title: Alteration of sensitivity to cis-diamine(glycolate)-platinum(II) (254-S) in oral tumor xenografts following multiple applications.
abstract: The emergence of resistance to platinum analogues is considered to be a major problem in the treatment of head and neck cancer. Therefore, it is important to clarify the mechanisms of resistance to these analogues and the mechanisms of the processes related to this resistance. The study of emergence of resistance in the solid tumors is particularly relevant. Ln the present study, the effect of a platinum analogue (254-S), on the response of an oral carcinoma cell line grown as a xenograft in nude mice, was studied. The effect of a full dose administered as a single intraperitoneal injection of 254-S (15 mg/kg X 1) on tumor growth was not significantly different from the effect of repeated intraperitoneal injections of 254-S, administered 3 times at 1/3 of this dose (5 mg/kg x3), or 5 times at 1/5 of this dose (3 mg/kg x5). However, when a single full-dose intraperitoneal injection of 254-S (15 mg/kg x1) was administered to each group of mice again at the 9th and 12th weeks after the initial treatment, different effects on tumor growth were observed among each group. The groups which received repeated treatment with 254-S (5 mg/kg, x3, or 3 mg/kg x5) showed a decrease in the inhibition of tumor growth, suggesting the emergence of resistance to 254-S. The study of platinum accumulation in the tumor tissues and a flow cytometric analysis of proliferating cell nuclear antigen (PCNA) supported the possibility that resistance to 254-S increases in tumor tissues treated repeatedly. These observations suggest that the potential use of this experimental assay as a model, may provide further insights into the therapeutic mechanisms of resistance to antineoplastic agents in the treatment of solid cancerous head and neck tumors.
authors.affiliation: KANSAI MED UNIV,DEPT OTOLARYNGOL,MORIGUCHI,OSAKA 570,JAPAN. KANSAI MED UNIV,DEPT NEUROSURG,MORIGUCHI,OSAKA 570,JAPAN.
authors.forename: S
authors.initials: S
authors.lastname: Sai
authors.forename: H
authors.initials: H
authors.lastname: Kumazawa
authors.forename: T
authors.initials: T
authors.lastname: Tachikawa
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: K
authors.initials: K
authors.lastname: Kawamoto