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https://www.readbyqxmd.com/read/29917169/a-novel-strategy-of-egfr%C3%A2-tki-combined-chemotherapy-in-the-treatment-of-human-lung-cancer-with-egfr%C3%A2-sensitive-mutation
#1
Lanlin Zhang, Yuan Qi, Kailin Xing, Song Qian, Ping Zhang, Xianghua Wu
The discovery of epidermal growth factor receptor (EGFR)‑sensitive mutations in non‑small cell lung cancer (NSCLC) and the successful clinical application of EGFR tyrosine kinase inhibitors (TKIs) have changed the regimen of lung cancer therapy from traditional cytotoxic chemotherapy to molecular‑targeted cancer therapy. However, the main limitation of EGFR‑TKI therapy is the heterogeneity of lung cancer harboring EGFR‑sensitive mutations. In addition, the synergistic effect of the administration of chemotherapy and EGFR‑TKIs, combined with tumor heterogeneity, on NSCLC remains unclear...
June 18, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29915248/effect-of-tyrosine-kinase-inhibitors-on-renal-handling-of-creatinine-by-mate1
#2
Saki Omote, Natsumi Matsuoka, Hiroshi Arakawa, Takeo Nakanishi, Ikumi Tamai
Creatinine is actively secreted across tubular epithelial cells via organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1). We previously showed that the tyrosine kinase inhibitor (TKI) crizotinib inhibits OCT2-mediated transport of creatinine. In the present work, we examined the inhibitory potency of TKIs, including crizotinib, on MATE1-mediated transport of creatinine. Then, we used the kinetic parameters estimated in this and the previous work to predict the potential impact of TKIs on serum creatinine level (SCr) via reversible inhibition of creatinine transport...
June 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29914238/egfr-mutation-is-associated-with-short-progression-free-survival-in-patients-with-stage-iii-non-squamous-cell-lung-cancer-treated-with-concurrent-chemoradiotherapy
#3
Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Purpose: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). Materials and Methods: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer (NSCLC) treated with definitive CCRT were analyzed to determine progression free survival (PFS) and overall survival (OS) according to EGFR mutation status...
June 18, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29913887/epithelial-growth-factor-receptor-egfr-inhibition-for-relief-of-neuropathic-pain-a-case-series
#4
Christian Kersten, Marte Grønlie Cameron, Svein Mjåland
Background Neuropathic pain remains a significant challenge with unsatisfactory therapeutic options. Its pathogenesis may involve the neuropathic triad of neuronal, glial and immune cells. Communication between these cells is possibly perpetuated by mitogen-activated protein kinase (MAPK)-signaling. For several years, we successfully treated a rectal cancer patient with the epithelial growth factor receptor (EGFR)-inhibitor cetuximab, for debilitating neuropathic pain due to progressive malignant invasion of the sacral plexus...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29912633/anxa2-could-act-as-a-moderator-of-egfr-directed-therapy-resistance-in-triple-negative-breast-cancer
#5
Yue Zhang, Jiajia Bi, Hongtao Zhu, Mei Shi, Xianlu Zeng
Triple negative breast cancer (TNBC) patients cannot benefit from EGFR-targeted therapy even though the EGFR is highly expressed, because patients exhibit resistance to these drugs. Unfortunately, the molecular mechanisms remain relatively unknown. ANXA2, highly expressed in invasive breast cancer cells, is closely related with poor prognosis, and acts as a molecular switch to EGFR activation. In this study, MDA-MB-231 cells and MCF7 cells were used. Our results showed that ANXA2 expression is inversely correlated with cell sensitivity to gefitinib...
