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https://www.readbyqxmd.com/read/28537911/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#1
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew Wb Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535016/nherf1-inhibits-proliferation-of-triple-negative-breast-cancer-cells-by-suppressing-gper-signaling
#2
Yan Wang, Zhiqiang Peng, Ran Meng, Tao Tao, Qiqi Wang, Chunjuan Zhao, Hua Liu, Ran Song, Junfang Zheng, Qiong Qin, Junqi He
G protein-coupled estrogen receptor (GPER) signaling is activated in triple-negative breast cancer (TNBC); however, the detailed mechanisms of its regulation remain unclear. The present study aimed to elucidate the molecular mechanisms involved in GPER activation in TNBC. In MDA-MB-231 cells, a TNBC cell line, NHERF1 interaction with GPER was verified by co-immunoprecipitation and immunofluorescent staining assays. Overexpression of NHERF1 in MDA-MB-231 cells inhibited GPER-mediated proliferation and phosphorylation of ERK1/2 and Akt...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534358/prognostic-implications-of-the-intrinsic-molecular-subtypes-in-male-breast-cancer
#3
Abdeljaoued Syrine, Bettaieb Lhem, Nasri Meher, Adouni Olfa, Goucha Aida, Bouzaiene Hatem, Boussen Hamouda, Rahal Khaled, Gamoudi Amor
PURPOSE: Intrinsic molecular subtyping has been widely used in female breast cancer, and it has proven its significance. In this article, we aimed to study the intrinsic subtypes of male breast cancer (MBC) in correlation with clinicopathological features. METHODS: We retrospectively identified 130 MBC cases from 2004 to 2013. Intrinsic molecular subtypes were determined by immunohistochemistry (IHC). RESULTS: From a total of 130 MBC cases, 45...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28533703/differential-expression-of-vegfr2-protein-in-her2-positive-primary-human-breast-cancer-potential-relevance-to-anti-angiogenic-therapies
#4
Aejaz Nasir, Timothy R Holzer, Mia Chen, Michael Z Man, Andrew E Schade
BACKGROUND: Clinically relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need. METHODS: We analyzed tumor vascular density and VEGFR2 protein expression in various subsets of primary human BRCs (186 females; Mean age: 59 years; range 33-88 years), using a tissue microarray. Discrete VEGFR2+ and CD34+ tumor vessels were manually scored in invasive ductal, lobular, mixed ductal-lobular and colloid (N = 139, 22, 18, 7) BRC cores...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28533055/high-asma-fibroblasts-and-low-cytoplasmic-hmgb1-breast-cancer-cells-predict-poor%C3%A2-prognosis
#5
Kamolporn Amornsupak, Pranisa Jamjuntra, Malee Warnnissorn, Pornchai O-Charoenrat, Doonyapat Sa-Nguanraksa, Peti Thuwajit, Suzanne A Eccles, Chanitra Thuwajit
INTRODUCTION: The influence of cancer-associated fibroblasts (CAFs) and high mobility group box 1 (HMGB1) has been recognized in several cancers, although their roles in breast cancer are unclear. The present study aimed to determine the levels and prognostic significance of α-smooth muscle actin-positive (ASMA(+)) CAFs, plus HMGB1 and receptor for advanced glycation end products (RAGE) in cancer cells. MATERIALS AND METHODS: A total of 127 breast samples, including 96 malignant and 31 benign, were examined for ASMA, HMGB1, and RAGE by immunohistochemistry...
