@article {pmid42572745,
year = {2026},
author = {Hirata, M and Morisaki, T and Asaka, Y and Matsuda, H and Henmi, S and Kikukawa, Y and Kochi, A and Watanabe, C and Takada, K and Tauchi, Y and Ogisawa, K and Kinoshita, H and Kohashi, K and Kashiwagi, S},
title = {Early Distant Metastasis in Synchronous Bilateral Breast Cancer including a Small Low-Grade Carcinoma with Osteoclast-Like Giant Cells: A Case Report.},
journal = {Surgical case reports},
volume = {12},
number = {1},
pages = {},
pmid = {42572745},
issn = {2198-7793},
abstract = {INTRODUCTION: Breast carcinoma with osteoclast-like giant cells (OGCs) is an uncommon morphological finding, and its clinical significance remains unclear. We report a case of synchronous bilateral hormone receptor-positive breast cancer including a small, low-grade carcinoma with OGCs, followed by early distant recurrence after surgery.

CASE PRESENTATION: A 47-year-old woman presented with a palpable mass in the left breast. Imaging revealed synchronous bilateral breast tumors without evidence of nodal or distant metastasis. She underwent bilateral mastectomy and bilateral sentinel lymph node biopsy. The right breast tumor was a carcinoma with OGCs measuring 6 mm in diameter; it was estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, had a Ki-67 labeling index of 10%, was nuclear grade 1/histological grade 1, and showed no lymphovascular invasion or nodal metastasis. The left breast tumor was an invasive ductal carcinoma (so-called scirrhous type), measuring 25 mm in diameter; it was ER-positive, PgR-positive, HER2-negative, had a Ki-67 labeling index of 10%, was nuclear grade 2/histological grade 2, showed lymphatic invasion, and had an Oncotype DX recurrence score of 16. Tamoxifen was initiated. CT performed 6 months after surgery as postoperative imaging follow-up for this patient revealed multiple pulmonary nodules, and PET-CT showed pulmonary and lumbar vertebral lesions. Pathological confirmation was not performed; therefore, the precise origin could not be determined. Fulvestrant plus abemaciclib was started for clinically suspected recurrent breast cancer.

CONCLUSIONS: This case illustrates that early distant recurrence can occur in synchronous bilateral hormone receptor-positive breast cancer even when available clinicopathological and genomic findings appear relatively favorable. However, because the left conventional invasive ductal carcinoma had more plausible recurrence-risk features than the small right-sided carcinoma with OGCs, and because the metastatic lesions were not pathologically confirmed, this case should not be interpreted as evidence that the OGC-containing carcinoma caused the recurrence. Rather, it highlights the diagnostic and risk-assessment complexity of synchronous bilateral breast cancer that includes a rare stromal-rich morphological pattern.},
}

@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 & 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.},
}

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

@article {pmid33437736,
year = {2020},
author = {Abdolahi, M and Salehi, M and Shokatian, I and Reiazi, R},
title = {Artificial intelligence in automatic classification of invasive ductal carcinoma breast cancer in digital pathology images.},
journal = {Medical journal of the Islamic Republic of Iran},
volume = {34},
number = {},
pages = {140},
pmid = {33437736},
issn = {1016-1430},
abstract = {Background: Breast cancer is one of the most causes of death in women. Early diagnosis and detection of Invasive Ductal Carcinoma (IDC) is an important key for the treatment of IDC. Computer-aided approaches have great potential to improve diagnosis accuracy. In this paper, we proposed a deep learning-based method for the automatic classification of IDC in whole slide images (WSI) of breast cancer. Furthermore, different types of deep neural networks training such as training from scratch and transfer learning to classify IDC were evaluated. Methods: In total, 277524 image patches with 50×50-pixel size form original images were used for model training. In the first method, we train a simple convolutional neural network (named it baseline model) on these images. In the second approach, we used the pre-trained VGG-16 CNN model via feature extraction and fine-tuning for the classification of breast pathology images. Results: Our baseline model achieved a better result for the automatic classification of IDC in terms of F-measure and accuracy (83%, 85%) in comparison with original paper on this data set and achieved a comparable result with a new study that introduced accepted-rejected pooling layer. Also, transfer learning via feature extraction yielded better results (81%, 81%) in comparison with handcrafted features. Furthermore, transfer learning via feature extraction yielded better classification results in comparison with the baseline model. Conclusion: The experimental results demonstrate that using deep learning approaches yielded better results in comparison with handcrafted features. Also, using transfer learning in histopathology image analysis yielded significant results in comparison with training from scratch in much less time.},
}

@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},
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.},
}

Breast Neoplasms/*genetics/*immunology
Carcinoma, Ductal, Breast/*genetics/*immunology
Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology
Female
Genomics
Humans
Immune System

@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.

