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Azfar Neyaz, Nuzhat Husain, Sameer Gupta, Swati Kumari, Aditi Arora, Namrata Puneet Awasthi, Kiran Preet Malhotra, Sanjeev Misra
Background: Gallbladder carcinoma, uncommon in most of the world, is frequent in South East Asia. It presents in advanced stages with limited therapeutic options. We investigated targetable predictive and prognostic Markers in 268 cases including 233 primary site lesions and 35 metastatic gallbladder carcinoma. Methods: EGFR, VEGF, HER2/Neu and p53 were assessed using immunohistochemistry. HER2/Neu was validated in a subset by fluorescent in situ hybridization (FISH) using tissue microarray (TMA)...
February 2018: Journal of Gastrointestinal Oncology
Sing-Han Huang, Yu-Shu Lo, Yong-Chun Luo, Yu-Yao Tseng, Jinn-Moon Yang
BACKGROUND: One of the crucial steps toward understanding the associations among molecular interactions, pathways, and diseases in a cell is to investigate detailed atomic protein-protein interactions (PPIs) in the structural interactome. Despite the availability of large-scale methods for analyzing PPI networks, these methods often focused on PPI networks using genome-scale data and/or known experimental PPIs. However, these methods are unable to provide structurally resolved interaction residues and their conservations in PPI networks...
March 19, 2018: BMC Systems Biology
Oğuz Ahmet Hasdemir, Serhat Tokgöz, Fulya Köybaşıoğlu, Harun Karabacak, Cüneyt Yücesoy, Gökşen İnanç İmamoğlu
BACKGROUND: Metaplastic carcinoma of the breast (MpBC) is defined as a group of heterogeneous malignant neoplasms that contain glandular and non-glandular components with mixed epithelial and mesenchymal differentiations. OBJECTIVES: The aim of this study was to research the clinical and pathological characteristics of MpBC determining its rank among all breast cancers. MATERIAL AND METHODS: Metaplastic carcinoma of the breast was found in 7 out of 1,164 patients who had been diagnosed with breast cancer within the period of 12 years in our hospital...
March 19, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Hidejiro Torigoe, Hiromasa Yamamoto, Masakiyo Sakaguchi, Chen Youyi, Kei Namba, Hiroki Sato, Kazuhiko Shien, Junichi Soh, Ken Suzawa, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations, and have been targeted for treatment in non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues...
March 13, 2018: Carcinogenesis
Ali Ben Djoudi Ouadda, Yi He, Viviane Calabrese, Hidetaka Ishii, Rony Chidiac, Jean-Philippe Gratton, Philippe P Roux, Nathalie Lamarche-Vane
Cdc42 GTPase-activating protein (CdGAP, also named ARHGAP31) is a negative regulator of the GTPases Rac1 and Cdc42. Associated with the rare developmental disorder Adams-Oliver Syndrome (AOS), CdGAP is critical for embryonic vascular development and VEGF-mediated angiogenesis. Moreover, CdGAP is an essential component in the synergistic interaction between TGFβ and ErbB-2 signaling pathways during breast cancer cell migration and invasion, and is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer...
February 20, 2018: Oncotarget
Chengqiang Wu, Chun Gui, Lang Li, Yiheng Pang, Zhongli Tang, Jing Wei
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h...
April 2018: Experimental and Therapeutic Medicine
Emma D Deeks, Gillian M Keating
Afatinib [Giotrif® (EU); Gilotrif® (USA)] is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases that provides an important first-line treatment option for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (i.e. EGFRactMUT+ ), and an additional treatment option for squamous NSCLC that has progressed following first-line platinum-based chemotherapy. Relative to gefitinib in the first-line treatment of EGFRactMUT+ advanced lung adenocarcinoma, afatinib prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS)...
2018: Drugs & Therapy Perspectives: for Rational Drug Selection and Use
Benjamin A Farber, Gadi Lalazar, Elana P Simon, William J Hammond, David Requena, Umesh K Bhanot, Michael P La Quaglia, Sanford M Simon
Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer found in adolescents and young adults without underlying liver disease. A deletion of ~400 kD has been found in one copy of chromosome 19 in the tumor tissue of all patients tested. This produces a fusion of the genes DNAJB1 and PRKACA which, in turn, produces a chimeric transcript and protein. Transcriptomic analysis of the tumor has shown upregulation of various oncologically relevant pathways, including EGF/ErbB, Aurora Kinase A, pak21 and wnt...
