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https://www.readbyqxmd.com/read/28538405/marked-response-to-nab-paclitaxel-in-egfr-mutated-lung-neuroendocrine-carcinoma-a-case-report
#1
Jin-Yan Liang, Fan Tong, Fei-Fei Gu, Yang-Yang Liu, Yu-Lan Zeng, Xiao-Hua Hong, Kai Zhang, Li Liu
RATIONALE: Lung cancer is the leading cause of cancer-related death in the world. Tyrosine kinase inhibitors (TKIs), which target mutated epidermal growth factor receptor (EGFR), have been the first-line treatment of late-stage lung adenocarcinoma harboring EGFR mutation. EGFR mutations are mostly identified in lung adenocarcinoma. However, it is rarely seen in lung neuroendocrine carcinoma, and treatment strategies remain under reported. PATIENT CONCERNS: Here, we describe a 54-year-old Chinese man diagnosed with lung adenocarcinoma (cT4N3M1b, stage IV) with neuroendocrine differentiation and L858R mutation on exon 21...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#2
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537764/gefitinib-and-egfr-gene-copy-number-aberrations-in-esophageal-cancer
#3
Russell D Petty, Asa Dahle-Smith, David A J Stevenson, Aileen Osborne, Doreen Massie, Caroline Clark, Graeme I Murray, Susan J Dutton, Corran Roberts, Irene Y Chong, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen J Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Jonathan Wadsley, Ian Chau, David R Ferry, Zosia Miedzybrodzka
Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status...
May 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28537707/the-tyrosine-kinase-inhibitor-gefitinib-restricts-mycobacterium-tuberculosis-growth-through-increased-lysosomal-biogenesis-and-modulation-of-cytokine-signaling
#4
Kimberly M Sogi, Katie A Lien, Jeffrey Johnson, Nevan J Krogan, Sarah Stanley
Host-directed therapeutics have the potential to combat the global tuberculosis pandemic. We previously identified gefitinib, an inhibitor of EGFR, as a potential host-targeted therapeutic effective against M. tuberculosis infection of macrophages and mice. Here we examine the functional consequences of gefitinib treatment on M. tuberculosis infected macrophages. Using phosphoproteomic and transcriptional profiling, we identify two mechanisms by which gefitinib influences macrophage responses to infection to impact cytokine responses and limit replication of M...
May 24, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28535513/pkc-%C3%AE-triggers-egfr-ubiquitination-endocytosis-and-erk-activation-in-podocytes-stimulated-with-high-glucose
#5
Chun-Tao Lei, Yan-Hong Wei, Hui Tang, Qian Wen, Chen Ye, Chun Zhang, Hua Su
BACKGROUND: Protein Kinase C-α (PKC-α) and epidermal growth factor receptor (EGFR) are both involved in diabetic kidney disease; however, the connection between these two proteins during high glucose-induced podocyte injury remains uncertain. METHODS: Diabetes was induced in SD rats by streptozotocin (STZ). Fourteen days later, the kidney cortex was removed and subjected to plasma membrane isolation and lipid raft fractionation. In vitro study human podocyte cell line was differentiated and subjected to various treatments...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28533646/image-findings-of-rare-case-of-peritoneal-carcinomatosis-from-non-small-cell-lung-cancer-and-response-to-erlotinib-in-f-18-fdg-positron-emission-tomography-computed-tomography
#6
Koramadai Karuppusamy Kamaleshwaran, Jephy Joseph, Radha Krishnan Kalarikal, Ajit Sugunan Shinto
Lung cancer is currently one of the most common malignancies in the world. Metastatic disease is observed in ~ 40% of patients with lung cancer, with the most common sites of metastasis being the bone, liver, brain and adrenal glands. Peritoneal carcinomatosis (PC) is defined as the progression of the primary cancer to the peritoneum. PC is a rare clinical event in lung cancer. Tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), such as erlotinib are used for the treatment of patients with advanced non-small cell lung cancer (NSCLC)...
April 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/28532474/detection-of-ikk%C3%AE%C2%B5-by-immunohistochemistry-in-primary-breast-cancer-association-with-egfr-expression-and-absence-of-lymph-node-metastasis
#7
Virginie Williams, Andrée-Anne Grosset, Natalia Zamorano Cuervo, Yves St-Pierre, Marie-Pierre Sylvestre, Louis Gaboury, Nathalie Grandvaux
BACKGROUND: IKKε is an oncogenic kinase that was found amplified and overexpressed in a substantial percentage of human breast cancer cell lines and primary tumors using genomic and gene expression analyses. Molecular studies have provided the rational for a key implication of IKKε in breast cancer cells proliferation and invasiveness through the phosphorylation of several substrates. METHODS: Here, we performed immunohistochemical detection of IKKε expression on tissue microarrays constituted of 154 characterized human breast cancer tumors...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28531814/targeting-egfr-her2-heterodimerization-with-a-novel-anti-her2-domain-ii-iii-antibody
#8
Xiaojie Yu, Lingfei Wang, Yafeng Shen, Chao Wang, Yajun Zhang, Yanchun Meng, Yang Yang, Beibei Liang, Bo Zhou, Huajing Wang, Huafeng Wei, Changhai Lei, Shi Hu, Bohua Li
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#9
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529640/lung-cancer-targeting-peptides-with-multi-subtype-indication-for-combinational-drug-delivery-and-molecular-imaging
#10
Yi-Hsuan Chi, Jong-Kai Hsiao, Ming-Huang Lin, Chen Chang, Chun-Hsin Lan, Han-Chung Wu
Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC). Therefore, we aimed to identify targeting peptides with diagnostic and therapeutic utility that possess broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC)...