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.

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).

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.},
}

COVID-19/diagnosis/*epidemiology/therapy
Czech Republic/epidemiology
Female
Hospitals, Military
Humans
Male
Middle Aged
Retrospective Studies
United States

@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.},
}

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

@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.},
}

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

@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 & 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.},
}

Aged
Axilla
*Breast Neoplasms/drug therapy
*Dermatitis/drug therapy/etiology
Female
Humans
Metronidazole
Trastuzumab/adverse effects

@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 ; },
}

Breast/pathology
*Breast Neoplasms
*Carcinoma, Ductal, Breast/epidemiology/pathology
Female
Humans
Neoplasm Staging
Prognosis
Risk Factors

@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},
pmid = {33484951},
issn = {2212-8778},
mesh = {Adipocytes/metabolism ; Animals ; Autophagy ; Diabetes Mellitus, Type 2/metabolism ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/*physiology ; Humans ; Inflammation/metabolism ; Insulin Resistance ; Lipid Metabolism ; Metabolic Diseases/*metabolism ; Obesity/metabolism ; Proteins/metabolism ; Ubiquitin ; Unfolded Protein Response ; },
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.

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.

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.},
}

Adipocytes/metabolism
Animals
Autophagy
Diabetes Mellitus, Type 2/metabolism
Endoplasmic Reticulum/metabolism
Endoplasmic Reticulum Stress/*physiology
Humans
Inflammation/metabolism
Insulin Resistance
Lipid Metabolism
Metabolic Diseases/*metabolism
Obesity/metabolism
Proteins/metabolism
Ubiquitin
Unfolded Protein Response

@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 & 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.},
}

*Antimalarials/therapeutic use
*Apicoplasts
*Fosfomycin/analogs & derivatives/pharmacology/therapeutic use
Humans
*Malaria, Falciparum/drug therapy
Plasmodium falciparum/genetics

@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 & development ; Glycine max/*genetics/growth & 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.},
}

Gene Expression Profiling
Gene Expression Regulation, Plant/genetics
Iron/metabolism
Nutrients/*metabolism
Phosphates/metabolism
Plant Roots/genetics/growth & development
Glycine max/*genetics/growth & development/metabolism
Stress, Physiological/*genetics
Transcriptome/*genetics

@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},
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.

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.

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.

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.

OUTCOMES: She became extremely thin, weighing only 50 kg at admission on July 23, 2018. This eventually led to multiple organ failure and death.

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.},
}

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Breast Neoplasms/*complications/therapy
Cachexia/etiology/*therapy
Fatal Outcome
Female
Humans
Mastectomy/*methods
Middle Aged

@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 & 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 & 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.

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.

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.

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.},
}

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 & control
Postoperative Complications
Prospective Studies
Radiation Injuries/pathology
Radiotherapy Dosage
Treatment Outcome

@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.},
}

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

@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.

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.

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).

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.

KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.},
}

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

@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.

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 3[rd], 6[th], 9[th],12[th] and 24[th] month.

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).

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.},
}

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

@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.},
}

Animals
Enhancer Elements, Genetic/*immunology
Inflammation/genetics/immunology
Macrophages/*immunology
Mice
*Multiprotein Complexes/genetics/immunology
*RNA-Seq
*Receptors, Glucocorticoid/genetics/immunology
Transcription, Genetic/*immunology

@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 & 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 & 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.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Antigens, Viral/immunology/*isolation & 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 & purification
Young Adult

@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 ; Erb-b2 Receptor Tyrosine Kinases/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.},
}

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
Erb-b2 Receptor Tyrosine Kinases/genetics
Sensitivity and Specificity

@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 & 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.

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).

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.

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.},
}

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 & numerical data
Survival Rate

@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 ; Erb-b2 Receptor Tyrosine Kinases/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.

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.

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.

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.},
}

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
Erb-b2 Receptor Tyrosine Kinases/analysis
Risk Factors
Sensitivity and Specificity

@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 = {UF110155//The Royal Society/ ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 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 & 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.

