmid = {30542725}, issn = {1791-2431}, mesh = {Animals ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinogenesis/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Connexins/genetics/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Receptors, Estrogen/*metabolism ; Up-Regulation ; }, abstract = {Gap junction β‑2 gene (GJB2, also known as connexin 26) is a member of the connexin family which forms gap junction channels. Many connexin genes have been considered to be tumor suppressor genes. However, the overexpression of GJB2 has been found to be associated with a poor prognosis in several human cancers. In our previous microarray study, we revealed the overexpression of GJB2 in breast cancer tissues. Hence, in this study, we investigated the expression of GJB2 in human breast cancer and its role in breast cancer cell proliferation and migration. The RT‑qPCR results revealed the upregulation of the GJB2 gene in invasive ductal carcinoma (P<0.001) of the breast. Immunohistochemical analysis revealed an intense cytoplasmic and membrane staining. We observed that the staining for GJB2 was more intense in the majority of the estrogen receptor (ER)‑negative breast cancer tissues compared to the normal breast tissues (P<0.0001). By contrast, the majority of the ER‑positive breast cancer samples exhibited weak to moderate staining; however, this difference was not statistically significant compared to the normal tisues. The knockdown of GJB2 in human breast cancer cell lines using shRNA led to a significant decrease in the proliferative ability and an increase in the migratory ability of breast cancer cells. In addition, the knockdown of GJB‑2 led to a significant reduction in tumor volume and proliferation (as demonstrated by MIB‑1 staining) in orthotopic xenografts in immunocompromised mice. On the whole, the findings of this study indicate that GJB2 may be an important regulator of breast tumorigenesis.}, }
@article {pmid30524164, year = {2018}, author = {Pusina, S}, title = {Correlation of Serum Levels of Urokinase Activation Plasminogen (uPA) and Its Inhibitor (PAI-1) with Hormonal and HER-2 Status in the Early Invasive Breast Cancer.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {72}, number = {5}, pages = {335-340}, pmid = {30524164}, issn = {1986-5961}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*blood/genetics/pathology ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Plasminogen Activator Inhibitor 1/*blood ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*physiology ; Urokinase-Type Plasminogen Activator/*blood ; Young Adult ; }, abstract = {Introduction: Breast cancer is the most common malignant tumor in women. On the list of causes of death immediately after lung cancer. It is a heterogeneous disease, considering the differences in morphological, cytogenetic, molecular, clinical and therapeutic aspects, so that the prognosis in a patient with the same histological grade and pathological status may vary.<br><br>Aim: In this paper we wanted to identify the correlation between the assay of the serum values of uPA-PAI-1 complexes and individual prognostic-predictive parameters, primarily with the status of estrogenic (Er), progesterogenic (PgR) and Her-2 receptors ("human epidermal growth factor).<br><br>Material and methods: The study was conducted at the Clinic for General and Abdominal Surgery, University Clinical Center of Sarajevo (CCUS), from September 2016 to April 2017. The study included 66 patients, ages 18 to 75, in whom by the needle biopsy preoperatively was pathohistologically verified primary invasive breast cancer.<br><br>Results: Two thirds of the sample were classified as invasive ductal carcinoma, similar to the percentage (68.2%) of pT2 size, and almost half in the grade G3. Lymph node status was negative in 54.5% of respondents, and positive in 31.8% of respondents. Most patients had positive estrogenic (83.3%) and progesterone receptors (62.1%). Almost 80% was Her-2 negative. The blood vessel invasion was present in 56.1%, while the neural invasion was present in less than a third of the sample (30.3%). Median values of uPA-PAI-1 complexes were 1.4 (interquartile range 0.9); almost 70% of the sample was negative for the status analysis of uPA-PAI-1 complex (<1).<br><br>Discussion: A statistically significant difference was determined in the mean values of uPA-PAI-1 complexes in subgroups according to menopausal status, tumor size, histological grade, histological type (invasive ductal carcinoma vs. invasive lobular cancer versus invasive ductal carcinoma vs. invasive lobular cancer), status axillary lymph nodes, Ki67 status (as binary variables), invasion of the blood vessels and neural invasion, as well as subgroups according to the status of expression of hormonal (estrogen and progesterone) receptors.<br><br>Conclusion: There is a statistically significant difference in the mean values of the uPA-PAI-1 complex and Her-2 receptor expression. Generally, in perspective, this would be the role played by the uPA/PAI-1 complex in breast cancer, which is that the elevated complex values have a negative prognosis and effect on survival, similar to the negative Her-2 receptor status. Complex uPA/PAI-1 is not a specific serum protein in breast cancer patients and cannot be taken as an individual prognostic-predictive marker for mass pre- or post treatment screening and prediction. Unfortunately, none of the biomarkers are able to independently and fully identify patients of the unknown stage of the disease with better or worse prognosis or to identify cases of more aggressive tumor behavior of the same stage for timely inclusion of adjuvant therapy and reduction of the risk of metastatic disease. The decision on treatment and prognosis should be the result of a combination of all diagnostic, therapeutic, pathohistological and molecular-genetic variables.}, }
@article {pmid30531838, year = {2019}, author = {Pearson, SJ and Roy Sarkar, T and McQueen, CM and Elswood, J and Schmitt, EE and Wall, SW and Scribner, KC and Wyatt, G and Barhoumi, R and Behbod, F and Rijnkels, M and Porter, WW}, title = {ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.}, journal = {Oncogene}, volume = {38}, number = {14}, pages = {2611-2626}, pmid = {30531838}, issn = {1476-5594}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; T32 ES026568/ES/NIEHS NIH HHS/United States ; R01 HD083952/HD/NICHD NIH HHS/United States ; R01 ES025209/ES/NIEHS NIH HHS/United States ; R21 CA190941/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*genetics ; BRCA1 Protein/genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cadherins/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Repair/genetics ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Genomic Instability/genetics ; Homologous Recombination/*genetics ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Phosphorylation/genetics ; Rad51 Recombinase/genetics ; }, abstract = {There is increasing evidence that genomic instability is a prerequisite for cancer progression. Here we show that SIM2s, a member of the bHLH/PAS family of transcription factors, regulates DNA damage repair through enhancement of homologous recombination (HR), and prevents epithelial-mesenchymal transitions (EMT) in an Ataxia-telangiectasia mutated (ATM)-dependent manner. Mechanistically, we found that SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR. Once stabilized, SIM2s interacts with BRCA1 and supports RAD51 recruitment to the site of DNA damage. Loss of SIM2s through the introduction of shSIM2 or the mutation of SIM2s at one of the predicted ATM phosphorylation sites (S115) reduces HR efficiency through disruption of RAD51 recruitment, resulting in genomic instability and induction of EMT. The EMT induced by the mutation of S115 is characterized by a decrease in E-cadherin and an induction of the basal marker, K14, resulting in increased invasion and metastasis. Together, these results identify a novel player in the DNA damage repair pathway and provides a link in ductal carcinoma in situ progression to invasive ductal carcinoma through loss of SIM2s, increased genomic instability, EMT, and metastasis.}, }
