@article {pmid33023170,
year = {2020},
author = {Petre, AR and Craciunescu, R and Fratu, O},
title = {Design, Implementation and Simulation of a Fringing Field Capacitive Humidity Sensor.},
journal = {Sensors (Basel, Switzerland)},
volume = {20},
number = {19},
pages = {},
pmid = {33023170},
issn = {1424-8220},
support = {51675/09.07.2019, SMIS code 125125//Operational Programme Human Capital of the Ministry of European Funds through the Financial Agreement/ ; 33PCCDI/2018//Ministry of Innovation and Research, UEFISCDI, MultiMonD2 within PNCDI III/ ; },
abstract = {The world population is growing in an accelerated way urging the need for a more efficient and sustainable agricultural industry. Initially developed for smart cities which face the same challenges caused by an increasing population, Internet of Things (IoT) technologies have evolved rapidly over the last few years and are now moving successfully to agriculture. Wireless Sensor Networks (WSNs) have been reported to be used in the agri-food sector and could answer the call for a more optimized agricultural management. This paper investigates a PCB-made interdigited capacitive (IDC) soil humidity sensor as a low-price alternative to the existing ones on the market. An in-depth comparative study is performed on 30 design variations, part of them also manufactured for further investigations. By measurements and simulations, the influence of the aspect ratio and dielectric thickness on the sensitivity and capacitance of the sensor are studied. In the end, a Humidity and Temperature Measurement Wireless Equipment (HTMWE) for IoT agriculture applications is implemented with this type of sensor.},
}

@article {pmid33024608,
year = {2020},
author = {Matich, A and Sud, S and Buxi, TBS and Dogra, V},
title = {Idiopathic Granulomatous Mastitis and its Mimics on Magnetic Resonance Imaging: A Pictorial Review of Cases from India.},
journal = {Journal of clinical imaging science},
volume = {10},
number = {},
pages = {53},
pmid = {33024608},
issn = {2156-7514},
abstract = {OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast, which is benign but potentially morbid. Mammographic and sonographic findings have been well characterized, but magnetic resonance imaging (MRI) findings have been less thoroughly documented. The objective of this study was to demonstrate characteristic findings for IGM and its mimics via a retrospective review.

MATERIAL AND METHODS: Breast MRI examinations performed at Sir Ganga Ram Hospital in New Delhi, India between 2014 and 2019 were retrospectively reviewed to identify cases in which a pattern suggestive of granulomatous mastitis was seen. Cases of known malignancy were excluded. Any available breast pathology results were then obtained, and cases with presumptive or definitive diagnoses were compiled for analysis.

RESULTS: Overall, cases identified with characteristic imaging findings and confirmed diagnosis included seven cases of IGM, four cases of invasive ductal carcinoma, two cases of tuberculous mastitis, one case of non- tuberculous infectious mastitis, one case of foreign body mastitis, and one case of eosinophilc mastitis. One case of IGM with masses rather than of non-mass enhancement was also identified.

CONCLUSION: In our review, cases with clustered ring enhancement were found to have inflammatory, idiopathic, infectious and malignant etiologies. While, these etiologies can only be reliably differentiated on pathology, familiarity with the pattern and an awareness of the differential may lead to decreased morbidity due to delays in diagnosis.},
}

@article {pmid33027370,
year = {2020},
author = {Gewehr, DM and Salgueiro, GR and Noronha, L and Kubrusly, FB and Kubrusly, LF and Coltro, GA and Preto, PC and Bertoldi, AS and Vieira, HI},
title = {Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.},
journal = {Arquivos brasileiros de cardiologia},
volume = {115},
number = {3},
pages = {480-490},
pmid = {33027370},
issn = {1678-4170},
mesh = {Animals ; Humans ; *Hypertension, Pulmonary/chemically induced ; Hypertrophy, Right Ventricular/chemically induced ; Male ; Monocrotaline/toxicity ; *Pulmonary Arterial Hypertension ; Rats ; Rats, Wistar ; },
abstract = {BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.

OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.

METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.

RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).

CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).},
}

Animals
Humans
*Hypertension, Pulmonary/chemically induced
Hypertrophy, Right Ventricular/chemically induced
Male
Monocrotaline/toxicity
*Pulmonary Arterial Hypertension
Rats
Rats, Wistar

@article {pmid33027710,
year = {2021},
author = {Thongpiya, J and Sa-Nguanraksa, D and Samarnthai, N and Sarasombath, PT},
title = {Filariasis of the breast caused by Brugia pahangi: A concomitant finding with invasive ductal carcinoma.},
journal = {Parasitology international},
volume = {80},
number = {},
pages = {102203},
pmid = {33027710},
issn = {1873-0329},
mesh = {Animals ; Breast Diseases/*diagnosis/parasitology ; Breast Neoplasms/*pathology ; Brugia pahangi/classification/*isolation & purification ; Carcinoma, Ductal, Breast/*pathology ; DNA, Ribosomal Spacer/analysis ; Female ; Filariasis/*diagnosis/parasitology ; Humans ; Middle Aged ; RNA, Helminth/analysis ; RNA, Ribosomal/analysis ; Thailand ; },
abstract = {Extralymphatic filariasis is an uncommon phenomenon that can be caused by several lymphatic filarial species, including zoonotic filaria of animal origins. In this study, we report a case of a 64-year-old Thai woman who presented with a lump in her left breast that was diagnosed with invasive ductal carcinoma. At the same time, a small nodule was found in her right breast, via imaging study, without any abnormal symptoms. A core needle biopsy of the right breast nodule revealed a filarial-like nematode compatible with the adult stage of Brugia sp. A molecular identification of the nematode partial mt 12rRNA gene and ITS1 suggested the causative species as closely related to Brugia pahangi, a zoonotic lymphatic filaria of animals such as cats and dogs. The sequence of the partial mt 12rRNA and ITS1 gene in this patient was 94% and 99% identical to the previously reported sequence of mt 12rRNA and ITS1 genes of B. pahangi. The sequence of ITS1 gene is 99% similar to B. pahangi microfilaria from infected dogs in Bangkok, which was highly suspected of having a zoonotic origin. As far as we know, this is the first case report of B. pahangi filariasis presented with a breast mass concomitantly found in a patient with invasive ductal carcinoma. This raised serious concern regarding the zoonotic transmission of filariasis from natural animal reservoirs.},
}

Animals
Breast Diseases/*diagnosis/parasitology
Breast Neoplasms/*pathology
Brugia pahangi/classification/*isolation & purification
Carcinoma, Ductal, Breast/*pathology
DNA, Ribosomal Spacer/analysis
Female
Filariasis/*diagnosis/parasitology
Humans
Middle Aged
RNA, Helminth/analysis
RNA, Ribosomal/analysis
Thailand

@article {pmid33039708,
year = {2020},
author = {Bitencourt, AGV and Gibbs, P and Rossi Saccarelli, C and Daimiel, I and Lo Gullo, R and Fox, MJ and Thakur, S and Pinker, K and Morris, EA and Morrow, M and Jochelson, MS},
title = {MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.},
journal = {EBioMedicine},
volume = {61},
number = {},
pages = {103042},
pmid = {33039708},
issn = {2352-3964},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; *Biomarkers ; Breast Neoplasms/*diagnostic imaging/*genetics/therapy ; Female ; *Gene Expression ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; *Machine Learning ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Neoadjuvant Therapy ; ROC Curve ; Erb-b2 Receptor Tyrosine Kinases/*genetics/metabolism ; Young Adult ; },
abstract = {BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC).

METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20).

FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test).

INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients.

FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.},
}

Adult
Aged
*Biomarkers
Breast Neoplasms/*diagnostic imaging/*genetics/therapy
Female
*Gene Expression
Humans
Image Processing, Computer-Assisted/methods
Imaging, Three-Dimensional
*Machine Learning
*Magnetic Resonance Imaging/methods
Middle Aged
Neoadjuvant Therapy
ROC Curve
Erb-b2 Receptor Tyrosine Kinases/*genetics/metabolism
Young Adult

@article {pmid33047834,
year = {2021},
author = {Nishimoto, A and Kuwahara, H and Ohashi, R and Ansai, SI},
title = {Multicentric endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report.},
journal = {Journal of cutaneous pathology},
volume = {48},
number = {1},
pages = {165-170},
doi = {10.1111/cup.13896},
pmid = {33047834},
issn = {1600-0560},
mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Mucins ; Neoplasms, Multiple Primary/*pathology ; Skin Neoplasms/*pathology ; Sweat Gland Neoplasms/*pathology ; Uterine Neoplasms/pathology ; },
abstract = {Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71-year-old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.},
}

Adenocarcinoma, Mucinous/*pathology
Aged
Breast Neoplasms/pathology
Carcinoma, Ductal, Breast/pathology
Female
Humans
Mucins
Neoplasms, Multiple Primary/*pathology
Skin Neoplasms/*pathology
Sweat Gland Neoplasms/*pathology
Uterine Neoplasms/pathology

@article {pmid33049657,
year = {2020},
author = {Zhang, J and Lu, CY and Qin, L and Chen, HM and Wu, SY},
title = {Breast-conserving surgery with or without irradiation in women with invasive ductal carcinoma of the breast receiving preoperative systemic therapy: A cohort study.},
journal = {Breast (Edinburgh, Scotland)},
volume = {54},
number = {},
pages = {139-147},
pmid = {33049657},
issn = {1532-3080},
mesh = {Adult ; Antineoplastic Protocols ; Breast/pathology ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/mortality/*therapy ; Chemotherapy, Adjuvant/methods/*mortality ; Cohort Studies ; Combined Modality Therapy ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/etiology/pathology ; Neoplasm Staging ; Neoplasm, Residual ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant/methods/*mortality ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; },
abstract = {PURPOSE: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival.