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.

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.

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.},
}

Animals
Anopheles/parasitology/*physiology
*Circadian Rhythm
Erythrocytes/parasitology
Female
Mosquito Vectors/parasitology/*physiology
Plasmodium berghei/growth & development/*physiology
*Reproduction, Asexual

@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},
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/ ; },
mesh = {Allografts ; Animals ; Anthracenes/pharmacology ; CD4-Positive T-Lymphocytes/cytology ; Calcium-Binding Proteins/*metabolism ; Cell Differentiation ; Cells, Cultured ; DNA Methyltransferase 3A/*metabolism ; Dendritic Cells/metabolism ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Microfilament Proteins/*metabolism ; Proto-Oncogene Proteins c-jun/*metabolism ; Pulmonary Disease, Chronic Obstructive/genetics ; Signal Transduction ; *Smoke ; Smoking/*adverse effects ; T-Lymphocytes, Regulatory/*metabolism ; Tetrazolium Salts/pharmacology ; Th17 Cells/metabolism ; Thiazoles/pharmacology ; },
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.},
}

Allografts
Animals
Anthracenes/pharmacology
CD4-Positive T-Lymphocytes/cytology
Calcium-Binding Proteins/*metabolism
Cell Differentiation
Cells, Cultured
DNA Methyltransferase 3A/*metabolism
Dendritic Cells/metabolism
Disease Models, Animal
Enzyme Inhibitors/pharmacology
Male
Mice
Mice, Inbred BALB C
Microfilament Proteins/*metabolism
Proto-Oncogene Proteins c-jun/*metabolism
Pulmonary Disease, Chronic Obstructive/genetics
Signal Transduction
*Smoke
Smoking/*adverse effects
T-Lymphocytes, Regulatory/*metabolism
Tetrazolium Salts/pharmacology
Th17 Cells/metabolism
Thiazoles/pharmacology

@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},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/pathology ; Carcinoma, Lobular/diagnosis/epidemiology/pathology ; Cross-Sectional Studies ; DNA Methylation ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; India/epidemiology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging/methods ; Phyllodes Tumor/diagnosis/epidemiology/pathology ; Prognosis ; Promoter Regions, Genetic/*genetics ; Tumor Suppressor Proteins/*genetics ; },
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.

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.

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.

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.

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.},
}

Adult
Aged
Breast Neoplasms/*genetics/pathology
Carcinogenesis/genetics/pathology
Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology
Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/pathology
Carcinoma, Lobular/diagnosis/epidemiology/pathology
Cross-Sectional Studies
DNA Methylation
Disease Progression
Epigenesis, Genetic/*genetics
Female
Humans
India/epidemiology
Middle Aged
Neoplasm Invasiveness/pathology
Neoplasm Staging/methods
Phyllodes Tumor/diagnosis/epidemiology/pathology
Prognosis
Promoter Regions, Genetic/*genetics
Tumor Suppressor Proteins/*genetics

@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.

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.

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.

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.},
}

*Breast Neoplasms/genetics
Cell Line, Tumor
Cell Proliferation
Female
Humans
*Phosphoglycerate Dehydrogenase/genetics
Prognosis
Serine

@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.

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.

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).

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.},
}

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

@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.

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 {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.},
}

*Breast Neoplasms/genetics/surgery
*Carcinoma, Ductal, Breast
*Carcinoma, Lobular/genetics/therapy
Female
Humans
Mastectomy, Segmental

@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 & numerical data ; Treatment Outcome ; },
}

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 & numerical data
Treatment Outcome

@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.},
}

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

@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 ; Erb-b2 Receptor Tyrosine Kinases/*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.

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.

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.

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.},
}

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
Erb-b2 Receptor Tyrosine Kinases/*analysis

@article {pmid33665961,
year = {2021},
author = {Hartleben, G and Schorpp, K and Kwon, Y and Betz, B and Tsokanos, FF and Dantes, Z and Schäfer, A and Rothenaigner, I and Monroy Kuhn, JM and Morigny, P and Mehr, L and Lin, S and Seitz, S and Tokarz, J and Artati, A and Adamsky, J and Plettenburg, O and Lutter, D and Irmler, M and Beckers, J and Reichert, M and Hadian, K and Zeigerer, A and Herzig, S and Berriel Diaz, M},
title = {Combination therapies induce cancer cell death through the integrated stress response and disturbed pyrimidine metabolism.},
journal = {EMBO molecular medicine},
volume = {13},
number = {4},
pages = {e12461},
pmid = {33665961},
issn = {1757-4684},
mesh = {*Antineoplastic Agents ; Cell Death ; Humans ; *Neoplasms ; Niclosamide ; Pyrimidines ; },
abstract = {By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi-agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using high-throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation-like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard-of-care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing.},
}

*Antineoplastic Agents
Cell Death
Humans
*Neoplasms
Niclosamide
Pyrimidines

@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 ; 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.},
}

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
Middle Aged
Mutation
Retrospective Studies

@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.

