Evaluation of Novel Agents which Target Neovasculature of Breast Tumors
Annual rept. 1 Apr 2003-31 Mar 2004
M D ANDERSON CANCER CENTER HOUSTON TX
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The unique fusion toxin VEGF121rGel can specifically kill both log-phase and confluent vascular endothelial cells expressing the KDR receptor for VEGFPNAS 997866,2002. We have discovered 19 unique genes upregulated5 fold in endothelial cells treated with VEGF121rGelconfirmed by Western and RT-PCR. VEGF121rGeli.v. treatment had a dramatic cytotoxic effect in both orthotopic and metastatic human breast tumor models. Against the orthotopic model, tumor growth was significantly delayed by 50. In addition, tumors completely regressed in 36 50 of treated mice. In the metastatic breast model, treatment with VEGF121rGel reduced both the number and area of lung foci by 58 and 50 respectively and we demonstrated VEGF121rGelby IHC on lung tumor vasculature but not 2. normal vasculature. In addition, the number of blood vessels per mm in metastatic foci was 198 3 versus 38821 for treated and control respectively. Approximately 62 of metastatic colonies from the VEGFrGel treated group had 10 vesselscolony compared to 23 in th1 receptor on blood vessel endothelium was intensely expressed on control tumors, but not expressed on treated tumors. Metastatic foci had a 3 fold lower Ki-67 labeling index compared to control tumors. This suggests that VEGF121rGel has impressive antitumor activity in breast cancer.
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