Acute delirious state after epsilon-aminocaproic acid.
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Biomedical subjects
Publications and source records attributed to A Sella.
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Immunogenic variants (Imm+) generated after the treatment of murine tumor cells with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) can produce a strong protective response against non-mutagenized parent tumor cells. The use of this methodology to treat human tumors is currently thwarted by technological difficulties in applying the findings obtained with murine models to human disease. Two of these difficulties are described in this study. The first is that Imm+ variants lose most of their immunogenicity after treatment with X-irradiation or mitomycin C. The second is that mutagen-treated tumor cells must be cloned so as to select for Imm+ variants, for the presence of as few as 0.001 per cent tumorigenic cells within the bulk population will result in the failure of the protective effect of the Imm+ variants. Because of these and other difficulties with mutagen-induced Imm+ variants, we have developed a different approach to producing such variants using transfection of tumor cells with foreign genes. In contrast to mutagen induced Imm+ variants, these variants have been shown to retain their immunogenicity after X-irradiation.
Seventy-seven patients with metastatic transitional cell carcinoma of the bladder who were unable to receive primary Cisplatin-based therapy or failed primary chemotherapy received one of three sequential 5-Fluorouracil-based salvage regimens: a) 5-Fluorouracil (1000 mg/m2 B.S.A. x 5 days) and Mitomycin-C (14 mg/m2 B.S.A. 6 week intervals), b) 5-Fluorouracil (750 mg/m2 B.S.A. x 5 days) and a-Interferon (5 miu/m2 B.S.A. daily x 5 then 3 times a week (TIW), c) 5-Fluorouracil (500 mg/m2 B.S.A. x 5 days), a-Interferon (5 miu/m2 B.S.A. x 5 days then TIW) and 13-Cis Retinoic Acid in escalating doses daily. Only 1 (6%) of the patients with regimen A responded, whereas 9 (30%) of the patients with regimen B and 8 (27%) in regimen C responded. Although all responses were partial remissions, responses were seen in patients with advanced and initially refractory transitional cell carcinomas. This data reveals that a-Interferon and 5-Fluorouracil is an effective combination in the treatment of metastatic transitional cell carcinoma and worthy of further study.