June 18, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29909007/early-emergence-of-de-novo-egfr-t790-m-gatekeeper-mutations-during-erlotinib-treatment-in-pc9-non-small-cell-lung-cancer-cells
#6
Sujin Kim, Angela Kj Park, Jeonghee Cho
The emergence of the T790 M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) gene is an important mechanism that can lead to the acquired resistance to EGFR-targeted tyrosine kinase inhibitors such as erlotinib or gefitinib. These drugs have been used in treating a subset of non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. Here we investigated the paths leading to the acquisition of the T790 M mutation by establishing an erlotinib resistant PC9 cell model harboring ectopically introduced EGFR cDNA...
June 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29907991/lipopolysaccharide-induced-the-proliferation-of-mouse-lung-fibroblasts-by-suppressing-foxo3a-p27-pathway
#7
Nannan Gu, Shunpeng Xing, Sihan Chen, Yuxi Zhou, Tao Jiang, Yingfu Jiao, Yuan Gao, Weifeng Yu, Zhengyu He, Daxiang Wen
Aberrant aggregation and activation of lung fibroblasts is a key process in pulmonary fibrosis, but the underlying mechanism remains enigmatic. Forkhead Box O3a (FoxO3a) is considered to be an important transcription factor that could regulate both cell cycle and cell viability. To investigate the role of FoxO3a on LPS-induced lung fibroblast proliferation, we transfected FoxO3a-SiRNA or FoxO3a-OE lentivirus into cultured mouse lung fibroblasts to knockdown or overexpress FoxO3a and pretreated mouse lung fibroblasts with gefitinib to enhance FoxO3a activity...
June 16, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29907952/bim-deletion-polymorphism-confers-resistance-to-osimertinib-in-egfr-t790m-lung-cancer-a-case-report-and-literature-review
#8
REVIEW
Xuanzong Li, Shijiang Wang, Butuo Li, Zhen Wang, Shuheng Shang, Yang Shao, Xindong Sun, Linlin Wang
The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against the EGFR T790M mutation in non-small cell lung cancer (NSCLC) patients. However, resistance inevitably occurs, and the mechanisms leading to treatment failure need to be further investigated. The B-cell lymphoma 2 (BCL-2)-like 11 (BIM) deletion polymorphism, which occurs at a frequency of 21% in East Asians but is absent in African and European populations, has been associated with resistance to first-generation EGFR TKIs, such as gefitinib and erlotinib; and is a poor prognostic factor for NSCLC patients with EGFR mutations...
June 16, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29906114/design-synthesis-and-biological-evaluation-of-pyrimido-4-5-d-pyrimidine-2-4-1-h-3-h-diones-as-potent-and-selective-epidermal-growth-factor-receptor-egfr-inhibitors-against-l858r-t790m-resistance-mutation
#9
Yongjia Hao, Jiankun Lyu, Rong Qu, Yi Tong, Deheng Sun, Fang Feng, Linjiang Tong, Tingyuan Yang, Zhenjiang Zhao, Lili Zhu, Jian Ding, Yufang Xu, Hua Xie, Honglin Li
First-generation epidermal growth factor receptor (EGFR) inhibitors, gefitinib and erlotinib have achieved initially marked clinical efficacy for non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, their clinical benefit was limited by the emergence of acquired resistance mutations. In most cases (approximately 60%), the resistance was caused by the secondary EGFR T790M gatekeeper mutation. Thus, it is still desirable to develop novel third-generation EGFR inhibitors to overcome T790M mutation while sparing wild-type (WT) EGFR...
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29904166/pharmacological-activation-of-epidermal-growth-factor-receptor-signaling-inhibits-colitis-associated-cancer-in-mice
#10
Philip E Dubé, Cambrian Y Liu, Nandini Girish, M Kay Washington, D Brent Polk
Current treatments for inflammatory bowel disease (IBD) target the overactive immune response of the intestinal mucosa. However, epidermal growth factor (EGF), an activating ligand of the EGF receptor (EGFR), has been shown to induce disease remission through direct targeting of intestinal mucosal healing. Despite promising preclinical and clinical results, this EGFR-activating therapy has not progressed, in part due to the potential for carcinogenesis associated with long-term use and the increased risk of colitis-associated cancer (CAC) in IBD...
