mitoguazone and Urinary-Bladder-Neoplasms

Topics: Adenosylmethionine Decarboxylase; Amidines; Animals; Carboxy-Lyases; Cell Adhesion; Cell Line; Cells, Cultured; Colorimetry; Culture Techniques; Enzyme Inhibitors; Humans; Indans; Indicators and Reagents; Liver; Mitoguazone; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Rats; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Transitional Cell; Drug Evaluation; Female; Humans; Male; Middle Aged; Mitoguazone; Urinary Bladder Neoplasms

To assess the effect of polyamine blockade on urinary epithelium, growth of normal human urothelial cell cultures and human transitional cell carcinoma (TCC) cell lines in the presence of various inhibitors of polyamine synthesis was evaluated. All four human TCC cell lines tested were quite sensitive to the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (DFMO), requiring less than or equal to 1.0 mM DFMO to double generation time. Alternatively, all three human urothelial cultures tested required 5-20-fold higher DFMO concentrations to achieve similar growth inhibition. The inhibitory effect of DFMO on TCC was found to act synergistically with that of the inhibitor of S-adenosylmethionine decarboxylase, methylglyoxal bis(guanylhydrazone), and additively with that of recombinant beta-serine interferon. Addition of individual polyamines entirely prevented the inhibitory effects of DFMO and/or methylglyoxal bis(guanylhydrazone) but not that of beta-serine interferon. It appears that inhibition of polyamine synthesis and/or interconversion holds promise in the management of TCC and that the in vitro model described will be of value in investigating such clinical applications.

Topics: Carcinoma, Transitional Cell; Eflornithine; Humans; Interferon beta-1a; Interferon beta-1b; Interferon Type I; Interferon-beta; Mitoguazone; Ornithine Decarboxylase; Polyamines; Recombinant Proteins; Tumor Cells, Cultured; Urinary Bladder; Urinary Bladder Neoplasms

A comparative study of the effect of cis-diamminedichloroplatinum(II) (cisplatin), diammine[1,1-cyclobutanedicarboxylato(2-)-O,O'-platinum] (carboplatin), and mitoguazone dihydrochloride on urothelial cancer was conducted using transitional cell carcinomas of the urinary bladder grown in the nude mouse. Tumors SW-780 and TCC-K1 represented transitional cell carcinoma, Grade II, whereas Tumor PR49 represented a fast-growing Grade III neoplasm. Of the agents studied, cisplatin was most effective, resulting in tumor response related to the dose administered. Response to carboplatin was clearly related to treatment schedule. For the same amount of total dose administered, better results were obtained when treatment was given three times weekly instead of once every week. Furthermore, cisplatin was more effective against the less differentiated PR49 tumor in contrast to carboplatin, which showed more activity against the better differentiated SW-780 and TCC-K1 tumors. None of the tumors tested responded to mitoguazone dihydrochloride. The results of the present study may assist in formulating better treatment modalities against urothelial cancer, taking into account factors such as tumor grade, growth rate, treatment schedule, and the patient's tolerance which may ultimately influence tumor response.

Topics: Aged; Animals; Antineoplastic Agents; Carboplatin; Carcinoma, Transitional Cell; Cisplatin; Female; Guanidines; Humans; Male; Mice; Mice, Nude; Middle Aged; Mitoguazone; Organoplatinum Compounds; Urinary Bladder Neoplasms