@article {pmid35963427, year = {2022}, author = {Brecklinghaus, T and Albrecht, W and Duda, J and Kappenberg, F and Gründler, L and Edlund, K and Marchan, R and Ghallab, A and Cadenas, C and Rieck, A and Vartak, N and Tolosa, L and Castell, JV and Gardner, I and Halilbasic, E and Trauner, M and Ullrich, A and Zeigerer, A and Turgunbayer, ÖD and Damm, G and Seehofer, D and Rahnenführer, J and Hengstler, JG}, title = {In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red Assay.}, journal = {Toxicology letters}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.toxlet.2022.08.006}, pmid = {35963427}, issn = {1879-3169}, abstract = {The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds.}, }
@article {pmid35958350, year = {2022}, author = {Fujita, K and Okamura, M and Imakita, T and Yamamoto, Y and Sawai, S and Moriyoshi, K and Mio, T}, title = {Natural course of pulmonary hyalinizing granuloma over a decade.}, journal = {Respiratory medicine case reports}, volume = {39}, number = {}, pages = {101715}, doi = {10.1016/j.rmcr.2022.101715}, pmid = {35958350}, issn = {2213-0071}, abstract = {Background: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response.<br><br>Case presentation: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG.<br><br>Conclusions: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.}, }
@article {pmid35945526, year = {2022}, author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X}, title = {Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {872}, pmid = {35945526}, issn = {1471-2407}, support = {2021KY1161 and 2022KY1316//Medical and Health Research Project of Zhejiang Province/ ; 2021ZA138//Zhejiang Province Chinese Medicine Science Research Fund Project/ ; }, mesh = {Bayes Theorem ; *Breast Neoplasms/diagnostic imaging/genetics ; *Carcinoma, Ductal ; China ; Female ; Humans ; Ki-67 Antigen ; Nomograms ; Retrospective Studies ; }, abstract = {BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.<br><br>METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).<br><br>RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram.<br><br>CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.}, }
@article {pmid35932126, year = {2022}, author = {Yaltirik Bilgin, E and Unal, O and Ciledag, N}, title = {Vasogenic Edema Pattern in Brain Metastasis.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {8}, pages = {1020-1025}, doi = {10.29271/jcpsp.2022.08.1020}, pmid = {35932126}, issn = {1681-7168}, mesh = {Brain/pathology ; *Brain Edema/diagnostic imaging/etiology ; *Brain Neoplasms/complications/diagnostic imaging/pathology ; Cross-Sectional Studies ; Edema/etiology ; Humans ; *Lung Neoplasms/complications ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: To determine the relationship of the presence and amount of vasogenic edema with origin, type, and grade of primary cancer.<br><br>STUDY DESIGN: Cross-sectional study.<br><br>PLACE AND DURATION OF STUDY: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiology Clinic, Ankara, Turkey, from July 2017 to October 2021.<br><br>METHODOLOGY: Brain MRI scans of 292 patients were retrospectively evaluated. Age, gender, origin, type, and grade of primary cancer were determined. Metastasis type, and presence of vasogenic edema accompanying metastatic lesion were questioned. In cases of vasogenic edema accompanying metastatic lesions, the largest diameter of the vasogenic edema mass complex was measured in T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured, and the edema-mass ratio (EMR) was calculated by proportioning the diameter of the edema mass complex to the diameter of the mass.<br><br>RESULTS: The frequency of vasogenic edema was found higher in patients with lung cancer compared to other primaries. The EMR was found statistically significantly higher in patients with primary lung cancer (p=0.001). This was particularly evident in the adenocarcinoma group. In the patient group with primary breast cancer, EMR was found significantly lower in patients with invasive ductal carcinoma. (IDC→1.95±0.66 vs. Other→2.48±0.52, Z=-2.301, p=0.021).<br><br>CONCLUSION: The amount and presence of vasogenic edema in patients with brain metastases may differ according to the origin and type of primary tumour.<br><br>KEY WORDS: Brain edema, Metastatic disease, Magnetic resonance imaging.}, }
@article {pmid35538300, year = {2022}, author = {D'Iorio, A and Baiano, C and Maraucci, G and Vitale, C and Amboni, M and Santangelo, G}, title = {A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {8}, pages = {4605-4609}, pmid = {35538300}, issn = {1590-3478}, mesh = {Aged ; Anhedonia ; *COVID-19 ; Humans ; Longitudinal Studies ; Pandemics ; *Parkinson Disease/complications/diagnosis/epidemiology ; Quality of Life/psychology ; }, abstract = {INTRODUCTION: The COVID-19 pandemic led to psychological consequences on people's mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson's disease (PD). This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status.<br><br>METHODS: Forty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated.<br><br>RESULTS: Results of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z = - 2.49; p = 0.013; Cohen dz = 0.691. Higher scores of the TEPS total score, Z = - 2.38; p = 0.025; Cohen dz = 0.621, and LEDD, Z = - 2.63; p = 0.008; Cohen dz = 0.731, were also reported at T1.<br><br>CONCLUSION: The present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.}, }
@article {pmid35907957, year = {2022}, author = {Oehler, D and Spychala, A and Gödecke, A and Lang, A and Gerdes, N and Ruas, J and Kelm, M and Szendroedi, J and Westenfeld, R}, title = {Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {169}, pmid = {35907957}, issn = {1741-7007}, support = {236177352- SFB 1116//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Alternative Splicing ; Animals ; Humans ; Mice ; *Myocardial Ischemia/genetics ; Obesity/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Protein Isoforms/genetics ; RNA, Messenger/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction.<br><br>RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1α isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1α isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1α-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice.<br><br>CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1α coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1α function in the injured and metabolically challenged heart.}, }
@article {pmid35906698, year = {2022}, author = {Lee, S and Osmanbeyoglu, HU}, title = {Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.}, journal = {Breast cancer research : BCR}, volume = {24}, number = {1}, pages = {54}, pmid = {35906698}, issn = {1465-542X}, support = {R00CA207871/BC/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Chromatin/genetics ; Female ; Humans ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.<br><br>METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset.<br><br>RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.<br><br>CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.}, }
@article {pmid35909232, year = {2022}, author = {Yang, ZJ and Liu, YX and Huang, Y and Chen, ZJ and Zhang, HZ and Yu, Y and Wang, X and Cao, XC}, title = {The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.}, journal = {Cancer medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/cam4.5089}, pmid = {35909232}, issn = {2045-7634}, support = {81372843//National Natural Science Foundation of China/ ; 81472472//National Natural Science Foundation of China/ ; 81502518//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed.<br><br>METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index ≥20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank χ2 value.<br><br>RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p < 0.001) and disease-free survival (DFS) (p < 0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p < 0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.}, }
@article {pmid35898837, year = {2023}, author = {Suzuki, Y and Hoshi, K and Tominaga, K and Inaba, Y and Yoshinaga, T and Kojimahara, S and Maki, R and Nemoto, R and Tetsuka, Y and Kawata, Y and Yamamiya, A and Sugaya, T and Iso, Y and Takada-Owada, A and Ishida, K and Goda, K and Irisawa, A}, title = {A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.}, journal = {DEN open}, volume = {3}, number = {1}, pages = {e144}, pmid = {35898837}, issn = {2692-4609}, abstract = {A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.}, }
@article {pmid35866222, year = {2022}, author = {Khanam, R and Islam, S and Rahman, S and Ahmed, S and Islam, A and Hasan, T and Hasan, E and Chowdhury, NH and Roy, AD and Jaben, IA and Nehal, AA and Yoshida, S and Manu, AA and Raqib, R and McCollum, ED and Shahidullah, M and Jehan, F and Sazawal, S and Bahl, R and Baqui, AH}, title = {Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05030}, doi = {10.7189/jogh.12.05030}, pmid = {35866222}, issn = {2047-2986}, mesh = {Antibodies, Viral ; Bangladesh/epidemiology ; *COVID-19/epidemiology ; Child ; Cohort Studies ; Communicable Disease Control ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Seroepidemiologic Studies ; }, abstract = {Background: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh.<br><br>Methods: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models.<br><br>Results: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16, 95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years.<br><br>Conclusions: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.}, }
@article {pmid35864546, year = {2022}, author = {Zhu, S and Zhao, J and Nie, L and Yin, W and Zhang, Y and Zhao, F and Ni, Y and Zhang, X and Wang, Z and Dai, J and Liu, Z and Chen, J and Zeng, Y and Wang, Z and Sun, G and Liang, J and Zhao, X and Zhu, X and Tao, R and Yang, J and He, B and Chen, N and Shen, P and Zeng, H}, title = {Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {237}, pmid = {35864546}, issn = {1741-7015}, mesh = {*Adenocarcinoma/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Homologous Recombination/genetics ; Humans ; Male ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.<br><br>METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.<br><br>RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.<br><br>CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.}, }
@article {pmid35855704, year = {2022}, author = {Bhatia, JK and Chaudhary, T and Boruah, D and Bharadwaj, R}, title = {Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.}, journal = {Medical journal, Armed Forces India}, volume = {78}, number = {3}, pages = {345-354}, pmid = {35855704}, issn = {0377-1237}, abstract = {Background: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.<br><br>Methods: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated.<br><br>Results: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels.<br><br>Conclusions: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.}, }
@article {pmid35855193, year = {2022}, author = {Somashekhar, SP and Jaiswal, R and Kumar, R and Ashok, BC and Rakshit, S and Rauthan, A and Patil, P and Yashas, N and Karthik, HK and Prasad, A and Islam, H and Ashwin, KR}, title = {An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.}, journal = {European journal of breast health}, volume = {18}, number = {3}, pages = {271-278}, pmid = {35855193}, issn = {2587-0831}, abstract = {Objective: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer.<br><br>Materials and Methods: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI ≥27.5 as obese category.<br><br>Results: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively.<br><br>Conclusion: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.}, }
@article {pmid35842661, year = {2022}, author = {Zhang, WT and Zhu, GL and Xu, WQ and Zhang, W and Wang, HZ and Wang, YB and Li, YX}, title = {Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer.}, journal = {Diagnostic pathology}, volume = {17}, number = {1}, pages = {61}, pmid = {35842661}, issn = {1746-1596}, support = {No.2008085QH408//Natural Science Foundation of Anhui Province/ ; No.81874063//National Natural Science Foundation of China/ ; }, mesh = {B7-H1 Antigen/metabolism ; Biomarkers, Tumor/analysis ; *Breast Neoplasms ; *Epstein-Barr Virus Infections/complications ; Female ; Herpesvirus 4, Human ; Humans ; Ligands ; Prognosis ; Programmed Cell Death 1 Receptor ; }, abstract = {PURPOSE: Causative factors of breast cancer include infections, such as Epstein-Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.<br><br>METHODS: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.<br><br>RESULTS: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P < 0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P < 0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P > 0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P < 0.05). The Kaplan-Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.<br><br>CONCLUSIONS: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.}, }
@article {pmid35661214, year = {2022}, author = {Sulaj, A and Kopf, S and von Rauchhaupt, E and Kliemank, E and Brune, M and Kender, Z and Bartl, H and Cortizo, FG and Klepac, K and Han, Z and Kumar, V and Longo, V and Teleman, A and Okun, JG and Morgenstern, J and Fleming, T and Szendroedi, J and Herzig, S and Nawroth, PP}, title = {Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {107}, number = {8}, pages = {2167-2181}, pmid = {35661214}, issn = {1945-7197}, support = {236360313-SFB 1118//German Research Foundation/ ; //Deutsches Zentrum für Diabetesforschung/ ; 82DZD07C2G//Diabetes Research/ ; 236360313-SFB 1118//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Albuminuria/etiology ; Biomarkers ; Creatinine ; DNA/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetic Nephropathies/etiology ; Fasting ; Humans ; *Insulin Resistance ; Lipids ; Receptors, Urokinase Plasminogen Activator ; }, abstract = {CONTEXT: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.<br><br>OBJECTIVE: Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.<br><br>DESIGN/PARTICIPANTS: Proof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up.<br><br>MAIN OUTCOMES MEASURES: Change in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints.<br><br>RESULTS: FMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [-30.3 (-35.7, -24.9) mg/g; P ≤ 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23]. FMD reduced HOMA-IR [-3.8 (-5.6, -2.0); P ≤ 0.05] and soluble urokinase plasminogen activator receptor [-156.6 (-172.9, -140.4) pg/mL; P ≤ 0.05], while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [-1.9 (-3.7, -0.1), P ≤ 0.05]) was sustained.<br><br>CONCLUSIONS: Improvement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.}, }
@article {pmid35834927, year = {2022}, author = {Syamsu, SA and Setiady, R and Smaradania, N and Prihantono,  and Irsandy, F and Faruk, M}, title = {Synchronous breast cancer and non-Hodgkin lymphoma: A case report.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107398}, doi = {10.1016/j.ijscr.2022.107398}, pmid = {35834927}, issn = {2210-2612}, abstract = {INTRODUCTION: Among women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.<br><br>PRESENTATION OF CASE: A 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.<br><br>CLINICAL DISCUSSION: Treating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.<br><br>CONCLUSION: The enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.}, }
@article {pmid35804316, year = {2022}, author = {Chang, C and Zhu, J and Li, H and Yang, Q}, title = {Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {400}, pmid = {35804316}, issn = {1471-2431}, abstract = {BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI).<br><br>CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed.<br><br>CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.}, }
@article {pmid35695563, year = {2022}, author = {Agostinetto, E and Nader-Marta, G and Paesmans, M and Ameye, L and Veys, I and Buisseret, L and Neven, P and Taylor, D and Fontaine, C and Duhoux, FP and Canon, JL and Denys, H and Coussy, F and Chakiba, C and Ribeiro, JM and Piccart, M and Desmedt, C and Ignatiadis, M and Aftimos, P}, title = {ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.}, journal = {Future oncology (London, England)}, volume = {18}, number = {22}, pages = {2383-2392}, doi = {10.2217/fon-2022-0358}, pmid = {35695563}, issn = {1744-8301}, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; Cadherins ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/pathology ; Clinical Trials, Phase II as Topic ; Female ; Humans ; Neoadjuvant Therapy ; Protein-Tyrosine Kinases/therapeutic use ; Proto-Oncogene Proteins ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.}, }
@article {pmid35397740, year = {2022}, author = {Ensenyat-Mendez, M and Rünger, D and Orozco, JIJ and Le, J and Baker, JL and Weidhaas, J and Marzese, DM and DiNome, ML}, title = {Epigenetic Signatures Predict Pathologic Nodal Stage in Breast Cancer Patients with Estrogen Receptor-Positive, Clinically Node-Positive Disease.}, journal = {Annals of surgical oncology}, volume = {29}, number = {8}, pages = {4716-4724}, pmid = {35397740}, issn = {1534-4681}, support = {CP17/00188//European Regional Development Fund/ ; PI19/01514)//European Regional Development Fund/ ; UL1TR000124UCLA//CTSI UCLA/ ; }, mesh = {Axilla/pathology ; *Breast Neoplasms/genetics/metabolism/surgery ; Epigenesis, Genetic ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node Biopsy/methods ; }, abstract = {BACKGROUND: Breast cancer patients with clinically positive nodes who undergo upfront surgery are often recommended for axillary lymph node dissection (ALND), yet more than half are found to have limited nodal disease (≤ 3 positive nodes, pN1) at surgery. In this study, we examined the efficiency of molecular classifiers in stratifying patients with clinically positive nodes to pN1 versus > pN1 disease.<br><br>METHODS: We evaluated the clinical and epigenetic data of patients in The Cancer Genome Atlas with estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive ductal carcinoma who underwent ALND for node-positive disease. Patients were divided into control (pN1, ≤ 3 positive nodes) and case (> pN1, > 3 positive nodes) groups. Machine learning algorithms were trained on 50% of the cohort and validated on the remaining 50% to identify DNA methylation signatures that predict > pN1 disease. Clinical variables and epigenetic signatures were compared.<br><br>RESULTS: Controls (n = 34) and case (n = 24) cohorts showed similar mean age (56.4 ± 12.2 vs. 57.6 ± 16.7 years; p = 0.77), number of nodes removed (16.1 ± 7.3 vs. 17.5 ± 6.2; p = 0.45), tumor grade (p = 0.76), presence of lymphovascular invasion (p = 0.18), extranodal extension (p = 0.17), tumor laterality (p = 0.89), and tumor location (p = 0.42). The mean number of positive nodes was significantly different (1.76 ± 0.82, pN1; 8.83 ± 5.36, > pN1; p < 0.001). Three epigenetic signatures (EpiSig14, EpiSig13, EpiSig10) based on DNA methylation patterns of the primary tumors demonstrated high accuracy in predicting > pN1 disease (area under the curve 0.98).<br><br>CONCLUSIONS: Epigenetic signatures have an excellent diagnostic accuracy for stratifying nodal disease in patients with clinically positive nodes. Validation of this tool is warranted and may provide an accurate and cost-effective method of identifying patients with predicted low nodal burden who could be spared the morbidity of ALND.}, }
@article {pmid35776197, year = {2022}, author = {Rakshit, S and Sunny, JS and George, M and Hanna, LE and Leela, KV and Sarkar, K}, title = {T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {35776197}, issn = {1432-1335}, support = {ECR/2016/000965//Science and Engineering Research Board/ ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.<br><br>METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.<br><br>RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.<br><br>CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.}, }
@article {pmid35666367, year = {2022}, author = {Zhang, Y and Luo, X and Chen, M and Yang, L and Lei, T and Pu, T and Wei, B and Bu, H and Zhang, Z}, title = {Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.}, journal = {Breast cancer research and treatment}, volume = {194}, number = {2}, pages = {279-295}, pmid = {35666367}, issn = {1573-7217}, support = {2022YFS0376//Department of Science and Technology of Sichuan Province/ ; }, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; }, abstract = {PURPOSE: To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.<br><br>METHODS: A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.<br><br>RESULTS: Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67 > 20% tumors (P < 0.05). P-ILCs were subdivided into ER+ (63.1%), HER2+ (21.1%) and TN (15.8%). ER+ P-ILCs were mainly showed trabecular and solid growth patterns. Apocrine and solid features were more strongly associated with HER2+ P-ILCs and TN-P-ILCs, respectively. The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had worse prognosis than the same subtypes in the IDC group, while there was no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC had the worst prognosis. Bone was the most common metastatic site in ER+ P-ILCs and TN-P-ILCs. HER2+ P-ILCs tended to metastasize to the brain and liver. DFS of HER2+ P-ILCs and TN-P-ILCs were worse than that of ER+ P-ILCs. Lacking lobular carcinoma in situ and sTILs ≤ 10% were associated with worse survival of ER+ P-ILCs and TN-P-ILCs, respectively. For HER2+ P-ILCs, Ki-67 > 20% and sTILs ≤ 10% were significant factors for lower DFS.<br><br>CONCLUSION: P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.}, }
@article {pmid35749404, year = {2022}, author = {Hardeman, AA and Han, YJ and Grushko, TA and Mueller, J and Gomez, MJ and Zheng, Y and Olopade, OI}, title = {Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0268693}, doi = {10.1371/journal.pone.0268693}, pmid = {35749404}, issn = {1932-6203}, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; DNA Copy Number Variations ; Female ; Humans ; Protein Serine-Threonine Kinases ; RNA, Messenger/genetics ; *Triple Negative Breast Neoplasms/genetics ; }, abstract = {Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.}, }
@article {pmid35749114, year = {2022}, author = {Weis, S and Hagel, S and Palm, J and Scherag, A and Kolanos, S and Bahrs, C and Löffler, B and Schmitz, RPH and Rißner, F and Brunkhorst, FM and Pletz, MW and , }, title = {Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {6}, pages = {e2218515}, doi = {10.1001/jamanetworkopen.2022.18515}, pmid = {35749114}, issn = {2574-3805}, abstract = {Importance: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.<br><br>Objectives: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.<br><br>This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361).<br><br>Interventions: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.<br><br>Main Outcomes and Measures: Thirty-day all-cause mortality.<br><br>Results: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01).<br><br>Conclusions and Relevance: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.<br><br>Trial Registration: drks.de Identifier: DRKS00010135.}, }
@article {pmid35743985, year = {2022}, author = {Ortega, MA and Fraile-Martinez, O and García-Montero, C and Borja-Vergel, S and Torres-Carranza, D and Pekarek, L and Arribas, CB and De León-Luis, JA and Sánchez-Rojo, C and Alvarez-Mon, MA and García-Honduvilla, N and Buján, J and Coca, S and Alvarez-Mon, M and Saez, MA and Guijarro, LG}, title = {Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {6}, pages = {}, doi = {10.3390/medicina58060722}, pmid = {35743985}, issn = {1648-9144}, support = {MITICAD//Comunidad de Madrid/ ; }, abstract = {Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.}, }
@article {pmid35711899, year = {2022}, author = {Choi, JDW and Hughes, TMD and Marx, G and Boyages, J and Rutovitz, J and Hasovits, C and Parasyn, A and Edirimanne, S and Ngui, NK}, title = {The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.}, journal = {The breast journal}, volume = {2022}, number = {}, pages = {1199245}, doi = {10.1155/2022/1199245}, pmid = {35711899}, issn = {1524-4741}, mesh = {Australia ; *Breast Neoplasms/drug therapy/genetics/pathology ; Female ; Gene Expression Profiling/methods ; Humans ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Receptors, Estrogen/genetics ; Retrospective Studies ; }, abstract = {Introduction: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.<br><br>Methods: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).<br><br>Conclusion: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.}, }
@article {pmid35538223, year = {2022}, author = {Simond, AM and Bui, T and Zuo, D and Sanguin-Gendreau, V and Rao, T and Phillips, WA and Cardiff, RD and Muller, WJ}, title = {Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.}, journal = {Oncogene}, volume = {41}, number = {25}, pages = {3445-3451}, pmid = {35538223}, issn = {1476-5594}, support = {CIHR-FDN-148373//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinase/genetics ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Receptor, ErbB-2/genetics ; }, abstract = {p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110αHR) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110αHR bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110αHR mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.}, }
@article {pmid35522890, year = {2022}, author = {Butcher, MR and White, MJ and Rooper, LM and Argani, P and Cimino-Mathews, A}, title = {MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.}, journal = {The American journal of surgical pathology}, volume = {46}, number = {7}, pages = {878-888}, doi = {10.1097/PAS.0000000000001913}, pmid = {35522890}, issn = {1532-0979}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Adenoid Cystic/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; In Situ Hybridization ; RNA ; *Salivary Gland Neoplasms/pathology ; *Triple Negative Breast Neoplasms/diagnosis/genetics/pathology ; }, abstract = {Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.}, }
@article {pmid35714104, year = {2022}, author = {Icht, M and Bergerzon-Bitton, O and Ben-David, BM}, title = {Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.}, journal = {International journal of language &amp; communication disorders}, volume = {}, number = {}, pages = {}, doi = {10.1111/1460-6984.12737}, pmid = {35714104}, issn = {1460-6984}, abstract = {'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.}, }
@article {pmid35697697, year = {2022}, author = {Rebbeck, CA and Xian, J and Bornelöv, S and Geradts, J and Hobeika, A and Geiger, H and Alvarez, JF and Rozhkova, E and Nicholls, A and Robine, N and Lyerly, HK and Hannon, GJ}, title = {Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3399}, pmid = {35697697}, issn = {2041-1723}, mesh = {Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Homeodomain Proteins/genetics/metabolism ; Humans ; Transcription Factors/genetics ; Transcriptome ; }, abstract = {Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.}, }
@article {pmid35687769, year = {2022}, author = {Silva, DJ and Miranda, G and Mesquita, A}, title = {Clinical relevance of receptor conversion in metastatic breast cancer: Case report.}, journal = {Medicine}, volume = {101}, number = {23}, pages = {e29136}, doi = {10.1097/MD.0000000000029136}, pmid = {35687769}, issn = {1536-5964}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/therapy ; Disease Progression ; Female ; Humans ; Mastectomy ; Quality of Life ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.<br><br>PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.<br><br>DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.<br><br>INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated.<br><br>OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.<br><br>CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.}, }
@article {pmid35337805, year = {2022}, author = {Rajabi, F and Mozdarani, H}, title = {Expression level of miR-155, miR-15a and miR-19a in peripheral blood of ductal carcinoma breast cancer patients: Possible bioindicators for cellular inherent radiosensitivity.}, journal = {Experimental and molecular pathology}, volume = {126}, number = {}, pages = {104758}, doi = {10.1016/j.yexmp.2022.104758}, pmid = {35337805}, issn = {1096-0945}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/genetics/radiotherapy ; Environmental Biomarkers ; Female ; Humans ; *MicroRNAs ; ROC Curve ; Radiation Tolerance/genetics ; }, abstract = {Examination of cellular radiosensitivity (RS) helps prevent the adverse side-effects of radiotherapy in radioresistant tumors. We aim to study whether miRNA-155 (miR-155), miR-19a and miR-15a can predict inherent RS according to cellular RS in breast cancer (BC) patients. This study was done on the blood samples of 40 invasive ductal carcinoma (IDC) BC patients and 15 healthy women. G2 assay was performed to evaluate cellular RS. To study the expression level of these miRNAs in blood, qRT-PCR was used. The sensitivity and specificity of the studied miRNAs were assessed by the receiver operating characteristic (ROC) curve. The yield of spontaneous (SY) and radiation-induced (RIY) chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.0001). A cut-off value was specified to recognize the patients with cellular RS from those without. Expression of miR-15a was significantly downregulated (p < 0.0001) in BC patients. However, miR-19a showed upregulation in the blood of BC patients. It was also found the expression level of miR-155 and miR-19a were significantly associated with frequency of CBs (FCB) (p < 0.05). ROC curve analysis manifested that the miR-15a and miR-19a differentiate BC patients and healthy women with 0.91 and 0.68 yielding an area under the ROC curve, respectively. miR-155 and miR-19a discriminate between BC patients with and without cellular RS with area under the ROC curve 0.98 and 0.68. Our findings uncovered miR-155 and miR-19a could be applied as a bioindicator to predict cellular radiosensitivity of BC patients.}, }