June 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29902802/relationship-between-paronychia-and-drug-concentrations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#11
Katsuhiro Masago, Kei Irie, Shiro Fujita, Fumiko Imamichi, Yutaka Okada, Nobuyuki Katakami, Shoji Fukushima, Yasushi Yatabe
PURPOSE: The purpose of the study was to evaluate the site of paronychia in patients with non-small cell lung cancer harboring an epidermal growth factor receptor (EGFR) gene activating mutation who were treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). PATIENTS AND METHODS: The study included 55 patients with non-small-cell lung cancer who were treated with an EGFR TKIs. Resulting all toxicities were graded using the Common Terminology Criteria for Adverse Events version 4...
June 14, 2018: Oncology
https://www.readbyqxmd.com/read/29901268/integrative-analysis-of-proteome-and-ubiquitylome-reveals-unique-features-of-lysosomal-and-endocytic-pathways-in-gefitinib-resistant-non-small-cell-lung-cancer-cells
#12
Wang Li, Heyong Wang, Yan Yang, Tian Zhao, Zhixiong Zhang, Ye Tian, Zhaomie Shi, Xiaojun Peng, Fei Li, Yonghong Feng, Lei Zhang, Gening Jiang, Fan Zhang
Non-small cell lung cancer (NSCLC) patients carrying EGFR activating mutations treated with gefitinib, a tyrosine kinase inhibitor, will develop drug resistance. Ubiquitylation is one of major posttranslational modifications of proteins affecting the stability or function of proteins. However, the role of protein ubiquitylation in gefitinib resistance is poorly understood. To systematically identify the global change in protein expression and ubiquitylation during gefitinib resistance, we carried out quantitative global proteome and ubiquitylome study in a pair of gefitinib resistant and sensitive NSCLC cells...
June 14, 2018: Proteomics
https://www.readbyqxmd.com/read/29901173/preliminary-mechanisms-of-regulating-pd%C3%A2-l1-expression-in-non%C3%A2-small-cell-lung-cancer-during-the-emt-process
#13
Fang Li, Tengjiao Zhu, Yao Yue, Xiang Zhu, Jiadong Wang, Li Liang
Non‑small cell lung cancer (NSCLC) is one of the most severe malignant tumor types worldwide. Recent studies have reported an important role of PD‑L1 in mediating immune evasion in the tumor microenvironment. In addition, increasing research has indicated that the expression of PD‑L1 is related to the epithelial‑mesenchymal transition (EMT) process, but the related mechanisms remain to be explored. In the present study, we explored the molecular mechanisms underlying the regulation of PD‑L1 expression during the EMT process in NSCLC cells treated with transforming growth factor‑β1 (TGF‑β1) and fibroblast growth factor 2 (FGF2)...
June 5, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29898872/gefitinib-for-epidermal-growth-factor-receptor-activated-osteoarthritis-subpopulation-treatment
#14
Heng Sun, Yan Wu, Zongyou Pan, Dongsheng Yu, Pengfei Chen, Xiaoan Zhang, Haoyu Wu, Xiaolei Zhang, Chengrui An, Yishan Chen, Tian Qin, Xiaoyue Lei, Chunhui Yuan, Shufang Zhang, Weiguo Zou, Hongwei Ouyang
Osteoarthritis (OA) is a leading cause of physical disability among aging populations, with no available drugs able to efficiently restore the balance between cartilage matrix synthesis and degradation. Also, OA has not been accurately classified into subpopulations, hindering the development toward personalized precision medicine. In the present study, we identified a subpopulation of OA patients displaying high activation level of epidermal growth factor receptor (EGFR). With Col2a1-creERT2 ; Egfrf/f mice, it was found that the activation of EGFR, indicated by EGFR phosphorylation (pEGFR), led to the destruction of joints...
