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https://www.readbyqxmd.com/read/28110457/reduced-proliferation-and-colony-formation-of-head-and-neck-squamous-cell-carcinoma-hnscc-after-dual-targeting-of-egfr-and-hedgehog-pathways
#1
Hannes Liebig, Georg Günther, Marlen Kolb, Christian Mozet, Andreas Boehm, Andreas Dietz, Gunnar Wichmann
PURPOSE: The hedgehog signalling pathway (Hh) is frequently active in head and neck squamous cell carcinoma (HNSCC). Overexpressed Hh associates with poor prognosis. The Hh inhibitor vismodegib targets smoothened, and based on molecular data, may prevent resistance to EGFR targeting. METHODS: To elucidate potential roles of vismodegib in HNSCC therapy, its sole effects and those combined with cisplatin, docetaxel, and cetuximab on HNSCC cell lines were assessed by MTT metabolisation and BrdU incorporation...
January 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28110331/distinct-benefit-of-overall-survival-between-patients-with-non-small-cell-lung-cancer-harboring-egfr-exon-19-deletion-and-exon-21-l858r-substitution
#2
Nobuyuki Koyama, Yasutaka Watanabe, Yuki Iwai, Rumi Kawamura, Chihiro Miwa, Yoshiaki Nagai, Koichi Hagiwara, Shinichiro Koyama
BACKGROUND: Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial. METHODS: The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib...
January 21, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28109944/synthesis-biological-evaluation-and-molecular-dynamics-md-simulation-studies-of-three-novel-f-18-labeled-and-focal-adhesion-kinase-fak-targeted-5-bromo-pyrimidines-as-radiotracers-for-tumor
#3
Yu Fang, Dawei Wang, Xingyu Xu, Jianping Liu, Aiqin Wu, Xiang Li, Qianqian Xue, Huan Wang, Hang Wang, Huabei Zhang
Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N(2)-(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N(4)-(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC50 in the range of 91...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28107397/efficacy-and-safety-of-everolimus-for-maintenance-immunosuppression-of-kidney-transplantation-a-meta-analysis-of-randomized-controlled-trials
#4
Jinyu Liu, Dong Liu, Juan Li, Lan Zhu, Chengliang Zhang, Kai Lei, Qiling Xu, Ruxu You
BACKGROUND: Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach. OBJECTIVES: To investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation. METHODS: Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data...
2017: PloS One
https://www.readbyqxmd.com/read/28107192/incidence-and-risk-of-infections-associated-with-egfr-tkis-in-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#5
Yingtian Wang, Mingzhen Wang, Qiaoxia Wang, Zhiying Geng, Mingxiang Sun
Currently, the overall incidence and risk of infections with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients remained undetermined. We searched Pubmed for related articles published from 1 January 1990 to 31 November 2015. Eligible studies included prospective randomized controlled trials (RCTs) evaluating therapy with or without EGFR-TKIs in patients with NSCLC. Data on infections were extracted. Pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107185/hyaluronan-synthase-3-mediated-oncogenic-action-through-forming-inter-regulation-loop-with-tumor-necrosis-factor-alpha-in-oral-cancer
#6
Yi-Zih Kuo, Wei-Yu Fang, Cheng-Chih Huang, Sen-Tien Tsai, Yi-Ching Wang, Chih-Li Yang, Li-Wha Wu
Hyaluronan (HA) is a major extracellular matrix component. However, its role and mediation in oral cancer remains elusive. Hyaluronan synthase 3 (HAS3), involved in pro-inflammatory short chain HA synthesis, was the predominant synthase in oral cancer cells and tissues. HAS3 overexpression significantly increased oral cancer cell migration, invasion and xenograft tumorigenesis accompanied with the increased expression of tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1). Conversely, HAS3 depletion abrogated HAS3-mediated stimulation...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105616/-interpretation-of-the-updates-of-nccn-2017-version-1-0-guideline-for-colorectal-cancer
#7
Gong Chen
The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting...
January 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28105360/long-term-disease-stabilization-following-treatment-with-erlotinib-in-heavily-pretreated-patients-with-wild-type-epidermal-growth-factor-receptor-non-small-cell-lung-carcinoma-two-case-reports
#8
Minas Sakellakis, Angelos Koutras, Maria Pittaka, Efstathios Tsitsopoulos, Fotini Kalofonou, Haralabos P Kalofonos
Lung adenocarcinomas carrying epidermal growth factor receptor (EGFR) mutations have been identified as a unique group of entities that depend on EGFR for their proliferation and metastasis. The introduction of reversible EGFR tyrosine kinase inhibitors, such as erlotinib, has significantly affected the management of metastatic disease in this subset of patients. Interestingly, although erlotinib is highly effective in patients with EGFR mutations, it may occasionally prove useful, even in the absence of mutations...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105244/her2-overexpression-reverses-the-relative-resistance-of-egfr-mutant-h1975-cell-line-to-gefitinib
#9
Jing Xu, Li Shen, Bi-Cheng Zhang, Wen-Hong Xu, Shu-Qin Ruan, Chi Pan, Qi-Chun Wei
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104619/osimertinib-benefit-in-egfr-mutant-nsclc-patients-with-t790m-mutation-detected-by-circulating-tumour-dna
#10
J Remon, C Caramella, C Jovelet, L Lacroix, A Lawson, S Smalley, K Howarth, D Gale, E Green, V Plagnol, N Rosenfeld, D Planchard, M V Bluthgen, A Gazzah, C Pannet, C Nicotra, E Auclin, J C Soria, B Besse
BACKGROUND: Approximately 50% of Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. MATERIAL AND METHODS: ctDNA T790M mutational status was assessed by Inivata InVision(TM) (eTAm-Seq(TM)) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28104566/targeting-epidermal-growth-factor-receptor-in-triple-negative-breast-cancer-new-discoveries-and-practical-insights-for-drug-development
#11
REVIEW
Ricardo Costa, Ami N Shah, Cesar A Santa-Maria, Marcelo R Cruz, Devalingam Mahalingam, Benedito A Carneiro, Young Kwang Chae, Massimo Cristofanilli, William J Gradishar, Francis J Giles
Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC...
