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https://www.readbyqxmd.com/read/27931797/erbb2-is-essential-for-the-growth-of-chemically-induced-skin-tumors-in-mice
#1
Maik Dahlhoff, Sukalp Muzumdar, Matthias Schäfer, Marlon R Schneider
While the epidermal growth factor receptor has established roles in skin carcinogenesis, inflammation, and wound healing, the functions of the structurally related receptor ERBB2 in this tissue remain poorly explored. To assess the functions of ERBB2 in skin homeostasis, tumorigenesis, and wound healing we employed keratin 5-directed, cre recombinase-mediated targeting of Erbb2 alleles in mice. Erbb2(del) mice, lacking ERBB2 specifically in keratinocytes, showed no noticeable spontaneous skin abnormalities...
December 5, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#2
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
December 7, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27924190/network-analysis-of-human-post-mortem-microarrays-reveals-novel-genes-micrornas-and-mechanistic-scenarios-of-potential-importance-in-fighting-huntington-s-disease
#3
Sreedevi Chandrasekaran, Danail Bonchev
Huntington's disease is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive decline, and neuropsychiatric symptoms. In this study, we utilized network-based analysis in an attempt to explore and understand the underlying molecular mechanism and to identify critical molecular players of this disease condition. Using human post-mortem microarrays from three brain regions (cerebellum, frontal cortex and caudate nucleus) we selected in a four-step procedure a seed set of highly modulated genes...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27918782/biosimilar-therapy-for-erbb2-her2-positive-breast-cancer-close-enough
#4
Harold J Burstein, Deborah Schrag
No abstract text is available yet for this article.
December 1, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27918780/effect-of-a-proposed-trastuzumab-biosimilar-compared-with-trastuzumab-on-overall-response-rate-in-patients-with-erbb2-her2-positive-metastatic-breast-cancer-a-randomized-clinical-trial
#5
Hope S Rugo, Abhijit Barve, Cornelius F Waller, Miguel Hernandez-Bronchud, Jay Herson, Jinyu Yuan, Rajiv Sharma, Mark Baczkowski, Mudgal Kothekar, Subramanian Loganathan, Alexey Manikhas, Igor Bondarenko, Guzel Mukhametshina, Gia Nemsadze, Joseph D Parra, Maria Luisa T Abesamis-Tiambeng, Kakhaber Baramidze, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Gopichand Mamillapalli, Sirshendu Ray, Eduardo P Yanez Ruiz, Eduardo Pennella
Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer...
December 1, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#6
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907855/lc-ms-ms-assay-for-the-quantitation-of-the-tyrosine-kinase-inhibitor-neratinib-in-human-plasma
#7
Brian F Kiesel, Robert A Parise, Alvin Wong, Kiana Keyvanjah, Samuel Jacobs, Jan H Beumer
Neratinib is an orally available tyrosine kinase inhibitor targeting HER2 (ERBB2) and EGFR (ERBB). It is being clinically evaluated for the treatment of breast and other solid tumors types as a single agent or in combination with other chemotherapies. In support of several phase I/II clinical trials investigating neratinib combinations, we developed and validated a novel LC-MS/MS assay for the quantification of neratinib in 100μL of human plasma with a stable isotopic internal standard. Analytes were extracted from plasma using protein precipitation and evaporation of the resulting supernatant followed by resuspension...
November 22, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27905513/whole-genome-scanning-for-the-litter-size-trait-associated-genes-and-snps-under-selection-in-dairy-goat-capra-hircus
#8
Fang-Nong Lai, Hong-Li Zhai, Ming Cheng, Jun-Yu Ma, Shun-Feng Cheng, Wei Ge, Guo-Liang Zhang, Jun-Jie Wang, Rui-Qian Zhang, Xue Wang, Ling-Jiang Min, Jiu-Zhou Song, Wei Shen
Dairy goats are one of the most utilized domesticated animals in China. Here, we selected extreme populations based on differential fecundity in two Laoshan dairy goat populations. Utilizing deep sequencing we have generated 68.7 and 57.8 giga base of sequencing data, and identified 12,458,711 and 12,423,128 SNPs in the low fecundity and high fecundity groups, respectively. Following selective sweep analyses, a number of loci and candidate genes in the two populations were scanned independently. The reproduction related genes CCNB2, AR, ADCY1, DNMT3B, SMAD2, AMHR2, ERBB2, FGFR1, MAP3K12 and THEM4 were specifically selected in the high fecundity group whereas KDM6A, TENM1, SWI5 and CYM were specifically selected in the low fecundity group...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902734/galectin-7-expression-potentiates-her-2-positive-phenotype-in-breast-cancer
#9
Andrée-Anne Grosset, Françoise Poirier, Louis Gaboury, Yves St-Pierre
HER-2 positive tumors are among the most aggressive subtypes of breast cancer and are frequently associated with metastasis and poor outcome. As with other aggressive subtypes of breast cancer, these tumors are associated with abnormally high expression of galectin-7 (gal-7), which confers metastatic breast tumor cells with increased invasive behavior. Although previous studies in the rat model of breast tumorigenesis have shown that gal-7 is also increased in primary breast tumor, its contribution to the development of the primary breast tumors remains unclear...
