Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare the effects of sirolimus (SRL) vs cyclosporine (CsA) concerning the cardiovascular mechanisms hypothetically contributing to hypertension development. Three rat groups were studied: control (vehicle), CsA (5 mg/kg/d), and SRL (1 mg/kg/d). The following parameters were evaluated after 7 weeks of treatment: blood pressured (BP) and heart rate (HR; tail cuff), lipid profile, hematology, plasma and platelet 5-HT and catecholamines (HPLC-ECD), and oxidative equilibrium (serum malondialdehyde [MDA] and total antioxidant status [TAS]). Systolic (SBP) and diastolic blood pressure (DBP) values were higher (P < .001) in both the CsA (146.2 +/- 4.5 and 124.9 +/- 4.5 mm Hg) and SRL (148.9 +/- 4.8 and 126.4 +/- 6.0 mm Hg) groups vs the controls (115.9 +/- 3.3 and 99.1 +/- 2.0 mm Hg). However, HR values were elevated in CsA but not SRL animals. The dyslipidemic pattern of CsA was even more enhanced in the SRL group, with significantly higher low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) levels vs CsA (P < .05); red blood cells, hematocrit, hemoglobin concentration, mean platelet volume, and platelet distribution width were significantly (P < .05) higher in the SRL vs CsA group. The pro-oxidative profile (increased MDA/TAS) in the CsA group was not reproduced in the SRL cohort. While plasma and platelet 5-HT were elevated in SRL rats, catecholamine content was higher in CsA animals. In conclusion, this study demonstrated that CsA and SRL produce identical hypertensive effects. However, while CsA promotes oxidative stress and sympathetic activation, SRL mainly interferes with lipid profile and hematological parameters. Thus, the hypertensive effects of CsA, a calcineurin inhibitor, and of SRL, an mTOR inhibitor, are associated with impairment of distinct cardiovascular pathways.
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PMID:Hypertension induced by immunosuppressive drugs: a comparative analysis between sirolimus and cyclosporine. 1937 75

The systemic treatment options for advanced gastric cancer (GC) have evolved rapidly in recent years. We have reviewed the recent data of clinical trial incorporating targeted agents, including inhibitors of angiogenesis, human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition, epidermal growth factor receptor, mammalian target of rapamycin, claudin-18.2, programmed death-1 and DNA. Addition of trastuzumab to platinum-based chemotherapy has become standard of care as front-line therapy in advanced GC overexpressing HER2. In the second-line setting, ramucirumab with paclitaxel significantly improves overall survival compared to paclitaxel alone. For patients with refractory disease, apatinib, nivolumab, ramucirumab and TAS-102 have demonstrated single-agent activity with improved overall survival compared to placebo alone. Pembrolizumab has demonstrated more than 50% response rate in microsatellite instability-high tumors, 15% response rate in tumors expressing programmed death ligand 1, and non-inferior outcome in first-line treatment compared to chemotherapy. This review summarizes the current state and progress of research on targeted therapy for advanced GC.
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PMID:Targeted and novel therapy in advanced gastric cancer. 3163 39