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Triple negative breast cancer

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https://www.readbyqxmd.com/read/29230610/predictive-value-of-vascular-endothelial-growth-factor-receptor-type-2-in-triple-negative-breast-cancer-patients-treated-with-neoadjuvant-chemotherapy
#1
Nataliya Babyshkina, Marina Zavyalova, Natalia Tarabanovskaya, Tatyana Dronova, Nadejda Krakhmal, Elena Slonimskaya, Julia Kzhyshkowska, Evgeny Choynzonov, Nadejda Cherdyntseva
The identification of informative biomarkers that could predict the treatment response is particularly important in the triple-negative (TN) breast cancer, which is characterized by biological diversity. The aim of this study was to investigate the impact of vascular endothelial growth factor receptor (VEGFR2) expression and its gene polymorphisms on pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in Russian patients with TN breast cancer. We performed a retrospective analysis of 70 women with operable TN breast cancer, who underwent NCT with 5-fluorouracil, adriamycin, and cyclophosphamide (FAC) or cyclophosphamide, adriamycin, and capecitabine (CAX) between 2007 and 2013...
December 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29229854/interferon-beta-represses-cancer-stem-cell-properties-in-triple-negative-breast-cancer
#2
Mary R Doherty, HyeonJoo Cheon, Damian J Junk, Shaveta Vinayak, Vinay Varadan, Melinda L Telli, James M Ford, George R Stark, Mark W Jackson
Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human mammary epithelial cells that undergo an epithelial-to-mesenchymal transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229759/jmjd6-induces-hotair-an-oncogenic-lincrna-by-physically-interacting-with-its-proximal-promoter
#3
Antara Biswas, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Kartiki V Desai
<span style="color: black;">Using microarray analysis we found that HOX transcript antisense intergenic RNA (HOTAIR) is upregulated by Jumonji domain containing-6 (JMJD6), a bifunctional lysyl hydroxylase and arginine demethylase. In breast cancer, JMJD6 and HOTAIR RNAs increase tumor growth and associate with poor prognosis but no molecular relationship between them is known. We show that overexpression of JMJD6 increased HOTAIR expression and JMJD6 siRNAs suppressed it in ER+ MCF-7, triple negative MDA-MB-231 and non-breast cancer HEK 293 cells...
December 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29229607/race-disparities-in-the-contribution-of-mirna-isoforms-and-trna-derived-fragments-to-triple-negative-breast-cancer
#4
Aristeidis G Telonis, Isidore Rigoutsos
Triple-Negative Breast Cancer (TNBC) is a breast cancer subtype characterized by marked differences between White and Black/African-American women. We performed a systems-level analysis on datasets from The Cancer Genome Atlas (TCGA) to elucidate how the expression patterns of messenger RNAs (mRNAs) are shaped by regulatory non-coding RNAs (ncRNAs). Specifically, we studied isomiRs, i.e. isoforms of microRNAs (miRNAs), and tRNA-derived fragments (tRFs). In normal breast tissue, we observed a marked cohesiveness in both the ncRNA and mRNA layers and the associations between them...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29229414/lipid-droplets-induced-by-secreted-phospholipase-a2and-unsaturated-fatty-acids-protect-breast-cancer-cells-from-nutrient-and-lipotoxic-stress
#5
Eva Jarc, Ana Kump, Petra Malavašič, Thomas O Eichmann, Robert Zimmermann, Toni Petan
Cancer cells driven by the Ras oncogene scavenge unsaturated fatty acids (FAs) from their environment to counter nutrient stress. The human group X secreted phospholipase A2(hGX sPLA2) releases FAs from membrane phospholipids, stimulates lipid droplet (LD) biogenesis in Ras-driven triple-negative breast cancer (TNBC) cells and enables their survival during starvation. Here we examined the role of LDs, induced by hGX sPLA2and unsaturated FAs, in protection of TNBC cells against nutrient stress. We found that hGX sPLA2releases a mixture of unsaturated FAs, including ω-3 and ω-6 polyunsaturated FAs (PUFAs), from TNBC cells...