@article {pmid35372457, year = {2022}, author = {Niknam, K and Safaei, A and Ghaderi, A}, title = {Evaluation of the Prognostic Value of CD56 (140 kDa Isoform) Expression in Breast Cancer Tissues: an Eight-Year Retrospective Study.}, journal = {Iranian biomedical journal}, volume = {26}, number = {3}, pages = {175-182}, doi = {10.52547/ibj.26.3.175}, pmid = {35372457}, issn = {2008-823X}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/pathology ; *CD56 Antigen/genetics ; Female ; Humans ; Mastectomy ; Prognosis ; Protein Isoforms/genetics ; Retrospective Studies ; }, abstract = {Background: Identification of specific antigens is highly beneficial for early detection, diagnosis, staging, and outcome prediction of cancer. This study aimed to evaluate the expression and prognostic value of CD56 (140 kDa isoform) in IDC.<br><br>Methods: Sixty-five patients with IDC who underwent radical surgery or mastectomy as the primary treatment were included. Proper formalin-fixed and paraffin embedded tissue blocks of the patients were prepared and stained by IHC for CD56 (140 kDa isoform) molecule. Chi-square and fisher exact tests were used to compare the results against the clinicopathologic data of patients. Kaplan-Meier and log-rank test were employed to study the prognostic value of the target antigen.<br><br>Results: The expression pattern of CD56 was granular and cytoplasmic. There were significant associations between the intensity of CD56 expression in invasive cells and carcinoma in situ (p = 0.005) and normal ducts (p = 0.010). Among all clinicipathologic parameters, there was only a significant association between the expression of ER and CD56 (p = 0.023). Neither OS (p = 0.356) nor DFS (p = 0.976) had significant correlation with CD56 expression.<br><br>Conclusion: Our data indicated that the CD56 marker offers no prognostic value in terms of predicting the OS or DFS for up to eight years after primary surgery. Furthermore, the intensity of its expression is similar between normal, non-invasive, and invasive cells. Considering the generally better outcome of ER+ BC patients than their ER- counterparts, the CD56 marker may be indirectly associated with a more favorable prognosis among IDC patients.}, }
@article {pmid35647336, year = {2022}, author = {Hamed, MM and Gouida, MS and Abd El-Aziz, SR and El-Sokkary, AMA}, title = {Evaluation PD-L1, CD8 and CD20 as early predictor and tracking markers for breast cancer (BC) in Egypt.}, journal = {Heliyon}, volume = {8}, number = {5}, pages = {e09474}, doi = {10.1016/j.heliyon.2022.e09474}, pmid = {35647336}, issn = {2405-8440}, abstract = {Background: Breast cancer (BC) is considered as a common type of cancer threatening women throughout the world. Therefore, development of early predication biomarkers for BC got more concern especially for Egyptian females. This study was aimed to evaluate PD-L1, CD8, and CD20 as early prediction breast cancer biomarkers.<br><br>Methods: Flow cytometry (FC), immunohistochemistry (IHC), Western Blot, and q-PCR were used to compare PD-L1, CD20, and CD8 levels in tissues and blood samples of Breast Cancer and controls.<br><br>Results: Blood samples showed a significant increase in PD-L1, CD20, and CD8 compared to controls (p˂0.005). A Significant correlation was shown between PD-L1, CD8, and CD20 in tissue and breast cancer subtypes. Whereas, invasive lobular carcinoma (ILC) was characterized by superior PD-L1 and CD20 levels compared to invasive ductal carcinoma (IDC). FC studies on Blood showed 83% and 45.7% PD-L1 expressions for IDC and ILC, respectively. CD20 in ILC and IDC were 78.2% and 62.5%, respectively. Nevertheless, CD8 was 74.2% for IDC and 67.7% for ILC. Whereas, FC studies for PD-L1, CD20, and CD8 in ILC in tissues gave 34.4%, 30.2% and 35.1%, respectively. In addition, IDC tissue samples showed 16%, 12.5, and 13.5% for PD-L1, CD20, and CD8. The moderate stage of adenocarcinoma caused expression of PD-L1 within inflammatory cells, while expression was within neoplastic glandular cells in late stage.<br><br>Conclusion: PD-L1, CD8, and CD20 are considered as early predictor and tracking markers for breast cancer.}, }
@article {pmid35636710, year = {2022}, author = {Willemsen, N and Arigoni, I and Studencka-Turski, M and Krüger, E and Bartelt, A}, title = {Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {101518}, doi = {10.1016/j.molmet.2022.101518}, pmid = {35636710}, issn = {2212-8778}, abstract = {OBJECTIVE: Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.<br><br>METHODS: In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.<br><br>RESULTS: Loss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.<br><br>CONCLUSIONS: Our study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.}, }
@article {pmid35621626, year = {2022}, author = {Cho, YA and Ko, SY and Suh, YJ and Kim, S and Park, JH and Park, HR and Seo, J and Choi, HG and Kang, HS and Lim, H and Park, HY and Kwon, MJ}, title = {PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.}, journal = {Current oncology (Toronto, Ont.)}, volume = {29}, number = {5}, pages = {2895-2908}, doi = {10.3390/curroncol29050236}, pmid = {35621626}, issn = {1718-7729}, support = {NRF-2019R1C1C1004463//National Research Foundation of Korea/ ; }, mesh = {B7-H1 Antigen/metabolism ; *Breast Neoplasms/drug therapy/genetics/metabolism ; Chemotherapy, Adjuvant ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Microsatellite Instability ; Middle Aged ; Mutation ; Prognosis ; }, abstract = {BACKGROUND: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy.<br><br>METHODS: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored.<br><br>RESULTS: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data.<br><br>CONCLUSIONS: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.}, }
@article {pmid35567670, year = {2022}, author = {Wilson, GM and Dinh, P and Pathmanathan, N and Graham, JD}, title = {Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {27}, number = {1}, pages = {101-131}, pmid = {35567670}, issn = {1573-7039}, mesh = {Biomarkers ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease Progression ; Female ; Humans ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.}, }
@article {pmid35585552, year = {2022}, author = {Oride, Y and Koi, Y and Sasada, T and Kajitani, K and Ohara, M and Kondo, T and Daimaru, Y and Kawamura, S}, title = {Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.}, journal = {Journal of medical case reports}, volume = {16}, number = {1}, pages = {194}, pmid = {35585552}, issn = {1752-1947}, abstract = {BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient.<br><br>CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment.<br><br>CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.}, }
@article {pmid35578939, year = {2022}, author = {Higashi, T and Ozawa, K and Takei, S and Takagi, S and Yokoyama, M and Mase, K and Moriya, T and Takeshita, A and Mizutani, M}, title = {[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {49}, number = {5}, pages = {581-583}, pmid = {35578939}, issn = {0385-0684}, abstract = {A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.}, }
@article {pmid35576836, year = {2022}, author = {He, S and Jia, Q and Zhou, L and Wang, Z and Li, M}, title = {SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.}, journal = {Pathology, research and practice}, volume = {235}, number = {}, pages = {153943}, doi = {10.1016/j.prp.2022.153943}, pmid = {35576836}, issn = {1618-0631}, abstract = {OBJECTIVE: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.<br><br>METHODS: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500 mg/L) and normal glucose (2000 mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1α, which play roles in aerobic glycolysis, was investigated using western blot.<br><br>RESULTS: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1α caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.<br><br>CONCLUSIONS: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.}, }
@article {pmid35547416, year = {2022}, author = {Smith, PD and Bhenderu, LS and Kommuri, S and Fleener, EE and Hoover, JM}, title = {Treatment of Leptomeningeal Carcinomatosis Following Treatment of Cerebellar Metastasis of HER2+ (Human Epidermal Growth Factor Receptor 2 Positive) Breast Cancer: Case Report and Review of Literature.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24008}, doi = {10.7759/cureus.24008}, pmid = {35547416}, issn = {2168-8184}, abstract = {Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.}, }
@article {pmid35324454, year = {2022}, author = {Wang, K and Schütze, I and Gulde, S and Bechmann, N and Richter, S and Helm, J and Lauseker, M and Maurer, J and Reul, A and Spoettl, G and Klink, B and William, D and Knösel, T and Friemel, J and Bihl, M and Weber, A and Fankhauser, M and Schober, L and Vetter, D and Broglie Däppen, M and Ziegler, CG and Ullrich, M and Pietzsch, J and Bornstein, SR and Lottspeich, C and Kroiss, M and Fassnacht, M and Wenter, VUJ and Ladurner, R and Hantel, C and Reincke, M and Eisenhofer, G and Grossman, AB and Pacak, K and Beuschlein, F and Auernhammer, CJ and Pellegata, NS and Nölting, S}, title = {Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures.}, journal = {Endocrine-related cancer}, volume = {29}, number = {6}, pages = {285-306}, doi = {10.1530/ERC-21-0355}, pmid = {35324454}, issn = {1479-6821}, mesh = {*Adrenal Gland Neoplasms/drug therapy/genetics/metabolism ; Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Everolimus/therapeutic use ; Humans ; Mice ; *Paraganglioma/drug therapy/genetics/pathology ; *Pheochromocytoma/drug therapy/genetics/metabolism ; Zoledronic Acid/therapeutic use ; }, abstract = {Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.}, }
@article {pmid35266635, year = {2022}, author = {Karabid, NM and Wiedemann, T and Gulde, S and Mohr, H and Segaran, RC and Geppert, J and Rohm, M and Vitale, G and Gaudenzi, G and Dicitore, A and Ankerst, DP and Chen, Y and Braren, R and Kaissis, G and Schilling, F and Schillmaier, M and Eisenhofer, G and Herzig, S and Roncaroli, F and Honegger, JB and Pellegata, NS}, title = {Angpt2/Tie2 autostimulatory loop controls tumorigenesis.}, journal = {EMBO molecular medicine}, volume = {14}, number = {5}, pages = {e14364}, doi = {10.15252/emmm.202114364}, pmid = {35266635}, issn = {1757-4684}, support = {//Deutsche Krebshilfe (German Cancer Aid)/ ; 2017.012.1//Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)/ ; 314061271-TRR 205//Deutsche Forschungsgemeinschaft (DFG)/ ; SFB-824//Deutsche Forschungsgemeinschaft (DFG)/ ; }, mesh = {*Angiopoietin-2/metabolism ; Animals ; Carcinogenesis ; Endothelial Cells/metabolism ; Humans ; Mice ; Neoplasm Recurrence, Local ; *Pituitary Neoplasms/genetics/metabolism/pathology ; Rats ; Receptor, TIE-2/genetics/metabolism ; Zebrafish ; }, abstract = {Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.}, }
@article {pmid35478129, year = {2022}, author = {Salih, MM and Higgo, AA and Khalifa, AS and Eed, EM}, title = {Incidence of Epstein-Barr Virus Among Women With Breast Cancer Using Monoclonal Antibodies for Latent Membrane Protein 1 (LMP1).}, journal = {In vivo (Athens, Greece)}, volume = {36}, number = {3}, pages = {1513-1518}, doi = {10.21873/invivo.12860}, pmid = {35478129}, issn = {1791-7549}, mesh = {Adult ; Antibodies, Monoclonal ; *Antineoplastic Agents, Immunological ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Ductal/complications ; *Epstein-Barr Virus Infections/complications/epidemiology/pathology ; Female ; Herpesvirus 4, Human ; Humans ; Incidence ; Male ; Membrane Proteins ; Middle Aged ; Viral Proteins ; }, abstract = {BACKGROUND/AIM: Breast cancer is a common type of cancer in Sudan. Numerous studies propose viral oncogenesis as an etiological factor for breast cancer. The aim of the study was to analyze the presence of the Epstein-Barr virus (EBV) using monoclonal antibodies against latent membrane protein 1 (LAMP1) and determine the correlation between the presence of EBV and clinicopathological characteristics.<br><br>PATIENTS AND METHODS: This study used immunohistochemistry to analyze the presence of EBV in 202 samples from Sudanese women diagnosed with breast cancer. Clinicopathological data were collected from patient records from the Radiation and Isotopes Centre in Khartoum State, Republic of Sudan.<br><br>RESULTS: This study included 202 patients 168 (83.2%), 16 (7.9%), and 18 (8.9%), diagnosed with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. Axillary lymph node metastasis was present in 57 (28.2%) of cases, while 11 patients (5.4%) tested positive for EBV. The mean age of patients was 48.14±14.4 years. EBV infection was more frequently detected in invasive ductal carcinoma cases, and EBV positivity was not associated with cancer type, grade, progesterone levels, and HER2 expression. On the other hand, a statistically significant association was found between EBV presence and lymph node involvement, estrogen receptor status, and age group.<br><br>CONCLUSION: EBV may not play a vital role in the pathogenesis of breast carcinoma in Sudanese women.}, }
@article {pmid35405500, year = {2022}, author = {Acevedo, DS and Fang, WB and Rao, V and Penmetcha, V and Leyva, H and Acosta, G and Cote, P and Brodine, R and Swerdlow, R and Tan, L and Lorenzi, PL and Cheng, N}, title = {Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.}, journal = {Neoplasia (New York, N.Y.)}, volume = {28}, number = {}, pages = {100791}, doi = {10.1016/j.neo.2022.100791}, pmid = {35405500}, issn = {1476-5586}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/metabolism ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/metabolism ; Cell Line, Tumor ; Chemokine CCL2/genetics ; Disease Progression ; Female ; Humans ; Neoplasm Recurrence, Local ; Proto-Oncogene Proteins c-met/genetics ; Receptors, CCR2/genetics/metabolism ; }, abstract = {With over 60,000 cases diagnosed annually in the US, ductal carcinoma in situ (DCIS) is the most prevalent form of early-stage breast cancer. Because many DCIS cases never progress to invasive ductal carcinomas (IDC), overtreatment remains a significant problem. Up to 20% patients experience disease recurrence, indicating that standard treatments do not effectively treat DCIS for a subset of patients. By understanding the mechanisms of DCIS progression, we can develop new treatment strategies better tailored to patients. The chemokine CCL2 and its receptor CCR2 are known to regulate macrophage recruitment during inflammation and cancer progression. Recent studies indicate that increased CCL2/CCR2 signaling in breast epithelial cells enhance formation of IDC. Here, we characterized the molecular mechanisms important for CCL2/CCR2-mediated DCIS progression. Phospho-protein array profiling revealed that CCL2 stimulated phosphorylation of MET receptor tyrosine kinases in breast cancer cells. Co-immunoprecipitation and proximity ligation assays demonstrated that CCL2-induced MET activity depended on interactions with CCR2 and SRC. Extracellular flux analysis and biochemical assays revealed that CCL2/CCR2 signaling in breast cancer cells enhanced glycolytic enzyme expression and activity. CRISPR knockout and pharmacologic inhibition of MET revealed that CCL2/CCR2-induced breast cancer cell proliferation, survival, migration and glycolysis through MET-dependent mechanisms. In animals, MET inhibitors blocked CCR2-mediated DCIS progression and metabolism. CCR2 and MET were significantly co-expressed in patient DCIS and IDC tissues. In summary, MET receptor activity is an important mechanism for CCL2/CCR2-mediated progression and metabolism of early-stage breast cancer, with important clinical implications.}, }
@article {pmid35456414, year = {2022}, author = {Zadrożna-Nowak, A and Romanowicz, H and Zadrożny, M and Bryś, M and Forma, E and Smolarz, B}, title = {Analysis of Long Non-Coding RNA (lncRNA) uc.38 and uc.63 Expression in Breast Carcinoma Patients.}, journal = {Genes}, volume = {13}, number = {4}, pages = {}, pmid = {35456414}, issn = {2073-4425}, mesh = {*Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Staging ; *RNA, Long Noncoding/genetics/metabolism ; }, abstract = {BACKGROUND: The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer.<br><br>AIM: The presented work assessed the expression of two transcribed-ultra conserved regions-uc.63 and uc.38-in breast cancer tissue samples.<br><br>MATERIAL AND METHODS: The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group).<br><br>RESULTS: As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient's age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035).<br><br>CONCLUSION: The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.}, }
@article {pmid33415472, year = {2022}, author = {Zimmerman-Brenner, S and Pilowsky-Peleg, T and Rachamim, L and Ben-Zvi, A and Gur, N and Murphy, T and Fattal-Valevski, A and Rotstein, M}, title = {Group behavioral interventions for tics and comorbid symptoms in children with chronic tic disorders.}, journal = {European child &amp; adolescent psychiatry}, volume = {31}, number = {4}, pages = {637-648}, pmid = {33415472}, issn = {1435-165X}, mesh = {Behavior Therapy ; Child ; Comorbidity ; Humans ; Severity of Illness Index ; *Tic Disorders/complications/therapy ; *Tics/therapy ; *Tourette Syndrome/complications/therapy ; }, abstract = {Exposure and Response Prevention (ERP), Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT) are effective in reducing tic severity. ERP and HRT have recently gained primary support in a group setting, while CBIT has not been examined similarly. We compared the efficacy of group-CBIT to group-Educational Intervention for Tics (group-EIT) for tics and comorbid symptoms. Children with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD) were randomized to group-CBIT or group-EIT. Tics and comorbid symptoms were assessed in forty-six children pre- and postintervention, and 3-month later. Yale Global Tic Severity Scale (YGTSS) Motor tic severity decreased following both interventions, and was maintained at follow-up for group-CBIT only. The Parent Tic Questionnaire (PTQ) showed significant decrease in total and motor tic severity following group-CBIT only, a gain maintained three months later. YGTSS impairment score decreased following both interventions and was maintained at follow-up. YGTSS vocal tic severity score increased following both interventions, and then decreased significantly at follow up. Co-morbid symptoms including anxiety, behavioral problems, and aggressive behavior decreased following both interventions. Children with behavioral problems benefitted less while children with higher intellectual ability benefit more from intervention. Both group interventions showed efficacy in reducing tic impairment and comorbid symptoms. Group-CBIT was superior to group-EIT in reducing motor tic severity at 3-month follow-up, showing an advantage for tic-focused treatment. Based on the PTQ, group-CBIT was superior to group-EIT in reducing motor, vocal, and total tic scores, a gain maintained three months later. Clinical trial registry information-Group Intervention for Children with Chronic Tics Syndrome: CBIT vs Psychoeducational Intervention URL: http://clinicaltrials.gov , Identifier: NCT02407951, http://www.controlled-trials.com).}, }
@article {pmid35231053, year = {2022}, author = {Troughton, LD and O'Loughlin, DA and Zech, T and Hamill, KJ}, title = {Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0264430}, pmid = {35231053}, issn = {1932-6203}, support = {BB/L020513/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P0257731/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; Cell Line, Tumor ; Cell Movement ; Female ; Humans ; Immunohistochemistry ; Laminin/genetics/metabolism ; Neoplasm Invasiveness ; }, abstract = {Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56% of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45% of samples. 65.8% of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target.}, }
@article {pmid34987224, year = {2022}, author = {Rasmussen, M and Reddy, M and Nolan, R and Camunas-Soler, J and Khodursky, A and Scheller, NM and Cantonwine, DE and Engelbrechtsen, L and Mi, JD and Dutta, A and Brundage, T and Siddiqui, F and Thao, M and Gee, EPS and La, J and Baruch-Gravett, C and Santillan, MK and Deb, S and Ame, SM and Ali, SM and Adkins, M and DePristo, MA and Lee, M and Namsaraev, E and Gybel-Brask, DJ and Skibsted, L and Litch, JA and Santillan, DA and Sazawal, S and Tribe, RM and Roberts, JM and Jain, M and Høgdall, E and Holzman, C and Quake, SR and Elovitz, MA and McElrath, TF}, title = {RNA profiles reveal signatures of future health and disease in pregnancy.}, journal = {Nature}, volume = {601}, number = {7893}, pages = {422-427}, pmid = {34987224}, issn = {1476-4687}, support = {P50 HD103556/HD/NICHD NIH HHS/United States ; }, mesh = {*Cell-Free Nucleic Acids ; Female ; Humans ; Placenta ; *Pre-Eclampsia/genetics ; Pregnancy ; RNA ; Retrospective Studies ; }, abstract = {Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.}, }
@article {pmid34597458, year = {2021}, author = {Viswanathan, K and Sadow, PM and Maleki, Z and Nishino, M and Baloch, ZW and Abbott, TE and Rao, R and Faquin, WC}, title = {Cytomorphologic features of intraductal salivary gland carcinoma: A multi-institutional study of 13 FNA cases with histologic, molecular, and clinical correlations.}, journal = {Cancer cytopathology}, volume = {129}, number = {12}, pages = {928-946}, doi = {10.1002/cncy.22504}, pmid = {34597458}, issn = {1934-6638}, support = {1PO1CA240239-01//National Cancer Institute of the National Institutes of Health/ ; }, mesh = {Biopsy, Fine-Needle/methods ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Gene Fusion ; Humans ; *Salivary Gland Neoplasms/pathology ; Salivary Glands/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data.<br><br>METHODS: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection.<br><br>RESULTS: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations.<br><br>CONCLUSIONS: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management.}, }
@article {pmid34185954, year = {2022}, author = {Zhao, J and Sun, G and Zhu, S and Dai, J and Chen, J and Zhang, M and Ni, Y and Zhang, H and Shen, P and Zhao, X and Zhang, B and Pan, X and Nie, L and Yin, X and Liang, J and Zhang, X and Wang, Z and Zhu, X and Liao, B and Liu, Z and Armstrong, CM and Gao, AC and Huang, H and Chen, N and Zeng, H}, title = {Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.}, journal = {BJU international}, volume = {129}, number = {3}, pages = {345-355}, doi = {10.1111/bju.15530}, pmid = {34185954}, issn = {1464-410X}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Circulating Tumor DNA/genetics ; Humans ; Male ; Phenotype ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P).<br><br>PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored.<br><br>RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of ≥10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P = 0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9 months, P = 0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9 months, P = 0.036).<br><br>CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.}, }
@article {pmid33132109, year = {2021}, author = {Zong, Y and Montironi, R and Massari, F and Jiang, Z and Lopez-Beltran, A and Wheeler, TM and Scarpelli, M and Santoni, M and Cimadamore, A and Cheng, L}, title = {Intraductal Carcinoma of the Prostate: Pathogenesis and Molecular Perspectives.}, journal = {European urology focus}, volume = {7}, number = {5}, pages = {955-963}, doi = {10.1016/j.euf.2020.10.007}, pmid = {33132109}, issn = {2405-4569}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Pelvis/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde spreading of cancer cells along benign ducts and acini, a small subset of IDC-P may arise from the transformation and intraductal proliferation of precancerous cells induced by various oncogenic events. These isolated IDC-P tumors possess a distinct mutational profile and may function as a carcinoma in situ lesion with de novo intraductal outgrowth of malignant cells. Further molecular characterization of these two types of IDC-P and better understanding of the mechanisms underlying IDC-P formation and progression could be translated into valuable biomarkers for differential diagnosis and actionable targets for therapeutic interventions. PATIENT SUMMARY: Intraductal carcinoma of the prostate is an aggressive type of prostate cancer associated with high risk for local recurrence and distant metastasis. In this review, we discussed pathogenesis, biomarkers, differential diagnoses, and therapeutic strategies for this tumor.}, }
@article {pmid35393463, year = {2022}, author = {Foroozani, E and Akbari, A and Amanat, S and Rashidi, N and Bastam, D and Ataee, S and Sharifnia, G and Faraouei, M and Dianatinasab, M and Safdari, H}, title = {Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5859}, pmid = {35393463}, issn = {2045-2322}, mesh = {*Breast Neoplasms/complications/etiology ; *Carcinoma, Ductal, Breast/complications/etiology ; *Carcinoma, Lobular/epidemiology/etiology/pathology ; Case-Control Studies ; Diet, Western ; Female ; Humans ; }, abstract = {Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.}, }
@article {pmid35389579, year = {2022}, author = {Clarey, D and DiMaio, D and Trowbridge, R}, title = {Deep Sweet Syndrome Secondary to Pegfilgrastim.}, journal = {Journal of drugs in dermatology : JDD}, volume = {21}, number = {4}, pages = {422-424}, doi = {10.36849/JDD.4794}, pmid = {35389579}, issn = {1545-9616}, mesh = {Filgrastim/adverse effects ; Granulocyte Colony-Stimulating Factor/adverse effects ; Humans ; Polyethylene Glycols/adverse effects ; *Sweet Syndrome/chemically induced/diagnosis/drug therapy ; }, abstract = {Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.}, }
@article {pmid35137951, year = {2022}, author = {Weiser, R and Polychronopoulou, E and Hatch, SS and Haque, W and Ghani, HA and He, J and Kuo, YF and Gradishar, WJ and Klimberg, VS}, title = {Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.}, journal = {Cancer}, volume = {128}, number = {9}, pages = {1738-1747}, doi = {10.1002/cncr.34127}, pmid = {35137951}, issn = {1097-0142}, support = {//Courtney M. Townsend, Jr. M.D. Distinguished Chair in General Surgery, University of Texas Medical Branch, Galveston, TX/ ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/drug therapy/genetics ; *Carcinoma, Lobular/drug therapy/genetics/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Prognosis ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients.<br><br>METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy.<br><br>RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease.<br><br>CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease.<br><br>LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.}, }
@article {pmid35178446, year = {2022}, author = {Li, X and Zhao, G and Mi, X and Xu, T and Li, X and Liu, B}, title = {Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {3321409}, pmid = {35178446}, issn = {2314-6141}, mesh = {*Breast Neoplasms/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; DNA-Binding Proteins/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; Glucose Transporter Type 3/metabolism ; Humans ; LIM Domain Proteins/genetics/metabolism ; Muscle Proteins/metabolism ; Survivin/genetics ; TEA Domain Transcription Factors ; Transcription Factors/genetics/metabolism ; }, abstract = {The LIM protein Ajuba has been implicated in the development of human cancers. To date, its expression pattern and biological significance in breast cancers (BC) have not been fully investigated. In the current study, we examined Ajuba protein levels in 93 invasive ductal carcinoma specimens by immunohistochemistry. The Ajuba expression level was elevated in breast cancer tissue compared with normal tissue. Ajuba overexpression is correlated with advanced tumor-node-metastasis (TNM) stage, positive node status, and adverse patient outcomes. The Ajuba protein level was also higher in BC cell lines compared to normal breast epithelial cell line MCF-10A. Ectopically expressed Ajuba in MCF-7 cells stimulated in vitro and in vivo cell growth, invasion, cell cycle progression, and decreased paclitaxel-induced apoptosis. RNA-sequencing (RNA-seq) followed by gene set enrichment analysis (GSEA) analysis showed that Ajuba overexpression regulated the Hippo signaling pathway. Ajuba overexpression also increased glucose uptake and increased expression of TAZ, GLUT3, and Survivin. TAZ knockdown abolished the role of Ajuba on GLUT3 and Survivin induction. The ChIP assay showed that TEAD4, a major TAZ binding transcription factor, could bind to the GLUT3 and Survivin promoter regions. In conclusion, our data demonstrated that elevated Ajuba expression is correlated with poor BC prognosis and regulated malignant behavior through TAZ-GLUT3/Survivin signaling in BC cells.}, }
@article {pmid35340411, year = {2022}, author = {Du, W and Miao, Y and Zhang, G and Luo, G and Yang, P and Chen, F and Zhang, B and Yang, C and Li, G and Chang, J}, title = {The Regulatory Role of Neuropeptide Gene Glucagon in Colorectal Cancer: A Comprehensive Bioinformatic Analysis.}, journal = {Disease markers}, volume = {2022}, number = {}, pages = {4262600}, pmid = {35340411}, issn = {1875-8630}, mesh = {Biomarkers, Tumor/metabolism ; *Colonic Neoplasms/genetics ; Computational Biology ; Gene Expression Regulation, Neoplastic ; *Glucagon/genetics/metabolism ; Humans ; }, abstract = {Background: Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer.<br><br>Methods: Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells.<br><br>Results: GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells.<br><br>Conclusions: GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.}, }
@article {pmid34083791, year = {2021}, author = {Zhao, E and Stone, MR and Ren, X and Guenthoer, J and Smythe, KS and Pulliam, T and Williams, SR and Uytingco, CR and Taylor, SEB and Nghiem, P and Bielas, JH and Gottardo, R}, title = {Spatial transcriptomics at subspot resolution with BayesSpace.}, journal = {Nature biotechnology}, volume = {39}, number = {11}, pages = {1375-1384}, pmid = {34083791}, issn = {1546-1696}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Cluster Analysis ; Gene Expression Profiling/methods ; Sequence Analysis, RNA/methods ; *Single-Cell Analysis/methods ; *Transcriptome/genetics ; }, abstract = {Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace's utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.}, }
@article {pmid35348061, year = {2021}, author = {Khan, NA and Nguyen, ST and Teh, PG and Ranpura, VN and Bhatia, T}, title = {Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature.}, journal = {The Permanente journal}, volume = {25}, number = {}, pages = {}, pmid = {35348061}, issn = {1552-5775}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/secondary ; *Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Mammography ; Receptors, Estrogen ; }, abstract = {Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor-, progesterone receptor-positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.}, }
