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ERBB3 AND cancer

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https://www.readbyqxmd.com/read/29453410/molecular-characterization-of-colorectal-adenomas-with-and-without-malignancy-reveals-distinguishing-genome-transcriptome-and-methylome-alterations
#1
Brooke R Druliner, Panwen Wang, Taejeong Bae, Saurabh Baheti, Seth Slettedahl, Douglas Mahoney, Nikolaos Vasmatzis, Hang Xu, Minsoo Kim, Matthew Bockol, Daniel O'Brien, Diane Grill, Nathaniel Warner, Miguel Munoz-Gomez, Kimberlee Kossick, Ruth Johnson, Mohamad Mouchli, Donna Felmlee-Devine, Jill Washechek-Aletto, Thomas Smyrk, Ann Oberg, Junwen Wang, Nicholas Chia, Alexej Abyzov, David Ahlquist, Lisa A Boardman
The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had tissues from the residual polyp of origin and contiguous cancer; CFPs had polyp tissues matched to CAPs based on polyp size, histology and dysplasia. To determine whether molecular features distinguish CAPs and CFPs, we conducted Whole Genome Sequencing, RNA-seq, and RRBS on over 90 tissues from 31 patients...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29434871/mechanisms-for-dna-damaging-agent-induced-inactivation-of-erbb2-and-erbb3-via-the-erk-and-p38-signaling-pathways
#2
Chul Min Park, Yuki Kawasaki, Alaa Refaat, Hiroaki Sakurai
Cisplatin (CDDP) and doxorubicin (DOX) are chemotherapeutic drugs that trigger apoptosis by inducing DNA-damage. A previous study using breast cancer cells demonstrated the negative feedback modulation of the epidermal growth factor receptor (EGFR) and receptor tyrosine-protein kinase erbB-2 (ErbB2) via extracellular signal-regulated kinase (ERK)-mediated phosphorylation of conserved Thr-669 and Thr-677 residues, respectively, in the juxtamembrane domain. In addition, CDDP has been identified to cause negative feedback inhibition of activated EGFR in lung cancer cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29420467/her-kinase-inhibition-in-patients-with-her2-and-her3-mutant-cancers
#3
David M Hyman, Sarina A Piha-Paul, Helen Won, Jordi Rodon, Cristina Saura, Geoffrey I Shapiro, Dejan Juric, David I Quinn, Victor Moreno, Bernard Doger, Ingrid A Mayer, Valentina Boni, Emiliano Calvo, Sherene Loi, Albert C Lockhart, Joseph P Erinjeri, Maurizio Scaltriti, Gary A Ulaner, Juber Patel, Jiabin Tang, Hannah Beer, S Duygu Selcuklu, Aphrothiti J Hanrahan, Nancy Bouvier, Myra Melcer, Rajmohan Murali, Alison M Schram, Lillian M Smyth, Komal Jhaveri, Bob T Li, Alexander Drilon, James J Harding, Gopa Iyer, Barry S Taylor, Michael F Berger, Richard E Cutler, Feng Xu, Anna Butturini, Lisa D Eli, Grace Mann, Cynthia Farrell, Alshad S Lalani, Richard P Bryce, Carlos L Arteaga, Funda Meric-Bernstam, José Baselga, David B Solit
Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials...
February 8, 2018: Nature
https://www.readbyqxmd.com/read/29413684/human-epidermal-receptor-family-inhibitors-in-patients-with-erbb3-mutated-cancers-entering-the-back-door
#4
Loic Verlingue, Antoine Hollebecque, Ludovic Lacroix, Sophie Postel-Vinay, Andrea Varga, Yolla El Dakdouki, Capucine Baldini, Rastilav Balheda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Olivier Mir, Monica Arnedos, Etienne Rouleau, Eric Solary, Thierry De Baere, Eric Angevin, Jean-Pierre Armand, Stefan Michiels, Fabrice André, Eric Deutsch, Jean-Yves Scoazec, Jean-Charles Soria, Christophe Massard
INTRODUCTION: Therapeutic inhibition of the human epidermal receptor 3 (ERBB3, HER3) has been challenged by the low frequency of ERBB3 somatic alterations across cancer types. We have evaluated the clinical utility to use available inhibitors of the HER family in the context of ERBB3 mutations. PATIENTS AND METHODS: In this study, we have selected patients with somatic ERBB3 alterations detected in their tumours from the molecular screening programs running at our institution...
