title: Antitumor activity of hexamethylmelamine on human tumor xenografts serially transplanted in nude mice.
abstract: The antitumor activity of hexamethylmelamine (HMM) was evaluated using four human tumor xenografts serially transplanted in nude mice. HMM was dissolved in 0.2 ml of 1% hydroxypropyl cellulose per mouse and administered perorally daily, except on Sunday, for 4 weeks, giving an estimated maximum tolerated dose (MTD) of HMM of 75 mg/kg. The MX-1 cell line showed dose-dependent sensitivity to HMM and was completely eradicated by treatment at the MTD. The minimum effective dose of HMM against MX-1 was calculated to be 22.1 mg HMM/kg, resulting in the chemotherapeutic index of 3.4. The demethylated derivatives of HMM, pentamethylmelamine and tetramethylmelamine, were also effective against MX-1, whereas trimethylmelamine was ineffective. The effect of HMM was more marked when the drug was administered on day 1 after tumor inoculation, compared with administration during the exponential growth phase. HMM is thought to be a promising agent for the treatment of several types of human carcinoma, producing active metabolites in vivo after peroral administration.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Tanino
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kitajima
mesh_terms: D006585:Altretamine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C092289:N(2),N(2),N(4)-trimethylmelamine; C031537:N(2),N(2),N(4),N(6)-tetramethylmelamine; D006585:Altretamine; C022048:pentamethylmelamine