mitoguazone and Skin-Neoplasms

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy, Fine-Needle; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Ifosfamide; Lymphoma, Large-Cell, Anaplastic; Male; Methotrexate; Mitoguazone; Neoplasm Recurrence, Local; Prednisone; Skin Neoplasms; Vincristine

Effects of methylglyoxal bis(butylamidinohydrazone) (MGBB), a reversible inhibitor of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases of ODC and AdoMetDC activities, ODC and mRNA level and polyamine contents in mouse skin were investigated in connection with tumor formation. Formation of papillomas by applications of TPA to 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin was effectively inhibited by simultaneous topical applications of MGBB, MGBB also dose-dependently inhibited the ability of TPA to induce increases of ODC activity, ODC mRNA level and the accumulation of putrescine and spermidine in mouse skin. Induction of AdoMetDC activity was not affected by the drug. These inhibitory effects of MGBB on ODC induction and tumor promotion were more evident in multiple application experiments than with a single application of the drug.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cocarcinogenesis; Male; Mice; Mice, Inbred Strains; Mitoguazone; Ornithine Decarboxylase Inhibitors; Papilloma; Polyamines; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate

The continuous human medulloblastoma cell line TE-671 was grown as s.c. and intracranial xenografts in athymic nude mice. Tumor-bearing animals were treated with chemotherapeutic agents at the 10% lethal dose; s.c. xenografts were sensitive to melphalan, 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea, and 5-azacytidine. No consistent response could be demonstrated to 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate, and no response to methylglyoxal bis(guanyl hydrazone), N-trifluoroacetyl adriamycin-14-valerate, or to 1-beta-D-arabinofuranosylcytosine was observed. Melphalan produced a significant (P = less than or equal to 0.007) increase in the median survival of mice bearing intracranial xenografts, whereas no response was seen to 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea or 5-azacytidine. This model will allow analysis of the chemotherapeutic profile of human medulloblastoma, and provides a means to differentiate cellular sensitivity and resistance from drug access to the intracranial site.

Topics: Animals; Azacitidine; Brain Neoplasms; Cell Line; Cytarabine; Doxorubicin; Humans; Medulloblastoma; Melphalan; Mice; Mice, Nude; Mitoguazone; Neoplasm Transplantation; Nitrosourea Compounds; Skin Neoplasms; Vidarabine Phosphate

Topics: Animals; Cricetinae; Female; Guanidines; Male; Melanoma; Mesocricetus; Mice; Mice, Inbred Strains; Mitoguazone; Neoplasms, Experimental; Skin Neoplasms