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.

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.

CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.},
}

*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

@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 ; Erb-b2 Receptor Tyrosine Kinases/analysis/antagonists & 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).

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.

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).

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.},
}

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
Erb-b2 Receptor Tyrosine Kinases/analysis/antagonists & 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

@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.

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.

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.},
}

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

@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.},
}

*Adrenal Cortex Neoplasms/genetics
*Adrenocortical Carcinoma/diagnosis/genetics
Adult
*Breast Neoplasms
Female
Genomics
Humans
*Li-Fraumeni Syndrome/genetics
Mastectomy
Neoplasm Recurrence, Local

@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 ; Erb-b2 Receptor Tyrosine Kinases/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.

OBJECTIVE: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.

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.

EXPOSURES: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.

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.

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).

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.},
}

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
Erb-b2 Receptor Tyrosine Kinases/analysis
Young Adult

@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},
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 ; Erb-b2 Receptor Tyrosine Kinases/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.

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).

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 -).

INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions).

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.

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.},
}

Brain Neoplasms/metabolism/*secondary
Breast Neoplasms, Male/metabolism/*pathology
Carcinoma, Ductal, Breast/metabolism/*secondary
Humans
Male
Middle Aged
Erb-b2 Receptor Tyrosine Kinases/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism

@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 & 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.

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.

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]).

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.},
}

Adult
*Alcoholism
Humans
Israel/epidemiology
Jews/statistics & numerical data
Prevalence
*Substance-Related Disorders/epidemiology
Young Adult

@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.},
}

*Alcoholism
*Behavior, Addictive/epidemiology
Checklist
Humans
Risk Factors
*Substance-Related Disorders/epidemiology

@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 ; Erb-b2 Receptor Tyrosine Kinases/genetics ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/*genetics ; Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology ; ERRalpha Estrogen-Related Receptor ; },
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.},
}

Adult
Aged
Aged, 80 and over
Carcinoma, Lobular/genetics/metabolism/*pathology
DNA Mutational Analysis
Female
Humans
Middle Aged
Mutation
Phosphatidylinositol 3-Kinases/genetics
Erb-b2 Receptor Tyrosine Kinases/genetics
Receptors, Androgen/genetics/*metabolism
Receptors, Estrogen/*genetics
Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology
ERRalpha Estrogen-Related Receptor

@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 ; Betulinic Acid ; },
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.},
}

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
Betulinic Acid

@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 {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 = {MR/P021220/1/MRC_/Medical Research Council/United Kingdom ; MR/T016736/1/MRC_/Medical Research Council/United Kingdom ; /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 & 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 [13]C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of [13]C-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.},
}

*Adipogenesis
*Cell Differentiation
Cells, Cultured
Dendritic Cells/drug effects/immunology/*metabolism
Fatty Acids/*biosynthesis
Glycolysis
Humans
*Immune Tolerance
Vitamin D/*analogs & derivatives/pharmacology

@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 ; Erb-b2 Receptor Tyrosine Kinases/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.},
}

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
Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism
Young Adult

@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.

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.

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.

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 {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 {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 {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.},
}

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

@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.},
}

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

@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 & dosage ; Female ; Herpesvirus 3, Human/physiology ; Insulin/*metabolism ; Insulysin/*antagonists & inhibitors/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Peptide Fragments/*administration & 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.},
}

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 & dosage
Female
Herpesvirus 3, Human/physiology
Insulin/*metabolism
Insulysin/*antagonists & inhibitors/genetics/metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Knockout
Peptide Fragments/*administration & dosage
Viral Envelope Proteins/*metabolism

@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.},
}

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

@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.},
}

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

@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 ; *Erb-b2 Receptor Tyrosine Kinases ; *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.},
}

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
*Erb-b2 Receptor Tyrosine Kinases
*Receptors, Estrogen
*Receptors, Progesterone
Spheroids, Cellular/pathology

@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 & derivatives ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Posterior Leukoencephalopathy Syndrome/*chemically induced/*diagnostic imaging ; Time Factors ; Gemcitabine ; },
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.

