Abstract

The major emphasis of this project revolves around the role that flavoprotein quinone reductases may play in antitumor quinone cytotoxicity. The first enzyme to be investigated is DT-diaphorase and the applicant wishes to determine its role in the response of human tumors to antitumor quinones. Within this objective the applicant will study the expression and function of an alternatively spliced DT- diaphorase product. The second theme of this grant application is the study of the Thioredoxin/Thioredoxin Reductase (T/TR) system. The applicant wishes to focus upon the effects that antitumor quinones have upon this system, the levels of T/TR in human tumors, the role of T/TR in cell growth and transformation, the role of T/TR is the redox control of transcription factor activity, and the role of T/TR in apoptosis or programmed cell death.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA048725-05A2
Application #
2093040
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1990-08-01
Project End
1997-11-30
Budget Start
1995-01-27
Budget End
1995-11-30
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Arizona
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721

  Publications

Ihle, Nathan T; Williams, Ryan; Chow, Sherry et al. (2004) Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling. Mol Cancer Ther 3:763-72
Meuillet, Emmanuelle J; Mahadevan, Daruka; Vankayalapati, Hariprasad et al. (2003) Specific inhibition of the Akt1 pleckstrin homology domain by D-3-deoxy-phosphatidyl-myo-inositol analogues. Mol Cancer Ther 2:389-99
Husbeck, B; Berggren, M I; Powis, G (2001) DNA microarray reveals increased expression of thioredoxin peroxidase in thioredoxin-1 transfected cells and its functional consequences. Adv Exp Med Biol 500:157-68
Powis, G; Montfort, W R (2001) Properties and biological activities of thioredoxins. Annu Rev Biophys Biomol Struct 30:421-55
Kakolyris, S; Giatromanolaki, A; Koukourakis, M et al. (2001) Thioredoxin expression is associated with lymph node status and prognosis in early operable non-small cell lung cancer. Clin Cancer Res 7:3087-91
Powis, G; Montfort, W R (2001) Properties and biological activities of thioredoxins. Annu Rev Pharmacol Toxicol 41:261-95
Berggren, M M; Powis, G (2001) Alternative splicing is associated with decreased expression of the redox proto-oncogene thioredoxin-1 in human cancers. Arch Biochem Biophys 389:144-9
Berggren, M I; Husbeck, B; Samulitis, B et al. (2001) Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1 transfected cells and results in enhanced protection against apoptosis caused by hydrogen peroxide but not by other agents including dexamethasone, etoposide, and doxorubicin. Arch Biochem Biophys 392:103-9
Baker, A; Santos, B D; Powis, G (2000) Redox control of caspase-3 activity by thioredoxin and other reduced proteins. Biochem Biophys Res Commun 268:78-81
Freemerman, A J; Powis, G (2000) A redox-inactive thioredoxin reduces growth and enhances apoptosis in WEHI7.2 cells. Biochem Biophys Res Commun 274:136-41

Showing the most recent 10 out of 44 publications