April 21, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28531218/autophagy-inhibitor-facilitates-gefitinib-sensitivity-in-vitro-and-in-vivo-by-activating-mitochondrial-apoptosis-in-triple-negative-breast-cancer
#6
Zhaoyun Liu, Kewen He, Qinghua Ma, Qian Yu, Chenyu Liu, Isabella Ndege, Xinzhao Wang, Zhiyong Yu
Epidermal growth factor receptor (EGFR) is over-expressed in about 50% of Triple negative breast cancers (TNBCs), but EGFR inhibitors have not been effective in treating TNBC patients. Increasing evidence supports that autophagy was related to drug resistance at present. However, the role and the mechanism of autophagy to the treatment of TNBC remain unknown. In the current study, we investigated the effect of autophagy inhibitor to gefitinib (Ge) in TNBC cells in vitro and in nude mice vivo. Our study demonstrated that inhibition of autophagy by 3-Methyladenine or bafilomycin A1 improved Ge's sensitivity to MDA-MB-231 and MDA-MB-468 cells, as evidence from stronger inhibition of cell vitality and colony formation, higher level of G0/G1 arrest and DNA damage, and these effects were verified in nude mice vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28531188/monitoring-tumor-response-to-neoadjuvant-chemotherapy-using-mri-and-18f-fdg-pet-ct-in-breast-cancer-subtypes
#7
Alexander M Th Schmitz, Suzana C Teixeira, Kenneth E Pengel, Claudette E Loo, Wouter V Vogel, Jelle Wesseling, Emiel J Th Rutgers, Renato A Valdés Olmos, Gabe S Sonke, Sjoerd Rodenhuis, Marie Jeanne T F D Vrancken Peeters, Kenneth G A Gilhuijs
PURPOSE: To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. MATERIALS AND METHODS: In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired before and during NAC. Baseline pathology was assessed from tumor biopsy. Tumors were stratified into HER2-positive, ER-positive/HER2-negative (ER-positive), and ER-negative/PR-negative/HER2-negative (triple-negative) subtypes, and treated according to subtype...
2017: PloS One
https://www.readbyqxmd.com/read/28530705/ccn5-wisp-2-restores-er-%C3%A2-in-normal-and-neoplastic-breast-cells-and-sensitizes-triple-negative-breast-cancer-cells-to-tamoxifen
#8
S Sarkar, A Ghosh, S Banerjee, G Maity, A Das, M A Larson, V Gupta, I Haque, O Tawfik, S K Banerjee
CCN5/WISP-2 is an anti-invasive molecule and prevents breast cancer (BC) progression. However, it is not well understood how CCN5 prevents invasive phenotypes of BC cells. CCN5 protein expression is detected in estrogen receptor-α (ER-α) -positive normal breast epithelial cells as well as BC cells, which are weakly invasive and rarely metastasize depending on the functional status of ER-α. A unique molecular relation between CCN5 and ER-α has been established as the components of the same signaling pathway that coordinate some essential signals associated with the proliferation as well as delaying the disease progression from a non-invasive to invasive phenotypes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28529458/targeting-hsp90-hdac6-regulating-network-implicates-precision-treatment-of-breast-cancer
#9
Shiyi Yu, Xiuxiu Cai, Chenxi Wu, Yan Liu, Jun Zhang, Xue Gong, Xin Wang, Xiaoli Wu, Tao Zhu, Lin Mo, Jun Gu, Zhenghong Yu, Jinfei Chen, Jean Paul Thiery, Renjie Chai, Liming Chen
Breast cancer is the leading cause of women death. Heat shock protein 90 (HSP90) and Histone deacetylase 6 (HDAC6) are promising anti-cancer drug targets. However, it's still unclear the applicability of anti-HSP90 and anti-HDAC6 strategies in precision treatment of breast cancer. In current study, we found that triple negative breast cancer (TNBC) cells, compared to T47D, an ERα+ breast cancer cell line, exhibited 7~40 times lower IC50 values, stronger cell cycle perturbation, increased cell apoptosis and stronger inhibition of cell migration upon 17-DMAG treatment, while T47D, compared to TNBC cells, expressed higher HDAC6 and showed stronger anti-cancer response upon treatment of Tubacin...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28529455/dipalmitoylphosphatidic-acid-inhibits-tumor-growth-in-triple-negative-breast-cancer
