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https://www.readbyqxmd.com/read/28545975/quinazolinone-derivatives-as-inhibitors-of-homologous-recombinase-rad51
#1
Ambber Ward, Lilong Dong, Jonathan M Harris, Kum Kum Khanna, Fares Al-Ejeh, David P Fairlie, Adrian P Wiegmans, Ligong Liu
RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28544579/frizzled7-antibody-functionalized-nanoshells-enable-multivalent-binding-for-wnt-signaling-inhibition-in-triple-negative-breast-cancer-cells
#2
Rachel S Riley, Emily S Day
Antibodies that antagonize cell signaling pathways specific to their targeted receptor are invaluable tools to study and treat malignancies, but their utility is limited by high production costs and treatment dosages. Researchers have shown that antibodies conjugated to nanoparticles display increased affinity for their target relative to freely delivered antibodies due to multivalency, and this study investigates how this multivalency can enable antibody-nanoparticle conjugates to inhibit oncogenic cell signaling more effectively than freely delivered antibodies...
May 22, 2017: Small
https://www.readbyqxmd.com/read/28542297/rim-sign-and-histogram-analysis-of-apparent-diffusion-coefficient-values-on-diffusion-weighted-mri-in-triple-negative-breast-cancer-comparison-with-er-positive-subtype
#3
Yangsean Choi, Sung Hun Kim, In Kyung Youn, Bong Joo Kang, Woo-Chan Park, Ahwon Lee
PURPOSE: To investigate associations between the clinicopathologic features and MRI features of triple-negative breast cancer (TNBC) and ER-positive breast cancer (BC) via apparent diffusion coefficient (ADC) histogram analysis. MATERIALS AND METHODS: In this study, 221 breast cancer patients with pre-operative MRI performed from August 2009 to March 2015 were included in a retrospective analysis. All patients had a pathologically confirmed diagnosis of invasive carcinoma and were grouped into ER-positive (149) or triple-negative (72) subtypes...
2017: PloS One
https://www.readbyqxmd.com/read/28540980/low-expression-of-circulating-microrna-34c-is-associated-with-poor-prognosis-in-triple-negative-breast-cancer
#4
Zhihao Zeng, Xiaowu Chen, Dajian Zhu, Zhongran Luo, Min Yang
PURPOSE: The microRNA-34 (miR-34) family is important in tumor regulation. This study aimed to investigate the association of circulating miR-34 family proteins with clinicopathological features and their prognostic value in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: In this cohort study, 173 TNBC patients admitted to First People's Hospital of Shunde from May 1, 2009 to April 30, 2013 were enrolled. Meanwhile, 75 age-matched healthy women volunteers were identified as healthy controls (HCs)...
July 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28536943/change-in-sonographic-brightness-can-predict-pathological-response-of-triple-negative-breast-cancer-to-neoadjuvant-chemotherapy
#5
Naoko Matsuda, Kumiko Kida, Sachiko Ohde, Koyu Suzuki, Hideko Yamauchi, Seigo Nakamura, Hiroko Tsunoda
INTRODUCTION: Ultrasound (US) is conventionally performed to determine effects of neoadjuvant chemotherapy (NAC) on breast cancer. In patients with triple-negative breast cancer (TNBC), higher pathological complete response (pCR) predicts the most favorable survival outcome. We aimed to predict pCR to NAC using echogenicity changes in US region of interest (ROI) in patients with TNBC. METHODS AND MATERIALS: We retrospectively determined clinicopathological characteristics of 52 patients with primary TNBC who underwent NAC...
