Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PTK787/ZK 222584 (PTK/ZK) is an oral potent and selective inhibitor of the vascular endothelial growth factor (VEGF)-mediated Flt-1 and KDR receptor tyrosine kinases. PTK/ZK has been shown to reduce growth and microvasculature in subcutaneously implanted human tumor xenografts in nude mice. A clinical difficulty in evaluating angiogenesis inhibitors has been the usefulness of conventional study endpoints. Therefore, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been studied as a pharmacodynamic marker of efficacy of PTK/ZK. Phase I studies are under way evaluating the optimum dose and schedule of oral PTK/ZK administered continuously to patients with advanced cancers of types known to overexpress VEGF. To date, particularly in patients with liver metastases from colorectal cancer treated with PTK/ZK, DCE-MRI has been a useful predictor of the biological response of VEGF-receptor inhibition. Toxicities have been manageable and have included lightheadedness, ataxia, nausea, vomiting, and hypertension. Stabilization of disease for >/= 6 months has been seen in heavily pretreated patients receiving PTK/ZK at higher doses. Preliminary data suggest that PTK/ZK can be administered safely on a continuous daily dosing schedule, efficacy data look promising, and DCE-MRI correlates with biological response. DCE-MRI will be used to guide dose optimization of PTK/ZK and perhaps of other angiogenesis inhibitors in future studies.
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PMID:Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK 222584. 1280 93

A 27-year old female had one episode of transient loss of consciousness and several of near-unconsciousness during strenuous exercise and sexual activity. Episodes started with abdominal discomfort or nausea and light headedness. Unconsciousness never exceeded one minute. When trying to stand up, she felt she would lose consciousness again. We performed a bicycle ergometer exercise test, continuously monitoring blood pressure via non-invasive finger photoplethysmography (Finometer, FMS, The Netherlands). Beat-to-beat changes in stroke volume, cardiac output and total peripheral resistance were calculated using Modelflow (FMS, The Netherlands). At a power of 140 W, the patient reported being near exhaustion; shortly after this she reported nausea. She stopped cycling 30 s later, then saw "black spots" and felt an oncoming loss of consciousness. Dismounting the ergometer and squatting provided immediate relief from symptoms. Symptoms during the test were similar to those during previous episodes. The diagnosis was exercise-induced vasovagal reactions. This is the first report that documents the beat-to-beat changes in blood pressure, stroke volume and total peripheral resistance during exercise-induced vasovagal syncope. It illustrates the usefulness of combining exercise testing with continuous non-invasive blood pressure monitoring in the diagnostic work-up of exercise-induced syncope, and shows the therapeutic value of squatting to prevent loss of consciousness in exercise-related vasovagal syncope.
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PMID:Syncope during exercise, documented with continuous blood pressure monitoring during ergometer testing. 1576 6

While strongly implicated in postural tachycardia syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) loss of function. POTS is characterized by the clinical symptoms of orthostatic intolerance, lightheadedness, tachycardia, and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence that the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with massive parallel sequencing (RICh-seq) we show that let-7i miRNA suppresses NET by methyl-CpG-binding protein 2 (MeCP2). Vorinostat restores epigenetic control and NET expression in leukocytes derived from POTS participants.
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PMID:NET silencing by let-7i in postural tachycardia syndrome. 2835 54