Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) relies on cholesterol-laden lipid raft membrane microdomains for entry into and egress out of susceptible cells. In the present study, we examine the need for intracellular cholesterol trafficking pathways with respect to HIV-1 biogenesis using Niemann-Pick type C-1 (NPC1)-deficient (NPCD) cells, wherein these pathways are severely compromised, causing massive accumulation of cholesterol in late endosomal/lysosomal (LE/L) compartments. We have found that induction of an NPC disease-like phenotype through treatment of various cell types with the commonly used hydrophobic amine drug U18666A resulted in profound suppression of HIV-1 release. Further, NPCD Epstein-Barr virus-transformed B lymphocytes and fibroblasts from patients with NPC disease infected with a CD4-independent strain of HIV-1 or transfected with an HIV-1 proviral clone, respectively, replicated HIV-1 poorly compared to normal cells. Infection of the NPCD fibroblasts with a vesicular stomatitis virus G-pseudotyped strain of HIV-1 produced similar results, suggesting a postentry block to HIV-1 replication in these cells. Examination of these cells using confocal microscopy showed an accumulation and stabilization of Gag in LE/L compartments. Additionally, normal HIV-1 production could be restored in NPCD cells upon expression of a functional NPC1 protein, and overexpression of NPC1 increased HIV-1 release. Taken together, our findings demonstrate that intact intracellular cholesterol trafficking pathways mediated by NPC1 are needed for efficient HIV-1 production.
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PMID:Deficiency of niemann-pick type C-1 protein impairs release of human immunodeficiency virus type 1 and results in Gag accumulation in late endosomal/lysosomal compartments. 1947 1

The aim of this study was to assess the feasibility and efficacy of a weekly cisplatin 40 mg/m(2) regimen in patients with nasopharyngeal carcinoma treated concurrently with definitive intensity-modulated radiation therapy (IMRT). The primary endpoints were treatment compliance and acute toxicities. Twenty-two patients with newly diagnosed NPC were recruited in this phase II trial. All patients received definitive IMRT concurrently with weekly cisplatin 40 mg/m(2) for six cycles. The treatment technique was split-field IMRT (SF-IMRT) before August 2009 and whole-field IMRT (WF-IMRT) thereafter. The median follow-up time was 15.1 months (range, 1.5-30 months). No patients experienced regional recurrence or distant metastasis. One patient developed local recurrence. One patient died of non-malignant disease. For all patients, the 1-year overall survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were 95.5%, 95.5%, 100%, and 100%, respectively. All patients received the full dose of RT. Twenty-one patients (95.5%) completed all six cycles of chemotherapy (CHT). Three patients experienced treatment delay. Of them, one had CHT delay, and the other two had IMRT delay. No treatment-related death was found. Acute toxicities were generally mild or moderate. Grade 3 and 4 toxicities accounted for less than 10% of overall occurrence in each corresponding category except for a relatively higher rate in stomatitis (Grade 3, 27%). Renal function impairment was not found. Weekly cisplatin with concurrent IMRT appears to be feasible and effective in treating NPC patients and these findings warrant further investigation.
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PMID:Feasibility and efficacy study of weekly cisplatin with concurrent intensity-modulated radiation therapy for nasopharyngeal carcinoma: preliminary results. 2083 79