@article {pmid35343265, year = {2022}, author = {Zhao, CM and Li, LL and Xu, JW and Li, ZW and Shi, P and Jiang, R}, title = {LINC00092 Suppresses the Malignant Progression of Breast Invasive Ductal Carcinoma Through Modulating SFRP1 Expression by Sponging miR-1827.}, journal = {Cell transplantation}, volume = {31}, number = {}, pages = {9636897221086967}, pmid = {35343265}, issn = {1555-3892}, mesh = {*Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; }, abstract = {Breast invasive ductal carcinoma (IDC) is a most common kind of breast cancer (BC), yet to date the corresponding effective therapies are limited. Extensive evidence has indicated that lncRNAs are involved in multiple cancers, and the potential mechanism of lncRNAs, such as LINC00092, mentioned in IDC remains elusive. IDC clinical samples from TCGA database were used to analyze the expression levels of LINC00092, miR-1827 and SFRP1. Kaplan-Meier method was applied to plot the overall survival curves. KEGG and GO were employed to screen the pathway that LINC00092 participated in. Pearson's correlation analysis determined the relationship between LINC00092 and SFRP1. Bioinformatics analysis and dual-luciferase reporter assay examined the association among LINC00092, miR-1827, and SFRP1. Cell counting kit-8, colony formation and transwell assays were performed to detect cell viability, colony formation, and migration and invasion, respectively. Quantitative reverse-transcription polymerase chain reaction and western blot were utilized to investigate the expression at RNA and protein levels. LINC00092 expression was down-regulated in IDC tissues and cells, which was correlated with poor prognosis. Down-regulated LINC00092 facilitated cell proliferation, colony formation, and cell migration and invasion, while up-regulated LINC00092 inhibited cell malignant behaviors. LINC00092/SFRP1 physically bound to miR-1827 in IDC. SFRP1 expression was proportional to LINC00092 expression and inversely proportional to miR-1827 expression. The inhibitory effects of LINC00092 on cell aggressive behaviors were partially regulated by miR-1827/SFRP1. In summary, our results indicated that overexpression of LINC00092 inhibited the development of IDC through modulating miR-1827/SFRP1 axis, suggesting new therapeutic targets to treat IDC.}, }
@article {pmid34999280, year = {2022}, author = {Kotschi, S and Jung, A and Willemsen, N and Ofoghi, A and Proneth, B and Conrad, M and Bartelt, A}, title = {NFE2L1-mediated proteasome function protects from ferroptosis.}, journal = {Molecular metabolism}, volume = {57}, number = {}, pages = {101436}, doi = {10.1016/j.molmet.2022.101436}, pmid = {34999280}, issn = {2212-8778}, mesh = {Animals ; *Ferroptosis ; Homeostasis ; Humans ; Mice ; Mitochondria/metabolism ; NF-E2-Related Factor 1/genetics/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {OBJECTIVE: Ferroptosis continues to emerge as a novel modality of cell death with important therapeutic implications for a variety of diseases, most notably cancer and degenerative diseases. While susceptibility, initiation, and execution of ferroptosis have been linked to reprogramming of cellular lipid metabolism, imbalances in iron-redox homeostasis, and aberrant mitochondrial respiration, the detailed mechanisms of ferroptosis are still insufficiently well understood.<br><br>METHODS AND RESULTS: Here we show that diminished proteasome function is a new mechanistic feature of ferroptosis. The transcription factor nuclear factor erythroid-2, like-1 (NFE2L1) protects from ferroptosis by sustaining proteasomal activity. In cellular systems, loss of NFE2L1 reduced cellular viability after the induction of both chemically and genetically induced ferroptosis, which was linked to the regulation of proteasomal activity under these conditions. Importantly, this was reproduced in a Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) patient-derived cell line carrying mutated glutathione peroxidase-4 (GPX4), a critical regulator of ferroptosis. Also, reduced proteasomal activity was associated with ferroptosis in Gpx4-deficient mice. In a mouse model for genetic Nfe2l1 deficiency, we observed brown adipose tissue (BAT) involution, hyperubiquitination of ferroptosis regulators, including the GPX4 pathway, and other hallmarks of ferroptosis.<br><br>CONCLUSION: Our data highlight the relevance of the NFE2L1-proteasome pathway in ferroptosis. Manipulation of NFE2L1 activity might enhance ferroptosis-inducing cancer therapies as well as protect from aberrant ferroptosis in neurodegeneration, general metabolism, and beyond.}, }
@article {pmid33828234, year = {2022}, author = {Hu, A and Hong, F and Li, D and Xie, Q and Chen, K and Zhu, L and He, H}, title = {KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.}, journal = {Cancer gene therapy}, volume = {29}, number = {2}, pages = {215-224}, pmid = {33828234}, issn = {1476-5500}, mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism ; LIM Domain Proteins ; Mice ; Mice, Nude ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.}, }
@article {pmid33667646, year = {2021}, author = {He, B and Chen, J and Song, W and Bai, Y}, title = {miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.}, journal = {Genomics}, volume = {113}, number = {3}, pages = {1469-1481}, doi = {10.1016/j.ygeno.2020.12.044}, pmid = {33667646}, issn = {1089-8646}, mesh = {*Carcinoma, Ductal ; Cell Line, Tumor ; DNA Methylation ; Demethylation ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; *MicroRNAs/genetics/metabolism ; Mixed Function Oxygenases/genetics/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: This study aimed to explore role of miR-646 in breast IDC.<br><br>METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.<br><br>RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.<br><br>CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.}, }
@article {pmid35155685, year = {2022}, author = {Zhang, L and Du, J and Song, Q and Zhang, C and Wu, X}, title = {A Novel In Situ Dendritic Cell Vaccine Triggered by Rose Bengal Enhances Adaptive Antitumour Immunity.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {1178874}, pmid = {35155685}, issn = {2314-7156}, mesh = {Adaptive Immunity ; Animals ; Antigen Presentation ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/*immunology ; Cell Differentiation ; Dendritic Cells/*immunology/transplantation ; Humans ; Immunization ; Immunotherapy/*methods ; Lung Neoplasms/*immunology/secondary ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma/*immunology/pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Rose Bengal/metabolism ; }, abstract = {Dendritic cell- (DC-) based vaccination has emerged as a promising antitumour immunotherapy. However, overcoming immune tolerance and immunosuppression in the tumour microenvironment (TME) is still a great challenge. Recent studies have shown that Rose Bengal (RB) can effectively induce immunogenic cell death (ICD) in cancer cells, presenting whole tumour antigens for DC processing and presentation. However, the synergistic antitumour effect of combining intralesional RB with immature DCs (RB-iDCs) remains unclear. In the present study, we investigated whether RB-iDCs have superior antitumour effects compared with either single agent and evaluated the immunological mechanism of RB-iDCs in a murine lung cancer model. The results showed that intralesional RB-iDCs suppressed subcutaneous tumour growth and lung metastasis, which resulted in 100% mouse survival and significantly increased TNF-α production by CD8+ T cells. These effects were closely related to the induction of the expression of distinct ICD hallmarks by RB in both bulk cancer cells and cancer stem cells (CSCs), especially calreticulin (CRT), thus enhancing immune effector cell (i.e., CD4+, CD8+, and memory T cells) infiltration and attenuating the accumulation of immunosuppressive cells (i.e., Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs)) in the TME. This study reveals that the RB-iDC vaccine can synergistically destroy the primary tumour, inhibit distant metastasis, and prevent tumour relapse in a lung cancer mouse model, which provides important preclinical data for the development of a novel combinatorial immunotherapy.}, }
@article {pmid34812516, year = {2022}, author = {Verbrugge, SAJ and Alhusen, JA and Kempin, S and Pillon, NJ and Rozman, J and Wackerhage, H and Kleinert, M}, title = {Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise.}, journal = {Journal of cellular biochemistry}, volume = {123}, number = {2}, pages = {202-214}, doi = {10.1002/jcb.30179}, pmid = {34812516}, issn = {1097-4644}, mesh = {Animals ; *Blood Glucose/genetics/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Humans ; Insulin Resistance/*genetics ; Muscle, Skeletal/*metabolism ; Physical Endurance/*genetics ; *Resistance Training ; }, abstract = {Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.}, }
@article {pmid34778983, year = {2022}, author = {O'Donnell, AJ and Greischar, MA and Reece, SE}, title = {Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.}, journal = {Parasite immunology}, volume = {44}, number = {3}, pages = {e12898}, doi = {10.1111/pim.12898}, pmid = {34778983}, issn = {1365-3024}, mesh = {Animals ; Circadian Rhythm/physiology ; Fasting ; *Malaria/parasitology/prevention &amp; control ; *Parasites ; *Plasmodium chabaudi/physiology ; }, abstract = {AIMS: Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.<br><br>METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours and ask whether the density of parasites affects the rescheduling process.<br><br>RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2-3 hours to become realigned to host feeding-fasting rhythms with 5-6 days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.}, }
@article {pmid33945869, year = {2021}, author = {Sethy, C and Goutam, K and Das, B and Dash, SR and Kundu, CN}, title = {Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis.}, journal = {Vascular pharmacology}, volume = {140}, number = {}, pages = {106865}, doi = {10.1016/j.vph.2021.106865}, pmid = {33945869}, issn = {1879-3649}, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Female ; Humans ; Lymphangiogenesis/physiology ; Lymphatic Metastasis/pathology ; *Lymphatic Vessels/metabolism ; Nectins/metabolism ; Receptors, CXCR4/metabolism ; }, abstract = {Tumor-induced lymphangiogenesis promotes tumor progression by generating new lymphatic vessels that helps in tumor dissemination to regional lymph nodes and distant sites. Recently, the role of Nectin-4 in cancer metastasis and angiogenesis has been studied, but its role in lymphangiogenesis is unknown. Here, we systematically delineated the role of Nectin-4 in lymphangiogenesis and its regulation in invasive duct carcinoma (IDC). Nectin-4 expression positively correlated with occurrence risk factors associated with breast cancer (alcohol, smoke, lifestyle habit, etc), CXCR4 expression, and LYVE-1-lymphatic vessel density (LVD). LVD was significantly higher in axillary lymph node (ALN) than primary tumor. Depleting Nectin-4, VEGF-C or both attenuated the important lymphangiogenic marker LYVE-1 expression, tube formation, and migration of ALN derived primary cells. Nectin-4 stimulated the expressions of CXCR4 and CXCL12 under hypoxic conditions in ALN derived primary cells. Further, Nectin-4 augmented expressions of lymphatic metastatic markers (e.g. eNOS, TGF-β, CD-105) and MMPs. Induced expressions of Nectin-4 along with other representative metastatic markers were noted in lymph and blood circulating tumor cells (LCTCs and BCTCs) of local and distant metastatic samples. Thus, Nectin-4 displayed a predominant role in promoting tumor-induced lymphangiogenesis and lymphatic metastasis by modulating CXCR4/CXCL12-LYVE-1- axis.}, }
@article {pmid35311108, year = {2022}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {708632}, pmid = {35311108}, issn = {2234-943X}, abstract = {Purpose: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) 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 TM 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 0.52 (0.28-0.96) 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 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT.<br><br>Conclusion: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.}, }
@article {pmid34401774, year = {2021}, author = {Madhavan, BK and Han, Z and Sickmann, A and Pepperkok, R and Nawroth, PP and Kumar, V}, title = {A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100700}, pmid = {34401774}, issn = {2666-1667}, mesh = {Biomechanical Phenomena/*physiology ; DNA/genetics ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Damage/genetics ; DNA Repair/genetics/*physiology ; Kinetics ; Lasers ; Microscopy, Confocal/*methods ; }, abstract = {With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2017, 2020).}, }
@article {pmid33983449, year = {2022}, author = {March, DS and Lai, KB and Neal, T and Graham-Brown, MPM and Highton, PJ and Churchward, DR and Young, HML and Dungey, M and Stensel, DJ and Smith, AC and Bishop, NC and Szeto, CC and Burton, JO}, title = {Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {2}, pages = {366-374}, doi = {10.1093/ndt/gfab178}, pmid = {33983449}, issn = {1460-2385}, mesh = {*Endotoxins ; Exercise ; Humans ; Inflammation/etiology ; Physical Fitness ; *Renal Dialysis/adverse effects ; }, abstract = {BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes.<br><br>METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months.<br><br>RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio.<br><br>CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.}, }
@article {pmid34014371, year = {2021}, author = {Giroud, M and Tsokanos, FF and Caratti, G and Kotschi, S and Khani, S and Jouffe, C and Vogl, ES and Irmler, M and Glantschnig, C and Gil-Lozano, M and Hass, D and Khan, AA and Garcia, MR and Mattijssen, F and Maida, A and Tews, D and Fischer-Posovszky, P and Feuchtinger, A and Virtanen, KA and Beckers, J and Wabitsch, M and Uhlenhaut, H and Blüher, M and Tuckermann, J and Scheideler, M and Bartelt, A and Herzig, S}, title = {HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.}, journal = {Diabetologia}, volume = {64}, number = {8}, pages = {1850-1865}, pmid = {34014371}, issn = {1432-0428}, mesh = {Adipocytes/*metabolism ; Adipogenesis/physiology ; Adipose Tissue, Brown/metabolism ; Adult ; Aged ; Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cross-Sectional Studies ; Female ; Gene Expression Regulation/*physiology ; Gene Silencing ; Glucocorticoids/*pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Obesity/*genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcription Factors/*genetics ; Young Adult ; }, abstract = {AIMS/HYPOTHESIS: Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.<br><br>METHODS: Human white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2AdipoqCre) and performed a large panel of metabolic tests.<br><br>RESULTS: We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.<br><br>CONCLUSIONS/INTERPRETATION: In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.<br><br>DATA AVAILABILITY: Array data have been submitted to the GEO database at NCBI (GSE148699).}, }
@article {pmid35260605, year = {2022}, author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and Young, K and Zein, RA and Baumert, A and Bilewicz, M and Bilgen, A and van Bezouw, MJ and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Paladino, MP and Petrović, N and Selvanathan, HP and Uluğ, ÖM and Wohl, MJ and Yeung, WLV and Burrows, B}, title = {Trust in scientific information mediates associations between conservatism and coronavirus responses in the U.S., but few other nations.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {3724}, pmid = {35260605}, issn = {2045-2322}, support = {2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; }, mesh = {Adult ; Aged ; Attitude ; COVID-19/*epidemiology/virology ; Canada ; Female ; Health Behavior ; Humans ; Indonesia ; Male ; Middle Aged ; *Politics ; Quarantine ; SARS-CoV-2/isolation &amp; purification ; Surveys and Questionnaires ; *Trust ; United States/epidemiology ; }, abstract = {U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (Ntotal = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1-2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.}, }
@article {pmid34725819, year = {2022}, author = {Chen, X and Zhang, C and Guo, D and Wang, Y and Hu, J and Hu, J and Wang, S and Liu, X}, title = {Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.}, journal = {European journal of clinical investigation}, volume = {52}, number = {4}, pages = {e13704}, doi = {10.1111/eci.13704}, pmid = {34725819}, issn = {1365-2362}, support = {2017YFC0108602//The National Key Research and Development Program of China/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*mortality/pathology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate ; }, abstract = {OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis.<br><br>METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry.<br><br>RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2 = 18784, p < 0.001; χ2 = 47.1, p < 0.001; χ2 = 20, p < 0.001).<br><br>CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.}, }
@article {pmid34561670, year = {2021}, author = {Kumar, V and Nawroth, PP}, title = {Is the association between diabetes mellitus and pulmonary fibrosis real?.}, journal = {Nature reviews. Endocrinology}, volume = {17}, number = {12}, pages = {703-704}, pmid = {34561670}, issn = {1759-5037}, mesh = {*Diabetes Mellitus/epidemiology ; Humans ; *Pulmonary Fibrosis/epidemiology ; Risk Factors ; }, }
@article {pmid34527961, year = {2021}, author = {Loft, A and Herzig, S and Schmidt, SF}, title = {Purification of GFP-tagged nuclei from frozen livers of INTACT mice for RNA- and ATAC-sequencing.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100805}, pmid = {34527961}, issn = {2666-1667}, mesh = {Animals ; Cell Nucleus/*chemistry/metabolism ; *Chromatin Immunoprecipitation Sequencing ; Cytological Techniques/*methods ; Female ; Green Fluorescent Proteins/*chemistry/genetics/metabolism ; Liver/chemistry/*cytology ; Male ; Mice ; *RNA-Seq ; }, abstract = {Isolation of nuclei tagged in specific cell types (INTACT) allows for stress-free and high-throughput analyses of cellular subpopulations. Here, we present an improved protocol for isolation of pure and high-quality GFP-labeled nuclei from frozen livers of INTACT mice, as well as protocols for downstream sequencing analyses. The adaptation to frozen tissue provides a pause point that allows sampling at multiple time points and/or phenotypic characterization of livers prior to nuclei isolation and downstream analyses. For complete details on the use of this protocol, please refer to Loft et al. (2021).}, }
@article {pmid34117742, year = {2021}, author = {Fortunato, A and Mallo, D and Rupp, SM and King, LM and Hardman, T and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC}, title = {A new method to accurately identify single nucleotide variants using small FFPE breast samples.}, journal = {Briefings in bioinformatics}, volume = {22}, number = {6}, pages = {}, pmid = {34117742}, issn = {1477-4054}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {*Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Computational Biology/*methods ; DNA, Neoplasm ; Female ; Genetic Heterogeneity ; Genetic Testing/methods/standards ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; *Polymorphism, Single Nucleotide ; Workflow ; }, abstract = {Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.}, }
@article {pmid35272171, year = {2022}, author = {Acikgoz, E and Duzagac, F and Guven, U and Yigitturk, G and Kose, T and Oktem, G}, title = {"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108684}, doi = {10.1016/j.intimp.2022.108684}, pmid = {35272171}, issn = {1878-1705}, abstract = {Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44+/CD24-/low breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.}, }
@article {pmid34624832, year = {2021}, author = {Mohammed, AA}, title = {The clinical behavior of different molecular subtypes of breast cancer.}, journal = {Cancer treatment and research communications}, volume = {29}, number = {}, pages = {100469}, doi = {10.1016/j.ctarc.2021.100469}, pmid = {34624832}, issn = {2468-2942}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous group of tumors classified, according to different gene expressions that encodes for the hormone receptor status, into 4 main categories which are: luminal types A and B, triple negative/basal-like, and Her-2 molecular subtypes.<br><br>PATIENTS AND METHODS: This retrospective study included 311 breast cancer females. Patients were classified according to the expression of hormone receptors into: Luminal-A, luminal-B, HER-2 enriched and basal-like types. All groups were then studied for differences in clinical course of the disease.<br><br>RESULTS: Luminal-B type was the commonest molecular type (43.73%). Invasive ductal carcinoma was the commonest histological type (89.1%). Stages IIB and IIIA were the commonest clinical stages (24.4% &amp; 22.2%) respectively. Most patients had no recurrence (85.5%), the commonest recurrence was local and axillary ones (7.1%). Low grade tumors were less frequent than intermediate and high grades (3.5%, 51.1%, and 45.3%). We found a significant correlation between molecular subtypes and survival status, tumor grade, and histopathological types (P values 0.029, 0.001, and 0.006) respectively, while it was not significant with age, BMI, recurrence &amp; metastatic disease, overall survival, and TNM stage (P values 0.648, 0.398, 0.5, 0.063 and 0.319).<br><br>CONCLUSION: Luminal types A and B are the commonest molecular subtypes of breast cancer. Luminal type A is associated with improved survival, and basal like has the highest breast cancer fatality rates. Invasive ductal carcinomas of specific types mostly found in patients with luminal types A and B, while other rare forms like Paget's disease was diagnosed HER-2 enriched types.}, }
@article {pmid33966256, year = {2021}, author = {Tsokanos, FF and Muley, C and Khani, S and Hass, D and Fleming, T and Wolff, G and Bartelt, A and Nawroth, P and Herzig, S}, title = {Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status.}, journal = {Thrombosis and haemostasis}, volume = {121}, number = {11}, pages = {1464-1475}, doi = {10.1055/s-0041-1726346}, pmid = {33966256}, issn = {2567-689X}, support = {Deutsche Forschungsgemeinschaft//SFB1118/ ; }, mesh = {Animals ; Cells, Cultured ; Gene Expression Profiling ; Glycolysis/*drug effects ; Macrophage Activation/*drug effects ; Macrophages/*drug effects/immunology/metabolism ; Mice ; Phenotype ; Phosphorylation ; Pyruvaldehyde/*toxicity ; Signal Transduction ; Transcriptome ; p38 Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.}, }
@article {pmid33370550, year = {2021}, author = {Wang, M and Zeng, W and Zhang, Z and Zhang, W and Su, H and Zhang, Z and Jiang, L and Liu, Y and Shi, Q}, title = {The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.}, journal = {Viral immunology}, volume = {34}, number = {2}, pages = {96-111}, doi = {10.1089/vim.2020.0052}, pmid = {33370550}, issn = {1557-8976}, mesh = {Animals ; *Hepatitis B/prevention &amp; control ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Mice ; Mice, Inbred BALB C ; *beta-Defensins/genetics ; }, abstract = {Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 μg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3+/CD4+ T cells and CD3+/CD8+ T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.}, }
@article {pmid35247977, year = {2022}, author = {Foster, GJ and Sievert, MAC and Button-Simons, K and Vendrely, KM and Romero-Severson, J and Ferdig, MT}, title = {Cyclical regression covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {180}, pmid = {35247977}, issn = {1471-2164}, support = {P01 AI127338/NH/NIH HHS/United States ; }, mesh = {Animals ; *Antimalarials/pharmacology/therapeutic use ; Drug Resistance ; Genes, Developmental ; Humans ; *Malaria, Falciparum/parasitology ; *Parasites/genetics ; Plasmodium falciparum ; Protozoan Proteins/genetics ; }, abstract = {BACKGROUND: The cyclical nature of gene expression in the intraerythrocytic development cycle (IDC) of the malaria parasite, Plasmodium falciparum, confounds the accurate detection of specific transcriptional differences, e.g. as provoked by the development of drug resistance. In lab-based studies, P. falciparum cultures are synchronized to remove this confounding factor, but the rapid detection of emerging resistance to artemisinin therapies requires rapid analysis of transcriptomes extracted directly from clinical samples. Here we propose the use of cyclical regression covariates (CRC) to eliminate the major confounding effect of developmentally driven transcriptional changes in clinical samples. We show that elimination of this confounding factor reduces both Type I and Type II errors and demonstrate the effectiveness of this approach using a published dataset of 1043 transcriptomes extracted directly from patient blood samples with different patient clearance times after treatment with artemisinin.<br><br>RESULTS: We apply this method to two publicly available datasets and demonstrate its ability to reduce the confounding of differences in transcript levels due to misaligned intraerythrocytic development time. Adjusting the clinical 1043 transcriptomes dataset with CRC results in detection of fewer functional categories than previously reported from the same data set adjusted using other methods. We also detect mostly the same functional categories, but observe fewer genes within these categories. Finally, the CRC method identifies genes in a functional category that was absent from the results when the dataset was adjusted using other methods. Analysis of differential gene expression in the clinical data samples that vary broadly for developmental stage resulted in the detection of far fewer transcripts in fewer functional categories while, at the same time, identifying genes in two functional categories not present in the unadjusted data analysis. These differences are consistent with the expectation that CRC reduces both false positives and false negatives with the largest effect on datasets from samples with greater variance in developmental stage.<br><br>CONCLUSIONS: Cyclical regression covariates have immediate application to parasite transcriptome sequencing directly from clinical blood samples and to cost-constrained in vitro experiments.}, }
@article {pmid35220223, year = {2022}, author = {Dantas, FT and Felix-Silva, PH and Angotti-Carrara, HH and Dos-Reis, FJC and Junior, MT and DE-Souza, SLS and Palioto, DB}, title = {A New Method for Obtaining Tumor Interstitial Fluid Applied to Cytokine Analysis of Breast Carcinoma Samples.}, journal = {Anticancer research}, volume = {42}, number = {3}, pages = {1327-1332}, doi = {10.21873/anticanres.15600}, pmid = {35220223}, issn = {1791-7530}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Large-Core Needle ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid/*immunology ; Female ; Humans ; Interleukin-1beta/*analysis ; Middle Aged ; Tumor Microenvironment ; }, abstract = {BACKGROUND/AIM: Tumor interstitial fluid (TIF), a component of the tumor microenvironment, is a valuable source of molecules and substances that help in diagnosis and prognosis of solid tumors. There is still no consensus on the optimal method for collecting TIF. Therefore, this study aimed to evaluate the effectiveness of a new method of collecting TIF in invasive ductal carcinoma (IDC) samples for cytokine interleukin 1β (IL1β) quantification.<br><br>MATERIALS AND METHODS: Forty women allowed the collection of TIF using absorbent paper strips during the performance of the core biopsy. The samples were stored at a temperature of -80°C and then analyzed using an enzyme-linked immunoassay.<br><br>RESULTS: The mean values for IL1β and total protein were 11.39 mg/ml and 2.15 mg/ml, respectively.<br><br>CONCLUSION: it was possible to quantify the cytokine IL1β and the total protein concentration present in the tumor tissue through TIF collection with the use of absorbent paper filters, demonstrating the effectiveness of this new method in oncology.}, }
@article {pmid34975349, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E}, title = {Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.}, journal = {TheScientificWorldJournal}, volume = {2021}, number = {}, pages = {6672274}, pmid = {34975349}, issn = {1537-744X}, mesh = {*Body Mass Index ; *Exercise Therapy ; Female ; Humans ; Lower Extremity/*physiopathology ; Male ; Middle Aged ; Obesity/*complications ; Osteoarthritis, Knee/complications/physiopathology/*rehabilitation ; Overweight/*complications ; Pain/*complications ; Range of Motion, Articular ; Single-Blind Method ; }, abstract = {Background: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups.<br><br>Results: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p ≤ 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG.<br><br>Conclusion: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.}, }
@article {pmid35245349, year = {2022}, author = {Hophan, SL and Odnokoz, O and Liu, H and Luo, Y and Khan, S and Gradishar, W and Zhou, Z and Badve, S and Torres, MA and Wan, Y}, title = {Ductal carcinoma in situ of breast: from molecular etiology to therapeutic management.}, journal = {Endocrinology}, volume = {}, number = {}, pages = {}, doi = {10.1210/endocr/bqac027}, pmid = {35245349}, issn = {1945-7170}, abstract = {Ductal Carcinoma in Situ (DCIS) makes up a majority of the non-invasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms for progression into an invasive status by approximately half of all DCIS lesions. New strategies that target molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.}, }
@article {pmid35130270, year = {2022}, author = {Khanam, R and Applegate, J and Nisar, I and Dutta, A and Rahman, S and Nizar, A and Ali, SM and Chowdhury, NH and Begum, F and Dhingra, U and Tofail, F and Mehmood, U and Deb, S and Ahmed, S and Muhammad, S and Das, S and Ahmed, S and Mittal, H and Minckas, N and Yoshida, S and Bahl, R and Jehan, F and Sazawal, S and Baqui, AH}, title = {Burden and risk factors for antenatal depression and its effect on preterm birth in South Asia: A population-based cohort study.}, journal = {PloS one}, volume = {17}, number = {2}, pages = {e0263091}, pmid = {35130270}, issn = {1932-6203}, mesh = {Adult ; Asia/epidemiology ; Bangladesh/epidemiology ; Cohort Studies ; Depression/complications/*epidemiology ; Female ; Humans ; Infant, Newborn ; Pakistan/epidemiology ; Pregnancy ; Pregnancy Complications/epidemiology/psychology ; Pregnancy Outcome/*epidemiology/psychology ; Premature Birth/*epidemiology ; Prenatal Care/statistics &amp; numerical data ; Risk Factors ; Young Adult ; }, abstract = {INTRODUCTION: Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal depression, its risk factors, and its effect on preterm birth.<br><br>METHODS: The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of ≥12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP).<br><br>RESULTS: About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of ≥2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74).<br><br>CONCLUSION: The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.}, }
