NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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ole of CE-Q in initiation of prostate cancer, we are (1) treating rats with E2 <strong>and</strong>/ or testosterone <strong>and</strong> analyzing the CE<br />
metabolites, CE-USH conjugates <strong>and</strong> depurinating CE-DNA adducts in the regions of the prostate by HPLC with<br />
electrochemical <strong>and</strong> mass spectrometric detection; (2) studying in the prostate conversion of testosterone into E2 <strong>and</strong> its<br />
metabolism; <strong>and</strong> (3) determining the expression at the mRNA level of four selected enzymes involved in estrogen activation<br />
<strong>and</strong> deactivation in the prostate of rats treated with E2 <strong>and</strong>/or testosterone. These studies will provide information critical to<br />
underst<strong>and</strong>ing the molecular etiology of prostate cancer, identify biomarkers for early detection of susceptibility <strong>and</strong> lead to<br />
development of strategies for prostate cancer prevention.<br />
DTIC<br />
Biomarkers; Cancer; Deoxyribonucleic Acid; Detection; Electrochemistry; Estrogens; Health; Metabolism; Prostate Gl<strong>and</strong><br />
20040111628 University of Southern California, Los Angeles, CA<br />
Estrogen <strong>and</strong> Retinoid Regulation of DNA Repair in Breast Cancer<br />
Crowe, David L.; May 2004; 11 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-02-1-0568<br />
Report No.(s): AD-A425727; No Copyright; Avail: CASI; A03, Hardcopy<br />
Chemotherapeutic agents used in the treatment breast cancer produce their cytotoxic effects by creating DNA damage.<br />
Estrogen (ER) <strong>and</strong> retinoic acid receptors (RAR) are members of a family of lig<strong>and</strong> dependent transcription factors. ER, RAR,<br />
<strong>and</strong> BRCAl require CREB binding protein (CBP) to activate target gene transcription. The application proposed a new<br />
mechanism by which ER <strong>and</strong> RAR regulate BRCAl mediated DNA repair via CBP. In the second year of the project, we<br />
determined that RARalpha overexpression in ER negative breast cancer cell lines enhances the deleterious effects of RA on<br />
DNA damage induced apoptosis. Treatment with the DNA methyltransferase inhibitor ADC failed to induce additional BRCAl<br />
expression in BR negative breast cancer cell lines. A novel BRCAl mutant protein repressed expression of a number of double<br />
str<strong>and</strong> break repair proteins in the Rad <strong>and</strong> XRCC groups. However, both T47D <strong>and</strong> MDA-MBA68 clones expressing the<br />
novel BRCAl mutant protein were more resistant to the effects of etoposide treatment These results may be due to the<br />
pronounced cell cycle inhibitory effect of the BRCAl mutant protein, thereby rendering the slower dividing cells less sensitive<br />
to the topoisomerase inhibitor.<br />
DTIC<br />
Cancer; Chemotherapy; Deoxyribonucleic Acid; Drugs; Estrogens; Mammary Gl<strong>and</strong>s; Receptors (Physiology)<br />
20040111629 Albert Einstein Coll. of Medicine, Bronx, NY<br />
Taxol Resistance <strong>and</strong> Microtubule Dynamics in Breast Cancer<br />
Orr, George A.; Jun. 2004; 52 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-01-1-0123<br />
Report No.(s): AD-A425729; No Copyright; Avail: CASI; A04, Hardcopy<br />
Alterations to microtubule dynamics, leading to a less stable polymer, may be a crucial determinant in the development<br />
of resistance towards Taxol, <strong>and</strong> other drugs with a binding site on the microtubule polymer. We propose that two potential<br />
mechanisms by which breast cancer cells could alter their microtubule dynamics are by (1) differential expression of the<br />
several a <strong>and</strong> B tubulin isoforms <strong>and</strong> (2) differential binding of endogenous regulators of microtubule assembly to the<br />
cytoskeleton as a result of posttranslational modifications to these tubulin isoforms. The overall goal of this proposal is to<br />
develop rapid <strong>and</strong> innovative protein-based technologies for both quantitating the alpha <strong>and</strong> Beta-tubulin isoform composition<br />
in drug-sensitive <strong>and</strong> -resistant human breast cell lines, <strong>and</strong> for characterizing the posttranslational modifications to these<br />
isoforms. It is only by thoroughly, underst<strong>and</strong>ing Taxol resistance in human breast cancer cells that we will be able to develop<br />
ways to overcome Taxol resistance in breast cancer.<br />
DTIC<br />
Cancer; Mammary Gl<strong>and</strong>s<br />
20040111630 Wisconsin Univ., Madison, WI<br />
Exploring a Link Between NF-kappaB <strong>and</strong> G2/M Cell Cycle Arrest in Breast Cancer Cells<br />
Davis, Shelly M.; Apr. 2004; 7 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-92-1-0623<br />
Report No.(s): AD-A425730; No Copyright; Avail: CASI; A02, Hardcopy<br />
The purpose of this grant is to underst<strong>and</strong> how activation of the NF-KB/Rel family of transcription factors leads to breast<br />
cancer cell survival following treatment with radiation. The NF-kB/Rel family of transcription factors are known to greatly<br />
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