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https://www.readbyqxmd.com/read/29352235/systems-modeling-accurately-predicts-responses-to-genotoxic-agents-and-their-synergism-with-bcl-2-inhibitors-in-triple-negative-breast-cancer-cells
#1
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351263/twenty-nine-new-limonoids-with-skeletal-diversity-from-the-mangrove-plant-xylocarpus-moluccensis
#2
Jianzhi Zhang, Wanshan Li, Yiguo Dai, Li Shen, Jun Wu
Twenty-nine new limonoids-named xylomolins A₁-A₇, B₁-B₂, C₁-C₂, D-F, G₁-G₅, H-I, J₁-J₂, K₁-K₂, L₁-L₂, and M-N, were isolated from the seeds of the mangrove plant, Xylocarpus moluccensis. Compounds 1-13 are mexicanolides with one double bond or two conjugated double bonds, while 14 belongs to a small group of mexicanolides with an oxygen bridge between C1 and C8. Compounds 15-19 are khayanolides containing a Δ8,14 double bond, whereas 20 and 21 are rare khayanolides containing a Δ14,15 double bond and Δ8,9, Δ14,15 conjugated double bonds, respectively...
January 19, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29350614/lipg-signaling-promotes-tumor-initiation-and-metastasis-of-human-basal-like-triple-negative-breast-cancer
#3
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29348905/bridging-the-divide-preclinical-research-discrepancies-between-triple-negative-breast-cancer-cell-lines-and-patient-tumors
#4
REVIEW
Andrew Sulaiman, Lisheng Wang
Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer and disproportionately accounts for the majority of breast cancer related deaths. Effective treatment of this disease remains an unmet medical need. Over the past several decades, TNBC cell lines have been used as the foundation for drug development and disease modeling. However, ever-mounting research demonstrates striking differences between cell lines and clinical TNBC tumors, disconnecting bench research and actual clinical responses...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348858/the-survival-benefit-of-neoadjuvant-chemotherapy-and-pcr-among-patients-with-advanced-stage-triple-negative-breast-cancer
#5
Tithi Biswas, Jimmy T Efird, Shreya Prasad, Charulata Jindal, Paul R Walker
Triple negative breast cancer (TNBC) is an aggressive subtype that accounts for 15-20% of cases, with a higher incidence of relapse/death. Even with adjuvant chemotherapy, the 5 year distant metastasis-free survival rate remains low. A total of 452 tumor registry patients with TNBC and no evidence of metastatic disease were identified over the period of 1996-2011. The median age and follow-up time were 51 (range=21-88) and 3.9 (range=0.14-14) years. Approximately 75% of patients with stage III disease received neoadjuvant chemotherapy (NACT) compared with 47% for stage II...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348684/mithramycin-a-suppresses-basal-triple-negative-breast-cancer-cell-survival-partially-via-down-regulating-kr%C3%A3-ppel-like-factor-5-transcription-by-sp1
#6
Rong Liu, Xu Zhi, Zhongmei Zhou, Hailin Zhang, Runxiang Yang, Tianning Zou, Ceshi Chen
As the most malignant breast cancer subtype, triple-negative breast cancer (TNBC) does not have effective targeted therapies clinically to date. As a selective Sp1 inhibitor, Mithramycin A (MIT) has been reported to have anti-tumor activities in multiple cancers. However, the efficacy and the mechanism of MIT in breast cancer, especially TNBC, have not been studied. In this study, we demonstrated that MIT suppressed breast cancer cell survival in a dosage-dependent manner. Interestingly, TNBC cells were more sensitive to MIT than non-TNBC cells...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345474/total-synthesis-of-antiproliferative-parvifloron-f
#7
Yohei Saito, Masuo Goto, Kyoko Nakagawa-Goto
The first total synthesis of parvifloron F, a bioactive highly oxidized abietane diterpene, was achieved. The abietane skeleton was constructed by Lewis acid promoted cyclization. Preliminary structure-activity relationship correlations were established for the synthetic intermediates against human tumor cell lines. Certain compounds showed unique selective antiproliferative activity against triple-negative breast cancer. The oxidation level of the abietane ring affected the selectivity.