@article {pmid30519573, year = {2018}, author = {Son, K and Yu, S and Shin, W and Han, K and Kang, K}, title = {A Simple Guideline to Assess the Characteristics of RNA-Seq Data.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {2906292}, pmid = {30519573}, issn = {2314-6141}, mesh = {Gene Expression ; High-Throughput Nucleotide Sequencing/*statistics &amp; numerical data ; Humans ; *Principal Component Analysis ; RNA/*genetics ; Sequence Analysis, RNA ; Transcriptome/*genetics ; }, abstract = {Next-generation sequencing (NGS) techniques have been used to generate various molecular maps including genomes, epigenomes, and transcriptomes. Transcriptomes from a given cell population can be profiled via RNA-seq. However, there is no simple way to assess the characteristics of RNA-seq data systematically. In this study, we provide a simple method that can intuitively evaluate RNA-seq data using two different principal component analysis (PCA) plots. The gene expression PCA plot provides insights into the association between samples, while the transcript integrity number (TIN) score plot provides a quality map of given RNA-seq data. With this approach, we found that RNA-seq datasets deposited in public repositories often contain a few low-quality RNA-seq data that can lead to misinterpretations. The effect of sampling errors for differentially expressed gene (DEG) analysis was evaluated with ten RNA-seq data from invasive ductal carcinoma tissues and three RNA-seq data from adjacent normal tissues taken from a Korean breast cancer patient. The evaluation demonstrated that sampling errors, which select samples that do not represent a given population, can lead to different interpretations when conducting the DEG analysis. Therefore, the proposed approach can be used to avoid sampling errors prior to RNA-seq data analysis.}, }
@article {pmid30499665, year = {2018}, author = {Okada, K and Moon, HJ and Finney, J and Meier, A and Mure, M}, title = {Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity.}, journal = {Biochemistry}, volume = {57}, number = {51}, pages = {6973-6983}, pmid = {30499665}, issn = {1520-4995}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM110761/GM/NIGMS NIH HHS/United States ; R01 GM113101/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Oxidoreductases/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Binding Sites ; Breast Neoplasms/enzymology ; Cell Line ; Collagen Type IV/metabolism ; Female ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Mutagenesis, Site-Directed ; Proprotein Convertases/antagonists &amp; inhibitors/genetics/metabolism ; Protein Domains ; Protein Processing, Post-Translational ; Protein-Lysine 6-Oxidase/chemistry/genetics/metabolism ; RNA, Small Interfering/genetics ; Serine Endopeptidases/genetics/metabolism ; }, abstract = {Overexpression of lysyl oxidase-like 2 (LOXL2) is associated with several hepatic and vascular fibrotic diseases and tumor progression in some aggressive cancers. Secreted LOXL2 promotes extracellular matrix cross-linking by catalyzing the oxidative deamination of peptidyl lysine. A great deal remains to be learned about the post-translational modifications of LOXL2, including whether such modifications modulate enzymatic and disease-promoting activities; such knowledge would inform the development of potential therapies. We discovered that upon secretion in cell culture, LOXL2 undergoes proteolytic processing of the first two of four scavenger receptor cysteine-rich domains at the N-terminus. A similar pattern of processing was also evident in tissue extracts from an invasive ductal carcinoma patient. Processing occurred at 314Arg-315Phe-316Arg-317Lys↓-318Ala-, implicating proprotein convertases. siRNA-mediated knockdown of proprotein convertases (furin, PACE4, and PC5/6), as well as incubation with their recombinant forms, showed that PACE4 is the major protease that acts on extracellular LOXL2. Unlike LOX, which requires cleavage of its propeptide for catalytic activation, cleavage of LOXL2 was not essential for tropoelastin oxidation or for cross-linking of collagen type IV in vitro. However, in the latter case, processing enhanced the extent of collagen cross-linking ∼2-fold at ≤10 nM LOXL2. These results demonstrate an important difference in the regulatory mechanisms for LOX and LOXL2 catalytic activity. Moreover, they pave the way for further studies of potential differential functions of LOXL2 isoforms in fibrosis and tumor progression.}, }
@article {pmid30470306, year = {2018}, author = {Schmidt, SF and Rohm, M and Herzig, S and Berriel Diaz, M}, title = {Cancer Cachexia: More Than Skeletal Muscle Wasting.}, journal = {Trends in cancer}, volume = {4}, number = {12}, pages = {849-860}, doi = {10.1016/j.trecan.2018.10.001}, pmid = {30470306}, issn = {2405-8025}, mesh = {Antineoplastic Agents/pharmacology/*therapeutic use ; Cachexia/etiology/mortality/*physiopathology/prevention &amp; control ; Combined Modality Therapy/methods ; Humans ; Muscle, Skeletal/physiopathology ; Neoplasms/*complications/drug therapy/mortality/physiopathology ; Nutritional Support/*methods ; Paraneoplastic Syndromes/etiology/mortality/*physiopathology/prevention &amp; control ; Quality of Life ; Treatment Outcome ; }, abstract = {Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.}, }
@article {pmid30423024, year = {2019}, author = {Sokol, ES and Feng, YX and Jin, DX and Basudan, A and Lee, AV and Atkinson, JM and Chen, J and Stephens, PJ and Frampton, GM and Gupta, PB and Ross, JS and Chung, JH and Oesterreich, S and Ali, SM and Hartmaier, RJ}, title = {Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {1}, pages = {115-123}, pmid = {30423024}, issn = {1569-8041}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*secondary ; Carcinoma, Lobular/drug therapy/genetics/*secondary ; Drug Resistance, Neoplasm/*genetics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neurofibromin 1/*genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed.<br><br>Patients and methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes.<br><br>Results: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%).<br><br>Conclusions: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.}, }
@article {pmid30412075, year = {2018}, author = {Lee, SJ and Chung, MS and Shin, SJ and Choi, YY}, title = {Correlation of tumor uptake on breast-specific gamma imaging and fluorodeoxyglucose PET/CT with molecular subtypes of breast cancer.}, journal = {Medicine}, volume = {97}, number = {43}, pages = {e12840}, doi = {10.1097/MD.0000000000012840}, pmid = {30412075}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Female ; Fluorodeoxyglucose F18/*pharmacology ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; Radiopharmaceuticals/pharmacology ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; }, abstract = {Mechanisms of technetium-99m sesta-methoxyisobutylisonitrile (sestamibi) and F-fluorodeoxyglucose (FDG) uptake by tumor are different. The purpose of this study was to investigate the association between the tumor uptake of these 2 tracers in invasive ductal carcinoma and to examine thecorrelation of uptake of each tracer with prognostic factors and tumor molecular subtypes.A total of 96 patients with invasive ductal carcinoma who underwent preoperative breast-specific gamma imaging and FDG positron-emission tomography/computed tomography were retrospectively enrolled. Tumor-to-background ratio (TBR) of sestamibi and maximum standardized uptake value (SUVmax) of FDG were correlated with each other. Each of them was then compared with prognostic factors and molecular subtypes.In all tumors, there was a moderate positive correlation between TBR and SUVmax (r = 0.520, P < .001). Both TBR and SUVmax were significantly correlated with tumor size, incidence of axillary lymph node metastasis, histologic grade, estrogen receptor, progesterone receptor status, and Ki-67.There is a moderate degree of association between TBR of sestamibi and SUVmax of FDG in the invasive breast cancer. Two imaging indexes showed the similar tendency related with prognostic factors and molecular subtypes. While both TBR and SUVmax were significantly different between luminal A and nonluminal A tumors, neither of them had high enough sensitivity or specificity to obviate pathologic and molecular diagnosis.}, }
@article {pmid30409703, year = {2019}, author = {Wolff, G and Taranko, AE and Meln, I and Weinmann, J and Sijmonsma, T and Lerch, S and Heide, D and Billeter, AT and Tews, D and Krunic, D and Fischer-Posovszky, P and Müller-Stich, BP and Herzig, S and Grimm, D and Heikenwälder, M and Kao, WW and Vegiopoulos, A}, title = {Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis.}, journal = {Molecular metabolism}, volume = {19}, number = {}, pages = {97-106}, pmid = {30409703}, issn = {2212-8778}, mesh = {Adipocytes/metabolism ; Adipose Tissue/metabolism ; Adipose Tissue, White/metabolism ; Adiposity/drug effects ; Adult ; Animals ; Diet, High-Fat ; Extracellular Matrix/metabolism ; Female ; Glucose/*metabolism ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat/metabolism ; Liver/metabolism ; Lumican/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/*metabolism ; Proteoglycans/metabolism ; }, abstract = {OBJECTIVE: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.<br><br>METHODS: Whole body ablation of Lumican (Lum-/-) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.<br><br>RESULTS: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.<br><br>CONCLUSIONS: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome.}, }
