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https://www.readbyqxmd.com/read/28430626/expression-of-pd-l1-and-prognosis-in-breast-cancer-a-meta-analysis
#1
Minghui Zhang, Houbin Sun, Shu Zhao, Yan Wang, Haihong Pu, Yan Wang, Qingyuan Zhang
The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest. However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to assess the association between PD-L1 protein expression and clinicopathological features and the impact of this relationship on breast cancer survival. We performed a systematic search of the PubMed, EMBASE, and Cochrane Library databases to determine the correlations among PD-L1 expression, clinicopathological features and overall survival (OS)...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#2
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427809/picrasidine-g-decreases-viability-of-mda-mb-468-egfr-overexpressing-triple-negative-breast-cancer-cells-through-inhibition-of-egfr-stat3-signaling-pathway
#3
Naoya Yamashita, Manami Kondo, Shuai Zhao, Wei Li, Kazuo Koike, Kiyomitsu Nemoto, Yuichiro Kanno
Targeted therapy is unavailable for treating patients with triple-negative breast cancer (TNBC), which accounts for approximately 15% of all breast cancers. Overexpression of epidermal growth factor receptor (EGFR) is observed in approximately 30-60% of TNBCs. Therefore, developing novel strategies for inhibiting EGFR signaling is required. In the present study, a natural compound library was screened to identify molecules that target TNBCs that overexpress EGFR. Picrasidine G (PG), a naturally occurring dimeric alkaloid produced by Picrasma quassioides, decreased the viability of the MDA-MB 468 cell line (TNBC(EGFR+)) compared with other breast cancer cell lines...
March 23, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28427212/high-myc-expression-and-transcription-activity-underlies-intra-tumoral-heterogeneity-in-triple-negative-breast-cancer
#4
Nidhi Gupta, Karen Jung, Chengsheng Wu, Abdulraheem Alshareef, Hind Alqahtani, Sambasivarao Damaraju, John R Mackey, Sunita Ghosh, Siham Sabri, Bassam S Abdulkarim, Gilbert Bigras, Raymond Lai
We have previously identified a novel intra-tumoral dichotomy in triple-negative breast cancer (TNBC) based on the differential responsiveness to a reporter containing the Sox2 regulatory region-2 (SRR2), with reporter responsive (RR) cells being more stem-like than reporter unresponsive (RU) cells. Using bioinformatics, we profiled the protein-DNA binding motifs of SRR2 and identified Myc as one of the potential transcription factors driving SRR2 activity. In support of its role, Myc was found to be highly expressed in RR cells as compared to RU cells...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425453/aptamer-mediated-impairment-of-egfr-integrin-%C3%AE-v%C3%AE-3-complex-inhibits-vasculogenic-mimicry-and-growth-of-triple-negative-breast-cancers
#5
Simona Camorani, Elvira Crescenzi, Matteo Gramanzini, Monica Fedele, Antonella Zannetti, Laura Cerchia
Current treatment options for triple-negative breast cancers (TNBCs) is limited by the absence of well-defined biomarkers, excluding a targeted therapy. Notably, epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of TNBCs and is a negative prognostic factor. In clinical trials, however, existing EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a valid alternative to antibodies for diagnostic and therapeutic uses. Here, we prove that, when applied to aggressive TNBC cell lines with unique stem-like plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents the vasculogenic mimicry (VM) capability of the cells and destroys previously formed channels in three-dimensional culture...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424227/onc201-demonstrates-anti-tumor-effects-in-both-triple-negative-and-non-triple-negative-breast-cancers-through-trail-dependent-and-trail-independent-mechanisms
#6
Marie D Ralff, Christina L B Kline, Ozan C Küçükkase, Jessica Wagner, Bora Lim, David T Dicker, Varun V Prabhu, Wolfgang Oster, Wafik S El-Deiry
Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13)--. A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2...
