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Molecular biology and breast cancer

Ju Hui Jeong, Yong Jin Oh, Yunmee Lho, Sun You Park, Kwang-Hyeon Liu, Eunyoung Ha, Young Ho Seo
The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC50 = 50...
October 18, 2016: European Journal of Medicinal Chemistry
Shanshan Li, Wenda Zhang, Yanwei Yang, Ting Ma, Jianpeng Guo, Shanshan Wang, Wenying Yu, Lingyi Kong
Constitutive activation of STAT3 has been found in a wide variety of cancers and demonstrated as a very attractive therapeutic target. Disrupting both acetylation and phosphorylation of STAT3 protein was hypothesized to greatly deactivate STAT3, therefore, treating cancers. To demonstrate the hypothesis, two series of novel resveratrol-caffeic acid hybrids were designed aiming to regulate both acetylation and phosphorylation of STAT3 protein, which is also the first report of the synthetic inhibitors simultaneously regulating two biological reactions of STAT3 to our knowledge...
October 15, 2016: European Journal of Medicinal Chemistry
Pat Whitworth, Peter Beitsch, Angela Mislowsky, James V Pellicane, Charles Nash, Mary Murray, Laura A Lee, Carrie L Dul, Michael Rotkis, Paul Baron, Lisette Stork-Sloots, Femke A de Snoo, Jennifer Beatty
PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity...
October 21, 2016: Annals of Surgical Oncology
Sanaz Tabarestani, Marzieh Motallebi, Mohammad Esmaeil Akbari
CONTEXT: Breast cancer is the most common cancer in women worldwide. Estrogen receptor (ER) positive breast cancer constitutes the majority of these cancers. Hormone therapy has significantly improved clinical outcomes for early- and late-stage hormone receptor positive breast cancer. Although most patients with early stage breast cancer are treated with curative intent, approximately 20% - 30% of patients eventually experience a recurrence. During the last two decades, there have been tremendous efforts to understand the biological mechanisms of hormone therapy resistance, with the ultimate goal of implementing new therapeutic strategies to improve the current treatments for ER positive breast cancer...
August 2016: Iranian Journal of Cancer Prevention
Olugbenga Awolaran, Susan A Brooks, Verna Lavender
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016...
October 14, 2016: Breast: Official Journal of the European Society of Mastology
A L R Bordinhão, A F Evangelista, R J S Oliveira, T Macedo, H C Silveira, R M Reis, M M Marques
Cediranib, a pan-tyrosine kinase inhibitor is showing promising results for the treatment of several solid tumours. In breast cancer, its effects remain unclear, and there are no predictive biomarkers. Several studies have examined the expression profiles of microRNAs (miRNAs) in response to different chemotherapy treatments and found that the expression patterns may be associated with the treatment response. Therefore, our aim was to evaluate the cellular behaviour and differential expression profiles of miRNAs in breast cancer cell lines exposed to cediranib...
October 7, 2016: Oncology Reports
Ciara M Kelly, Yelena Y Janjigian
Gastric cancer is a biologically heterogeneous tumor. The identification of human epidermal growth factor receptor-2 (HER2) biomarker overexpression in gastric cancer represented a significant step towards unraveling the molecular complexity of this disease. Trastuzumab in combination with chemotherapy, in the first-line setting of patients with metastatic, HER2-positive gastric and gastroesophageal, represents the first targeted therapeutic to demonstrate improvement in response rate and survival in gastric cancer...
October 2016: Journal of Gastrointestinal Oncology
Priyakshi Kalita-de Croft, Fares Al-Ejeh, Amy E McCart Reed, Jodi M Saunus, Sunil R Lakhani
Our understanding of the natural history of breast cancer has evolved alongside technologies to study its genomic, transcriptomic, proteomic, and metabolomics landscapes. These technologies have helped decipher multiple molecular pathways dysregulated in breast cancer. First-generation 'omics analyses considered each of these dimensions individually, but it is becoming increasingly clear that more holistic, integrative approaches are required to fully understand complex biological systems. The 'omics represent an exciting era of discovery in breast cancer research, although important issues need to be addressed to realize the clinical utility of these data through precision cancer care...
November 2016: Advances in Anatomic Pathology
Ling Mao, Ai-Jun Sun, Jian-Zhong Wu, Jin-Hai Tang
The prognostic value of HER2 has been demonstrated in many human cancer types such us breast cancer, gastric cancer and ovarian cancer. Trastuzumab is the first anti-HER2 monoclonal antibody that has remarkably improved outcomes of patients with HER2-positive breast cancer. For HER2-positive metastatic gastric cancers, the addition of trastuzumab to traditional chemotherapy also significantly prolonged overall survival. However, intrinsic and acquired resistance to trastuzumab is common and results in disease progression...
October 12, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Frederick L Baehner
In vitro diagnostic multivariate index assays are highly complex molecular assays that can provide clinically actionable information regarding the underlying tumour biology and facilitate personalised treatment. These assays are only useful in clinical practice if all of the following are established: analytical validation (i.e., how accurately/reliably the assay measures the molecular characteristics), clinical validation (i.e., how consistently/accurately the test detects/predicts the outcomes of interest), and clinical utility (i...
2016: Ecancermedicalscience
Min Huang, Zhongjie Chen, Lu Zhang, Zhimin Huang, Yiying Chen, Jianrong Xu, Jian Zhang, Xiaohong Shu
It is now established that the specificity in signaling of signal transducer and activator of transcription 3 (STAT3) is mediated by the SH2 domain of STAT3, which mediates its interaction with the phosphopeptide docking sites displayed by receptors and JAKs, dimerization and subsequent DNA binding. Thus, we aimed to identify and design a class of strong potential small molecular inhibitors of STAT3 for the discovery and development of novel anticancer agents. Several classes of small molecules have been identified as STAT3 inhibitors after structure-based screening of the STAT3 SH2 domain...
