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https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#1
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107584/targeting-of-tumor-growth-and-angiogenesis-underlies-the-enhanced-antitumor-activity-of-lenvatinib-in-combination-with-everolimus
#2
Masahiro Matsuki, Yusuke Adachi, Yoichi Ozawa, Takayuki Kimura, Taisuke Hoshi, Kiyoshi Okamoto, Osamu Tohyama, Kaoru Mitsuhashi, Atsumi Yamaguchi, Junji Matsui, Yasuhiro Funahashi
The combination of lenvatinib-a multiple receptor tyrosine kinase (RTK) inhibitor-plus everolimus-a mammalian target of rapamycin (mTOR) inhibitor-significantly improved clinical outcomes versus everolimus monotherapy in a phase 2 clinical study of metastatic renal cell carcinoma (RCC). Here, we investigated potential mechanisms underlying the antitumor activity of the combination treatment in preclinical RCC models. Lenvatinib plus everolimus showed greater antitumor activity than either monotherapy in 3 human RCC xenograft mouse models (A-498, Caki-1, and Caki-2)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28107192/incidence-and-risk-of-infections-associated-with-egfr-tkis-in-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#3
Yingtian Wang, Mingzhen Wang, Qiaoxia Wang, Zhiying Geng, Mingxiang Sun
Currently, the overall incidence and risk of infections with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients remained undetermined. We searched Pubmed for related articles published from 1 January 1990 to 31 November 2015. Eligible studies included prospective randomized controlled trials (RCTs) evaluating therapy with or without EGFR-TKIs in patients with NSCLC. Data on infections were extracted. Pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105602/ibrutinib-a-review-in-chronic-lymphocytic-leukaemia
#4
Emma D Deeks
Ibrutinib (Imbruvica(®)) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...
January 20, 2017: Drugs
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#5
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28105360/long-term-disease-stabilization-following-treatment-with-erlotinib-in-heavily-pretreated-patients-with-wild-type-epidermal-growth-factor-receptor-non-small-cell-lung-carcinoma-two-case-reports
#6
Minas Sakellakis, Angelos Koutras, Maria Pittaka, Efstathios Tsitsopoulos, Fotini Kalofonou, Haralabos P Kalofonos
Lung adenocarcinomas carrying epidermal growth factor receptor (EGFR) mutations have been identified as a unique group of entities that depend on EGFR for their proliferation and metastasis. The introduction of reversible EGFR tyrosine kinase inhibitors, such as erlotinib, has significantly affected the management of metastatic disease in this subset of patients. Interestingly, although erlotinib is highly effective in patients with EGFR mutations, it may occasionally prove useful, even in the absence of mutations...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105244/her2-overexpression-reverses-the-relative-resistance-of-egfr-mutant-h1975-cell-line-to-gefitinib
#7
Jing Xu, Li Shen, Bi-Cheng Zhang, Wen-Hong Xu, Shu-Qin Ruan, Chi Pan, Qi-Chun Wei
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105215/role-of-axl-expression-in-non-small-cell-lung-cancer
#8
Xiaohan Qu, Jinlu Liu, Xinwen Zhong, Xi Li, Qigang Zhang
The present study aimed to investigate the expression profile of AXL in non-small cell lung cancer (NSCLC) and its clinical significance. The current study included 257 NSCLC patients, tyrosine-protein kinase receptor UFO (AXL) expression in paired lung cancer and adjacent normal lung tissues of NSCLC patients were compared by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction (qPCR). These methods were used to detect the expression of the AXL gene and protein in fresh tissues from 35 patients...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105150/ovarian-metastasis-from-non-small-cell-lung-cancer-with-alk-and-egfr-mutations-a-report-of-two-cases
#9
Rosemary T Mushi, Yumei Yang, Qian Cai, Ruiguang Zhang, Gang Wu, Xiaorong Dong
Ovarian metastasis from non-small cell lung cancer (NSCLC) is a rare condition. The current study presents the cases of 2 female patients aged 38 and 47 years old, respectively, who were initially diagnosed with NSCLC adenocarcinoma on histology. Both patients initially presented with chest pain and a cough, and subsequently developed ovarian metastases following multiple treatments. The 38-year old patient exhibited an epidermal growth factor receptor mutation, confirmed by scorpion/amplified refractory mutation system analysis from a lung biopsy...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104619/osimertinib-benefit-in-egfr-mutant-nsclc-patients-with-t790m-mutation-detected-by-circulating-tumour-dna
#10
J Remon, C Caramella, C Jovelet, L Lacroix, A Lawson, S Smalley, K Howarth, D Gale, E Green, V Plagnol, N Rosenfeld, D Planchard, M V Bluthgen, A Gazzah, C Pannet, C Nicotra, E Auclin, J C Soria, B Besse
BACKGROUND: Approximately 50% of Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. MATERIAL AND METHODS: ctDNA T790M mutational status was assessed by Inivata InVision(TM) (eTAm-Seq(TM)) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28104566/targeting-epidermal-growth-factor-receptor-in-triple-negative-breast-cancer-new-discoveries-and-practical-insights-for-drug-development
#11
REVIEW
Ricardo Costa, Ami N Shah, Cesar A Santa-Maria, Marcelo R Cruz, Devalingam Mahalingam, Benedito A Carneiro, Young Kwang Chae, Massimo Cristofanilli, William J Gradishar, Francis J Giles
Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC...
