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https://www.readbyqxmd.com/read/28428257/the-size-speed-force-relationship-governs-migratory-cell-response-to-tumorigenic-factors
#1
Aldo Leal-Egaña, Gaelle Letort, Jean-Louis Martiel, Andreas Christ, Timothée Vignaud, Caroline Roelants, Odile Filhol, Manuel Théry
Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction followed by cell de-adhesion, scattering and invasion. Tumorigenic factors may act specifically on one of these steps or have wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type-I/fibronectin on deformable surfaces to standardize cell behavior and to measure simultaneously cell size, speed of motion and the magnitude of the associated traction forces at the level of a single cell...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#2
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28424560/an-exploratory-study-of-host-polymorphisms-in-genes-that-clinically-characterize-breast-cancer-tumors-and-pretreatment-cognitive-performance-in-breast-cancer-survivors
#3
Theresa A Koleck, Catherine M Bender, Beth Z Clark, Christopher M Ryan, Puja Ghotkar, Adam Brufsky, Priscilla F McAuliffe, Priya Rastogi, Susan M Sereika, Yvette P Conley
PURPOSE: Inspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28423734/gata3-and-trps1-are-distinct-biomarkers-and-prognostic-factors-in-breast-cancer-database-mining-for-gata-family-members-in-malignancies
#4
Hao-Yu Lin, De Zeng, Yuan-Ke Liang, Xiao-Long Wei, Chun-Fa Chen
GATA transcription factors are zinc finger DNA binding proteins that activate transcription during development and cell differentiation. To date, 7 members of GATA family have been reported. However, the expression patterns and the exact roles of distinct GATA family members contributing to tumorigenesis and progression of breast cancer (BC) remain to be elucidated. Here, we studied the expression of GATA transcripts in a variety of tumor types compared with the normal controls using the ONCOMINE and GOBO databases, along with their corresponding expression profiles in an array of cancer cell lines through CCLE analysis...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423512/kinase-analysis-of-penile-squamous-cell-carcinoma-on-multiple-platforms-to-identify-potential-therapeutic-targets
#5
Eddy S Yang, Christopher D Willey, Amitkumar Mehta, Michael R Crowley, David K Crossman, Dongquan Chen, Joshua C Anderson, Gurudatta Naik, Deborah L Della Manna, Tiffiny S Cooper, Guru Sonpavde
Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. Given that kinases may be drivers and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor and normal tissue. Fresh frozen tumors were collected from 11 patients with PSCC. After macrodissection to demarcate tumor from normal tissue, the samples underwent multiplatform analysis of kinases. Next Generation Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture and run on the Illumina MiSeq at PE150bp...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422721/functional-analysis-implicating-the-snp-rs61552325-in-erbb2-as-an-effector-for-androgen-insensitive-prostate-cancer-cell-invasion
#6
Xianxiang Xin, Yinmin Gu, Yang Chen, Yuanjie Huang, Zengnan Mo, Yanling Hu
BACKGROUND: As one of the most common cancers in men, the pathogenesis of prostate cancer has been widely researched. Aberrant activation of the erb-b2 receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in metastatic prostate cancer. In our previous study, we demonstrated that rs61552325 (Pro1140Ala) located in ERBB2 is strongly correlated to prostate cancer. Therefore, we initially studied the effect of rs61552325 on androgen-independent prostate cancer cell metastasis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420510/gene-set-based-analysis-of-mucinous-ovarian-carcinoma
#7
Chia-Ming Chang, Peng-Hui Wang, Huann-Cheng Horng
OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon subtype of epithelial ovarian cancers, and the pathogenesis is still poorly understood because of its rarity. We conducted a gene set-based analysis to investigate the pathogenesis of MOC by integrating microarray gene expression datasets based on the regularity of functions defined by gene ontology or canonical pathway databases. MATERIALS AND METHODS: Forty-five pairs of MOC and normal ovarian tissue sample gene expression profiles were downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database...
