Abstract

This Core Component will evaluate reagents developed in the Projects for acute toxicity and the ability to enhance the radiosensitizing effects of moderate hyperthermia in tumor xenografts heated in vivo in mice. The Core will also determine if the parameters that relate to heat-induced radiosensitization (HIR) and/or its enhancement in vitro (as established in the Projects) also relate to HIR or its enhancement in vivo. A long-range goal of this effort is to develo methods to image these parameters non-invasively. Briefly, this Core will collaborate with the Project researchers to extend their in vitro studies to initial pre-clinical models utilizing human tumors grown as xenografts in nude mice. The establishment of this Core will provide an efficient and cost effective resource for evaluating the in vivo efficacy and toxicity of compounds developed in Projects 3 and 4. In addition, the Core will collaborate with all of the Projects to confirm that the parameters (i.e. molecular alterations) that contribute to increased HIR in vitro are also related to HIR or its enhancement in vivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA104457-05
Application #
7664000
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
5
Fiscal Year
2008
Total Cost
$307,351
Indirect Cost

  Institution

Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Wang, Rongsheng E; Pandita, Raj K; Cai, Jianfeng et al. (2012) Inhibition of heat shock transcription factor binding by a linear polyamide binding in an unusual 1:1 mode. Chembiochem 13:97-104
Wang, Rongsheng E; Hunt, Clayton R; Chen, Jiawei et al. (2011) Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem 19:4710-20
Reddy, Y Thirupathi; Sekhar, Konjeti R; Sasi, Nidhish et al. (2010) Novel substituted (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-diones and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones as potent radio-sensitizing agents. Bioorg Med Chem Lett 20:600-2
Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L et al. (2010) Radiosensitization of cancer cells by hydroxychalcones. Bioorg Med Chem Lett 20:5997-6000
Penthala, Narsimha Reddy; Yerramreddy, Thirupathi Reddy; Crooks, Peter A (2010) Microwave assisted synthesis and in vitro cytotoxicities of substituted (Z)-2-amino-5-(1-benzyl-1H-indol-3-yl)methylene-1-methyl-1H-imidazol-4(5H)-ones against human tumor cell lines. Bioorg Med Chem Lett 20:591-3
Thirupathi Reddy, Y; Narsimha Reddy, P; Koduru, Srinivas et al. (2010) Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones. Bioorg Med Chem 18:3570-4
Geng, Ling; Rachakonda, Girish; Morré, D James et al. (2009) Indolyl-quinuclidinols inhibit ENOX activity and endothelial cell morphogenesis while enhancing radiation-mediated control of tumor vasculature. FASEB J 23:2986-95
Zeng, Sicong; Xiang, Tao; Pandita, Tej K et al. (2009) Telomere recombination requires the MUS81 endonuclease. Nat Cell Biol 11:616-23
Wang, Rongsheng E; Kao, Jeffrey L-F; Hilliard, Carolyn A et al. (2009) Inhibition of heat shock induction of heat shock protein 70 and enhancement of heat shock protein 27 phosphorylation by quercetin derivatives. J Med Chem 52:1912-21
Vanderwaal, Robert P; Maggi Jr, Leonard B; Weber, Jason D et al. (2009) Nucleophosmin redistribution following heat shock: a role in heat-induced radiosensitization. Cancer Res 69:6454-62

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