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Breast cancer triple negative

Ya Chen, Yong Tang, Beibei Mao, Wenchao Li, Hongwei Jin, Liangren Zhang, Zhenming Liu
Any type of breast cancer not expressing genes of the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) is referred to as triple-negative breast cancer (TNBC). Accordingly, TNBCs do not respond to hormonal therapies or medicines targeting the ER, PR, or HER2. Systemic chemotherapy is therefore the only treatment option available today and prognoses remain poor. We report the discovery and characterization of N-(naphtho[1,2-b]furan-5-yl)benzenesulfonamides as selective inhibitors of TNBCs...
March 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Fariba Tayyari, G A Nagana Gowda, Olufunmilayo F Olopade, Richard Berg, Howard H Yang, Maxwell P Lee, Wilfred F Ngwa, Suresh K Mittal, Daniel Raftery, Sulma I Mohammed
Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology...
February 20, 2018: Oncotarget
Jingxiao Wang, Xinjie Yang, Haibo Han, Limin Wang, Weiqian Bao, Shanshan Wang, Robert M Hoffman, Meng Yang, Hui Qi, Chao An, Kaiwen Hu
Objective: Triple-negative breast cancer (TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu (TBM), the rhizome of Bolbostemma paniculatum (Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu (ETBM) on TNBC orthotopic mouse models and cell lines. Methods: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Rokaya El Ansari, Madeleine L Craze, Maria Diez-Rodriguez, Christopher C Nolan, Ian O Ellis, Emad A Rakha, Andrew R Green
Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. SLC3A2 was assessed at the genomic level, using METABRIC data (n = 1980), and at the proteomic level, using immunohistochemistry on tissue microarray (TMA) sections constructed from a large well-characterised primary BC cohort (n = 2500)...
March 16, 2018: British Journal of Cancer
Ivana Vrhovac Madunić, Josip Madunić, Maja Antunović, Mladen Paradžik, Vera Garaj-Vrhovac, Davorka Breljak, Inga Marijanović, Goran Gajski
Apigenin is found in several dietary plant foods such as vegetables and fruits. To investigate potential anticancer properties of apigenin on human breast cancer, ER-positive MCF-7 and triple-negative MDA MB-231 cells were used. Moreover, toxicological safety of apigenin towards normal cells was evaluated in human lymphocytes. Cytotoxicity of apigenin towards cancer cells was evaluated by MTT assay whereas further genotoxic and oxidative stress parameters were measured by comet and lipid peroxidation assays, respectively...
March 14, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Balraj Singh, Vanessa N Sarli, Laura J Washburn, Milan R Raythatha, Anthony Lucci
We previously described a strategy for selecting highly adaptable rare triple-negative breast cancer (TNBC) cells based on their ability to survive a severe and prolonged metabolic challenge, e.g., a lack of glutamine. We hypothesized that metabolically adaptable (MA) cancer cells selected from the SUM149 cell line in this manner have the capacity to survive a variety of challenges that postulated "decathlon winner" cancer cells must survive to succeed in metastasis. These MA cells were resistant to glutaminase inhibitor CB-839, as predicted from their ability to proliferate without exogenous glutamine...
February 16, 2018: Oncotarget
Jia-Ming Zhang, Kai Wei, Ming Jiang
BACKGROUND: Octamer-binding transcription factor 4 (OCT4) and SRY (sex determining region Y)-box 2 (SOX2) are common biomarkers of cancer stem cells, which contribute to the pathological processes of several carcinomas, while little is known about the effects of OCT4 and SOX2 on the prognosis of triple-negative breast cancer (TNBC). The purpose was to evaluate the correlation of tumor tissue OCT4 and SOX2 expressions with clinicopathological features and overall survival (OS) in surgical TNBC patients...
March 13, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Zhenya Jia, Jian Zhang, Zhonghua Wang, Biyun Wang, Leiping Wang, Jun Cao, Zhonghua Tao, Xichun Hu
Serum lactate dehydrogenase (LDH) level is predictive of prognosis in various malignancies. Nevertheless, the association between the prognosis of patients with advanced triple-negative breast cancer (TNBC) and LDH is not well understood. This explorative and retrospective study was conducted to clarify the issue. We found that abnormal baseline LDH levels (> 250 IU/L) were significantly associated with age (> 40 y vs. ≤ 40 y, OR: 0.383, P = 0.031) and number of metastatic sites (2 vs. 1, OR: 4.619, P = 0...
