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Egfr kinase

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https://www.readbyqxmd.com/read/29150923/pkg-ii-effectively-reversed-egf-induced-protein-expression-alterations-in-human-gastric-cancer-cell-lines
#1
Hai Qian, Yan Tao, Lu Jiang, Ying Wang, Ting Lan, Min Wu, Ji Pang, Kwaku Appiah-Kubi, Yongchang Chen, Yan Wu
Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP-dependent protein kinase (PKG II) could block the EGF-EGFR axis as well as down-stream signaling pathways for example, MAPK, PI3K and PLC in gastric cancer cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human gastric cancer cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad-PKG II) to up-regulate PKG II and then treated with 8-pCPT-cGMP...
November 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29150249/accuracy-of-the-cobas-egfr-mutation-assay-in-non-small-cell-lung-cancer-compared-with-three-laboratory-developed-tests
#2
Haruhiko Nakamura, Hirotaka Koizumi, Hiroki Sakai, Hiroyuki Kimura, Tomoyuki Miyazawa, Hideki Marushima, Hisashi Saji, Masayuki Takagi
BACKGROUND: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory-developed tests (LDTs). MATERIALS AND METHODS: After screening for EGFR mutations using formalin-fixed-paraffin-embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays...
October 28, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29143897/anaplastic-lymphoma-kinase-testing-ihc-vs-fish-vs-ngs
#3
REVIEW
Xiaomin Niu, Jody C Chuang, Gerald J Berry, Heather A Wakelee
Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4-7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29143497/detection-and-monitoring-of-driver-mutations-by-next-generation-sequencing-in-squamous-cell-lung-cancer-patient-and-possible-predictive-biomarker-of-third-generation-egfr-tyrosine-kinase-inhibitors
#4
Xiaoyan Shen, Jie Shen, Hang Zhang, Yuxin Cheng, Yang Yang, Jiahui Gao, Yu Zhang, Rutian Li, Baorui Liu, Lifeng Wang
Driver mutation detection and the development of targeted drugs have significantly improved survival of advanced lung adenocarcinoma patients with driver mutations. However, we still lack understanding of druggable mutations in patients with advanced squamous cell lung cancer (SQCLC). Less than 10% of SQCLC patients have EGFR gene mutations, thus we have limited knowledge of biological molecular changes with first generation EGFR-tyrosine kinase inhibitor (TKI) resistance. We report a case of an SQCLC patient treated with first-line platinum-doublet chemotherapy...
November 16, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29141884/a-method-of-high-throughput-functional-evaluation-of-egfr-gene-variants-of-unknown-significance-in-cancer
#5
Shinji Kohsaka, Masaaki Nagano, Toshihide Ueno, Yoshiyuki Suehara, Takuo Hayashi, Naoko Shimada, Kazuhisa Takahashi, Kenji Suzuki, Kazuya Takamochi, Fumiyuki Takahashi, Hiroyuki Mano
Numerous variants of unknown significance (VUS) have been identified through large-scale cancer genome projects, although their functional relevance remains uninvestigated. We developed a mixed-all-nominated-mutants-in-one (MANO) method to evaluate the transforming potential and drug sensitivity of oncogene VUS in a high-throughput manner and applied this method to 101 nonsynonymous epidermal growth factor receptor (EGFR) mutants. We discovered a number of mutations conferring resistance to EGFR tyrosine kinase inhibitors (TKIs), including gefitinib- and erlotinib-insensitive missense mutations within exon 19 and other gefitinib-resistant mutations, such as L833V, A839T, V851I, A871T, and G873E...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29140528/evaluation-of-renal-function-change-during-first-line-tyrosine-kinase-inhibitor-therapy-for-metastatic-renal-cell-carcinoma
#6
Hiroki Ishihara, Tsunenori Kondo, Hironori Fukuda, Kazuhiko Yoshida, Kenji Omae, Toshio Takagi, Junpei Iizuka, Hirohito Kobayashi, Kazunari Tanabe
Background: The change in renal function induced by first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma remains unclear. Methods: One hundred and thirty-four patients were evaluated. Sunitinib (SU) and sorafenib (SO) were administered to 91 (67.9%) and 43 (32.1%) patients, respectively. The change in estimated glomerular filtration rate (ΔeGFR) was calculated as [(eGFR at each time point - pre-treatment eGFR)/pre-treatment eGFR] × 100...
