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Egfr kinase

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https://www.readbyqxmd.com/read/28432840/detection-of-egfr-mutations-in-patients-with-non-small-cell-lung-cancer-by-high-resolution-melting-comparison-with-other-methods
#1
Carlos Martínez-Carretero, Fernando Iguaz Pascual, Antonio Rus, Ivan Bernardo
BACKGROUND: The discovery of mutations in the epidermal growth factor receptor gene (EGFR) related to the clinical response to tyrosine kinase inhibitors, has transformed the management of non-small cell lung cancer (NSCLC). Several methods have been developed for determination of mutations in EGFR, with different sensitivity and potential ability to detect a different number of mutations. METHODS: We developed a screening method by high resolution melting (HRM) to detect EGFR mutations, and compared the results of 123 fixed in formalin and paraffin embedded (FFPE) tumor tissue samples with the detection of mutations by allele-specific PCR...
April 22, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28432586/cdc20-with-malignant-progression-and-poor-prognosis-of-astrocytoma-revealed-by-analysis-on-gene-expression
#2
Yiming Ding, Shuqing Yu, Zhaoshi Bao, Yanwei Liu, Tingyu Liang
The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#3
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430623/clinical-efficacy-of-icotinib-in-lung-cancer-patients-with-different-egfr-mutation-status-a-meta-analysis
#4
REVIEW
Jian Qu, Ya-Nan Wang, Ping Xu, Da-Xiong Xiang, Rui Yang, Wei Wei, Qiang Qu
Icotinib is a novel and the third listed epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which exerts a good anti-tumor efficacy on non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs has been shown to be associated with the EGFR mutation status, especially exon 19 deletion (19Del) and exon 21 L858R mutation. Therefore, a meta-analysis was performed to assess the efficacy of icotinib in NSCLC patients harboring EGFR mutations (19Del or L858R) and wild type (19Del and L858R loci wild type)...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429795/cd200-positive-cancer-associated-fibroblasts-augment-the-sensitivity-of-epidermal-growth-factor-receptor-mutation-positive-lung-adenocarcinomas-to-egfr-tyrosine-kinase-inhibitors
#5
Masayuki Ishibashi, Shinya Neri, Hiroko Hashimoto, Tomoyuki Miyashita, Tatsuya Yoshida, Yuka Nakamura, Hibiki Udagawa, Keisuke Kirita, Shingo Matsumoto, Shigeki Umemura, Kiyotaka Yoh, Seiji Niho, Masahiro Tsuboi, Kenkichi Masutomi, Koichi Goto, Atsushi Ochiai, Genichiro Ishii
Cancer associated fibroblasts (CAFs) play important roles in the chemotherapeutic process, especially through influencing the resistance of tumor cells to molecular targeted therapy. Here we report the existence of a special subpopulation of patient-specific-CAFs that augment the sensitivity of EGFR gene mutation-positive lung cancer to the EGFR-tyrosine kinase inhibitor (EGFR-TKI), gefitinib. When cocultured with EGFR mutation positive lung cancer cells, these CAFs increased the apoptic effect of gefitinib on cancer cells, whereas, in the absence of gefitinib, they did not affect cancer cell viability...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428274/egfr-mediates-responses-to-small-molecule-drugs-targeting-oncogenic-fusion-kinases
#6
Aria Vaishnavi, Laura Schubert, Uwe Rix, Lindsay A Marek, Anh T Le, Stephen Keysar, Magdalena J Glogowska, Matthew A Smith, Severine L Kako, Natalia J Sumi, Kurtis D Davies, Kathryn E Ware, Marileila Varella-Garcia, Eric B Haura, Antonio Jimeno, Lynn E Heasley, Dara L Aisner, Robert C Doebele
Oncogenic kinase fusions of ALK, ROS1, RET and NTRK1 act as drivers in human lung and other cancers. Residual tumor burden following treatment of ALK or ROS1+ lung cancer patients with oncogene-targeted therapy ultimately enables the emergence of drug-resistant clones, limiting the long-term effectiveness of these therapies. To determine the signaling mechanisms underlying incomplete tumor cell killing in oncogene-addicted cancer cells, we investigated the role of EGFR signaling in drug-naive cancer cells harboring these oncogene fusions...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428148/plasma-ctdna-analysis-for-detection-of-the-egfr-t790m-mutation-in-patients-with-advanced-non-small-cell-lung-cancer
#7
Suzanne Jenkins, James C-H Yang, Suresh S Ramalingam, Karen Yu, Sabina Patel, Susie Weston, Rachel Hodge, Mireille Cantarini, Pasi A Jänne, Tetsuya Mitsudomi, Glenwood D Goss
INTRODUCTION: Tumor biopsies for detecting epidermal growth factor receptor mutations (EGFRm) in advanced non-small cell lung cancer (NSCLC) are invasive, costly and not always feasible for patients with late-stage disease. The clinical utility of the cobas(®) EGFR Mutation Test v2 with plasma samples from patients with NSCLC at disease progression following previous EGFR-tyrosine kinase inhibitor (TKI) therapy was investigated to determine osimertinib treatment eligibility. METHODS: Matched tumor tissue and plasma samples from patients screened for AURA extension and AURA2 phase II studies were tested for EGFRm using tissue- and plasma-based cobas(®) EGFR Mutation Tests v2...