December 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29228721/dek-promoted-emt-and-angiogenesis-through-regulating-pi3k-akt-mtor-pathway-in-triple-negative-breast-cancer
#6
Yang Yang, Meihua Gao, Zhenhua Lin, Liyan Chen, Yu Jin, Guang Zhu, Yixuan Wang, Tiefeng Jin
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis. As an oncogene, DEK involves in regulation of various cellular metabolisms and plays an important role in tumor growth and progression. Increasing evidences suggested that abnormal expression of DEK is closely related to multiple malignant tumors. However, the possible involvement of DEK in epithelial to mesenchymal transition (EMT) and angiogenesis in TNBC remains unclear. In the present study, we revealed that the over-expression of DEK was significantly correlated with clinical stage, differentiation, and lymph node (LN) metastasis of TNBC and indicated poor overall survival of TNBC patients...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228705/yap1-inhibition-radiosensitizes-triple-negative-breast-cancer-cells-by-targeting-the-dna-damage-response-and-cell-survival-pathways
#7
Daniel Andrade, Meghna Mehta, James Griffith, Janani Panneerselvam, Akhil Srivastava, Tae-Dong Kim, Ralf Janknecht, Terence Herman, Rajagopal Ramesh, Anupama Munshi
The Hippo pathway is an evolutionarily conserved signaling pathway that regulates proliferation and apoptosis to control organ size during developmental growth. Yes-associated protein 1 (YAP1), the terminal effector of the Hippo pathway, is a transcriptional co-activator and a potent growth promoter that has emerged as a critical oncogene. Overexpression of YAP1 has been implicated in promoting resistance to chemo-, radiation and targeted therapy in various cancers. However, the role of YAP1 in radioresistance in triple-negative breast cancer (TNBC) is currently unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228549/er%C3%AE-inhibits-cyclin-dependent-kinases-1-and-7-in-triple-negative-breast-cancer
#8
Jordan M Reese, Elizabeth S Bruinsma, David G Monroe, Vivian Negron, Vera J Suman, James N Ingle, Matthew P Goetz, John R Hawse
Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential drug target. Treatment of ERβ expressing MDA-MB-231 cells with estrogen or the ERβ selective agonist, LY500307, was shown to result in suppression of cell proliferation...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228315/comparison-of-neoadjuvant-nab-paclitaxel-carboplatin-vs-nab-paclitaxel-gemcitabine-in-triple-negative-breast-cancer-randomized-wsg-adapt-tn-trial-results
#9
Oleg Gluz, Ulrike Nitz, Cornelia Liedtke, Matthias Christgen, Eva-Maria Grischke, Helmut Forstbauer, Michael Braun, Mathias Warm, John Hackmann, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, Nikola Bangemann, Christoph Lindner, Sherko Kuemmel, Michael Clemens, Jochem Potenberg, Peter Staib, Andreas Kohls, Raquel von Schumann, Ronald Kates, Ronald Kates, Johannes Schumacher, Rachel Wuerstlein, Hans Heinrich Kreipe, Nadia Harbeck
Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). The optimal chemotherapy regimen is unclear. Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact. We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response. Methods: Patients with TNBC (estrogen receptor/progesterone receptor < 1%, human epidermal growth factor receptor 2-negative, cT1c-cT4c, cN0/+) were randomly assigned to A: nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly (q3w); vs B: nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w...
December 8, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29224274/-correlation-analysis-of-pd-l1-expression-and-prognosis-in-triple-negative-breast-cancers
#10
B J Pan, C Xu, G Q Ping, G X Song, W M Zhang, C Wang, Z H Zhang
Objective: To investigate the relationship between PD-L1 expression and the clinicopathologic features and prognosis in triple-negative breast carcinomas (TNBC). Methods: All 142 cases of TNBC were collected from the First Affiliated Hospital of Nanjing Medical University from February 2011 to December 2014, and the surgical excision or biopsy specimens from patients without chemotherapy and radiotherapy were included. Histopathologic analysis of stromal tumor infiltrating lymphocyte (sTIL) was performed on HE sections, and PD-L1 immunohistochemical staining was done with MaxVision...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29222734/tert-promoter-hotspot-mutations-in-breast-cancer
#11
Tatsunori Shimoi, Masayuki Yoshida, Yuka Kitamura, Tomomi Yoshino, Asuka Kawachi, Akihiko Shimomura, Emi Noguchi, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Takayuki Kinoshita, Koichi Ichimura, Takahiro Fukuda, Yasuhiro Fujiwara, Kenji Tamura
BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations have been discovered in solid and hematological malignancies, where they reflect TERT activation and cell-cycle progression. In melanoma, glioma, and thyroid cancers, TERT promoter mutations are associated with a poor prognosis. However, no studies have evaluated the prevalence and prognostic significance of TERT promoter mutations in breast cancer. METHODS: We analyzed TERT promoter hotspot mutations (C228T and C250T) using direct sequencing of DNA from 319 tumor tissues...