February 13, 2018: Oncotarget
Nirmesh Patel, Daniel Weekes, Konstantinos Drosopoulos, Patrycja Gazinska, Elodie Noel, Mamun Rashid, Hasan Mirza, Jelmar Quist, Fara Brasó-Maristany, Sumi Mathew, Riccardo Ferro, Ana Mendes Pereira, Cynthia Prince, Farzana Noor, Erika Francesch-Domenech, Rebecca Marlow, Emanuele de Rinaldis, Anita Grigoriadis, Spiros Linardopoulos, Pierfrancesco Marra, Andrew N J Tutt
Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies and validates gene addictions in TNBCs. CNAs and gene expression alterations are integrated and genes scored for pre-specified target features revealing 130 candidate genes. We test functional dependence on each of these genes using RNAi in breast cancer and non-malignant cells, validating malignant cell selective dependence upon 37 of 130 genes...
March 13, 2018: Nature Communications
Emilie Clement, Hiroyuki Inuzuka, Naoe T Nihira, Wenyi Wei, Alex Toker
The PI3K-AKT kinase signaling pathway is frequently deregulated in human cancers, particularly breast cancer, where amplification and somatic mutations of PIK3CA occur with high frequency in patients. Numerous small-molecule inhibitors targeting both PI3K and AKT are under clinical evaluation, but dose-limiting toxicities and the emergence of resistance limit therapeutic efficacy. Various resistance mechanisms to PI3K inhibitors have been identified, including de novo mutations, feedback activation of AKT, or cross-talk pathways...
March 13, 2018: Science Signaling
J J Zhu, D C Jiao, J H Qiao, L N Wang, Y Z Ma, Z D Lu, Z Z Liu
Objective: To explore the expression of androgen receptor (AR) in the tissues as well as its association with the clinicopathological factors of primary breast cancer patients treated with neoadjuvant chemotherapy (NAC), and analyze the effect of AR in the prediction of pathologic complete response (PCR) rate. Method: A total of 668 breast cancer patients treated with NAC in Henan Cancer Hospital between March 2014 and June 2017 were retrospectively reviewed. The relationship of AR expression and clinicopathological characteristics was calculated using chi square test...
February 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Katyayani Tatiparti, Samaresh Sau, Kaustubh A Gawde, Arun K Iyer
Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of the logical and economical approaches is to develop a tumor hypoxia-targeting drug formulation platform for selective delivery of payload to the drug-resistant and invasive cell population of TNBC tumors...
March 13, 2018: International Journal of Molecular Sciences
Glenwood D Goss, Everett E Vokes, Michael S Gordon, Leena Gandhi, Kyriakos P Papadopoulos, Drew W Rasco, JuDee S Fischer, Katharine L Chu, William W Ames, Rajendar K Mittapalli, Ho-Jin Lee, Jiewei Zeng, Lisa A Roberts-Rapp, Lise I Loberg, Peter J Ansell, Edward B Reilly, Christopher J Ocampo, Kyle D Holen, Anthony W Tolcher
BACKGROUND: Epidermal growth factor receptor (EGFR) alterations are associated with multiple cancers. Current EGFR-directed therapies have led to increased efficacy but are associated with specific side effects. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) targets EGFR with a monoclonal antibody linked to a cytotoxin, and is highly tumor-specific. METHODS: This phase 1/2 study evaluated the safety, pharmacokinetics, and efficacy of depatux-m in patients who had advanced solid tumors with known wild-type EGFR overexpression, amplification, or mutated EGFR variant III...
March 13, 2018: Cancer
Artur Beberok, Dorota Wrześniok, Jakub Rok, Zuzanna Rzepka, Michalina Respondek, Ewa Buszman
Fluoroquinolone antibiotics induce cytotoxicity in various cancer cell lines and may therefore represent a potentially important source of novel anticancer agents. The aim of the present study was to examine the effect of ciprofloxacin on the viability, redox balance, apoptosis, expression of p53, Bax and Bcl-2, cell cycle distribution and DNA fragmentation of triple-negative MDA-MB-231 breast cancer cells. The results of the present study demonstrated that ciprofloxacin decreases cell viability in a dose- and time-dependent manner...