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.

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.},
}

Antimetabolites, Antineoplastic/*adverse effects
Deoxycytidine/adverse effects/*analogs & derivatives
Diagnosis, Differential
Female
Humans
Middle Aged
Posterior Leukoencephalopathy Syndrome/*chemically induced/*diagnostic imaging
Time Factors
Gemcitabine

@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},
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 = {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.},
}

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

@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 & 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.},
}

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 & 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

@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 {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},
pmid = {33927073},
issn = {1672-7347},
mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnostic imaging/genetics ; Female ; Humans ; Erb-b2 Receptor Tyrosine Kinases/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.

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.

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).

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.},
}

Biomarkers, Tumor
*Breast Neoplasms/diagnostic imaging/genetics
Female
Humans
Erb-b2 Receptor Tyrosine Kinases/genetics
Receptors, Estrogen
Receptors, Progesterone
X-Rays

@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 & medicine (1982)},
volume = {278},
number = {},
pages = {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.

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.

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.

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.

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.},
}

*COVID-19
Humans
Israel/epidemiology
Longitudinal Studies
Pandemics
*Prisoners of War
SARS-CoV-2
*Stress Disorders, Post-Traumatic/epidemiology/etiology
*Veterans

@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 ; *Cell Adhesion Molecules/metabolism ; Female ; Humans ; Lymphangiogenesis/physiology ; Lymphatic Metastasis/pathology ; *Lymphatic Vessels/metabolism ; *Nectins/metabolism ; *Receptors, CXCR4/metabolism ; *Vesicular Transport Proteins/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.},
}

*Breast Neoplasms/genetics/metabolism/pathology
*Cell Adhesion Molecules/metabolism
Female
Humans
Lymphangiogenesis/physiology
Lymphatic Metastasis/pathology
*Lymphatic Vessels/metabolism
*Nectins/metabolism
*Receptors, CXCR4/metabolism
*Vesicular Transport Proteins/metabolism

@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.},
}

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

@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 & 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.},
}

Erythrocytes/*metabolism
*Gene Expression Regulation
Humans
*Life Cycle Stages
Malaria, Falciparum/*parasitology
*Nucleic Acid Conformation
Plasmodium falciparum/*genetics/growth & development/pathogenicity
Protozoan Proteins/genetics/metabolism
RNA, Protozoan/*chemistry
Transcriptome

@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.},
}

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

@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.

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.

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.

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.},
}

*Endotoxins
Exercise
Humans
Inflammation/etiology
Physical Fitness
*Renal Dialysis/adverse effects

@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},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/complications/*mortality/therapy ; Carcinoma, Ductal, Breast/complications/*mortality/therapy ; Carcinoma, Lobular/complications/*mortality/therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hypoglycemic Agents/*therapeutic use ; Middle Aged ; Prognosis ; Registries/statistics & numerical data ; Survival Analysis ; },
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.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/complications/*mortality/therapy
Carcinoma, Ductal, Breast/complications/*mortality/therapy
Carcinoma, Lobular/complications/*mortality/therapy
Diabetes Mellitus, Type 2/complications/*drug therapy
Female
Follow-Up Studies
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use
Hypoglycemic Agents/*therapeutic use
Middle Aged
Prognosis
Registries/statistics & numerical data
Survival Analysis

@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 & medicine},
volume = {18},
number = {3},
pages = {900-909},
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.

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.

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.

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 {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 = {Asian People ; 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.},
}

Asian People
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

@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 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.

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.

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.

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.},
}

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

@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 Proteins/*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.

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 (Hand2[AdipoqCre]) and performed a large panel of metabolic tests.

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.

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.