January 5, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28104537/correlation-between-classic-driver-oncogene-mutations-in-egfr-alk-or-ros1-and-22c3-pd-l1-%C3%A2-50-expression-in-lung-adenocarcinoma
#12
Deepa Rangachari, Paul A VanderLaan, Meghan Shea, Xiuning Le, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Targeted somatic genomic analysis (EGFR, ALK and ROS1) and PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC) are used for selection of 1(st)-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. METHODS: We retrospectively probed the first 71 lung adenocarcinoma-patient pairs from our institution analyzed for PD-L1 IHC using the clone 22C3 pharmDx kit and evaluated co-occurrence of genomic aberrations along with clinical-pathologic characteristics...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28103975/-research-progress-of-targeted-therapy-for-egfr-gene-in-non-small-cell-lung-cancer
#13
Hui Zhang, Shucai Zhang
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have brought great clinical benefit to patients with EGFR-sensitive mutations. With the deepening of clinical and basic research, EGFR-TKIs have received more and more attention. In this review, we summarize the latest research development about EGFR-targeted drugs in 2016.
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103738/pharmacological-management-of-relapsed-refractory-nsclc-with-chemical-drugs
#14
Niki Karachaliou, Aaron E Sosa, Feliciano Barron Barron, Maria Gonzalez Cao, Mariacarmela Santarpia, Rafael Rosell
Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach...
January 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28102344/predicting-drug-combination-index-and-simulating-the-network-regulation-dynamics-by-mathematical-modeling-of-drug-targeted-egfr-erk-signaling-pathway
#15
Lu Huang, Yuyang Jiang, Yuzong Chen
Synergistic drug combinations enable enhanced therapeutics. Their discovery typically involves the measurement and assessment of drug combination index (CI), which can be facilitated by the development and applications of in-silico CI predictive tools. In this work, we developed and tested the ability of a mathematical model of drug-targeted EGFR-ERK pathway in predicting CIs and in analyzing multiple synergistic drug combinations against observations. Our mathematical model was validated against the literature reported signaling, drug response dynamics, and EGFR-MEK drug combination effect...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102288/acetylcholine-acts-through-m3-muscarinic-receptor-to-activate-the-egfr-signaling-and-promotes-gastric-cancer-cell-proliferation
#16
Huangfei Yu, Hongwei Xia, Qiulin Tang, Huanji Xu, Guoqing Wei, Ying Chen, Xinyu Dai, Qiyong Gong, Feng Bi
Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101945/epidermal-growth-factor-receptor-egfr-mapk-nuclear-factor-nf-%C3%AE%C2%BAb-il8-a-possible-mechanism-of-particulate-matter-pm-2-5-induced-lung-toxicity
#17
Seung-Chan Jeong, Yoon Cho, Mi-Kyung Song, Eunil Lee, Jae-Chun Ryu
Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2...
January 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28101799/antitumor-efficacy-of-slpi-promoter-controlled-expression-of-artificial-microrna-targeting-egfr-in-a-squamous-cell-carcinoma-cell-line
#18
Jia Chen, Shoude Zhang, Yi Lin, Beibei Yang, Jiang Cao
The purpose of this study was to develop a recombinant adenovirus with secretory leukoprotease inhibitor (SLPI) promoter-controlled expression for gene therapy of squamous cell carcinoma (SCC). An artificial microRNA targeting epidermal growth factor receptor (EGFR) was designed, and used to construct a replication-defective recombinant adenovirus with SLPI promoter-controlled expression. The silencing efficiency of this vector (Ad-SLPI-EGFRamiR) was detected in Hep-2 cells. Western blotting showed that the expression of 170 kD EGFR was significantly reduced in Hep-2 cells 72 h after infection with Ad-SLPI-EGFRamiR...
January 18, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#19
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101233/lipid-raft-localization-of-epidermal-growth-factor-receptor-alters-matrix-metalloproteinase-1-expression-in-siha-cells-via-the-mapk-erk-signaling-pathway
#20
Zongfeng Zhang, Lina Wang, Juan Du, Yuanbo Li, Huilun Yang, Chenxi Li, Hui Li, Haiyang Hu
Matrix metalloproteinase-1 (MMP-1) has been identified as an important participant in tumor invasion, metastasis and angiogenesis. The purpose of the present study was to investigate the effects of epidermal growth factor receptor (EGFR) localization to lipid rafts on signaling pathways involved in the regulation of MMP-1 expression in SiHa cells, a cervical cancer cell line. EGFR activation by EGF specifically induced MMP-1 expression at both the messenger RNA and protein levels. Additionally, it was observed that EGFR localized to lipid rafts, and that the redistribution of EGFR induced by lipid raft disruption strengthened EGF-induced MMP-1 expression...
December 2016: Oncology Letters
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