Anti-Angiogenesis Therapeutic Indicators in Breast Cancer
Final rept. 2 Jul 2001-1 Jul 2004
CALIFORNIA UNIV IRVINE
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This project was proposed to study therapeutic indicators for anti-angiogenic therapy. Two different animal tumor models were studied, R323O AC adenocarcinoma and carcinogen ENU induced tumors. Longitudinal MRI studies were performed before and during therapy to monitor the changes occurring over the entire treatment period. Immunohistochemical analysis was performed to measure 4 molecular markers p53, TSP-l, VEGF and factor VIII microvessel density in pre-treatment and post-treatment specimens. ENU induced tumors came with different types, thus could simulate the wide variation of human breast cancer. However, the tumor also showed a very complicated response pattern. All MRI markers and IHC markers were correlated with final treatment outcome. Unlike in humans, the early volumetric changes did not predict outcome. The contrast enhancement kinetics measured using the blood pool agent Gadomer-l7 may provide an indication for therapy response. The vascular volume measured by Gadomer-l7 decreased in responder, and increased in non-responders. Also the baseline vascularity measured by Gadomer-l7 was associated with future response, possibly due to a higher blood supply thus more delivery of therapeutic agents. The developed methodology is currently applied in human studies, and that is expected to yield more interesting results in understanding chemotherapy induced changes.
- Anatomy and Physiology
- Medicine and Medical Research