PATIENTS AND METHODS: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs).

RESULTS: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2-4) or nodal (ypN2-3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03-0.81), 0.32 (0.16-0.64), 0.43 (0.23-0.79), 0.23 (0.13-0.42), 0.52 (0.20-1.33), and 0.34 (0.13-0.87) in the ypT0, ypT1, ypT2-4, ypN0, ypN1, and ypN2-3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00-4.07), 0.46 (0.26-0.83), 0.18 (0.06-0.51), 0.28 (0.06-1.34), 0.25 (0.10-0.63), 0.47 (0.23-0.88), and 0.32 in the cT0-1, cT2, cT3, cT4, cN0, cN1, and cN2-3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST.

CONCLUSION: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.},
}

Adult
Antineoplastic Protocols
Breast/pathology
Breast Neoplasms/*therapy
Carcinoma, Ductal, Breast/mortality/*therapy
Chemotherapy, Adjuvant/methods/*mortality
Cohort Studies
Combined Modality Therapy
Databases, Factual
Disease-Free Survival
Female
Humans
Lymph Nodes/pathology
Mastectomy, Segmental/methods/*mortality
Middle Aged
Neoplasm Recurrence, Local/etiology/pathology
Neoplasm Staging
Neoplasm, Residual
Prognosis
Proportional Hazards Models
Radiotherapy, Adjuvant/methods/*mortality
Registries
Regression Analysis
Taiwan
Treatment Outcome
Young Adult

@article {pmid33073677,
year = {2020},
author = {Qi, P and Bai, QM and Yao, QL and Yang, WT and Zhou, XY},
title = {Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.},
journal = {Technology in cancer research & treatment},
volume = {19},
number = {},
pages = {1533033820960760},
pmid = {33073677},
issn = {1533-0338},
mesh = {Breast Neoplasms/*genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction/*methods ; Erb-b2 Receptor Tyrosine Kinases/genetics ; Receptors, Estrogen/genetics ; Transcriptome/*genetics ; },
abstract = {This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.},
}

Breast Neoplasms/*genetics/pathology
Female
Gene Expression Regulation, Neoplastic/genetics
Humans
Ki-67 Antigen/genetics
Middle Aged
Neoplasm Recurrence, Local/*genetics/pathology
Paraffin Embedding
Real-Time Polymerase Chain Reaction/*methods
Erb-b2 Receptor Tyrosine Kinases/genetics
Receptors, Estrogen/genetics
Transcriptome/*genetics

@article {pmid33086236,
year = {2021},
author = {Bishop, JA and Rooper, LM and Sangoi, AR and Gagan, J and Thompson, LDR and Inagaki, H},
title = {The Myoepithelial Cells of Salivary Intercalated Duct-type Intraductal Carcinoma Are Neoplastic: A Study Using Combined Whole-slide Imaging, Immunofluorescence, and RET Fluorescence In Situ Hybridization.},
journal = {The American journal of surgical pathology},
volume = {45},
number = {4},
pages = {507-515},
doi = {10.1097/PAS.0000000000001605},
pmid = {33086236},
issn = {1532-0979},
mesh = {Aged ; Automation, Laboratory ; *Biomarkers, Tumor/analysis/genetics ; Calcium-Binding Proteins/*analysis ; *Carcinoma, Ductal/chemistry/genetics/pathology ; Female ; *Fluorescent Antibody Technique ; Gene Fusion ; Humans ; Image Interpretation, Computer-Assisted ; *In Situ Hybridization, Fluorescence ; Male ; Microfilament Proteins/*analysis ; Middle Aged ; Predictive Value of Tests ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/chemistry/genetics/pathology ; Calponins ; },
abstract = {Intraductal carcinoma (IDC) is a salivary gland tumor currently believed to be analogous to breast ductal carcinoma in situ, consisting of a complex neoplastic epithelial proliferation surrounded by a continuous layer of myoepithelial cells presumed to be native and non-neoplastic. Recent molecular insights have shown that there are at least 3 different types of IDC: (1) intercalated duct-like, with frequent NCOA4-RET fusions; (2) apocrine, with multiple mutations similar to salivary duct carcinoma; and (3) mixed intercalated duct-like and apocrine with frequent RET fusions, especially TRIM27-RET. Recent observations (eg, IDC occurring in lymph nodes) have challenged the notion that the myoepithelial cells of IDC are non-neoplastic. Five IDCs with known RET fusions by RNA sequencing were retrieved from the authors' archives, including 4 intercalated duct-like IDCs with NCOA4-RET, and 1 mixed intercalated duct-like/apocrine IDC with TRIM27-RET. A panel of immunohistochemistry antibodies (S100 protein, p63 or p40, mammaglobin, smooth muscle actin, calponin, androgen receptor) was tested. To precisely localize RET split-positive cells, each case was subjected to sequential retrieval of whole-slide imaging data of hematoxylin and eosin (HE) staining, immunofluorescence staining for calponin, and fluorescence in situ hybridization (FISH) for RET. Because NCOA4-RET is an inversion difficult to visualize on conventional RET FISH, a novel 3-color FISH technique was utilized to demonstrate it clearly. In all 5 cases, the proliferative ducts were completely surrounded by a layer of myoepithelial cells that were positive for p63 or p40, smooth muscle actin, and calponin. Using combined HE, calponin immunofluorescence, and RET FISH imaging, the positive signals were unmistakably identified in both calponin-negative ductal cells and peripheral, calponin-positive myoepithelial cells in all 5 cases. Utilizing combined HE, calponin immunofluorescence, and RET FISH imaging, we demonstrated that IDCs with RET fusions harbored this alteration in both the ductal and myoepithelial cells. This is compelling evidence that the myoepithelial cells of IDC are not mere bystanders, but are rather a component of the neoplasm itself, similar to other biphasic salivary gland neoplasms like pleomorphic adenoma and epithelial-myoepithelial carcinoma. This finding raises questions about the appropriate terminology, classification, and staging of IDC.},
}

Aged
Automation, Laboratory
*Biomarkers, Tumor/analysis/genetics
Calcium-Binding Proteins/*analysis
*Carcinoma, Ductal/chemistry/genetics/pathology
Female
*Fluorescent Antibody Technique
Gene Fusion
Humans
Image Interpretation, Computer-Assisted
*In Situ Hybridization, Fluorescence
Male
Microfilament Proteins/*analysis
Middle Aged
Predictive Value of Tests
Proto-Oncogene Proteins c-ret/*genetics
*Salivary Gland Neoplasms/chemistry/genetics/pathology
Calponins

@article {pmid33090732,
year = {2020},
author = {Morigny, P and Zuber, J and Haid, M and Kaltenecker, D and Riols, F and Lima, JDC and Simoes, E and Otoch, JP and Schmidt, SF and Herzig, S and Adamski, J and Seelaender, M and Berriel Diaz, M and Rohm, M},
title = {High levels of modified ceramides are a defining feature of murine and human cancer cachexia.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {11},
number = {6},
pages = {1459-1475},
pmid = {33090732},
issn = {2190-6009},
support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Animals ; *Cachexia/etiology ; *Ceramides/metabolism ; Humans ; Mice ; Muscular Atrophy ; *Neoplasms/complications ; Quality of Life ; },
abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.

METHODS: Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, Apc[Min/+] mutant mice), and plasma from weight stable and cachectic patients with gastrointestinal cancer, were analysed using the Lipidyzer™ platform. In total, 13 lipid classes and more than 1100 lipid species, including sphingolipids, neutral and polar glycerolipids, were covered by the analysis. Correlation analysis between specific lipid species and readouts of CCx were performed. Lipidomics data were confirmed by gene expression analysis of metabolic organs to analyse enzymes involved in sphingolipid synthesis and degradation.

RESULTS: A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.

CONCLUSIONS: High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.},
}

Animals
*Cachexia/etiology
*Ceramides/metabolism
Humans
Mice
Muscular Atrophy
*Neoplasms/complications
Quality of Life

@article {pmid33097605,
year = {2021},
author = {Kurley, SJ and Tischler, V and Bierie, B and Novitskiy, SV and Noske, A and Varga, Z and Zürrer-Härdi, U and Brandt, S and Carnahan, RH and Cook, RS and Muller, WJ and Richmond, A and Reynolds, AB},
title = {A requirement for p120-catenin in the metastasis of invasive ductal breast cancer.},
journal = {Journal of cell science},
volume = {134},
number = {6},
pages = {},
pmid = {33097605},
issn = {1477-9137},
support = {R01 CA200681/CA/NCI NIH HHS/United States ; IK6 BX005225/BX/BLRD VA/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R01 CA055724/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30 HD015052/HD/NICHD NIH HHS/United States ; R01 CA243326/CA/NCI NIH HHS/United States ; R01 CA111947/CA/NCI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; },
mesh = {Animals ; *Breast Neoplasms/genetics ; Cadherins/genetics ; Catenins/genetics ; Cell Adhesion ; Female ; Humans ; Mice ; Tumor Microenvironment ; Delta Catenin ; },
abstract = {We report here the effects of targeted p120-catenin (encoded by CTNND1; hereafter denoted p120) knockout (KO) in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment, ultimately leading to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.},
}

Animals
*Breast Neoplasms/genetics
Cadherins/genetics
Catenins/genetics
Cell Adhesion
Female
Humans
Mice
Tumor Microenvironment
Delta Catenin