December 8, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29221130/development-and-cytotoxic-response-of-two-proliferative-mda-mb-231-and-non-proliferative-sum1315-three-dimensional-cell-culture-models-of-triple-negative-basal-like-breast-cancer-cell-lines
#12
Dubois Clémence, Dufour Robin, Daumar Pierre, Aubel Corinne, Szczepaniak Claire, Blavignac Christelle, Mounetou Emmanuelle, Penault-Llorca Frédérique, Mahchid Bamdad
Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers, are very aggressive and with poor prognosis. Targeted therapies have been developed extensively in preclinical and clinical studies to open the way for new treatment strategies. The present study has focused on developing 3D cell cultures from SUM1315 and MDA-MB-231, two triple-negative basal-like (TNBL) breast cancer cell lines, using the liquid overlay technique. Extracellular matrix concentration, cell density, proliferation, cell viability, topology and ultrastructure parameters were determined...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221122/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#13
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220513/integrating-5hmc-and-gene-expression-data-to-infer-regulatory-mechanisms
#14
Cristina Mitrea, Priyanga Wijesinghe, Greg Dyson, Adéle Kruger, Douglas M Ruden, Sorin Draghici, Aliccia Bollig-Fischer
Motivation: Epigenetic mechanisms are known to play a major role in breast cancer. However, the role of 5-hydroxymethylcytosine (5hmC) remains understudied. We hypothesize that 5hmC mediates redox regulation of gene expression in an aggressive subtype known as triple negative breast cancer (TNBC). To address this, our objective was to highlight genes that may be the target of this process by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC changes associated with mRNA changes in TNBC cells...
December 6, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29217770/protein-c-receptor-stimulates-multiple-signaling-pathways-in-breast-cancer-cells
#15
Daisong Wang, Chunye Liu, Jingqiang Wang, Yingying Jia, Xin Hu, Hai Jiang, Zhi-Ming Shao, Yi Arial Zeng
The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and trans-activation of insulin-like growth factor 1 receptor (IGF-1R)...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29217458/imp2-and-imp3-cooperate-to-promote-the-metastasis-of-triple-negative-breast-cancer-through-destabilization-of-progesterone-receptor
#16
Hye-Youn Kim, Huyen Trang Ha Thi, Suntaek Hong
Triple-negative breast cancer (TNBC) is one of the most aggressive malignancies and is associated with high mortality rates due to the lack of effective therapeutic targets. In this study, we demonstrated that insulin-like growth factor-II mRNA-binding protein 2 and 3 (IMP2 and IMP3) are specifically overexpressed in TNBC and cooperate to promote cell migration and invasion. Downregulation of both IMP2 and IMP3 in TNBC cells was found to produce a synergistic effect in suppressing cell invasion and invadopodia formation, whereas overexpression of IMP2 and IMP3 in luminal subtype cells enhanced epithelial-mesenchymal transition and metastasis...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29216867/protein-kinase-c-%C3%AE-enhances-migration-of-breast-cancer-cells-through-foxc2-mediated-repression-of-p120-catenin
#17
Thao N D Pham, Bethany E Perez White, Huiping Zhao, Fariborz Mortazavi, Debra A Tonetti
BACKGROUND: Despite recent advances in the diagnosis and treatment of breast cancer, metastasis remains the main cause of death. Since migration of tumor cells is considered a prerequisite for tumor cell invasion and metastasis, a pressing goal in tumor biology has been to elucidate factors regulating their migratory activity. Protein kinase C alpha (PKCα) is a serine-threonine protein kinase implicated in cancer metastasis and associated with poor prognosis in breast cancer patients...
December 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29216863/ccl5-ccr5-interactions-modulate-metabolic-events-during-tumor-onset-to-promote-tumorigenesis
#18
Darrin Gao, Lisa H Cazares, Eleanor N Fish
BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces the proliferation and survival of breast cancer cells in a mechanistic target of rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in the context of regulating tumor metabolism...
December 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29216710/a-novel-prognostic-nomogram-for-predicting-risks-of-distant-failure-in-patients-with-invasive-breast-cancer-following-postoperative-adjuvant-radiotherapy
#19
Yu Jin Lim, Sea-Won Lee, Noorie Choi, Jeanny Kwon, Keun-Yong Eom, Eunyoung Kang, Eun-Kyu Kim, Jee Hyun Kim, Yu Jung Kim, Se Hyun Kim, So Yeon Park, In Ah Kim
Purpose: This study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer. Materials and Methods: A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model. Results: The 7-year overall survival and 5-year post-progression survival of locoregional vs...
December 7, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29216628/mir-212-5p-suppresses-the-epithelial-mesenchymal-transition-in-triple-negative-breast-cancer-by-targeting-prrx2
#20
Zhi-Dong Lv, Dong-Xia Yang, Xiang-Ping Liu, Li-Ying Jin, Xin-Gang Wang, Zhao-Chuan Yang, Dong Liu, Jiao-Jiao Zhao, Bin Kong, Fu-Nian Li, Hai-Bo Wang
BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of miR-212-5p in TNBC. METHODS: Realtime PCR was used to quantify miR-212-5p expression levels in 30 paired TNBC samples and adjacent normal tissues. Wound healing and Transwell assays were used to evaluate the effects of miR-212-5p expression on the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p...
December 6, 2017: Cellular Physiology and Biochemistry
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