Interactions between inhibitors of mTOR and EGFR/ERK signaling in SiHa cervical carcinoma.
Published: 2004
Language: eng
Number of pages: 105
Description: PI3K/PKB/mTOR and MAPK signaling pathways display multiple cross-connections, one of the principal common targets being p70S6K---major kinase for S6, which plays important role in translation. Since HER1/EGFR inhibition can impair MAPK signaling in some cell types, we tested the combination of rapamycin and OSI-774 (already in clinical trials as anticancer agents) in human cervical carcinomas xenografts. Suppression of P-S6 was induced by either drug alone and P-ERK decreased with OSI-774, while enhancement of these effects was obtained using both drugs together. Continuous treatment with the combination of drugs led to significantly greater tumor growth delay and antiangiogenic effect than single agents, whereas rapamycin alone induced significant inhibition of tumoral proliferation. The quantification of the biological markers was performed by computerized analysis of wide field multispectral fluorescence imaging on triple labeled tissue sections. These results support the further clinical investigations of rapamycin and EGFR inhibitor combinations in anticancer therapy.
Notes: Adviser:  David Hedley.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0766.

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