TITLE

Treatment of colorectal and hepatocellular carcinomas by adenoviral mediated gene transfer of endostatin and angiostatin-like molecule in mice

AUTHOR(S)
Schmitz, V; Wang, L; Barajas, M; Gomar, C; Prieto, J
PUB. DATE
April 2004
SOURCE
Gut;Apr2004, Vol. 53 Issue 4, p561
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aim and method: In this study, we explored the responsiveness of different tumor entities (colorectal carcinoma (CRC), hepatocellular carcinoma (HCC), and the murine Lewis lung carcinoma (LLC)) to angiostatic antitumour treatment with two recombinant adenoviral vectors encoding angiostatin-like molecule (AdK1 -3) and endostatin (Adendo). Results: ACIKI -3 and Adendo exerted inhibitory biological functions on endothelial cell proliferation, migration, and tube formation in vitro. AdK1 -3 inhibited significantly endothelial cell infiltration in vascular endothelial growth factor embedded Matrigel plugs in mice whereas Adendo showed only minor effects. Both AdK1 -3 and Adendo induced similar antitumour effects in the LIC tumour model in immune competent C5781/6 mice but AdK1 -3 had stronger inhibitory effects in athymic mice. Furthermore, AdK1 -3 inhibited tumour growth in a murine CRC and human 11CC model but was ineffective in a human CRC model. In contrast, Adendo did not reduce tumour progress in either of these tumour models although AdK1 -3 and Adendo effectively reduced intratumoral microvessel density in LLC tumours. Conclusion: Our data demonstrate that angiostatic gene therapy may form a feasible strategy for the treatment of established hepatocellular carcinomas and that in viva antitumour efficacy of angiostatic proteins is tumour specific.
ACCESSION #
13120623

 

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