January 18, 2018: Organic Letters
https://www.readbyqxmd.com/read/29345290/role-of-nestin-expression-in-angiogenesis-and-breast-cancer-progression
#8
Aleksandra Nowak, Jędrzej Grzegrzółka, Alicja Kmiecik, Aleksandra Piotrowska, Rafał Matkowski, Piotr Dzięgiel
Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344857/adaptation-of-laser-microdissection-technique-to-nanostring-rna-analysis-in-the-study-of-a-spontaneous-metastatic-mammary-carcinoma-mouse-model
#9
Nadia P Castro, Yelena G Golubeva
The mouse model characterized by spontaneous lung metastasis from JygMC (A) cells closely resembles the human triple negative breast cancer (TNBC) subtype. The primary tumors morphologically present both epithelial and spindle-like cells, but metastases in lung parenchyma display only adenocarcinoma properties. In the study of molecular signatures, laser capture microdissection (LCM) on frozen tissue sections was used to separate the following regions of interest: the epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET), carcinoma, lung metastases, normal mammary gland and normal lung parenchyma...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344663/adeno-associated-virus-type-2-mediated-gene-transfer-of-a-short-hairpin-rna-targeting-human-igfbp-2-suppresses-the-proliferation-and-invasion-of-mda-mb-468-cells
#10
Chao Gao, Ru-Song Zhang, Nan Zheng, Chen Wang
Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of breast tumor because of its low pathogenicity and immunogenicity. Our previous study demonstrated that insulin‑like growth factor‑binding protein 2 (IGFBP‑2) was highly expressed in patients with breast metastasis. In the present study, the effects of recombinant AAV2 on the growth and metastasis of breast cancer cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and rAAV2‑ZsGreen‑shRNA‑hIGFBP‑2 were used to transfect MDA‑MB‑468, and MCF‑10A cells respectively, and observed that these virus could not penetrate the normal human breast epithelia MCF‑10A cell line...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344641/inhibition-of-rptor-overcomes-resistance-to-egfr-inhibition-in-triple-negative-breast-cancer-cells
#11
Kyu Sic You, Yong Weon Yi, Sahng-June Kwak, Yeon-Sun Seong
Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth factor signaling and resistance to inhibitors for epidermal growth factor receptor (EGFR), despite the overexpression of EGFR protein, and this is associated with a malignant behavior and a poor prognosis. In this study, to elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify inhibitors that exert a synergistic effect with EGFR inhibition, we examined the inhibitory effects of selected protein kinase inhibitors (PKIs) in combination with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC cell line...
January 15, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344276/the-clinicopathological-features-and-survival-outcomes-of-different-histological-subtypes-in-triple-negative-breast-cancer
#12
Hong-Ye Liao, Wen-Wen Zhang, Jia-Yuan Sun, Feng-Yan Li, Zhen-Yu He, San-Gang Wu
Purpose: To determine the clinicopathological features and survival outcomes of triple-negative breast cancer (TNBC) according to different histological subtypes. Methods: Using the Surveillance, Epidemiology, and End Results database, we included TNBC cases in 2010-2013. The effect of histological subtype on breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed using univariate and multivariate analyses. Results: A total of 19,900 patients were identified. Infiltrating ductal carcinoma not otherwise specified accounted for 91...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344201/elevation-of-serum-cea-and-ca15-3-levels-during-antitumor-therapy-predicts-poor-therapeutic-response-in-advanced-breast-cancer-patients
#13
Yue Yang, Huijuan Zhang, Mingyan Zhang, Qingwei Meng, Li Cai, Qingyuan Zhang
The aim of the present study was to assess the correlation between therapeutic response and carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) levels in advanced breast cancer patients with non-assessable lesions or stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors. A total of 232 female patients with recurrent tumors following radical mastectomy were recruited, including 76 patients with non-assessable lesions and 60 patients with SD. The correlation between CEA and CA15-3 changes, progression-free survival (PFS) and therapeutic response were analyzed in the non-assessable and SD patient groups...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29341321/interleukin-6-contributes-to-chemoresistance-in-mda-mb-231-cells-via-targeting-hif-1%C3%AE
#14
Ke Wang, Xue Zhu, Kai Zhang, Yongxiang Yin, Yu Chen, Ting Zhang
Chemoresistance is a critical challenge in the clinical treatment of triple-negative breast cancer (TNBC). It has been well documented that inflammatory mediators from tumor microenvironment are involved in the pathogenesis of TNBC and might be related to chemoresistance of cancer cells. In this study, the contribution of interleukin-6 (IL-6), one of the principal oncogenic molecules, in chemoresistance of a TNBC cell line MDA-MB-231 was first investigated. The results showed that IL-6 treatment could induce upregulation of HIF-1α via the activation of STAT3 in MDA-MB-231 cells, which consequently contributed to its effect against chemotherapeutic drug-induced cytotoxicity and cell apoptosis...