April 19, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28423652/suppressive-role-exerted-by-microrna-29b-1-5p-in-triple-negative-breast-cancer-through-spin1-regulation
#7
Rosa Drago-Ferrante, Francesca Pentimalli, Daniela Carlisi, Anna De Blasio, Christian Saliba, Shawn Baldacchino, James Degaetano, Joseph Debono, Gordon Caruana-Dingli, Godfrey Grech, Christian Scerri, Giovanni Tesoriere, Antonio Giordano, Renza Vento, Riccardo Di Fiore
MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423538/gene-regulatory-pattern-analysis-reveals-essential-role-of-core-transcriptional-factors-activation-in-triple-negative-breast-cancer
#8
Li Min, Cheng Zhang, Like Qu, Jialiang Huang, Lan Jiang, Jiafei Liu, Luca Pinello, Guo-Cheng Yuan, Chengchao Shou
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Genome-scale molecular characteristics and regulatory mechanisms that distinguish TNBC from other subtypes remain incompletely characterized. RESULTS: By combining gene expression analysis and PANDA network, we defined three different TF regulatory patterns. A core TNBC-Specific TF Activation Driven Pattern (TNBCac) was specifically identified in TNBC by computational analysis...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423492/onc201-activates-er-stress-to-inhibit-the-growth-of-triple-negative-breast-cancer-cells
#9
Xun Yuan, Dhonghyo Kho, Jing Xu, Ambikai Gajan, Kongming Wu, Gen Sheng Wu
ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC cells that have developed acquired TRAIL resistance...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422142/g-protein-coupled-kiss1-receptor-is-overexpressed-in-triple-negative-breast-cancer-and-promotes-drug-resistance
#10
Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya
Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421181/mct1-in-invasive-ductal-carcinoma-monocarboxylate-metabolism-and-aggressive-breast-cancer
#11
Jennifer M Johnson, Paolo Cotzia, Roberto Fratamico, Lekha Mikkilineni, Jason Chen, Daniele Colombo, Mehri Mollaee, Diana Whitaker-Menezes, Marina Domingo-Vidal, Zhao Lin, Tingting Zhan, Madalina Tuluc, Juan Palazzo, Ruth C Birbe, Ubaldo E Martinez-Outschoorn
Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28418843/cd24-expression-and-differential-resistance-to-chemotherapy-in-triple-negative-breast-cancer
#12
Xinyu Deng, Sophia Apple, Hong Zhao, Jeongyoon Song, Minna Lee, William Luo, Xiancheng Wu, Debra Chung, Richard J Pietras, Helena R Chang
Breast cancer (BC) is a leading cause of cancer-related death in women. Adjuvant systemic chemotherapies are effective in reducing risks of recurrence and have contributed to reduced BC mortality. Although targeted adjuvant treatments determined by biomarkers for endocrine and HER2-directed therapies are largely successful, predicting clinical benefit from chemotherapy is more challenging. Drug resistance is a major reason for treatment failures. Efforts are ongoing to find biomarkers to select patients most likely to benefit from chemotherapy...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418078/induction-of-mitochondrial-apoptotic-pathway-in-triple-negative-breast-carcinoma-cells-by-methylglyoxal-via-generation-of-reactive-oxygen-species
#13
Anirban Roy, Manisha Ahir, Saurav Bhattacharya, Pravat Kumar Parida, Arghya Adhikary, Kuladip Jana, Manju Ray
Triple negative breast cancer (TNBC) tends to form aggressive tumors associated with high mortality and morbidity which urge the need for development of new therapeutic strategies. Recently the normal metabolite Methylglyoxal (MG) has been documented for its anti-proliferative activity against human breast cancer. However, the mode of action of MG against triple negative breast cancer remains open to question. In our study, we investigated the anticancer activity of MG in MDA MB 231 and 4T1 TNBC cell lines and elucidated the underlying mechanisms...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28417335/poor-prognosis-of-patients-with-triple-negative-breast-cancer-can-be-stratified-by-rank-and-rankl-dual-expression
#14
Monica E Reyes, Takeo Fujii, Daniel Branstetter, Savitri Krishnamurthy, Hiroko Masuda, Xiaoping Wang, James M Reuben, Wendy A Woodward, Beatrice J Edwards, Gabriel N Hortobagyi, Debu Tripathy, William C Dougall, Bedrich L Eckhardt, Naoto T Ueno
PURPOSE: As clinical studies have correlated RANK expression levels with survival in breast cancer, and that RANK signaling is dependent on its cognate ligand RANKL, we hypothesized that dual protein expression further stratifies the poor outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC using genomic databases, cell lines and in a tissue microarray of curated primary tumor samples derived from 87 patients with TNBC. RANK expression was evaluated either by Mann-Whitney U test on log-normalized gene expression data or by Student's t test on FACS data...