@article {pmid33106505,
year = {2020},
author = {Tsai, HT and Huang, CS and Tu, CC and Liu, CY and Huang, CJ and Ho, YS and Tu, SH and Tseng, LM and Huang, CC},
title = {Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {18276},
pmid = {33106505},
issn = {2045-2322},
mesh = {Bayes Theorem ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Calcinosis/*diagnosis/genetics ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Taiwan ; Exome Sequencing ; },
abstract = {Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ[2]-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.},
}

Bayes Theorem
Biomarkers, Tumor/*genetics
Breast Neoplasms/*diagnosis/genetics
Calcinosis/*diagnosis/genetics
Early Detection of Cancer
Female
Gene Expression Profiling/*methods
Gene Expression Regulation, Neoplastic
Humans
Oligonucleotide Array Sequence Analysis
Prognosis
Taiwan
Exome Sequencing

@article {pmid33126344,
year = {2020},
author = {Liu, C and Wang, C and Du, Z and Xue, H and Liu, Z},
title = {Clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia.},
journal = {Medicine},
volume = {99},
number = {44},
pages = {e22904},
pmid = {33126344},
issn = {1536-5964},
mesh = {Age Factors ; Anticarcinogenic Agents/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; China/epidemiology ; Female ; Humans ; Imatinib Mesylate/*therapeutic use ; Incidence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology ; Male ; Middle Aged ; *Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Time Factors ; },
abstract = {This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.},
}

Age Factors
Anticarcinogenic Agents/therapeutic use
*Breast Neoplasms/drug therapy/pathology
China/epidemiology
Female
Humans
Imatinib Mesylate/*therapeutic use
Incidence
*Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology
Male
Middle Aged
*Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology
Prognosis
Retrospective Studies
Risk Factors
Sex Factors
Survival Analysis
Time Factors

@article {pmid33130707,
year = {2020},
author = {Kosaka, Y and Kikuchi, M and Nishimiya, H and Katoh, H and Kawaguchi, R and Araki, N and Shimazu, M and Tsumura, H and Waraya, M and Takada, F and Sengoku, N and Sangai, T},
title = {[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {47},
number = {9},
pages = {1387-1389},
pmid = {33130707},
issn = {0385-0684},
mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Child ; Female ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery ; Humans ; Mastectomy ; },
abstract = {A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy(CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.},
}

*Breast Neoplasms/genetics/surgery
*Carcinoma, Ductal
*Carcinoma, Ductal, Breast/surgery
*Carcinoma, Intraductal, Noninfiltrating
Child
Female
*Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery
Humans
Mastectomy

@article {pmid33132109,
year = {2021},
author = {Zong, Y and Montironi, R and Massari, F and Jiang, Z and Lopez-Beltran, A and Wheeler, TM and Scarpelli, M and Santoni, M and Cimadamore, A and Cheng, L},
title = {Intraductal Carcinoma of the Prostate: Pathogenesis and Molecular Perspectives.},
journal = {European urology focus},
volume = {7},
number = {5},
pages = {955-963},
doi = {10.1016/j.euf.2020.10.007},
pmid = {33132109},
issn = {2405-4569},
mesh = {*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Pelvis/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde spreading of cancer cells along benign ducts and acini, a small subset of IDC-P may arise from the transformation and intraductal proliferation of precancerous cells induced by various oncogenic events. These isolated IDC-P tumors possess a distinct mutational profile and may function as a carcinoma in situ lesion with de novo intraductal outgrowth of malignant cells. Further molecular characterization of these two types of IDC-P and better understanding of the mechanisms underlying IDC-P formation and progression could be translated into valuable biomarkers for differential diagnosis and actionable targets for therapeutic interventions. PATIENT SUMMARY: Intraductal carcinoma of the prostate is an aggressive type of prostate cancer associated with high risk for local recurrence and distant metastasis. In this review, we discussed pathogenesis, biomarkers, differential diagnoses, and therapeutic strategies for this tumor.},
}

*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy
Diagnosis, Differential
Humans
Male
Pelvis/pathology
Prostate/pathology
*Prostatic Neoplasms/diagnosis/genetics/therapy

@article {pmid33135196,
year = {2021},
author = {Bishop, JA and Nakaguro, M and Whaley, RD and Ogura, K and Imai, H and Laklouk, I and Faquin, WC and Sadow, PM and Gagan, J and Nagao, T},
title = {Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.},
journal = {Histopathology},
volume = {79},
number = {3},
pages = {338-346},
pmid = {33135196},
issn = {1365-2559},
support = {P01 CA240239/CA/NCI NIH HHS/United States ; //UT Southwestern Medical Center/ ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Carcinoma, Ductal/diagnosis/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Mutation ; Oncogene Fusion ; Oxyphil Cells/pathology ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/diagnosis/genetics/pathology ; Salivary Glands/pathology ; Sequence Analysis, RNA ; Transcription Factors/*genetics ; },
abstract = {AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.

METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.

CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.},
}

Adult
Aged
Biomarkers, Tumor/analysis/genetics
Carcinoma, Ductal/diagnosis/genetics/pathology
*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology
Diagnosis, Differential
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Middle Aged
Mutation
Oncogene Fusion
Oxyphil Cells/pathology
Proto-Oncogene Proteins B-raf/*genetics
Proto-Oncogene Proteins c-ret/*genetics
*Salivary Gland Neoplasms/diagnosis/genetics/pathology
Salivary Glands/pathology
Sequence Analysis, RNA
Transcription Factors/*genetics

@article {pmid33140128,
year = {2021},
author = {Chen, XY and Thike, AA and Koh, VCY and Nasir, NDM and Bay, BH and Tan, PH},
title = {Breast ductal Carcinoma in situ associated with microinvasion induces immunological response and predicts ipsilateral invasive recurrence.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {478},
number = {4},
pages = {679-686},
pmid = {33140128},
issn = {1432-2307},
support = {SHF/FG668S/2015//SingHealth Foundation/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention & control ; Prognosis ; Proportional Hazards Models ; },
abstract = {Although microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and established invasive ductal carcinoma, survival outcomes and biological behaviour of DCIS-Mi are still poorly understood. This study investigated the potential influence of Mi on disease-free survival (DFS) and assessed its correlations with clinicopathological parameters, prognosis, molecular, and immune markers. CD4, CD8, forkhead box P3 (FOXP3), CD68, CD163, programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression in pure DCIS and DCIS-Mi, from a cohort of 198 patients, were determined by immunohistochemistry. DFS, clinicopathological parameters, immune markers, and biomarker expression were correlated with presence of Mi. Twelve out of 198 DCIS cases were associated with Mi. DCIS-Mi was significantly linked with ipsilateral invasive recurrence (p = 0.032). Kaplan-Meier analysis revealed that DCIS-Mi had worse DFS for ipsilateral invasive recurrence (p = 0.011) and this was affirmed by multivariate Cox regression analysis (95% CI 1.181-9.010, HR = 3.262, p = 0.023). DCIS-Mi was associated with higher densities of immune infiltrates positive for CD4 (p = 0.037), FOXP3 (p = 0.037), CD163 (p = 0.01), and PD-L1 (p = 0.015). This study demonstrated that DCIS-Mi was correlated with high densities of immune infiltrates and predicted ipsilateral invasive recurrence.},
}

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/*metabolism
Breast Neoplasms/*immunology/metabolism/*pathology/therapy
Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy
Disease-Free Survival
Female
Follow-Up Studies
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention & control
Prognosis
Proportional Hazards Models

@article {pmid33148628,
year = {2022},
author = {Pareja, F and Vahdatinia, M and Marchio, C and Lee, SSK and Da Cruz Paula, A and Derakhshan, F and da Silva, EM and Selenica, P and Dopeso, H and Chandarlapaty, S and Wen, HY and Vincent-Salomon, A and Brogi, E and Weigelt, B and Reis-Filho, JS},
title = {Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.},
journal = {Journal of clinical pathology},
volume = {75},
number = {1},
pages = {10-17},
pmid = {33148628},
issn = {1472-4146},
support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; },
mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; Female ; Genomics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neuroendocrine Tumors/*genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Receptors, Estrogen/genetics ; Transcription Factors/genetics ; *Transcriptome ; Exome Sequencing ; },
abstract = {AIMS: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.

METHODS: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).

RESULTS: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.

CONCLUSIONS: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.},
}

Adenocarcinoma, Mucinous/*genetics/pathology
Breast/pathology
Breast Neoplasms/*genetics/pathology
Chromosome Aberrations
Female
Genomics
Humans
Lung Neoplasms/*genetics/pathology
Mutation
Neuroendocrine Tumors/*genetics/pathology
Pancreatic Neoplasms/*genetics/pathology
Receptors, Estrogen/genetics
Transcription Factors/genetics
*Transcriptome
Exome Sequencing

@article {pmid33148662,
year = {2021},
author = {Chen, F and Ding, K and Priedigkeit, N and Elangovan, A and Levine, KM and Carleton, N and Savariau, L and Atkinson, JM and Oesterreich, S and Lee, AV},
title = {Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells.},
journal = {Cancer research},
volume = {81},
number = {2},
pages = {268-281},
pmid = {33148662},
issn = {1538-7445},
support = {F30 CA203154/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; },
mesh = {Antigens, CD/genetics/metabolism ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Cadherins/antagonists & inhibitors/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Prognosis ; Single-Cell Analysis/*methods ; *Transcriptome ; Tumor Cells, Cultured ; },
abstract = {Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. SIGNIFICANCE: This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.},
}

Antigens, CD/genetics/metabolism
Biomarkers, Tumor/*genetics
Breast Neoplasms/genetics/*pathology
Cadherins/antagonists & inhibitors/genetics/metabolism
Carcinoma, Ductal, Breast/genetics/*pathology
Carcinoma, Lobular/genetics/*pathology
Female
*Gene Expression Regulation, Neoplastic
Humans
Mutation
Prognosis
Single-Cell Analysis/*methods
*Transcriptome
Tumor Cells, Cultured

@article {pmid33154304,
year = {2020},
author = {Oral, O and Unverdi, H and Kumcu, E and Turkbey, D and Dogan, S and Hucumenoglu, S},
title = {Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.},
journal = {Indian journal of pathology & microbiology},
volume = {63},
number = {4},
pages = {551-558},
doi = {10.4103/IJPM.IJPM_637_18},
pmid = {33154304},
issn = {0974-5130},
mesh = {Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mucin 5AC/*genetics ; Mucin-1/*genetics ; Mucin-2/*genetics ; Mucin-6/*genetics ; Prognosis ; },
abstract = {AIMS: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters.

