Tumor Oxygen Dynamics as a Prognostic Indicator of Effective Antiangiogenic Therapy

Tumor survival, growth and metastasis depend critically on the development of new blood vessels: so called angiogenesis. One major goal of this project is to fully understand and precisely assess the dynamic changes in blood perfusion and oxygenation, both during normal growth and following anti-ang...

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Bibliographic Details
Main Authors: Zhao, Dawen, Mason, Ralph P
Format: Report
Language:English
Subjects:
ANGIOGENESIS
ANTI-ANGIOGENIC THERAPY
Biochemistry
BLOOD PERFUSION
BLOOD VESSELS
GROWTH(PHYSIOLOGY)
HYPOXIA
MAGNETIC RESONANCE IMAGING
Medicine and Medical Research
METASTASIS
NEOPLASMS
OXYGEN
OXYGENATION
PROSTATE GLAND
THERAPY
VEGF(VASCULAR ENDOTHELIAL GROWTH FACTOR)
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Summary:Tumor survival, growth and metastasis depend critically on the development of new blood vessels: so called angiogenesis. One major goal of this project is to fully understand and precisely assess the dynamic changes in blood perfusion and oxygenation, both during normal growth and following anti-angiogenic therapy in several prostate tumors with differential characteristics, so that we may predict response and optimize the therapy. Combined BOLD (Blood oxygen level dependent) MRI with our FREDOM (Fluorocarbon Relaxometry using Echo planar imaging for Dynamic Oxygen Mapping) MR, our results showed that significantly better oxygenation was found in the well differentiated and slower growing H and HI tumors, compared with anaplastic or metastatic, faster growing ATl and MAT-Lu tumors. These MRI data has been compared and validated by cellular and molecular biology. Compared with the level of hypoxia (pimonidazole) and vasculature (CD3l) in H and HI tumors, the ATl tumors have a higher labelling index for pimonidazole and lower vascular density. An interesting finding is that expression of HIF-la and VEGF was found in relatively well differentiated and oxygenated H and HI tumors, which did not overlap with hypoxic regions recognized by pimonidazole. However, there was no expression in the ATl tumors.