#10
Qian-Qian Zhang, Jian Chen, Da-Lei Zhou, You-Fa Duan, Cui-Ling Qi, Jiang-Chao Li, Xiao-Dong He, Min Zhang, Yong-Xia Yang, Lijing Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis, accounting for approximately 12-24% of breast cancer cases. Accumulating evidence has indicated that there is no effective targeted therapy available for TNBC. Dipalmitoylphosphatidic acid (DPPA) is a bioactive phospholipid. However, the function of DPPA in the growth of TNBC has not yet been studied. In this study, we employed TNBC cells and a subcutaneous tumor model to elucidate the possible effect of DPPA on tumor growth in TNBC...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28529129/estrogen-receptor-%C3%AE-36-is-involved-in-icaritin-induced-growth-inhibition-of-triple-negative-breast-cancer-cells
#11
Xue Wang, Nan Zheng, Jing Dong, Xuming Wang, Lijiang Liu, Jian Huang
A sub-class of ER-negative breast cancer that is negative for ER, PR and HER2 expression known as triple-negative breast cancer (TNBC) is highly malignant and lacks effective treatment. Recently, it has been reported that an isoform of estrogen receptor-alpha ER-α36 is expressed and plays a critical role in development of TNBC. ER-α36 forms a positive regulatory loop with epidermal growth factor receptor (EGFR), which promotes malignant growth of TNBC cells. Thus, ER-α36 has been proposed as an important target for development of novel drugs for TNBC...
May 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28529029/metaplastic-carcinoma-of-the-breast-is-more-aggressive-than-triple-negative-breast-cancer-a%C3%A2-study-from-a-single-institution-and-review-of%C3%A2-literature
#12
Dima El Zein, Melissa Hughes, Shicha Kumar, Xuan Peng, Tolutope Oyasiji, Hossam Jabbour, Thaer Khoury
BACKGROUND: We aimed to describe our experience with metaplastic breast carcinoma (MBC), evaluate its clinical outcome compared with triple-negative breast cancer (TNBC), and provide a through and comprehensive review of the literature to date. MATERIALS AND METHODS: We reviewed MBC cases (n = 46) from our institution. The following variables were recorded: tumor histologic subtype, Nottingham grade, tumor size, lymph node status, Tumor, Node, Metastases stage, biomarkers profile, patient's age and race, therapy modality (chemotherapy and radiation), and survival (disease-free survival [DFS] and overall survival [OS])...
April 26, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28528518/a-multi-gene-panel-study-in-hereditary-breast-and-ovarian-cancer-in-colombia
#13
A M Cock-Rada, C A Ossa, H I Garcia, L R Gomez
Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis...
May 20, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28528300/treating-metastatic-triple-negative-breast-cancer-with-cd44-neuropilin-dual-molecular-targets-of-multifunctional-nanoparticles
#14
De-Sheng Liang, Wen-Jie Zhang, Ai-Ting Wang, Hai-Tao Su, Hai-Jun Zhong, Xian-Rong Qi
Metastasis of cancer makes up the vast majority of cancer-related deaths, and it usually initiates from tumor cells invasiveness and develops through tumor neovasculature. In this work, we have fabricated a CD44/neuropilin dual receptor-targeting nanoparticulate system (tLyP-1-HT NPs) with endogenous or FDA approved components for treating metastatic triple negative breast cancer (TNBC). The enhanced specific targeting of tLyP-1-HT NPs to both metastatic tumor cells and metastasis-supporting tumor neovasculature was contributed by means of CD44/neuropilin dual receptor-mediated interaction...