2017: Theranostics
https://www.readbyqxmd.com/read/28528303/discovery-of-a-potent-dual-alk-and-egfr-t790m-inhibitor
#11
Jaebong Jang, Jung Beom Son, Ciric To, Magda Bahcall, So Young Kim, Seock Yong Kang, Mierzhati Mushajiang, Younho Lee, Pasi A Jänne, Hwan Geun Choi, Nathanael S Gray
The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#12
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28525890/a-novel-egfr-tki-inhibitor-camp-h3bo3%C3%A2-complex-combined-with-thermal-therapy-is-a-promising-strategy-to-improve-lung-cancer-treatment-outcomes
#13
Yongpeng Tong, Chunliu Huang, Junfang Zhang
PURPOSE: Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. RESULTS: The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525838/design-synthesis-and-evaluation-of-azaacridine-derivatives-as-dual-target-egfr-and-src-kinase-inhibitors-for-antitumor-treatment
#14
Zhishan Cui, Shaopeng Chen, Yanwei Wang, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549 cells...
May 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28522751/targeting-fbw7-as-a-strategy-to-overcome-resistance-to-targeted-therapy-in-non-small-cell-lung-cancer
#15
Mingxiang Ye, Yong Zhang, Xinxin Zhang, Jian-Bin Zhang, Pengyu Jing, Liang Cao, Nan Li, Xia Li, Libo Yao, Jian Zhang, Jian Zhang
Inhibition of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non-small cell lung cancer (NSCLC) patients with distinct clinicopathological features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/Erk-independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of anti-apoptotic protein MCL-1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522592/sensitization-of-egfr-wild-type-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitor-erlotinib
#16
Judith Raimbourg, Marie-Pierre Joalland, Mathilde Cabart, Ludmilla de Plater, Fanny Bouquet, Ariel Savina, Didier Decaudin, Jaafar Bennouna, François M Vallette, Lisenn Lalier
The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of Patient-Derived Xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR expressing cells to erlotinib, contrary to what happens in mutant-EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521447/ct-guided-aspiration-lung-biopsy-for-egfr-and-alk-gene-mutation-analysis-of-lung-cancer
#17
Weisheng Lian, Yong Ouyang
The present study investigated the rates of detection and the positive rates of computed tomography (CT)-guided aspiration of lung biopsy for epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) gene, and analyzed the relationship between gene mutation and clinical characteristics to improve the rate of related factors of gene detection. The clinical data and CT-guided aspiration biopsy specimen of 250 patients with lung cancer. Data showed that the rate of EGFR gene mutation was 41...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521430/reduced-expression-levels-of-pten-are-associated-with-decreased-sensitivity-of-hcc827-cells-to-icotinib
#18
Yang Zhai, Yanjun Zhang, Kejun Nan, Xuan Liang
The clinical resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been linked to EGFR T790M resistance mutations or MET amplifications. Additional mechanisms underlying EGFR-TKI drug resistance remain unclear. The present study demonstrated that icotinib significantly inhibited the proliferation and increased the apoptosis rate of HCC827 cells; the cellular mRNA and protein expression levels of phosphatase and tensin homolog (PTEN) were also significantly downregulated...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521404/silencing-tak1-alters-gene-expression-signatures-in-bladder-cancer-cells
#19
Jimin Chen, Nan Zhang, Jiaming Wen, Zhewei Zhang
The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 (TAK1) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 (FGFR3) bladder cancer cells transfected with control siRNA or TAK1-specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520821/the-percentage-of-epidermal-growth-factor-receptor-egfr-mutated-neoplastic-cells-correlates-to-response-to-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma
#20
Dario de Biase, Giovenzio Genestreti, Michela Visani, Giorgia Acquaviva, Monica Di Battista, Giovanna Cavallo, Alexandro Paccapelo, Alessandra Cancellieri, Rocco Trisolini, Roberta Degli Esposti, Stefania Bartolini, Annalisa Pession, Giovanni Tallini, Alba A Brandes
BACKGROUND: Epidermal Growth Factor Receptor (EGFR) molecular analysis is performed to assess the responsiveness to Tyrosine Kinase Inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). The existence of molecular intra-tumoral heterogeneity has been observed in lung cancers. The aim of the present study is to investigate if the percentage of mutated neoplastic cells within the tumor sample might influence the responsiveness to TKIs treatment. MATERIAL AND METHODS: A total of 931 cases of NSCLC were analyzed for EGFR mutational status (exon 18, 19, 20, 21) using Next Generation Sequencer...
2017: PloS One
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