January 27, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29413056/egfr-mediated-interleukin-enhancer-binding-factor-3-contributes-to-formation-and-survival-of-cancer-stem-like-tumorspheres-as-a-therapeutic-target-against-egfr-positive-non-small-cell-lung-cancer
#5
Chun-Chia Cheng, Kuei-Fang Chou, Cheng-Wen Wu, Nai-Wen Su, Cheng-Liang Peng, Ying-Wen Su, Jungshan Chang, Ai-Sheng Ho, Huan-Chau Lin, Caleb Gon-Shen Chen, Bi-Ling Yang, Yu-Cheng Chang, Ya-Wen Chiang, Ken-Hong Lim, Yi-Fang Chang
OBJECTIVES: YM155, an inhibitor of interleukin enhancer-binding factor 3 (ILF3), significantly suppresses cancer stemness property, implying that ILF3 contributes to cell survival of cancer stem cells. However, the molecular function of ILF3 inhibiting cancer stemness remains unclear. This study aimed to uncover the potential function of ILF3 involving in cell survival of epidermal growth factor receptor (EGFR)-positive lung stem-like cancer, and to investigate the potential role to improve the efficacy of anti-EGFR therapeutics...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29388752/iron-oxide-nanoparticles-synergize-with-erlotinib-to-suppress-refractory-non-small-cell-lung-cancer-cell-proliferation-through-the-inhibition-of-erbb-pi3k-akt-and-pten-activation
#6
Meili Zhang, Buqing Sai, Pengfei Cao, Zheng Li, Liyang Zhang, Cijun Shuai, Xinye Wang, Jia Wang, Guiyuan Li, Juanjuan Xiang, Jingqun Tang
Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib, are currently approved for the management of NSCLC. However, primary and acquired resistances to EGFR-TKIs are the major obstacles in the treatment of NSCLC. These resistances have been associated with the development of secondary mutations in EGFR or continued oncogenic signaling despite TKI treatment. In this study, NSCLC cells with wild-type EGFR, A549, H460, H358, H157 which do not respond to EGFR-TKIs, were used...
April 2017: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/29383036/development-of-a-personalized-therapeutic-strategy-for-erbb-gene-mutated-cancers
#7
Malgorzata Milewska, Mattia Cremona, Clare Morgan, John O'Shea, Aoife Carr, Sri H Velanki, Ann M Hopkins, Sinead Toomey, Stephen F Madden, Bryan T Hennessy, Alex J Eustace
Background: The application of genomic technologies to patient tumor samples identified groups of signaling pathways which acquire activating mutations. Some cancers are dependent on these mutations and the aberrant proteins resulting from these mutations can be targeted by novel drugs which can eradicate the cancer. Methods: We used www.cbioportal.org to determine the frequency of ERBB mutations in solid tumors. We then determined the sensitivity of a panel of cell lines to clinically available PI3K inhibitors...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29338072/targeting-her2-in-colorectal-cancer-the-landscape-of-amplification-and-short-variant-mutations-in-erbb2-and-erbb3
#8
Jeffrey S Ross, Marwan Fakih, Siraj M Ali, Julia A Elvin, Alexa B Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, James Sun, Vincent A Miller, Philip J Stephens, Laurie M Gay
BACKGROUND: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#9
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29321661/differential-recruitment-of-cd44-isoforms-by-erbb-ligands-reveals-an-involvement-of-cd44-in-breast-cancer
#10
Iris Morath, Christian Jung, Romain Lévêque, Chen Linfeng, Robert-Alain Toillon, Arne Warth, Véronique Orian-Rousseau
Members of the CD44 family of transmembrane glycoproteins control cell signaling pathways from numerous cell surface receptors, including receptor tyrosine kinases (RTKs). The decisive factor (ligand, RTKs or both) that controls the recruitment of specific CD44 isoforms is still unknown. We investigated this question by using the EGFR signaling pathway, in which one receptor can be activated by a broad range of ligands. By means of siRNA-mediated downregulation of CD44 expression and blocking experiments, we identified CD44v6 as a co-receptor for EGF- and ER-induced ErbB1 activation and for NRG1-induced ErbB3 and ErbB4 activation...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29286064/mir-152-is-involved-in-the-proliferation-and-metastasis-of-ovarian-cancer-through-repression-of-erbb3
#11
Lian-Wei Li, Hong-Qi Xiao, Rong Ma, Meng Yang, Wan Li, Ge Lou
MicroRNAs (miRNAs) participate in post-transcriptional regulation by targeting the 3' untranslated region of target genes that are involved in diverse biological processes. To the best of our knowledge, the association between miR‑152 and ERBB3 in ovarian cancer remains unclear. In the present study, a negative correlation between miR‑152 and ERBB3 in ovarian cancer was observed. The luciferase reporter gene assay results demonstrated that miR‑152 negatively regulated ERBB3 in SKOV3 and OVCAR3 ovarian cancer cells...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29199595/epidermal-growth-factor-receptor-tyrosine-kinase-a-potential-target-in-treatment-of-non-small-cell-lung-carcinoma
#12
REVIEW
Venugopal Vinod Prabhu, Niranjali Devaraj
Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29182685/mir205-inhibits-stem-cell-renewal-in-sum159pt-breast-cancer-cells
#13
Víctor Mayoral-Varo, Annarica Calcabrini, María Pilar Sánchez-Bailón, Jorge Martín-Pérez
miR205 has a dual activity, as tumor suppressor and as oncogene. Here we analyzed the impact of miR205 ectopic expression in the initial tumorigenic processes of SUM159PT, a triple negative breast cancer cell line with low endogenous levels of miR205. In SUM159PT, miR205 inhibited expression of its targets VEGFA, ErbB3, Zeb1, Fyn and Lyn A/B; it reduced cell proliferation, and Myc/cyclin D1 levels, while increased p27kip1 expression. miR205 abolished anchorage-independent growth, inhibited migration and invasion, Src-kinases/Stat3 axis activation, and levels of secreted MMP9...
