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https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#1
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28096505/the-neuropilin-2-isoform-nrp2b-uniquely-supports-tgf%C3%AE-mediated-progression-in-lung-cancer
#2
Robert M Gemmill, Patrick Nasarre, Joyce Nair-Menon, Federico Cappuzzo, Lorenza Landi, Armida D'Incecco, Hidetaka Uramoto, Takeshi Yoshida, Eric B Haura, Kent Armeson, Harry A Drabkin
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28093061/polyphyllin-ii-restores-sensitization-of-the-resistance-of-pc-9-zd-cells-to-gefitinib-by-a-negative-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#3
Ruzhen Zheng, Hao Jiang, Jinhui Li, Xinge Liu, Hongwei Xu
: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restrict their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia...
December 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28089942/targeting-egfr-t790m-mutation-in-nsclc-from-biology-to-evaluation-and-treatment
#4
Antonio Passaro, Elena Guerini-Rocco, Alessia Pochesci, Davide Vacirca, Gianluca Spitaleri, Chiara Matilde Catania, Alessandra Rappa, Massimo Barberis, Filippo de Marinis
The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life...
January 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28086832/norcantharidin-inhibits-cell-growth-by-suppressing-the-expression-and-phosphorylation-of-both-egfr-and-c-met-in-human-colon-cancer-cells
#5
Peiju Qiu, Siwen Wang, Ming Liu, He Ma, Xuan Zeng, Meng Zhang, Lingling Xu, Yidi Cui, Huixin Xu, Yang Tang, Yanli He, Lijuan Zhang
BACKGROUND: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study. METHODS: Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28075527/recent-development-of-the-second-and-third-generation-irreversible-egfr-inhibitors
#6
REVIEW
Weiwei Han, Yongli Du
Recent reports suggested that essential directions for new lung cancer, breast carcinoma therapies, as well as the roomier realm of targeted cancer therapies were provided through targeting the epidermal growth factor receptor (EGFR). Patients who carrying non-small cell lung carcinoma (NSCLC) with activating mutations in EGFR initially respond well to the EGFR inhibitors erlotinib and gefitinib, which were located the active site of the EGFR kinase and designed to act as competitive inhibitors of combining with the ATP...
January 11, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28065465/a-multicenter-double-blind-phase-ii-study-of-metformin-with-gefitinib-as-first-line-therapy-of-locally-advanced-non-small-cell-lung-cancer
#7
Kun-Lin Li, Li Li, Peng Zhang, Jun Kang, Yu-Bo Wang, Heng-Yi Chen, Yong He
We present the rationale and study design of the CGMT (combined gefitinib and metformin therapy) trial (www.ClinicalTrials.gov Identifier: NCT01864681), which is aimed at treating locally advanced non-small-cell lung cancer. The CGMT trial is a multicenter, phase II randomized, double-blinded, and placebo-controlled study, which is designed to evaluate the safety and efficacy of metformin in combination with gefitinib as first-line therapy in patients presenting with stage IIIb-IV non-small-cell lung cancer expressing the epidermal growth factor receptor mutant...
December 22, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28064206/retrospective-analysis-of-survival-in-patients-with-leptomeningeal-carcinomatosis-from-lung-adenocarcinoma-treated-with-erlotinib-and-gefitinib
#8
Jumpei Kashima, Yusuke Okuma, Maki Miwa, Yukio Hosomi
BACKGROUND: Leptomeningeal carcinomatosis is a relatively rare metastatic form of non-small cell lung cancer, which can impact prognosis. There is an increasing need for selecting suitable epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors among those currently included in standard care for EGFR mutation-positive patients. We compared the efficacy of gefitinib and erlotinib in survival of patients with leptomeningeal carcinomatosis. PATIENTS AND METHODS: The medical records of 269 patients who received tyrosine kinase inhibitors at a single center were retrospectively reviewed...
