Abstract
We have evaluated the antitumor activity of Altretamine (hexamethylmelamine, HMM) on human carcinoma xenografts serially transplanted in nude mice. Five human breast carcinoma xenografts, MX‐1, T‐61, MCF‐7, R‐27 and Br‐10, were inoculated subcutaneously into female nude mice. Two human stomach carcinoma xenografts, SC‐1‐NU and St‐4, and three human colon carcinoma xenografts, Co‐3, Co‐4 and Co‐6, were inoculated subcutaneously into male nude mice. One pellet of 17β‐estradiol (0.1 mg/mouse) was inoculated subcutaneously in the mice transplanted with MCF‐7 when the tumors were inoculated. HMM was administered per os daily for 4 weeks. MX‐1 and T‐61 tumors regressed completely after treatment with HMM at a dose of 75 mg/kg (the maximum tolerated dose: MTD) for MX‐1 and 25 mg/kg for T‐61. Br‐10 was sensitive, whereas MCF‐7 and R‐27 were resistant to HMM at its MTD. HMM exerted the most potent antitumor effect against T‐61. Against MX‐1, it exerted an antitumor effect equivalent to that of cisplatin or cyclophosphamide. In addition, this agent was effective against all stomach and colon carcinoma xenografts, in particular St‐4 (T/C%= 10.7: the mean tumor weight of treated group/the mean tumor weight of control group) and Co‐3 (T/C%=31.5%) which are insensitive to presently available agents. HMM seems worthy of further clinical investigation as a candidate agent to treat breast, stomach, colon and other carcinomas.
Keywords: Altretamine, Hexamethylmelamine, Nude mouse, Chemotherapy
Full Text
The Full Text of this article is available as a PDF (371.7 KB).
REFERENCES
- 1. ) Rosen , G. P. , Lourain , J. R. and Newton , M.Hexamethylmelamine in ovarian cancer after failure of cisplatin‐based multiple‐agent chemotherapy . Gynecol. Oncol. , 27 , 173 – 179 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Manetta , A. , MacNeill , C. , Lyter , J. A. , Sheffler , B. , Podczaski , E. S. , Larson , J. E. and Schein , J.Hexamethylmelamine as a single second‐line agent in ovarian cancer . Gynecol. Oncol. , 36 , 93 – 96 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Wilson , W. L. , Bisel , H. F. , Cole , D. , Rochlin , D. , Ramirez , G. and Madden , R.Prolonged low‐dosage administration of hexamethylmelamine (NC 13875) . Cancer , 25 , 568 – 570 ( 1970. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Kubota , T. , Ishibiki , K. and Abe , O.The clinical usefulness of human xenografts in nude mice , In “ Prediction of Response to Cancer Therapy ,” pp. 213 – 225 ( 1988. ). Alan R. Liss. Inc. , New York . [PubMed] [Google Scholar]
- 5. ) Geran , R. I. , Greenberg , N. H. , MacDonald , M. M. , Schumacher , A. M. and Abbott , B. J.Protocols for screening chemical and natural products against animal tumors and other biological systems . Cancer Chemother. Rep. , 3 , 51 – 61 ( 1972. ). [Google Scholar]
- 6. ) Shimosato , Y. , Oboshi , S. and Baba , K.Histological evaluation of effects of radiotherapy and chemotherapy for carcinomas . Jpn. J. Clin. Oncol. , 1 , 19 – 35 ( 1971. ). [Google Scholar]
- 7. ) Kaiser , D. W. , Thurston , J. T. , Duley , J. R. , Schaefer , F. C. , Hechenbleikner , I. and Holm‐Hansen , D.Cyanuric acid derivatives. II. Substituted melamines . J. Am. Chem. Soc. , 73 , 2984 – 2986 ( 1951. ). [Google Scholar]
- 8. ) Foster , B. J. , Harding , B. J. , Leyland‐Jones , B. and Hoth , D.Hexamethylmelamine. A critical review of an active drug . Cancer Treat. Rev. , 13 , 197 – 217 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Ames , M. M. , Sanders , M. E. and Tiede , W. S.Role of N‐methylolpentamethylmelamine in the metabolic activation of hexamethylmelamine . Cancer Res. , 43 , 500 – 504 ( 1983. ). [PubMed] [Google Scholar]
- 10. ) Buckley , S. M. , Stock , C. C. , Grossley , M. L. and Rhoads , C. P.Inhibition of Crocker mouse sarcoma 180 by certain ethylenimine derivatives and related compounds . Cancer , 5 , 144 – 152 ( 1952. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Rosen , G. F. , Lurain , J. R. and Newton , M.Hexamethylmelamine in ovarian cancer after failure of cisplatin‐based multiple‐agent chemotherapy . Gynecol. Oncol. , 27 , 173 – 179 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Stolinsky , D. C. and Bateman , J. R.Further experience with hexamethylmelamine (NSC 13875) in the treatment of carcinoma of the cervix . Cancer Chemother. Rep. , 57 , 497 – 499 ( 1973. ). [PubMed] [Google Scholar]