May 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28528184/synergistic-antitumor-effect-of-nvp-bez235-and-cape-on-mda-mb-231-breast-cancer-cells
#15
Samira Torki, Amin Soltani, Hedayatollah Shirzad, Nafiseh Esmaeil, Mahdi Ghatrehsamani
Triple negative breast cancer (TNBC) is the most lethal and aggressive kind of breast cancer. Studies with TNBC cells suggest that tumor environmental cytokines such as Transforming Growth Factor β1 (TGF-β1) have important roles in tumors fate. In the present study, we aimed to investigate, the effect of phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway dual inhibitor, NVP-BEZ235 and Caffeic acid phenyl ester (CAPE) on TNBC cell line (MDA-MB-231), stimulated with TGF-β1 for 14days in vitro...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28527916/cadmium-stimulates-metastasis-associated-phenotype-in-triple-negative-breast-cancer-cells-through-integrin-and-%C3%AE-catenin-signaling
#16
Zhengxi Wei, Zahir A Shaikh
Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer development. While the mechanisms of Cd-induced breast cancer initiation and promotion have been studied, the molecular processes involved in breast cancer progression remain to be investigated. The purpose of the present study was to evaluate the influence of Cd on metastasis-associated phenotypes, such as cell adhesion, migration, and invasion in triple-negative breast cancer cells. Treatment of MDA-MB-231 cells with 1μM Cd increased cell spreading and cell migration...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527420/factors-predictive-of-locoregional-recurrence-following-neoadjuvant-chemotherapy-in-patients-with-large-operable-or-locally-advanced-breast-cancer-an-analysis-of-the-eortc-10994-big-1-00-study
#17
Pauline Gillon, Nathan Touati, Christel Breton-Callu, Leen Slaets, David Cameron, Hervé Bonnefoi
PURPOSE: Identification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). METHODS: Patients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines...
May 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28526992/epithelial-mesenchymal-transition-emt-in-metastatic-breast-cancer-in-omani-women
#18
Ritu Lakhtakia, Adil Aljarrah, Muhammad Furrukh, Shyam S Ganguly
Breast cancer (BC) in Oman affects younger women and has a more aggressive course. Clinical and biological variables like age, pregnancy, tumor size, type, grade, receptor expression and proliferation predict disease aggression but there is no direct predictor of metastasis except lymphovascular invasion. Epithelial-mesenchymal transition (EMT) is characterized by epithelial cells losing epithelial and acquiring mesenchymal morpho-immunophenotypic characteristics. In tumors, EMT-like transitions may signify a metastatic phenotype and have features in common with cancer stem cells (CSC) which show resistance to chemotherapy...
May 19, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28526455/comparison-of-3d-and-2d-shear-wave-elastography-for-differentiating-benign-and-malignant-breast-masses-focus-on-the-diagnostic-performance
#19
H Y Choi, Y-M Sohn, M Seo
AIM: To evaluate the diagnostic performance of three-dimensional (3D) image shear-wave elastography (SWE) for differentiating benign from malignant breast masses compared to two-dimensional (2D) SWE and B-mode ultrasound (US). MATERIALS AND METHODS: This study consisted of 205 breast lesions from 199 patients who underwent B-mode US and SWE before biopsy from January 2014 to March 2016. Quantitative elasticity values (maximum and mean elasticity, Emax and Emean) obtained from 2D and 3D SWE (axial, sagittal, and coronal images) were reviewed retrospectively, in addition to the histopathological findings including immunohistochemistry profiles (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer) in cases of malignancy...
May 16, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28525844/the-discovery-of-novel-potent-err-alpha-inverse-agonists-for-the-treatment-of-triple-negative-breast-cancer
#20
Yongli Du, Lianhua Song, Liudi Zhang, Hao Ling, Yanhui Zhang, Haifei Chen, Huijie Qi, Xiaojin Shi, Qunyi Li
The estrogen-related receptor α (ERRα) is an orphan receptor and a novel target for solid tumor therapy, conceivably through effects on the regulation of tumor cell energy metabolism associated with energy stress within solid tumor micro environments. Here we describe the discovery of novel potent inverse agonists of ERRα. In vitro, compound 11 potently inhibits ERRα's transcriptional activity by preventing endogenous PGC-1α and ERRα binding and suppresses the proliferation of different human cancer cell lines and the migration of breast cancer cells (MDA-MB-231)...
April 22, 2017: European Journal of Medicinal Chemistry
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