2016: PloS One
https://www.readbyqxmd.com/read/27901097/sequencing-based-breast-cancer-diagnostics-as-an-alternative-to-routine-biomarkers
#10
Mattias Rantalainen, Daniel Klevebring, Johan Lindberg, Emma Ivansson, Gustaf Rosin, Lorand Kis, Fuat Celebioglu, Irma Fredriksson, Kamila Czene, Jan Frisell, Johan Hartman, Jonas Bergh, Henrik Grönberg
Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900589/intrinsic-her2-v777l-mutation-mediates-resistance-to-trastuzumab-in-a-breast-cancer-patient
#11
Yosuke Hirotsu, Hiroshi Nakagomi, Kenji Amemiya, Toshio Oyama, Masayuki Inoue, Hitoshi Mochizuki, Masao Omata
HER2 (ERBB2) is an oncogene and 20% of breast cancers display HER2 amplification. The HER2 monoclonal antibody, trastuzumab, is used to treat breast cancers that display HER2 amplification, with good responses in 80-90% of cases; however, 10% of tumours develop resistance to trastuzumab. In this study, we collected data of primary breast cancer patients who treated at hospital during 2004-2014. In our cohort, 205 of 1497 primary breast cancer patients showed HER2-amplification, and 20 experienced recurrence after trastuzumab therapy...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27900369/genomic-profiling-of-multiple-sequentially-acquired-tumor-metastatic-sites-from-an-exceptional-responder-lung-adenocarcinoma-patient-reveals-extensive-genomic-heterogeneity-and-novel-somatic-variants-driving-treatment-response
#12
Romi Biswas, Shaojian Gao, Constance M Cultraro, Tapan K Maity, Abhilash Venugopalan, Zied Abdullaev, Alexey K Shaytan, Corey A Carter, Anish Thomas, Arun Rajan, Young Song, Stephanie Pitts, Kevin Chen, Sara Bass, Joseph Boland, Ken-Ichi Hanada, Jinqiu Chen, Paul S Meltzer, Anna R Panchenko, James C Yang, Svetlana Pack, Giuseppe Giaccone, David S Schrump, Javed Khan, Udayan Guha
We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899083/tumor-characteristics-and-prognosis-in-familial-breast-cancer
#13
G Arpino, M Pensabene, C Condello, R Ruocco, I Cerillo, R Lauria, V Forestieri, M Giuliano, C De Angelis, M Montella, A Crispo, S De Placido
BACKGROUND: Approximately 5-10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome...
November 29, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27889996/elevated-microsatellite-alterations-at-selected-tetranucleotide-repeats-emast-and-microsatellite-instability-in-patients-with-colorectal-cancer-and-its-clinical-features
#14
H S Lee, K U Park, D-W Kim, M H Ihn, W H Kim, A N Seo, H E Chang, S K Nam, S Y Lee, H-K Oh, S-B Kang
PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status...
November 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27882385/a-role-for-neuregulin-1-in-promoting-keloid-fibroblast-migration-via-erbb2-mediated-signaling
#15
Natalie Jumper, Tom Hodgkinson, Ralf Paus, Ardeshir Bayat
Keloid disease is a fibroproliferative tumour characterised by aggressive local invasion, evident from a clinically and histologically active migrating margin. During combined laser capture microdissection and microarray analysis-based in situ gene expression profiling, we identified upregulation of the polypeptide growth factor neuregulin-1 (NRG1) and ErbB2 oncogene in keloid margin dermis, leading to the hypothesis that NRG1 contributed to keloid margin migration through ErbB2-mediated signalling. The aim of this study was to probe this hypothesis through functional in vitro studies...