MATERIALS AND METHODS: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas.

RESULTS: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion.

CONCLUSIONS: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.},
}

Adenocarcinoma, Mucinous/genetics/pathology
Adult
Aged
Breast Neoplasms/*genetics/*pathology
Female
Gene Expression
Humans
Immunohistochemistry
Middle Aged
Mucin 5AC/*genetics
Mucin-1/*genetics
Mucin-2/*genetics
Mucin-6/*genetics
Prognosis

@article {pmid33163131,
year = {2021},
author = {Chung, HL and Leung, JWT},
title = {Breast cancer recurrences in myocutaneous flap reconstruction.},
journal = {Radiology case reports},
volume = {16},
number = {1},
pages = {40-46},
pmid = {33163131},
issn = {1930-0433},
abstract = {Autologous flap reconstruction is widely used after skin sparing mastectomy to reconstruct the appearance of the breast. We present 2 cases of breast cancer recurrence in a deep inferior epigastric perforator reconstruction, including a 65-year-old female with history of papillary carcinoma and a 35-year-old female with history of a high grade invasive ductal carcinoma with extensive ductal carcinoma in situ. Differential imaging considerations of the post mastectomy patient are reviewed. Typical appearance of a deep inferior epigastric perforator flap reconstruction as well as location and timing of presentation may help differentiate a recurrence from the more commonly encountered postsurgical etiologies.},
}

@article {pmid33163280,
year = {2020},
author = {Zhang, J and Sun, M and Chang, E and Lu, CY and Chen, HM and Wu, SY},
title = {Pathologic response as predictor of recurrence, metastasis, and survival in breast cancer patients receiving neoadjuvant chemotherapy and total mastectomy.},
journal = {American journal of cancer research},
volume = {10},
number = {10},
pages = {3415-3427},
pmid = {33163280},
issn = {2156-6976},
abstract = {To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the pathologic response (PR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of PR; other independent predictors were controlled for or stratified in the analysis. We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13-0.34), 0.19 (0.08-0.48), and 0.33 (0.23-0.47), respectively, for pCR; 0.56 (0.48-0.65), 0.67 (0.51-0.89), and 0.61 (0.52-0.70), respectively, for AJCC downstaging; and 1.85 (1.56-2.18), 1.17 (0.84-1.62), and 1.61 (1.36-1.90), respectively, for AJCC upstaging. The PR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment.},
}

@article {pmid33191115,
year = {2021},
author = {Shah, OS and Soran, A and Sahin, M and Knapick, BA and Ugras, S and Celik, E and Lucas, PC and Lee, AV},
title = {Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.},
journal = {Clinical breast cancer},
volume = {21},
number = {3},
pages = {210-217},
pmid = {33191115},
issn = {1938-0666},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/genetics ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; },
abstract = {BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples.

MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants.

RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively.

CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeq[TM]. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.},
}

Breast Neoplasms/*genetics/pathology
Carcinoma, Ductal, Breast/genetics
Carcinoma, Lobular/genetics
*DNA Copy Number Variations
Female
Gene Expression Regulation, Neoplastic/*genetics
High-Throughput Nucleotide Sequencing/*methods
Humans
Neoplasm Invasiveness
Neoplasm Staging

@article {pmid33204409,
year = {2020},
author = {Missori, G and Serra, F and Prestigiacomo, G and Ricciardolo, AA and Brugioni, L and Gelmini, R},
title = {Case Report: Metastatic breast cancer to the gallbladder.},
journal = {F1000Research},
volume = {9},
number = {},
pages = {343},
pmid = {33204409},
issn = {2046-1402},
mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; *Cholecystitis, Acute/etiology/surgery ; Female ; *Gallbladder Neoplasms/secondary/surgery ; Humans ; },
abstract = {Cholecystitis is one of the leading causes of emergency surgical interventions; the occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. Metastatic breast cancer to the gallbladder is even less frequent; in fact, breast cancer usually metastasizes to bone, lung, lymph nodes, liver and brain. We report the case of an 83-year-old female patient with a previous history of breast surgery with axillary dissection in 1997, followed by adjuvant chemotherapy due to invasive ductal carcinoma of the left breast. The patient was admitted at the emergency department for sepsis and an episode of acute kidney failure, anuria and fever. Right-upper quadrant abdominal pain triggered by food intake and abdominal tenderness was also present, placing the diagnostic suspicion of biliary sepsis due to acute cholecystitis. The histological examination of the surgical specimen highlighted the presence of metastasis from an infiltrating ductal breast carcinoma with positive hormone receptors. We also report here the results of a review of the literature looking at articles describing cases of gallbladder metastasis from breast cancer.},
}

Aged, 80 and over
Breast Neoplasms/*pathology/therapy
*Cholecystitis, Acute/etiology/surgery
Female
*Gallbladder Neoplasms/secondary/surgery
Humans

@article {pmid33209168,
year = {2020},
author = {Fouhi, ME and Benider, A and Gaëtan, KZA and Mesfioui, A},
title = {[Epidemiological and anatomopathological profile of breast cancer at the Ibn Rochd University Hospital, Casablanca].},
journal = {The Pan African medical journal},
volume = {37},
number = {},
pages = {41},
pmid = {33209168},
issn = {1937-8688},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Delayed Diagnosis ; Female ; Hospitals, University ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Young Adult ; },
abstract = {The present study aims to determine the various epidemiological characteristics among newly diagnosed patients with breast cancer in Casablanca during 2018. During that period, 668 cases were collected, the average age was 51.6 years, the female was the most represented with 662 cases (99.1%) and men with 6 cases (0.9%), a sex ratio (M/F) of 0.009. The average age of menopause was 49.8 years and the average age of menarche was 13.5 years, 31.7% had a history of cancer (breast 14.1%, stomach and 9% liver 7%). The average diagnosis delay was 10 months, the thyroid disease was the most represented pathology, the left breast was diagnosed in 50.2% and the right breast in 44.7% and 1.3% in the bilateral location. The most common histological type was invasive ductal carcinoma (73.2%). The vascular and lymphatic invasion was observed in 42.2%, axillary nodes were affected in 71.1% of cases. The histological prognosis (SBR) revealed a predominance of grade II in 55.9% of cases. The Luminal B continues to be the most common phenotype (46%) followed by Triple Negative (15.3%) and Luminal A (14.2%) and HER2 (7.4%). The immediate prognosis is a cause for concern because of delayed diagnosis. It seems urgent to develop the health information policy and education.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/diagnosis/*epidemiology/pathology
Breast Neoplasms, Male/diagnosis/*epidemiology/pathology
Delayed Diagnosis
Female
Hospitals, University
Humans
Male
Middle Aged
Morocco/epidemiology
Neoplasm Grading
Prognosis
Retrospective Studies
Young Adult

@article {pmid33229203,
year = {2021},
author = {Madabhavi, I and Sarkar, M and Chavan, C and Trivedi, M},
title = {Maxillary bone metastasis, as an early sign of breast cancer; an unusual & rare site of metastasis from the common cancer.},
journal = {Oral oncology},
volume = {115},
number = {},
pages = {105098},
doi = {10.1016/j.oraloncology.2020.105098},
pmid = {33229203},
issn = {1879-0593},
mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Maxilla/*pathology ; Maxillary Neoplasms/*secondary ; Neoplasm Metastasis ; },
abstract = {Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual & exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck & non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.},
}

Aged
Bone Neoplasms/secondary
Breast Neoplasms/*diagnosis
Female
Humans
Maxilla/*pathology
Maxillary Neoplasms/*secondary
Neoplasm Metastasis

@article {pmid33238073,
year = {2021},
author = {Okada, K and Takahara, T and Suzuki, Y and Kohno, K and Sakakibara, A and Satou, A and Takahashi, E and Nakamura, S},
title = {Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.},
journal = {Pathology international},
volume = {71},
number = {1},
pages = {24-32},
doi = {10.1111/pin.13044},
pmid = {33238073},
issn = {1440-1827},
mesh = {Adolescent ; Adult ; Aged ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/analysis ; *Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology ; Dendritic Cells/metabolism/pathology ; Female ; Histiocytes/metabolism/pathology ; *Histiocytic Sarcoma/immunology/metabolism/pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Langerhans Cell Sarcoma/immunology/metabolism/pathology ; Lymphoma, Follicular/immunology/metabolism/pathology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes/metabolism ; },
abstract = {Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.},
}

Adolescent
Adult
Aged
B7-H1 Antigen/*metabolism
Biomarkers, Tumor/analysis
*Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology
Dendritic Cells/metabolism/pathology
Female
Histiocytes/metabolism/pathology
*Histiocytic Sarcoma/immunology/metabolism/pathology
Humans
Immunohistochemistry
Immunophenotyping
In Situ Hybridization, Fluorescence
Japan
Langerhans Cell Sarcoma/immunology/metabolism/pathology
Lymphoma, Follicular/immunology/metabolism/pathology
Male
Middle Aged
Retrospective Studies
T-Lymphocytes/metabolism

@article {pmid33238981,
year = {2020},
author = {Huang, Z and Hu, C and Liu, K and Yuan, L and Li, Y and Zhao, C and Hu, C},
title = {Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {1145},
pmid = {33238981},
issn = {1471-2407},
mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*secondary/therapy ; Brain Neoplasms/*secondary/therapy ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary/therapy ; Male ; Middle Aged ; *Nomograms ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients.

METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University.

RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally.

CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.},
}

Adult
Aged
Aged, 80 and over
Bone Neoplasms/*secondary/therapy
Brain Neoplasms/*secondary/therapy
Breast Neoplasms/*pathology/therapy
Carcinoma, Ductal, Breast/*pathology/therapy
Combined Modality Therapy
Female
Follow-Up Studies
Humans
Lung Neoplasms/*secondary/therapy
Male
Middle Aged
*Nomograms
Prognosis
Retrospective Studies
Risk Factors
SEER Program
Young Adult

@article {pmid33239449,
year = {2021},
author = {Chen, J and Fleming, T and Katz, S and Dewenter, M and Hofmann, K and Saadatmand, A and Kronlage, M and Werner, MP and Pokrandt, B and Schreiter, F and Lin, J and Katz, D and Morgenstern, J and Elwakiel, A and Sinn, P and Gröne, HJ and Hammes, HP and Nawroth, PP and Isermann, B and Sticht, C and Brügger, B and Katus, HA and Hagenmueller, M and Backs, J},
title = {CaM Kinase II-δ Is Required for Diabetic Hyperglycemia and Retinopathy but Not Nephropathy.},
journal = {Diabetes},
volume = {70},
number = {2},
pages = {616-626},
doi = {10.2337/db19-0659},
pmid = {33239449},
issn = {1939-327X},
mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Diabetes Mellitus, Type 2/genetics/*metabolism ; Diabetic Nephropathies/genetics/*metabolism ; Diabetic Retinopathy/genetics/*metabolism ; Gene Expression ; Hyperglycemia/genetics/*metabolism ; Mice ; Mice, Knockout ; Receptors, Leptin/genetics/metabolism ; },
abstract = {Type 2 diabetes has become a pandemic and leads to late diabetic complications of organs, including kidney and eye. Lowering hyperglycemia is the typical therapeutic goal in clinical medicine. However, hyperglycemia may only be a symptom of diabetes but not the sole cause of late diabetic complications; instead, other diabetes-related alterations could be causative. Here, we studied the role of CaM kinase II-δ (CaMKIIδ), which is known to be activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor-mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we provide evidence for improved insulin sensing with increased glucose transport into skeletal muscle and also reduced hepatic glucose production. Despite normoglycemia, CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy, but diabetic retinopathy was prevented. We also unmasked a retina-specific gene expression signature that might contribute to CaMKII-dependent retinal diabetic complications. These data challenge the clinical concept of normalizing hyperglycemia in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolic signals in different diabetic organs.},
}

Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism
Diabetes Mellitus, Type 2/genetics/*metabolism
Diabetic Nephropathies/genetics/*metabolism
Diabetic Retinopathy/genetics/*metabolism
Gene Expression
Hyperglycemia/genetics/*metabolism
Mice
Mice, Knockout
Receptors, Leptin/genetics/metabolism

@article {pmid33243732,
year = {2020},
author = {Xu, X and Wang, J and Yan, C and Men, Y and Jiang, H and Fang, H and Xu, X and Yang, J},
title = {[Association of JMJD3, MMP-2 and VEGF expressions with clinicopathological features of invasive ductal breast carcinoma].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {40},
number = {11},
pages = {1593-1600},
pmid = {33243732},
issn = {1673-4254},
mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A ; },
abstract = {OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.

METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.

RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue (P < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes (P < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients (P < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (r=-0.569, P < 0.05) and VEGF (r=-0.533, P < 0.05) and a positive correlation between MMP2 and VEGF (r=0.923, P < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.

CONCLUSIONS: The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.},
}

*Breast Neoplasms/genetics
*Carcinoma, Ductal, Breast/genetics
Humans
Jumonji Domain-Containing Histone Demethylases
Lymphatic Metastasis
Matrix Metalloproteinase 2
Prognosis
Vascular Endothelial Growth Factor A

@article {pmid33247280,
year = {2020},
author = {Puzis, R and Farbiash, D and Brodt, O and Elovici, Y and Greenbaum, D},
title = {Increased cyber-biosecurity for DNA synthesis.},
journal = {Nature biotechnology},
volume = {38},
number = {12},
pages = {1379-1381},
pmid = {33247280},
issn = {1546-1696},
mesh = {*Computer Security ; DNA/*biosynthesis ; Genetic Engineering ; Plasmids/genetics ; },
}

*Computer Security
DNA/*biosynthesis
Genetic Engineering
Plasmids/genetics

@article {pmid33251496,
year = {2020},
author = {Li, X and Schmöhl, F and Qi, H and Bennewitz, K and Tabler, CT and Poschet, G and Hell, R and Volk, N and Poth, T and Hausser, I and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J},
title = {Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish.},
journal = {iScience},
volume = {23},
number = {12},
pages = {101763},
pmid = {33251496},
issn = {2589-0042},
abstract = {Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b [-/-] mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b [-/-] embryos. Akr1a1b [-/-] mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b [-/-] mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis.},
}

@article {pmid33263939,
year = {2021},
author = {D'Alfonso, TM and Pareja, F and Da Cruz Paula, A and Vahdatinia, M and Gazzo, A and Ferrando, L and da Silva, EM and Cheng, E and Sclafani, L and Chandarlapaty, S and Zhang, H and Hoda, SA and Wen, HY and Brogi, E and Weigelt, B and Reis-Filho, JS},
title = {Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma.},
journal = {The journal of pathology. Clinical research},
volume = {7},
number = {2},
pages = {113-120},
pmid = {33263939},
issn = {2056-4538},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Breast Neoplasms/complications/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; *DNA Copy Number Variations ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Papilloma/complications/diagnosis/*genetics/pathology ; Exome Sequencing ; },
abstract = {Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.},
}

Adult
Breast Neoplasms/complications/diagnosis/*genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology
Class I Phosphatidylinositol 3-Kinases/*genetics
*DNA Copy Number Variations
DNA Mutational Analysis
Female
Humans
Mutation
Papilloma/complications/diagnosis/*genetics/pathology
Exome Sequencing

@article {pmid33278619,
year = {2021},
author = {Hadano, Y and Kakuma, T and Matsumoto, T and Ishibashi, K and Isoda, M and Yasunaga, H},
title = {Reduction of 30-day death rates from Staphylococcus aureus bacteremia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {103},
number = {},
pages = {308-315},
doi = {10.1016/j.ijid.2020.11.199},
pmid = {33278619},
issn = {1878-3511},
mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/microbiology/mortality ; Case Management ; Female ; Hospitals ; Humans ; Japan ; Male ; Middle Aged ; *Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Specialization ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/*drug effects ; Treatment Outcome ; },
abstract = {OBJECTIVES: Most Japanese hospitals need to keep to higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximize the effect of these QCIs with only a small number of infectious disease specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious disease consultations (IDCs).

METHODS: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalized structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB.

RESULTS: A total of 114 patients with SAB were analyzed. The 30-day all-cause mortality differed significantly between the two periods (17.3% vs. 4.8%, P = 0.02). Age, three-QCI point ≥ 1, and Pitt bacteremia score ≥ 3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs.

CONCLUSION: Mandatory IDCs for SAB improved 30-day mortality and adherence to QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.},
}

Aged
Aged, 80 and over
Anti-Bacterial Agents/*therapeutic use
Bacteremia/*drug therapy/microbiology/mortality
Case Management
Female
Hospitals
Humans
Japan
Male
Middle Aged
*Quality of Health Care
Referral and Consultation
Retrospective Studies
Specialization
Staphylococcal Infections/*drug therapy/microbiology
Staphylococcus aureus/*drug effects
Treatment Outcome

@article {pmid33302909,
year = {2020},
author = {Desa, DE and Strawderman, RL and Wu, W and Hill, RL and Smid, M and Martens, JWM and Turner, BM and Brown, EB},
title = {Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {1217},
pmid = {33302909},
issn = {1471-2407},
support = {R21 CA208921/CA/NCI NIH HHS/United States ; W81XWH-15-1-0040//U.S. Department of Defense/ ; W81XWH-17-1-0011//U.S. Department of Defense/ ; R21CA208921//Foundation for the National Institutes of Health/ ; },
mesh = {Breast Neoplasms/chemistry/*ultrastructure ; Carcinoma, Ductal, Breast/chemistry/secondary/*ultrastructure ; *Estrogens ; Female ; Fibrillar Collagens/*ultrastructure ; Humans ; Image Processing, Computer-Assisted ; *Neoplasm Metastasis ; Neoplasm Proteins/*ultrastructure ; Neoplasms, Hormone-Dependent/chemistry/*ultrastructure ; Prognosis ; Risk ; *Second Harmonic Generation Microscopy ; Single-Blind Method ; Stromal Cells/chemistry/ultrastructure ; Tumor Microenvironment ; },
abstract = {BACKGROUND: Metastases are the leading cause of breast cancer-related deaths. The tumor microenvironment impacts cancer progression and metastatic ability. Fibrillar collagen, a major extracellular matrix component, can be studied using the light scattering phenomenon known as second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time (MFS). Here we assess the effects of heterogeneity in the tumor matrix on the possible use of F/B as a prognostic tool.