January 6, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28059038/toxicities-of-receptor-tyrosine-kinase-inhibitors-in-cancer-pharmacotherapy-management-with-clinical-pharmacology
#9
Ken-Ichi Fujita, Hiroo Ishida, Yutaro Kubota, Yasutsuna Sasaki
A number of molecularly targeted anticancer drugs that efficiently inhibit receptor tyrosine kinases, so-called receptor tyrosine kinase inhibitors (TKIs), have been developed. Although these receptor TKIs are generally well tolerated, unexpected toxicities sometimes occur in various organs. TKI-induced adverse events not only lower the quality of life of cancer patients but also reduce dose intensity, and sometimes result in treatment discontinuation. To reduce adverse drug events and increase treatment efficacy, oncologists and clinical pharmacologists have made efforts to establish strategies to treat patients via optimal selection and dosing of TKIs...
January 5, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#10
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
December 19, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28043153/outcome-of-egfr-inhibitors-treatment-in-advanced-nsclc-patients-not-enrolled-in-clinical-trials
#11
M Mencoboni, R A Filiberti, P Taveggia, A Bruzzone, A Garuti, L Del Corso, E Ginocchio, A Brianti, C Simonassi, P Zucali
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a treatment after first-line chemotherapy in patients with advanced NSCLC. We assessed the predictive and prognostic role of EGFR and Kras mutations in NSCLC patients treated with TKIs after progression, not included in clinical trials. Gefitinib 250 mg or Erlotinib 150 mg per os were administered to 70 patients. Radiological assessment was performed every six weeks. EGFR and Kras mutations were found in 21.4% and 24.3% of patients, respectively...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28040594/transcriptome-analysis-of-egfr-tyrosine-kinase-inhibitors-resistance-associated-long-noncoding-rna-in-non-small-cell-lung-cancer
#12
Pei Ma, Meiling Zhang, Fengqi Nie, Zebo Huang, Jing He, Wei Li, Liang Han
The non-small cell lung cancer (NSCLC) patients harbor mutations in the epidermal growth factor receptor (EGFR) can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib, and show improved progression-free survival. However, most of the patients who are initially responsive to EGFR TKIs with activating EGFR mutations eventually develop acquired resistance after long-term therapy, and are followed by disease progression. Recently, diverse mechanisms of acquired EGFR TKI resistance have been reported, but little is known about the role of long noncoding RNAs in EGFR TKIs resistance...
December 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28036283/cost-effectiveness-of-gefitinib-icotinib-and-pemetrexed-based-chemotherapy-as-first-line-treatments-for-advanced-non-small-cell-lung-cancer-in-china
#13
Shun Lu, Ming Ye, Lieming Ding, Fenlai Tan, Jie Fu, Bin Wu
Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031837/carcinomatous-pleuritis-and-pericarditis-accompanied-by-pulmonary-tuberculosis
#14
Munechika Hara, Shin-Ichiro Iwakami, Naohisa Matsumoto, Taichi Miyawaki, Ryo Wada, Kazuhisa Takahashi
Although both lung cancer and pulmonary tuberculosis (TB) commonly occur in clinical practice, little attention has been paid to their coexistence. A 62-year-old female was admitted with acute dyspnoea secondary to cardiac tamponade. During her admission, a mass lesion harbouring air bronchograms in the right upper lobe rapidly increased in size. Surgical lung, pericardial, and pleural specimens yielded TB from a nodule in the right upper lobe and lung adenocarcinoma from the pericardium and pleura. Anti-tuberculous therapy was administered and gefitinib was subsequently started after the positive identification of epidermal growth factor receptor (EGFR) mutation (exon 19 deletion)...
November 2016: Respirology Case Reports
https://www.readbyqxmd.com/read/28031832/effectiveness-of-afatinib-in-lung-cancer-with-paralytic-ileus-due-to-peritoneal-carcinomatosis
#15
Haruki Kobayashi, Kazushige Wakuda, Toshiaki Takahashi
A 61-year-old never-smoking woman with stage IV lung adenocarcinoma with initially unknown epidermal growth factor receptor (EGFR) status, lung metastasis, pleural dissemination, and malignant pleural effusion in 2007 received 10 prior anti-cancer regimens including gefitinib as second- and ninth-line treatments, with minimal efficacy with gefitinib. EGFR mutation analysis performed in pleural effusion specimens during ninth-line gefitinib was negative. In 2015, she developed progressive disease with peritoneal dissemination...