@article {pmid30409127, year = {2018}, author = {Ye, FG and Xia, C and Ma, D and Lin, PY and Hu, X and Shao, ZM}, title = {Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1085}, pmid = {30409127}, issn = {1471-2407}, support = {MOST2016YFC0900300//Ministry of Science and Technology of the People's Republic of China/ ; 81672601//National Natural Science Foundation of China (CN)/ ; 15410724000//Shanghai Committee of Science and Technology Funds/ ; }, mesh = {Aged ; Axilla/pathology ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Papillary/*epidemiology/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nomograms ; Odds Ratio ; Population Surveillance ; Preoperative Period ; ROC Curve ; Reproducibility of Results ; Risk Factors ; SEER Program ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement.<br><br>METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software.<br><br>RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767).<br><br>CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.}, }
@article {pmid30407355, year = {2018}, author = {Liu, A and Feng, Y and Chen, B and Li, L and Wu, D and Qian, J and Yang, A}, title = {A case report of metastatic breast cancer initially presenting with esophageal dysphagia.}, journal = {Medicine}, volume = {97}, number = {45}, pages = {e13184}, pmid = {30407355}, issn = {1536-5964}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Deglutition Disorders/*etiology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Esophageal Neoplasms/*secondary/therapy ; Esophagectomy/methods ; Esophagus/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tomography, X-Ray Computed ; }, abstract = {RATIONALE: Breast cancer metastasis to the esophagus is uncommon. To our knowledge, the present case is the first report of breast cancer with dysphagia as the initial symptom.<br><br>PATIENT CONCERNS: A 62-year-old woman was admitted to our hospital for progressive dysphagia.<br><br>DIAGNOSES: Endoscopic ultrasound-guided fine needle biopsy of the esophageal lesion found poorly differentiated carcinoma, and surgical resection of the breast nodule revealed invasive ductal carcinoma.<br><br>INTERVENTIONS: The patient underwent an esophagectomy, and the immunohistochemistry of surgical specimen was identified as metastatic breast cancer. Then patient was treated with chemotherapy and hormone therapy.<br><br>OUTCOMES: The patient remained symptom-free during 5 months of follow-up examinations.<br><br>LESSONS: This case indicates that metastatic breast cancer to the esophagus should be considered as a cause of esophageal stricture in older women.}, }
@article {pmid30388104, year = {2018}, author = {Golan, Y and Alhadeff, R and Glaser, F and Ganoth, A and Warshel, A and Assaraf, YG}, title = {Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.}, journal = {PLoS computational biology}, volume = {14}, number = {11}, pages = {e1006503}, pmid = {30388104}, issn = {1553-7358}, support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; R01 AI055926/AI/NIAID NIH HHS/United States ; }, mesh = {Cation Transport Proteins/genetics/*metabolism ; Computational Biology/methods ; Deficiency Diseases/metabolism/therapy ; Homeostasis ; Humans ; *Models, Theoretical ; Monte Carlo Method ; Mutagenesis, Site-Directed ; Permeability ; Zinc/deficiency/*metabolism ; }, abstract = {Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2. Zinc is an essential trace element with 10% of the proteins in the human proteome capable of zinc binding. Thus, zinc deficiency or impairment of zinc homeostasis disrupt key cellular functions. Mammalian zinc transport proceeds via two transporter families: ZnT and ZIP; however, little is known about the zinc permeation pathway through these transporters. As a step towards this end, we herein undertook comprehensive computational analyses employing multiscale techniques, focusing on the human zinc transporter ZnT2 and its bacterial homologue, YiiP. Energy calculations revealed a favorable pathway for zinc translocation via alternating access. We then identified key residues presumably involved in the passage of zinc ions through ZnT2 and YiiP, and functionally validated their role in zinc transport using site-directed mutagenesis of ZnT2 residues. Finally, we use a CG Monte Carlo simulation approach to sample the transition between the inward-facing and the outward-facing states. We present our structural models of the inward- and outward-facing conformations of ZnT2 as a blueprint prototype of the transporter conformations, including the putative permeation pathway and participating residues. The insights gained from this study may facilitate the delineation of the pathways of other zinc transporters, laying the foundations for the molecular basis underlying ion permeation. This may possibly facilitate the development of therapeutic interventions in pathological states associated with zinc deficiency and other disorders based on loss-of-function mutations in solute carriers.}, }
@article {pmid30385093, year = {2019}, author = {Shee, K and Muller, KE and Marotti, J and Miller, TW and Wells, WA and Tsongalis, GJ}, title = {Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing.}, journal = {The American journal of pathology}, volume = {189}, number = {5}, pages = {956-965}, pmid = {30385093}, issn = {1525-2191}, support = {F30 CA216966/CA/NCI NIH HHS/United States ; R01 CA200994/CA/NCI NIH HHS/United States ; R01 CA211869/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; Humans ; Neoplasm Invasiveness ; *Precision Medicine ; Prognosis ; }, abstract = {Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiotherapy because of a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence that suggests that DCIS can be stratified according to risk of recurrence or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Recent technological advancements have enabled an era of precision medicine, where DCIS can be molecularly analyzed by tools, such as next-generation DNA and RNA sequencing, to identify molecular biomarkers for risk stratification. These findings have led to the development of tools such as the Oncotype DX Breast DCIS Score, a gene expression-based assay with the potential to prevent overtreatment in low-risk disease.}, }
@article {pmid30375263, year = {2018}, author = {Talei, A and Tahmasebi, S and Akrami, M and Zangouri, V and Rezaianzadeh, A and Arasteh, P and Eghbali, T and Hosseini, S}, title = {The Shiraz Breast Cancer Registry (SBCR): study design and primary reports.}, journal = {Personalized medicine}, volume = {15}, number = {6}, pages = {471-479}, doi = {10.2217/pme-2018-0047}, pmid = {30375263}, issn = {1744-828X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology ; Female ; Humans ; Iran/epidemiology ; Male ; Middle Aged ; Neoplasm Staging ; Preliminary Data ; Prognosis ; Registries ; Research Design ; Young Adult ; }, abstract = {AIM: This is a description of the largest breast cancer (BC) registry in Iran, termed the Shiraz Breast Cancer Registry (SBCR).<br><br>METHODS: Data on baseline and clinical characteristics, socioeconomic status, imaging, physical examination, histopathology, treatment and prognosis have been recorded for each individual.<br><br>RESULTS: Overall, 5937 were included in the report. Mean age of first presentation was 49.05 ± 11.69 years. Mean tumor size was 2.78 ± 1.76 cm. Most patients had stage 2 (46.9%) and 3 (25.5%) BCs, respectively. Most common type of BC was invasive ductal carcinoma (83.3%), followed by medullary carcinoma (3.8%). Overall, 12.9% were triple negative (HER2-, ER- and PR-).<br><br>CONCLUSION: The study provides an overview on the status of BC's in Iran and a wide opportunity for future studies.}, }
@article {pmid30372658, year = {2019}, author = {Steger, M and Bermejo-Jambrina, M and Yordanov, T and Wagener, J and Brakhage, AA and Pittl, V and Huber, LA and Haas, H and Lass-Flörl, C and Posch, W and Wilflingseder, D}, title = {β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells.}, journal = {Virulence}, volume = {10}, number = {1}, pages = {957-969}, doi = {10.1080/21505594.2018.1528843}, pmid = {30372658}, issn = {2150-5608}, mesh = {Aspergillosis/microbiology ; Aspergillus fumigatus/*chemistry/genetics/*immunology ; *Complement Activation ; Cytokines/immunology ; Dendritic Cells/*immunology ; Echinocandins/therapeutic use ; Humans ; Immunity, Innate ; Mutation ; Spores, Fungal/immunology ; THP-1 Cells ; *beta-Glucans ; }, abstract = {Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOnrep under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1tetOnrep mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1tetOnrep induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1tetOnrep-mediated induction of an inflammatory cytokine profile.Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms.Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal-regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.}, }
