Search

Introduction: The multidrug resistance-1 (MDR1) gene encodes a pump that prevents potentially carcinogenic substances from crossing the blood-brain barrier. We compare adult glioma cases and controls for the C3435T polymorphism that has been associated with reduced MDR1 expression. Methods: Adult glioma in the San Francisco Bay area and population-based controls were identified between 1991–1994 and 1997–1999. Genotyped cases (n = 458) and controls (n = 528) were compared using logistic regression controlling for age, gender and ethnicity, with later stratification by ethnicity, gender and histology. Results: With CC as the referent, the TT genotype was nonsignificantly less frequent among cases compared to controls (OR, 0.87; 95% CI: 0.6, 1.2). After stratification, only male glioblastoma was associated with TT genotype (OR, 0.51; 95% CI: 0.3, 1.0). Conclusions: Although the C3435T polymorphism does not appear to be associated with other types of glioma, we cannot rule out that this MDR1 polymorphism may be associated with glioblastoma among men. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Evidence from epidemiologic and experimental studies suggests that use of nonsteroidal antiinflammatory drugs (NSAIDs) reduces risk of colon and breast cancer. The association between use of aspirin and other NSAIDs and risk of adult glioblastoma multiforme (GBM) was evaluated among 236 incident GBM cases and 401 population-based controls frequency-matched on age, gender, and ethnicity from the San Francisco Bay Area Adult Glioma Study. Cases (or proxies) and controls were interviewed in person between May 1997 and August 2000. Cases with self-reported GBM reported less use of at least 600 pills of all types of NSAIDs combined during the 10-year prediagnostic period than did controls (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.3, 0.8). Findings were consistent for aspirin (OR = 0.51, 95% CI: 0.3, 0.8), ibuprofen (OR = 0.41, 95% CI: 0.2, 0.8), and naproxen/other NSAIDs (OR = 0.34, 95% CI: 0.1, 0.8). GBM cases also reported less use of acetaminophen than did controls (OR = 0.51, 95% CI: 0.3, 1.0). Eliminating participants who initiated NSAID use within 2 years of diagnosis yielded similar results. These findings show an inverse association between NSAID use and GBM. Further studies are warranted to determine whether NSAIDs might be effective in the inhibition of GBM development or progression. [ABSTRACT FROM AUTHOR]

Background: Monoamine oxidase (MAO) A catalyzes oxidative deamination of monoamine neurotransmitters and dietary amines and regulates brain development and functions. Recently, we showed that MAO A mediates the progression and migration of glioma and MAO A inhibitors reduce glioma cell growth. Glioblastoma (GBM) is a common and most malignant brain tumor which is difficult to treat. Temozolomide (TMZ) is the current standard chemotherapy for glioma, but tumors usually become resistant and recur. So far, no effective therapy for TMZ-resistant glioma is available. Natural plant antimicrobial solution (PAMs) is a Chinese herbal medicine which has been used for decades without toxicity and has multiple medical functions including anti- inflammatory effects. Here, we report the effects of PAMs on glioblastoma growth. Methods: The growth of TMZ -sensitive (U251S),-resistant (U251R) human glioma cells, and mouse glioma cell line GL-26 were assessed by MTS colorimetric assay, colony formation, and cell migration assays. Male C57BL/6 mice were implanted subcutaneously or intracranial with luciferase-positive mouse glioma GL-26 cells and treated with vehicle; MAO A inhibitor clorgyline (10 mg/kg); TMZ (1 mg/kg); PAMs (48 mg/kg) alone or in combination with TMZ (1 mg/kg) for 14 days. At the end of the treatment, mice were sacrificed, MAO A catalytic activity in tumors was measured, and tumor sizes were determined by imaging and weight. Results: These results show that PAMs inhibits MAO A catalytic activity in all three glioma cell lines studied U251S, U251R, and GL-26. PAMs reduced glioma growth and has greater effects in combination with low dose of TMZ than PAMS or TMZ alone in all three cell lines as shown by MTS, colony formation, and cell migration assays. Using the subcutaneous or intracranial GL-26 glioma mouse model, PAMs reduced the tumor growth and MAO A activity, similar to the MAO A inhibitor clorgyline. Combining PAMs with non-toxic dose TMZ increased survival to a greater extent than those of PAMs or TMZ alone. Conclusions: This is the first study which suggests that PAMs alone or co-administration with low doses of TMZ may be a potential adjuvant to reduce the toxicity of TMZ and to abrogate drug resistance for the effective treatment of glioma. [ABSTRACT FROM AUTHOR]