November 24, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27880046/docosahexaenoic-acid-mediated-inhibition-of-heat-shock-protein-90-p23-chaperone-complex-and-downstream-client-proteins-in-lung-and-breast-cancer
#16
Michael Mouradian, Irvin V Ma, Erika D Vicente, Keith D Kikawa, Ronald S Pardini
The molecular chaperone, heat shock protein 90 (Hsp90), is a critical regulator for the proper folding and stabilization of several client proteins, and is a major contributor to carcinogenesis. Specific Hsp90 inhibitors have been designed to target the ATP-binding site in order to prevent Hsp90 chaperone maturation. The current study investigated the effects of docosahexaenoic acid (DHA; C22:6 n-3) on Hsp90 function and downstream client protein expression. In vitro analyses of BT-474 human breast carcinoma and A549 human lung adenocarcinoma cell lines revealed dose-dependent decreases in intracellular ATP levels by DHA treatment, resulting in a significant reduction of Hsp90 and p23 association in both cell lines...
November 23, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27879270/breast-cancer-resistance-to-antiestrogens-is-enhanced-by-increased-er-degradation-and-erbb2-expression
#17
Tomohiro Shibata, Kosuke Watari, Hiroto Izumi, Akihiko Kawahara, Satoshi Hattori, Chihiro Fukumitsu, Yuichi Murakami, Ryuji Takahashi, Uhi Toh, Ken-Ichi Ito, Shigehiro Ohdo, Maki Tanaka, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono
Endocrine therapies effectively improve the outcomes of patients with estrogen receptor (ER)-positive breast cancer. However, the emergence of drug-resistant tumors creates a core clinical challenge. In breast cancer cells rendered resistant to the antiestrogen fulvestrant, we defined causative mechanistic roles for the transcription factor YBX1 and the levels of ER and the ERBB2 receptor. Enforced expression of YBX1 in parental cells conferred resistance against tamoxifen and fulvestrant in vitro and in vivo...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27876799/irs4-induces-mammary-tumorigenesis-and-confers-resistance-to-her2-targeted-therapy-through-constitutive-pi3k-akt-pathway-hyperactivation
#18
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, John Hilkens
In search of oncogenic drivers and mechanisms affecting therapy resistance in breast cancer, we identified Irs4, a poorly studied member of the insulin receptor substrate (IRS) family, as a mammary oncogene by insertional mutagenesis. Whereas normally silent in the postnatal mammary gland, IRS4 is found to be highly expressed in a subset of breast cancers. We show that Irs4 expression in mammary epithelial cells induces constitutive PI3K/AKT pathway hyperactivation, insulin/IGF1-independent cell proliferation, anchorage-independent growth and in vivo tumorigenesis...
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27872096/polyi-c-and-cpg-synergize-with-anti-erbb2-mab-for-treatment-of-breast-tumors-resistant-to-immune-checkpoint-inhibitors
#19
Roxanne Charlebois, Bertrand Allard, David Allard, Laurence Buisseret, Martin Turcotte, Sandra Pommey, Pavel Chrobak, John Stagg
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab and patients have a worse prognosis. Because type I and II interferons (IFNs) are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long lasting CD8+ T cell-dependent anti-tumor immunity...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27870944/application-of-single-molecule-amplification-and-resequencing-technology-for-broad-surveillance-of-plasma-mutations-in-patients-with-advanced-lung-adenocarcinoma
#20
Zheng Wang, Gang Cheng, Xiaohong Han, Xinlin Mu, Yuhui Zhang, Di Cui, Chang Liu, Li Zhang, Zaiwen Fan, Lingyun Ma, Li Yang, Jing Di, David S Cram, Yuankai Shi, Dongge Liu
Liquid biopsy to access the circulating tumor DNA is a promising surrogate for invasive tumor genotyping. We designed a multiplex assay based on circulating single-molecule amplification and resequencing technology (cSMART) to simultaneously detect and quantitate hot spot EGFR, KRAS, BRAF, ERBB2, and ALK plasma DNA variants in 103 patients with advanced lung adenocarcinoma. In validation studies using an analytical mutation standard, the sensitivity of the assay for EGFR mutation detection was at least 0.1% and specificity was 100%...
November 18, 2016: Journal of Molecular Diagnostics: JMD
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