DATA AVAILABILITY: Array data have been submitted to the GEO database at NCBI (GSE148699).},
}

Adipocytes/*metabolism
Adipogenesis/physiology
Adipose Tissue, Brown/metabolism
Adult
Aged
Animals
Basic Helix-Loop-Helix Proteins/*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

@article {pmid34015750,
year = {2021},
author = {de Araújo, RA and Cordero da Luz, FA and da Costa Marinho, E and Mendes, TR and Nascimento, CP and Ribeiro Delfino, PF and Antonioli, RM and Ruas, AC and Alves, AR and Araújo, BJ and de Paula Machado, JP and Guedes Pereira, TO and França do Espírito Santo, M and Barbosa Silva, MJ},
title = {Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors.},
journal = {Surgical oncology},
volume = {38},
number = {},
pages = {101596},
doi = {10.1016/j.suronc.2021.101596},
pmid = {34015750},
issn = {1879-3320},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; *Margins of Excision ; Mastectomy/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*surgery ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/pathology/*surgery ; },
abstract = {INTRODUCTION: Oncological surgery must follow some fundamental principles to be truly curative, one of which is the resection of the tumor with surgical margins free of neoplasia. In breast cancer, surgery with positive margins should be expanded immediately. There are probably different intensities, between the stages and molecular subtypes of operable breast cancer, of worsening prognosis due to the surgical margin compromised by the neoplasia in women not submitted to the necessary enlargement of the positive surgical margin. MATERIALS AND.

METHODS: Seven hundred and forty-seven women with invasive ductal carcinoma of the breast, analyzing anatomical-pathological information, types of surgery, molecular subtypes, and the presence or absence of the surgical margin compromised by neoplasia.

RESULTS: Sixty-one (8.2%) patients had positive surgical margin, causing 2.85 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. In subgroup analysis, among stages I, II and III, stage II was the most negatively impacted, with those patients presenting 2.42 times more risk of distant metastasis and 4.94 times more risk of locoregional relapses compared to negative surgical margin by multivariate analysis. Among the molecular subtypes, Triple Negative tumors with a positive surgical margin had 3.56 times more risk of death, 4.98 times more risk of distant metastasis and 5.55 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis.

CONCLUSIONS: The positive surgical margin, especially in Stage II and Triple-Negative breast cancer patients negatively impact the patient's evolution, increasing risk of distant metastasis and death.},
}

Adult
Aged
Aged, 80 and over
Female
Follow-Up Studies
Humans
*Margins of Excision
Mastectomy/*mortality
Middle Aged
Neoplasm Recurrence, Local/pathology/*surgery
Neoplasm Staging
Retrospective Studies
Survival Rate
Triple Negative Breast Neoplasms/pathology/*surgery

@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 & 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.},
}

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

@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 & 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 & 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 & dosage/genetics/isolation & purification ; Young Adult ; Fibronectins ; },
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.},
}

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 & 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 & 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 & dosage/genetics/isolation & purification
Young Adult
Fibronectins

@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.},
}

Ascites/*diagnosis/etiology
Breast Neoplasms/*pathology
Female
Humans
Liver Cirrhosis/*diagnosis/etiology
Liver Neoplasms/complications/*diagnosis/secondary
Magnetic Resonance Imaging
Tomography, X-Ray Computed

@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 ; Empty Spiracles Homeobox Proteins ; },
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.},
}

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
Empty Spiracles Homeobox Proteins

@article {pmid34044580,
year = {2021},
author = {Markus, HS and Egle, M and Croall, ID and Sari, H and Khan, U and Hassan, A and Harkness, K and MacKinnon, A and O'Brien, JT and Morris, RG and Barrick, TR and Blamire, AM and Tozer, DJ and Ford, GA and , },
title = {PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease.},
journal = {Stroke},
volume = {52},
number = {8},
pages = {2484-2493},
doi = {10.1161/STROKEAHA.120.032054},
pmid = {34044580},
issn = {1524-4628},
mesh = {Aged ; Antihypertensive Agents/*therapeutic use ; Blood Pressure ; Cerebral Small Vessel Diseases/complications/*diagnostic imaging/physiopathology ; *Cognition ; Diffusion Tensor Imaging ; Disease Progression ; Female ; Humans ; Hypertension/complications/*drug therapy/physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; *Patient Care Planning ; Stroke, Lacunar/complications/*diagnostic imaging/physiopathology ; White Matter/*diagnostic imaging ; },
abstract = {[Figure: see text].},
}

Aged
Antihypertensive Agents/*therapeutic use
Blood Pressure
Cerebral Small Vessel Diseases/complications/*diagnostic imaging/physiopathology
*Cognition
Diffusion Tensor Imaging
Disease Progression
Female
Humans
Hypertension/complications/*drug therapy/physiopathology
Magnetic Resonance Imaging
Male
Middle Aged
Neuropsychological Tests
*Patient Care Planning
Stroke, Lacunar/complications/*diagnostic imaging/physiopathology
White Matter/*diagnostic imaging