@article {pmid34841287, year = {2021}, author = {Erener, S and Ellis, CE and Ramzy, A and Glavas, MM and O'Dwyer, S and Pereira, S and Wang, T and Pang, J and Bruin, JE and Riedel, MJ and Baker, RK and Webber, TD and Lesina, M and Blüher, M and Algül, H and Kopp, JL and Herzig, S and Kieffer, TJ}, title = {Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice.}, journal = {Cell reports. Medicine}, volume = {2}, number = {11}, pages = {100434}, pmid = {34841287}, issn = {2666-3791}, support = {//CIHR/Canada ; }, mesh = {Animals ; Apoptosis ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; Diet, High-Fat ; *Disease Progression ; *Gene Deletion ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism/*pathology ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Organ Specificity ; Pancreatic Neoplasms/*genetics/*pathology ; Rats ; }, abstract = {miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line Kras G12D ;Ptf1a CreER reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.}, }
@article {pmid34781210, year = {2021}, author = {Jeong, JS and Cho, KJ and Kim, D and Lee, YS and Song, JS}, title = {Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.}, journal = {Pathology, research and practice}, volume = {228}, number = {}, pages = {153678}, doi = {10.1016/j.prp.2021.153678}, pmid = {34781210}, issn = {1618-0631}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Middle Aged ; Salivary Ducts/pathology ; Salivary Gland Neoplasms/genetics/*pathology ; }, abstract = {AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC.<br><br>METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas.<br><br>CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.}, }
@article {pmid34702045, year = {2021}, author = {Ilbeigi, S and Naeimzadeh, Y and Davoodabadi Farahani, M and Rafi Monjezi, M and Dastsooz, H and Daraei, A and Farahani, F and Dastgheib, A and Mansoori, Y and Tabei, SMB}, title = {Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {34}, number = {5}, pages = {382-391}, doi = {10.48095/ccko2021382}, pmid = {34702045}, issn = {1802-5307}, mesh = {Adult ; Aged ; Breast/metabolism ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Computational Biology ; Female ; Humans ; Middle Aged ; *RNA, Long Noncoding ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC.<br><br>METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done.<br><br>RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10).<br><br>CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.}, }
@article {pmid34219706, year = {2022}, author = {Avau, F and Chintinne, M and Baudry, S and Buxant, F}, title = {Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {5-13}, doi = {10.3233/BD-210001}, pmid = {34219706}, issn = {1558-1551}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*complications/drug therapy/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/drug therapy/*secondary ; Carcinoma, Papillary/classification/*diagnostic imaging/drug therapy ; Humans ; Male ; Mammography ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.}, }
@article {pmid35114136, year = {2022}, author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR}, title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.}, journal = {The lancet. Diabetes &amp; endocrinology}, volume = {10}, number = {3}, pages = {221-230}, doi = {10.1016/S2213-8587(21)00346-6}, pmid = {35114136}, issn = {2213-8595}, mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; }, abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.}, }
@article {pmid34717732, year = {2021}, author = {Ropri, AS and DeVaux, RS and Eng, J and Chittur, SV and Herschkowitz, JI}, title = {Cis-acting super-enhancer lncRNAs as biomarkers to early-stage breast cancer.}, journal = {Breast cancer research : BCR}, volume = {23}, number = {1}, pages = {101}, pmid = {34717732}, issn = {1465-542X}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line ; Disease Progression ; Enhancer Elements, Genetic/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/*genetics ; Receptors, Estrogen/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {BACKGROUND: Increased breast cancer screening over the past four decades has led to a substantial rise in the diagnosis of ductal carcinoma in situ (DCIS). Although DCIS lesions precede invasive ductal carcinoma (IDC), they do not always transform into cancer. The current standard-of-care for DCIS is an aggressive course of therapy to prevent invasive and metastatic disease resulting in over-diagnosis and over-treatment. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive disease. Recent studies show that super-enhancers, in addition to promoting other gene transcription, are themselves transcribed producing super-enhancer associated long noncoding RNAs (SE-lncRNAs). These SE-lncRNAs can interact with their associated enhancer regions in cis and influence activities and expression of neighboring genes. Furthermore, they represent a novel, untapped group of therapeutic targets.<br><br>METHODS: With an integrative analysis of enhancer loci with global expression of SE-lncRNAs in the MCF10A progression series, we have identified differentially expressed SE-lncRNAs which can identify mechanisms for DCIS to IDC progression. Furthermore, cross-referencing these SE-lncRNAs with patient samples in the The Cancer Genome Atlas (TCGA) database, we have unveiled 27 clinically relevant SE-lncRNAs that potentially interact with their enhancer to regulate nearby gene expression. To complement SE-lncRNA expression studies, we conducted an unbiased global analysis of super-enhancers that are acquired or lost in progression.<br><br>RESULTS: Here we designate SE-lncRNAs RP11-379F4.4 and RP11-465B22.8 as potential markers of progression of DCIS to IDC through regulation of the expression of their neighboring genes (RARRES1 and miR-200b, respectively). Moreover, we classified 403 super-enhancer regions in MCF10A normal cells, 627 in AT1, 1053 in DCIS, and 320 in CA1 cells. Comparison analysis of acquired/lost super-enhancer regions with super-enhancer regions classified in 47 ER positive patients, 10 triple negative breast cancer (TNBC) patients, and 11 TNBC cell lines reveal critically acquired pathways including STAT signaling and NF-kB signaling. In contrast, protein folding, and local estrogen production are identified as major pathways lost in progression.<br><br>CONCLUSION: Collectively, these analyses identify differentially expressed SE-lncRNAs and acquired/lost super-enhancers in progression of breast cancer important for promoting DCIS lesions to IDC.}, }
@article {pmid34560418, year = {2021}, author = {Wan, D and Zhang, Y and Yu, Q and Li, F and Zhuo, J}, title = {14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression.}, journal = {Pathology, research and practice}, volume = {227}, number = {}, pages = {153619}, doi = {10.1016/j.prp.2021.153619}, pmid = {34560418}, issn = {1618-0631}, mesh = {14-3-3 Proteins/genetics/*metabolism ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/analysis ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/analysis ; Up-Regulation ; Young Adult ; Zinc Finger Protein Gli2/analysis ; }, abstract = {BACKGROUND: HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14-3-3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too.<br><br>METHODS: Immunohistochemistry experiment was performed to detect expression status of 14-3-3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC.<br><br>RESULTS: The positive expression rates of 14-3-3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14-3-3ζ was significantly increased in ADH, DCIS and IDC groups. 14-3-3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14-3-3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14-3-3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14-3-3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14-3-3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14-3-3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14-3-3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively.<br><br>CONCLUSION: 14-3-3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14-3-3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14-3-3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.}, }
@article {pmid34812466, year = {2021}, author = {Feresin, RG and Johnson, SA and Elam, ML and Pourafshar, S and Navaei, N and Akhavan, NS and Tenenbaum, G and Figueroa, A and Arjmandi, BH}, title = {Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.}, journal = {Food &amp; function}, volume = {12}, number = {24}, pages = {12526-12534}, doi = {10.1039/d1fo01555a}, pmid = {34812466}, issn = {2042-650X}, mesh = {Aged ; Biomarkers/blood ; Bone Density/*drug effects ; Bone Resorption/blood/drug therapy ; Female ; *Fragaria ; Humans ; Hypertension/blood/complications/*drug therapy ; Middle Aged ; Osteoporosis, Postmenopausal/blood/complications/*prevention &amp; control ; Plant Extracts/blood/*pharmacology ; Polyphenols/blood/*pharmacology ; Postmenopause ; }, abstract = {Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.}, }
@article {pmid35207775, year = {2022}, author = {Huang, CC and Chang, CL and Sun, M and Chiang, MF and Sum, SY and Zhang, J and Wu, SY}, title = {Adjuvant Radiotherapy Is Associated with an Increase in the Survival of Old (Aged over 80 Years) and Very Old (Aged over 90 Years) Women with Breast Cancer Receiving Breast-Conserving Surgery.}, journal = {Journal of personalized medicine}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/jpm12020287}, pmid = {35207775}, issn = {2075-4426}, abstract = {This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44-0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19-0.45) and 0.45 (0.32-0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.}, }
@article {pmid35200056, year = {2022}, author = {Hannarici, Z and Yılmaz, A and Buyukbayram, ME and Turhan, A and Tekin, SB and Bilici, M}, title = {Lipegfilgrastim may cause hyperleukocytosis.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {}, number = {}, pages = {10781552221082645}, doi = {10.1177/10781552221082645}, pmid = {35200056}, issn = {1477-092X}, abstract = {INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well.<br><br>CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420 mg), trastuzumab (8-6mg/kg), and docetaxel (75 mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift.<br><br>MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems.<br><br>DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.}, }
@article {pmid34592934, year = {2021}, author = {Mathew, D and Gupta, S and Ashman, N}, title = {A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies.}, journal = {BMC nephrology}, volume = {22}, number = {1}, pages = {324}, pmid = {34592934}, issn = {1471-2369}, mesh = {Adult ; Autoantibodies/*blood ; Breast Neoplasms/*complications ; Estrogen Receptor beta/analysis ; Female ; Glomerulonephritis, Membranous/*complications/immunology ; Humans ; Kidney/pathology ; Receptors, Phospholipase A2/*immunology ; }, abstract = {BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer.<br><br>CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome.<br><br>DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.}, }
@article {pmid33960872, year = {2021}, author = {Alvarez, DR and Ospina, A and Barwell, T and Zheng, B and Dey, A and Li, C and Basu, S and Shi, X and Kadri, S and Chakrabarti, K}, title = {The RNA structurome in the asexual blood stages of malaria pathogen plasmodium falciparum.}, journal = {RNA biology}, volume = {18}, number = {12}, pages = {2480-2497}, pmid = {33960872}, issn = {1555-8584}, mesh = {Erythrocytes/*metabolism ; *Gene Expression Regulation ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*parasitology ; *Nucleic Acid Conformation ; Plasmodium falciparum/*genetics/growth &amp; development/pathogenicity ; Protozoan Proteins/genetics/metabolism ; RNA, Protozoan/*chemistry ; Transcriptome ; }, abstract = {Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and non-coding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis that combined high-throughput nuclease mapping of RNA structures by duplex RNA-seq, SHAPE-directed RNA structure validation, immunoaffinity purification and characterization of antisense RNAs collectively measured differentially base-paired RNA regions throughout the parasite's asexual RBC cycle. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, approximately 71% of the genes with secondary structures are found to be protein coding mRNAs. The mapping pattern of these base-paired RNAs corresponded to all regions of mRNAs, including the 5' UTR, CDS and 3' UTR as well as the start and stop codons. Histone family genes which are known to form secondary structures in their mRNAs and transcripts from genes which are important for transcriptional and post-transcriptional control, such as the unique plant-like transcription factor family, ApiAP2, DNA-/RNA-binding protein, Alba3 and proteins important for RBC invasion and malaria cytoadherence also showed strong accumulation of duplex RNA reads in various asexual stages in P. falciparum. Intriguingly, our study determined stage-specific, dynamic relationships between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs. Abbreviations: CDS: Coding Sequence; DNA: Deoxyribonucleic Acid; dsRNA: double-stranded RNA; IDC: Intra-erythrocytic Developmental Cycle (IDC); m6A: N6-methyladenosine; mRNA: Messenger RNA; ncRNA: Non-coding RNA; RBC: Red Blood cells; RBP: RNA-Binding Protein; REC: Relative Expression Counts; RNA-seq: RNA-sequencing; RNA: Ribonucleic Acid; RNP: Ribonucleoprotein; RPKM: Reads Per Kilobase of transcript Per Million; rRNA: Ribosomal RNA 16. RUFs: RNAs of Unknown Function; SHAPE: Selective 2'-hydroxyl acylation analysed by primer extension; snoRNA: Small Nucleolar RNA; snRNA: Small Nuclear RNA; SRP-RNA: Signal Recognition Particle RNA; ssRNA: (Single-stranded RNA); TE: Translation Efficiency; tRNA: transfer RNA; UTR: Untranslated Region.}, }
@article {pmid35074971, year = {2022}, author = {Kumari, S and Mishra, S and Husain, N and Verma, T and Tiwari, V and Kaif, M and Agarwal, A and Rastogi, M and Shukla, S and Sonkar, AA}, title = {Comparison of circulating DNA in malignant neoplasia from diverse locations: Investigating a diagnostic role.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {65}, number = {1}, pages = {93-99}, doi = {10.4103/IJPM.IJPM_474_20}, pmid = {35074971}, issn = {0974-5130}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/genetics ; Brain Neoplasms/blood/diagnosis/genetics ; Carcinoma, Squamous Cell/blood/diagnosis/genetics ; Cell-Free Nucleic Acids/*blood ; Female ; Gallbladder Neoplasms/blood/diagnosis/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/blood/classification/*diagnosis/*genetics ; Young Adult ; }, abstract = {Context: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage.<br><br>Design: Serum samples were collected from treatment naïve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis.<br><br>Results: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases.<br><br>Conclusion: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.}, }
@article {pmid35011590, year = {2021}, author = {Greulich, F and Bielefeld, KA and Scheundel, R and Mechtidou, A and Strickland, B and Uhlenhaut, NH}, title = {Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages.}, journal = {Cells}, volume = {11}, number = {1}, pages = {}, pmid = {35011590}, issn = {2073-4409}, support = {GR 5179/1-1//Deutsche Forschungsgemeinschaft/ ; UH 275/1-1//Deutsche Forschungsgemeinschaft/ ; ERC-2014-StG 638573/ERC_/European Research Council/International ; TRR205, The Adrenal//Deutsche Forschungsgemeinschaft/ ; CRC1064 Chromatin Dynamics//Deutsche Forschungsgemeinschaf/ ; }, mesh = {Acetylation/drug effects ; Animals ; Binding Sites ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Glucocorticoids/*pharmacology ; Histones/metabolism ; Lysine/metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism ; Organ Specificity/drug effects ; RNA/*genetics/metabolism ; Receptors, Glucocorticoid/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; }, abstract = {Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR's transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.}, }
@article {pmid34272624, year = {2021}, author = {Considine, B and Adeniran, A and Hurwitz, ME}, title = {Current Understanding and Management of Intraductal Carcinoma of the Prostate.}, journal = {Current oncology reports}, volume = {23}, number = {9}, pages = {110}, pmid = {34272624}, issn = {1534-6269}, mesh = {Carcinoma, Ductal/*genetics/pathology/therapy ; DNA Mismatch Repair/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; *Microsatellite Instability ; *Mutation ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/pathology/therapy ; Signal Transduction/genetics ; }, abstract = {PURPOSE OF REVIEW: This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts.<br><br>RECENT FINDINGS: The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.}, }
@article {pmid34816360, year = {2022}, author = {Mizukoshi, K and Fujii, M and Yamauchi, Y and Fukuda, A and Seno, H}, title = {A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.}, journal = {Clinical journal of gastroenterology}, volume = {15}, number = {1}, pages = {199-204}, pmid = {34816360}, issn = {1865-7265}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal/surgery ; Constriction, Pathologic/etiology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Retroperitoneal Neoplasms/surgery ; }, abstract = {A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&amp;E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.}, }
@article {pmid35187122, year = {2022}, author = {Neves, EGA and Koh, CC and Souza-Silva, TG and Passos, LSA and Silva, ACC and Velikkakam, T and Villani, F and Coelho, JS and Brodskyn, CI and Teixeira, A and Gollob, KJ and Nunes, MDCP and Dutra, WO}, title = {T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {787423}, doi = {10.3389/fcvm.2022.787423}, pmid = {35187122}, issn = {2297-055X}, abstract = {Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.}, }
@article {pmid33827325, year = {2021}, author = {Weaver, KD and Isom, J and Esnakula, A and Daily, K and Asirvatham, JR}, title = {Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies.}, journal = {International journal of surgical pathology}, volume = {29}, number = {8}, pages = {882-886}, doi = {10.1177/10668969211008508}, pmid = {33827325}, issn = {1940-2465}, mesh = {Adult ; Anoctamin-1/analysis/metabolism ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Breast/*pathology/surgery ; Carcinoma, Acinar Cell/*diagnosis/genetics/pathology ; DNA Mutational Analysis ; Female ; GATA3 Transcription Factor/analysis/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Mastectomy ; Neoplasm Proteins/analysis/metabolism ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/genetics/pathology ; Proto-Oncogene Proteins c-ret/genetics ; Sentinel Lymph Node Biopsy ; Triple Negative Breast Neoplasms/*diagnosis/genetics/pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.}, }
@article {pmid34538726, year = {2022}, author = {Ramotar, M and Chua, MLK and Truong, H and Hosni, A and Pintilie, M and Davicioni, E and Fleshner, NE and Dicker, AP and Bristow, RG and He, HH and van der Kwast, T and Den, RB and Berlin, A}, title = {Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.}, journal = {Urologic oncology}, volume = {40}, number = {1}, pages = {5.e1-5.e13}, doi = {10.1016/j.urolonc.2021.08.013}, pmid = {34538726}, issn = {1873-2496}, mesh = {Adult ; Aged ; Cohort Studies ; Combined Modality Therapy ; Genome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; *Prostatectomy ; Prostatic Neoplasms/*classification/genetics/*radiotherapy/surgery ; }, abstract = {PURPOSE/OBJECTIVE: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.<br><br>MATERIAL/METHODS: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.<br><br>RESULTS: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P = 0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P = 0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index = 0.737 (95%CI 0.662-0.813)).<br><br>CONCLUSIONS: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.}, }
@article {pmid34881777, year = {2022}, author = {Sidhanth, C and Bindhya, S and Shabna, A and Krishnapriya, S and Manasa, P and Nagare, RP and Joshua, T and Sneha, S and Murhekar, K and Ganesan, TS}, title = {LASP-1 interacts with ErbB2 in ovarian cancer cells.}, journal = {The Biochemical journal}, volume = {479}, number = {1}, pages = {23-38}, doi = {10.1042/BCJ20210173}, pmid = {34881777}, issn = {1470-8728}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Ovarian Epithelial/*metabolism/pathology ; Cell Line, Tumor ; Cohort Studies ; Cytoskeletal Proteins/genetics/*metabolism ; Female ; HEK293 Cells ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Lapatinib/pharmacology ; Middle Aged ; Ovarian Neoplasms/*metabolism/pathology ; Phosphorylation/drug effects/genetics ; Plasmids ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Receptor, ErbB-2/genetics/*metabolism ; Signal Transduction/drug effects/*genetics ; Transfection ; }, abstract = {LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.}, }
@article {pmid34801929, year = {2022}, author = {Mampel, A and Sottile, ML and Denita-Juárez, SP and Vargas, AL and Vargas-Roig, LM}, title = {Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer.}, journal = {Cancer genetics}, volume = {260-261}, number = {}, pages = {14-17}, doi = {10.1016/j.cancergen.2021.11.003}, pmid = {34801929}, issn = {2210-7762}, mesh = {Adult ; Aged ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Heterozygote ; Humans ; Male ; Neoplasms, Second Primary/*genetics ; Pedigree ; *Point Mutation ; Sequence Analysis, DNA ; *Sequence Deletion ; }, abstract = {Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.}, }
@article {pmid34321100, year = {2021}, author = {Meyer, D and Kames, J and Bar, H and Komar, AA and Alexaki, A and Ibla, J and Hunt, RC and Santana-Quintero, LV and Golikov, A and DiCuccio, M and Kimchi-Sarfaty, C}, title = {Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {122}, pmid = {34321100}, issn = {1756-994X}, support = {R01 HL151392/HL/NHLBI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; *Codon ; *Codon Usage ; Computational Biology/*methods ; *Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Kaplan-Meier Estimate ; Neoplasms/*diagnosis/*genetics/mortality ; Prognosis ; Transcriptome ; }, abstract = {BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.<br><br>METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.<br><br>RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.<br><br>CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.}, }
@article {pmid35159086, year = {2022}, author = {Pantazopoulos, H and Diop, MK and Grosset, AA and Rouleau-Gagné, F and Al-Saleh, A and Boblea, T and Trudel, D}, title = {Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/cancers14030820}, pmid = {35159086}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is one of the most aggressive types of prostate cancer (PCa). IDC-P is identified in approximately 20% of PCa patients and is associated with recurrence, metastasis, and PCa-specific death. The main feature of this histological variant is the colonization of benign glands by PCa cells. Although IDC-P is a well-recognized independent parameter for metastasis, mechanisms by which IDC-P cells can spread and colonize other tissues are not fully known. In this review, we discuss the molecular portraits of IDC-P determined by immunohistochemistry and genomic approaches and highlight the areas in which more research is needed.}, }
@article {pmid35159065, year = {2022}, author = {Chen, YC and Chen, WM and Chiang, MF and Shia, BC and Wu, SY}, title = {Association between Pre-Existing Sleep Disorders and Survival Rates of Patients with Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/cancers14030798}, pmid = {35159065}, issn = {2072-6694}, abstract = {PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC).<br><br>METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I-III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching.<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001).<br><br>CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.}, }
@article {pmid34098822, year = {2021}, author = {Maitre, T and Ok, V and Calin, R and Lassel, L and Canestri, A and Denis, M and Hamidi, M and Tavolaro, S and Verdet, C and Parrot, A and Cadranel, J and Pialoux, G}, title = {Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.}, journal = {Therapeutic advances in respiratory disease}, volume = {15}, number = {}, pages = {17534666211003012}, pmid = {34098822}, issn = {1753-4666}, mesh = {Hospital Units ; Humans ; *Liver Abscess, Pyogenic/epidemiology/therapy ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors.<br><br>METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded.<br><br>RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p = 0.03), the absence of smoking or emphysema (p = 0.05), Staphylococcus aureus (p = 0.001) or Streptococcus spp. (p = 0.05) isolation, and the smaller size of their abscess (p = 0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p = 0.02), particularly when they spontaneously discharged (p = 0.04). Relapses were more frequent in patients with emphysema (p = 0.04) and when Haemophilus influenzae was isolated (p = 0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p = 0.02), and in those who received antibiotics during less than 6 weeks (p = 0.05).<br><br>CONCLUSION: A duration of antibiotic treatment of less than 6 weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.}, }
@article {pmid35151355, year = {2022}, author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY}, title = {Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy.}, journal = {Radiation oncology (London, England)}, volume = {17}, number = {1}, pages = {33}, pmid = {35151355}, issn = {1748-717X}, abstract = {BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).<br><br>PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).<br><br>RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P = 0.0356) and 0.89 (0.54-1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group.<br><br>CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.}, }
@article {pmid34058243, year = {2021}, author = {Hesterberg, AB and Gordetsky, JB and Hurley, PJ}, title = {Cribriform Prostate Cancer: Clinical Pathologic and Molecular Considerations.}, journal = {Urology}, volume = {155}, number = {}, pages = {47-54}, doi = {10.1016/j.urology.2021.05.028}, pmid = {34058243}, issn = {1527-9995}, mesh = {Humans ; Male ; Molecular Diagnostic Techniques ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*genetics/pathology ; }, abstract = {Intraductal cribriform (IDC) and invasive cribriform morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations.}, }
@article {pmid33947745, year = {2021}, author = {Sottnik, JL and Bordeaux, EK and Mehrotra, S and Ferrara, SE and Goodspeed, AE and Costello, JC and Sikora, MJ}, title = {Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {8}, pages = {1270-1282}, pmid = {33947745}, issn = {1557-3125}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; R00 CA193734/CA/NCI NIH HHS/United States ; T32 GM007635/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Breast/pathology ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Lobular/drug therapy/*genetics/pathology ; Cell Cycle Proteins/*genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; MCF-7 Cells ; Promoter Regions, Genetic/drug effects/genetics ; Receptors, Estrogen/*genetics ; Signal Transduction/genetics ; Tamoxifen/therapeutic use ; Transcriptome/drug effects/genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer, and nearly all ILC tumors express estrogen receptor alpha (ER). However, clinical and laboratory data suggest ILC are strongly estrogen-driven but not equally antiestrogen-sensitive. We hypothesized ILC-specific ER coregulators mediate ER functions and antiestrogen resistance in ILC, and profiled ER-associated proteins by mass spectrometry. Three ER+ ILC cell lines (MDA MB 134VI, SUM44PE, and BCK4) were compared with ER+ invasive ductal carcinoma (IDC) line data, and we examined whether siRNA of identified proteins suppressed ER-driven proliferation in ILC cells. This identified mediator of DNA damage checkpoint 1 (MDC1), a tumor suppressor in DNA damage response (DDR), as a novel ER coregulator in ILC. We confirmed ER:MDC1 interaction was specific to ILC versus IDC cells, and found MDC1 knockdown suppressed ILC cell proliferation and tamoxifen resistance. Using RNA-sequencing, we found in ILC cells MDC1 knockdown broadly dysregulates the ER transcriptome, with ER:MDC1 target genes enriched for promoter hormone response elements. Importantly, our data are inconsistent with MDC1 tumor suppressor functions in DDR, but suggest a novel oncogenic role for MDC1 as an ER coregulator. Supporting this, in breast tumor tissue microarrays, MDC1 protein was frequently low or absent in IDC, but MDC1 loss was rare in ER+ ILC. ER:MDC1 interaction and MDC1 coregulator functions may underlie ER function in ILC and serve as targets to overcome antiestrogen resistance in ILC. IMPLICATIONS: MDC1 has novel ER coregulator activity in ILC, which may underlie ILC-specific ER functions, estrogen response, and antiestrogen resistance.}, }
@article {pmid33561470, year = {2021}, author = {Kabay, S and Kabay, SC}, title = {The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results.}, journal = {Urology}, volume = {153}, number = {}, pages = {49-55}, doi = {10.1016/j.urology.2021.01.044}, pmid = {33561470}, issn = {1527-9995}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lower Urinary Tract Symptoms/etiology/*therapy ; Male ; Middle Aged ; Parkinson Disease/complications ; Prospective Studies ; *Tibial Nerve ; Time Factors ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology/*therapy ; Urodynamics ; }, abstract = {OBJECTIVE: To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months.<br><br>METHODS: After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3rd, 6th, 9th,12th and 24th month.<br><br>RESULTS: A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P ˃.05).<br><br>CONCLUSIONS: These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.}, }