November 13, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29140271/molecular-targeted-therapies-for-epidermal-growth-factor-receptor-and-its-resistance-mechanisms
#7
REVIEW
Toshimitsu Yamaoka, Motoi Ohba, Tohru Ohmori
Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29137977/downregulation-of-caveolin-1-increased-egfr-tkis-sensitivity-in-lung-adenocarcinoma-cell-line-with-egfr-mutation
#8
Yujie Cui, Tienian Zhu, Xuejing Song, Jiankun Liu, Shuang Liu, Ruijing Zhao
Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, have shown notable effects in lung adenocarcinoma patients harboring EGFR mutations, there are significant differences between individual patients in the degree of benefits provided by EGFR-TKIs. Some evidence supports a role for caveolin-1 (Cav-1) in modulating drug sensitivity. This study aimed to investigate whether Cav-1 plays an important role in sensitivity to EGFR-TKIs in lung adenocarcinoma cells...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137335/inhibition-of-cell-cycle-progression-by-the-hydroxytyrosol-cetuximab-combination-yields-enhanced-chemotherapeutic-efficacy-in-colon-cancer-cells
#9
Erika Terzuoli, Ginevra Nannelli, Maria Frosini, Antonio Giachetti, Marina Ziche, Sandra Donnini
Hydroxytyrosol (HT), a polyphenol of olive oil, downregulates epidermal growth factor (EGFR) expression and inhibits cell proliferation in colon cancer (CC) cells, with mechanisms similar to that activated by the EGFR inhibitor, cetuximab. Here, we studied whether HT treatment would enhance the cetuximab inhibitory effects on cell growth in CC cells. HT-cetuximab combination showed greater efficacy in reducing cell growth in HT-29 and WiDr cells at concentrations 10 times lower than when used as single agents...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#10
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29136465/recent-progress-of-small-molecule-epidermal-growth-factor-receptor-egfr-inhibitors-against-c797s-resistance-in-non-small-cell-lung-cancer
#11
Lingfeng Chen, Weitao Fu, Lulu Zheng, Zhiguo Liu, Guang Liang
The epidermal growth factor receptor (EGFR) has been a particular interest for drug development for treatment of non-small-cell lung cancer (NSCLC). The current third-generation EGFR small-molecule inhibitors, especially osimertinib, are at the forefront clinically for treatment of patients with NSCLC. However, a high percentage of these treated patients developed a tertiary cystein797 to serine790 (C797S) mutation in the EGFR kinase domain. This C797S mutation is thought to induce resistance to all current irreversible EGFR TKIs...
November 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29134959/targeting-ret-driven-cancers-lessons-from-evolving-preclinical-and-clinical-landscapes
#12
REVIEW
Alexander Drilon, Zishuo I Hu, Gillianne G Y Lai, Daniel S W Tan
The gene encoding the receptor-tyrosine kinase RET was first discovered more than three decades ago, and activating RET rearrangements and mutations have since been identified as actionable drivers of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, and confirmed responses to targeted therapy with these agents have been observed in patients with RET-rearranged lung cancers or RET-mutant thyroid cancers. Nevertheless, response rates to RET-directed therapy are modest compared with those achieved using targeted therapies matched to other oncogenic drivers of solid tumours, such as sensitizing EGFR or BRAF(V600E) mutations, or ALK or ROS1 rearrangements...
November 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29134648/pharmacokinetics-pharmacodynamics-and-proposed-dosing-of-the-oral-jak1-and-jak2-inhibitor-baricitinib-in-pediatric-and-young-adult-candle-and-savi-patients
#13
Hanna Kim, Kristina M Brooks, Cheng Cai Tang, Paul Wakim, Mary Blake, Stephen R Brooks, Gina A Montealegre Sanchez, Adriana A de Jesus, Yan Huang, Wanxia Li Tsai, Massimo Gadina, Apurva Prakash, Jonathan Marcus Janes, Xin Zhang, William L Macias, Parag Kumar, Raphaela Goldbach-Mansky
Population pharmacokinetic (popPK) modeling was used to characterize the PK profile of the oral janus kinase (JAK)1/JAK2 inhibitor, baricitinib, in 18 patients with Mendelian interferonopathies who are enrolled in a compassionate use program. Patients received doses between 0.1 to 17 mg per day. Covariates of weight and renal function significantly influenced volume-of-distribution and clearance respectively. The half-life of baricitinib in patients less than 40kg was substantially shorter than in adult populations, requiring the need for dosing up to 4 times daily...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29133145/egfr-and-ras-regulate-ddx59-during-lung-cancer-development
#14
Lin Yang, Hanyin Zhang, Dan Chen, Peikun Ding, Yunchang Yuan, Yandong Zhang
Oncogenes EGFR and ras are frequently mutated and activated in human lung cancers. In this report, we found that both EGFR and Ras signaling can upregulate RNA helicase DDX59 in lung cancer cells. DDX59 can be induced through the mitogen activated protein kinase (MAPK) pathway after EGFR or Ras activation. Inhibitors for Ras/Raf/MAP pathway significantly decreased DDX59 expression at both protein and mRNA levels. Through immunohistochemistry, we found that DDX59 protein expression correlated with Ras and EGFR mutation status in human lung adenocarcinoma...