June 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29898592/efficacy-and-safety-of-afatinib-for-egfr-mutant-non-small-cell-lung-cancer-compared-with-gefitinib-or-erlotinib
#15
Youjin Kim, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Purpose: We tried to evaluate whether there is any specific features in treatment outcomes of first-line afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. Materials and Methods: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. Results: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72)...
June 13, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29891789/design-synthesis-cytotoxic-evaluation-and-molecular-docking-of-new-fluoroquinazolinones-as-potent-anticancer-agents-with-dual-egfr-kinase-and-tubulin-polymerization-inhibitory-effects
#16
Mohamed F Zayed, Sahar Ahmed, Saleh Ihmaid, Hany E A Ahmed, Heba S Rateb, Sabrin R M Ibrahim
A series of new fluoroquinazolinone 6 ⁻ 8 and 10a ⁻ g derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds 6 (IC50 = 0.35 ± 0.01 µM), 10f (IC50 = 0.71 ± 0.01 µM), 10d (IC50 = 0.89 ± 0.02 µM) and 10a (IC50 = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC50 = 0.97 ± 0.02 µM) against MCF-7. Compounds 10e (IC50 = 0...
June 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29891456/-activation-of-nuclear-factor-%C3%AE%C2%BAb-subunit-p50-p65-enhances-gefitinib-resistance-of-lung-adenocarcinoma-h1650-cell-line
#17
Ying Pan, Si-Chao Huang, Xia Wang, Wu-Xing Gong, Cui-Wei Liang, Jun-Xiang DU, Dong-Xu Peng, Yun Xie, Li-Ping Zheng, Nan Zhang, Wen Quan
OBJECTIVE: To explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells. METHODS: Human lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells. The expressions of P-IκBα, P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells, parental H1650 cells and gefitinib-resistant H1650 cells...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29885023/tyrosine-kinase-inhibitor-induced-il-6-stat3-activation-decreases-sensitivity-of-egfr-mutant-non-small-cell-lung-cancer-to-icotinib
#18
Jinyao Wang, Yizhe Wang, Chunlei Zheng, Kezuo Hou, Tieqiong Zhang, Xiujuan Qu, Yunpeng Liu, Jian Kang, Xuejun Hu, Xiaofang Che
Tyrosine kinase Inhibitors (TKIs) of epidermal growth factor receptor (EGFR) has considerably benefited for non-small cell lung carcinomas (NSCLC) harbor mutations in EGFR. However, the factors attenuating EGFR-TKI efficiency are obstacles to inhibit the proliferation of EGFR-mutant NSCLC cells successfully. Clarifying the insensitivity mechanisms of EGFR-TKI would help to develop new treatment strategy. In this study, the sensitivity of EGFR-mutant NSCLC cell lines, PC9 and HCC827, to icotinib was detected...
June 8, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29882195/the-effects-of-different-mtor-inhibitors-in-egfr-inhibitor-resistant-colon-carcinoma-cells
#19
Tamás Sticz, Anna Molnár, Titanilla Dankó, Zoltán Hujber, Gábor Petővári, Noémi Nagy, Gyula Végső, László Kopper, Anna Sebestyén
Several monoclonal antibodies and inhibitors targeting signalling pathways are being used in personalised medicine. Anti-EGFR antibodies seem to be effective, however, therapy resistance often occurs in colon carcinoma cases. mTOR inhibitors (mTORIs) could have a potential role in the breakthrough of therapy resistance. The mTOR activity related protein expression patterns and the in vitro effects of EGFR inhibitors (EGFRIs), mTORIs and their combinations were studied in different colon carcinoma cell lines (with different genetic backgrounds)...
June 7, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29881714/mechanisms-and-therapy-for-cancer-metastasis-to-the-brain
#20
REVIEW
Federica Franchino, Roberta Rudà, Riccardo Soffietti
Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs). Intracranial metastases are symptomatic in 60-70% of patients. Magnetic resonance imaging (MRI) with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry...
2018: Frontiers in Oncology
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