@article {pmid34022480, year = {2021}, author = {Hoshina, H and Takei, H and Nakamura, M and Nishimoto, F and Hanamura, S}, title = {Carcinomatous cirrhosis as radiographically occult liver metastases of breast cancer: A systematic literature review.}, journal = {Cancer treatment and research communications}, volume = {28}, number = {}, pages = {100388}, doi = {10.1016/j.ctarc.2021.100388}, pmid = {34022480}, issn = {2468-2942}, mesh = {Ascites/*diagnosis/etiology ; Breast Neoplasms/*pathology ; Female ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Liver Neoplasms/complications/*diagnosis/secondary ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; }, abstract = {In the present study, we aimed to clarify features of carcinomatous cirrhosis from breast cancer presenting as refractory transudate ascites and acute liver failure. In our systematic literature review, we identified 26 studies and 31 cases including our case of this rare condition. Our patient was a 49-year-old woman with a history of ascites and liver failure for the past 4 years and currently being treated for invasive ductal breast cancer. On radiography, she had occult liver metastases that were confirmed using laparoscopic liver biopsy. In the 31 cases, data on the reported year, age, type of primary breast cancer, time from breast cancer diagnosis, presence of ascites and/or varices, liver biopsy, diagnostic modalities, outcomes, and survival were documented and analyzed. All cases were reported during 1984-2020, with a mean patient age of 52.9 years. Eighteen patients (58.1%) were diagnosed with ductal breast cancer. Twenty-two patients (70.9%) had ascites. All patients had gradual progression to liver dysfunction. The following tests were performed: computed tomography (77.4%); ultrasound (58.0%); liver biopsy (100%); postmortem biopsy (35.5%), transjugular liver biopsy (32.3%), and laparoscopic liver biopsy (3.2%). Outcomes were reported for 29 patients, of whom 24 (82.3%) died after 1 day to 16 months. Invasive ductal carcinoma was the most common histological type; however, invasive lobular carcinoma was more frequent (32.3%) than its reported incidence in the breast. Carcinomatous cirrhosis has poor prognosis at relatively rash and is difficult to diagnose with usual modalities. It may be associated with E-cadherin loss or CD44 pronouncement.}, }
@article {pmid34673584, year = {2021}, author = {Senel, F}, title = {The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {4}, pages = {671-676}, doi = {10.4103/IJPM.IJPM_606_20}, pmid = {34673584}, issn = {0974-5130}, mesh = {Adult ; Age Factors ; Biomarkers, Tumor/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/*physiopathology ; Female ; Genetic Variation ; Genotype ; Humans ; Middle Aged ; Pathology, Clinical/methods ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; }, abstract = {Aim: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features.<br><br>Materials and Methods: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded.<br><br>Results and Conclusions: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.}, }
@article {pmid34668757, year = {2021}, author = {Saelens, JW and Petersen, JEV and Freedman, E and Moseley, RC and Konaté, D and Diakité, SAS and Traoré, K and Vance, N and Fairhurst, RM and Diakité, M and Haase, SB and Taylor, SM}, title = {Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0075521}, pmid = {34668757}, issn = {2379-5042}, support = {R21 AI125988/AI/NIAID NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Hemoglobin A/*genetics ; Hemoglobin, Sickle/*genetics ; Hemoglobins/metabolism ; Humans ; Malaria, Falciparum/blood/*genetics/parasitology ; Male ; Plasmodium falciparum/physiology ; Sickle Cell Trait/blood/*genetics/parasitology ; Transcriptional Activation ; }, abstract = {Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both in vitro cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During in vitro cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen in vitro and in vivo indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites. IMPORTANCE Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in in vitro time series experiments and in vivo samples from natural infections. Our in vitro time series data reveal that, during its blood stage, P. falciparum's gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our in vitro and in vivo data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.}, }
@article {pmid35071526, year = {2022}, author = {Wang, L and Jiang, Q and He, MY and Shen, P}, title = {HER2 changes to positive after neoadjuvant chemotherapy in breast cancer: A case report and literature review.}, journal = {World journal of clinical cases}, volume = {10}, number = {1}, pages = {260-267}, pmid = {35071526}, issn = {2307-8960}, abstract = {BACKGROUND: As the most common cancer in women, breast cancer is the leading cause of death. Most patients are initially diagnosed as stage I-III. Among those without distant metastases, 64% are local tumors and 27% are regional tumors. Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy (NACT). It is worth noting that the status of tumor cell biomarkers is not consistently static. Endocrine-related estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa, especially in luminal B subtype after NACT. In addition, determination of HER2 status currently mainly relies on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), but FISH is commonly used when the result of IHC is uncertain. HER2 is regarded as negative when the IHC result is 0/1+ without the addition of FISH. To the best of our knowledge, this is the first report of a case harboring HER2 status transformation and IHC1+ with positive amplification by FISH after NACT.<br><br>CASE SUMMARY: A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup. Biopsies of the right breast lesion and axillary lymph nodes were obtained. The results pointed to invasive ductal carcinoma with the IHC result for ER (80%), PR (60%), Ki-67 (20%) and ambiguous expression of HER2 (IHC 2+) with negative amplification by FISH (HER2/CEP17 ratio of 1.13). She underwent surgery after NACT. The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm × 0.8 cm × 0.5 cm and had spread to one of fifteen dissected lymph nodes. Retesting of the specimen showed that the tumor was positive for ER (2+, 85%) and PR (2+, 10%) but negative for HER2 by IHC (1+). Also Ki-67 had dropped to 2%. The patient was regularly monitored every 3 mo without evidence of recurrence.<br><br>CONCLUSION: Biomarker status should be reassessed after NACT especially in luminal subtypes.}, }
@article {pmid35064153, year = {2022}, author = {Tewari, SG and Kwan, B and Elahi, R and Rajaram, K and Reifman, J and Prigge, ST and Vaidya, AB and Wallqvist, A}, title = {Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1167}, pmid = {35064153}, issn = {2045-2322}, support = {W81XWH-14-2-0134//U.S. Army Medical Research and Development Command (MRDC)/ ; W81XWH-20-C-0031//U.S. Army Medical Research and Development Command (MRDC)/ ; T32 AI007417/AI/NIAID NIH HHS/United States ; R01AI125534//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command (MRDC)/ ; }, abstract = {Due to the recurring loss of antimalarial drugs to resistance, there is a need for novel targets, drugs, and combination therapies to ensure the availability of current and future countermeasures. Pyrazoleamides belong to a novel class of antimalarial drugs that disrupt sodium ion homeostasis, although the exact consequences of this disruption in Plasmodium falciparum remain under investigation. In vitro experiments demonstrated that parasites carrying mutations in the metabolic enzyme PfATP4 develop resistance to pyrazoleamide compounds. However, the underlying mechanisms that allow mutant parasites to evade pyrazoleamide treatment are unclear. Here, we first performed experiments to identify the sublethal dose of a pyrazoleamide compound (PA21A092) that caused a significant reduction in growth over one intraerythrocytic developmental cycle (IDC). At this drug concentration, we collected transcriptomic and metabolomic data at multiple time points during the IDC to quantify gene- and metabolite-level alterations in the treated parasites. To probe the effects of pyrazoleamide treatment on parasite metabolism, we coupled the time-resolved omics data with a metabolic network model of P. falciparum. We found that the drug-treated parasites adjusted carbohydrate metabolism to enhance synthesis of myoinositol-a precursor for phosphatidylinositol biosynthesis. This metabolic adaptation caused a decrease in metabolite flux through the pentose phosphate pathway, causing a decreased rate of RNA synthesis and an increase in oxidative stress. Our model analyses suggest that downstream consequences of enhanced myoinositol synthesis may underlie adjustments that could lead to resistance emergence in P. falciparum exposed to a sublethal dose of a pyrazoleamide drug.}, }
@article {pmid35046349, year = {2021}, author = {Adachi, K and Kubota, H and Suzuki, S and Hirano, T and Ishibashi, N and Sakurai, K}, title = {[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {48}, number = {13}, pages = {1843-1845}, pmid = {35046349}, issn = {0385-0684}, mesh = {Adult ; Axilla ; *Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Nodes ; Mastectomy ; *Ovarian Neoplasms/genetics/surgery ; }, abstract = {We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.}, }
@article {pmid34547924, year = {2022}, author = {Moghalu, O and Stoffel, JT and Elliott, SP and Welk, B and Zhang, C and Presson, A and Myers, J}, title = {Time-Related Changes in Patient Reported Bladder Symptoms and Satisfaction after Spinal Cord Injury.}, journal = {The Journal of urology}, volume = {207}, number = {2}, pages = {392-399}, pmid = {34547924}, issn = {1527-3792}, support = {UL1 RR025764/RR/NCRR NIH HHS/United States ; UL1 TR001067/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UL1 TR000105/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects/statistics &amp; numerical data ; Cross-Sectional Studies ; Female ; Humans ; Intermittent Urethral Catheterization/*adverse effects/psychology/statistics &amp; numerical data ; Male ; Patient Reported Outcome Measures ; Patient Satisfaction/*statistics &amp; numerical data ; Prospective Studies ; Quality of Life ; Registries ; Self Report/statistics &amp; numerical data ; Spinal Cord Injuries/*complications/therapy ; Time Factors ; Urinary Bladder/physiopathology ; Urinary Bladder, Neurogenic/etiology/psychology/*therapy ; Young Adult ; }, abstract = {PURPOSE: Increased time after spinal cord injury (SCI) is associated with a migration to bladder managements with higher morbidity such as indwelling catheter (IDC). Still, it is unclear how this affects bladder-related quality of life (QoL). We hypothesized that time from injury (TFI) would be associated with changes in bladder management, symptoms and satisfaction.<br><br>MATERIALS AND METHODS: Cross-sectional analysis of time-related changes in patient-reported bladder management, symptoms and satisfaction using the Neurogenic Bladder Research Group SCI Registry. Outcomes included Neurogenic Bladder Symptom Score (NBSS) and bladder-related satisfaction (NBSS-satisfaction). Multivariable regression was performed to assess associations between TFI and outcomes, adjusting for participant characteristics, injury specifics, and psychosocial aspects of health-related QoL. Participants with TFI <1 year were excluded and TFI was categorized 1-5 (reference), 6-10, 11-15, 16-20 and >20 years.<br><br>RESULTS: Of 1,420 participants mean age at injury was 29.7 years (SD 13.4) and mean TFI was 15.2 years (SD 11.6). Participants grouped by TFI included 298 (21%) 1-5, 340 (24%) 6-10, 198 (14%) 11-15, 149 (10%) 16-20 and 435 (31%) >20 years. As TFI increased, clean intermittent catheterization (CIC) declined (55% 1-5 vs 45% >20 years, p <0.001) and IDC increased (16% 1-5 vs 21% >20 years, p <0.001). On multivariable analysis, increased TFI was associated with fewer bladder symptoms at >20 years from injury (-3.21 [CI -1.29, -5.14, p <0.001]) and better satisfaction (6-10 years -0.20 [CI -0.41, 0.01, p=0.070], 11-15 years -0.36 [CI -0.60, -0.11, p=0.002], 16-20 years -0.59 [CI -0.86, -0.32, p <0.001], >20 years -0.85 [CI -1.07, -0.63, <0.001]).<br><br>CONCLUSIONS: After SCI, CIC decreases and IDC increases over time; however, increasing TFI is associated with reduced urinary symptoms and improved bladder-related satisfaction.}, }
@article {pmid33753865, year = {2021}, author = {Bergeron, A and MacGrogan, G and Bertaut, A and Ladoire, S and Arveux, P and Desmoulins, I and Bonnefoi, H and Loustalot, C and Auriol, S and Beltjens, F and Degrolard-Courcet, E and Charon-Barra, C and Richard, C and Boidot, R and Arnould, L}, title = {Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {34}, number = {7}, pages = {1282-1296}, pmid = {33753865}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Lobular/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Female ; Humans ; Middle Aged ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/*genetics ; Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology ; }, abstract = {Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analysis (whole-exome and RNA sequencing using next-generation technology) was also performed. We found that TN-ILC patients were older than those with HR + ILC (P = 0.002) or TN-IDC (P < 0.001). Morphologically, TN-ILCs had aggressive phenotypes, with more pleomorphism (P = 0.003) and higher nuclear grades than HR + ILCs (P = 0.009). Immunohistochemistry showed that TN-ILCs less frequently expressed basal markers (CK5/6, EGFR and SOX10) than TN-IDCs (P < 0.001), while androgen receptor (AR) positivity was more prevalent (P < 0.001). Survival curves analysis did not show differences between TN-ILC and TN-IDC patients, while overall and distant metastasis-free survival were significantly worse compared to those with HR + ILCs (P = 0.047 and P = 0.039, respectively). At a molecular level, we found that TN-ILCs had particular transcriptomic profiles, characterized by increased AR signaling, and associated with frequent alterations in the PI3K network and ERBB2. Interestingly, whole-exome analysis also identified three specific recurrent ESRRA hotspot mutations in these tumors, which have never been described in breast cancer to date and which were absent in the other two tumor subtypes. Our findings highlight that TN-ILC is a unique aggressive breast cancer associated with elderly age, which belong to the luminal androgen receptor subtype as determined by immunohistochemistry and transcriptomic profiling. Moreover, it harbors specific molecular alterations (PI3K, ERBB2 and ESRRA) which may pave the way for new targeted therapeutic strategies.}, }
@article {pmid34225099, year = {2021}, author = {Pariyar, M and Johns, A and Thorne, RF and Scott, RJ and Avery-Kiejda, KA}, title = {Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.}, journal = {Neoplasia (New York, N.Y.)}, volume = {23}, number = {8}, pages = {743-753}, doi = {10.1016/j.neo.2021.05.016}, pmid = {34225099}, issn = {1476-5586}, mesh = {*Biomarkers, Tumor ; Chromosome Mapping ; Computational Biology/methods ; *DNA Copy Number Variations ; DNA Methylation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Ontology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Molecular Sequence Annotation ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*etiology/mortality/*pathology ; }, abstract = {Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.}, }
@article {pmid34062284, year = {2021}, author = {Salles, DC and Vidotto, T and Faisal, FA and Tosoian, JJ and Guedes, LB and Muranyi, A and Bai, I and Singh, S and Yan, D and Shanmugam, K and Lotan, TL}, title = {Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {23}, number = {8}, pages = {1030-1041}, pmid = {34062284}, issn = {1943-7811}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Molecular Diagnostic Techniques/methods/standards ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/genetics/*metabolism ; Prognosis ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/*diagnosis/genetics/*metabolism/mortality ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Reproducibility of Results ; }, abstract = {This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.}, }
@article {pmid33567280, year = {2021}, author = {Greulich, F and Wierer, M and Mechtidou, A and Gonzalez-Garcia, O and Uhlenhaut, NH}, title = {The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers.}, journal = {Cell reports}, volume = {34}, number = {6}, pages = {108742}, pmid = {33567280}, issn = {2211-1247}, mesh = {Animals ; Enhancer Elements, Genetic/*immunology ; Inflammation/genetics/immunology ; Macrophages/*immunology ; Mice ; *Multiprotein Complexes/genetics/immunology ; *RNA-Seq ; *Receptors, Glucocorticoid/genetics/immunology ; Transcription, Genetic/*immunology ; }, abstract = {Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. We show that SETD1A/COMPASS is recruited by GR to specific cis-regulatory elements, coinciding with H3K4 methylation dynamics at subsets of sites, upon treatment with lipopolysaccharide (LPS) and GCs. By chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq, we identify subsets of GR target loci that display SETD1A occupancy, H3K4 mono-, di-, or tri-methylation patterns, and transcriptional changes. However, our data on methylation status and COMPASS recruitment suggest that SETD1A has additional transcriptional functions. Setd1a loss-of-function studies reveal that SETD1A/COMPASS is required for GR-controlled transcription of subsets of macrophage target genes. We demonstrate that the SETD1A/COMPASS complex cooperates with GR to mediate anti-inflammatory effects.}, }
@article {pmid33148628, year = {2022}, author = {Pareja, F and Vahdatinia, M and Marchio, C and Lee, SSK and Da Cruz Paula, A and Derakhshan, F and da Silva, EM and Selenica, P and Dopeso, H and Chandarlapaty, S and Wen, HY and Vincent-Salomon, A and Brogi, E and Weigelt, B and Reis-Filho, JS}, title = {Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.}, journal = {Journal of clinical pathology}, volume = {75}, number = {1}, pages = {10-17}, pmid = {33148628}, issn = {1472-4146}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; Female ; Genomics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neuroendocrine Tumors/*genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Receptors, Estrogen/genetics ; Transcription Factors/genetics ; *Transcriptome ; Whole Exome Sequencing ; }, abstract = {AIMS: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.<br><br>METHODS: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).<br><br>RESULTS: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.<br><br>CONCLUSIONS: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.}, }
@article {pmid34969739, year = {2022}, author = {Takada, K and Kashiwagi, S and Asano, Y and Goto, W and Morisaki, T and Shibutani, M and Tanaka, H and Hirakawa, K and Ohira, M}, title = {The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.}, journal = {Anticancer research}, volume = {42}, number = {1}, pages = {311-320}, doi = {10.21873/anticanres.15487}, pmid = {34969739}, issn = {1791-7530}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/chemically induced/*diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis/*diagnosis/diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy/methods ; Smoking/*adverse effects ; }, abstract = {BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy.<br><br>PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy.<br><br>RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327).<br><br>CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.}, }
@article {pmid34396426, year = {2021}, author = {Kobayashi, H and Nakai, T and Nakanishi, Y and Esumi, M and Masuda, S}, title = {Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.}, journal = {Molecular medicine reports}, volume = {24}, number = {4}, pages = {}, pmid = {34396426}, issn = {1791-3004}, mesh = {Adult ; Breast ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Carcinoma, Lobular/*classification/genetics/pathology ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; *Phylogeny ; Polymorphism, Single Nucleotide ; }, abstract = {Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.}, }
@article {pmid34009452, year = {2021}, author = {Kusafuka, K and Ito, I and Hirata, K and Miyamoto, K and Shimizu, T and Satomi, H and Inagaki, H and Suzuki, M}, title = {A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.}, journal = {Medical molecular morphology}, volume = {54}, number = {3}, pages = {281-288}, pmid = {34009452}, issn = {1860-1499}, mesh = {Asians ; Biomarkers, Tumor/analysis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/surgery ; ErbB Receptors/analysis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Japan ; Keratin-19/analysis/genetics ; Keratin-5/analysis/genetics ; Keratin-6/analysis/genetics ; Lip/surgery ; Lip Neoplasms/*diagnosis/metabolism/surgery ; Middle Aged ; Receptors, Androgen/analysis/genetics ; SOXE Transcription Factors/analysis/genetics ; }, abstract = {Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.}, }
@article {pmid33443130, year = {2021}, author = {Trinh, A and Gil Del Alcazar, CR and Shukla, SA and Chin, K and Chang, YH and Thibault, G and Eng, J and Jovanović, B and Aldaz, CM and Park, SY and Jeong, J and Wu, C and Gray, J and Polyak, K}, title = {Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {4}, pages = {623-635}, doi = {10.1158/1541-7786.MCR-20-0949}, pmid = {33443130}, issn = {1557-3125}, support = {R35 CA197623/CA/NCI NIH HHS/United States ; U01 CA195469/CA/NCI NIH HHS/United States ; U54 CA209988/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; U24 CA224331/CA/NCI NIH HHS/United States ; R50 CA211482/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*immunology ; Carcinoma, Ductal, Breast/*genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology ; Female ; Genomics ; Humans ; Immune System ; }, abstract = {The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.}, }
@article {pmid34884926, year = {2021}, author = {Kang, M and Lee, H and Byeon, SJ and Kwon, GY and Jeon, SS}, title = {Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884926}, issn = {1422-0067}, support = {NRF-2020R1A2C2007662//National Research Foundation of Korea/ ; NRF-2020R1C1C1005054//National Research Foundation of Korea/ ; }, mesh = {Animals ; DNA Repair/genetics ; Genomic Instability ; Humans ; Male ; *Mutation ; Precision Medicine ; Prostatic Neoplasms/*genetics/*pathology/therapy ; Xenograft Model Antitumor Assays ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2-ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate-ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.}, }
@article {pmid34185678, year = {2021}, author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, S and Aerts, HJWL and Homeyer, A and Lewis, R and Akbarzadeh, A and Bontempi, D and Clifford, W and Herrmann, MD and Höfener, H and Octaviano, I and Osborne, C and Paquette, S and Petts, J and Punzo, D and Reyes, M and Schacherer, DP and Tian, M and White, G and Ziegler, E and Shmulevich, I and Pihl, T and Wagner, U and Farahani, K and Kikinis, R}, title = {NCI Imaging Data Commons.}, journal = {Cancer research}, volume = {81}, number = {16}, pages = {4188-4193}, pmid = {34185678}, issn = {1538-7445}, support = {P41 EB015898/EB/NIBIB NIH HHS/United States ; HHSN261201500001G/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; HHSN261201500001W/CA/NCI NIH HHS/United States ; }, mesh = {Biomedical Research/trends ; Cloud Computing ; Computational Biology/methods ; Computer Graphics ; Computer Security ; Data Interpretation, Statistical ; Databases, Factual ; Diagnostic Imaging/*methods/standards ; Humans ; Image Processing, Computer-Assisted ; *National Cancer Institute (U.S.) ; Neoplasms/*diagnostic imaging/*genetics ; Pilot Projects ; Programming Languages ; Radiology/methods/standards ; Reproducibility of Results ; Software ; United States ; User-Computer Interface ; }, abstract = {The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research. SIGNIFICANCE: This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.}, }
@article {pmid34769077, year = {2021}, author = {Kohlhase, DR and McCabe, CE and Singh, AK and O'Rourke, JA and Graham, MA}, title = {Comparing Early Transcriptomic Responses of 18 Soybean (Glycine max) Genotypes to Iron Stress.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769077}, issn = {1422-0067}, support = {3625-21220-006-00D//USDA-ARS/ ; IOW04714//USDA/ ; FAR0024859//North Central Soybean Research Program/ ; }, mesh = {*Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Iron/*metabolism ; Quantitative Trait Loci ; Soybeans/*genetics/metabolism ; Stress, Physiological ; Transcriptome ; }, abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress that negatively affects soybean (Glycine max [L.] Merr.) production. Much of our knowledge of IDC stress responses is derived from model plant species. Gene expression, quantitative trait loci (QTL) mapping, and genome-wide association studies (GWAS) performed in soybean suggest that stress response differences exist between model and crop species. Our current understanding of the molecular response to IDC in soybeans is largely derived from gene expression studies using near-isogenic lines differing in iron efficiency. To improve iron efficiency in soybeans and other crops, we need to expand gene expression studies to include the diversity present in germplasm collections. Therefore, we collected 216 purified RNA samples (18 genotypes, two tissue types [leaves and roots], two iron treatments [sufficient and deficient], three replicates) and used RNA sequencing to examine the expression differences of 18 diverse soybean genotypes in response to iron deficiency. We found a rapid response to iron deficiency across genotypes, most responding within 60 min of stress. There was little evidence of an overlap of specific differentially expressed genes, and comparisons of gene ontology terms and transcription factor families suggest the utilization of different pathways in the stress response. These initial findings suggest an untapped genetic potential within the soybean germplasm collection that could be used for the continued improvement of iron efficiency in soybean.}, }
@article {pmid34340541, year = {2021}, author = {Pickford, AK and Michel-Todó, L and Dupuy, F and Mayor, A and Alonso, PL and Lavazec, C and Cortés, A}, title = {Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0163621}, pmid = {34340541}, issn = {2150-7511}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antigens, Protozoan/immunology ; *Gene Expression Profiling ; *Genetic Variation ; Host-Parasite Interactions/*genetics/immunology ; Humans ; Malaria, Falciparum/immunology/*parasitology ; Plasmodium falciparum/*genetics/immunology ; Protozoan Proteins/*genetics/immunology ; Transcriptome ; }, abstract = {Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.}, }
@article {pmid34315379, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E and Chaudhary, FA and Khan, MI}, title = {Feasibility and Acceptability of Instructions of Daily Care in Overweight and Obese Knee Osteoarthritis Participants.}, journal = {Current rheumatology reviews}, volume = {17}, number = {4}, pages = {421-427}, doi = {10.2174/1573397117666210727095552}, pmid = {34315379}, issn = {1875-6360}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Feasibility Studies ; Humans ; *Obesity/complications ; *Osteoarthritis, Knee/drug therapy/therapy ; *Overweight/complications ; Pain ; *Self Care/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: Knee Osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of Instructions of Daily Care (IDC) on pain, mobility, and Body Mass Index (BMI) among knee OA participants who are overweight or obese.<br><br>MATERIALS AND METHODS: The study was an open-label randomized controlled trial of six weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.<br><br>RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05). The results of descriptive statistics showed a significantly higher satisfaction score for participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.<br><br>CONCLUSION: The IDC is effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.}, }
@article {pmid34972731, year = {2022}, author = {Salih, MM and Higgo, AA and Eed, EM}, title = {Prognostic Significance of p16 Protein Expression in Breast Cancer.}, journal = {In vivo (Athens, Greece)}, volume = {36}, number = {1}, pages = {336-340}, doi = {10.21873/invivo.12707}, pmid = {34972731}, issn = {1791-7549}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Female ; Humans ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle.<br><br>PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry.<br><br>RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively.<br><br>CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.}, }
@article {pmid34011405, year = {2021}, author = {Dinca, SC and Greiner, D and Weidenfeld, K and Bond, L and Barkan, D and Jorcyk, CL}, title = {Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.}, journal = {Breast cancer research : BCR}, volume = {23}, number = {1}, pages = {56}, pmid = {34011405}, issn = {1465-542X}, support = {R25 GM123927/GM/NIGMS NIH HHS/United States ; 1C06RR020533/GM/NIGMS NIH HHS/United States ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; 0619737//National Science Foundation/ ; 0923535//National Science Foundation/ ; AR298//Smylie Family Cancer Fund (US)/ ; 2017237//United States - Israel Binational Science Foundation/ ; }, mesh = {Amino Acid Oxidoreductases/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Collagen Type I/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Matrix/*metabolism ; Female ; Glycosylation ; Humans ; Inflammation ; Neoplasm Metastasis ; Oncostatin M/genetics/*metabolism/pharmacology ; Oncostatin M Receptor beta Subunit/genetics/metabolism ; Prognosis ; Signal Transduction ; Tumor Microenvironment ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is a serious problem for patients as it metastasizes, decreasing 5-year patient survival from > 95 to ~ 27%. The breast tumor microenvironment (TME) is often saturated with proinflammatory cytokines, such as oncostatin M (OSM), which promote epithelial-to-mesenchymal transitions (EMT) in IDC and increased metastasis. The extracellular matrix (ECM) also plays an important role in promoting invasive and metastatic potential of IDC. Specifically, the reorganization and alignment of collagen fibers in stromal ECM leads to directed tumor cell motility, which promotes metastasis. Lysyl oxidase like-2 (LOXL2) catalyzes ECM remodeling by crosslinking of collagen I in the ECM. We propose a novel mechanism whereby OSM induces LOXL2 expression, mediating stromal ECM remodeling of the breast TME.<br><br>METHODS: Bioinformatics was utilized to determine survival and gene correlation in patients. IDC cell lines were treated with OSM (also IL-6, LIF, and IL-1β) and analyzed for LOXL2 expression by qRT-PCR and immunolabelling techniques. Collagen I contraction assays, 3D invasion assays, and confocal microscopy were performed with and without LOXL2 inhibition to determine the impact of OSM-induced LOXL2 on the ECM.<br><br>RESULTS: Our studies demonstrate that IDC patients with high LOXL2 and OSM co-expression had worse rates of metastasis-free survival than those with high levels of either, individually, and LOXL2 expression is positively correlated to OSM/OSM receptor (OSMR) expression in IDC patients. Furthermore, human IDC cells treated with OSM resulted in a significant increase in LOXL2 mRNA, which led to upregulated protein expression of secreted, glycosylated, and enzymatically active LOXL2. The expression of LOXL2 in IDC cells did not affect OSM-promoted EMT, and LOXL2 was localized to the cytoplasm and/or secreted. OSM-induced LOXL2 promoted an increase in ECM collagen I fiber crosslinking, which led to significant fiber alignment between cells and increased IDC cell invasion.<br><br>CONCLUSIONS: Aligned collagen fibers in the ECM provide pathways for tumor cells to migrate more easily through the stroma to nearby vasculature and tissue. These results provide a new paradigm through which proinflammatory cytokine OSM promotes tumor progression. Understanding the nuances in IDC metastasis will lead to better potential therapeutics to combat against the possibility.}, }