@article {pmid30371651, year = {2018}, author = {Drucis, K and Brzeziński, M and Gniadek, K}, title = {[Synchronous gastrointestinal stromal tumor of stomach and invasive ductal carcinoma of both breasts].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {45}, number = {268}, pages = {161-163}, pmid = {30371651}, issn = {1426-9686}, mesh = {Breast Neoplasms/*complications/diagnostic imaging/surgery ; Carcinoma, Ductal/*complications/diagnostic imaging/surgery ; Female ; Gastrointestinal Stromal Tumors/*complications/diagnostic imaging/surgery ; Humans ; Mastectomy ; Middle Aged ; Stomach/diagnostic imaging/surgery ; Stomach Neoplasms/*complications/diagnostic imaging/surgery ; }, abstract = {Gastrointestinal stromal tumor (GIST), despite the fact that it accounts for less than 5% of all sarcomas, is the most common mesenchymal tumor of the alimentary canal. Synchronous and metachronous stromal tumors are very rare findings. Only a few such cases can be found in the literature, and yet most of them is connected with Von Recklinghausen's disease or Carney's triad in which it is proved a much higher frequency of occurrence of this kind of tumors.<br><br>CASE REPORT: We present a case of 64 years old women, who was diagnosed with invasive ductal carcinoma of both breast due to screening mammography. Patent was qualified to bilateral mastectomy. Perioperative computer tomography scan revealed an additional pathological abnormality situated beyond stomach light, which after resection and immunohistochemistry was found to be a gastrointestinal stromal tumor. This case emphasize the problem of synchronous stromal tumors, the detection of which is often difficult due to nonspecific symptoms. Despite the fact that the most common localization of coexisting tumors is the digestive tract, one should remember about the possibility of occurrence in less frequent locations such as the breast.}, }
@article {pmid30362328, year = {2018}, author = {Abood, RA}, title = {Breast Cancer in Basra Oncology Center: A Clinico- Epidemiological Analysis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {19}, number = {10}, pages = {2943-2946}, pmid = {30362328}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Iraq/epidemiology ; Male ; Middle Aged ; Neoplasm Staging/methods ; Retrospective Studies ; Young Adult ; }, abstract = {Background: Breast cancer is the most common cancer affecting women, and the leading cause of cancer-related deaths. Objective: This study was performed to evaluate clinico-epidemiological features of breast cancer from Iraq during a five-year period. Methodology: This is a retrospective descriptive study. Medical notes and histopathological reports of patients with confirmed diagnosis of breast cancer between January 2011 and December 2015 were reviewed for age, gender, site, laterality, histopathological type, grade of differentiation and TNM stage at diagnosis. Results: A total of 1,000 patients were included in the study. Mean age at diagnosis was 50 years (range 22-85 years), and females constituted 99.2% of cases. Most cases (98.7%) were unilateral and most common (85.5%) histological subtype was invasive ductal carcinoma. Majority of the cases (58%) were moderately differentiated (grade II), wherein 45% belonged to stage II in TNM system, and nearly half (49%) of patients had locally advanced or metastatic cancer. Conclusion: Breast cancer presents at least a decade earlier and at a more advanced stage in Iraqi women when compared to the Western World. Steps for early detection are essential for initiation of prompt therapy and reduction of mortality.}, }
@article {pmid30350269, year = {2019}, author = {Jerevall, PL and Brock, J and Palazzo, J and Wieczorek, T and Misialek, M and Guidi, AJ and Wu, Y and Erlander, MG and Zhang, Y and Schnabel, CA and Goss, PE and Horick, N and Sgroi, DC}, title = {Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.}, journal = {Breast cancer research and treatment}, volume = {173}, number = {2}, pages = {375-383}, doi = {10.1007/s10549-018-5013-6}, pmid = {30350269}, issn = {1573-7217}, mesh = {Adult ; Age Factors ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/epidemiology ; Prognosis ; Prospective Studies ; Risk Assessment/methods ; Risk Factors ; Tumor Burden ; }, abstract = {PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients.<br><br>METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed.<br><br>RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk.<br><br>CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.}, }
@article {pmid30339213, year = {2019}, author = {Jacob, T and Bracha, J}, title = {Identification of Signs and Symptoms of Axillary Web Syndrome and Breast Seroma During a Course of Physical Therapy 7 Months After Lumpectomy: A Case Report.}, journal = {Physical therapy}, volume = {99}, number = {2}, pages = {229-239}, doi = {10.1093/ptj/pzy110}, pmid = {30339213}, issn = {1538-6724}, mesh = {Aged ; Axilla/*physiopathology ; Female ; Humans ; Lymphatic Diseases/etiology/*therapy ; Lymphedema/*therapy ; Mastectomy/*adverse effects ; *Physical Therapy Modalities ; Postoperative Complications/etiology ; Seroma/etiology/*therapy ; Syndrome ; }, abstract = {Background and Purpose: Axillary web syndrome (AWS) and seroma are common and function-limiting side effects following treatments for breast cancer. Studies of AWS and seroma are rare, and there are no guidelines for physical therapy in these cases.<br><br>Case Description: After left breast lumpectomy due to invasive ductal carcinoma, a 65-year-old female patient underwent intraoperative radiation therapy and whole breast radiation. Seven months later, during treatment for breast swelling, AWS and breast seroma were identified by a physical therapist certified in lymphedema treatment. Treatment goals were to reduce breast swelling and pain and to improve shoulder movements. Interventions included manual lymph drainage, left arm stretching, and instruction about self-lymphatic-drainage and stretching exercise. Also, a compression bra was ordered, and continued daily activities and physical activity were recommended.<br><br>Outcomes: Improvement in shoulder movement, breast swelling, and pain.<br><br>Discussion: Because evidence for treatment guidelines following treatments for breast cancer is lacking, close follow-up for treatment-related complications is recommended. Management should be chosen according to signs and symptoms. Realistic expectations can reduce patient frustration and improve coping strategies and compliance with self-treatment demands. Clinical studies to support these conclusions are required.}, }
@article {pmid30332671, year = {2019}, author = {Kitamura, M and Nakayama, T and Mukaisho, KI and Mori, T and Umeda, T and Moritani, S and Kushima, R and Tani, M and Sugihara, H}, title = {Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {86}, number = {2-3}, pages = {92-101}, doi = {10.1159/000492833}, pmid = {30332671}, issn = {1423-0291}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Comparative Genomic Hybridization ; *DNA Copy Number Variations ; *Disease Progression ; Female ; GATA3 Transcription Factor/genetics ; Humans ; Middle Aged ; Paraffin Embedding ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors.<br><br>METHODS: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering.<br><br>RESULTS: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters.<br><br>CONCLUSION: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.}, }
