title: Antitumor activity of the proteinase inhibitor tetra-p-amidinophenoxyneopentane in a nude mouse model of human melanoma.
abstract: An aromatic poly-amidine (tetra-p-amidinophenoxyneopentane, TAPP-Br) exhibiting anti-proteinase activity and known to exert antitumor activity in vitro was analysed for its ability to inhibit the in vivo growth of a human melanoma cell line transplanted in nude mice. 5 X 10(6) melanoma cells were injected subcutaneously in groups of nude mice and treatment with TAPP-Br was performed (0.125-1 mg/0.2 ml injections, repeated three times at the beginning of the experiment and after 20 days). After 25 days tumors displaying a volume of 0.9-1.8 cm3 were detectable in control untreated mice. Mice treated with TAPP-Br on the other hand did not develop sizable tumors or consistently developed tumors of significantly smaller sizes. Despite these therapeutic effects, significant chronic toxicity of the compound was observed when administered at higher dosage (500-1000 micrograms). These side effects, which may hamper the therapeutic use of TAPP-Br, are likely to be circumvented by alternative routes of administration or by vehiculation into liposomes. These alternative strategies of treatment are currently investigated.
authors.affiliation: Laboratorio di Immunologia, Istituto Regina Elena, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bartolazzi
authors.forename: R
authors.initials: R
authors.lastname: Barbieri
authors.forename: C
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: P G
authors.initials: PG
authors.lastname: Natali
authors.forename: R
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001550:Benzamidines / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011480:Protease Inhibitors / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001550:Benzamidines; D011480:Protease Inhibitors; C057885:1,3-di-(4-amidinophenoxy)-2,2-bis-(4-amidinophenoxymethyl)propane