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https://www.readbyqxmd.com/read/29675214/controllable-extension-of-hairpin-structured-flaps-to-allow-low-background-cascade-invasive-reaction-for-a-sensitive-dna-logic-sensor-for-mutation-detection
#1
Yun-Long Liu, Hai-Ping Wu, Qiang Zhou, Qin-Xin Song, Jian-Zhong Rui, Xiao-Xiang Guan, Guo-Hua Zhou, Bing-Jie Zou
A DNA logic sensor was constructed for gene mutation analysis based on a novel signal amplification cascade by controllably extending a hairpin-structured flap to bridge two invasive reactions. The detection limit was as low as 0.07 fM, and the analytical specificity is high enough to unambiguously pick up 0.02% mutants from a large amount of wild-type DNA. Gene mutations related to the personalized medicine of gefitinib, a typical tyrosine kinase inhibitor, were analyzed by the DNA logic sensor with only a 15 minute response time...
February 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29673089/non-small-cell-lung-cancer-harboring-a-rare-egfr-l747p-mutation-showing-intrinsic-resistance-to-both-gefitinib-and-osimertinib-azd9291-a-case-report
#2
Jing Huang, Yiyin Wang, Yachao Zhai, Jin Wang
The most common EGFR mutations in non-small cell lung cancer are exon 19 deletions and exon 21 point mutations, which are both sensitive to EGFR-tyrosine kinase inhibitors. However, rare EGFR mutations do exist and how these mutations respond to tyrosine kinase inhibitors is not well understood. A Chinese woman diagnosed with stage IV lung adenocarcinoma harbored a rare EGFR L747P (2239-2240 TT > CC) mutation, and treatment with gefitinib and osimertinib failed to achieve the desired effect. Herein, possible correlations between gene analysis and the outcomes of subsequent treatment are discussed...
April 19, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29668619/gefitinib-provides-similar-effectiveness-and-improved-safety-than-erlotinib-for-advanced-non-small-cell-lung-cancer-a-meta-analysis
#3
Wenxiong Zhang, Yiping Wei, Dongliang Yu, Jianjun Xu, Jinhua Peng
BACKGROUND: The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. METHODS: We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29664235/mir-1-3p-and-mir-206-sensitizes-hgf-induced-gefitinib-resistant-human-lung-cancer-cells-through-inhibition-of-c-met-signalling-and-emt
#4
Demin Jiao, Jun Chen, Yu Li, Xiali Tang, Jian Wang, Wei Xu, Jia Song, You Li, Huimin Tao, Qingyong Chen
Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR-1-3p and miR-206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR-1-3p and miR-206 can overcome HGF-induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF...
April 17, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29662665/molecular-mechanism-of-action-and-potential-biomarkers-of-growth-inhibition-of-synergistic-combination-of-afatinib-and-dasatinib-against-gefitinib-resistant-non-small-cell-lung-cancer-cells
#5
Miao Wang, Alex Yuang-Chi Chang
Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) is the first choice of treatment for advanced non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, single agent usually has limited efficacy due to heterogeneous resistant mechanisms of cancer cells. Thus drug combination therapy would offer more benefits by synergistic interactions and avoidance of resistance emergence. In this study, we selected 8 NSCLC cell lines with different genetic characteristics as research models to investigate the efficacy of 4 agents (gefitinib, cetuximab, afatinib and dasatinib) and their combinations...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29660315/metronomic-vinorelbine-is-directly-active-on-non-small-cell-lung-cancer-cells-and-sensitizes-the-egfr-l858r-t790m-cells-to-reversible-egfr-tyrosine-kinase-inhibitors
#6
Paola Orlandi, Teresa Di Desidero, Giada Salvia, Beatrice Muscatello, Giulio Francia, Guido Bocci
Metronomic vinorelbine (mVNR) has been described primarily as an antiangiogenic therapy, and no direct effects of mVNR on Non Small Cell Lung Cancer (NSCLC) cells has yet been demonstrated. The aims of this study were i) to establish the direct activity of mVNR on NSCLC cells either EGFR wt or EGFRL858R/T790M , and ii) to quantify the synergism of the combination with reversible EGFR tyrosine kinase inhibitors (TKIs), investigating the underlying mechanism of action. Proliferation assays were performed on A-549 (EGFR-wthigh ), H-292 (EGFR-wt), H-358 (EGFR-wt), H-1975 (EGFRL858R/T790M ) NSCLC cell lines exposed to mVNR, its active metabolite deacetyl-VNR (D-VNR), gefitinib and erlotinib for 144h treatments...