2017: PloS One
https://www.readbyqxmd.com/read/29113229/fatty-acid-synthase-affects-expression-of-erbb-receptors-in-epithelial-to-mesenchymal-transition-of-breast-cancer-cells-and-invasive-ductal-carcinoma
#14
Tingting Chen, Lan Zhou, Hua Li, Yuan Tian, Junqin Li, Lihua Dong, Yuhua Zhao, Dapeng Wei
The aim of the present study was to investigate changes in the expression of ErbBs during epithelial-mesenchymal transition (EMT) of breast cancer cells and its association with the expression of fatty acid synthase (FASN). MCF-7-MEK5 cells were used as the experimental model, while MCF-7 cells were used as a control. Tumor cells were implanted into nude mice for in vivo analysis. Cerulenin was used as a FASN inhibitor. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect expression levels of FASN and ErbB1-4...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29080385/evaluation-of-patritumab-with-or-without-erlotinib-in-combination-with-standard-cytotoxic-agents-against-pediatric-sarcoma-xenograft-models
#15
Abhik Bandyopadhyay, Edward Favours, Doris A Phelps, Vanessa Del Pozo, Samson Ghilu, Dias Kurmashev, Joel Michalek, Aron Trevino, Denis Guttridge, Cheryl London, Kenji Hirotani, Ling Zhang, Raushan T Kurmasheva, Peter J Houghton
BACKGROUND: Integrating molecularly targeted agents with cytotoxic drugs used in curative treatment of pediatric cancers is complex. An evaluation was undertaken with the ERBB3/Her3-specific antibody patritumab (P) either alone or with the ERBB1/epidermal growth factor receptor inhibitor erlotinib (E) in combination with standard cytotoxic agents, cisplatin, vincristine, and cyclophosphamide, in pediatric sarcoma xenograft models that express receptors and ligands targeted by these agents...
October 28, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29050225/hcarg-commd5-inhibits-erbb-receptor-driven-renal-cell-carcinoma
#16
Hiroyuki Matsuda, Carole G Campion, Kyoko Fujiwara, Jin Ikeda, Suzanne Cossette, Thomas Verissimo, Maiko Ogasawara, Louis Gaboury, Kosuke Saito, Kenya Yamaguchi, Satoru Takahashi, Morito Endo, Noboru Fukuda, Masayoshi Soma, Pavel Hamet, Johanne Tremblay
Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048654/telmisartan-inhibits-hepatocellular-carcinoma-cell-proliferation-in-vitro-by-inducing-cell-cycle-arrest
#17
Kyoko Oura, Tomoko Tadokoro, Shintaro Fujihara, Asahiro Morishita, Taiga Chiyo, Eri Samukawa, Yoshimi Yamana, Koji Fujita, Teppei Sakamoto, Takako Nomura, Hirohito Yoneyama, Hideki Kobara, Hirohito Mori, Hisakazu Iwama, Keiichi Okano, Yasuyuki Suzuki, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28978093/molecular-characterization-of-circulating-colorectal-tumor-cells-defines-genetic-signatures-for-individualized-cancer-care
#18
Say Li Kong, Xingliang Liu, Nur-Afidah Mohamed Suhaimi, Kenneth Jia Hao Koh, Min Hu, Daniel Yoke San Lee, Igor Cima, Wai Min Phyo, Esther Xing Wei Lee, Joyce A Tai, Yu Miin Foong, Jess Honganh Vo, Poh Koon Koh, Tong Zhang, Jackie Y Ying, Bing Lim, Min-Han Tan, Axel M Hillmer
Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28939861/multiplexed-exchange-paint-imaging-reveals-ligand-dependent-egfr-and-met-interactions-in-the-plasma-membrane
#19
Jeffrey L Werbin, Maier S Avendaño, Verena Becker, Ralf Jungmann, Peng Yin, Gaudenz Danuser, Peter K Sorger
Signal transduction by receptor tyrosine kinases (RTKs) involves complex ligand- and time-dependent changes in conformation and modification state. High resolution structures are available for individual receptors dimers, but less is known about receptor clusters that form in plasma membranes composed of many different RTKs with the potential to interact. We report the use of multiplexed super-resolution imaging (Exchange-PAINT) followed by mean-shift clustering and random forest analysis to measure the precise distributions of five receptor tyrosine kinases (RTKs) from the ErbB, IGF-1R and Met families in breast cancer cells...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28938595/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#20
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
August 29, 2017: Oncotarget
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