April 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28418920/complementary-utility-of-targeted-next-generation-sequencing-and-immunohistochemistry-panels-as-a-screening-platform-to-select-targeted-therapy-for-advanced-gastric-cancer
#8
Hyo Song Kim, Hanna Lee, Su-Jin Shin, Seung-Hoon Beom, Minkyu Jung, Sujin Bae, Eun Young Lee, Kyu Hyun Park, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Woong Sub Koom, Joon Seok Lim, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Hyunki Kim, Soonmyung Paik
We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415602/errf-sensitizes-erbb2-positive-breast-cancer-cells-to-lapatinib-treatment-likely-by-attenuating-mcl1-and-erbb2-expression
#9
Leilei Qi, Baotong Zhang, Shiying Zhang, Xinpei Ci, Qiao Wu, Gui Ma, Ang Luo, Liya Fu, Jamie L King, Rita Nahta, Jin-Tang Dong
Previously we found that the estrogen receptor (ER) related factor ERRF regulates cell proliferation and tumor growth, and its expression is positively associated with ER status and better survival but inversely associated with ERBB2 (also named HER2) status in breast cancer. Here we report that ERRF also plays an important role in the response of ERBB2-positive breast cancer cells to lapatinib, a dual tyrosine kinase inhibitor that interrupts the ERBB2 and EGFR pathway. In ERBB2-positive breast cancer cell lines, lower levels of ERRF expression correlated with lapatinib resistance, restoration of ERRF expression in lapatinib-resistant cell lines JIMT-1 and MDA-MB-453 enhanced their lapatinib responses, and knockdown of ERRF in lapatinib sensitive cell lines BT-474 and SK-BR-3 caused lapatinib resistance...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411283/systematic-functional-perturbations-uncover-a-prognostic-genetic-network-driving-human-breast-cancer
#10
Tristan Gallenne, Kenneth N Ross, Nils L Visser, Salony, Christophe J Desmet, Ben S Wittner, Lodewyk F A Wessels, Sridhar Ramaswamy, Daniel S Peeper
Prognostic classifiers conceivably comprise biomarker genes that functionally contribute to the oncogenic and metastatic properties of cancer, but this has not been investigated systematically. The transcription factor Fra-1 not only has an essential role in breast cancer, but also drives the expression of a highly prognostic gene set. Here, we systematically perturbed the function of 31 individual Fra-1-dependent poor-prognosis genes and examined their impact on breast cancer growth in vivo. We find that stable shRNA depletion of each of nine individual signature genes strongly inhibits breast cancer growth and aggressiveness...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398609/potentially-functional-variants-in-lncrnas-are-associated-with-breast-cancer-risk-in-a-chinese-population
#11
Yue Jiang, Fangzhi Du, Fei Chen, Na Qin, Zhu Jiang, Jing Zhou, Tao Jiang, Zhening Pu, Yue Cheng, Jiaping Chen, Juncheng Dai, Hongxia Ma, Guangfu Jin, Zhibin Hu, Hao Yu, Hongbing Shen
Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1,486 breast cancer cases and 1,519 cancer-free controls in a Chinese population...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28394918/a-novel-technique-of-serial-biopsy-in-mouse-brain-tumour-models
#12
Sasha Rogers, Hilary Hii, Joel Huang, Mathew Ancliffe, Nick G Gottardo, Peter Dallas, Sharon Lee, Raelene Endersby
Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804) is a tyrosine kinase inhibitor (TKI), which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4) are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used...
2017: PloS One
https://www.readbyqxmd.com/read/28388586/her2-and-egfr-amplification-and-expression-in-urothelial-carcinoma-occurs-in-distinct-biological-and-molecular-contexts
#13
Pontus Eriksson, Gottfrid Sjödahl, Gunilla Chebil, Fredrik Liedberg, Mattias Höglund
We analyzed a cohort of 599 cases of urothelial carcinoma for EGFR, ERBB2, and ERBB3 gene expression and genomic alterations. The cohort consisted of a reference set (n = 292) comprising all stages and grades and one set (n = 307) of advanced tumors. All cases were previously classified into urothelial carcinoma molecular subtypes. Genomic amplifications were established by array-CGH or in-situ hybridization, and gene expression both at mRNA and protein levels. Clinical HER2 status was independently evaluated using standard clinical procedures...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382162/incorporating-gold-nanoclusters-and-target-directed-liposomes-as-a-synergistic-amplified-colorimetric-sensor-for-her2-positive-breast-cancer-cell-detection
#14
Yu Tao, Mingqiang Li, Bumjun Kim, Debra T Auguste
Breast cancer is the second leading cause of cancer-related mortality in women. Successful development of sensitive nanoprobes for breast cancer cell detection is of great importance for breast cancer diagnosis and symptomatic treatment. Herein, inspired by the intrinsic peroxidase property of gold nanoclusters, high loading, and targeting ability of ErbB2/Her2 antibody functionalized liposomes, we report that gold nanoclusters-loaded, target-directed, functionalized liposomes can serve as a robust sensing platform for amplified colorimetric detection of HER2-positive breast cancer cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28382134/an-investigation-of-the-role-of-gene-copy-number-variations-in-sorafenib-sensitivity-in-metastatic-hepatocellular-carcinoma-patients
#15
Ji Yun Lee, Mineui Hong, Jeeyun Lee, Sujin Lee, Kyoung-Mee Kim, Cheolkeun Park, Ho Yeong Lim
Background: Metastatic hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options. While sorafenib has recently been shown to provide a survival advantage in patients with advanced HCC, the overall outcomes such as time to progression (TTP) and overall survival (OS) ought to be further improved. To that end, several targeted agents aimed at amplified oncogenes such as HER2 and FGFR2 have recently been developed. In this study, we aimed to identify genetic markers in the form of copy number variations (CNVs) that influence clinical outcomes post-sorafenib treatment in advanced HCC patients...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28376302/multimodal-recognition-of-diverse-peptides-by-the-c-terminal-sh2-domain-of-plc%C3%AE-1
#16
Marissa Ann McKercher, Xiaoyang Guan, Zhongping Tan, Deborah Sharon Wuttke
SH2 domains recognize phosphotyrosine (pY)-containing peptide ligands, and play key roles in the regulation of receptor tyrosine kinase pathways. Each SH2 domain has individualized specificity, encoded in the amino acids neighboring the pY, for defined targets which convey their distinct functions. The C-terminal SH2 domain of PLCγ1 (PLCC) typically binds peptides containing small and hydrophobic amino acids adjacent to the pY, including a peptide derived from the platelet-derived growth factor receptor B (PDGFRB) and an intra-protein recognition site (Y783 of PLCγ1) involved in the regulation of the protein's lipase activity...