@article {pmid33421821, year = {2021}, author = {Hoshina, H and Takei, H and Sakatani, T and Naito, Z}, title = {CDX2-positive breast cancer presented with axillary lymph node metastases: A case report.}, journal = {Cancer treatment and research communications}, volume = {26}, number = {}, pages = {100300}, doi = {10.1016/j.ctarc.2020.100300}, pmid = {33421821}, issn = {2468-2942}, mesh = {Axilla ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/therapy ; CDX2 Transcription Factor/analysis/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Ultrasonography ; }, abstract = {BACKGROUND: The caudal type homeobox 2 transcription factor (CDX2) is a specific and sensitive marker for intestinal carcinoma, but usually not expressed in breast cancer. In CDX2-positive metastatic cancer of occult primary, the origin is highly suspicious of an enteric carcinoma.<br><br>CASE PRESENTATION: A 50-year-old woman complained of enlarged lymph nodes (LNs) in the right axilla. Mammography and ultrasonography scans showed no abnormal findings in her breasts. Core needle biopsy (CNB) revealed metastatic adenocarcinoma. Immunohistochemical staining was positive for CDX2 intensely. The primary tumor was suspicious of intestinal adenocarcinoma. A dynamic contrast-enhanced magnetic resonance imaging scan revealed an accentuated lesion which was detected using a second-look ultrasound, and diagnosed invasive ductal carcinoma by CNB. A partial mastectomy of the right breast with level I and II axillary LN dissection was performed. A few cells of primary cancer were expressed CDX2 and estrogen receptor. The final pathological diagnosis was T1bN3aM0 stage IIIC. The fluorescent double staining showed that CDX2 simultaneously expressed on the Ki67 positive cells of metastatic tumors. The adjuvant treatment included chemotherapy and radiation, followed by tamoxifen administration. The patient survived without any recurrences over the following 36 months.<br><br>CONCLUSIONS: We report a rare case of CDX2-positive metastatic breast cancer in the axillary LNs. As some literatures reported vitamin D pathways induced cancer cell apoptosis and inhibition, these metastatic cells of our case might play the effort of autoregulation of inhibiting progression.}, }
@article {pmid34689837, year = {2021}, author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E}, title = {The effect of rehabilitation protocol using mobile health in overweight and obese patients with knee osteoarthritis: a clinical trial.}, journal = {Advances in rheumatology (London, England)}, volume = {61}, number = {1}, pages = {63}, pmid = {34689837}, issn = {2523-3106}, mesh = {Clinical Protocols ; Humans ; Middle Aged ; *Obesity/complications ; *Osteoarthritis, Knee/rehabilitation ; *Overweight/complications ; *Telemedicine ; Treatment Outcome ; }, abstract = {OBJECTIVE: The objective of this randomized controlled trial (RCT) was to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) combined with mobile health (mHealth) applications on knee pain, mobility, functional activity and activities of daily living (ADL) among knee osteoarthritis (OA) patients who were overweight and obese.<br><br>METHODS: This study was a single-blind, RCT conducted at Teaching Bay of Rehmatul-Lil-Alameen Post Graduate Institute of Cardiology between February and November 2020. 114 knee OA patients who were overweight and obese were randomly divided by a computer-generated number into the rehabilitation group with mHealth (RGw-mHealth) to receive LLRP + instructions of daily care (IDC) combined with mHealth intervention, rehabilitation group without mHealth (RGwo-mHealth) to receive LLRP + IDC intervention and control group (CG) to receive IDC intervention. All three groups were also provided leaflets explaining about their intervention. The primary outcome measure was knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index score. The secondary outcome measures were mobility measured by the Timed up and go (TUG) test, functional activity measured by the patient-specific functional scale (PSFS), and ADL measured by the Katz Index of independence in ADL scores.<br><br>RESULTS: Among the 114 patients who were randomized (mean age, 53 years), 96 (84%) completed the trial. After 3-months of intervention, patients in all three groups had statistically significant knee pain reduction (RGw-mHealth: 2.54; RGwo-mHealth: 1.47; and CG: 0.37) within groups (P < 0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in mobility, functional activity, and ADL within groups (P < 0.05), but no improvement was noted in the CG (p > 0.05). As indicated in the overall analysis of covariance, there were statistically significant differences in the mean knee pain, mobility, functional activity, and ADL changes between groups after 3-months (p < 0.001). The pairwise between-group comparisons (Bonferroni post hoc analysis) of the knee pain, mobility, functional activity, and ADL scores at 3-months revealed that patients in the RGw-mHealth had significantly higher mean change in the knee pain, TUG test, functional activity, and ADL scores compared to patients in the RGwo-mHealth or CG.<br><br>CONCLUSION: Reduction in knee pain, improvement in mobility, functional activity, and ADL were more among patients in the RGw-mHealth compared with the RGwo-mHealth or CG. Trial registration National Medical Research Registry: NMRR-20-1094-52911. Date of registration: 05-05-2020. URL: https://www.nmrr.gov.my .}, }
@article {pmid34949235, year = {2021}, author = {Mavhungu, R and Bhuiyan, M and Ooko, F}, title = {Profile of patients seen at Pietersburg and Mankweng breast cancer clinics in Limpopo.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {111}, number = {11b}, pages = {1129-1131}, doi = {10.7196/SAMJ.2021.v111i11b.16108}, pmid = {34949235}, issn = {2078-5135}, abstract = {BACKGROUND: Breast cancer is the most common cancer diagnosed among women worldwide. It is the most prevalent cancer and leading cause of death among South African (SA) women. The increasing incidence of breast cancer is a major health concern. Until now, the distribution of breast cancer demography, stage at first presentation, and histological characterisation have not been studied in Limpopo Province, SA.<br><br>OBJECTIVES: To record the demographic profile of breast cancer patients, to report the stage at the time of presentation and to characterise the pattern of malignant disease in Limpopo, SA.<br><br>METHODS: We conducted a retrospective descriptive review of the records of patients managed at Pietersburg Hospital oncology and Mankweng Hospital breast cancer clinics during the period 1 March 2015 - 28 February 2017. Stata was used to analyse data.<br><br>RESULTS: A total of 248 patients with a mean age of 55 years were included for analysis, 7 males (3%) and 241 females (97%). Capricorn and Vhembe districts constituted 32% and 27% respectively. The majority (69%) of patients were diagnosed with disease stage III or IV. The most common histological type was invasive ductal cell carcinoma (IDC) (87%).<br><br>CONCLUSIONS: More than one-third of patients were younger than 50 years. The majority (69%) had an advanced breast cancer (stage III or IV). We recommend provision of mammography services in regional hospitals.}, }
@article {pmid34945830, year = {2021}, author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY}, title = {Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.}, journal = {Journal of personalized medicine}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/jpm11121358}, pmid = {34945830}, issn = {2075-4426}, abstract = {BACKGROUND: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).<br><br>PATIENTS AND METHODS: we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).<br><br>RESULTS: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group.<br><br>CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.}, }
@article {pmid34672684, year = {2021}, author = {Yadav, S and Hu, C and Nathanson, KL and Weitzel, JN and Goldgar, DE and Kraft, P and Gnanaolivu, RD and Na, J and Huang, H and Boddicker, NJ and Larson, N and Gao, C and Yao, S and Weinberg, C and Vachon, CM and Trentham-Dietz, A and Taylor, JA and Sandler, DR and Patel, A and Palmer, JR and Olson, JE and Neuhausen, S and Martinez, E and Lindstrom, S and Lacey, JV and Kurian, AW and John, EM and Haiman, C and Bernstein, L and Auer, PW and Anton-Culver, H and Ambrosone, CB and Karam, R and Chao, E and Yussuf, A and Pesaran, T and Dolinsky, JS and Hart, SN and LaDuca, H and Polley, EC and Domchek, SM and Couch, FJ}, title = {Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {39}, number = {35}, pages = {3918-3926}, pmid = {34672684}, issn = {1527-7755}, support = {P01 CA087969/CA/NCI NIH HHS/United States ; R01 CA097396/CA/NCI NIH HHS/United States ; K07 CA092044/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; R35 CA253187/CA/NCI NIH HHS/United States ; Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; U01 CA199277/CA/NCI NIH HHS/United States ; R01 CA225662/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA098663/CA/NCI NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; R01 CA204819/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; R01 CA067264/CA/NCI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 CA058860/CA/NCI NIH HHS/United States ; R01 CA047147/CA/NCI NIH HHS/United States ; U01 CA082004/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; Z01 ES049033/ImNIH/Intramural NIH HHS/United States ; R01 CA192393/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genetic Testing/*methods ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {PURPOSE: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.<br><br>MATERIALS AND METHODS: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).<br><br>RESULTS: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC.<br><br>CONCLUSION: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.}, }
@article {pmid34423517, year = {2021}, author = {Yun, NK and Slostad, JA and Naqib, A and Frankenberger, C and Perez, CB and Ghai, R and Usha, L}, title = {Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.}, journal = {The oncologist}, volume = {26}, number = {12}, pages = {1000-1005}, pmid = {34423517}, issn = {1549-490X}, mesh = {*Breast Neoplasms/genetics ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Precision Medicine ; Sequence Analysis, DNA ; }, abstract = {Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.}, }
@article {pmid34884498, year = {2021}, author = {Betz, IR and Qaiyumi, SJ and Goeritzer, M and Thiele, A and Brix, S and Beyhoff, N and Grune, J and Klopfleisch, R and Greulich, F and Uhlenhaut, NH and Kintscher, U and Foryst-Ludwig, A}, title = {Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884498}, issn = {1422-0067}, mesh = {Animals ; Cardiomegaly/chemically induced/*drug therapy/metabolism/pathology ; Cardiotonic Agents/*pharmacology ; Catecholamines/*toxicity ; Fatty Acids, Monounsaturated/*pharmacology ; Gene Expression Regulation/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/drug effects/metabolism/pathology ; PPAR alpha/genetics/*metabolism ; PPAR delta/genetics/*metabolism ; }, abstract = {Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.}, }
@article {pmid34645713, year = {2021}, author = {Teodorescu, K and Plonsky, O and Ayal, S and Barkan, R}, title = {Frequency of enforcement is more important than the severity of punishment in reducing violation behaviors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {42}, pages = {}, pmid = {34645713}, issn = {1091-6490}, mesh = {COVID-19/*prevention &amp; control/virology ; Decision Making ; Humans ; Probability ; *Punishment ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {External enforcement policies aimed to reduce violations differ on two key components: the probability of inspection and the severity of the punishment. Different lines of research offer different insights regarding the relative importance of each component. In four studies, students and Prolific crowdsourcing participants (Ntotal = 816) repeatedly faced temptations to commit violations under two enforcement policies. Controlling for expected value, we found that a policy combining a high probability of inspection with a low severity of fines (HILS) was more effective than an economically equivalent policy that combined a low probability of inspection with a high severity of fines (LIHS). The advantage of prioritizing inspection frequency over punishment severity (HILS over LIHS) was greater for participants who, in the absence of enforcement, started out with a higher violation rate. Consistent with studies of decisions from experience, frequent enforcement with small fines was more effective than rare severe fines even when we announced the severity of the fine in advance to boost deterrence. In addition, in line with the phenomenon of underweighting of rare events, the effect was stronger when the probability of inspection was rarer (as in most real-life inspection probabilities) and was eliminated under moderate inspection probabilities. We thus recommend that policymakers looking to effectively reduce recurring violations among noncriminal populations should consider increasing inspection rates rather than punishment severity.}, }
@article {pmid33692758, year = {2021}, author = {Togashi, K and Nishitsuka, K and Hayashi, S and Namba, H and Goto, S and Takeda, Y and Suzuki, S and Kato, T and Yamada, Y and Konno, E and Yoshioka, T and Yamakawa, M and Sonoda, Y and Suzuki, T and Yamashita, H}, title = {Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {625663}, pmid = {33692758}, issn = {1664-2392}, mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*secondary ; Exophthalmos/diagnostic imaging/*etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Orbital Neoplasms/complications/diagnostic imaging/*secondary ; }, abstract = {Background: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.<br><br>Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.<br><br>Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.}, }
@article {pmid33135196, year = {2021}, author = {Bishop, JA and Nakaguro, M and Whaley, RD and Ogura, K and Imai, H and Laklouk, I and Faquin, WC and Sadow, PM and Gagan, J and Nagao, T}, title = {Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.}, journal = {Histopathology}, volume = {79}, number = {3}, pages = {338-346}, pmid = {33135196}, issn = {1365-2559}, support = {P01 CA240239/CA/NCI NIH HHS/United States ; //UT Southwestern Medical Center/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Carcinoma, Ductal/diagnosis/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Mutation ; Oncogene Fusion ; Oxyphil Cells/pathology ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/diagnosis/genetics/pathology ; Salivary Glands/pathology ; Sequence Analysis, RNA ; Transcription Factors/*genetics ; }, abstract = {AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.<br><br>METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.<br><br>CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.}, }
@article {pmid33191115, year = {2021}, author = {Shah, OS and Soran, A and Sahin, M and Knapick, BA and Ugras, S and Celik, E and Lucas, PC and Lee, AV}, title = {Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.}, journal = {Clinical breast cancer}, volume = {21}, number = {3}, pages = {210-217}, doi = {10.1016/j.clbc.2020.08.009}, pmid = {33191115}, issn = {1938-0666}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/genetics ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; }, abstract = {BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples.<br><br>MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants.<br><br>RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively.<br><br>CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeqTM. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.}, }
@article {pmid32943456, year = {2020}, author = {Richard, F and Majjaj, S and Venet, D and Rothé, F and Pingitore, J and Boeckx, B and Marchio, C and Clatot, F and Bertucci, F and Mariani, O and Galant, C and Eynden, GVD and Salgado, R and Biganzoli, E and Lambrechts, D and Vincent-Salomon, A and Pruneri, G and Larsimont, D and Sotiriou, C and Desmedt, C}, title = {Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {23}, pages = {6254-6265}, doi = {10.1158/1078-0432.CCR-20-2268}, pmid = {32943456}, issn = {1557-3265}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/immunology/metabolism/*secondary ; Carcinoma, Lobular/genetics/immunology/metabolism/*secondary ; Female ; Follow-Up Studies ; Genomics/*methods ; Humans ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Stromal Cells/*immunology ; Survival Rate ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.<br><br>EXPERIMENTAL DESIGN: We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT.<br><br>RESULTS: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that >50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases.<br><br>CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.}, }
@article {pmid34899603, year = {2021}, author = {Kopf, S and Kumar, V and Kender, Z and Han, Z and Fleming, T and Herzig, S and Nawroth, PP}, title = {Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {765201}, doi = {10.3389/fendo.2021.765201}, pmid = {34899603}, issn = {1664-2392}, abstract = {Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.}, }
@article {pmid33534078, year = {2021}, author = {Oses, G and Cases, C and Valduvieco, I and Farrús, B and Alonso, I and Caparrós, X and Mases, J and Muñoz-Guglielmetti, D and Biete, A and Castro, C and Escudero, E and Molina, M and Herreros, A and Saez, J and Mollà, M}, title = {Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {23}, number = {8}, pages = {1593-1600}, pmid = {33534078}, issn = {1699-3055}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*radiation effects ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/secondary/surgery ; Electrons/*therapeutic use ; Female ; Fibrosis/pathology ; Humans ; Intraoperative Period ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/prevention &amp; control ; Postoperative Complications ; Prospective Studies ; Radiation Injuries/pathology ; Radiotherapy Dosage ; Treatment Outcome ; }, abstract = {PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost.<br><br>MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0.<br><br>RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema.<br><br>CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.}, }
@article {pmid34829743, year = {2021}, author = {Liu, PF and Shu, CW and Yang, HC and Lee, CH and Liou, HH and Ger, LP and Tzeng, YT and Wang, WC}, title = {Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.}, journal = {Biomedicines}, volume = {9}, number = {11}, pages = {}, doi = {10.3390/biomedicines9111514}, pmid = {34829743}, issn = {2227-9059}, support = {MOST 108-2320-B-037-038, MOST 109-2320-B-037-015-MY3//The Ministry of Science and Technology/ ; KMU-Q109008; KMU-Q110002//Kaohsiung Medical University Research Foundation/ ; NSYSUKMU 109-I007; NSYSUKMU-110-I006//The National Sun Yat-sen University-KMU Joint Research Project/ ; KMU-TC108A04//Kaohsiung Medical University Research Center Grant/ ; VGHKS106-015; VGHKS107-014//Kaohsiung Veterans General Hospital/ ; }, abstract = {Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.}, }
@article {pmid34427055, year = {2021}, author = {Morigny, P and Kaltenecker, D and Zuber, J and Machado, J and Mehr, L and Tsokanos, FF and Kuzi, H and Hermann, CD and Voelkl, M and Monogarov, G and Springfeld, C and Laurent, V and Engelmann, B and Friess, H and Zörnig, I and Krüger, A and Krijgsveld, J and Prokopchuk, O and Fisker Schmidt, S and Rohm, M and Herzig, S and Berriel Diaz, M}, title = {Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {12}, number = {5}, pages = {1333-1351}, pmid = {34427055}, issn = {2190-6009}, support = {J4224-B34/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {1-Alkyl-2-acetylglycerophosphocholine Esterase ; Animals ; Benzaldehydes ; Biomarkers ; *Cachexia/drug therapy/etiology ; Humans ; Mice ; Oximes ; *Pancreatic Neoplasms ; Prospective Studies ; }, abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour-derived and host-derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.<br><br>METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia-inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well-established mouse models of CCx and in different cohorts of weight-stable and weight-losing cancer patients with different tumour entities. Genetic PLA2G7 knock-down in tumours and pharmacological treatment using the well-studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour-bearing mice.<br><br>RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia-inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock-down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.<br><br>CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre-cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.}, }
@article {pmid32561662, year = {2020}, author = {Sestak, I and Filipits, M and Buus, R and Rudas, M and Balic, M and Knauer, M and Kronenwett, R and Fitzal, F and Cuzick, J and Gnant, M and Greil, R and Dowsett, M and Dubsky, P}, title = {Prognostic Value of EndoPredict in Women with Hormone Receptor-Positive, HER2-Negative Invasive Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {17}, pages = {4682-4687}, doi = {10.1158/1078-0432.CCR-20-0260}, pmid = {32561662}, issn = {1557-3265}, support = {5032/CRUK_/Cancer Research UK/United Kingdom ; C569/A16891/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast/*pathology/surgery ; Breast Neoplasms/genetics/*mortality/pathology/therapy ; Carcinoma, Lobular/genetics/*mortality/pathology/therapy ; Chemotherapy, Adjuvant/methods ; Clinical Trials, Phase III as Topic ; Datasets as Topic ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/genetics/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Risk Assessment/methods ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) accounts for approximately 5%-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC).<br><br>EXPERIMENTAL DESIGN: The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in postmenopausal women with ILC. The primary outcome was DR.<br><br>RESULTS: 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54-4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73-2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0-35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63-4.02)] and node-positive disease [HR = 3.70 (2.49-5.50)].<br><br>CONCLUSIONS: EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.}, }
@article {pmid34610495, year = {2021}, author = {Rousseau, S and Katz, D and Shlomi-Polachek, I and Frenkel, TI}, title = {Prospective risk from prenatal anxiety to post traumatic stress following childbirth: The mediating effects of acute stress assessed during the postnatal hospital stay and preliminary evidence for moderating effects of doula care.}, journal = {Midwifery}, volume = {103}, number = {}, pages = {103143}, doi = {10.1016/j.midw.2021.103143}, pmid = {34610495}, issn = {1532-3099}, mesh = {Anxiety/etiology ; *Doulas ; Female ; Humans ; Length of Stay ; Parturition ; Postpartum Period ; Pregnancy ; Prospective Studies ; *Stress Disorders, Post-Traumatic/etiology ; }, abstract = {OBJECTIVE: Growing literature has identified childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth. The current study is the first to prospectively examine a pathway of risk from mothers' prenatal trait-anxiety, to Acute-Stress-Immediately-Following-Childbirth, and later symptoms of Post-Traumatic-Stress-Following-Childbirth, in a low-risk community sample. Auxiliary analyses explored whether doula care during childbirth moderated risk.<br><br>METHOD: 149 pregnant women were randomly selected. Prenatal trait-anxiety was assessed toward the end of pregnancy, Acute-Stress-Immediately-Following-Childbirth at two-days post-partum, and symptoms of Post-Traumatic-Stress-Following-Childbirth at one-month post-partum.<br><br>RESULTS: Results indicated a significant indirect pathway from prenatal trait-anxiety to Post-Traumatic-Stress-Following-Childbirth, through Acute-Stress-Immediately-Following-Childbirth. Two groups were generated ad hoc for auxiliary analyses: participants who opted to receive doula care during childbirth (n=21; 14%) versus participants who received care as usual (n=128; 86%). Analyses provided preliminary support for doula care as a potential moderator of risk.<br><br>CONCLUSIONS: Results point toward prenatal trait-anxiety and Acute-Stress-Immediately-Following-Childbirth as significant risk factors for Post-Traumatic-Stress-Following-Childbirth. Findings inform preventive screening implicating the prenatal period as well as the postnatal hospital stay as important time windows for preventive screening. Finally, preliminary support for moderating effects of doula care suggest that preventive interventions administered during the perinatal period may effectively reduce anxiety-related risk for Post-Traumatic-Stress-Following-Childbirth.}, }
@article {pmid32532588, year = {2020}, author = {Brings, S and Fleming, T and Herzig, S and Nawroth, PP and Kopf, S}, title = {Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study.}, journal = {Journal of diabetes and its complications}, volume = {34}, number = {9}, pages = {107648}, doi = {10.1016/j.jdiacomp.2020.107648}, pmid = {32532588}, issn = {1873-460X}, mesh = {*Albuminuria/diagnosis/etiology ; Cathepsin D/urine ; Cathepsin L/*urine ; Cohort Studies ; *Diabetes Mellitus, Type 2/complications/diagnosis ; *Glycation End Products, Advanced/urine ; Humans ; Tandem Mass Spectrometry ; }, abstract = {AIMS: Cathepsin D (CTSD) and L (CTSL) are lysosomal proteases which degrade and detoxify advanced glycation end product (AGE)-modified proteins which are predictive of the development of diabetic nephropathy. We aimed to quantify cathepsin levels in urine from patients with type 2 diabetes and to relate these to the amount of urinary free AGEs at baseline and with kidney function after four years of follow-up in this closed cohort study.<br><br>METHODS: We established and validated a LC MS/MS method for the quantification of CTSD and CTSL in urine. Patients with type 2 diabetes were screened for diabetic kidney disease and 141 patients were seen at baseline and after four years. CTSD and CTSL and free AGEs were quantified in urine by LC MS/MS at baseline in these patients.<br><br>RESULTS: The detection limit of CTSD and CTSL in urine was 2.4 ng/l and 19.1 ng/l, respectively. CTSD (p < 0.0001, r = 0.555) and CTSL (p < 0.0001, r = 0.608) correlated positively with albuminuria at time of recruitment. In addition levels of the proteases but not albuminuria correlated with urinary levels of the major cross-linking AGE glucosepane (CTSD: p = 0.012, r = 0.225; CTSL: p < 0.001, r = 0.376). A strong non-linear association between CTSD (r = 0.568), CTSL (r = 0.588) and change in albuminuria over four years was present. High levels of CTSL (p = 0.007, beta = -0.366) were associated with an improvement of albuminuria after four years.<br><br>CONCLUSIONS: A sensitive LC MS/MS assay for the quantification of CTSD and CTSL in urine was established. High CTSL baseline levels were associated with an improvement in albuminuria at follow-up. An increased excretion and thus detoxification of the free form of the pathogenic cross-linking AGE glucosepane could explain the positive predictive value of high CTSL levels on albuminuria.}, }
@article {pmid33863935, year = {2021}, author = {Nobili, S and Mannini, A and Parenti, A and Raggi, C and Lapucci, A and Chiorino, G and Paccosi, S and Di Gennaro, P and Vezzosi, V and Romagnoli, P and Susini, T and Coronnello, M}, title = {Establishment and characterization of a new spontaneously immortalized ER-/PR-/HER2+ human breast cancer cell line, DHSF-BR16.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8340}, pmid = {33863935}, issn = {2045-2322}, mesh = {Aged ; Breast Neoplasms/drug therapy/*genetics/*pathology/surgery ; CD24 Antigen/genetics/metabolism ; Carcinoma, Ductal/drug therapy/*genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Movement ; Chemotherapy, Adjuvant ; Epithelial Cell Adhesion Molecule/genetics/metabolism ; Female ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Intracellular Membranes/metabolism ; Keratin-7/genetics/metabolism ; Keratin-8/genetics/metabolism ; Neoadjuvant Therapy ; *Receptor, ErbB-2 ; *Receptors, Estrogen ; *Receptors, Progesterone ; Spheroids, Cellular/pathology ; }, abstract = {Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER-/PR-/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24-/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.}, }
@article {pmid34781971, year = {2021}, author = {Kostoglou, A and Vlastos, D and Bakalis, A and Ghosh, D}, title = {Breast cancer-associated opsoclonus-myoclonus syndrome: a case report.}, journal = {World journal of surgical oncology}, volume = {19}, number = {1}, pages = {328}, pmid = {34781971}, issn = {1477-7819}, mesh = {Adult ; *Breast Neoplasms/complications ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Opsoclonus-Myoclonus Syndrome/etiology ; Positron Emission Tomography Computed Tomography ; Prognosis ; }, abstract = {BACKGROUND: Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.<br><br>CASE PRESENTATION: A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.<br><br>CONCLUSIONS: In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.}, }
@article {pmid34556291, year = {2021}, author = {Mangiardi-Veltin, M and Chamming's, F and Jaffre, A and Rousvoal, A and Tunon de Lara, C and Brouste, V and Hoppe, S and Sénéchal, C}, title = {[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center].}, journal = {Bulletin du cancer}, volume = {108}, number = {11}, pages = {999-1009}, doi = {10.1016/j.bulcan.2021.05.007}, pmid = {34556291}, issn = {1769-6917}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*epidemiology/genetics ; Cancer Care Facilities ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Neoplasms, Unknown Primary/diagnostic imaging/*epidemiology/genetics ; Postoperative Complications/*epidemiology ; Prevalence ; Prophylactic Mastectomy/*adverse effects/methods ; Reoperation ; Retrospective Studies ; Time Factors ; }, abstract = {INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.<br><br>METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.<br><br>RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).<br><br>DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.}, }
