Dfmo and sulindac combination in cancer chemoprevention

Details Dfmo and sulindac combination in cancer chemoprevention Dfmo and sulindac combination in cancer chemoprevention

A - Human Necessities

61

K

A61K 31/195 (2006.01)

Patent

CA 2325080

Activation of the Ki-ras proto-oncogene is common in colon carcinogenesis. Non- steroidal anti-inflammatory drugs (NSAIDs) inhibit carcinogen-induced colon carcinogenesis, decrease the frequency of Ki-ras mutations in the azoxymethane- treated rat model, and induce apoptosis in a variety of cell types. Sulindac, as well as other non-steroidal anti-inflammatory agents, are provided in combination with DFMO for the prevention and/or treatment of cancers characterized by the expression of an activated Ki-ras. Provided with the present invention are pharmaceutically acceptable compositions that include a non-steroidal anti-inflammatory agent, sulindac, together with an effective amount of difluoromethylornithine.

L'activation du proto-oncogène Ki-ras est fréquente dans la carcinogenèse du colon. Des médicaments anti-inflammatoires non stéroïdaux (NSAID) empêchent la carcinogenèse du colon induite par le carcinogène, réduisent la fréquence de mutations Ki-ras dans le modèle de rat traité à l'azoxyméthane et induisent l'apoptose dans toute une gamme de types cellulaires. Le sulindac, ainsi que d'autres agents anti-inflammatoires non stéroïdaux sont administrés en combinaison avec de la .alpha.-difluorométhylornithine (DFMO) pour la prévention et/ou le traitement de cancers caractérisés par l'expression d'un Ki-ras activé. La présente invention concerne également des compositions pharmaceutiquement acceptables qui comportent un agent anti-inflammatoire non stéroïdal, le sulindac, en combinaison avec une quantité efficace de difluorométhylornithine.

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