METHODS: SHG imaging was performed on sectioned primary tumor excisions from 95 untreated, estrogen receptor-positive, lymph node negative invasive ductal carcinoma patients. We identified two distinct regions whose collagen displayed different average F/B values, indicative of spatial heterogeneity: the cellular tumor bulk and surrounding tumor-stroma interface. To evaluate the impact of heterogeneity on F/B's prognostic ability, we performed SHG imaging in the tumor bulk and tumor-stroma interface, calculated a 21-gene recurrence score (surrogate for OncotypeDX®, or S-ODX) for each patient and evaluated their combined prognostic ability.

RESULTS: We found that F/B measured in tumor-stroma interface, but not tumor bulk, is prognostic of MFS using three methods to select pixels for analysis: an intensity threshold selected by a blinded observer, a histogram-based thresholding method, and an adaptive thresholding method. Using both regression trees and Random Survival Forests for MFS outcome, we obtained data-driven prediction rules that show F/B from tumor-stroma interface, but not tumor bulk, and S-ODX both contribute to predicting MFS in this patient cohort. We also separated patients into low-intermediate (S-ODX < 26) and high risk (S-ODX ≥26) groups. In the low-intermediate risk group, comprised of patients not typically recommended for adjuvant chemotherapy, we find that F/B from the tumor-stroma interface is prognostic of MFS and can identify a patient cohort with poor outcomes.

CONCLUSIONS: These data demonstrate that intratumoral heterogeneity in F/B values can play an important role in its possible use as a prognostic marker, and that F/B from tumor-stroma interface of primary tumor excisions may provide useful information to stratify patients by metastatic risk.},
}

Breast Neoplasms/chemistry/*ultrastructure
Carcinoma, Ductal, Breast/chemistry/secondary/*ultrastructure
*Estrogens
Female
Fibrillar Collagens/*ultrastructure
Humans
Image Processing, Computer-Assisted
*Neoplasm Metastasis
Neoplasm Proteins/*ultrastructure
Neoplasms, Hormone-Dependent/chemistry/*ultrastructure
Prognosis
Risk
*Second Harmonic Generation Microscopy
Single-Blind Method
Stromal Cells/chemistry/ultrastructure
Tumor Microenvironment

@article {pmid33316685,
year = {2021},
author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY},
title = {Pathologic response rates for breast cancer stages as a predictor of outcomes in patients receiving neoadjuvant chemotherapy followed by breast-conserving surgery.},
journal = {Surgical oncology},
volume = {36},
number = {},
pages = {91-98},
doi = {10.1016/j.suronc.2020.11.015},
pmid = {33316685},
issn = {1879-3320},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*pathology/therapy ; Chemotherapy, Adjuvant/*methods ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Prognosis ; Young Adult ; },
abstract = {PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.

PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients' PRRs; other independent predictors were controlled for or stratified in the analysis.

RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13-0.56), 0.36 (0.15-0.85), and 0.15 (0.08-0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35-0.89), 0.91 (0.62-0.96), and 0.63 (0.43-0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06-2.24), 1.08 (1.03-1.82), and 1.19 (1.07-2.01) for all-cause mortality, LRR, and DM, respectively.

CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.},
}

Adult
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Breast Neoplasms/*pathology/therapy
Chemotherapy, Adjuvant/*methods
Combined Modality Therapy
Female
Follow-Up Studies
Humans
Mastectomy, Segmental/*methods
Middle Aged
Neoadjuvant Therapy/*methods
Prognosis
Young Adult

@article {pmid33328559,
year = {2020},
author = {Wu, SG and Yang, SP and Zhang, WW and Wang, J and Lian, CL and Chen, YX and He, ZY},
title = {The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {22070},
pmid = {33328559},
issn = {2045-2322},
mesh = {Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; Survival Rate ; },
abstract = {The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.},
}

Aged
Breast Neoplasms/*mortality/pathology
Carcinoma, Ductal, Breast/*mortality/pathology
Disease-Free Survival
Female
Humans
Longitudinal Studies
Middle Aged
Neoplasm Invasiveness
Risk Factors
Survival Rate

@article {pmid33329538,
year = {2020},
author = {Niespolo, C and Johnston, JM and Deshmukh, SR and Satam, S and Shologu, Z and Villacanas, O and Sudbery, IM and Wilson, HL and Kiss-Toth, E},
title = {Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells.},
journal = {Frontiers in immunology},
volume = {11},
number = {},
pages = {574046},
pmid = {33329538},
issn = {1664-3224},
support = {PG/16/44/32146/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {3' Untranslated Regions ; Animals ; Binding Sites ; Cell Line, Tumor ; Cytokines/*metabolism ; Gene Expression Regulation ; Humans ; Inflammation ; Interleukin-8/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology ; Macrophages/*metabolism ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Phenotype ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics/metabolism/physiology ; RNA, Messenger/genetics/metabolism ; },
abstract = {The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate TRIB1 itself remain elusive. Here, we show that the long and conserved 3'untranslated region (3'UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple "high confidence" miRNAs potentially binding to the 3'UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3'UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.},
}

3' Untranslated Regions
Animals
Binding Sites
Cell Line, Tumor
Cytokines/*metabolism
Gene Expression Regulation
Humans
Inflammation
Interleukin-8/metabolism
Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology
Macrophages/*metabolism
Male
Mice
Mice, Transgenic
MicroRNAs/genetics/*metabolism
Phenotype
Prostatic Neoplasms/genetics/*metabolism/pathology
Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics/metabolism/physiology
RNA, Messenger/genetics/metabolism

@article {pmid33331427,
year = {2020},
author = {Bertoldi, AS and Guetter, CR and Coltro, GA and Vosgerau, LM and Brighenti, LMV and Fauat, NI and Kubrusly, FB and Marques, CAM and Kubrusly, LF},
title = {CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.},
journal = {Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery},
volume = {33},
number = {3},
pages = {e1525},
pmid = {33331427},
issn = {2317-6326},
mesh = {Adrenergic beta-Antagonists/*administration & dosage ; Animals ; Antihypertensive Agents/*administration & dosage ; Carvedilol/*administration & dosage ; Esophageal and Gastric Varices/complications/prevention & control ; Gastrointestinal Hemorrhage/etiology/*prevention & control ; Hypertension, Portal/*complications ; Rats ; Rats, Wistar ; },
abstract = {BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy.

AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model.

METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days.

RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups.

CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.},
}

Adrenergic beta-Antagonists/*administration & dosage
Animals
Antihypertensive Agents/*administration & dosage
Carvedilol/*administration & dosage
Esophageal and Gastric Varices/complications/prevention & control
Gastrointestinal Hemorrhage/etiology/*prevention & control
Hypertension, Portal/*complications
Rats
Rats, Wistar

@article {pmid33335279,
year = {2021},
author = {Zeng, Y and Gao, W and Chen, X and Shen, K},
title = {Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component.},
journal = {British journal of cancer},
volume = {124},
number = {5},
pages = {975-981},
pmid = {33335279},
issn = {1532-1827},
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.

METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.

RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.

CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.},
}

Biomarkers, Tumor/*genetics
Breast Neoplasms/genetics/*pathology
Carcinoma, Ductal, Breast/genetics/*pathology
Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology
Female
Follow-Up Studies
Gene Expression Profiling
Humans
Middle Aged
Prognosis
Retrospective Studies
Survival Rate

@article {pmid33336932,
year = {2021},
author = {Liang, RB and Yu, K and Wu, JL and Liu, JX and Lin, Q and Li, B and Zhang, YQ and Ge, QM and Li, QY and Shu, HY and Shao, Y},
title = {Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma.},
journal = {Cancer medicine},
volume = {10},
number = {3},
pages = {824-832},
pmid = {33336932},
issn = {2045-7634},
mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/metabolism/*pathology/surgery ; Case-Control Studies ; Eye Neoplasms/epidemiology/metabolism/*secondary/surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; },
abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p < 0.001, p < 0.001, p = 0.038, respectively). In the single risk factor ROC analysis, cutoff values of CA153, ApoA1, and Hb were 43.3 u/mL (CI: 0.966-0.984, p < 0.001), 1.11 g/L (CI: 0.923-0.951, p < 0.001), and 112 g/L (CI: 0.815-0.857, p < 0.001), respectively. Among the ROC curves of combined risk factors, CA153+ApoA1+Hb had the best accuracy, with the sensitivity and specificity of 89.47% and 99.32%, respectively (CI: 0.964-0.983, p < 0.001). CA153, ApoA1, and Hb are risk factors for OM in IDC. In clinical practice, the three parameters could be used as predictive factors for the early detection of OM.},
}

Adult
Biomarkers, Tumor/*metabolism
Breast Neoplasms/epidemiology/metabolism/*pathology/surgery
Carcinoma, Ductal, Breast/epidemiology/metabolism/*pathology/surgery
Case-Control Studies
Eye Neoplasms/epidemiology/metabolism/*secondary/surgery
Female
Follow-Up Studies
Humans
Lymphatic Metastasis
Middle Aged
Prognosis
Retrospective Studies
Risk Factors

@article {pmid33342987,
year = {2020},
author = {Shinseki, K and Takahashi, M and Kushima, A and Nakamoto, T and Wakata, M and Nakajima, T and Toda, T and Ito, K and Fujibayashi, M},
title = {[One Case of Accessory Breast Cancer Complicated by Contralateral Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {47},
number = {12},
pages = {1703-1705},
pmid = {33342987},
issn = {0385-0684},
mesh = {Axilla ; *Breast Diseases ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/complications/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; },
abstract = {We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.},
}

Axilla
*Breast Diseases
*Breast Neoplasms/surgery
*Carcinoma, Ductal, Breast/complications/surgery
Female
Humans
Lymph Node Excision
Lymph Nodes
Lymphatic Metastasis
Mastectomy
Middle Aged
Sentinel Lymph Node Biopsy

@article {pmid33348399,
year = {2020},
author = {Reis, APAM and Teixeira, CMS and Medeiros, ARL and Chaves, KZC and Albuquerque, CR and Melo, MR},
title = {Sociodemographic and Clinical-pathological Study of Molecular Subtitles of Breast Carcinoma in a Reference Unit of Maranhão.},
journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia},
volume = {42},
number = {12},
pages = {820-828},
pmid = {33348399},
issn = {1806-9339},
mesh = {Brazil/epidemiology ; Breast Neoplasms/*epidemiology/etiology/pathology ; Cross-Sectional Studies ; Demography ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Medical Records ; Middle Aged ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Social Class ; },
abstract = {OBJECTIVE: To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry.