@article {pmid30325954, year = {2018}, author = {Dhage, S and Ernlund, A and Ruggles, K and Axelrod, D and Berman, R and Roses, D and Schneider, RJ}, title = {A genomic ruler to assess oncogenic transition between breast tumor and stroma.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205602}, pmid = {30325954}, issn = {1932-6203}, support = {T32 CA009161/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/surgery ; Cell Transformation, Neoplastic/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genomics ; Humans ; Mastectomy ; Microarray Analysis ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; RNA, Messenger/metabolism ; Stromal Cells/*metabolism/pathology ; }, abstract = {BACKGROUND: Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary. We therefore investigated the extent to which breast tumors alter stromal gene expression in three dimensions in women undergoing mastectomy with the intent of providing a genomic determination for development of future risk of recurrence criteria, and to inform the need for adjuvant full-breast irradiation.<br><br>METHODS AND FINDINGS: Genome-wide gene expression changes were determined in histopathologically normal breast tissue in 33 women undergoing mastectomy for stage II and III primary invasive ductal carcinoma at serial distances in three dimensions from the tumor. Gene expression was determined by genome-wide mRNA analysis and subjected to metagene mRNA characterization. Tumor-like gene expression signatures in stroma were identified that surprisingly transitioned to a plastic, normalizing homeostatic signature with distance from tumor. Stroma closest to tumor displayed a pronounced tumor-like signature enriched in cancer-promoting pathways involved in disruption of basement membrane, cell migration and invasion, WNT signaling and angiogenesis. By 2 cm from tumor in all dimensions, stromal tissues were in transition, displaying homeostatic and tumor suppressing gene activity, while also expressing cancer supporting pathways.<br><br>CONCLUSIONS: The dynamics of gene expression in the post-tumor breast stroma likely co-determines disease outcome: reversion to normality or transition to transformation in morphologically normal tissue. Our stromal genomic signature may be important for personalizing surgical and adjuvant therapeutic decisions and risk of recurrence.}, }
@article {pmid30306389, year = {2018}, author = {DeVaux, RS and Herschkowitz, JI}, title = {Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {23}, number = {4}, pages = {223-235}, pmid = {30306389}, issn = {1573-7039}, mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA/*genetics ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; }, abstract = {Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment. Interrogating the transcriptome alone has yet to define clear functional determinants of progression from DCIS to IDC. Epigenetic changes, critical for imprinting and tissue specific development, in the incorrect context can lead to global signaling rewiring driving pathological phenotypes. Epigenetic signaling pathways, and the molecular players that interpret and sustain their signals, are critical to understanding the underlying pathology of breast cancer progression. The types of epigenetic changes, as well as the molecular players, are expanding. In addition to DNA methylation, histone modifications, and chromatin remodeling, we must also consider enhancers as well as the growing field of noncoding RNAs. Herein we will review the epigenetic interactions that have been uncovered in early stage lesions that impact breast cancer progression, and how these players may be utilized as biomarkers to mitigate overdiagnosis and overtreatment.}, }
@article {pmid30303137, year = {2018}, author = {Jafarian, AH and Tasbandi, A and Gilan, H and Sheikhi, M and Roshan, NM}, title = {Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {61}, number = {4}, pages = {500-504}, doi = {10.4103/IJPM.IJPM_67_18}, pmid = {30303137}, issn = {0974-5130}, mesh = {Adult ; Aged ; CD4 Antigens/*analysis ; CD8 Antigens/*analysis ; Carcinoma, Ductal, Breast/*immunology/mortality/pathology ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Ki-1 Antigen/*analysis ; Middle Aged ; Prognosis ; Triple Negative Breast Neoplasms/*immunology/mortality/pathology ; }, abstract = {Background: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors.<br><br>Materials and Methods: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels.<br><br>Results: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes.<br><br>Conclusion: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.}, }
@article {pmid30290054, year = {2018}, author = {Gaowa, S and Futamura, M and Tsuneki, M and Kamino, H and Tajima, JY and Mori, R and Arakawa, H and Yoshida, K}, title = {Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor suppressor in human breast cancer.}, journal = {Cancer science}, volume = {109}, number = {12}, pages = {3910-3920}, pmid = {30290054}, issn = {1349-7006}, support = {15ck0106006 h0002 (to HA)//AMED/ ; H26-practical-general-001 (to HA)//Ministry of Health, Labour and Welfare for the Practical Research for Innovative Cancer/ ; 23659178 (to HA)//KAKENIHI/ ; 24240117 (to HA)//KAKENIHI/ ; 17K10542 (to MF)//KAKENIHI/ ; 25670169 (to HA)//KAKENIHI/ ; 29-E-1 (to HA), 30-A-3 (to HA)//The National Cancer Center Research and Development Fund/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Caspases/metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; DNA Methylation ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Mitochondria/metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Mutation ; Promoter Regions, Genetic ; Tumor Suppressor Protein p53/*genetics/*metabolism ; }, abstract = {Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA; P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in 6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%). Interestingly, all tumors derived from the 12 patients with Mieap promoter methylation or p53 mutations pathologically exhibited more aggressive and malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway resulted in significantly shorter disease-free survival (DFS) (P = 0.021), although p53 status is more prognostic in DFS than Mieap promoter methylation. These results indicate that p53/Mieap-regulated MQC has a critical role in tumor suppression in breast cancer, possibly in part through mitochondrial apoptotic pathway.}, }
@article {pmid30287681, year = {2018}, author = {Ng, CS and Sinha, A and Aniweh, Y and Nah, Q and Babu, IR and Gu, C and Chionh, YH and Dedon, PC and Preiser, PR}, title = {tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum.}, journal = {Molecular systems biology}, volume = {14}, number = {10}, pages = {e8009}, pmid = {30287681}, issn = {1744-4292}, mesh = {Codon ; Epigenesis, Genetic ; Erythrocytes ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Humans ; Plasmodium falciparum/genetics/*physiology ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Proteomics/methods ; Protozoan Proteins/*genetics/*metabolism ; RNA, Transfer/*metabolism ; }, abstract = {Among components of the translational machinery, ribonucleoside modifications on tRNAs are emerging as critical regulators of cell physiology and stress response. Here, we demonstrate highly coordinated behavior of the repertoire of tRNA modifications of Plasmodium falciparum throughout the intra-erythrocytic developmental cycle (IDC). We observed both a synchronized increase in 22 of 28 modifications from ring to trophozoite stage, consistent with tRNA maturation during translational up-regulation, and asynchronous changes in six modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed that up- and down-regulated proteins in late but not early stages have a marked codon bias that directly correlates with parallel changes in tRNA modifications and enhanced translational efficiency. We thus propose a model in which tRNA modifications modulate the abundance of stage-specific proteins by enhancing translation efficiency of codon-biased transcripts for critical genes. These findings reveal novel epitranscriptomic and translational control mechanisms in the development and pathogenesis of Plasmodium parasites.}, }
@article {pmid30287091, year = {2018}, author = {Schumacher, D and Morgenstern, J and Oguchi, Y and Volk, N and Kopf, S and Groener, JB and Nawroth, PP and Fleming, T and Freichel, M}, title = {Compensatory mechanisms for methylglyoxal detoxification in experimental &amp; clinical diabetes.}, journal = {Molecular metabolism}, volume = {18}, number = {}, pages = {143-152}, pmid = {30287091}, issn = {2212-8778}, mesh = {Aged ; Aldo-Keto Reductases/metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Female ; Glycation End Products, Advanced/metabolism ; Humans ; Kidney/metabolism ; Lactoylglutathione Lyase/genetics/metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pyruvaldehyde/*metabolism ; }, abstract = {OBJECTIVES: The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown.<br><br>METHODS: CRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1-/-) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions.<br><br>RESULTS: Glo1-/- mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1-/- mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes.<br><br>CONCLUSIONS: These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.}, }
