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ERBB3 AND cancer

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https://www.readbyqxmd.com/read/28294470/exome-sequencing-deciphers-a-germline-met-mutation-in-familial-epidermal-growth-factor-receptor-mutant-lung-cancer
#1
Naoki Tode, Toshiaki Kikuchi, Tomohiro Sakakibara, Taizou Hirano, Akira Inoue, Shinya Ohkouchi, Tsutomu Tamada, Tatsuma Okazaki, Akira Koarai, Hisatoshi Sugiura, Tetsuya Niihori, Yoko Aoki, Keiko Nakayama, Kunio Matsumoto, Yoichi Matsubara, Masayuki Yamamoto, Akira Watanabe, Toshihiro Nukiwa, Masakazu Ichinose
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a kindred with familial EGFR-mutant lung adenocarcinoma...
March 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#2
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28285962/the-erk-mapk-pathway-is-overexpressed-and-activated-in-gallbladder-cancer
#3
Kurt Buchegger, Ramón Silva, Jaime López, Carmen Ili, Juan Carlos Araya, Pamela Leal, Priscilla Brebi, Ismael Riquelme, Juan Carlos Roa
Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues...
February 24, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28223167/intracavitary-t4-immunotherapy-of-malignant-mesothelioma-using-pan-erbb-re-targeted-car-t-cells
#4
Astero Klampatsa, Daniela Y Achkova, David M Davies, Ana C Parente-Pereira, Natalie Woodman, James Rosekilly, Georgina Osborne, Thivyan Thayaparan, Andrea Bille, Michael Sheaf, James F Spicer, Juliet King, John Maher
Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28209614/distinct-interactions-of-ebp1-isoforms-with-fbxw7-elicits-different-functions-in-cancer
#5
Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
The ErbB3 receptor binding protein EBP1 encodes two alternatively spliced isoforms p48 and p42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 p48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 p48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197371/prophylactic-vaccination-targeting-erbb3-decreases-polyp-burden-in-a-mouse-model-of-human-colorectal-cancer
#6
David J Bautz, Ang T Sherpa, David W Threadgill
Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-Apc(Min) mice, a model of familial adenomatous polyposis (FAP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28174229/effects-of-erbb2-overexpression-on-the-proteome-and-erbb-ligand-specific-phosphosignalling-in-mammary-luminal-epithelial-cells
#7
Jenny Worthington, Georgia Spain, John F Timms
Most breast cancers arise from luminal epithelial cells and 25-30% of these tumours overexpress the ErbB2/HER2 receptor which correlates with disease progression and poor prognosis. The mechanisms of ErbB2 signalling and the effects of its overexpression are not fully understood. Herein, SILAC expression profiling and phosphopeptide enrichment of a relevant, non-transformed, immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGFR (EGF treatment) and ErbB3 (HRG1β treatment) in the context of ErbB2 overexpression...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28112728/integrated-genomic-and-molecular-characterization-of-cervical-cancer
#8
(no author information available yet)
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#9
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#10
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28036286/her3-and-linc00052-interplay-promotes-tumor-growth-in-breast-cancer
#11
Ahmad Salameh, Xuejun Fan, Byung-Kwon Choi, Shu Zhang, Ningyan Zhang, Zhiqiang An
Here we report that the lncRNA LINC00052 expression correlates positively with HER3/ErbB3 levels in breast cancer cells. Gene silencing of LINC00052 diminished both LINC00052 and HER3 expression and reduced cancer cell growth in vitro and in vivo. LINC00052 overexpression promoted cancer cell growth in vitro and in vivo and increased HER3-mediated downstream signaling. Importantly, neutralization of HER3 signaling with HER3 targeting monoclonal antibodies blocked LINC00052 mediated cancer cell proliferation in vitro and tumor growth in vivo, suggesting LINC00052 promoting cancer growth through HER3 signaling...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28004068/-up-regulation-of-erbb3-binding-protein-1-inhibits-the-growth-of-esophageal-carcinoma-cells
#12
Hao Jiang, Dong-Ping Liu, Dong Xie, Dong-Zhi Wei
The objective of this study was to investigate the role of ErbB3-binding protein 1 (Ebp1) in the growth of esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanism. Eca109 and KYSE150 cells were transfected with lentiviral vector carrying Ebp1 gene. The mRNA levels of Ebp1 in esophageal cancer tissues and paired adjacent normal tissues were examined by real-time PCR. The growth and viability of esophageal carcinoma cells were assessed using MTT and crystal violet assays, respectively. Clone-forming abilities of Eca109 and KYSE150 cells were analyzed by soft agar assay...