@article {pmid33229203, year = {2021}, author = {Madabhavi, I and Sarkar, M and Chavan, C and Trivedi, M}, title = {Maxillary bone metastasis, as an early sign of breast cancer; an unusual &amp; rare site of metastasis from the common cancer.}, journal = {Oral oncology}, volume = {115}, number = {}, pages = {105098}, doi = {10.1016/j.oraloncology.2020.105098}, pmid = {33229203}, issn = {1879-0593}, mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Maxilla/*pathology ; Maxillary Neoplasms/*secondary ; Neoplasm Metastasis ; }, abstract = {Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual &amp; exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck &amp; non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.}, }
@article {pmid34765304, year = {2021}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study.}, journal = {American journal of cancer research}, volume = {11}, number = {10}, pages = {4966-4980}, pmid = {34765304}, issn = {2156-6976}, abstract = {To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA-GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.}, }
@article {pmid33416185, year = {2021}, author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD}, title = {miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {45}, number = {2}, pages = {706-716}, doi = {10.3892/or.2020.7880}, pmid = {33416185}, issn = {1791-2431}, mesh = {Animals ; Breast/pathology/surgery ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery ; Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Disease Progression ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mastectomy ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasm Recurrence, Local/*epidemiology/genetics ; RNA-Binding Proteins/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA‑MB‑231, compared to the non‑metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA‑MB‑468. The expression of miR‑490‑3p was induced following transforming growth factor (TGF)‑β‑induced epithelial‑to‑mesenchymal transition (EMT) in MCF10A cells. Gain‑and loss‑of‑function assays revealed that the expression of miR‑490‑3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA‑MB‑468 and MDA‑MB‑231 cells. The knockdown of miR‑490‑3p expression in MDA‑MB‑231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR‑490‑3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR‑490‑3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR‑490‑3p expression in patients with IDC compared to those with DCIS. The expression of miR‑490‑3p was negatively associated with both overall and disease‑free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro‑metastatic role of miR‑490‑3p in IDC, establishing it as a biomarker for disease progression in these patients.}, }
@article {pmid33263939, year = {2021}, author = {D'Alfonso, TM and Pareja, F and Da Cruz Paula, A and Vahdatinia, M and Gazzo, A and Ferrando, L and da Silva, EM and Cheng, E and Sclafani, L and Chandarlapaty, S and Zhang, H and Hoda, SA and Wen, HY and Brogi, E and Weigelt, B and Reis-Filho, JS}, title = {Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma.}, journal = {The journal of pathology. Clinical research}, volume = {7}, number = {2}, pages = {113-120}, pmid = {33263939}, issn = {2056-4538}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/complications/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; *DNA Copy Number Variations ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Papilloma/complications/diagnosis/*genetics/pathology ; Whole Exome Sequencing ; }, abstract = {Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.}, }
@article {pmid32686908, year = {2020}, author = {Ma, L and Qi, L and Li, S and Yin, Q and Liu, J and Wang, J and She, C and Li, P and Liu, Q and Wang, X and Li, W}, title = {Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.}, journal = {Thoracic cancer}, volume = {11}, number = {9}, pages = {2493-2505}, pmid = {32686908}, issn = {1759-7714}, support = {81702481//National Natural Science Foundation of China/ ; 15JCQNJC44800//Natural Science Foundation of Tianjin City/ ; 18JCYBJC27600//Natural Science Foundation of Tianjin City/ ; }, mesh = {Brain Neoplasms/*enzymology/*secondary ; Breast Neoplasms/*complications/*enzymology/pathology ; Female ; Histone Deacetylases/*metabolism ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.<br><br>METHODS: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.<br><br>RESULTS: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.<br><br>CONCLUSIONS: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.<br><br>KEY POINTS: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.}, }
@article {pmid32661669, year = {2021}, author = {Rooper, LM and Thompson, LDR and Gagan, J and Oliai, BR and Weinreb, I and Bishop, JA}, title = {Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.}, journal = {Head and neck pathology}, volume = {15}, number = {1}, pages = {179-185}, pmid = {32661669}, issn = {1936-0568}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Ductal/genetics/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Parotid Neoplasms/genetics/*pathology ; }, abstract = {Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.}, }
@article {pmid33428505, year = {2021}, author = {Nevagi, RJ and Good, MF and Stanisic, DI}, title = {Plasmodium infection and drug cure for malaria vaccine development.}, journal = {Expert review of vaccines}, volume = {20}, number = {2}, pages = {163-183}, doi = {10.1080/14760584.2021.1874923}, pmid = {33428505}, issn = {1744-8395}, mesh = {Animals ; Antigens, Protozoan/immunology ; Antimalarials/administration &amp; dosage ; Humans ; Malaria/immunology/parasitology/*prevention &amp; control ; Malaria Vaccines/*administration &amp; dosage/immunology ; Plasmodium/*immunology/parasitology ; }, abstract = {Introduction: Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials. The advantage of whole parasite vaccines is that they induce immune responses against multiple parasite antigens, thus lowering the impact of antigenic diversity. Deliberate Plasmodium IDC, as a vaccine approach, involves administering infectious, live parasites in combination with an anti-malarial drug, which controls the infection and enables induction of protective immune responses.}, }
@article {pmid33073677, year = {2020}, author = {Qi, P and Bai, QM and Yao, QL and Yang, WT and Zhou, XY}, title = {Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.}, journal = {Technology in cancer research &amp; treatment}, volume = {19}, number = {}, pages = {1533033820960760}, pmid = {33073677}, issn = {1533-0338}, mesh = {Breast Neoplasms/*genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Transcriptome/*genetics ; }, abstract = {This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.}, }
@article {pmid34708717, year = {2021}, author = {Wang, YY and Liu, C and Chen, X and Ji, J and Zhu, SL and Sun, Q and Zhang, K and Zhu, J and Zhao, S and Wang, YW and Ma, R and Wang, JL}, title = {Heat shock protein 90α in nipple discharge as a potential tumor marker for breast cancer.}, journal = {The Chinese journal of physiology}, volume = {64}, number = {5}, pages = {251-256}, doi = {10.4103/cjp.cjp_72_21}, pmid = {34708717}, issn = {0304-4920}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; Female ; HSP90 Heat-Shock Proteins/*genetics ; Humans ; *Nipple Discharge ; }, abstract = {Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.}, }
@article {pmid34238275, year = {2021}, author = {Samson, J and Derlipanska, M and Zaheed, O and Dean, K}, title = {Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {790}, pmid = {34238275}, issn = {1471-2407}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; }, abstract = {BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.<br><br>METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.<br><br>RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.<br><br>CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.}, }
@article {pmid32220886, year = {2020}, author = {Pareja, F and Brown, DN and Lee, JY and Da Cruz Paula, A and Selenica, P and Bi, R and Geyer, FC and Gazzo, A and da Silva, EM and Vahdatinia, M and Stylianou, AA and Ferrando, L and Wen, HY and Hicks, JB and Weigelt, B and Reis-Filho, JS}, title = {Whole-Exome Sequencing Analysis of the Progression from Non-Low-Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {14}, pages = {3682-3693}, pmid = {32220886}, issn = {1557-3265}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA Copy Number Variations ; DNA Mutational Analysis ; Disease Progression ; Female ; *Genetic Heterogeneity ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/diagnosis/*genetics/pathology ; Whole Exome Sequencing ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Here, we sought to investigate the level of intralesion genetic heterogeneity in DCIS and the patterns of clonal architecture changes in the progression from DCIS to invasive disease.<br><br>EXPERIMENTAL DESIGN: Synchronous DCIS (n = 27) and invasive ductal carcinomas of no special type (IDC-NSTs; n = 26) from 25 patients, and pure DCIS (n = 7) from 7 patients were microdissected separately and subjected to high-depth whole-exome (n = 56) or massively parallel sequencing targeting ≥410 key cancer-related genes (n = 4). Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic analyses were defined using validated computational methods.<br><br>RESULTS: DCIS revealed genetic alterations similar to those of synchronously diagnosed IDC-NSTs and of non-related IDC-NSTs from The Cancer Genome Atlas (TCGA), whereas pure DCIS lacked PIK3CA mutations. Clonal decomposition and phylogenetic analyses based on somatic mutations and copy number alterations revealed that the mechanisms of progression of DCIS to invasive carcinoma are diverse, and that clonal selection might have constituted the mechanism of progression from DCIS to invasive disease in 28% (7/25) of patients. DCIS displaying a pattern of clonal selection in the progression to invasive cancer harbored higher levels of intralesion genetic heterogeneity than DCIS where no clonal selection was observed.<br><br>CONCLUSIONS: Intralesion genetic heterogeneity is a common feature in DCIS synchronously diagnosed with IDC-NST. DCIS is a nonobligate precursor of IDC-NST, whose mechanisms of progression to invasive breast cancer are diverse and vary from case to case.}, }
@article {pmid34716548, year = {2021}, author = {Cattaneo, C and Rieg, S and Schwarzer, G and Müller, MC and Blümel, B and Kern, WV}, title = {Enterococcus faecalis bloodstream infection: does infectious disease specialist consultation make a difference?.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {34716548}, issn = {1439-0973}, abstract = {PURPOSE: To evaluate the relationship between mortality or relapse of bloodstream infection (BSI) due to Enterococcus faecalis and infectious diseases specialist consultation (IDC) and other factors potentially associated with outcomes.<br><br>METHODS: In a tertiary-care center, consecutive adult patients with E. faecalis BSI between January 1, 2016 and January 31, 2019, were prospectively followed. The management of E. faecalis BSI was evaluated in terms of adherence to evidence-based quality-of-care indicators (QCIs). IDC and other factors potentially associated with 90-day-mortality or relapse of E. faecalis BSI were analyzed by multivariate logistic regression.<br><br>RESULTS: A total of 151 patients with a median age of 68 years were studied. IDC was performed in 38% of patients with E. faecalis BSI. 30 cases of endocarditis (20%) were diagnosed. All-cause in-hospital mortality was 23%, 90-day mortality was 37%, and 90-day relapsing E. faecalis BSI was 8%. IDC was significantly associated with better adherence to 5 QCIs. Factors significantly associated with 90-day mortality or relapsing EfB in multivariate analysis were severe sepsis or septic shock at onset (HR 4.32, CI 2.36e7.88) and deep-seated focus of infection (superficial focus HR 0.33, CI 0.14e0.76).<br><br>CONCLUSION: Enterococcus faecalis bacteremia is associated with a high mortality. IDC contributed to improved diagnostic and therapeutic management.}, }
@article {pmid34707969, year = {2021}, author = {Blum, K and Bowirrat, A and Gondre Lewis, MC and Simpatico, TA and Ceccanti, M and Steinberg, B and Modestino, EJ and Thanos, PK and Baron, D and McLaughlin, T and Brewer, R and Badgaiyan, RD and Ponce, JV and Lott, L and Gold, MS}, title = {Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.}, journal = {Current psychopharmacology}, volume = {10}, number = {}, pages = {}, doi = {10.2174/2211556010666210215155509}, pmid = {34707969}, issn = {2211-5560}, abstract = {Background: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.<br><br>Objective: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.<br><br>Method: Genetic Addiction Risk Score (GARS®) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.<br><br>Results: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).<br><br>Conclusion: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.}, }
@article {pmid34048471, year = {2021}, author = {Brock, EJ and Jackson, RM and Boerner, JL and Li, Q and Tennis, MA and Sloane, BF and Mattingly, RR}, title = {Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.}, journal = {PloS one}, volume = {16}, number = {5}, pages = {e0252314}, pmid = {34048471}, issn = {1932-6203}, support = {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 ; }, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mitogen-Activated Protein Kinase 1/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; }, abstract = {Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Patients often receive surgery and radiotherapy, but this early intervention has not produced substantial decreases in late-stage disease. Sprouty proteins are important regulators of ERK/MAPK signaling and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry, we found reduced Sprouty4 expression in IDC patient samples compared to DCIS, and that ERK/MAPK phosphorylation had an inverse relationship to Sprouty4 expression. These observations were reproduced using a 3D culture model of disease progression. Knockdown of Sprouty4 in MCF10.DCIS cells increased ERK/MAPK phosphorylation as well as their invasive capability, while overexpression of Sprouty4 in MCF10.CA1d IDC cells reduced ERK/MAPK phosphorylation, invasion, and the aggressive phenotype exhibited by these cells. Immunofluorescence experiments revealed reorganization of the actin cytoskeleton and relocation of E-cadherin back to the cell surface, consistent with the restoration of adherens junctions. To determine whether these effects were due to changes in ERK/MAPK signaling, MEK1/2 was pharmacologically inhibited in IDC cells. Nanomolar concentrations of MEK162/binimetinib restored an epithelial-like phenotype and reduced pericellular proteolysis, similar to Sprouty4 overexpression. From these data we conclude that Sprouty4 acts to control ERK/MAPK signaling in DCIS, thus limiting the progression of these premalignant breast lesions.}, }
@article {pmid34698916, year = {2021}, author = {Deshpande, SS and Malik, SC and Conforti, P and Lin, JD and Chu, YH and Nath, S and Greulich, F and Dumbach, MA and Uhlenhaut, NH and Schachtrup, C}, title = {P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.}, journal = {Cell and tissue research}, volume = {}, number = {}, pages = {}, pmid = {34698916}, issn = {1432-0878}, support = {1442/8-1//Deutsche Forschungsgemeinschaft/ ; 1442/9-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75NTR-/-) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75NTR-/- NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75NTR abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75NTR-/- NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75NTR-/- NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75NTR abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.}, }
@article {pmid34133406, year = {2021}, author = {Akhavan, AA and Wirtz, EC and Ollila, DW and Bhatt, N}, title = {An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab.}, journal = {Plastic and reconstructive surgery}, volume = {148}, number = {2}, pages = {299-303}, doi = {10.1097/PRS.0000000000008155}, pmid = {34133406}, issn = {1529-4242}, mesh = {Adalimumab/*adverse effects ; Breast Implantation/*adverse effects/instrumentation ; Breast Implants/*adverse effects ; Breast Neoplasms/diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant/adverse effects/methods ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/etiology/surgery ; Mastectomy/adverse effects ; Middle Aged ; Surface Properties ; Tissue Expansion Devices/*adverse effects ; }, abstract = {SUMMARY: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.}, }
@article {pmid34349234, year = {2021}, author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL}, title = {Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.}, journal = {Spinal cord}, volume = {59}, number = {9}, pages = {948-958}, pmid = {34349234}, issn = {1476-5624}, support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; 90IF0121/ACL/ACL HHS/United States ; 90IF0121/ACL/ACL HHS/United States ; }, mesh = {Catheters, Indwelling ; Humans ; Psychometrics ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; }, abstract = {STUDY DESIGN: Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).<br><br>SETTING: Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n = 306; MS, n = 8), or by voiding (SCI, n = 103; MS, n = 383). A total of n = 381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.<br><br>METHODS: Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".<br><br>RESULTS: Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.<br><br>CONCLUSIONS: The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.}, }
@article {pmid34345005, year = {2021}, author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL}, title = {Reliability of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.}, journal = {Spinal cord}, volume = {59}, number = {9}, pages = {939-947}, pmid = {34345005}, issn = {1476-5624}, support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; }, mesh = {Bayes Theorem ; Catheters, Indwelling ; Humans ; Reproducibility of Results ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; United States ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; }, abstract = {STUDY DESIGN: This is a descriptive psychometrics study.<br><br>OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), also called Neurogenic Bladder (NB), is a common and disruptive condition in a variety of neurologic diagnoses. Our team developed patient-centered instruments, Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB), specific to people with NLUTD who manage their bladders with intermittent catheterization (IC), indwelling catheters (IDC), or who void (V). This article reports evidence of reliability of the IDC and V instruments.<br><br>SETTING: Online surveys completed by individuals in the United States with NLUTD due to spinal cord injury (SCI), or multiple sclerosis (MS) who manage their bladder with IDC (SCI, n = 306), or by voiding (SCI, n = 103; MS, n = 383).<br><br>METHODS: Reliability estimates were based on endorsement of the items on the USQNB-IDC and USQNB-V. Reliability evidence was representativeness of these symptoms for a national sample (by determining if endorsement > 10%); internal consistency estimates (by Cronbach's alpha and item correlation coefficient, ICC); and interrelatedness of the items (by inferred Bayesian network, BN). We also tested whether a one-factor conceptualization of "urinary symptoms in NLUTD" was supportable for either instrument.<br><br>RESULTS: All items were endorsed by >20% of our samples. Urine quality symptoms tended to be the most commonly endorsed on both instruments. Cronbach's alpha and ICC estimates were high (>0.74), but not suggestive of redundancy. BNs showed interpretable associations among the items, and did not discover uninterpretable or unexpected associations. Neither instrument fit a one-factor model, as expected.<br><br>CONCLUSIONS: The USQNB-IDC and USQNB-V instruments show sufficient, multidimensional reliability for implementation and further study.}, }
@article {pmid33090732, year = {2020}, author = {Morigny, P and Zuber, J and Haid, M and Kaltenecker, D and Riols, F and Lima, JDC and Simoes, E and Otoch, JP and Schmidt, SF and Herzig, S and Adamski, J and Seelaender, M and Berriel Diaz, M and Rohm, M}, title = {High levels of modified ceramides are a defining feature of murine and human cancer cachexia.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {11}, number = {6}, pages = {1459-1475}, pmid = {33090732}, issn = {2190-6009}, mesh = {Animals ; *Cachexia/etiology ; *Ceramides/metabolism ; Humans ; Mice ; Muscular Atrophy ; *Neoplasms/complications ; Quality of Life ; }, abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.<br><br>METHODS: Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, ApcMin/+ mutant mice), and plasma from weight stable and cachectic patients with gastrointestinal cancer, were analysed using the Lipidyzer™ platform. In total, 13 lipid classes and more than 1100 lipid species, including sphingolipids, neutral and polar glycerolipids, were covered by the analysis. Correlation analysis between specific lipid species and readouts of CCx were performed. Lipidomics data were confirmed by gene expression analysis of metabolic organs to analyse enzymes involved in sphingolipid synthesis and degradation.<br><br>RESULTS: A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.<br><br>CONCLUSIONS: High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.}, }
@article {pmid32467291, year = {2020}, author = {Shan, NL and Minden, A and Furmanski, P and Bak, MJ and Cai, L and Wernyj, R and Sargsyan, D and Cheng, D and Wu, R and Kuo, HD and Li, SN and Fang, M and Maehr, H and Kong, AN and Suh, N}, title = {Analysis of the Transcriptome: Regulation of Cancer Stemness in Breast Ductal Carcinoma In Situ by Vitamin D Compounds.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {13}, number = {8}, pages = {673-686}, pmid = {32467291}, issn = {1940-6215}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 AT007036/AT/NCCIH NIH HHS/United States ; R01 AT009152/AT/NCCIH NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology/*prevention &amp; control ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Methylation/drug effects ; Datasets as Topic ; Disease Progression ; Down-Regulation/drug effects ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness/pathology/prevention &amp; control ; Neoplastic Stem Cells/*drug effects/pathology ; RNA-Seq ; Signal Transduction/drug effects/genetics ; Up-Regulation/drug effects ; Vitamin D/*administration &amp; dosage/analogs &amp; derivatives ; }, abstract = {Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell-like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken of MCF10DCIS cells grown in mammosphere cultures, in which cancer stem-like cells grow preferentially and produce colonies by self-renewal and maturation, in the presence and absence of 1α25(OH)2D3 and a vitamin D analog, BXL0124. Using next-generation RNA-sequencing, we found that vitamin D compounds downregulated genes involved in maintenance of breast cancer stem-like cells (e.g., GDF15), epithelial-mesenchymal transition, invasion, and metastasis (e.g., LCN2 and S100A4), and chemoresistance (e.g., NGFR, PPP1R1B, and AGR2), while upregulating genes associated with a basal-like phenotype (e.g., KRT6A and KRT5) and negative regulators of breast tumorigenesis (e.g., EMP1). Gene methylation status was analyzed to determine whether the changes in expression induced by vitamin D compounds occurred via this mechanism. Ingenuity pathway analysis was performed to identify upstream regulators and downstream signaling pathway genes differentially regulated by vitamin D, including TP63 and vitamin D receptor -mediated canonical pathways in particular. This study provides a global profiling of changes in the gene signature of DCIS regulated by vitamin D compounds and possible targets for chemoprevention of DCIS progression to IDC in patients.}, }
@article {pmid34461516, year = {2022}, author = {Meng, J and Yang, Q and Wan, W and Zhu, Q and Zeng, X}, title = {Physicochemical properties and adaptability of amine-producing Enterobacteriaceae isolated from traditional Chinese fermented fish (Suan yu).}, journal = {Food chemistry}, volume = {369}, number = {}, pages = {130885}, doi = {10.1016/j.foodchem.2021.130885}, pmid = {34461516}, issn = {1873-7072}, mesh = {Animals ; *Biogenic Amines ; China ; Enterobacter ; *Enterobacteriaceae/genetics ; Fermentation ; }, abstract = {The formation of biogenic amines (BAs) is an important potential danger in traditional fermented fish (Suan yu), and Enterobacteriaceae play an important role in the formation of BAs. The amine production abilities of 97 strains of Enterobacteriaceae screened from traditional fermented Suan yu were analyzed by reversed-phased high-performance liquid chromatography (HPLC). The genotypic diversity of amino acid decarboxylase on 23 strains of high-yield BAs was verified by PCR. Enterobacteriaceae with the highest production of amines was determined by analysis of the effects of physicochemical factors (pH, NaCl, temperature, and aerobic/anaerobic) on BA production and principal component analysis (PCA). The adaptability of the strains was examined using surimi simulation fermentation system, and the correlations among the indicators were analyzed using Cytoscape. Results showed that 97 strains of Enterobacteriaceae had strong amine-producing ability. Furthermore, 23 strains producing high yields of putrescine, cadaverine, and histamine were identified. All of the strains carried Idc, odc, speA, speB, and adiA, and five strains carried hdc. pH mainly affected the BA production of amine-producing bacteria. Three strains (Enterobacter asburiae 26C3, Klebsiella pneumoniae 47C2, and Morganella morganii 45C3) had the best amine-producing ability and used as the inoculated group. In this group, the values of BA (228.70-290.05 mg/kg) and the total volatile base nitrogen (TVB-N, 173.87-221.87 mg/100 g) exceeded the limit. Moreover, myofibrillar protein degradation was significant as indicated by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and decreased FAA content. Cytoscape software and principal component analysis (PCA) indicated that Enterobacteriaceae and pH were related to BA formation in Suan yu. These results provide a theoretical basis for controlling the BA of fermented fish products.}, }
@article {pmid34659834, year = {2021}, author = {Ntirenganya, F and Twagirumukiza, JD and Bucyibaruta, G and Rugwizangoga, B and Rulisa, S}, title = {Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study.}, journal = {International journal of breast cancer}, volume = {2021}, number = {}, pages = {5560559}, doi = {10.1155/2021/5560559}, pmid = {34659834}, issn = {2090-3170}, abstract = {Background: Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women.<br><br>Objectives: The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda.<br><br>Methods: This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis.<br><br>Results: 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake (AOR = 3.73, 95%CI 2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI 4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI 3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI 1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI 1.19 - 30.73, p = 0.03) were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype.<br><br>Conclusion: Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.}, }
@article {pmid34657058, year = {2021}, author = {Takagi, H and Fukai, H and Misawa, S and Kurogochi, A and Kirii, Y}, title = {[A Case of Bone Marrow Carcinomatosis Associated with Breast Cancer with Anemia and Thrombocytopenia Successfully Treated with Aromatase Inhibitor Therapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {48}, number = {10}, pages = {1255-1257}, pmid = {34657058}, issn = {0385-0684}, mesh = {*Anemia/drug therapy/etiology ; Aromatase Inhibitors ; Bone Marrow ; *Breast Neoplasms/complications/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Peritoneal Neoplasms ; *Thrombocytopenia/drug therapy/etiology ; }, abstract = {The patient was a 61-year-old woman who presented to the hospital with the chief complaints of anemia and thrombocytopenia. There was a mass in her left breast, and a needle biopsy with pathology revealed invasive ductal carcinoma, which was HR-positive and HER2-negative. A PET scan revealed multiple bone metastases, which were confirmed on bone marrow biopsy, leading to the diagnosis of bone marrow carcinomatosis. As the patient was in good general condition, an aromatase inhibitor(AI)therapy was selected. Rapid improvements in her hemoglobin level and platelet count were observed. At 19 months after the start of treatment, we were able to perform a left mastectomy with left axillary lymph node dissection. The histological evaluation of her response to treatment was Grade 2a, and severe lymph node metastasis was observed. The patient continued to receive the AI postoperatively. Thirty-two months after the start of treatment, there was no evidence of cancer on clinical imaging. Although it is rare for bone marrow carcinomatosis to occur, as in the present case, it is also notable that the patient had been in long-term remission with consistent AI therapy.}, }
@article {pmid34392891, year = {2021}, author = {Roberts, WC and Jeong, M}, title = {Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {157}, number = {}, pages = {101-106}, doi = {10.1016/j.amjcard.2021.07.023}, pmid = {34392891}, issn = {1879-1913}, mesh = {Adult ; Aged ; Cardiomyopathies/complications/epidemiology ; Cardiomyopathy, Dilated/*complications/epidemiology ; Female ; Follow-Up Studies ; *Forecasting ; Heart Failure/epidemiology/etiology/surgery ; Heart Transplantation ; Humans ; Incidence ; Middle Aged ; Peripartum Period ; Pregnancy ; *Pregnancy Complications, Cardiovascular ; Retrospective Studies ; Texas/epidemiology ; Young Adult ; }, abstract = {Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.}, }