November 2016: Respirology Case Reports
https://www.readbyqxmd.com/read/28031719/potential-role-of-immunotherapy-in-advanced-non-small-cell-lung-cancer
#16
REVIEW
Ramon Andrade de Mello, Ana Flávia Veloso, Paulo Esrom Catarina, Sara Nadine, Georgios Antoniou
Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28031710/a-quality-by-design-approach-on-polymeric-nanocarrier-delivery-of-gefitinib-formulation-in-vitro-and-in-vivo-characterization
#17
Navya Sree Kola Srinivas, Ruchi Verma, Girish Pai Kulyadi, Lalit Kumar
Gefitinib is an anticancer agent which acts by inhibiting epidermal growth factor receptor tyrosine kinase receptors. The aim of the present study was to prepare gefitinib nanosuspension. Gefitinib was encapsulated in Eudragit(®) RL100 and then dispersed in stabilizer solution, polyvinyl alcohol, and polyvinylpyrrolidone K30. Nanosuspension was prepared by using homogenization and ultrasonication techniques. The quality by design approach was also used in the study to understand the effect of critical material attributes (CMAs) and critical processing parameters (CPPs) on critical quality attributes and to improve the quality and safety of formulation...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28031519/remarkable-bone-formation-following-gefitinib-for-extensive-lytic-bone-metastasis-a-report-of-two-cases
#18
Elrofai Suliman Bashir, Angel Khor Nee Kwan, Chris Yin Wei Chan, Kwan Mun Keong
Gefitinib inhibits the epidermal growth factor receptor tyrosine kinase and improves survival in patients with non-small-cell lung cancer. We report 2 patients with extensive lytic bony metastasis in the spine and pelvis secondary to advanced pulmonary adenocarcinoma who were treated with gefitinib and had remarkable bone formation in the lytic bone lesions in the spine and pelvis. Surgery for stabilisation was avoided.
December 2016: Journal of Orthopaedic Surgery
https://www.readbyqxmd.com/read/28024692/synchronous-occurrence-of-squamous-cell-carcinoma-transformation-and-egfr-exon-20-s768i-mutation-as-a-novel-mechanism-of-resistance-in-egfr-mutated-lung-adenocarcinoma
#19
Lucia Longo, Maria Cecilia Mengoli, Federica Bertolini, Stefania Bettelli, Samantha Manfredini, Giulio Rossi
The occurrence of secondary EGFR mutation T790M in exon 20 and histologic "transformation" are common mechanisms underlying resistance to EGFR first- or second-generation tyrosine kinase inhibitors (TKI). We describe here on a hitherto unreported mechanism of EGFR TKI resistance synchronously combining squamous-cell carcinoma change and occurrence of the EGFR exon 20 S768I secondary mutation in a 43 year-old woman with stage IV adenocarcinoma harbouring EGFR exon 21 L858R mutation. After 8 months of response to gefitinib, the patient experienced EGFR TKI resistance and died of leptomeningeal neoplastic dissemination...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28007626/risk-of-treatment-related-toxicities-from-egfr-tyrosine-kinase-inhibitors-a-meta-analysis-of-clinical-trials-of-gefitinib-erlotinib-and-afatinib-in-advanced-egfr-mutated-non-small-cell-lung-cancer
#20
Pei Ni Ding, Sarah J Lord, Val Gebski, Matthew Links, Victoria Bray, Richard J Gralla, James Chih-Hsin Yang, Chee Khoon Lee
BACKGROUND: Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC). Estimating differences in toxicity between these EGFR-TKIs is important for personalizing treatment. METHODS: We performed a meta-analysis of randomized trials that compared EGFR-TKI against chemotherapy or placebo. We extracted data from the EGFR-TKI arm for indirect comparisons to estimate the relative risk of toxic death, grade 3-4 (G3/4) adverse events (AEs) and treatment discontinuation due to AE for each EGFR-TKI...
December 19, 2016: Journal of Thoracic Oncology
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