@article {pmid30276443, year = {2019}, author = {Fortis, SP and Vaxevanis, CK and Mahaira, LG and Sofopoulos, M and Sotiriadou, NN and Dinou, A and Arnogiannaki, N and Stavropoulos-Giokas, C and Thanos, D and Baxevanis, CN and Perez, SA}, title = {Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {68}, number = {1}, pages = {57-70}, doi = {10.1007/s00262-018-2252-7}, pmid = {30276443}, issn = {1432-0851}, support = {Grant GER_1968 (ISPEBREAST)//GSTR/ ; Donation//Haegeman-Goossens family/ ; }, mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/classification/*genetics/immunology ; Cytokines/blood ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Leukocytes, Mononuclear/metabolism ; MicroRNAs/blood/*genetics ; Prognosis ; }, abstract = {Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy. These miRNAs, known to be involved in both tumor cell progression and immune pathways regulation, were analyzed in relation to circulating cytokines, tumor immune-cell infiltration and established prognostic clinicopathological characteristics. We have identified three different clusters, with overall low (C1), moderate (C2) or high (C3) expression levels of these six circulating miRNAs, which define three distinct groups of non-metastatic BCa patients characterized by different clinicopathological and immune-related characteristics, with possibly different clinical outcomes. Our data provide the proof-of-principle to support the notion that, up- or down-regulation of the same circulating miRNA may reflect different prognosis in BCa. Nonetheless, the prognostic and/or predictive potential of these three "signatures" needs to be further evaluated in larger cohorts of BCa patients with an, at least, 5-year clinical follow-up.}, }
@article {pmid30273605, year = {2019}, author = {Hannafon, BN and Ding, WQ}, title = {Functional Role of miRNAs in the Progression of Breast Ductal Carcinoma in Situ.}, journal = {The American journal of pathology}, volume = {189}, number = {5}, pages = {966-974}, pmid = {30273605}, issn = {1525-2191}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {miRNAs are small RNAs that influence gene expression by targeting mRNAs. Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the preinvasive stage, and these events include changes in the expression of miRNAs. Aberrant expression of miRNAs can influence specific oncogenic or tumor-suppressive pathways required for breast cancer progression. miRNAs in DCIS have been shown to influence hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor β signaling, maintenance of cancer stem cells, and modulation of the extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those found in exosomes, may promote invasive progression by modifying the tumor microenvironment. Here, we review the miRNAs that have been identified in DCIS and how they may contribute to the progression to invasive disease. We also touch on the current state of miRNA therapy development, including the current challenges, and discuss the key future perspectives for research into miRNA function for the purpose of miRNA therapy development for DCIS.}, }
@article {pmid30253811, year = {2018}, author = {Abu-Sbeih, H and Ali, FS and Luo, W and Qiao, W and Raju, GS and Wang, Y}, title = {Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis.}, journal = {Journal for immunotherapy of cancer}, volume = {6}, number = {1}, pages = {95}, pmid = {30253811}, issn = {2051-1426}, mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological/*adverse effects/therapeutic use ; Biomarkers ; Biopsy ; Colitis/*diagnosis/*etiology ; Comorbidity ; Disease Management ; *Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*complications/drug therapy/immunology ; Odds Ratio ; Retrospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes.<br><br>METHODS: Our study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2 mm, larger than 1 cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes.<br><br>RESULTS: A total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60 years. Median time from ICPI initiation to IDC was 7 weeks. Fifty-three percent had grade 3-4 diarrhea, and 32% grade 3-4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P = 0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7 days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7 days of IDC onset (P = 0.026 and P = 0.053, respectively). Patients who underwent endoscopy > 30 days of symptom onset required longer duration of steroids (P = 0.02), had more recurrent symptoms (P < 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy ≤30 days (P = 0.03). High-risk features were associated with more frequent (P = 0.03) and longer duration (P = 0.02) hospitalization and infliximab/vedolizumab requirement (P < 0.01). Patients with active histological inflammation had more recurrence (P < 0.01) and repeat endoscopy (P < 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00-1.01; P < 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68-9.01; P < 0.01).<br><br>CONCLUSION: High risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms.}, }
@article {pmid30247211, year = {2018}, author = {Cai, M and Feng, G and Zhang, G}, title = {A Case of Radioactivity Concentrated in Orbital Implant in 99mTc-MDP Bone Scan and SPECT/CT.}, journal = {Clinical nuclear medicine}, volume = {43}, number = {12}, pages = {e453-e454}, doi = {10.1097/RLU.0000000000002277}, pmid = {30247211}, issn = {1536-0229}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Orbital Implants/*adverse effects ; Orbital Neoplasms/*diagnostic imaging/secondary ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; Technetium Tc 99m Medronate ; }, abstract = {A 27-year-old woman, who has received a hydroxyapatite orbital implant in the right eye due to a trauma 6 years ago, was newly diagnosis with left breast invasive ductal carcinoma. Tc-MDP bone scan showed an increased radiotracer accumulation in the right orbit and SPECT/CT confirmed the focal accumulation at the site of the implant, without any sign of local malignant lesions or orbital infection. Radionuclide imaging could provide certain useful information in diagnosing or differential diagnosing orbital disease.}, }
@article {pmid30236106, year = {2018}, author = {Schultz, S and Bartsch, H and Sotlar, K and Petat-Dutter, K and Bonin, M and Kahlert, S and Harbeck, N and Vogel, U and Seeger, H and Fehm, T and Neubauer, HJ}, title = {Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers.}, journal = {BMC medical genomics}, volume = {11}, number = {1}, pages = {80}, pmid = {30236106}, issn = {1755-8794}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Formaldehyde/chemistry ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Paraffin Embedding ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: The transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS that progress to IBC. Here, we describe a transcriptomic profiling analysis of matched formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual breast tumours, containing both tumour compartments. The study was performed to validate progression-associated transcripts detected in an earlier gene profiling project using fresh frozen breast cancer tissue. In addition, FFPE tissues from patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts characterizing DCIS with a high or low risk of progressing to IBC.<br><br>METHODS: Fifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL technology and used for expression validation by qPCR. Differential expression was independently validated using further 25 laser microdissected DCIS/IBC sample pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were investigated for expression of candidate transcripts using qPCR.<br><br>RESULTS: Multiple statistical calculation methods revealed 1784 mRNAs which are differentially expressed between DCIS and IBC (P < 0.05), of which 124 have also been identified in the gene profiling project using fresh frozen breast cancer tissue. Nine mRNAs that had been selected from the gene list obtained using fresh frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1, SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from the same 15 microdissected specimens and the 25 independent tissue samples by qPCR. All selected transcripts were also detected in tumour cells from pDCIS. Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of DCIS/IBC mixed tumours.<br><br>CONCLUSION: We confirm differential expression of progression-associated transcripts in FFPE breast cancer samples which might mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure DCIS with a high risk developing IDC.}, }