METHODS:  A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranhão, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive.

RESULTS:  A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level < 9 years (40%), staging > IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5 cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others.

CONCLUSION:  It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.},
}

Brazil/epidemiology
Breast Neoplasms/*epidemiology/etiology/pathology
Cross-Sectional Studies
Demography
Female
Humans
Immunohistochemistry
Mastectomy
Medical Records
Middle Aged
Receptors, Estrogen/metabolism
Retrospective Studies
Social Class

@article {pmid33356097,
year = {2021},
author = {Zhong, S and Wong, HC and Low, HY and Zhao, R},
title = {Phototriggerable Transient Electronics via Fullerene-Mediated Degradation of Polymer:Fullerene Encapsulation Layer.},
journal = {ACS applied materials & interfaces},
volume = {13},
number = {1},
pages = {904-911},
doi = {10.1021/acsami.0c18795},
pmid = {33356097},
issn = {1944-8252},
abstract = {Transient electronics is an emerging class of electronics that has attracted a lot of attention because of its potential as an environmental-friendly alternative to the existing end-of-life product disposal or treatments. However, the controlled degradation of transient electronics under environmentally benign conditions remains a challenge. In this work, the tunable degradation of transient electronics including passive resistor devices and active memory devices was realized by photodegradable thin polymer films comprising fullerene derivatives, [6,6]-phenyl-C61-butyric acid methyl esters (PCBM). The photodegradation of polymer:PCBM under an aqueous environment is triggered by ultraviolet (UV) light. Experimental results demonstrate that the addition of PCBM in commodity polymers, including but not limited to polystyrene, results in a catalytic effect on polymer photodegradation when triggered by UV light. The degradation mechanism of transient electronics is ascribed to the photodegradation of polymer:PCBM encapsulation layers caused by the synergistic effect between UV and water exposure. The polymer:PCBM encapsulation system presented herein offers a simple way to achieve the realization of light-triggered device degradation for bioapplication and expands the material options for tailorable degradation of transient electronics.},
}

@article {pmid33370550,
year = {2021},
author = {Wang, M and Zeng, W and Zhang, Z and Zhang, W and Su, H and Zhang, Z and Jiang, L and Liu, Y and Shi, Q},
title = {The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.},
journal = {Viral immunology},
volume = {34},
number = {2},
pages = {96-111},
doi = {10.1089/vim.2020.0052},
pmid = {33370550},
issn = {1557-8976},
mesh = {Animals ; *Hepatitis B/prevention & control ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunity ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/immunology/therapeutic use ; *beta-Defensins/immunology/therapeutic use ; },
abstract = {Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 μg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3[+]/CD4[+] T cells and CD3[+]/CD8[+] T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.},
}

Animals
*Hepatitis B/prevention & control
Hepatitis B Antibodies
Hepatitis B Surface Antigens/genetics
Hepatitis B Vaccines
Hepatitis B virus
Humans
Immunity
Mice
Mice, Inbred BALB C
Recombinant Proteins/immunology/therapeutic use
*beta-Defensins/immunology/therapeutic use

@article {pmid33371069,
year = {2020},
author = {Yue, L and Wentao, L and Xin, Z and Jingjing, H and Xiaoyan, Z and Na, F and Tonghui, M and Dalin, L},
title = {Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.},
journal = {Medicine},
volume = {99},
number = {51},
pages = {e23406},
pmid = {33371069},
issn = {1536-5964},
mesh = {Acrylamides/administration & dosage/*therapeutic use ; Adult ; Aminoquinolines/administration & dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; ErbB Receptors/*genetics/*metabolism ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis ; Neoplasm Staging ; Erb-b2 Receptor Tyrosine Kinases/antagonists & inhibitors/metabolism ; },
abstract = {INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs.

PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2.

DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed.

INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy.

OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months.

CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.},
}

Acrylamides/administration & dosage/*therapeutic use
Adult
Aminoquinolines/administration & dosage/*therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Breast Neoplasms/*pathology
Carcinoma, Ductal, Breast
Chemotherapy, Adjuvant
ErbB Receptors/*genetics/*metabolism
Female
Humans
Mastectomy
Neoplasm Metastasis
Neoplasm Staging
Erb-b2 Receptor Tyrosine Kinases/antagonists & inhibitors/metabolism

@article {pmid33391657,
year = {2020},
author = {De Pauw, V and Navez, J and Holbrechts, S and Lemaitre, J},
title = {Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.},
journal = {Journal of surgical case reports},
volume = {2020},
number = {12},
pages = {rjaa535},
pmid = {33391657},
issn = {2042-8812},
abstract = {Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.},
}

@article {pmid33402291,
year = {2021},
author = {Mnejja, M and Kallel, S and Thabet, W and Regaieg, M and Kallel, R and Boudawara, T and Daoud, J and Hammami, B and Charfeddine, I},
title = {[Ductal carcinomas of the parotid gland].},
journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique},
volume = {25},
number = {2},
pages = {155-160},
doi = {10.1016/j.canrad.2020.06.034},
pmid = {33402291},
issn = {1769-6658},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery ; Carcinoma, Ductal, Breast/pathology/secondary ; Facial Nerve/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neck Dissection/statistics & numerical data ; Neoplasm Invasiveness ; Parotid Gland/diagnostic imaging/surgery ; Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery ; Prognosis ; Retrospective Studies ; Skin Neoplasms/pathology ; },
abstract = {PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland.

MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed.

RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression.

CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/pathology
Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery
Carcinoma, Ductal, Breast/pathology/secondary
Facial Nerve/surgery
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neck Dissection/statistics & numerical data
Neoplasm Invasiveness
Parotid Gland/diagnostic imaging/surgery
Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery
Prognosis
Retrospective Studies
Skin Neoplasms/pathology

@article {pmid33413755,
year = {2020},
author = {Zeng, XQ and Jiang, SS and Peng, YY and Liu, MF and Ye, CS and Dong, JY},
title = {Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review.},
journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih},
volume = {35},
number = {4},
pages = {377-382},
doi = {10.24920/003799},
pmid = {33413755},
issn = {1001-9294},
mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Platelet Count ; Thrombocytopenia/blood/*chemically induced/drug therapy ; Trastuzumab/*adverse effects ; },
abstract = {We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×10[9]/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.},
}

Adult
Antineoplastic Agents/therapeutic use
Breast Neoplasms/drug therapy
Female
Humans
Platelet Count
Thrombocytopenia/blood/*chemically induced/drug therapy
Trastuzumab/*adverse effects

@article {pmid33415472,
year = {2022},
author = {Zimmerman-Brenner, S and Pilowsky-Peleg, T and Rachamim, L and Ben-Zvi, A and Gur, N and Murphy, T and Fattal-Valevski, A and Rotstein, M},
title = {Group behavioral interventions for tics and comorbid symptoms in children with chronic tic disorders.},
journal = {European child & adolescent psychiatry},
volume = {31},
number = {4},
pages = {637-648},
pmid = {33415472},
issn = {1435-165X},
mesh = {Behavior Therapy ; Child ; Comorbidity ; Humans ; Severity of Illness Index ; *Tic Disorders/complications/therapy ; *Tics/therapy ; *Tourette Syndrome/complications/therapy ; },
abstract = {Exposure and Response Prevention (ERP), Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT) are effective in reducing tic severity. ERP and HRT have recently gained primary support in a group setting, while CBIT has not been examined similarly. We compared the efficacy of group-CBIT to group-Educational Intervention for Tics (group-EIT) for tics and comorbid symptoms. Children with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD) were randomized to group-CBIT or group-EIT. Tics and comorbid symptoms were assessed in forty-six children pre- and postintervention, and 3-month later. Yale Global Tic Severity Scale (YGTSS) Motor tic severity decreased following both interventions, and was maintained at follow-up for group-CBIT only. The Parent Tic Questionnaire (PTQ) showed significant decrease in total and motor tic severity following group-CBIT only, a gain maintained three months later. YGTSS impairment score decreased following both interventions and was maintained at follow-up. YGTSS vocal tic severity score increased following both interventions, and then decreased significantly at follow up. Co-morbid symptoms including anxiety, behavioral problems, and aggressive behavior decreased following both interventions. Children with behavioral problems benefitted less while children with higher intellectual ability benefit more from intervention. Both group interventions showed efficacy in reducing tic impairment and comorbid symptoms. Group-CBIT was superior to group-EIT in reducing motor tic severity at 3-month follow-up, showing an advantage for tic-focused treatment. Based on the PTQ, group-CBIT was superior to group-EIT in reducing motor, vocal, and total tic scores, a gain maintained three months later. Clinical trial registry information-Group Intervention for Children with Chronic Tics Syndrome: CBIT vs Psychoeducational Intervention URL: http://clinicaltrials.gov , Identifier: NCT02407951, http://www.controlled-trials.com).},
}