December 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27998236/randomized-phase-ii-trial-of-seribantumab-in-combination-with-paclitaxel-in-patients-with-advanced-platinum-resistant-or-refractory-ovarian-cancer
#13
Joyce F Liu, Isabelle Ray-Coquard, Frederic Selle, Andrés M Poveda, David Cibula, Hal Hirte, Felix Hilpert, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Salvatore Siena, Josep Maria Del Campo, Isabelle Tabah-Fisch, Joseph Pearlberg, Victor Moyo, Kaveh Riahi, Rachel Nering, William Kubasek, Bambang Adiwijaya, Akos Czibere, R Wendel Naumann, Robert L Coleman, Ignace Vergote, Gavin MacBeath, Eric Pujade-Lauraine
Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27906435/down-regulation-of-microrna-143-is-associated-with-colorectal-cancer-progression
#14
J-W Bai, H-Z Xue, C Zhang
OBJECTIVE: Colorectal cancer (CRC) is one of the most prevalent carcinomas worldwide. Tumor metastasis and recurrence are leading causes of CRC-related deaths. Given the role of microRNA (miRNA) in CRC invasion and metastasis, we explored the association between miRNA-143 expression and clinicopathologic characteristics in CRC, as well as the effects of miRNA-143 on CRC cell invasion in vitro. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to assess the expression of miR-143 in tissue specimens and cell lines...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27906180/mir-148a-3p-represses-proliferation-and-emt-by-establishing-regulatory-circuits-between-erbb3-akt2-c-myc-and-dnmt1-in-bladder-cancer
#15
Xiao Wang, Zhen Liang, Xin Xu, Jiangfeng Li, Yi Zhu, Shuai Meng, Shiqi Li, Song Wang, Bo Xie, Alin Ji, Ben Liu, Xiangyi Zheng, Liping Xie
miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27845906/specific-micro-rna-expression-patterns-distinguish-the-basal-and-luminal-subtypes-of-muscle-invasive-bladder-cancer
#16
Andrea E Ochoa, Woonyoung Choi, Xiaoping Su, Arlene Siefker-Radtke, Bogdan Czerniak, Colin Dinney, David J McConkey
The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3)...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27776045/microrna-148a-suppresses-the-proliferation-and-migration-of-pancreatic-cancer-cells-by-down-regulating-erbb3
#17
Hui Feng, Yalei Wang, Jiaojiao Su, Hongwei Liang, Chen-Yu Zhang, Xi Chen, Weiyan Yao
OBJECTIVES: ErbB3 (HER3) has been associated with pancreatic cancer progression, but little is known about its regulatory mechanisms. We investigated whether microRNAs (miRNAs) regulate levels of ErbB3 in pancreatic cancer cells. METHODS: We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Furthermore, the biological consequences of the targeting of ERBB3 by miR-148a were examined by cell proliferation and migration assays in vitro...
October 2016: Pancreas
https://www.readbyqxmd.com/read/27709558/dna-copy-number-alterations-gene-expression-changes-and-disease-free-survival-in-patients-with-colorectal-cancer-a-10-year-follow-up
#18
Elisabetta Bigagli, Carlotta De Filippo, Cinzia Castagnini, Simona Toti, Francesco Acquadro, Francesco Giudici, Marilena Fazi, Piero Dolara, Luca Messerini, Francesco Tonelli, Cristina Luceri
BACKGROUND: DNA copy number alterations (CNAs) and gene expression changes have amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs affect gene expression, as well as their relevance for tumor development, are still poorly defined. Here we aimed at assessing the clinical relevance of these parameters in a 10 year follow-up study. METHODS: Tumors and normal adjacent colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii) microarray-based transcriptome profiling for the detection of gene expression (GE) changes...
December 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27648936/kitenin-functions-as-a-fine-regulator-of-erbb4-expression-level-in-colorectal-cancer-via-protection-of-erbb4-from-e3-ligase-nrdp1-mediated-degradation
#19
Eun Gene Sun, Kyung Hwa Lee, Yoo-Seung Ko, Hui Jeong Choi, Jung-In Yang, Jae Hyuk Lee, Ik Joo Chung, Yun-Woong Paek, Hangun Kim, Jeong A Bae, Kyung Keun Kim
Understanding the complex biological functions of E3-ubiquitin ligases may facilitate the development of mechanism-based anti-cancer drugs. We recently identified that the KITENIN/ErbB4-Dvl2-c-Jun axis works as a novel unconventional downstream signal of epidermal growth factor (EGF) in colorectal cancer (CRC) tissues. Here we addressed whether E3-ubiquitin ligases are required for operation of this axis. We found that Nrdp1, an E3-ligase for ErbB3/ErbB4, interacted with KITENIN (KAI1 C-terminal interacting tetraspanin) to form a functional KITENIN/ErbB4/Nrdp1 complex and is responsible for down-regulating Dvl2 within this complex...
March 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27633099/lapatinib-resistant-cancer-cells-possessing-epithelial-cancer-stem-cell-properties-develop-sensitivity-during-sphere-formation-by-activation-of-the-erbb-akt-cyclin%C3%A2-d2-pathway
#20
Yuichi Ohnishi, Hiroki Yasui, Kenji Kakudo, Masami Nozaki
Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR)/ErbB2, has antiproliferative effects and is used to treat patients with ErbB2-positive metastatic breast cancer. In the present study, we examined the effects of lapatinib on growth of oral and prostate cancer cells. Oral squamous cell carcinoma (OSCC) cell lines HSC3, HSC4 and Ca9-22 were sensitive to the antiproliferative effects of lapatinib in anchorage-dependent culture, but the OSCC cell lines KB and SAS and the prostate cancer cell line DU145 were resistant to lapatinib...
November 2016: Oncology Reports
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