November 10, 2017: Gene
https://www.readbyqxmd.com/read/29133033/design-synthesis-and-evaluation-of-a-ring-modified-lamellarin-n-analogues-as-noncovalent-inhibitors-of-the-egfr-t790m-l858r-mutant
#15
Tsutomu Fukuda, Teppei Umeki, Keiji Tokushima, Gao Xiang, Yuki Yoshida, Fumito Ishibashi, Yusuke Oku, Naoyuki Nishiya, Yoshimasa Uehara, Masatomo Iwao
A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory profile against the T790M/L858R mutant [IC50 (WT) = 31.8 nM; IC50 (T790M/L858R) = 8.9 nM]. The effects of A-ring-substituents on activity were rationalized by docking studies...
October 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29132432/ac-93253-iodide-a-novel-src-inhibitor-suppresses-nsclc-progression-by-modulating-multiple-src-related-signaling-pathways
#16
Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J W Chen
BACKGROUND: The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment...
November 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29130514/involvement-of-src-signaling-in-the-synergistic-effect-between-cisplatin-and-digoxin-on-cancer-cell-viability
#17
Duane Gischewski Pereira, Mariana Alves Resende Salgado, Sayonarah Carvalho Rocha, Hérica L Santos, José Augusto Fp Villar, Ruben G Contreras, Carlos Frederico Leite Fontes, Leandro Augusto Barbosa, Vanessa Faria Cortes
Cisplatin and other platinum-containing drugs have played a crucial role in anticancer treatments for over 30 years. However, treatment with cisplatin may cause serious side effects, such as myelosuppression, nausea, ototoxicity, nephrotoxicity and cell resistance processes. In addition, cardiotonic steroids, particularly digoxin, have recently been suggested to exert potent anticancer effects. Therefore, it is possible that the combined treatment of HeLa cells with cisplatin and digoxin can ameliorate the cytotoxic effects and decrease the side effects of cisplatin...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29126017/epidermal-growth-factor-receptor-overexpression-and-outcomes-in-early-breast-cancer-a-systematic-review-and-a-meta-analysis
#18
REVIEW
Galileo A Gonzalez-Conchas, Laura Rodriguez-Romo, David Hernandez-Barajas, Juan F Gonzalez-Guerrero, Ivan A Rodriguez-Fernandez, Adrian Verdines-Perez, Arnoud J Templeton, Alberto Ocana, Bostjan Seruga, Ian F Tannock, Eitan Amir, Francisco E Vera-Badillo
BACKGROUND: The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane tyrosine-kinase receptors. Studies exploring the prognostic role of EGFR-overexpression in early breast cancer have shown variable results, and the true prognostic value of EGFR is unknown. METHODS: A systematic review of identified publications exploring the association between EGFR-overexpression (as defined from different techniques and cut-offs) and outcomes [disease-free (DFS) and, overall survival (OS)] in women with early breast cancer...
October 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29125548/liquid-biopsy-and-therapeutic-targets-present-and-future-issues-in-thoracic-oncology
#19
REVIEW
Paul Hofman
The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the detection of activating or resistance mutations in EGFR. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors. ALK is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in ALK identified with tumor tissue...
November 10, 2017: Cancers
https://www.readbyqxmd.com/read/29125233/in-vivo-imaging-xenograft-models-for-the-evaluation-of-anti-brain-tumor-efficacy-of-targeted-drugs
#20
Kenji Kita, Sachiko Arai, Akihiro Nishiyama, Hirokazu Taniguchi, Koji Fukuda, Rong Wang, Tadaaki Yamada, Shinji Takeuchi, Shoichiro Tange, Atsushi Tajima, Mitsutoshi Nakada, Kazuo Yasumoto, Yoshiharu Motoo, Takashi Murakami, Seiji Yano
Molecular-targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR-L858R/T790M-positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)-dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3-NTRK1 gene fusion...
November 10, 2017: Cancer Medicine
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