Behavior Therapy
Child
Comorbidity
Humans
Severity of Illness Index
*Tic Disorders/complications/therapy
*Tics/therapy
*Tourette Syndrome/complications/therapy

@article {pmid33416185,
year = {2021},
author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD},
title = {miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.},
journal = {Oncology reports},
volume = {45},
number = {2},
pages = {706-716},
pmid = {33416185},
issn = {1791-2431},
mesh = {Animals ; Breast/pathology/surgery ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery ; Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Disease Progression ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mastectomy ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasm Recurrence, Local/*epidemiology/genetics ; RNA-Binding Proteins/*genetics ; Xenograft Model Antitumor Assays ; },
abstract = {MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA‑MB‑231, compared to the non‑metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA‑MB‑468. The expression of miR‑490‑3p was induced following transforming growth factor (TGF)‑β‑induced epithelial‑to‑mesenchymal transition (EMT) in MCF10A cells. Gain‑and loss‑of‑function assays revealed that the expression of miR‑490‑3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA‑MB‑468 and MDA‑MB‑231 cells. The knockdown of miR‑490‑3p expression in MDA‑MB‑231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR‑490‑3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR‑490‑3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR‑490‑3p expression in patients with IDC compared to those with DCIS. The expression of miR‑490‑3p was negatively associated with both overall and disease‑free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro‑metastatic role of miR‑490‑3p in IDC, establishing it as a biomarker for disease progression in these patients.},
}

Animals
Breast/pathology/surgery
Breast Neoplasms/*genetics/mortality/pathology/surgery
Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery
Cell Line, Tumor
DNA-Binding Proteins/*genetics
Disease Progression
Disease-Free Survival
Epithelial-Mesenchymal Transition/genetics
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mastectomy
Mice
MicroRNAs/genetics/*metabolism
Neoplasm Recurrence, Local/*epidemiology/genetics
RNA-Binding Proteins/*genetics
Xenograft Model Antitumor Assays

@article {pmid33421821,
year = {2021},
author = {Hoshina, H and Takei, H and Sakatani, T and Naito, Z},
title = {CDX2-positive breast cancer presented with axillary lymph node metastases: A case report.},
journal = {Cancer treatment and research communications},
volume = {26},
number = {},
pages = {100300},
doi = {10.1016/j.ctarc.2020.100300},
pmid = {33421821},
issn = {2468-2942},
mesh = {Axilla ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/therapy ; CDX2 Transcription Factor/analysis/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Ultrasonography ; },
abstract = {BACKGROUND: The caudal type homeobox 2 transcription factor (CDX2) is a specific and sensitive marker for intestinal carcinoma, but usually not expressed in breast cancer. In CDX2-positive metastatic cancer of occult primary, the origin is highly suspicious of an enteric carcinoma.

CASE PRESENTATION: A 50-year-old woman complained of enlarged lymph nodes (LNs) in the right axilla. Mammography and ultrasonography scans showed no abnormal findings in her breasts. Core needle biopsy (CNB) revealed metastatic adenocarcinoma. Immunohistochemical staining was positive for CDX2 intensely. The primary tumor was suspicious of intestinal adenocarcinoma. A dynamic contrast-enhanced magnetic resonance imaging scan revealed an accentuated lesion which was detected using a second-look ultrasound, and diagnosed invasive ductal carcinoma by CNB. A partial mastectomy of the right breast with level I and II axillary LN dissection was performed. A few cells of primary cancer were expressed CDX2 and estrogen receptor. The final pathological diagnosis was T1bN3aM0 stage IIIC. The fluorescent double staining showed that CDX2 simultaneously expressed on the Ki67 positive cells of metastatic tumors. The adjuvant treatment included chemotherapy and radiation, followed by tamoxifen administration. The patient survived without any recurrences over the following 36 months.

CONCLUSIONS: We report a rare case of CDX2-positive metastatic breast cancer in the axillary LNs. As some literatures reported vitamin D pathways induced cancer cell apoptosis and inhibition, these metastatic cells of our case might play the effort of autoregulation of inhibiting progression.},
}

Axilla
Biopsy, Large-Core Needle
Breast/diagnostic imaging/pathology/surgery
Breast Neoplasms/*diagnosis/pathology/therapy
CDX2 Transcription Factor/analysis/*metabolism
Carcinoma, Ductal, Breast/*diagnosis/secondary
Chemoradiotherapy, Adjuvant
Female
Humans
Lymph Nodes/pathology
Lymphatic Metastasis/*diagnosis/pathology
Mammography
Mastectomy, Segmental
Middle Aged
Neoplasm Staging
Ultrasonography

@article {pmid33428505,
year = {2021},
author = {Nevagi, RJ and Good, MF and Stanisic, DI},
title = {Plasmodium infection and drug cure for malaria vaccine development.},
journal = {Expert review of vaccines},
volume = {20},
number = {2},
pages = {163-183},
doi = {10.1080/14760584.2021.1874923},
pmid = {33428505},
issn = {1744-8395},
mesh = {Animals ; Antigens, Protozoan/immunology ; Antimalarials/administration & dosage ; Humans ; Malaria/immunology/parasitology/*prevention & control ; Malaria Vaccines/*administration & dosage/immunology ; Plasmodium/*immunology/parasitology ; },
abstract = {Introduction: Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials. The advantage of whole parasite vaccines is that they induce immune responses against multiple parasite antigens, thus lowering the impact of antigenic diversity. Deliberate Plasmodium IDC, as a vaccine approach, involves administering infectious, live parasites in combination with an anti-malarial drug, which controls the infection and enables induction of protective immune responses.},
}

Animals
Antigens, Protozoan/immunology
Antimalarials/administration & dosage
Humans
Malaria/immunology/parasitology/*prevention & control
Malaria Vaccines/*administration & dosage/immunology
Plasmodium/*immunology/parasitology

@article {pmid33429799,
year = {2021},
author = {Karatas, M and Zengel, B and Durusoy, R and Tasli, F and Adibelli, Z and Simsek, C and Uslu, A},
title = {Clinicopathologic features of single bone metastasis in breast cancer.},
journal = {Medicine},
volume = {100},
number = {1},
pages = {e24164},
pmid = {33429799},
issn = {1536-5964},
mesh = {Adult ; Aged ; Bone Neoplasms/*classification/pathology ; Bone and Bones/*pathology/physiopathology ; Breast Neoplasms/*complications ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis/*physiopathology ; },
abstract = {The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.},
}

Adult
Aged
Bone Neoplasms/*classification/pathology
Bone and Bones/*pathology/physiopathology
Breast Neoplasms/*complications
Female
Humans
Middle Aged
Neoplasm Metastasis/*physiopathology

@article {pmid33433407,
year = {2021},
author = {Farrag, MS and Anter, AH and Farrag, NS and Ibrahiem, AT},
title = {"Switch of E-Cadherin to N-Cadherin expression in different molecular subtypes of breast invasive duct carcinomas and its correlation with clinicopathological features".},
journal = {Indian journal of pathology & microbiology},
volume = {64},
number = {1},
pages = {38-46},
doi = {10.4103/IJPM.IJPM_924_19},
pmid = {33433407},
issn = {0974-5130},
mesh = {Antigens, CD/*genetics ; Biomarkers, Tumor ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/classification/*genetics/*pathology/secondary ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paraffin Embedding ; Prognosis ; Young Adult ; },
abstract = {BACKGROUND: In breast cancer, metastasis and recurrence is the main culprit in treatment failure. This study aimed to explore the role of E-cadherin/N-cadherin Switch in progression, spread and metastasis in breast invasive duct carcinoma.

MATERIALS AND METHODS: A cross-sectional study on 118 formalinfixed paraffinembedded mastectomy specimens of invasive breast duct carcinoma. Primary antibodies for E-cadherin (monoclonal, clone HECD-1; Zymed Laboratories; dilution 1:600) and N-cadherin (monoclonal, clone 3B9; Zymed Laboratories, Inc., Montrouge, France; dilution 1:200) were applied for all cases. The study revealed that E-cadherin high expression was significantly associated with advanced TNM clinical stage (P = 0.021), and nodal metastasis (P < 0.001). High expression of N-cadherin was significantly positively correlated with tumor sizes (P < 0.00), advanced clinical stage (P < 0.00), and nodal metastasis (P < 0.008). Mean OS was 39.99 months in cases with negative expression versus 41.8 months in cases with positive expression. Mean DFS in cases with positive E. cadh expression was 41.89 months was higher than mean DFS in cases with negative E. cadh expression which was 40.52 months, but it showed no statistical significance (P = 0.57).

CONCLUSIONS/SIGNIFICANCE: This study demonstrated that loss of E-cadherin and gain of N-cadherin promotes invasion, migration, and metastasis in invasive ductal carcinoma cells. Importantly, these findings may exploit new cancer therapies using N-cadherin antagonists.},
}

Antigens, CD/*genetics
Biomarkers, Tumor
Cadherins/*genetics
Carcinoma, Ductal, Breast/classification/*genetics/*pathology/secondary
Cross-Sectional Studies
Female
Humans
Immunohistochemistry
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Paraffin Embedding
Prognosis
Young Adult

@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