April 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29656750/afatinib-in-heavily-pretreated-advanced-nsclc-patients-who-progressed-following-prior-gefitinib-or-erlotinib-compassionate-use-program-in-korea
#7
Moon Ki Choi, Jin Seok Ahn, Young-Chul Kim, Byoung Chul Cho, In-Jae Oh, Sang-We Kim, Jong Seok Lee, Joo-Hang Kim, Myung-Ju Ahn, Keunchil Park
INTRODUCTION: Afatinib, an irreversible ErbB family blocker, approved for first-line treatment of epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC). This study investigated experience of afatinib within a compassionate use program (CUP). METHODS: The afatinib CUP was an open-label, multicenter, single-arm program in Korea. We enrolled patients with stage IV NSCLC and who had received at least one line of previous cytotoxic chemotherapy and previous EGFR TKI treatment with either an EGFR mutation or documented clinical benefit...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29655550/proteomic-investigating-the-cooperative-lethal-effect-of-egfr-and-mdm2-inhibitors-on-ovarian-carcinoma
#8
Shing-Jyh Chang, En-Chi Liao, Hsin-Yueh Yeo, Wen-Hong Kuo, Hsin-Yi Chen, Yi-Ting Tsai, Yu-Shan Wei, Ying-Jen Chen, Yi-Shiuan Wang, Ji-Min Li, Chuan-Chi Shih, Chia-Hao Chan, Hsiu-Chuan Chou, Yung-Jen Chuang, Hong-Lin Chan
With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate...
April 12, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29650895/-chemoradiotherapy-using-molecular-targeted-therapy
#9
Hiroaki Akamatsu
Instead of the combination treatment with cytotoxic chemotherapy and radiation therapy, molecular targeted drugs is testing in many clinical trials. Because unexpected adverse events were reported in the previous trials using molecular targeted drugs with radiotherapy, attention should be paid to this combination. In EGFR mutated lung cancer, gefitinib with radiotherapy is testing.
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29650685/osimertinib-a-novel-dermatologic-adverse-event-profile-in-patients-with-lung-cancer
#10
Chia-Yu Chu, Jennifer Choi, Beth Eaby-Sandy, Corey J Langer, Mario E Lacouture
Dermatologic adverse events (dAEs) are common with the use of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. First- and second-generation agents (erlotinib, gefitinib, and afatinib) are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; the incidence and characterization of these dAEs have been well described. However, there is evidence that the dAE profile is different with third-generation EGFR-TKIs. Herein, we describe the dAEs associated with third-generation EGFR-TKIs and our clinical experience with osimertinib, a third-generation EGFR-TKI approved by the U...
April 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29630116/effects-of-mir-143-overexpression-on-proliferation-apoptosis-egfr-and-downstream-signaling-pathways-in-pc9-gr-cell-line
#11
Y-Z Dong, T Hu
OBJECTIVE: The functions of microRNAs in the regulation of apoptosis in non-small cell lung cancer (NSCLC) and the application in the therapeutical treatments were intensively studied. However, whether overexpression of miR-143 in lung cancer cells will affect the cell behaviors, such as proliferation or some underlying pathway, is largely unknown. This study aimed to examine the effect of miR-143 in PC9/GR cell line on the proliferation, apoptosis, EGFR and downstream signal pathways...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29624806/klf4-promotes-c-met-amplification-mediated-gefitinib-resistance-in-nsclc
#12
Wei Feng, Qianyi Xie, Suo Liu, Ying Ji, Chunyun Li, Chunle Wang, Longyu Jin
Gefitinib have been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells...
April 6, 2018: Cancer Science
https://www.readbyqxmd.com/read/29623068/nuclear-insulin-like-growth-factor-binding-protein-3-as-a-biomarker-in-triple-negative-breast-cancer-xenograft-tumors-effect-of-targeted-therapy-and-comparison-with-chemotherapy
#13
Sohel M Julovi, Janet L Martin, Robert C Baxter
Triple-negative breast cancer (TNBC) typically has a worse outcome than other breast cancer subtypes, in part owing to a lack of approved therapeutic targets or prognostic markers. We have previously described an oncogenic pathway in basal-like TNBC cells, initiated by insulin-like growth factor binding protein-3 (IGFBP-3), in which the epidermal growth factor receptor (EGFR) is transactivated by sphingosine-1-phosphate (S1P) resulting from sphingosine kinase (SphK)-1 activation. Oncogenic IGFBP-3 signaling can be targeted by combination treatment with the S1P receptor modulator and SphK inhibitor, fingolimod, and the EGFR kinase inhibitor, gefitinib (F + G)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29620166/antitumour-effects-and-mechanisms-of-action-of-the-panher-inhibitor-dacomitinib-alone-and-in-combination-with-the-stat3-inhibitor-s3i-201-in-human-sarcoma-cell-lines
#14
Xiaochun Wang, David Goldstein, Philip J Crowe, Jia-Lin Yang
The 5-year survival rate for metastatic sarcoma is 16%. Although the phosphorylated human epidermal growth factor receptor (pEGFR/HER1) has been shown to be an independent predictor of overall survival in patients with sarcoma, we have previously demonstrated that sarcoma cell lines exhibit resistance, despite gefitinib blocking p-EGFR and signal transducers in EGFR downstream pathways. Gefitinib failed to decrease the ratio of phosphorylated (p-)signal transducer and activator of transcription (STAT3)/p-STAT1, suggesting that relative STAT3 abundance and activation may be involved in drug resistance...