@article {pmid34103599, year = {2021}, author = {Bin Kanner, Y and Ganoth, A and Tsfadia, Y}, title = {Extracellular mutation induces an allosteric effect across the membrane and hampers the activity of MRP1 (ABCC1).}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12024}, pmid = {34103599}, issn = {2045-2322}, mesh = {Allosteric Regulation ; Amino Acid Substitution ; Humans ; Multidrug Resistance-Associated Proteins/*chemistry/*genetics ; *Mutation, Missense ; Protein Domains ; Protein Structure, Secondary ; }, abstract = {Dynamic conformational changes play a major role in the function of proteins, including the ATP-Binding Cassette (ABC) transporters. Multidrug Resistance Protein 1 (MRP1) is an ABC exporter that protects cells from toxic molecules. Overexpression of MRP1 has been shown to confer Multidrug Resistance (MDR), a phenomenon in which cancer cells are capable to defend themselves against a broad variety of drugs. In this study, we used varied computational techniques to explore the unique F583A mutation that is known to essentially lock the transporter in a low-affinity solute binding state. We demonstrate how macro-scale conformational changes affect MRP1's stability and dynamics, and how these changes correspond to micro-scale structural perturbations in helices 10-11 and the nucleotide-binding domains (NBDs) of the protein in regions known to be crucial for its ATPase activity. We demonstrate how a single substitution of an outward-facing aromatic amino acid causes a long-range allosteric effect that propagates across the membrane, ranging from the extracellular ECL5 loop to the cytoplasmic NBD2 over a distance of nearly 75 Å, leaving the protein in a non-functional state, and provide the putative allosteric pathway. The identified allosteric structural pathway is not only in agreement with experimental data but enhances our mechanical understanding of MRP1, thereby facilitating the rational design of chemosensitizers toward the success of chemotherapy treatments.}, }
@article {pmid32343605, year = {2021}, author = {Liu, CR and Meng, FH}, title = {DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial-Mesenchymal Transition Process.}, journal = {Cancer biotherapy &amp; radiopharmaceuticals}, volume = {36}, number = {2}, pages = {180-188}, doi = {10.1089/cbr.2019.3504}, pmid = {32343605}, issn = {1557-8852}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Proliferation/physiology ; Deoxyribonuclease I/*metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Middle Aged ; Phenotype ; Prognosis ; Transfection ; }, abstract = {Purpose: The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Methods: Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Results: Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. Conclusion: This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.}, }
@article {pmid33667422, year = {2021}, author = {Schwartz, CJ and Boroujeni, AM and Khodadadi-Jamayran, A and Heguy, A and Snuderl, M and Jour, G and Cotzia, P and Darvishian, F}, title = {Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.}, journal = {Human pathology}, volume = {111}, number = {}, pages = {67-74}, doi = {10.1016/j.humpath.2021.02.005}, pmid = {33667422}, issn = {1532-8392}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; }, abstract = {Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.}, }
@article {pmid32457515, year = {2020}, author = {Goodes, LM and King, GK and Goodwin, DM and Watts, A and Bardsley, J and Middleton, J and Bragge, P and Dunlop, SA}, title = {Barriers and facilitators to optimising inpatient bladder management after spinal cord injury.}, journal = {Spinal cord}, volume = {58}, number = {12}, pages = {1291-1300}, pmid = {32457515}, issn = {1476-5624}, mesh = {Humans ; Inpatients ; Longitudinal Studies ; *Spinal Cord Injuries/therapy ; *Urinary Bladder, Neurogenic/etiology/therapy ; }, abstract = {STUDY DESIGN: Qualitative survey.<br><br>OBJECTIVES: Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.<br><br>SETTING: Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).<br><br>METHODS: Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.<br><br>RESULTS: Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6 hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.<br><br>CONCLUSIONS: Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.}, }
@article {pmid32239352, year = {2020}, author = {Maggi, G and D'Iorio, A and Di Meglio, D and Vinciguerra, A and Amboni, M and Vitale, C and Santangelo, G}, title = {The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {127}, number = {6}, pages = {893-898}, doi = {10.1007/s00702-020-02179-x}, pmid = {32239352}, issn = {1435-1463}, mesh = {Anxiety/etiology ; *Cognitive Dysfunction/etiology ; *Gait Disorders, Neurologic ; Humans ; Neuropsychological Tests ; *Parkinson Disease/complications ; }, abstract = {Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.}, }
@article {pmid34016957, year = {2021}, author = {Egea, V and Kessenbrock, K and Lawson, D and Bartelt, A and Weber, C and Ries, C}, title = {Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release.}, journal = {Cell death &amp; disease}, volume = {12}, number = {6}, pages = {516}, pmid = {34016957}, issn = {2041-4889}, mesh = {Animals ; Cell Communication/physiology ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Chemokine CXCL12/*metabolism ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/genetics/*metabolism/pathology ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/biosynthesis/*genetics ; Transfection ; Tumor Hypoxia/*physiology ; }, abstract = {Bone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.}, }
@article {pmid33238073, year = {2021}, author = {Okada, K and Takahara, T and Suzuki, Y and Kohno, K and Sakakibara, A and Satou, A and Takahashi, E and Nakamura, S}, title = {Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.}, journal = {Pathology international}, volume = {71}, number = {1}, pages = {24-32}, doi = {10.1111/pin.13044}, pmid = {33238073}, issn = {1440-1827}, mesh = {Adolescent ; Adult ; Aged ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/analysis ; *Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology ; Dendritic Cells/metabolism/pathology ; Female ; Histiocytes/metabolism/pathology ; *Histiocytic Sarcoma/immunology/metabolism/pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Langerhans Cell Sarcoma/immunology/metabolism/pathology ; Lymphoma, Follicular/immunology/metabolism/pathology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes/metabolism ; }, abstract = {Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.}, }
@article {pmid32511899, year = {2020}, author = {Yamaguchi, T and Akahane, T and Harada, O and Kato, Y and Aimono, E and Takei, H and Tasaki, T and Noguchi, H and Nishihara, H and Kamata, H and Tanimoto, A}, title = {Next-generation sequencing in residual liquid-based cytology specimens for cancer genome analysis.}, journal = {Diagnostic cytopathology}, volume = {48}, number = {11}, pages = {965-971}, doi = {10.1002/dc.24511}, pmid = {32511899}, issn = {1097-0339}, mesh = {Carcinoma/*genetics ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Gene Frequency/genetics ; Genome/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lymph Nodes/pathology ; Mutation/genetics ; Neoplasms/*genetics ; Sequence Analysis, DNA/methods ; Thyroid Gland/pathology ; }, abstract = {BACKGROUND: Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage.<br><br>METHODS: We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes.<br><br>RESULTS: NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5% ± 4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5% ± 2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.<br><br>CONCLUSION: The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.}, }
@article {pmid34634714, year = {2021}, author = {Kufel, WD and Mastro, KA and Steele, JM and Wang, D and Riddell, SW and Paolino, KM and Thomas, SJ}, title = {Impact of a pharmacist-facilitated, evidence-based bundle initiative on Staphylococcus aureus bacteremia management.}, journal = {Diagnostic microbiology and infectious disease}, volume = {101}, number = {4}, pages = {115535}, doi = {10.1016/j.diagmicrobio.2021.115535}, pmid = {34634714}, issn = {1879-0070}, abstract = {OBJECTIVE: To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).<br><br>METHODS: This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.<br><br>RESULTS: Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P = 0.009), persistent SAB (18.9% vs 9.0%, P = 0.041), and length of stay (14 vs 13 days, P = 0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.<br><br>CONCLUSIONS: Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.}, }
@article {pmid33662042, year = {2021}, author = {Mohamed, RI and Bargal, SA and Mekawy, AS and El-Shiekh, I and Tuncbag, N and Ahmed, AS and Badr, E and Elserafy, M}, title = {The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.}, journal = {PloS one}, volume = {16}, number = {3}, pages = {e0247837}, pmid = {33662042}, issn = {1932-6203}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Precision Medicine ; Transcriptome ; Up-Regulation ; }, abstract = {In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients' response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients' samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients' samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients' samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.}, }
@article {pmid32871469, year = {2020}, author = {Molocea, CE and Tsokanos, FF and Herzig, S}, title = {Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies.}, journal = {Current opinion in pharmacology}, volume = {53}, number = {}, pages = {101-116}, doi = {10.1016/j.coph.2020.07.006}, pmid = {32871469}, issn = {1471-4973}, mesh = {Animals ; Appetite Regulation ; *Cachexia/etiology/immunology/metabolism/therapy ; Humans ; Inflammation Mediators/immunology ; Macrophages/immunology ; *Neoplasms/complications/immunology/metabolism/therapy ; *Obesity/immunology/metabolism/therapy ; }, abstract = {Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.}, }
@article {pmid32650989, year = {2020}, author = {Kaviani, A and Tabary, M and Zand, S and Araghi, F and Patocskai, E and Nouraie, M}, title = {Oncoplastic Repair in Breast Conservation: Comprehensive Evaluation of Techniques and Oncologic Outcomes of 937 Patients.}, journal = {Clinical breast cancer}, volume = {20}, number = {6}, pages = {511-519}, doi = {10.1016/j.clbc.2020.05.016}, pmid = {32650989}, issn = {1938-0666}, mesh = {Adult ; Breast/pathology/surgery ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Chemotherapy, Adjuvant/statistics &amp; numerical data ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Iran/epidemiology ; Mammaplasty/*adverse effects/methods/statistics &amp; numerical data ; Margins of Excision ; Mastectomy, Segmental/*adverse effects/statistics &amp; numerical data ; Middle Aged ; Neoadjuvant Therapy/methods/statistics &amp; numerical data ; Neoplasm Recurrence, Local/*epidemiology ; Neoplasm Staging ; Postoperative Complications/*epidemiology/etiology ; Prospective Studies ; Reoperation/statistics &amp; numerical data ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast-conserving surgery, especially with oncoplastic breast surgery (OBS), is becoming the standard of care in the surgical management of breast cancer. We investigated the applied technique of OBS and oncologic outcomes in a large series of patients.<br><br>PATIENTS AND METHODS: This study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS. Early and late postoperative complications, oncologic outcomes, and follow-up data were documented.<br><br>RESULTS: Nine hundred thirty-seven patients with a mean ± standard deviation age of 48.1 ± 11.3 underwent OBS. Most of the patients were diagnosed with early-stage disease, of which the most common pathology was invasive ductal carcinoma (83.3%). Lateral oncoplasty was the most commonly used OBS technique (324 cases, 34.6%). The most common complication was seroma formation. Reduction-type OBS technique had the highest rate of complications (13.1%). Thirty-four patients (5.4%) experienced local recurrence, with a median recurrence time of 26.4 months. Nine patients (1.3%) died from cancer recurrence.<br><br>CONCLUSION: OBS is a safe procedure with minor complications and good oncologic outcomes. These techniques can be applied to most patients who are candidates for breast-conserving surgery.}, }
@article {pmid32416533, year = {2020}, author = {Syed, AP and Greulich, F and Ansari, SA and Uhlenhaut, NH}, title = {Anti-inflammatory glucocorticoid action: genomic insights and emerging concepts.}, journal = {Current opinion in pharmacology}, volume = {53}, number = {}, pages = {35-44}, doi = {10.1016/j.coph.2020.03.003}, pmid = {32416533}, issn = {1471-4973}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Genomics ; Glucocorticoids/*pharmacology ; Humans ; RNA, Untranslated ; Receptors, Glucocorticoid/genetics ; Transcription, Genetic ; }, abstract = {Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furthermore, the involvement of non-coding RNAs such as lncRNAs, miRNAs and eRNAs adds another level of regulation to the GR's transcriptional activity. Characterizing and understanding these multiple mechanisms will be crucial for developing more targeted immunomodulatory therapies with reduced adverse effects such as obesity, diabetes and osteoporosis.}, }
@article {pmid34587404, year = {2021}, author = {Yang, L and Xiong, Y and Sun, Z and Lin, X and Ni, H}, title = {Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {40}, number = {3}, pages = {51-61}, doi = {10.1615/JEnvironPatholToxicolOncol.2021038118}, pmid = {34587404}, issn = {2162-6537}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/*drug effects/physiology ; Benzylisoquinolines/*pharmacology ; Body Weight/drug effects ; Carcinogens/toxicity ; Cell Proliferation/drug effects/physiology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Lipid Peroxidation/drug effects ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/metabolism/pathology ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Signal Transduction/drug effects ; }, abstract = {AIM: To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals.<br><br>METHODS: Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats.<br><br>RESULTS: We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-κB, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-κB signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats.<br><br>CONCLUSION: In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.}, }
@article {pmid32362500, year = {2020}, author = {Dianatinasab, M and Rezaian, M and HaghighatNezad, E and Bagheri-Hosseinabadi, Z and Amanat, S and Rezaeian, S and Masoudi, A and Ghiasvand, R}, title = {Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis.}, journal = {Clinical breast cancer}, volume = {20}, number = {4}, pages = {e516-e528}, doi = {10.1016/j.clbc.2020.03.007}, pmid = {32362500}, issn = {1938-0666}, mesh = {Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diet Surveys/*statistics &amp; numerical data ; *Feeding Behavior ; Female ; Humans ; Risk Assessment/statistics &amp; numerical data ; Risk Factors ; }, abstract = {The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case-control studies (RR = 0.47; 95% CI, 0.39-0.55; I2 = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I2 = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I2 = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I2 = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I2 = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.}, }
@article {pmid32299754, year = {2020}, author = {El Abbass, KA and Abdellateif, MS and Gawish, AM and Zekri, AN and Malash, I and Bahnassy, AA}, title = {The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer.}, journal = {Clinical breast cancer}, volume = {20}, number = {4}, pages = {e373-e384}, doi = {10.1016/j.clbc.2019.11.008}, pmid = {32299754}, issn = {1938-0666}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*genetics/secondary/therapy ; Case-Control Studies ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Healthy Volunteers ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; Primary Cell Culture ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Cells, Cultured ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).<br><br>METHODS: Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.<br><br>RESULTS: The number of CD44+CD24-/low cells associated significantly at the end of culture with the expression level of Wnt, β-catenin, and distant metastasis (P < .001, P = .015 and P = .003, respectively). There was significant association between the mammosphere number and CD44+CD24-/low cells as well as AKT expression (P = .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P < .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P = .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P < .001, P = .001, P = .014, respectively).<br><br>CONCLUSION: BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.}, }
@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 {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 {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 {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}, 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 {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 {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}, 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 {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}, 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 {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 = {}, 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 {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 {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 {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}, 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 {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 = {15}, number = {12}, pages = {951-963}, 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 {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 {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 = {39}, number = {9}, pages = {756-768}, doi = {10.1080/07357907.2021.1950757}, pmid = {34279157}, issn = {1532-4192}, mesh = {Biomarkers, Tumor/*genetics/metabolism ; Carcinoma, Hepatocellular/*genetics/metabolism/pathology ; Cell Line, Tumor ; Exosomes/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/*genetics/metabolism/pathology ; MicroRNAs/genetics ; Myristoylated Alanine-Rich C Kinase Substrate/*genetics/metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; THP-1 Cells ; Tumor-Associated Macrophages/*metabolism ; }, 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 = {8}, number = {18}, pages = {e2101281}, 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 {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}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/mortality/surgery ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Prospective Studies ; Pseudomonas Infections/*drug therapy/mortality/surgery ; *Pseudomonas aeruginosa ; *Referral and Consultation ; Retrospective Studies ; Treatment Outcome ; }, 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 {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 {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 {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 {pmid34181649, year = {2021}, author = {Aftab, F and Ahmed, I and Ahmed, S and Ali, SM and Amenga-Etego, S and Ariff, S and Bahl, R and Baqui, AH and Begum, N and Bhutta, ZA and Biemba, G and Cousens, S and Das, V and Deb, S and Dhingra, U and Dutta, A and Edmond, K and Esamai, F and Ghosh, AK and Gisore, P and Grogan, C and Hamer, DH and Herlihy, J and Hurt, L and Ilyas, M and Jehan, F and Juma, MH and Kalonji, M and Khanam, R and Kirkwood, BR and Kumar, A and Kumar, A and Kumar, V and Manu, A and Marete, I and Mehmood, U and Minckas, N and Mishra, S and Mitra, DK and Moin, MI and Muhammad, K and Newton, S and Ngaima, S and Nguwo, A and Nisar, MI and Otomba, J and Quaiyum, MA and Sarrassat, S and Sazawal, S and Semrau, KE and Shannon, C and Singh, VP and Soofi, S and Soremekun, S and Suleiman, AM and Sunday, V and Dilip, TR and Tshefu, A and Wasan, Y and Yeboah-Antwi, K and Yoshida, S and Zaidi, AK and , }, title = {Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.}, journal = {PLoS medicine}, volume = {18}, number = {6}, pages = {e1003644}, pmid = {34181649}, issn = {1549-1676}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Africa South of the Sahara/epidemiology ; Asia/epidemiology ; Female ; Humans ; Infant ; *Infant Mortality ; Infant, Newborn ; *Maternal Mortality ; Pregnancy ; Pregnancy Complications/diagnosis/*mortality ; Pregnancy Outcome ; Prospective Studies ; Risk Assessment ; Risk Factors ; Stillbirth/*epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.<br><br>METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.<br><br>CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.<br><br>TRIAL REGISTRATION: The study is not a clinical trial.}, }
@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 = {49}, number = {12}, pages = {7154-7163}, pmid = {34142156}, issn = {1362-4962}, mesh = {Adenine ; Adenomatous Polyposis Coli/genetics ; Amino Acid Motifs ; Animals ; DNA/chemistry ; DNA Glycosylases/*chemistry/genetics ; DNA Repair ; DNA Replication ; Guanine/analogs &amp; derivatives ; Humans ; Mice ; Models, Molecular ; Mutation ; Proliferating Cell Nuclear Antigen/chemistry ; Zinc ; }, 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 {pmid34119440, year = {2021}, author = {Gnangnon, B and Duraisingh, MT and Buckee, CO}, title = {Deconstructing the parasite multiplication rate of Plasmodium falciparum.}, journal = {Trends in parasitology}, volume = {37}, number = {10}, pages = {922-932}, doi = {10.1016/j.pt.2021.05.001}, pmid = {34119440}, issn = {1471-5007}, mesh = {Animals ; Erythrocytes/parasitology ; Host-Parasite Interactions ; Humans ; Malaria, Falciparum/parasitology ; *Plasmodium falciparum/growth &amp; development ; *Protozoan Proteins/metabolism ; }, abstract = {Epidemiological indicators describing population-level malaria transmission dynamics are widely used to guide policy recommendations. However, the determinants of malaria outcomes within individuals are still poorly understood. This conceptual gap partly reflects the fact that there are few indicators that robustly predict the trajectory of individual infections or clinical outcomes. The parasite multiplication rate (PMR) is a widely used indicator for the Plasmodium intraerythrocytic development cycle (IDC), for example, but its relationship to clinical outcomes is complex. Here, we review its calculation and use in P. falciparum malaria research, as well as the parasite and host factors that impact it. We also provide examples of metrics that can help to link within-host dynamics to malaria clinical outcomes when used alongside the PMR.}, }
@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 {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 = {}, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 = {27}, number = {5}, pages = {362-370}, doi = {10.1159/000513776}, pmid = {33730716}, issn = {1421-9891}, mesh = {Adult ; *Alcoholism ; Humans ; Israel/epidemiology ; Jews/statistics &amp; numerical data ; Prevalence ; *Substance-Related Disorders/epidemiology ; Young Adult ; }, 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 {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 {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 {pmid33626496, year = {2021}, author = {Lozano, R and Salles, DC and Sandhu, S and Aragón, IM and Thorne, H and López-Campos, F and Rubio-Briones, J and Gutierrez-Pecharroman, AM and Maldonado, L and di Domenico, T and Sanz, A and Prieto, JD and García, I and Pacheco, MI and Garcés, T and Llacer, C and Romero-Laorden, N and Zambrana, F and López-Casas, PP and Lorente, D and Mateo, J and Pritchard, CC and Antonarakis, ES and Olmos, D and Lotan, TL and Castro, E}, title = {Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {147}, number = {}, pages = {74-83}, doi = {10.1016/j.ejca.2021.01.027}, pmid = {33626496}, issn = {1879-0852}, support = {R01 CA185297/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA2 Protein/*genetics ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; DNA Mutational Analysis ; Gene Deletion ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; *Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics ; Phenotype ; Prostatic Neoplasms/*genetics/pathology ; Risk Assessment ; Risk Factors ; Spain ; }, abstract = {BACKGROUND: Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour.<br><br>PATIENTS AND METHODS: To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.<br><br>RESULTS: No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p = 0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p = 0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3).<br><br>CONCLUSIONS: While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.}, }
@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 {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 {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 {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 {pmid33582923, year = {2021}, author = {Hu, XQ and Peng, L and Wintermark, M and Lipson, JA and Zhang, YR and Gao, Y}, title = {Shear Wave Elastography of Invasive Ductal Carcinoma: Correlations between Shear Wave Velocity and Histological Prognostic Factors.}, journal = {Current medical science}, volume = {41}, number = {1}, pages = {173-179}, pmid = {33582923}, issn = {2523-899X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Ductal/classification/*diagnostic imaging/pathology ; Elasticity Imaging Techniques/*methods/standards ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Sensitivity and Specificity ; }, abstract = {The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.}, }
@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 {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 {pmid33536239, year = {2021}, author = {Bühler, L and Maida, A and Vogl, ES and Georgiadi, A and Takacs, A and Kluth, O and Schürmann, A and Feuchtinger, A and von Toerne, C and Tsokanos, FF and Klepac, K and Wolff, G and Sakurai, M and Ekim Üstünel, B and Nawroth, P and Herzig, S}, title = {Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control.}, journal = {Life science alliance}, volume = {4}, number = {4}, pages = {}, pmid = {33536239}, issn = {2575-1077}, mesh = {Animals ; Biomarkers ; *Energy Metabolism ; Fluorescent Antibody Technique ; Gene Expression ; Gene Knockdown Techniques ; Glucose/metabolism ; *Insulin Secretion ; Islets of Langerhans/cytology/metabolism ; Lipid Metabolism ; Lipocalins/blood/*genetics/*metabolism ; Liver/metabolism ; Male ; Mice ; Obesity/etiology/metabolism ; }, abstract = {Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.}, }
@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 {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 {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 {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 {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 {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 {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 {pmid33413755, year = {2020}, author = {Zeng, XQ and Jiang, SS and Peng, YY and Liu, MF and Ye, CS and Dong, JY}, title = {Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review.}, journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih}, volume = {35}, number = {4}, pages = {377-382}, doi = {10.24920/003799}, pmid = {33413755}, issn = {1001-9294}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Platelet Count ; Thrombocytopenia/blood/*chemically induced/drug therapy ; Trastuzumab/*adverse effects ; }, abstract = {We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×109/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.}, }
@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 {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 {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 {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 {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 {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 {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 {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 ; IK6 BX005225/BX/BLRD VA/United States ; P30 DK058404/DK/NIDDK 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 ; P30 HD015052/HD/NICHD NIH HHS/United States ; R01 CA243326/CA/NCI NIH HHS/United States ; R01 CA111947/CA/NCI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/genetics ; Cadherins/genetics ; Catenins/genetics ; Cell Adhesion ; Female ; Humans ; Mice ; Tumor Microenvironment ; }, 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}, mesh = {Adult ; Antineoplastic Protocols ; Breast/pathology ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/mortality/*therapy ; Chemotherapy, Adjuvant/methods/*mortality ; Cohort Studies ; Combined Modality Therapy ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/etiology/pathology ; Neoplasm Staging ; Neoplasm, Residual ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant/methods/*mortality ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; }, 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}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Mucins ; Neoplasms, Multiple Primary/*pathology ; Skin Neoplasms/*pathology ; Sweat Gland Neoplasms/*pathology ; Uterine Neoplasms/pathology ; }, 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 {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 {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}, mesh = {Bone Neoplasms/diagnosis/secondary ; Breast Neoplasms/diagnosis/therapy ; Carcinoma, Ductal, Breast/diagnosis/therapy ; Chemoradiotherapy, Adjuvant ; Contrast Media/administration &amp; dosage ; Female ; Heterotaxy Syndrome/*diagnosis ; Humans ; Incidental Findings ; Liver Neoplasms/diagnosis/secondary ; Mastectomy, Segmental ; Middle Aged ; Spleen/*abnormalities/diagnostic imaging ; Time Factors ; Tomography, X-Ray Computed ; }, 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 {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 {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}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postoperative Period ; Proportional Hazards Models ; *Radiotherapy, Adjuvant ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; }, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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}, 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 ; R03 CA216114/CA/NCI NIH HHS/United States ; }, mesh = {*Antineoplastic Agents/administration &amp; dosage/pharmacology ; Breast Neoplasms/*drug therapy/pathology/radiotherapy ; Cell Line, Tumor ; *Disulfiram/administration &amp; dosage/pharmacology ; *Drug Repositioning ; Female ; Humans ; Immunogenic Cell Death/*drug effects ; Neoplastic Stem Cells ; Radiation Tolerance/*drug effects ; }, 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 {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 {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. Epi