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W Liu, J B Li, T Wang, L Bian, S H Zhang, H Q Zhang, J M Zhou, S T Song, Z F Jiang
Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS)...
September 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Meiou Dai, Chenjing Zhang, Ayad Ali, Xinyuan Hong, Jun Tian, Chieh Lo, Nadège Fils-Aimé, Sergio A Burgos, Suhad Ali, Jean-Jacques Lebrun
Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients...
October 19, 2016: Scientific Reports
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
Eva Gross, Harm van Tinteren, Zhou Li, Sandra Raab, Christina Meul, Stefanie Avril, Nadja Laddach, Michaela Aubele, Corinna Propping, Apostolos Gkazepis, Manfred Schmitt, Alfons Meindl, Petra M Nederlof, Marion Kiechle, Esther H Lips
BACKGROUND: Triple-negative breast cancer (TNBC) with a BRCA1-like molecular signature has been demonstrated to remarkably respond to platinum-based chemotherapy and might be suited for a future treatment with poly(ADP-ribose)polymerase (PARP) inhibitors. In order to rapidly assess this signature we have previously developed a multiplex-ligation-dependent probe amplification (MLPA)-based assay. Here we present an independent validation of this assay to confirm its important clinical impact...
October 19, 2016: BMC Cancer
Domenico Ribatti, Beatrice Nico, Simona Ruggieri, Roberto Tamma, Giovanni Simone, Anita Mangia
Several data support a central role for angiogenesis in breast cancer growth and metastasis. Observational studies have demonstrated that microvascular density (MVD) is a prognostic factor in invasive breast cancer, whereas others reached the opposite conclusion. Vascular endothelial growth factor is the most important angiogenic factor with proven significance in breast cancer, as it has been assessed in both experimental and clinical studies. Triple-negative breast cancer (TNBC) is a type of breast cancer which lacks estrogen, progesterone, and HER-2/neu receptors...
October 2016: Translational Oncology
Egidio Iorio, Maria José Caramujo, Serena Cecchetti, Francesca Spadaro, Giulia Carpinelli, Rossella Canese, Franca Podo
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. (1)H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment...
2016: Frontiers in Oncology
Chun-Hui Zhang, Kai Chen, Yan Jiao, Lin-Li Li, Ya-Ping Li, Rong-Jie Zhang, Ming-Wu Zheng, Lei Zhong, Shen-Zhen Huang, Chun-Li Song, Wan-Ting Lin, Jiao Yang, Rong Xiang, Bing Peng, Jun-Hong Han, Guang-Wen Lu, Yu-Quan Wei, Sheng-Yong Yang
Herein we report the sophisticated process of structural optimization towards a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo, but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays, and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an)...
October 14, 2016: Journal of Medicinal Chemistry
Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im
Purpose: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. Materials and Methods: The anti-tumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay...
October 6, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Jue Wang, Jun Yin, Qing Yang, Feng Ding, Xiao Chen, Bingjie Li, Xingsong Tian
Based on a large cohort of clinical studies involving a total of 8024 patients and reporting the effects of HER4 on breast cancer prognosis, we conducted the first meta-analysis and review of this type. We identified 26 studies published between 1985 and 2016 and assessed the prognostic value of HER4 in breast cancer by either real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR, for mRNA levels) or immunohistochemistry (IHC, for protein levels). Elevated expression of HER4 was significantly associated with longer relapse-free survival (RFS) (HR = 0...
October 5, 2016: Oncotarget
Lingmi Hou, Maoshan Chen, Hongwei Yang, Tianyong Xing, Jingdong Li, Guangwu Li, Lina Zhang, Shishan Deng, Jiani Hu, Xiaobo Zhao, Jun Jiang
BACKGROUND Breast cancer is the main type of cancer in women, and triple-negative breast cancer (TNBC) is a unique subtype of breast cancer. The expression of miR-940 has been shown to play an important role in various cancers; however, the role of miR-940 in TNBC remains unknown. MATERIAL AND METHODS The expression of miR-940 in TNBC tissues or cells were tested by qRT-PCR; the expression of miR-940 in cells were overexpressed by miR-940 mimics, and suppressed by anti-miR-940. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-940...
October 12, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jane Date C Hon, Baljit Singh, Aysegul Sahin, Gang Du, Jinhua Wang, Vincent Y Wang, Fang-Ming Deng, David Y Zhang, Marie E Monaco, Peng Lee
Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy...
2016: American Journal of Cancer Research
Chandran Murugan, Kathirvel Rayappan, Ramar Thangam, Ramasamy Bhanumathi, Krishnamurthy Shanthi, Raju Vivek, Ramasamy Thirumurugan, Atanu Bhattacharyya, Srinivasan Sivasubramanian, Palani Gunasekaran, Soundarapandian Kannan
Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT...