January 5, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28103975/-research-progress-of-targeted-therapy-for-egfr-gene-in-non-small-cell-lung-cancer
#12
Hui Zhang, Shucai Zhang
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have brought great clinical benefit to patients with EGFR-sensitive mutations. With the deepening of clinical and basic research, EGFR-TKIs have received more and more attention. In this review, we summarize the latest research development about EGFR-targeted drugs in 2016.
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103968/-gene-expression-and-clinical-characteristics-of-molecular-targeted-therapy-%C3%A2-in-non-small-cell-lung-cancer-patients-in-shandong
#13
Xiuli Qiao, Dan Ai, Honglu Liang, Dianbin Mu, Qisen Guo
BACKGROUND: Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KRAS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to benefit from molecular target therapy treatment...
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103904/safety-and-efficacy-of-fruquintinib-in-patients-with-previously-treated-metastatic-colorectal-cancer-a-phase-ib-study-and-a-randomized-double-blind-phase-ii-study
#14
Rui-Hua Xu, Jin Li, Yuxian Bai, Jianming Xu, Tianshu Liu, Lin Shen, Liwei Wang, Hongming Pan, Junning Cao, Dongsheng Zhang, Songhua Fan, Ye Hua, Weiguo Su
BACKGROUND: To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients. METHODS: A phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of fruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ≥2 lines of prior therapies. The primary endpoint was progression-free survival (PFS)...
January 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28103766/long-term-exposure-to-imatinib-mesylate-downregulates-hippo-pathway-and-activates-yap-in-a-model-of-chronic-myelogenous-leukemia
#15
Anna Chorzalska, Javier Flores Kim, Karim Roder, Alexander Tepper, Nagib Ahsan, R Shyama Prasad Rao, Adam J Olszewski, Xiaoqing Yu, Dmitry Terentyev, John Morgan, Diana O Treaba, Ting Zhao, Olin Liang, Philip Gruppuso, Patrycja Dubielecka
Despite the success of tyrosine kinase inhibitor (TKI) therapy in chronic myelogenous leukemia (CML), leukemic stem/progenitor cells remain detectable even in the state of deep molecular remission. Mechanisms that allow them to persist despite continued kinase inhibition remain unclear. We have previously shown that prolonged exposure to imatinib mesylate results in dysregulation of Akt/Erk 1/2 signaling, upregulation of miR-181a, enhanced adhesiveness, and resistance to high imatinib mesylate. In order to characterize the molecular basis and reversibility of those effects, we applied gene and protein expression analysis, quantitative phosphoproteomic, and direct miR-181a inhibition to our cellular model of CML cells subjected to prolonged exposure to imatinib mesylate...
January 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28103611/phase-ii-randomised-discontinuation-trial-of-the-met-vegf-receptor-inhibitor-cabozantinib-in-metastatic-melanoma
#16
Adil Daud, Harriet M Kluger, Razelle Kurzrock, Frauke Schimmoller, Aaron L Weitzman, Thomas A Samuel, Ali H Moussa, Michael S Gordon, Geoffrey I Shapiro
BACKGROUND: A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma. METHODS: Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS)...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28103584/significant-efficacy-and-well-safety-of-apatinib-in-an-advanced-liver-cancer-patient-a-case-report-and-literature-review
#17
Peisi Kou, Yan Zhang, Wenbo Shao, Hui Zhu, Jingze Zhang, Haiyong Wang, Li Kong, Jinming Yu
Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102887/clinical-trial-of-nintedanib-in-patients-with-recurrent-or-metastatic-salivary-gland-cancer-of-the-head-and-neck-a-multicenter-phase-2-study-korean-cancer-study-group-hn14-01
#18
Youjin Kim, Su Jin Lee, Ji Yun Lee, Se-Hoon Lee, Jong-Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha-Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß)...
January 19, 2017: Cancer
https://www.readbyqxmd.com/read/28102297/whsc1l1-mediated-egfr-mono-methylation-enhances-the-cytoplasmic-and-nuclear-oncogenic-activity-of-egfr-in-head-and-neck-cancer
#19
Vassiliki Saloura, Theodore Vougiouklakis, Makda Zewde, Xiaolan Deng, Kazuma Kiyotani, Jae-Hyun Park, Yo Matsuo, Mark Lingen, Takehiro Suzuki, Naoshi Dohmae, Ryuji Hamamoto, Yusuke Nakamura
While multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102081/deep-coverage-of-global-protein-expression-and-phosphorylation-in-breast-tumor-cell-lines-using-tmt-10-plex-isobaric-labeling
#20
Fang-Ke Huang, Guoan Zhang, Kevin Lawlor, Arpi Nazarian, John Philip, Paul Tempst, Noah Dephoure, Thomas A Neubert
Labeling peptides with isobaric tags is a popular strategy in quantitative bottom-up proteomics. In this study, we labeled six breast tumor cell lysates (1.34 mg proteins per channel) using 10-plex tandem mass tag reagents and analyzed the samples on a Q Exactive HF Quadrupole-Orbitrap mass spectrometer. We identified a total of 8706 proteins and 28186 phosphopeptides, including 7394 proteins and 23739 phosphosites common to all channels. The majority of technical replicates correlated with a R2 ≥ 0.98, indicating minimum variability was introduced after labeling...
January 19, 2017: Journal of Proteome Research
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