@article {pmid30227836, year = {2018}, author = {Jouali, F and Marchoudi, N and Talbi, S and Bilal, B and El Khasmi, M and Rhaissi, H and Fekkak, J}, title = {Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {900}, pmid = {30227836}, issn = {1471-2407}, mesh = {Adult ; Aged ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Exons/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Morocco/epidemiology ; Oncogene Protein v-akt/*genetics ; PTEN Phosphohydrolase/*genetics ; Retrospective Studies ; Signal Transduction/genetics ; Triple Negative Breast Neoplasms/epidemiology/*genetics/pathology ; }, abstract = {BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.<br><br>METHODS: We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.<br><br>RESULTS: All patients were female with a median age of 46 years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.<br><br>CONCLUSION: The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.}, }
@article {pmid30208271, year = {2018}, author = {Nuñez, NN and Khuu, C and Babu, CS and Bertolani, SJ and Rajavel, AN and Spear, JE and Armas, JA and Wright, JD and Siegel, JB and Lim, C and David, SS}, title = {The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn2+ Ligands and Roles in Damage Recognition and Repair.}, journal = {Journal of the American Chemical Society}, volume = {140}, number = {41}, pages = {13260-13271}, pmid = {30208271}, issn = {1520-5126}, support = {R01 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Base Sequence ; Binding Sites ; Cysteine/chemistry ; DNA Glycosylases/chemistry/genetics/*metabolism ; Geobacillus stearothermophilus/enzymology ; Humans ; Ligands ; Mice ; Mutation ; Protein Binding ; Sequence Alignment ; Zinc/*metabolism ; }, abstract = {The DNA base excision repair (BER) glycosylase MUTYH prevents DNA mutations by catalyzing adenine (A) excision from inappropriately formed 8-oxoguanine (8-oxoG):A mismatches. The importance of this mutation suppression activity in tumor suppressor genes is underscored by the association of inherited variants of MUTYH with colorectal polyposis in a hereditary colorectal cancer syndrome known as MUTYH-associated polyposis, or MAP. Many of the MAP variants encompass amino acid changes that occur at positions surrounding the two-metal cofactor-binding sites of MUTYH. One of these cofactors, found in nearly all MUTYH orthologs, is a [4Fe-4S]2+ cluster coordinated by four Cys residues located in the N-terminal catalytic domain. We recently uncovered a second functionally relevant metal cofactor site present only in higher eukaryotic MUTYH orthologs: a Zn2+ ion coordinated by three Cys residues located within the extended interdomain connector (IDC) region of MUTYH that connects the N-terminal adenine excision and C-terminal 8-oxoG recognition domains. In this work, we identified a candidate for the fourth Zn2+ coordinating ligand using a combination of bioinformatics and computational modeling. In addition, using in vitro enzyme activity assays, fluorescence polarization DNA binding assays, circular dichroism spectroscopy, and cell-based rifampicin resistance assays, the functional impact of reduced Zn2+ chelation was evaluated. Taken together, these results illustrate the critical role that the "Zn2+ linchpin motif" plays in MUTYH repair activity by providing for proper engagement of the functional domains on the 8-oxoG:A mismatch required for base excision catalysis. The functional importance of the Zn2+ linchpin also suggests that adjacent MAP variants or exposure to environmental chemicals may compromise Zn2+ coordination, and ability of MUTYH to prevent disease.}, }
@article {pmid30185420, year = {2019}, author = {Lee, JY and Schizas, M and Geyer, FC and Selenica, P and Piscuoglio, S and Sakr, RA and Ng, CKY and Carniello, JVS and Towers, R and Giri, DD and de Andrade, VP and Papanastasiou, AD and Viale, A and Harris, RS and Solit, DB and Weigelt, B and Reis-Filho, JS and King, TA}, title = {Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {2}, pages = {674-686}, pmid = {30185420}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Breast Carcinoma In Situ/*genetics/*pathology ; Carcinoma, Lobular/*genetics/*pathology ; Clonal Evolution/*genetics ; Disease Progression ; *Genetic Heterogeneity ; *Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neoplasm Metastasis ; Neoplasm Staging ; Tumor Burden ; Whole Exome Sequencing ; }, abstract = {PURPOSE: Lobular carcinoma in situ (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.Experimental Design: We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas in situ (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.<br><br>RESULTS: WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with CDH1 mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.<br><br>CONCLUSIONS: Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions.}, }
@article {pmid30185184, year = {2018}, author = {Du, JJ and Chen, YF and Peng, Y and Li, XJ and Ma, W}, title = {Calcification of the intervertebral disc and ossification of posterior longitudinal ligament in children.}, journal = {BMC musculoskeletal disorders}, volume = {19}, number = {1}, pages = {316}, pmid = {30185184}, issn = {1471-2474}, support = {81501929//National Natural Science Foundation of China/ ; No. Z161100000116057//Beijing Municipal Science and Technology Commission/ ; }, mesh = {Adolescent ; Calcinosis/*complications/*diagnostic imaging/therapy ; Cervical Vertebrae/*diagnostic imaging ; Child ; Conservative Treatment ; Humans ; Male ; Neck Pain/diagnostic imaging/etiology/therapy ; Ossification of Posterior Longitudinal Ligament/*complications/*diagnostic imaging/therapy ; }, abstract = {BACKGROUND: IDC in children, first reported by Baron in 1924, is very rare. OPLL of the cervical spine mainly affect people ages 50-70 years. The coexistence of IDC and OPLL in children is very rare, only six cases with 3 to 24 months' follow-up were reported to date.<br><br>CASE PRESENTATION: A 6-year-old boy presented with complains of neck pain at July 2007. The boy was treated by conservative treatment and observed up for 9 years. Neck pain greatly improved after a one-month conservative treatment and never recur. Laboratory tests revealed elevated ESR and CRP at admission and found nothing abnormal at 19-month and 9-year follow-up. Computed tomography and magnetic resonance imaging revealed IDC at C2/3, C3/4 and OPLL at C3/4 at admission and found minor calcification at C2/3 remained but calcification at C3/4 and OPLL at C3/4 completely disappeared at 19-month and 9-year follow-up. Nineteen months after initial diagnosis, restoration of T2-weighted signal intensity of C2/3 and C3/4 discs was observed through MRI. Loss of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal intensity of C3/4 disc was observed at 9-year follow-up.<br><br>CONCLUSIONS: IDC with OPLL in children is very rare. Conservative treatments are recommended with affirmative short-term and long-term clinical effects. More intensive observation with long-term follow-ups may be needed to warrant the clinical effects.}, }
@article {pmid30183588, year = {2018}, author = {Abdalla, AS and Lazarevska, A and Omer, MM and Tan, E and Asaad, A and Sathananthan, S}, title = {Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding During Chemotherapy: A Case Report and Literature Review.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {113}, number = {4}, pages = {564-570}, doi = {10.21614/chirurgia.113.4.564}, pmid = {30183588}, issn = {1221-9118}, mesh = {Antineoplastic Agents/*adverse effects ; Breast Neoplasms/complications/drug therapy/*secondary ; Female ; Humans ; Uterine Cervical Neoplasms/complications/*secondary ; Uterine Hemorrhage/chemically induced/*etiology ; }, abstract = {The most common sites of invasive breast cancer metastasis are the lungs, liver, bones and brain. Less frequent sites include the gastrointestinal tract, pancreas, spleen, thyroid, adrenals, kidneys, heart and female genital tract. The uterus is reported as a rare site for metastasis, and even more so for an isolated metastasis. Other sites of extra-genital sources for uterine metastases include the colon, stomach, pancreas, gallbladder, lung, cutaneous melanoma, urinary bladder and thyroid. The rarity of breast cancer metastasis to the uterine cervix could be explained by the fact that the cervix has a small blood supply and an afferent lymph drainage system alone. It is rare to diagnose a cervical metastasis prior to eliciting the primary breast disease. Invasive lobular carcinoma metastasises to the female reproductive system more frequently than invasive ductal carcinoma. This paper presents a case of breast cancer metastasis to the cervix.}, }