October 11, 2016: Scientific Reports
Marta Nekulova, Jitka Holcakova, Xiaolian Gu, Vaclav Hrabal, Sotiris Galtsidis, Paulina Orzol, Yajing Liu, Stella Logotheti, Vassilis Zoumpourlis, Karin Nylander, Philip J Coates, Borivoj Vojtesek
BACKGROUND: p63, a member of the p53 protein family, plays key roles in epithelial development and carcinogenesis. In breast cancer, p63 expression has been found predominantly in basal-A (epithelial-type) triple-negative breast carcinomas (TNBC). To investigate the functional role of p63 in basal-A TNBC, we created MDA-MB-468 cell lines with inducible expression of the two major N-terminal p63 isoforms, TAp63α and ∆Np63α. RESULTS: TAp63α did not have significant effect on gene expression profile and cell phenotype, whilst the main effect of ΔNp63α was reduction of cell adhesion...
October 10, 2016: BMC Cancer
Yoon Yang Jung, Chang Lim Hyun, Min-Sun Jin, In Ae Park, Yul Ri Chung, Bobae Shim, Kyu Ho Lee, Han Suk Ryu
PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled...
September 2016: Journal of Breast Cancer
Sung Gwe Ahn, Seung Jun Kim, Cheungyeul Kim, Joon Jeong
Tumor heterogeneity of triple-negative breast cancer (TNBC) has been the main barrier in conquering breast cancer. To dissect the molecular diversity of TNBC and discover therapeutic targets for TNBC, the molecular classification of TNBC is a prioritized issue in research area. Accordingly, recent studies have been successful in classifying TNBC into several distinct subtypes with specific biologic pathways. Despite the different methodologies used and varied number of final subtypes, these studies identically suggested that TNBC consists of four major subtypes: basal-like, mesenchymal, luminal androgen receptor, and immune-enriched...
September 2016: Journal of Breast Cancer
Valentina Damiano, Giulia Brisotto, Silvia Borgna, Alessandra di Gennaro, Michela Armellin, Tiziana Perin, Michela Guardascione, Roberta Maestro, Manuela Santarosa
Loss of expression of miR-200 family members has been implicated in cellular plasticity, a phenomenon that accounts for epithelial-to-mesenchymal transition (EMT) and stem-like features of many carcinomas and is considered a major cause of tumor aggressiveness and drug resistance. Nevertheless, the mechanisms of miR-200 downregulation in breast cancer are still largely unknown. Here we show that miR-200c expression inversely correlates with miR-200c/miR-141 locus methylation in triple-negative breast tumors (TNBC)...
September 22, 2016: Genes, Chromosomes & Cancer
Peng Li, Tingting Sun, Qingzhong Yuan, Guozheng Pan, Jian Zhang, Diwen Sun
BACKGROUND: Neural precursor cell expressed, developmentally downregulated 9 (NEDD9), a member of Crk-associated substrate family, is involved in cancer cell adhesion, migration, invasion, and epithelial-mesenchymal transition. E-cadherin is a key event in the cellular invasion during the epithelial-mesenchymal transition mechanism. The aim of this study was to evaluate the association among NEDD9 expression, E-cadherin expression, and survival in triple-negative breast cancer (TNBC) patients...
2016: OncoTargets and Therapy
Danian Dai, Bo Chen, Bin Wang, Hailin Tang, Xing Li, Zhiping Zhao, Xuan Li, Xiaoming Xie, Weidong Wei
PURPOSE: Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. METHODS: We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR...
2016: Journal of Cancer
Kimberly Maxfield, Jennifer Macion, Hariprasad Vankayalapati, Angelique W Whitehurst
Triple negative breast cancer (TNBC) is a highly heterogeneous disease with multiple, distinct molecular subtypes that exhibit unique transcriptional programs and clinical progression trajectories. Despite knowledge of the molecular heterogeneity of the disease, most patients are limited to generic, indiscriminate treatment options: cytotoxic chemotherapy, surgery and radiation. To identify new intervention targets in TNBC, we used large-scale, loss of function screening to identify molecular vulnerabilities among different oncogenomic backgrounds...
October 3, 2016: Molecular and Cellular Biology
H Liu, H Qiu, Y Song, Y Liu, H Wang, M Lu, M Deng, Y Gu, J Yin, K Luo, Z Zhang, X Jia, G Zheng, Z He
Triple-negative breast cancer (TNBC) is very aggressive and currently has no specific therapeutic targets; as a consequence, TNBC exhibits poor clinical outcome. In this study, we showed that cancerous inhibitor of protein phosphatase 2A (Cip2a) represents a promising target in TNBC because Cip2a was highly expressed in TNBC cells and tumor tissues, and its expression showed an inverse correlation with overall survival in patients with TNBC. We found that inhibition of Cip2a in TNBC cells induced cell cycle arrest at the G2/M phase, inhibited cell proliferation and delayed tumor growth in the xenograft model...
October 3, 2016: Oncogene
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