Cancer research
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Combinations of inhibitors directed at the individual components of ribonucleotide reductase were studied for their effects on L1210 cell growth in culture. The combinations included pyrozoloimidazole (IMPY) plus deoxyadenosine and hydroxyurea plus deoxyadenosine. Modulators were utilized to potentiate the effects of hydroxyurea, IMPY, or deoxyadenosine. ⋯ While the combinations of deoxyadenosine-EHNA, hydroxyurea-Desferal, or IMPY-Desferal caused increased growth inhibition of L1210 cells at high drug concentrations, combinations which consisted of deoxyadenosine-EHNA-IMPY-Desferal or deoxyadenosine-EHNA-hydroxyurea-Desferal gave strong synergistic inhibition of L1210 cell growth in culture at concentrations of each of the drugs which alone had minimal inhibitory effects on tumor cell growth. The four-drug combination was clearly more effective than any three-drug combination in terms of inhibition of tumor cell growth. It was also observed that the concentrations of the modulators (Desferal or EHNA) were as critical as the concentrations of hydroxyurea, IMPY, or deoxyadenosine in establishing an effective drug combination.
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A comparative study of the pituitary and testicular response to luteinizing releasing hormone (LHRH), thyrotrophic releasing hormone (TRH), and human chorionic gonadotrophin (HCG) administration was carried out in (a) low-risk young South African black men and high-risk North American black men for prostatic cancer and (b) healthy elderly South African men and South African black men with prostatic cancer. A comparable HCG response occurred in young South African and North American black men, while a greater release of prolactin, but a lesser release of luteinizing hormone in response to LHRH:TRH occurred in South African black men. The response to HCG was comparable in elderly and young South African black men, although the prolactin release in response to TRH was greater in elderly men. ⋯ Higher estradiol and estrone but lower androstenedione levels occurred in men with prostatic cancer. Data suggest that, in the elderly South African black men with prostatic cancer, estrogen metabolism is modified and that either the estrogen level or the higher estrogen:androgen levels modify the pituitary response to LHRH:TRH. A Western diet enhanced the changes in hormone profiles evident in black South African men with prostatic cancer.
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Comparative Study
Combined modality treatment using radiation and/or chemotherapy in an athymic nude mouse-human medulloblastoma and glioblastoma xenograft model.
A human medulloblastoma (BN-2) and a glioblastoma (BN-3) which were previously established in nude mice were used to determine the effect of combined modality therapy with gamma-radiation, and three chemotherapeutic agents, procarbazine, 1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)-3,6-dioxo diethylester (AZQ), and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The tumor cells were grown in tissue culture and implanted intracranially in the right cerebral hemisphere of NIH Swiss nude mice to a depth of 3 mm. The mice were randomized, and treatment was started 3 days after tumor implantation. ⋯ The combination treatment using AZQ and BCNU showed no ILS for the medulloblastoma tumor. Combination treatment of the human glioblastoma xenograft using BCNU produced significant ILSs of 105 and 119% and was superior to single-modality treatment with a drug dose of 10 mg/kg and radiation doses of 540 and 800 rads, respectively. The nude mouse-human tumor xenograft model was found to be useful for combined modality studies and should give valuable information for the experimental design of pilot Phase III clinical studies against a variety of brain tumors.