September 30, 2016: Bioorganic & Medicinal Chemistry Letters
Ahmad Arouri, Kira E Lauritsen, Henriette L Nielsen, Ole G Mouritsen
Because of the amphipathicity and conical molecular shape of fatty acids, they can efficiently incorporate into lipid membranes and disturb membrane integrity, chain packing, and lateral pressure profile. These phenomena affect both model membranes as well as biological membranes. We investigated the feasibility of exploiting fatty acids as permeability enhancers in drug delivery systems for enhancing drug release from liposomal carriers and drug uptake by target cells. Saturated fatty acids, with acyl chain length from C8 to C20, were tested using model drug delivery liposomes of 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the breast cancer MCF-7 cell line as a model cell...
October 7, 2016: Chemistry and Physics of Lipids
Zibo Li, Jianfu Heng, Jinhua Yan, Xinwu Guo, Lili Tang, Ming Chen, Limin Peng, Yepeng Wu, Shouman Wang, Zhi Xiao, Zhongping Deng, Lizhong Dai, Jun Wang
PURPOSE: Gene-specific methylation and expression have shown biological and clinical importance for breast cancer diagnosis and prognosis. Integrated analysis of gene methylation and gene expression may identify genes associated with biology mechanism and clinical outcome of breast cancer and aid in clinical management. METHODS: Using high-throughput microfluidic quantitative PCR, we analyzed the expression profiles of 48 candidate genes in 96 Chinese breast cancer patients and investigated their correlation with gene methylation and associations with breast cancer clinical parameters...
November 2016: Breast Cancer Research and Treatment
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
Muhammet A Kaplan, Ulku Y Arslan, Abdurrahman Işıkdogan, Faysal Dane, Berna Oksuzoglu, Mevlude Inanc, Tulay Akman, Mehmet Kucukoner, Havva Y Cinkir, Rashad Rzazade, Metin Ozkan, Ugur Yilmaz, Ibrahim V Bayoglu, Yusuf Gunaydin, Meltem Baykara, Dogan Yazilitas, Erdem Cubukcu, Ali Suner, Ugur Ersoy, Mehmet Bilici, Ozan Yazici, Kerim Cayır, Umut Demirci, Mukremin Uysal
PURPOSE: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. METHODS: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B...
August 2016: Breast Care
Umair Baig, M A Gondal, Md Fazle Alam, Waseem A Wani, Hina Younus
Cancer and pathogenic microbial diseases have terribly affected human health over a longer period of time. In response to the increasing casualties due to cancer and microbial diseases, unique poly(3-methylthiophene) and poly(3-methylthiophene)-titanium(IV)phosphate composite were prepared via in-situ oxidative chemical polymerization in this work. The poly(3-methylthiophene) and poly(3-methylthiophene)-titanium(IV)phosphate composite were well characterized by Fourier transform infrared spectroscopy and field emission scanning electron microscopy...
September 28, 2016: Journal of Photochemistry and Photobiology. B, Biology
Renata Duchnowska, Michał Jarząb, Jadwiga Żebracka-Gala, Rafał Matkowski, Anna Kowalczyk, Barbara Radecka, Małgorzata Kowalska, Aleksandra Pfeifer, Małgorzata Foszczyńska-Kłoda, Antonino Musolino, Bogumiła Czartoryska-Arłukowicz, Maria Litwiniuk, Anna Surus-Hyla, Sylwia Szabłowska-Siwik, Bożenna Karczmarek-Borowska, Sylwia Dębska-Szmich, Beata Głodek-Sutek, Katarzyna Sosińska-Mielcarek, Ewa Chmielowska, Ewa Kalinka-Warzocha, Wojciech P Olszewski, Janusz Patera, Anton Żawrocki, Agnieszka Pliszka, Tomasz Tyszkiewicz, Dagmara Rusinek, Małgorzata Oczko-Wojciechowska, Jacek Jassem, Wojciech Biernat
BACKGROUND: Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches. PATIENTS AND METHODS: Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes...
September 8, 2016: Clinical Breast Cancer
Perumal Manivel, Manickam Paulpandi, Kadarkarai Murugan, Giovanni Benelli, Malaichamy Ilanchelian
The studies on protein-dye interactions are important in biological process and it is regarded as vital step in rational drug design. The interaction of thionine (TH) with human serum albumin (HSA) was analyzed using isothermal titration calorimetry (ITC), spectroscopic and molecular docking technique. The emission spectral titration of HSA with TH revealed the formation of HSA-TH complex via static quenching process. The results obtained from absorption, synchronous emission, circular dichroism (CD) and three dimensional (3D) emission spectral studies demonstrated that TH induces changes in the microenvironment and secondary structure of HSA...
October 3, 2016: Journal of Biomolecular Structure & Dynamics
L A Naleskina, N Yu Lukianova, S O Sobchenko, D M Storchai, V F Chekhun
UNLABELLED: To determine the patterns of lactoferrin (LF) expression in breast cancer (BC) in relation to biologic properties of the neoplasms and clinical features of the disease course. MATERIALS AND METHODS: Clinical specimens of 266 BC patients (115 patients with BC of stages I-II - retrospective study, and 151 BC patients - prospective study) were analyzed. Morphological, immunohistochemical and statistical methods were used. RESULTS: The number of LF-positive tumors in retrospective and prospective groups was similar (52...
September 2016: Experimental Oncology
Bernd L Groner, Nancy E Hynes
Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women...
September 2016: PLoS Biology
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