beta-carotene and Brain-Neoplasms

We studied the toxicity and efficacy of adding in sequence 4 resistance modulators to combination chemotherapy and radiotherapy in the treatment of glioblastoma multiforme and poor prognosis anaplastic astrocytomas. Patients received cisplatin plus mitomycin-C concurrently with and following 60 Gy of radiotherapy administered over 6 weeks. Resistance modulators were added in sequence to chemotherapy in each cohort of 6 patients as follows: metronidazole + pentoxifylline (cohort 1); + dipyridamole (cohort 2), + beta carotene (cohort 3). Central nervous system toxicity (which ranged from drowsiness to seizures and loss of consciousness) was frequent. The incidence of gastrointestinal symptoms was substantial, but was usually mild to moderate in severity. Three of 11 patients evaluable for response achieved a partial remission with treatment. The median survival duration for all patients was 26 weeks from initial diagnosis. The study was terminated prematurely because of significant toxicity (in this study as well as in parallel concurrent studies of similar design in other tumor types) and apparent lack of benefit.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta Carotene; Brain Neoplasms; Cisplatin; Combined Modality Therapy; Dipyridamole; Drug Synergism; Drug Therapy, Combination; Female; Glioblastoma; Humans; Male; Metronidazole; Middle Aged; Mitomycin; Pentoxifylline; Treatment Outcome

According to our previous study suggesting that antioxidant properties of phytochemicals in the diet decrease glioma aggressiveness, we used a SUVIMAX-like diet ("Supplementation en VItamines et Minéraux AntioXydants") (enriched with alpha-tocopherol, beta carotene, vitamin C, zinc, and sodium selenite), adapted to rats. The present results showed that each of the antioxidants inhibited growth of glioma cells in vitro. When used in combination for in vivo studies, we showed a highly significant delay in the clinical signs of the disease, but not a statistical significant difference in the incidence of glioma in an Ethyl-nitrosourea (ENU)-model. The SUVIMAX-like diet decreased candidate markers of tumoral aggressiveness and gliomagenesis progression. The mRNA expressions of 2 common markers in human glioma: Mn-SOD (Manganese Superoxide Dismutase) and IGFBP5 (insulin growth factor binding protein) were reduced in the tumors of rats fed the antioxidant diet. In addition, the transcripts of two markers linked to brain tumor proliferation, PDGFRb (platelet-derived growth factor receptor beta) and Ki-67, were also significantly decreased. On the whole, our results suggest a protective role for antioxidants to limit aggressiveness and to some extent, progression of gliomas, in a rat model.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Brain Neoplasms; Cell Proliferation; Ethylnitrosourea; Female; Glioma; Insulin-Like Growth Factor Binding Protein 5; Ki-67 Antigen; Male; Rats; Receptor, Platelet-Derived Growth Factor beta; RNA, Messenger; Sodium Selenite; Superoxide Dismutase; Zinc

The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.

Topics: Antineoplastic Agents, Phytogenic; Brain Neoplasms; Chromatography, High Pressure Liquid; Colonic Neoplasms; Drug Screening Assays, Antitumor; Female; Humans; Japan; Kidney Neoplasms; Lanosterol; Leukemia, Myeloid; Lung Neoplasms; Melanoma; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Polyporaceae; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Triterpenes; Tumor Cells, Cultured

In addition to the provitamin A function of some carotenoids, many of them exhibit antioxidant activity. Epidemiological studies show that high serum levels and/or elevated intake of carotenoids have a protector effect against several chronic and degenerative diseases. We determined the levels and studied the behavior of the major carotenoids and retinol in serum of a brain tumor patient receiving standard (carotenoid-free) artificial enteral nutrition for eight months. After nearly two months on this diet, the retinol level was in the upper region of normal range and the beta-carotene concentration was unusually high. Analyses after several months on this diet showed a decrease in retinol, whereas the beta-carotene concentration had doubled (up to 203 micrograms/dl). Other carotenoids usually found in serum were present in very small amounts or not at all. We conclude that, although diet is an important factor in the presence and proportion of carotenoids in serum, the case we report here appears to indicate that other factors related to the development of certain diseases may be relevant determinants of changes in the carotenoid profile.

Topics: Adult; beta Carotene; Brain Neoplasms; Carotenoids; Cholesterol; Enteral Nutrition; Female; Humans; Triglycerides; Vitamin A; Vitamin E

N-nitroso compounds and their precursors, nitrites and nitrates, have been hypothesized as risk factors, and vitamins C and E, which inhibit N-nitroso formation, as protective factors for brain tumors. A case-control study of maternal diet during pregnancy and risk of astrocytoma, the most common childhood brain tumor, was conducted by the Childrens Cancer Group. The study included 155 cases under age six at diagnosis and the same number of matched controls selected by random-digit dialing. A trend was observed for consumption of cured meats, which contain preformed nitrosamines (a class of N-nitroso compounds) and their precursors (adjusted odds ratio [OR] for highest quartile of intake relative to lowest = 1.7, P trend = 0.10). However, no strong trends were observed for nitrosamine (OR = 0.8, P = 0.60); nitrite (OR = 1.3, P = 0.54); nitrate (OR = 0.7, P = 0.43); vitamin C (OR = 0.7, P = 0.37); or vitamin E (OR = 0.7, P = 0.48). Iron supplements were associated with a significant decrease in risk (OR = 0.5, 95 percent confidence interval = 0.3-0.8). The effect of several dietary factors differed by income level, making interpretation of the results difficult. Future research should investigate the effect of dietary components not assessed in this study, as these may explain the disparate effects by income level. The results of this study provide limited support for the nitrosamine hypothesis.

Topics: Astrocytoma; beta Carotene; Brain Neoplasms; Canada; Carotenoids; Child, Preschool; Diet; Female; Humans; Income; Iron; Meat; Neuroectodermal Tumors, Primitive; Nitroso Compounds; Pregnancy; Risk Factors; United States; Vitamin A; Vitamin E