March 8, 2018: International Journal of Oncology
Eunpi Cho, Qian Wu, Lena Rubinstein, Hannah Linden, Julie Gralow, Jennifer Specht, Vijayakrishna Gadi, Georgiana Ellis
Many studies have sought to optimize the dosing schedule of adjuvant chemotherapy in early-stage breast cancer. Here, we assessed the use of continuous metronomic weekly doxorubicin plus daily oral cyclophosphamide (AC) with continuous G-CSF growth factor support for 12 weeks followed by weekly nab-paclitaxel (nP) for 12 weeks. A nonrandomized phase II clinical trial was designed to assess (1) DFS at 2 years, (2) dose delivered, (3) use of nP in the adjuvant setting, and (4) toxicities. The dosing of A was 24 mg/m2 IV weekly and C was 60 mg/m2 oral daily (with scheduled filgrastim 5mcg/kg 6 days/week); nP, 100 mg/m2 IV weekly...
March 13, 2018: Breast Journal
Tia H Turner, Mohammad A Alzubi, Sahib S Sohal, Amy L Olex, Mikhail G Dozmorov, J Chuck Harrell
PURPOSE: Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. METHODS: We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro...
March 12, 2018: Breast Cancer Research and Treatment
A Mukherjee, R Russell, Suet-Feung Chin, B Liu, O M Rueda, H R Ali, G Turashvili, B Mahler-Araujo, I O Ellis, S Aparicio, C Caldas, E Provenzano
The integration of genomic and transcriptomic profiles of 2000 breast tumours from the METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort revealed ten subtypes, termed integrative clusters (IntClust/s), characterised by distinct genomic drivers. Central histopathology ( N  = 1643) review was undertaken to explore the relationship between these ten molecular subtypes and traditional clinicopathological features. IntClust subtypes were significantly associated with histological type, tumour grade, receptor status, and lymphocytic infiltration ( p  < 0...
2018: NPJ Breast Cancer
Quan Li, Zhou-Ci Zheng, Chun-Jue Ni, Wen-Xu Jin, Yi-Xiang Jin, Yao Chen, Xiao-Hua Zhang, En-Dong Chen, Ye-Feng Cai
BACKGROUND: Among all kinds of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive, with the poorest prognosis and highest mortality rates. Thus, novel biomarkers that personalize the therapeutic regimen and evaluate prognosis for TNBC patients should be determined. METHODS: We analyzed the cystatin E/M (CST6) expression profiles of 161 TNBC tissues and 14 noncancerous tissues through multiple statistical analyses. We also investigated the relationship of CST6 expression with clinical parameters and evaluated the prognostic value of CST6 in 161 TNBC patients...
January 2018: Annals of Clinical and Laboratory Science
Ye Ding, Dengfeng Li, Chunyong Ding, Pingyuan Wang, Zhiqing Liu, Eric A Wold, Na Ye, Haiying Chen, Mark Andrew White, Qiang Shen, Jia Zhou
Covalent drug discovery has undergone a resurgence in recent years due to comprehensive optimization of structure-activity relationship (SAR) and structure-reactivity relationship (SRR) for covalent drug candidates. The natural product oridonin maintains an impressive pharmacological profile through its covalent enone warhead on the D-ring and has attracted substantial SAR studies to characterize its potential in the development of new molecular entities for the treatment of various human cancers and inflammation...
March 12, 2018: Journal of Medicinal Chemistry
Xuanxuan Wang, Hai Liu, Liming Shi, Xiaoli Yu, Yanjun Gu, Xiaonan Sun
LncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) is an lncRNA which promotes therapeutic resistance in triple-negative breast cancer (TNBC). However, the expression and function of LINP1 in cervical cancer is not yet well-understood. In this study, we evaluated the expression levels of LINP1 in tumor tissues and cell lines of cervical cancer. We found that LINP1 associates with NHEJ proteins (Ku80 and DNA-PKcs). LINP1 translocates from cytosol to nucleus in response to irradiation. In addition, LINP1 knockdown significantly increases the levels of cleaved caspase3 and PARP, leading to enhanced cell apoptosis after ionizing radiation (IR)...
March 12, 2018: Cell Cycle
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