@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.},
}

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

@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},
pmid = {34058243},
issn = {1527-9995},
support = {R01 CA211695/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; },
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.},
}

Humans
Male
Molecular Diagnostic Techniques
Neoplasm Grading
Prostatic Neoplasms/*diagnosis/*genetics/pathology

@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.},
}

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

@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.},
}

Bayes Theorem
Cluster Analysis
Gene Expression Profiling/methods
Sequence Analysis, RNA/methods
*Single-Cell Analysis/methods
*Transcriptome/genetics

@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 = {92},
number = {},
pages = {565-574},
pmid = {34096509},
issn = {2239-253X},
mesh = {*Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; Neoplasm Metastasis ; Xanthophylls/pharmacology ; },
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.

MATERIAL AND 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.

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.

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.

KEY WORDS: Breast, cancer, metastasis.},
}

*Breast Neoplasms/drug therapy
*Carcinoma, Ductal, Breast/drug therapy
*Carcinoma, Intraductal, Noninfiltrating
Female
Humans
Neoplasm Metastasis
Xanthophylls/pharmacology

@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.

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.

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).

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.},
}

Hospital Units
Humans
*Liver Abscess, Pyogenic/epidemiology/therapy
Retrospective Studies
Risk Factors

@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.},
}

*Autism Spectrum Disorder/complications
Emotions
Humans
*Intellectual Disability/complications
Language

@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 ; ATP-Binding Cassette, Sub-Family C 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.},
}

Allosteric Regulation
Amino Acid Substitution
Humans
ATP-Binding Cassette, Sub-Family C Proteins/*chemistry/*genetics
*Mutation, Missense
Protein Domains
Protein Structure, Secondary

@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 ; R01 CA170595/CA/NCI NIH HHS/United States ; P30 CA014236/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.},
}

*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

@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 & 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.},
}

Animals
Erythrocytes/parasitology
Host-Parasite Interactions
Humans
Malaria, Falciparum/parasitology
*Plasmodium falciparum/growth & development
*Protozoan Proteins/metabolism

@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 = {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.},
}

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

@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 & 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.},
}

Adenine
Adenomatous Polyposis Coli/genetics
Amino Acid Motifs
Animals
DNA/chemistry
DNA Glycosylases/*chemistry/genetics
DNA Repair
DNA Replication
Guanine/analogs & derivatives
Humans
Mice
Models, Molecular
Mutation
Proliferating Cell Nuclear Antigen/chemistry
Zinc

@article {pmid34166430,
year = {2021},
author = {Nkadimeng, MV and Makombe, G and Mapiye, O and Mapiye, C and Oluwatayo, I and Dzama, K and Mojapelo, C and Mollel, N and Ngambi, J and Mautjana, MH},
title = {A gross margin analysis for Nguni cattle farmers in Limpopo Province, South Africa.},
journal = {PloS one},
volume = {16},
number = {6},
pages = {e0253657},
pmid = {34166430},
issn = {1932-6203},
mesh = {Animal Husbandry/*economics ; Animals ; Cattle ; *Farmers ; Farms/*economics ; Humans ; South Africa ; },
abstract = {Factors such as increases in population, urbanization, growth in per capita income and changes in consumer taste and preferences are causing gradual increases in livestock product consumption and demand. South Africa is addressing this predicted increase in livestock products demand by commercializing smallholder livestock producers. The Limpopo Industrial Development Corporation (IDC) Nguni Cattle Development Project is an example of such effort. The economic performance of these efforts needs to be evaluated. We use gross margin analysis to evaluate the performance of the Limpopo IDC Nguni Cattle Development Project. Additionally, we use regression analysis to identify factors influencing gross margins. Our results indicate that although smallholders show potential to commercialize, they lack commercial farming experience and require that a strong extension support system be used as one of the strategies to improve profitability. We also noted that individual farmers were more profitable than group farmers. Multiple regression analysis shows that three variables could be used to stimulate gross margin among the Limpopo IDC Nguni Cattle Development Project farmers. These are herd size, distance to market and farm size. Since farm size is a given, policy should focus on assisting farmers to build their herds and to have better access to markets.},
}

Animal Husbandry/*economics
Animals
Cattle
*Farmers
Farms/*economics
Humans
South Africa