April 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28428083/the-roles-of-subcellularly-located-egfr-in-autophagy
#8
REVIEW
Hongsen Li, Liangkun You, Jiansheng Xie, Hongming Pan, Weidong Han
The epidermal growth factor receptor (EGFR) is a well-studied receptor-tyrosine kinase that serves vital roles in regulation of organ development and cancer progression. EGFR not only exists on the plasma membrane, but also widely expressed in the nucleus, endosomes, and mitochondria. Most recently, several lines of evidences indicated that autophagy is regulated by EGFR in kinase-active and -independent manners. In this review, we summarized recent advances in our understanding of the functions of different subcellularly located EGFR on autophagy...
April 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28428040/design-synthesis-and-docking-studies-of-quinazoline-analogues-bearing-aryl-semicarbazone-scaffolds-as-potent-egfr-inhibitors
#9
Yuanbiao Tu, Caolin Wang, Shan Xu, Zhou Lan, Wei Li, Jiaqian Han, Yuanzhang Zhou, Pengwu Zheng, Wufu Zhu
Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a-o and 10a-o) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o was further evaluated for the inhibitory activity against EGFR kinases. Four of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM to nanomole range. Two of them are equal to more active than positive control afatinib against one or more cell lines...
April 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28427247/molecular-testing-of-lung-cancers
#10
Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee
Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics...
April 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28427238/clinical-features-and-treatment-outcome-of-non-small-cell-lung-cancer-nsclc-patients-with-uncommon-or-complex-epidermal-growth-factor-receptor-egfr-mutations
#11
Stefano Frega, Martina Lorenzi, Matteo Fassan, Stefano Indraccolo, Fiorella Calabrese, Adolfo Favaretto, Laura Bonanno, Valentina Polo, Giulia Zago, Francesca Lunardi, Ilaria Attili, Alberto Pavan, Massimo Rugge, Valentina Guarneri, PierFranco Conte, Giulia Pasello
INTRODUCTION: Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. RESULTS: Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427161/efficacy-of-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-tkis-in-targeted-therapy-of-lung-squamous-cell-carcinoma-patients-with-egfr-mutation-a-pooled-analysis
#12
Jingqi Zhuang, Yongfeng Yu, Ziming Li, Shun Lu
PURPOSE: This pooled analysis aims to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in lung squamous cell carcinoma with EGFR mutation. METHODS: Advanced stage (IIIB/IV) lung squamous cell carcinoma patients with EGFR mutations treated with EGFR-TKIs were extracted from the publications searched from the databases of EMBASE, Medline (Ovid SP), Web of Science, Cochrane library, PubMed Publisher, ASCO meeting abstract and Google Scholar before August 2016, or identified from the database of Shanghai Chest Hospital from July 2014 to August 2016...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#13
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28424775/second-line-treatment-of-non-small-cell-lung-cancer-focus-on-the-clinical-development-of-dacomitinib
#14
REVIEW
Jon Zugazagoitia, Asunción Díaz, Elisabeth Jimenez, Juan Antonio Nuñez, Lara Iglesias, Santiago Ponce-Aix, Luis Paz-Ares
Dacomitinib is a second-generation, irreversible, covalent pan-HER tyrosine-kinase inhibitor (TKI). It showed potent EGFR signaling inhibition in experimental models, including first-generation TKI-resistant non-small cell lung cancer (NSCLC) cell lines. This preclinical efficacy did not translate into clinically meaningful treatment benefits for advanced, pretreated, molecularly unselected NSCLC patients enrolled in two parallel phase III trials. Dacomitinib and erlotinib showed overlapping efficacy data in chemotherapy-pretreated EGFR wild-type (WT) patients in the ARCHER 1009 trial...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28424220/gababr-induced-egfr-transactivation-promotes-migration-of-human-prostate-cancer-cells
#15
Shuai Xia, Cong He, Yini Zhu, Suyun Wang, Huiping Li, Zhongling Zhang, Xinnong Jiang, Jianfeng Liu
G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been detected in human cancer tissues and cancer cell lines, but the role of GABABR in these cells is controversial and the underlying mechanism remains poorly understood. Here, we investigated whether GABABR hijacks RTK signaling to modulate the fates of human prostate cancer cells...