April 4, 2017: Biochemistry
https://www.readbyqxmd.com/read/28369073/her2-signaling-regulates-her2-localization-and-membrane-retention
#17
Jaekwang Jeong, Wonnam Kim, Lark Kyun Kim, Joshua VanHouten, John J Wysolmerski
ErbB2/HER2/Neu is a receptor tyrosine kinase that is overexpressed in 25-30% of human breast cancers, usually associated with amplification of the ERBB2 gene. HER2 has no recognized ligands and heterodimers between HER2 and EGFR (ErbB1/HER1) or HER2 and ErbB3/HER3 are important in breast cancer. Unlike other ErbB family members, HER2 is resistant to internalization and degradation, and remains at the cell surface to signal for prolonged periods after it is activated. Although the mechanisms underlying retention of HER2 at the cell surface are not fully understood, prior studies have shown that, in order to avoid internalization, HER2 must interact with the chaperone, HSP90, and the calcium pump, PMCA2, within specific plasma membrane domains that protrude from the cell surface...
2017: PloS One
https://www.readbyqxmd.com/read/28368009/entire-cd3%C3%AE%C2%B5-%C3%AE-and-%C3%AE-humanized-mouse-to-evaluate-human-cd3-mediated-therapeutics
#18
Otoya Ueda, Naoko A Wada, Yasuko Kinoshita, Hiroshi Hino, Mami Kakefuda, Tsuneo Ito, Etsuko Fujii, Mizuho Noguchi, Kiyoharu Sato, Masahiro Morita, Hiromi Tateishi, Kaoru Matsumoto, Chisato Goto, Yosuke Kawase, Atsuhiko Kato, Kunihiro Hattori, Junichi Nezu, Takahiro Ishiguro, Kou-Ichi Jishage
T cell-mediated immunotherapy is an attractive strategy for treatment in various disease areas. In this therapeutic approach, the CD3 complex is one of the key molecules to modulate T cell functions; however, in many cases, we cannot evaluate the drug candidates in animal experiments because the therapeutics, usually monoclonal antibodies specific to human CD3, cannot react to mouse endogenous Cd3. Although immunodeficient mice transfused with human hematopoietic stem or precursor cells, known as humanized mice, are available for these studies, mice humanized in this manner are not completely immune competent...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28364002/tissue-specific-signaling-networks-rewired-by-major-somatic-mutations-in-human-cancer-revealed-by-proteome-wide-discovery
#19
Junfei Zhao, Feixiong Cheng, Zhongming Zhao
Massive somatic mutations discovered by large cancer genome sequencing projects provide unprecedented opportunities in the development of precision oncology. However, deep understanding of functional consequences of somatic mutations and identifying actionable mutations and the related drug responses currently remain formidable challenges. Dysfunction of protein post-translational modification plays critical roles in tumorigenesis and drug responses. In this study, we proposed a novel computational oncoproteomics approach, named kinome-wide network module for cancer pharmacogenomics (KNMPx), for identifying actionable mutations that rewired signaling networks and further characterized tumorigenesis and anticancer drug responses...
March 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28363396/the-requirement-of-integrins-for-breast-epithelial-proliferation
#20
Paulina Moreno-Layseca, Ahmet Ucar, Heyuan Sun, Amber Wood, Safiah Olabi, Andrew P Gilmore, Keith Brennan, Charles H Streuli
Epithelial cells forming mammary gland ducts and alveoli require adhesion to the extracellular matrix for their function. Mammary epithelial cells need β1-integrins for normal cell cycle regulation. However, the role of β1-integrins in tumorigenesis has not been fully resolved. β1-integrin is necessary for tumour formation in transgenic mice expressing the Polyomavirus Middle T antigen, but it is dispensable in those overexpressing ErbB2. This suggests that some oncogenes can manage without β1-integrin to proliferate and form tumours, while others still require it...
March 14, 2017: European Journal of Cell Biology
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