January 17, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29340907/harnessing-a-different-dependency-how-to-identify-and-target-androgen-receptor-positive-versus-quadruple-negative-breast-cancer
#15
REVIEW
Jessica L Christenson, Jane B Trepel, Haythem Y Ali, Sunmin Lee, Joel R Eisner, Edwina S Baskin-Bey, Anthony D Elias, Jennifer K Richer
The androgen receptor (AR) is a promising therapeutic target for a subset of triple-negative breast cancers (TNBCs) in which AR is expressed. However, the mechanistic action of AR and the degree to which primary and metastatic tumors depend on AR, both before and after conventional treatment, remain to be defined. We discuss preclinical and clinical data for AR+ TNBC, the difficulties in monitoring AR protein levels, new methods for determining AR status, the influence of AR on "stemness" in the context of TNBC, the role of combined inhibition of sex steroid production and AR, and the role of AR in regulation of the immune system...
January 16, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29340880/gata-3-is-superior-to-gcdfp-15-and-mammaglobin-to-identify-primary-and-metastatic-breast-cancer
#16
Yun-Bi Ni, Julia Y S Tsang, Mu-Min Shao, Siu-Ki Chan, Sai-Yin Cheung, Joanna Tong, Ka-Fai To, Gary M Tse
PURPOSE: Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear. METHODS: To address these questions, totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23 distant metastases, and 208 lung carcinomas were included. GATA-3 expression was analyzed by immunohistochemistry and compared to other breast markers [gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)]...
January 16, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29340027/dual-sirt1-expression-patterns-strongly-suggests-its-bivalent-role-in-human-breast-cancer
#17
Khaldoun Rifaï, Gaëlle Judes, Mouhamed Idrissou, Marine Daures, Yves-Jean Bignon, Frédérique Penault-Llorca, Dominique Bernard-Gallon
Breast cancer is the most common cancer in women, and the leading cause of cancer death in women worldwide. SIRT1 (silent mating type information regulation 2 homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation, DNA repair and tumorigenesis. However, its role in breast carcinoma remains controversial, as both tumor-suppressive and tumor-promoting functions have been reported. Also, there are very few reports available where expression of SIRT1 is comprehensively analyzed in breast tumors classified by molecular subtype...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339815/mcl-1-is-a-prognostic-indicator-and-drug-target-in-breast-cancer
#18
Kirsteen J Campbell, Sandeep Dhayade, Nicola Ferrari, Andrew H Sims, Emma Johnson, Susan M Mason, Ashley Dickson, Kevin M Ryan, Gabriela Kalna, Joanne Edwards, Stephen G W Tait, Karen Blyth
Analysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options...
January 16, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29339084/mir-613-inhibits-cell-migration-and-invasion-by-downregulating-daam1-in-triple-negative-breast-cancer
#19
Huaping Xiong, Ting Yan, Weijie Zhang, Fangfang Shi, Xuesong Jiang, Xiaohua Wang, Shoushan Li, Ying Chen, Cheng Chen, Yichao Zhu
Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613...
January 12, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29337092/germline-brca-mutation-and-outcome-in-young-onset-breast-cancer-posh-a-prospective-cohort-study
#20
Ellen R Copson, Tom C Maishman, Will J Tapper, Ramsey I Cutress, Stephanie Greville-Heygate, Douglas G Altman, Bryony Eccles, Sue Gerty, Lorraine T Durcan, Louise Jones, D Gareth Evans, Alastair M Thompson, Paul Pharoah, Douglas F Easton, Alison M Dunning, Andrew Hanby, Sunil Lakhani, Ros Eeles, Fiona J Gilbert, Hisham Hamed, Shirley Hodgson, Peter Simmonds, Louise Stanton, Diana M Eccles
BACKGROUND: Retrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer. METHODS: We did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer...
January 11, 2018: Lancet Oncology
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