March 27, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29618949/a-cross-talk-between-integrin-%C3%AE-4-and-epidermal-growth-factor-receptor-induces-gefitinib-chemoresistance-to-gastric-cancer
#15
Jia Huafeng, Zhang Deqing, Ding Yong, Zhang Yulian, Hu Ailing
Background: Gastric cancer presents a major health burden worldwide. Therefore, many molecular targeting agents have been evaluated for treatment of gastric cancer. Gefitinib has shown anticancer activity against gastric cancer which work through inhibiting epidermal growth factor receptor (EGFR). However, the effect of gefitinib is limited due to its resistance. Therefore, understanding the mechanisms of gefitinib resistance is desperately needed to formulate novel strategies against gastric cancer...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29616327/whole-exome-sequencing-identifies-key-mutated-genes-in-t790m-wildtype-cmet-unamplified-lung-adenocarcinoma-with-acquired-resistance-to-first-generation-egfr-tyrosine-kinase-inhibitors
#16
Chenguang Li, Hailin Liu, Bin Zhang, Liqun Gong, Yanjun Su, Zhenfa Zhang, Changli Wang
PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma harboring EGFR-activating mutations will inevitably acquire resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). EGFR T790M mutation and cMET amplification are common mechanisms. Further study is needed to explore unknown genomic alterations contributing to drug resistance. METHODS: Tumor and blood samples from 69 stage IIIB-IV NSCLC patients defined as acquired resistance to first-generation EGFR TKIs (gefitinib, erlotinib or ecotinib) were collected...
April 3, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29599332/phenethyl-isothiocyanate-induces-apoptotic-cell-death-through-the-mitochondria-dependent-pathway-in-gefitinib-resistant-nci-h460-human-lung-cancer-cells-in-vitro
#17
Te-Chun Hsia, Yi-Ping Huang, Yi-Wen Jiang, Hsin-Yu Chen, Zheng-Yu Cheng, Yung-Ting Hsiao, Cheng-Yen Chen, Shu-Fen Peng, Fu-Shin Chueh, Yu-Cheng Chou, Jing-Gung Chung
BACKGROUND/AIM: Some lung cancer patients treated with gefitinib develop resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits anticancer activities in many human cancer cell lines. Currently, there is no available information on the possible modification of gefitinib resistance of lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant lung cancer NCI-H460 cells were investigated in vitro...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29594931/validation-of-18-f-flt-as-a-perfusion-independent-imaging-biomarker-of-tumour-response-in-egfr-mutated-nsclc-patients-undergoing-treatment-with-an-egfr-tyrosine-kinase-inhibitor
#18
R Iqbal, G M Kramer, V Frings, E F Smit, O S Hoekstra, R Boellaard
BACKGROUND: 3'-Deoxy-3'-[18 F]fluorothymidine ([18 F]FLT) was proposed as an imaging biomarker for the assessment of in vivo cellular proliferation with positron emission tomography (PET). The current study aimed to validate [18 F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [18 F]FLT uptake and perfusion in non-small cell lung cancer (NSCLC) patients undergoing treatment with a tyrosine kinase inhibitor (TKI). Six patients with metastatic NSCLC, having an activating epidermal growth factor receptor (EGFR) mutation, were included in this study...
March 27, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29594878/acquired-resistance-to-an-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-egfr-tki-in-an-uncommon-g719s-egfr-mutation
#19
Atsushi Osoegawa, Takafumi Hashimoto, Yohei Takumi, Miyuki Abe, Tomonori Yamada, Ryoji Kobayashi, Michiyo Miyawaki, Hideya Takeuchi, Tatsuro Okamoto, Kenji Sugio
Background Acquired resistance (AR) to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is a common event, and several underlying mechanisms, including T790 M, MET amplification and PTEN downregulation, have been reported for the common EGFR mutations. EGFR G719X is an uncommon mutation that has been reported to show sensitivity to EGFR-TKIs. However, no established cell lines harboring the EGFR G719X have been reported in the literature. Materials and Methods G719S-GR cells were established from malignant pleural effusion of a patient whose tumor developed AR from gefitinib treatment...
March 28, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29592872/the-long-non-coding-rna-snhg5-regulates-gefitinib-resistance-in-lung-adenocarcinoma-cells-by-targeting-mir-377-casp1-axis
#20
Zhenxing Wang, Liming Pan, Haixiang Yu, Yue Wang
Gefitinib resistance is one the major obstacles for the treatment of lung adenocarcinoma (LAD). The present study aimed to investigate the effects of the long non-coding RNA, SNHG5 on gefitinib resistance in LAD and explore the underlying mechanisms. The quantitative real-time PCR results showed that SNHG5 expression was significantly downregulated in LAD patients with acquired gefitinib resistance and gefitinib resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib sensitive LAD cells to gefitinib treatment...
March 28, 2018: Bioscience Reports
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