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https://www.readbyqxmd.com/read/27923843/therapeutic-activity-of-anti-axl-antibody-against-triple-negative-breast-cancer-patient-derived-xenografts-and-metastasis
#1
Wilhem Leconet, Myriam Chentouf, Stanislas Du Manoir, Clément Chevalier, Audrey Sirevnt, Imade Aït-Arsa, Muriel Busson, Marta Jarlier, Nina Radosevic-Robin, Charles G Theillet, Dany Chalbos, Jean-Max Pasquet, Christel Larbouret, André Pèlegrin, Bruno Robert
PURPOSE: AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple negative breast cancer (TNBC). EXPERIMENTAL DESIGN: We evaluate the anti-tumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration and invasion signaling pathways...
December 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27920426/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#2
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919946/in-vivo-selection-of-intermediately-and-highly-malignant-variants-of-triple-negative-breast-cancer-in-orthotopic-nude-mouse-models
#3
Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M Hoffman
AIM: Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2 (HER2), is a recalcitrant disease in need of effective therapy. We previously isolated very-highly metastatic variants of the TNBC cell line MDA-MB-231 using serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. MATERIALS AND METHODS: MDA-MB-231 cells expressing red fluorescent protein (MDA-MB-231-RFP) (1×10(7) cells/site) were initially injected subcutaneously in the flank of nude mice...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27915434/differences-in-the-mutational-landscape-of-triple-negative-breast-cancer-in-african-americans-and-caucasians
#4
Foluso O Ademuyiwa, Yu Tao, Jingqin Luo, Katherine Weilbaecher, Cynthia X Ma
BACKGROUND: Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC. METHODS: Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data...
December 3, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#5
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27906681/sirna-mediated-suppression-of-collagen-type-iv-alpha-2-col4a2-mrna-inhibits-triple-negative-breast-cancer-cell-proliferation-and-migration
#6
He Jing Song, Guan Hong, Jianbo Yang, Zheng Duo, Fu Li, Chen Wei Cai, Luo Xue Ying, Mao You Sheng, Ou Yang YiWen, Pan Yue, Chang Zou
Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. Collagen type IV alpha 2 (COL4A2), a major component of the basement membrane, dynamically influences a wide range of biological processes, including cancer pathogenesis and progression. This study evaluated the effects of COL4A2 siRNA delivered by lentiviral vector to TNBC cells. COL4A2 siRNA lenti-viral vector was constructed and transfected into MDA-MB-231 and MDA-MB-468 cells. The COL4A2 mRNA levels were quantified by RT-PCR...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904868/predictive-ability-of-18-f-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-for-pathological-complete-response-and-prognosis-after-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer-patients
#7
Sachiko Kiyoto, Yoshifumi Sugawara, Kohei Hosokawa, Rieko Nishimura, Natsumi Yamashita, Shozo Ohsumi, Teruhito Mochizuki
OBJECTIVES: The mortality of patients with locally advanced triple-negative breast cancer (TNBC) is high, and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This retrospective study was designed and powered to investigate the ability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) to predict pathological response to NAC and prognosis after NAC. METHODS: The data of 32 consecutive women with clinical stage II or III TNBC from January 2006 to December 2013 in our institution who underwent FDG-PET/CT at baseline and after NAC were retrospectively analyzed...
2016: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/27904710/the-comt-rs165599-gene-polymorphism-contributes-to-chemotherapy-induced-cognitive-impairment-in-breast-cancer-patients
#8
Huaidong Cheng, Wen Li, Chen Gan, Bo Zhang, Qianqian Jia, Kai Wang
The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#9
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902967/the-non-receptor-tyrosine-kinase-tnk2-ack1-is-a-novel-therapeutic-target-in-triple-negative-breast-cancer
#10
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Dhanashree S Kelkar, Mustafa A Bharbuiya, Pamela L Rojas, Vered Stearns, Edward Gabrielson, Pavani Malla, Saraswati Sukumar, Nupam P Mahajan, Akhilesh Pandey
Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers do not express estrogen receptor, progesterone receptor or HER2 receptor and hence are collectively classified as triple negative breast cancer (TNBC). These tumors are often relatively aggressive when compared to other types of breast cancer, and this issue is compounded by the lack of effective targeted therapy. In our previous phosphoproteomic profiling effort, we identified the non-receptor tyrosine kinase TNK2 as activated in a majority of aggressive TNBC cell lines...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#11
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#12
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27896700/fat4-functions-as-a-tumor-suppressor-in-triple-negative-breast-cancer
#13
Lingmi Hou, Maoshan Chen, Xiaobo Zhao, Jingdong Li, Shishan Deng, Jiani Hu, Hongwei Yang, Jun Jiang
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with biologic behavior with frequent distant metastasis. FAT tumor suppressor homolog 4 (FAT4), a cadherin-related protein, is involved in a variety of biological processes as a tumor suppressor; however, the role of FAT4 in TNBC is still unclear. The aim of our study was to identify the role of FAT4 in TNBC and examine the underlying molecular mechanisms. The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in a series of TNBC tissues...