@article {pmid30171046, year = {2019}, author = {Hess, J and Unger, K and Maihoefer, C and Schüttrumpf, L and Wintergerst, L and Heider, T and Weber, P and Marschner, S and Braselmann, H and Samaga, D and Kuger, S and Pflugradt, U and Baumeister, P and Walch, A and Woischke, C and Kirchner, T and Werner, M and Werner, K and Baumann, M and Budach, V and Combs, SE and Debus, J and Grosu, AL and Krause, M and Linge, A and Rödel, C and Stuschke, M and Zips, D and Zitzelsberger, H and Ganswindt, U and Henke, M and Belka, C}, title = {A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {5}, pages = {1505-1516}, doi = {10.1158/1078-0432.CCR-18-0776}, pmid = {30171046}, issn = {1557-3265}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; *Biomarkers, Tumor ; Female ; Head and Neck Neoplasms/*etiology/*mortality/pathology/therapy ; Humans ; Kaplan-Meier Estimate ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Papillomaviridae ; Papillomavirus Infections/complications ; Prognosis ; Proportional Hazards Models ; *Transcriptome ; Treatment Outcome ; }, abstract = {PURPOSE: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.<br><br>EXPERIMENTAL DESIGN: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA-mRNA target network was generated and analyzed.<br><br>RESULTS: For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98-9.88, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40-12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50-6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65-6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88-13.92, P < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001).<br><br>CONCLUSIONS: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.See related commentary by Clump et al., p. 1441.}, }
@article {pmid30149270, year = {2018}, author = {Yirmiya, K and Djalovski, A and Motsan, S and Zagoory-Sharon, O and Feldman, R}, title = {Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth.}, journal = {Psychoneuroendocrinology}, volume = {98}, number = {}, pages = {153-160}, doi = {10.1016/j.psyneuen.2018.08.016}, pmid = {30149270}, issn = {1873-3360}, mesh = {Adolescent ; Adult ; Adverse Childhood Experiences ; Anxiety/*etiology/metabolism/psychology ; Biomarkers/blood ; Child ; Female ; Humans ; Hydrocortisone/analysis ; Hypothalamo-Hypophyseal System ; Immunity, Innate/physiology ; Immunoglobulin A, Secretory ; Male ; Mother-Child Relations/*psychology ; Mothers ; Parenting/*psychology ; Pituitary-Adrenal System ; Saliva/chemistry ; Social Behavior ; Stress Disorders, Post-Traumatic/metabolism ; Stress, Psychological/metabolism ; }, abstract = {The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-exposed children and their mothers, compared to matched controls, were followed from infancy and the current study reports findings from early adolescence (mean age = 11.66, SD = 1.23; N = 111; exposed = 58 control = 53). Youth and mothers' salivary cortisol (CT) and secretory immunoglobulin (s-IgA) levels were measured three times during a 4-hour lab visit, mother-child interaction patterns were quantified from a joint task, and children's anxiety symptoms diagnosed. Trauma-exposed children had higher levels of CT and s-IgA, exhibited more anxiety symptoms, and showed lower social collaboration with mother during the joint task. Trauma-exposed mothers had higher CT and s-IgA levels and showed less supportive parenting during mother-child interaction. Structural equation modeling defined three bio-behavioral paths by which trauma increases anxiety in youth. While the first path charted a behavioral link from exposure to child anxiety via diminished maternal support, the other two paths described mediated biological paths, one through HPA-axis functioning, the other via the immune system. Paths via the child's HPA and immune system were mediated by the parallel maternal variable. Findings are the first to describe the complex bio-behavioral interplay of stress and immune biomarkers and parenting behavior in shaping to the development of risk and resilience trajectories in youth growing up amidst chronic trauma.}, }
@article {pmid30144784, year = {2018}, author = {Shah, S and Brock, EJ and Jackson, RM and Ji, K and Boerner, JL and Sloane, BF and Mattingly, RR}, title = {Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation.}, journal = {Neoplasia (New York, N.Y.)}, volume = {20}, number = {9}, pages = {951-963}, pmid = {30144784}, issn = {1476-5586}, support = {U54 CA193489/CA/NCI NIH HHS/United States ; F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; R21 CA175931/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Cell Line, Tumor ; Cytoskeleton/metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; GTPase-Activating Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunohistochemistry ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Invasiveness ; RNA Interference ; }, abstract = {Diagnosis of breast ductal carcinoma in situ (DCIS) presents a challenge since we cannot yet distinguish those cases that would remain indolent and not require aggressive treatment from cases that may progress to invasive ductal cancer (IDC). The purpose of this study is to determine the role of Rap1Gap, a GTPase activating protein, in the progression from DCIS to IDC. Immunohistochemistry (IHC) analysis of samples from breast cancer patients shows an increase in Rap1Gap expression in DCIS compared to normal breast tissue and IDCs. In order to study the mechanisms of malignant progression, we employed an in vitro three-dimensional (3D) model that more accurately recapitulates both structural and functional cues of breast tissue. Immunoblotting results show that Rap1Gap levels in MCF10.Ca1D cells (a model of invasive carcinoma) are reduced compared to those in MCF10.DCIS (a model of DCIS). Retroviral silencing of Rap1Gap in MCF10.DCIS cells activated extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK), induced extensive cytoskeletal reorganization and acquisition of mesenchymal phenotype, and enhanced invasion. Enforced reexpression of Rap1Gap in MCF10.DCIS-Rap1GapshRNA cells reduced Rap1 activity and reversed the mesenchymal phenotype. Similarly, introduction of dominant negative Rap1A mutant (Rap1A-N17) in DCIS-Rap1Gap shRNA cells caused a reversion to nonmalignant phenotype. Conversely, expression of constitutively active Rap1A mutant (Rap1A-V12) in noninvasive MCF10.DCIS cells led to phenotypic changes that were reminiscent of Rap1Gap knockdown. Thus, reduction of Rap1Gap in DCIS is a potential switch for progression to an invasive phenotype. The Graphical Abstract summarizes these findings.}, }
@article {pmid30124442, year = {2018}, author = {Clement, Z and McLeay, W and Hoffmann, C and Shin, P and Kiu, A and Eaton, M}, title = {Role of radiotherapy in women over the age of 65 after breast conserving surgery for breast cancer: A 5-year retrospective study.}, journal = {Breast disease}, volume = {37}, number = {4}, pages = {197-205}, doi = {10.3233/BD-180340}, pmid = {30124442}, issn = {1558-1551}, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Female ; Humans ; Mammography ; Mastectomy, Segmental/*statistics &amp; numerical data ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND/OBJECTIVE: This study aimed to analyse the local recurrence (LR) and breast cancer related mortality (BCRM) in older women who underwent breast-conserving surgery (BCS) with and without adjuvant radiotherapy (XRT).<br><br>METHODS: This retrospective study included a total of 299 women who underwent BCS for early breast carcinoma, between the years of 2007 and 2011. Predictive risk factors, local recurrence (LR) and breast cancer related mortality (BCRM) were assessed with a mean follow-up period of 84 months.<br><br>RESULTS: Women over the age of 65 in the XRT and No-XRT groups showed similar incidence of LR (5.8% vs 5%, p = 0.838). Women over 65 years old with XRT had a higher rate of BCRM (5.8% vs 0%, p = 0.05). Resection margins >5 mm had a lower rate of BCRM (HR 0.395, p = 0.05). Women under the age of 65, invasive ductal carcinoma, grade-3 tumours, HER-2 positive, triple negative, lympho-vascular invasion, axillary lymph node positivity, high breast density on mammography were associated with increased risk of LR and BCRM.<br><br>CONCLUSIONS: XRT in women over the age of 65 did not decrease the risk of LR. Adjuvant XRT in older women should be offered to selective patients with high risk patient and tumour factors.}, }
@article {pmid30110018, year = {2018}, author = {Yildirim, N and Bahceci, A}, title = {Use of pertuzumab and trastuzumab during pregnancy.}, journal = {Anti-cancer drugs}, volume = {29}, number = {8}, pages = {810-813}, doi = {10.1097/CAD.0000000000000658}, pmid = {30110018}, issn = {1473-5741}, mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use ; Breast Neoplasms/*drug therapy ; Docetaxel/administration &amp; dosage/ad