The biochemistry group has a dual role in this program project. It is responsible for the initial biochemical characterization of agents synthesized under this grant, and also performs in-depth biochemical routine determinations and hence appears appropriate for support as a core. Our proposed core consists of (a) a cell culture laboratory that determines cytotoxicities of new agents, collaborates with the biochemists in the performance of routine metabolic experiments in cell culture, and provides cells in quantity for enzyme isolations, and (b) a component for rapidly obtaining a biochemical profile of a new agent by subjecting it to a series of assays including examination by HPLC of its phosphorylation and its effects on nucleotide pools, determinations of its effects on macromolecular syntheses, and determination of its activity as substrate or inhibitor of selected enzymes of nucleoside metabolism.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA034200-15
Application #
6269171
Study Section
Project Start
1998-02-01
Project End
1999-01-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Southern Research Institute
Department
Type
DUNS #
006900526
City
Birmingham
State
AL
Country
United States
Zip Code
35205
Thottassery, Jaideep V; Sambandam, Vijaya; Allan, Paula W et al. (2014) Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4'-thio-2'-deoxycytidine and 5-aza-4'-thio-2'-deoxycytidine. Cancer Chemother Pharmacol 74:291-302
Waud, William R; Parker, William B; Gilbert, Karen S et al. (2012) Isolation and characterization of a murine P388 leukemia line resistant to thiarabine. Nucleosides Nucleotides Nucleic Acids 31:14-27
Waud, William R; Gilbert, Karen S; Secrist 3rd, John A (2012) Preclinical antitumor activity of thiarabine in human leukemia and lymphoma xenograft models. Nucleosides Nucleotides Nucleic Acids 31:647-60
Waud, William R; Gilbert, Karen S; Secrist 3rd, John A (2012) Preclinical combination therapy of thiarabine plus various clinical anticancer agents. Nucleosides Nucleotides Nucleic Acids 31:630-46
Waud, William R; Gilbert, Karen S; Secrist 3rd, John A (2011) Lack of in vivo cross-resistance with 4'-thio-ara-C against drug-resistant murine P388 and L1210 leukemias. Cancer Chemother Pharmacol 68:399-403
Waud, William R; Gilbert, Karen S; Parker, William B et al. (2011) Isolation and characterization of a murine P388 leukemia line resistant to clofarabine. Nucleosides Nucleotides Nucleic Acids 30:826-38
Parker, William B; Shaddix, Sue C; Gilbert, Karen S et al. (2009) Enhancement of the in vivo antitumor activity of clofarabine by 1-beta-D-[4-thio-arabinofuranosyl]-cytosine. Cancer Chemother Pharmacol 64:253-61
Tiwari, Kamal N; Shortnacy-Fowler, Anita T; Parker, William B et al. (2009) Synthesis and anticancer evaluation of 4'-C-methyl-2'-fluoro arabino nucleosides. Nucleosides Nucleotides Nucleic Acids 28:657-77
Someya, Hitoshi; Waud, William R; Parker, William B (2006) Long intracellular retention of 4'-thio-arabinofuranosylcytosine 5'-triphosphate as a critical factor for the anti-solid tumor activity of 4'-thio-arabinofuranosylcytosine. Cancer Chemother Pharmacol 57:772-80
Thottassery, Jaideep V; Westbrook, Louise; Someya, Hitoshi et al. (2006) c-Abl-independent p73 stabilization during gemcitabine- or 4'-thio-beta-D-arabinofuranosylcytosine-induced apoptosis in wild-type and p53-null colorectal cancer cells. Mol Cancer Ther 5:400-10

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