November 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#14
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894092/a-novel-fully-human-anti-ncl-immunornase-for-triple-negative-breast-cancer-therapy
#15
Chiara D'Avino, Dario Palmieri, Ashley Braddom, Nicola Zanesi, Cindy James, Sara Cole, Francesco Salvatore, Carlo M Croce, Claudia De Lorenzo
Breast cancer is the most common cancer in women worldwide. A new promising anti-cancer therapy involves the use of monoclonal antibodies specific for target tumor-associated antigens (TAAs). A TAA of interest for immunotherapy of Triple Negative Breast Cancer (TNBC) is nucleolin (NCL), a multifunctional protein, selectively expressed on the surface of cancer cells, which regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and drug-resistance. We previously isolated a novel human anti-NCL scFv, called 4LB5, that is endowed with selective anti-tumor effects...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893626/molecular-profiling-using-breast-cancer-subtype-to-plan-for-breast-reconstruction
#16
Lars Johan Sandberg, Mark W Clemens, W F Symmans, Vicente Valero, Abigail S Caudle, Benjamin Smith, Henry M Kuerer, Limin Hsu, Steven J Kronowitz
BACKGROUND: Molecular profiling using breast cancer subtype has an increasing role in the multidisciplinary care of the breast cancer patient. We sought to determine the role of breast cancer subtyping in breast reconstruction and specifically if breast cancer subtyping can determine the need for postmastectomy radiation therapy (PMRT) and predict recurrence-free survival (RFS) to plan for the timing and technique of breast reconstruction. METHODS: We reviewed prospectively collected data from 1931 reconstructed breasts in breast cancer patients who underwent mastectomy between November 1999 and December 2012...
November 21, 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27893038/targeting-the-pi3k-akt-mtor-pathway-for-the-treatment-of-mesenchymal-triple-negative-breast-cancer-evidence-from-a-phase-1-trial-of-mtor-inhibition-in-combination-with-liposomal-doxorubicin-and-bevacizumab
#17
Reva K Basho, Michael Gilcrease, Rashmi K Murthy, Thorunn Helgason, Daniel D Karp, Funda Meric-Bernstam, Kenneth R Hess, Shelley M Herbrich, Vicente Valero, Constance Albarracin, Jennifer K Litton, Mariana Chavez-MacGregor, Nuhad K Ibrahim, James L Murray, Kimberly B Koenig, David Hong, Vivek Subbiah, Razelle Kurzrock, Filip Janku, Stacy L Moulder
Importance: Triple-negative breast cancer (TNBC) classified by transcriptional profiling as the mesenchymal subtype frequently harbors aberrations in the phosphoinositide 3-kinase (PI3K) pathway, raising the possibility of targeting this pathway to enhance chemotherapy response. Up to 30% of mesenchymal TNBC can be classified histologically as metaplastic breast cancer, a chemorefractory group of tumors with a mixture of epithelial and mesenchymal components identifiable by light microscopy...
November 23, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27888707/up-regulation-of-rfc3-promotes-triple-negative-breast-cancer-metastasis-and-is-associated-with-poor-prognosis-via-emt
#18
Zhen-Yu He, San-Gang Wu, Fang Peng, Qun Zhang, Ying Luo, Ming Chen, Yong Bao
Triple-negative breast cancer (TNBC) was regarded as the most aggressive and mortal subtype of breast cancer (BC) since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway...
November 23, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27888421/triple-negative-breast-cancer-has-worse-overall-survival-and-cause-specific-survival-than-non-triple-negative-breast-cancer
#19
Xiaoxian Li, Jing Yang, Limin Peng, Aysegul A Sahin, Lei Huo, Kevin C Ward, Ruth O'Regan, Mylin A Torres, Jane L Meisel
PURPOSE: The current American Joint Committee on Cancer (AJCC) staging manual uses tumor size, lymph node, and metastatic status to stage breast cancer across different subtypes. We examined the prognosis of triple-negative breast cancer (TNBC) versus non-TNBC within the same stages and sub-stages to evaluate whether TNBC had worse prognosis than non-TNBC. METHODS: We reviewed the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) data and identified 158,358 patients diagnosed with breast cancer from 2010 to 2012...
November 25, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27888420/endocan-as-a-prognostic-biomarker-of-triple-negative-breast-cancer
#20
Atsunobu Sagara, Katsuhide Igarashi, Maky Otsuka, Akihiro Kodama, Mutsumi Yamashita, Rei Sugiura, Takeshi Karasawa, Kazuhiko Arakawa, Michiko Narita, Naoko Kuzumaki, Minoru Narita, Yoshinori Kato
PURPOSE: Triple-negative breast cancer (TNBC) has aggressive characteristics and fewer treatment options than other subtypes. The purpose of this study was to explore prognostic biomarkers for TNBC that can be easily detected from the blood samples. METHODS: MDA-MB-231 and MDA-MB-231BR, a brain metastatic variant of the human TNBC cell line MDA-MB-231, were used as less and more aggressive models of TNBC, respectively. The extent to which the candidate gene/protein identified by RNA sequencing correlated well with aggressiveness of TNBC and how much protein was detected from the blood of tumor-bearing mice were evaluated...
November 25, 2016: Breast Cancer Research and Treatment
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