April 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28416606/tra2a-promoted-paclitaxel-resistance-and-tumor-progression-in-triple-negative-breast-cancers-via-regulating-alternative-splicing
#15
Tieju Liu, Huizhi Sun, Dongwang Zhu, Xueyi Dong, Fang Liu, Xiaohui Liang, Chen Chen, Bing Shao, Meili Wang, Yi Wang, Baocun Sun
Treatment of triple-negative breast cancer (TNBC) has been challenging and paclitaxel (PTX) resistance is one of the major obstacles to the better prognosis. Deregulation of alternative splicing (AS) may contribute to tumor progression and chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival and therapeutic sensitivity. However the individual role of TRA2A in cancer progression has not been reported. Here we report that TRA2A facilitates proliferation and survival, migration and invasion of TNBC cells...
April 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28415882/rage-receptor-targeted-bioconjuguate-lipid-nanoparticles-of-diallyl-disulfide-for-improved-apoptotic-activity-in-triple-negative-breast-cancer-in-vitro-studies
#16
Venkata Talluri Siddhartha, Sai Kiran S S Pindiprolu, Pavan Kumar Chintamaneni, Shashank Tummala, S Nandha Kumar
In the present study, we have demonstrated receptor for advanced glycation endproducts (RAGE) as a target for delivery of drugs specifically to triple negative breast cancer cells. We have prepared solid lipid nanoparticle formulation of cytotoxic agent di-allyl-disulfide (DADS) to overcome its bioavailability issues. Then, we have surface modified DADS-loaded solid lipid nanoparticles (DADS-SLN) with RAGE antibody to achieve site-specific delivery of DADS to TNBC cells. We found a significant cellular internalization of RAGE surface modified DADS-SLN (DADS-RAGE-SLN) when compared to DADS-SLN...
April 17, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28415798/tumor-derived-il-18-induces-pd-1-expression-on-immunosuppressive-nk-cells-in-triple-negative-breast-cancer
#17
In Hae Park, Han Na Yang, Kyoung Joo Lee, Tae-Sik Kim, Eun Sook Lee, So-Youn Jung, Youngmee Kwon, Sun-Young Kong
PURPOSE: While the inflammatory cytokine interleukin-18 (IL-18) is known to activate natural killer (NK) cells, its precise role in cancer is controversial. In this study, we investigated the role of tumor-derived IL-18 on peripheral blood NK cells in breast cancer patients. RESULTS: In breast cancer cell lines, IL-18 was expressed and secreted in the triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and HCC-70 but not in MCF-7 cells. The immature and non-cytotoxic CD56dimCD16dim/- NK cell fraction was increased following co-culture with MDA-MB-231 cells, and this increase was not observed with tumor cells transfected with siRNA for IL-18 or in MCF-7 cells...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415760/binding-of-galectin-1-to-integrin-%C3%AE-1-potentiates-drug-resistance-by-promoting-survivin-expression-in-breast-cancer-cells
#18
KeeSoo Nam, Seog-Ho Son, Sunhwa Oh, Donghwan Jeon, Hyungjoo Kim, Dong-Young Noh, Sangmin Kim, Incheol Shin
Galectin-1 is a β-galactoside binding protein secreted by many types of aggressive cancer cells. Although many studies have focused on the role of galectin-1 in cancer progression, relatively little attention has been paid to galectin-1 as an extracellular therapeutic target. To elucidate the molecular mechanisms underlying galectin-1-mediated cancer progression, we established galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA) against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415749/hmagea2-promotes-progression-of-breast-cancer-by-regulating-akt-and-erk1-2-pathways
#19
Song Park, Yonghun Sung, Jain Jeong, Minjee Choi, Jinhee Lee, Wookbong Kwon, Soyoung Jang, Si Jun Park, Hyeng-Soo Kim, Mee-Hyun Lee, Dong Joon Kim, Kangdong Liu, Sung-Hyun Kim, Zigang Dong, Zae Young Ryoo, Myoung Ok Kim
Breast cancer is the most abundant cancer worldwide and a severe problem for women. Notably, breast cancer has a high mortality rate, mainly because of tumor progression and metastasis. Triple-negative breast cancer (TNBC) is highly progressive and lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Therefore, there are no established therapeutic targets against TNBC. In this study, we investigated whether the expression of human melanoma-associated antigen A2 (MAGEA2) is associated with TNBC...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415597/phosphorylation-of-androgen-receptors-at-serine-515-is-a-potential-prognostic-marker-for-triple-negative-breast-cancer
#20
Antonia K Roseweir, Pamela McCall, Alison Scott, Benjamin Liew, Zhi Lim, Elizabeth A Mallon, Joanne Edwards
1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry...
March 21, 2017: Oncotarget
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