May 23, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28536704/calpain-1-expression-in-triple-negative-breast-cancer-a-potential-prognostic-factor-independent-of-the-proliferative-apoptotic-index
#6
Shadia M Al-Bahlani, Ruqaya M Al-Rashdi, Shiyam Kumar, Shadia S Al-Sinawi, Maiya A Al-Bahri, Asem A Shalaby
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer in which calpain system plays an important role in its cellular processes including apoptosis and proliferation. Although such roles have been assessed in tumor pathogenesis, the correlation of its expression to the proliferating/apoptotic index has not been studied yet. Immunohistochemical staining of calpain-1 was performed on paraffin-embedded tissues to correlate its expression with clinicopathological variables and outcome. The proliferation activity was determined by calculating the percentage of cells expressing the Ki-67 antigen...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28535016/nherf1-inhibits-proliferation-of-triple-negative-breast-cancer-cells-by-suppressing-gper-signaling
#7
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/28533703/differential-expression-of-vegfr2-protein-in-her2-positive-primary-human-breast-cancer-potential-relevance-to-anti-angiogenic-therapies
#8
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/28531218/autophagy-inhibitor-facilitates-gefitinib-sensitivity-in-vitro-and-in-vivo-by-activating-mitochondrial-apoptosis-in-triple-negative-breast-cancer
#9
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/28530705/ccn5-wisp-2-restores-er-%C3%A2-in-normal-and-neoplastic-breast-cells-and-sensitizes-triple-negative-breast-cancer-cells-to-tamoxifen
#10
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
#11
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
#12
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
#13
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
#14
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/28528300/treating-metastatic-triple-negative-breast-cancer-with-cd44-neuropilin-dual-molecular-targets-of-multifunctional-nanoparticles
#15
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
#16
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/28523352/interim-heterogeneity-changes-measured-using-entropy-texture-features-on-t2-weighted-mri-at-3-0%C3%A2-t-are-associated-with-pathological-response-to-neoadjuvant-chemotherapy-in-primary-breast-cancer
#17
Shelley Henderson, Colin Purdie, Caroline Michie, Andrew Evans, Richard Lerski, Marilyn Johnston, Sarah Vinnicombe, Alastair M Thompson
OBJECTIVES: To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim)...
May 18, 2017: European Radiology
https://www.readbyqxmd.com/read/28521427/immunoexpression-of-lactoferrin-in-triple-negative-breast-cancer-patients-a-proposal-to-select-a-less-aggressive-subgroup
#18
Antonio Ieni, Valeria Barresi, Luana Licata, Roberta Cardia, Carmine Fazzari, Giuseppe Nuciforo, Francesco Caruso, Michele Caruso, Vincenzo Adamo, Giovanni Tuccari
Triple-negative breast cancer (TNBC) indicates a subset of breast carcinomas that does not express estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). According to the literature, TNBCs are aggressive tumors, characterized by a high incidence of recurrence and a high risk of disease progression. Lactoferrin (LF) is a single-chain, iron-binding glycoprotein of ~700 amino acids, which is involved in a wide range of biological activities, including iron-trafficking and carcinogenesis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520849/beta-blockers-and-improved-progression-free-survival-in-patients-with-advanced-her2-negative-breast-cancer-a-retrospective-analysis-of-the-rose-trio-012-study
#19
G Spera, R Fresco, H Fung, J R B Dyck, E Pituskin, I Paterson, J R Mackey
Background: Recent retrospective studies suggest that beta-adrenergic blocking drugs (BB) are associated with improved outcomes in people with a range of cancers. Although limited and discordant data suggest that BB may increase overall survival (OS) of patients with localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC. Patients and Methods: To explore the association between BB use and BC outcomes, we retrospectively reviewed the ROSE/TRIO-012, a double-blinded, multinational phase III trial that randomized 1,144 patients with HER2-negative advanced BC to first-line docetaxel in combination with ramucirumab or placebo...
May 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28515445/protein-kinase-c-inhibitor-chelerythrine-selectively-inhibits-proliferation-of-triple-negative-breast-cancer-cells
#20
Wanjun Lin, Jiajun Huang, Zhongwen Yuan, Senling Feng, Ying Xie, Wenzhe Ma
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targeted therapy currently. Recent studies imply that protein kinase C may play important roles in TNBC development and could be a specific target. In this study, we evaluated the anti-proliferative activity of PKC inhibitor chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as demonstrated by in vitro cell proliferation assay and colony formation assay, as well as evidenced by in vivo xenograft assay...
May 17, 2017: Scientific Reports
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