February 13, 2018: Oncotarget
Zheng Shi, Jie Chen, Xiaolan Guo, Lijia Cheng, Xiaoheng Guo, Tian Yu
Background: The receptor tyrosine kinase of the epidermal growth factor receptor (EGFR, ErbB) family played an important role in multisignaling pathways, which controlled numerous biological activities including proliferation, differentiation, apoptosis, etc. EGFR abnormalities have been associated with a variety of human tumors, which was a well-characterized target for cancer treatment. It was known to all that drug repositioning has been considered as a useful tool to accelerate the process of drug development...
January 2018: Journal of Cancer Research and Therapeutics
Maria Elena de Bellard, Blanca Ortega, Sothy Sao, Lino Kim, Joshua Herman, Nora Zuhdi
BACKGROUND: Trunk neural crest cells migrate rapidly along characteristic pathways within the developing vertebrate embryo. Proper trunk neural crest cell migration is necessary for the morphogenesis of much of the peripheral nervous system, melanocytes, and the adrenal medulla. Numerous molecules help guide trunk neural crest cell migration throughout the early embryo. RESULTS: Here, we show that the trophic factor NRG1 is a chemoattractant through in vitro chemotaxis assays and in vivo silencing via a DN-erbB receptor...
March 8, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Nivya James, K Ramanathan
Targeting ErbB family of receptors is an important therapeutic option, because of its essential role in the broad spectrum of human cancers, including non-small cell lung cancer (NSCLC). Therefore, in the present work, considerable effort has been made to develop an inhibitor against HER family proteins, by combining the use of pharmacophore modelling, docking scoring functions, and ADME property analysis. Initially, a five-point pharmacophore model was developed using known HER family inhibitors. The generated model was then used as a query to screen a total of 468,880 compounds of three databases namely ZINC, ASINEX, and DrugBank...
March 6, 2018: Applied Biochemistry and Biotechnology
Ye Liu, Mei Yuan, Chao Wu, Tianhui Zhu, Wei Sun
Breast cancer is the most common invasive cancer in women worldwide, and can be subdivided into Luminal A, Luminal B, Her2, and Basal subtype (the PAM50 subtyping system). The lmo2 gene was traditionally recognized as a proto-oncogene in hematopoietic system but its functions in breast cancers remained largely unclear. Based on the Cancer Genome Atlas (TCGA) breast cancer dataset, herein we found that the significantly LMO2-correlated genes in normal or malignant samples were enriched in rather divergent cellular pathways, suggesting the function complexity of LMO2 in breast tissues...
February 6, 2018: Oncotarget
Yunli Zhang, Yanming Li, Hongling Li, Wei Chen, Wenen Liu
Clostridium difficile toxin B (cdtB) is a critical virulence factor characterized with potential cytotoxicity and pro-inflammatory activity. This study aims to investigate anti-tumor effects of cdtB on breast cancer development. Clostridium difficile strain was cultured and cdtB recombinant protein (rcdtB) was synthesized. Breast cancer cell line, MDA-MB-231, was divided into Normal control, rcdtB 50, 100, 200 and 400 ng/ml group in vitro. Mice were divided into Normal control and rcdtB treatment group (400 ng/ml) in vivo...
February 28, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Juexiao Gong, Chuan Qiu, Dan Huang, Yiyan Zhang, Shengyong Yu, Chunping Zeng
Clinical research in coronary artery disease (CAD) primarily focused on genetic variants located in protein-coding regions. Recently, mutations fall within non-coding regions have been suggested to be essential to the pathogenesis of human complex disease. Super enhancer is a densely spaced cluster of transcriptional enhancers located in non-coding regions, which is critical for regulating cell-type specific gene expression. However, the underlying mechanism of the super enhancer single-nucleotide polymorphisms (SNPs) affecting the risk of CAD remains unclear...
