Complementary therapeutic strategies are required to destroy solid tumors and inhibit regrowth of metastatic or residual primary tumor. In theory, the combination of radiation therapy and antiangiogenesis therapy fully meet these requirements. We have preliminary data using a potent antiangiogenic designed peptide, Anginex, indicating preferential tumor binding, tumor growth inhibition and synergistic anti-tumor effects in combination with radiotherapy equal or better than angiostatin or Sugen 6668 and radiation against our tumor models. Anginex is a non-toxic and stable beta-sheet forming 33-mer, developed at the University of Minnesota. We, and others, have recently demonstrated the potential of various anti-vascular or anti-angiogenic compounds to impact the success of radiation therapy via a modification of the existing tumor physiology or tumor endothelial radiosensitivity. Therefore, the use of Anginex to enhance radiation response represents a rational and prudent approach to develop better methods of cancer therapy. This project aims to maximize our understanding of the effects of Anginex on tumor physiology and radiation response and the influence of circulating endothelial cells on these processes. The three specific aims of this work will (1) expand our initial observations that tumor growth is retarded and radiation response in enhanced with the application of Anginex (2) assess the mechanism of Anginex binding and radiosensitization of tumor-endothelium and anginex effect on endothelial progenitor cells (3) Elucidate the effects of anginex treatment and fractionated radiotherapy on one another and on the role of circulating endothelial cells during fractionated treatment. The information to be obtained in this study will be a vital part of design and implementation of large animal and human clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA107160-03
Application #
7350616
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Stone, Helen B
Project Start
2005-05-01
Project End
2009-04-30
Budget Start
2007-04-09
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$149,674
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Asur, Rajalakshmi; Butterworth, Karl T; Penagaricano, Jose A et al. (2015) High dose bystander effects in spatially fractionated radiation therapy. Cancer Lett 356:52-7
Upreti, Meenakshi; Jamshidi-Parsian, Azemat; Apana, Scott et al. (2013) Radiation-induced galectin-1 by endothelial cells: a promising molecular target for preferential drug delivery to the tumor vasculature. J Mol Med (Berl) 91:497-506
Asur, Rajalakshmi S; Sharma, Sunil; Chang, Ching-Wei et al. (2012) Spatially fractionated radiation induces cytotoxicity and changes in gene expression in bystander and radiation adjacent murine carcinoma cells. Radiat Res 177:751-65
Griffin, Robert J; Koonce, Nathan A; Dings, Ruud P M et al. (2012) Microbeam radiation therapy alters vascular architecture and tumor oxygenation and is enhanced by a galectin-1 targeted anti-angiogenic peptide. Radiat Res 177:804-12
Suva, Larry J; Washam, Charity; Nicholas, Richard W et al. (2011) Bone metastasis: mechanisms and therapeutic opportunities. Nat Rev Endocrinol 7:208-18
Dings, Ruud P M; Loren, Melissa L; Zhang, Yan et al. (2011) Tumour thermotolerance, a physiological phenomenon involving vessel normalisation. Int J Hyperthermia 27:42-52
Jia, Dan; Koonce, Nathan A; Griffin, Robert J et al. (2010) Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC). Radiat Res 173:579-89
Upreti, M; Koonce, N A; Hennings, L et al. (2010) Pegylated IFN-? sensitizes melanoma cells to chemotherapy and causes premature senescence in endothelial cells by IRF-1 mediated signaling. Cell Death Dis 1:e67
Jia, Dan; Koonce, Nathan A; Halakatti, Roopa et al. (2010) Repression of multiple myeloma growth and preservation of bone with combined radiotherapy and anti-angiogenic agent. Radiat Res 173:809-17
Suva, Larry J; Griffin, Robert J; Makhoul, Issam (2009) Mechanisms of bone metastases of breast cancer. Endocr Relat Cancer 16:703-13

Showing the most recent 10 out of 13 publications