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Effect of indomethacin on tumorigenicity and immunity induction in a murine model of mammary carcinoma
Author(s) -
Morecki S.,
Yacovlev L.,
Slavin S.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980316)75:6<894::aid-ijc12>3.0.co;2-3
Subject(s) - medicine , immune system , immunotherapy , immunity , adenocarcinoma , immunization , vaccination , mammary tumor , cancer , cancer research , immunology , ratón , chemotherapy , mammary carcinoma , carcinoma , breast cancer
Indomethacin, an inhibitor of cyclo‐oxygenase given orally, reduced the tumorigenicity of cancer cells in a non‐immunogenic murine model of mammary adenocarcinoma (4T 1 ). In the presence of indomethacin, a dose‐dependent immune protection could be induced most effectively by immunizing mice with 1 to 3 doses of irradiated tumor cells inoculated at intervals of 7 days prior to challenge with a tumorigenic cell dose. Three immunizations given without indomethacin resulted in tumor growth in 88% of the recipients, and indomethacin treatment started 28 days prior to the challenge dose and given without immunizations led to tumor onset in 83% of mice. In contrast, tumor was documented only in 12% of mice vaccinated with 3 immunization doses and given concomitantly indomethacin. Moreover, 53% of disease‐free survivors resisted a second challenge with a high tumorigenic dose. Induction of an anti‐tumor immunity in indomethacin‐treated mice was further studied as a therapy for tumor‐bearing mice. Complete cure was induced in 50% of mice, and a significant reduction in tumor size as well as prolonged survival time were observed in the remaining animals. Immunostimulation by tumor cell vaccination given in the presence of a tolerable dose of indomethacin, therefore, may be incorporated into immunotherapy protocols to activate an anti‐tumor response against residual tumor cells that escaped surgery and/or high‐dose chemo/radiotherapy. Int. J. Cancer 75:894–899, 1998. © 1998 Wiley‐Liss, Inc.