Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell (EC) survival is critical in the maintenance of endothelial function as well as in the regulation of angiogenesis and vessel integrity since endothelial dysfunction is the initial lesion of atherosclerosis. The goal of this study was to examine the effect of diazoxide, a mitochondrial ATP-sensitive K(+)(mito K(ATP)) channel opener, on aorta ECs apoptosis and its potential mechanism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats at prediabetic stage. Diazoxide (25 mg kg(-1) day(-1)) was administered intraperitoneally from age 8 weeks to age 30 weeks. Thoracic aorta and cultured thoracic aortic ECs were used. The thickening of thoracic aortic wall and apoptosis of ECs were markedly increased in OLETF rats early from the age of 16 weeks, at the impaired glucose tolerance stage, compared with Long-Evans Tokushima Otsuka rats, in conjunction with intimal hyperplasia and perivascular fibrosis. In contrast, diazoxide treatment inhibited these changes. Further study strongly demonstrated that extracellular signal-regulated kinases (ERKs) are key regulatory proteins in protecting ECs from apoptosis. Diazoxide could significantly enhance phosphorylation of ERK via opening mito K(ATP) channels. This role was reversed by both 5-hydroxydecanoate, selectively closing mito K(ATP) channels, and PD-98509, MEK inhibitors. The present studies demonstrate that diazoxide prevents the onset and development of macrovascular disease in OLETF rats by inhibiting apoptosis directly via phosphorylated ERK increase in aorta ECs. Our findings establish the basis for the therapeutic potential of diazoxide in atherosclerotic disease.
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PMID:Diazoxide inhibits aortic endothelial cell apoptosis in diabetic rats via activation of ERK. 2153 63

Vassiliki A Papadimitrakopoulou speaks to Roshaine Wijayatunga, Managing Commissioning Editor: Dr Papadimitrakopoulou is the Jay and Lori Eisenberg Distinguished Professor of Medicine and Chief of the section of Thoracic Medical Oncology in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas/MD Anderson Cancer Center. Her areas of expertise include design and development of novel therapeutic clinical trials for lung and head and neck neoplasms, personalized genomics-driven lung cancer therapy and translational research and cancer chemoprevention. Her extensive experience in design, development and implementation of translational research in the context of multidisciplinary research teams has led to research funding from National Cancer Institute (NCI), American Society of Clinical Oncology (ASCO) and Department of Defense (DOD) both independently and as a member of a research team in the Head and Neck SPORE program. Currently, she serves as the principal investigator and leads numerous clinical and translational research projects with a focus on the development of biomarker-based targeted therapy to overcome therapeutic resistance in advanced disease and immunotherapy. Most notably, she has led the multidisciplinary clinical and translational research infrastructure dedicated to the treatment of metastatic refractory NSCLC as part of the BATTLE-2 program, designed and developed the first-in-the-world comprehensive genomics-driven umbrella approach in Squamous Lung Cancer, the Lung Master protocol, jointly sponsored by NCI-Cancer Therapy Evaluation Program (CTEP) and Foundation for the National Institutes of Health (FNIH)/industry, aiming at bringing personalized medicine to patients with this disease. She is the Co-PI of an R01 award focusing on the role of KRAS mutations and targeting in lung cancer. She is the lead author or coauthor of over 150 published articles, book chapters and reviews, and numerous abstracts involving cancer therapeutics, prevention and translational research and she has received several awards including the ASCO Young Investigator and Career Development Award. On this R01 application, she will serve as Co-PI, working closely with Roy Herbst (Yale Cancer Center) and Don Gibbons (UT/MD Anderson Cancer Center), building on the recently completed BATTLE-2 program, and capitalizing on both laboratory findings supporting MEK targeted therapy and clinical effectiveness of immunotherapy and their combinations in addressing KRAS mutated lung cancer.
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PMID:AURA3 trial: does Tagrisso (osimertinib) have the potential to become the new standard of care for second-line treatment of patients with EGFR T790M mutation-positive locally advanced or metastatic NSCLC. 3064 60

Interstitial pneumonitis is a rare drug adverse effect. We report two cases of cobimetinib-induced and vemurafenib-induced reversible interstitial pneumonitis. Two patients presenting a BRAF-mutated metastatic melanoma were treated with cobimetinib and vemurafenib. After 3 months, they developed severe feverish dyspnea. Thoracic imaging showed a pattern of organizing pneumonia in one case and a pattern of hypersensitivity pneumonitis in the other case. Infectious and cardiogenic causes were eliminated. An improvement was noted after discontinuation of cobimetinib, vemurafenib, and introducing steroids. Treatment was switched to dabrafenib (a BRAF inhibitor) with no recurrence of drug pneumonitis. To the best of our knowledge, it appears that cases of targeted-therapy-induced pneumonitis are predominantly an MEK-inhibitor effect. We, therefore, propose a management strategy of discontinuing targeted therapy, introducing steroid treatment and switching to dabrafenib.
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PMID:Two cases of pneumonitis induced by targeted therapy. 3126 Apr 21