QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.069450v1 311/1/382    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nakase, Y. Articles by Yamagishi, H. Search for Related Content PubMed PubMed Citation Articles by Nakase, Y. Articles by Yamagishi, H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHARCOAL METHOTREXATE

CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

Intratumoral Administration of Methotrexate Bound to Activated Carbon Particles: Antitumor Effectiveness against Human Colon Carcinoma Xenografts and Acute Toxicity in Mice

Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

We previously developed a new formulation of methotrexate (MTX) that is adsorbed onto a suspension of activated carbon particles (MTX-CH) and reported the usefulness of local administration in murine tumors. The present study examines the effects of human colon carcinoma (LoVo) xenografts and the acute toxicity of MTX-CH compared with MTX aqueous solution (MTX-AQ) in mice. In therapeutic experiments, LoVo cells were implanted into the backs of BALB/c nude mice. When the cells had developed into tumors, we performed an intratumoral administration of a weekly dose of 30 mg/kg. The MTX concentration in the tumor was compared between the MTX-CH group and MTX-AQ group. In experiments on acute toxicity, MTX-CH and MTX-AQ were injected subcutaneously in BDF1 mice, and intoxication symptoms, changes in body weight, and date of death were recorded. In the therapeutic experiments, intratumoral administration of MTX-CH was much more effective in suppressing the tumor growth compared with MTX-AQ. In experiments of acute toxicity, the death time of the MTX-CH group was delayed to a greater extent, and the 50% lethal dose (LD₅₀) values of MTX-CH were lower than those of MTX-AQ. The LD₅₀ values of MTX-CH are 75 times higher than the efficacious dose of 30 mg/kg. The present results suggest that intratumoral administration of MTX-CH is useful for local therapy and the therapeutic dose of MTX-CH can be safely injected subcutaneously.

Address correspondence to: Dr. Yuen Nakase, Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji Kajiicho 465, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail: yuen-n{at}koto.kpu-m.ac.jp