April 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28423644/disulfide-bond-disrupting-agents-activate-the-unfolded-protein-response-in-egfr-and-her2-positive-breast-tumor-cells
#16
Renan B Ferreira, Mengxiong Wang, Mary E Law, Bradley J Davis, Ashton N Bartley, Paul J Higgins, Michael S Kilberg, Katherine E Santostefano, Naohiro Terada, Coy D Heldermon, Ronald K Castellano, Brian K Law
Many breast cancer deaths result from tumors acquiring resistance to available therapies. Thus, new therapeutic agents are needed for targeting drug-resistant breast cancers. Drug-refractory breast cancers include HER2+ tumors that have acquired resistance to HER2-targeted antibodies and kinase inhibitors, and "Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets Estrogen Receptor, Progesterone Receptor, and HER2. A significant fraction of TNBCs overexpress the HER2 family member Epidermal Growth Factor Receptor (EGFR)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422737/generation-of-lung-cancer-cell-lines-harboring-egfr-t790m-mutation-by-crispr-cas9-mediated-genome-editing
#17
Mi-Young Park, Min Hee Jung, Eun Young Eo, Seokjoong Kim, Sang Hoon Lee, Yeon Joo Lee, Jong Sun Park, Young Jae Cho, Jin Haeng Chung, Cheol Hyeon Kim, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
Tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are effective against lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations. However, cancer cells can develop resistance to these agents with prolonged exposure; in over 50% of cases, this is attributable to the EGFR T790M mutation. Moreover, additional resistance mutations can arise with the use of new drugs. Cancer cell lines with specific mutations can enable the study of resistance mechanisms. In this study, we introduced the EGFR T790M mutation into the PC9 human lung cancer cell line-which has a deletion in exon 19 of the EGFR gene-by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9-mediated genome editing...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422715/a-novel-bmx-variant-promotes-tumor-cell-growth-and-migration-in-lung-adenocarcinoma
#18
Ye Wang, Jufeng Xia, Zhaoyuan Fang, Fei Li, Duo Li, Zuoyun Wang, Yan Feng, Jian Zhang, Haiquan Chen, Hongbin Ji, Hongyan Liu
The non-receptor tyrosine kinase BMX has been reported in several solid tumors. However, the alternative splicing of BMX and its clinical relevance in lung cancer remain to be elucidated. Exon1.0 array was used to identify a novel alternative splicing of BMX, BMXΔN, which was confirmed by rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. BMXΔN, resulting from exon skipping with excluding exon 1 to exon 8 of BMX gene, was found in 12% human lung adenocarcinoma specimens...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420725/monitoring-daily-dynamics-of-early-tumor-response-to-targeted-therapy-by-detecting-circulating-tumor-dna-in-urine
#19
Hatim Husain, Vladislava O Melnikova, Karena Kosco, Brian Woodward, Soham More, Sandeep C Pingle, Elizabeth Weihe, Ben Ho Park, Muneesh Tewari, Mark G Erlander, Ezra E W Cohen, Scott M Lippman, Razelle Kurzrock
Purpose: Non-invasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine. Experimental Design : We tested the hypothesis that dynamic changes in epidermal growth factor receptor (EGFR) activating (exon 19del and L858R) and resistance (T790M) mutation levels detected in urine could inform tumor response within days of therapy for advanced non-small cell lung cancer (NSCLC) patients receiving osimertinib, a second line third generation anti-EGFR tyrosine kinase inhibitor...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28420162/hepatocyte-growth-factor-a-key-tumor-promoting-factor-in-the-tumor-microenvironment
#20
REVIEW
Benjamin Yaw Owusu, Robert Galemmo, James Janetka, Lidija Klampfer
The tumor microenvironment plays a key role in tumor development and progression. Stromal cells secrete growth factors, cytokines and extracellular matrix proteins which promote growth, survival and metastatic spread of cancer cells. Fibroblasts are the predominant constituent of the tumor stroma and Hepatocyte Growth Factor (HGF), the specific ligand for the tyrosine kinase receptor c-MET, is a major component of their secretome. Indeed, cancer-associated fibroblasts have been shown to promote growth, survival and migration of cancer cells in an HGF-dependent manner...
April 17, 2017: Cancers
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