NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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Metastasis-suppressor genes suppress the growth of metastases without affecting tumor growth. We have been studying<br />
the role of inactivation of one such metastasis suppressor gene, Map Kinase 4 (MKK4) in the process of metastatic<br />
colonization. Work proposed in this application is aimed at extending our ongoing studies in the AT6.1 model system into new<br />
transgenic models of prostate cancer. In the past year we have made significant progress in the immunohistochemical studies<br />
proposed in the initial application <strong>and</strong> the development of gene targeting vectors for animal studies.<br />
DTIC<br />
Cancer; Genes; Metastasis; Prostate Gl<strong>and</strong>; Suppressors<br />
20040111752 Henry Ford Health System, Detroit, MI<br />
Hormone Receptors in Breast Cancer Prognosis - Racial <strong>and</strong> Quantitative Effects<br />
Tammemagi, Carl M.; Jun. 2003; 56 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-00-1-0287<br />
Report No.(s): AD-A425960; No Copyright; Avail: CASI; A04, Hardcopy<br />
Breast cancer survivors compose the largest group of cancer survivors in the USA. As heterogeneity exists within stages<br />
<strong>and</strong> between races in breast cancer survival, it is important to develop a better underst<strong>and</strong>ing of prognostic factors. Tumor<br />
estrogen <strong>and</strong> progesterone receptors are one of the more important prognostic factors in breast cancer patients. However,<br />
currently in clinical practice hormone receptor status is treated as either being present or absent <strong>and</strong> is treated similarly in all<br />
groups. The dichotomization of hormone status may lead to loss of valuable information <strong>and</strong> hormone receptor status may not<br />
have the same effect in African Americans <strong>and</strong> Whites. This historical cohort study evaluates quantitative differences in tumor<br />
hormone receptors in African Americans <strong>and</strong> Whites <strong>and</strong> determines whether survival effects differ between the two groups.<br />
This study also assesses whether a dose-response relationship, linear or nonlinear, exists between hormone receptors <strong>and</strong><br />
survival. Findings of this study may lead to better prediction of survival <strong>and</strong> to identification of subsets of patients at higher<br />
risk that may have gone unrecognized by the application of a single cutpoint. Our preliminary findings indicate that African<br />
American breast cancer patients have more estrogen receptor negativity <strong>and</strong> a worse survival.<br />
DTIC<br />
Cancer; Hormones; Mammary Gl<strong>and</strong>s; Prognosis<br />
20040111753 National Jewish Medical <strong>and</strong> Research Center, Denver, CO<br />
Cloning <strong>and</strong> Characterization of Genes That Inhibit TRAIL-Induced Apoptosis of Breast Cancer Cells<br />
Shu, Hong-Bing; Apr. 2004; 13 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-00-1-0358<br />
Report No.(s): AD-A425962; No Copyright; Avail: CASI; A03, Hardcopy<br />
TRAIL is a tumor necrosis factor family member that can specifically induce apoptosis of cancer cells but not of normal<br />
cells. However, some cancer cells are resistant to TRAIL-induced apoptosis. The purpose of this proposed study is to clone<br />
<strong>and</strong> characterize such inhibitory genes of TRAIL- induced apoptosis. Using cDNA subtraction <strong>and</strong> retroviral cDNA- based<br />
expression cloning approaches, we have obtained more than multiple c<strong>and</strong>idate clones of TRAIL-inhibitory genes. Among the<br />
c<strong>and</strong>idate clones, the short splice form of Casper/c- FLIP (Casper-S were shown to confer resistance to TRAIL- induced<br />
apoptosis. Casper deficient embryonic cells were sensitive to TRAIL-induced apoptosis. Re- introduction of Casper-S into<br />
Casper deficient cells conferred resistance to TRAIL-induced apoptosis. This project has identified <strong>and</strong> validated Casper-S as<br />
a major cellular inhibitor of TRAIL- induced apoptosis.<br />
DTIC<br />
Apoptosis; Cancer; Cloning (Biology); Genes; Mammary Gl<strong>and</strong>s<br />
20040111755 V<strong>and</strong>erbilt Univ., Nashville, TN<br />
Regulation of ErbB-2 Metabolic Stability<br />
Carpenter, Graham F.; Mar. 2004; 43 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-00-1-0483<br />
Report No.(s): AD-A425964; No Copyright; Avail: CASI; A03, Hardcopy<br />
This grant has focused on the mechanism by which geldanamycin controls the metabolic stability of ErbB-2, a coreceptor<br />
tyrosine kinase. ErbB-2 is overexpressed in breast cancer <strong>and</strong> is known to increase cell proliferation. Geldanamycin<br />
decreases ErbB-2 levels in cells <strong>and</strong> is in clinical trials for the treatment of breast cancer. Our studies in this grant have<br />
examined the mechanism by which geldanamycin decreases ErbB-2 levels. Published data demonstrate that geldanamycin<br />
provokes prpteolytic cleavage events within the ErbB-2 intracellular domain <strong>and</strong> thereby decreases the level of the mature<br />
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