Abstract

Radiation Therapy is an important treatment modality of cancer. However, its effectiveness is limited due to the resistance of certain tumors to ionizing radiation. Although diverse factors dictate the cellular response to radiation, this study will focus on the importance of the product of the human proto-oncogene c-raf-1 (Raf-1) in the in vitro and in vivo tumor responses to gamma radiation. We have previously demonstrated the potential of antisense raf oligo as a sequence-specific inhibitor of Raf-1 expression and activity, as well as in vitro radiosensitizer. We will extend these observations to further investigate the potential of free and liposome-encapsulated antisense oligos (bFgf, ras, raf) as sequence- specific inhibitors of gene expression and as radiosensitizers. In addition, we will test the hypothesis that antisense raf oligonucleotide inhibits Raf-1 protein expression in vivo, and enhances the response of solid tumors to radiation. Overall, these studies should (i) generate a better understanding of the novel radiosensitizing property of antisense raf oligonucleotide, for the first time in a rodent system, and (ii) advance technological and scientific bases for the future translational application of antisense raf oligonucleotide.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA074175-04S1
Application #
6334986
Study Section
Project Start
2000-04-01
Project End
2001-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
2000
Total Cost
$348,824
Indirect Cost

  Institution

Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Sakabe, Isamu; Hu, Rong; Jin, Lu et al. (2015) TMEM33: a new stress-inducible endoplasmic reticulum transmembrane protein and modulator of the unfolded protein response signaling. Breast Cancer Res Treat 153:285-97
Zhang, Chuanbo; Kallakury, Bhaskar V; Ross, Jeffrey S et al. (2013) The significance of TNFAIP8 in prostate cancer response to radiation and docetaxel and disease recurrence. Int J Cancer 133:31-42
Cheema, Amrita K; Varghese, Rency S; Timofeeva, Olga et al. (2013) Functional proteomics analysis to study ATM dependent signaling in response to ionizing radiation. Radiat Res 179:674-683
Jung, Mira; Timofeeva, Olga; Cheema, Amrita K et al. (2011) Human fibroblasts for large-scale ""omics"" investigations of ATM gene function. Adv Exp Med Biol 720:181-90
Cheema, Amrita K; Timofeeva, Olga; Varghese, Rency et al. (2011) Integrated analysis of ATM mediated gene and protein expression impacting cellular metabolism. J Proteome Res 10:2651-7
Konsoula, Zacharoula; Velena, Alfredo; Lee, Rachel et al. (2011) Histone deacetylase inhibitor: antineoplastic agent and radiation modulator. Adv Exp Med Biol 720:171-9
Hu, Zhang-Zhi; Huang, Hongzhan; Wu, Cathy H et al. (2011) Omics-based molecular target and biomarker identification. Methods Mol Biol 719:547-71
Varghese, Rency S; Cheema, Amrita; Cheema, Prabhdeep et al. (2010) Analysis of LC-MS data for characterizing the metabolic changes in response to radiation. J Proteome Res 9:2786-93
Broustas, Constantinos G; Ross, Jeffrey S; Yang, Qifeng et al. (2010) The proapoptotic molecule BLID interacts with Bcl-XL and its downregulation in breast cancer correlates with poor disease-free and overall survival. Clin Cancer Res 16:2939-48
Popowycz, Florence; Fournet, Guy; Schneider, Cédric et al. (2009) Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue. J Med Chem 52:655-63

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