February 28, 2018: Journal of Human Genetics
Wen-Ling Kuo, Shir-Hwa Ueng, Chun-Hsing Wu, Li-Yu Lee, Yun-Shien Lee, Ming-Chin Yu, Shin-Cheh Chen, Chi-Chang Yu, Chi-Neu Tsai
The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements...
February 26, 2018: Human Cell
Ke Zhang, Xiangjun Kong, Guangde Feng, Wei Xiang, Long Chen, Fang Yang, Chunyu Cao, Yifei Ding, Hang Chen, Mingxing Chu, Pingqing Wang, Baoyun Zhang
BACKGROUND: Ovarian cancer is a leading cause of the death from gynecologic malignancies. Hypoxia is closely related to the malignant growth of cells. However, the molecular mechanism of hypoxia-regulated ovarian cancer cells remains unclear. Thus, this study was conducted to identify the key genes and pathways implicated in the regulation of hypoxia by bioinformatics analysis. METHODS: Using the datasets of GSE53012 downloaded from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were screened by comparing the RNA expression from cycling hypoxia group, chronic hypoxia group, and control group...
February 26, 2018: Journal of Ovarian Research
Wei Guo, Bin Zhang, Kun Mu, Shi-Qing Feng, Zhan-Yin Dong, Guang-Zhi Ning, Hao-Ran Li, Shen Liu, Ling Zhao, Yan Li, Bing-Bing Yu, Hui-Quan Duan, Chao Sun, Yong-Jin Li
Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the underlying mechanisms remain poorly understood. Compared with normal nucleus pulposus (NP) tissues, the expression of circ-GRB10 was downregulated in IDD. Furthermore, overexpression of circ-GRB10 inhibited NP cell apoptosis. circ-GRB10 could sequester miR-328-5p, which could potentially lead to the upregulation of target genes related to cell proliferation via the ErbB pathway. In conclusion, the present study revealed that circ-GRB10/miR-328-5p/ERBB2 signaling pathway is involved in IDD development, suggesting that circ-GRB10 might be a novel therapeutic target for IDD...
February 23, 2018: Cell Death & Disease
Jing Zhao, Xiaotong Chen, J Zheng, M Kong, B Wang, W Ding
BACKGROUND: ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for screening patients with non-small cell lung cancer (NSCLC) slated for targeted therapy. Many studies and our data have identified cases that express the ROS1 protein strongly but are negative for ROS1 by fluorescent in situ hybridization (FISH). The present study investigated the driver mutation and clinicopathologic characteristics of 26 discordant cases (ROS1 IHC-positive but FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases...
February 21, 2018: Histopathology
Matthew A Ingersoll, Yu-Wei Chou, Jamie S Lin, Ta-Chun Yuan, Dannah Miller, Yan Xie, Yaping Tu, Rebecca E Oberley-Deegan, Surinder K Batra, Ming-Fong Lin
Metastatic castration-resistant (CR) prostate cancer (PCa) is a lethal disease for which no effective treatment is currently available. p66Shc is an oxidase previously shown to promote androgen-independent cell growth through generation of reactive oxygen species (ROS) and elevated in clinical PCa and multiple CR PCa cell lines. We hypothesize p66Shc also increases the migratory activity of PCa cells through ROS and investigate the associated mechanism. Using the transwell assay, our study reveals that the level of p66Shc protein correlates with cell migratory ability across several PCa cell lines...
February 17, 2018: Cellular Signalling
Xiaoran Guo, Kenneth K W To, Zhen Chen, Xiaokun Wang, Jianye Zhang, Min Luo, Fang Wang, Shirong Yan, Liwu Fu
BACKGROUND: ATP-binding cassette subfamily G member 2 (ABCG2), a member of the ABC transporter superfamily proteins, mediates multidrug resistance (MDR) by transporting substrate anticancer drugs out of cancer cells and decreasing their intracellular accumulation. MDR is a major hurdle to successful chemotherapy. A logical approach to overcome MDR is to inhibit the transporter. However, no safe and effective MDR inhibitor has been approved in the clinic. METHODS: The MTT assay was used to evaluate cell cytotoxicity and MDR reversal effect...
February 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
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