We propose to test a novel hypothesis that angiogenesis in non-tumor tissue induced independently of tumor, contributes to the growth of tumor. Thus if a therapeutic intervention to treat tumor induces angiogenesis in adjacent non-tumor tissue, this angiogenesis increases the likelihood of tumor regrowth from residual tumor cells. We propose to test this hypothesis in a model of human glioma in the nude mouse. The anti tumor treatment employed is photodynamic therapy (PDT) using Photofrin as the photosensitizer.
In specific aim A, the angiogenic response of normal brain to PDT is tested and the effects of implantation of tumor in PDT induced angiogenic brain are analyzed. As a logical consequence of experiments performed in specific Aim A, we test the effects of combination treatment of U87 human glioma in the mouse brain using PDT and antiangiogenic agents in specific aim B. We expect that the combination treatment will significantly reduce the rate of tumor regrowth and thereby extend the life of animals compared to the individual treatments. The anti-angiogenic agents employed are antibodies against the vascular endothelial growth factor receptors (VEGFR1 and VEGFR2). If we are correct, that endogenous brain angiogenesis contributes to tumor regrowth, then our study has important implications for the treatment of brain tumor using most forms of anti tumor agents. Thus, the use of a combination anti-angiogenic and direct tumoricidal treatment may translate into improved therapeutic opportunity. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA100486-02
Application #
6906504
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Wong, Rosemary S
Project Start
2004-06-16
Project End
2008-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
2
Fiscal Year
2005
Total Cost
$265,680
Indirect Cost
Name
Henry Ford Health System
Department
Neurology
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Katakowski, Mark; Zheng, Xuguang; Jiang, Feng et al. (2010) MiR-146b-5p suppresses EGFR expression and reduces in vitro migration and invasion of glioma. Cancer Invest 28:1024-30
Zheng, Xuguang; Jiang, Feng; Katakowski, Mark et al. (2009) ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT activation. Cancer Biol Ther 8:1045-54
Hong, Xin; Jiang, Feng; Kalkanis, Steven N et al. (2009) Intracellular free calcium mediates glioma cell detachment and cytotoxicity after photodynamic therapy. Lasers Med Sci 24:777-86
Gullo, Francesca; Maffezzoli, Andrea; Dossi, Elena et al. (2009) Short-latency cross- and autocorrelation identify clusters of interacting cortical neurons recorded from multi-electrode array. J Neurosci Methods 181:186-98
Szalad, Alexandra; Katakowski, Mark; Zheng, Xuguang et al. (2009) Transcription factor Sp1 induces ADAM17 and contributes to tumor cell invasiveness under hypoxia. J Exp Clin Cancer Res 28:129
Zhang, Xuepeng; Zheng, Xuguang; Jiang, Feng et al. (2009) Dual-color fluorescence imaging in a nude mouse orthotopic glioma model. J Neurosci Methods 181:178-85
Katakowski, Mark; Jiang, Feng; Zheng, XuGuang et al. (2009) Tumorigenicity of cortical astrocyte cell line induced by the protease ADAM17. Cancer Sci 100:1597-604
Jiang, Feng; Zhang, Xuepeng; Kalkanis, Steven N et al. (2008) Combination therapy with antiangiogenic treatment and photodynamic therapy for the nude mouse bearing U87 glioblastoma. Photochem Photobiol 84:128-37
Zheng, Xuguang; Jiang, Feng; Katakowski, Mark et al. (2008) Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17/TACE and promotes glioma cell invasion. Cancer Lett 265:177-87
Hong, Xin; Jiang, Feng; Kalkanis, Steven N et al. (2008) Increased chemotactic migration and growth in heparanase-overexpressing human U251n glioma cells. J Exp Clin Cancer Res 27:23

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