ascorbic-acid and Medulloblastoma

N-(4-hydroxyphenyl) retinamide (4-HPR, fenretinide) a synthetic retinoid is in clinical trials for the treatment of several malignancies. However, its biological effects and therapeutic value in childhood brain tumor medulloblastoma (MB) has not been investigated. In this study, we report for the first time that fenretinide (2.5-10 microM) induces apoptotic cell death in human MB cells. We observed significant inhibition of cell survival in four MB cell lines (D425MED, D458MED, D283MED and D341MED) as determined by MTT assays. These results were further supported by inhibition of anchorage-independent colony formation in soft agar. Fenretinide-induced decrease in cell viability was in part due to activation of caspase-3 dependent cell death, which was further supported by the cleavage of poly(ADP-ribose) polymerase-1 (PARP-1), a caspase-3 substrate. Cell death was partially prevented by the antioxidant, l-ascorbic acid suggesting that free radical intermediates might be involved in fenretinide effects. These results suggest that pharmacologically achievable concentrations of fenretinide are effective in killing MB cells and thus show its therapeutic potential to treat human MB.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Caspase 3; Caspases; Cell Proliferation; Cerebellar Neoplasms; Enzyme Activation; Fenretinide; Humans; Medulloblastoma; Poly(ADP-ribose) Polymerases; Tumor Cells, Cultured

Fruit, vegetables, vitamin C, and folate during pregnancy have been suggested as protective factors for medulloblastoma/primitive neuroectodermal tumor (PNET), a common brain tumor in children. The authors sought to replicate these findings and investigate other aspects of diet. Mothers of 315 cases under age six at diagnosis and 315 controls were interviewed about their pregnancy diet. The authors observed modest, inverse associations for fruits/juices (odds ratio (OR) for highest compared to lowest category = 0.6, 95% confidence interval (CI): 0.3, 1.1) and vitamin C (OR = 0.6, 95% CI: 0.4, 1.1). In contrast to the previous study, folate and vegetables showed no association. As hypothesized, cured meats were not associated with medulloblastoma/PNET, in contrast to other childhood brain tumors. An inverse association with non-fresh peaches and similar fruits (OR = 0.5, 95% CI: 0.3, 0.8) and a positive association with non-chocolate candy (OR = 1.7, 95% CI: 1.0, 3.0) replicated previous findings. French fries (OR = 2.4, 95% CI: 1.2, 4.9) and chili peppers (OR = 1.8, 95% CI: 1.0, 3.0) were associated with medulloblastoma/PNET. The results suggest that some aspects of diet are worthy of further research.

Topics: Adult; Antioxidants; Ascorbic Acid; Candy; Cerebellar Neoplasms; Feeding Behavior; Female; Folic Acid; Fruit; Humans; Maternal Welfare; Meat; Medulloblastoma; Micronutrients; Odds Ratio; Pregnancy; United States; Vegetables; Vitamin B Complex

Topics: Arachnoid; Ascorbic Acid; Astrocytoma; Ependymoma; Glioblastoma; Glioma; Hemangioendothelioma; Histocytochemistry; Humans; Medulloblastoma; Meningioma; Neoplasms, Nerve Tissue

Topics: Adult; Ascorbic Acid; Brain Neoplasms; Child; Female; Humans; Iodine Radioisotopes; Iron; Male; Medulloblastoma; Middle Aged; Neoplasm Metastasis; Radiometry; Radionuclide Imaging; Sarcoma, Synovial; Technetium