Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IPdR (5-iodo-2-pyrimidinone-2'-deoxyribose) is a novel orally available, halogenated thymidine (TdR) analog and is a potential radiosensitizer for use in human tumors, such as rectal, pancreas, sarcoma and glioma tumors. IPdR is a prodrug that is efficiently converted to IUdR (5-iodo-2'-deoxyuridine), an intravenous radiosensitizer by a hepatic aldehyde oxidase, resulting in high IPdR and IUdR plasma levels in mice for > or = 1 h after oral IPdR. Athymic mice tolerated oral IPdR to doses up to 1500 mg/kg/day t.i.d. for 6 - 14 days without significant systemic toxicities. A number of in vivo preclinical studies have demonstrated that IPdR is a superior radiosensitizer compared with IUdR given as a continuous infusion in terms of safety and efficacy with a significantly lower toxicity profile, including gastrointestinal and hematologic side effects. A preclinical study has shown that IPdR is effective in inducing human colon cancer xenograft radiosensitization in drug-resistant DNA mismatch repair-proficient and -deficient tumor models, as well as in human globlastoma xenograft. In anticipation of performing a clinical Phase I trial in humans, investigators also studied the drug pharmacokinetics and host toxicities in two non-rodent, animal species during a 14-day treatment course. Dose-limiting systemic toxicities (diarrhea, emesis, weight loss and decreased motor activity) were observed in ferrets receiving IPdR at 1500 mg/kg/day on a 14-day schedule that were not found previously in athymic mice. Recently, a once-daily IPdR dosing up to 2000/mg/kg for 28 days in Fischer-344 rats showed reversible mild-to-moderate systemic toxicities without any severe or life-threatening toxicities. However, in all preclinical toxicity studies so far, no significant hematologic, biochemical or histopathologic changes have been found. Hepatic aldehyde oxidase activity was reduced in a dose-dependent fashion in the ferret liver, suggesting partial enzyme inactivation by this IPdwR schedule, but that is not found in Fischer-344 rats. The plasma pharmacokinetic profile in Rhesus monkeys showing biexponential clearance are similar to previously published data in athymic mice. In this paper, the authors review the development, mechanism of action, preclinical data and rationale for clinical studies.
 ...
PMID:IPdR: a novel oral radiosensitizer. 1771 27

Curcumin (diferuloyl), from the Indian spice turmeric, reduces oxidative damage and induces apoptosis. Utilizing DNA microarrays, we have demonstrated that a low (5 microM) dose of curcumin added to a mixture of astrocytes and oligodendrocytes (C6 rat glioma cells) in culture for 24 and 48 h significantly modulates gene expression in four primary pathways: oxidative stress, cell cycle control, and DNA transcription and metabolism. Contribution of the pentose phosphate pathway to the pool of NADH upregulates glutathione and activates aldehyde oxidase. We have identified also several new genes, up- or downregulated by curcumin, namely, aldo-keto reductase, glucose-6-phosphate dehydrogenase, and aldehyde oxidase that protect against oxidative stress. The identification of several new cell cycle control genes, including the apoptosis-related protein (pirin) and insulin-like growth factor (IGF), and of the neurofilament M protein involved in neurogenesis suggests that curcumin may have applicability in the treatment of a spectrum of neurodegenerative diseases.
 ...
PMID:Early anti-oxidative and anti-proliferative curcumin effects on neuroglioma cells suggest therapeutic targets. 1829 80