NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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that are required for DNA replication, including induction of histone gene transcription. We examined the function of p220<br />
through the development of human somatic HCTl 16 cells that conditionally express p220. We found that p220 is required<br />
for the transition from GO/Gi into S-phase, the activation of endogenous histone gene transcription, <strong>and</strong> the localization of<br />
Cajal body component p80(sub coilin) Expression of human papillomavirus E7 abrogated cell cycle arrest in response to<br />
p220-depletion, but not the defects in hi stone gene transcription activation. Basal histone 114 expression in GO/GI, although<br />
p220-dependent, occurs in the absence of detectable phosphorylation of p220 on Cdk2 sites. These findings indicate that p220<br />
is an essential downstream component of the cyclin E/Cdk2 signaling pathway <strong>and</strong> functions to coordinate multiple elements<br />
of the Gl/S transition.<br />
DTIC<br />
Cancer; Deoxyribonucleic Acid; Dissection; Mammary Gl<strong>and</strong>s; Phosphorylation<br />
20040111639 Tulane Univ., New Orleans, LA<br />
SDF-1 DC1/DC2 <strong>and</strong> Tumor Angiogenesis<br />
Zou, Weiping; Apr. 2004; 25 pp.; In English; Original contains color illustrations<br />
Contract(s)/Grant(s): DAMD17-03-1-0078<br />
Report No.(s): AD-A425742; No Copyright; Avail: CASI; A03, Hardcopy<br />
Ovarian carcinomas have a poor prognosis, often associated with multifocal intraperitoneal dissemination accompanied<br />
by intense neovascularization. To examine tumor angiogenesis in the tumor microenvironment, we studied malignant ascites<br />
of patients with untreated ovarian carcinoma. We observed high numbers of plasmacytoid dendritic cells (PDC) <strong>and</strong> significant<br />
stromal derived factor (cxcL-12/sDF)-l in their malignant ascites attracting PDC into the tumor environment. We now show<br />
that tumor associated PDC induced angiogenesis in vivo. By contrast, myeloid dendritic cells (MDC) were absent from<br />
malignant ascites. MDC derived in vitro suppressed angiogenesis in vivo. Thus, the tumor may attract PDC to augment<br />
angiogenesis, while excluding MDC to prevent angiogenesis inhibition. Although dendritic cells have long been known to<br />
affect tumor immunity, these data also implicate them in tumor neoangiogenesis.<br />
DTIC<br />
Cancer; Neoplasms; Ovaries; Tumors<br />
20040111640 Oregon Health Sciences Univ., Portl<strong>and</strong>, OR<br />
Effects of Herstatin an Alternative Her-2 (erbB-2) Product on Hormonal Responsiveness of Breast Cancer<br />
Clinton, Gail M.; Jun. 2004; 8 pp.; In English; Original contains color illustrations<br />
Contract(s)/Grant(s): DAMD17-03-1-0336<br />
Report No.(s): AD-A425743; No Copyright; Avail: CASI; A02, Hardcopy<br />
The establishment <strong>and</strong> progression of breast cancer is controlled by receptors for estrogens (ER) <strong>and</strong> peptide growth<br />
factors (1, 2, 3). Several lines of evidence suggest that estrogen responsiveness <strong>and</strong> resistance to anti-estrogens may be<br />
influenced by cross- talk between ER <strong>and</strong> erbB receptor pathways. Overexpression of HER-2 (erbB2) <strong>and</strong> signaling triggered<br />
by the erbB growth factor, Heregulin (HRG), has been found to confer resistance to the antiestrogen, tamoxifen (4- 7). The<br />
involvement of erbB receptors has led to suggestions that receptor targeted inhibitors may enhance the therapeutic efficacy of<br />
tamoxifen. We recently discovered an alternative HER-2 product called Herstatin, which binds to HER-2 <strong>and</strong> the EUF receptor<br />
(EGFR) <strong>and</strong> blocks their activation (8-10). Preliminary studies indicate that Herstatin blocks both EUF <strong>and</strong> HRG signaling<br />
in estrogen responsive MCF7 cells <strong>and</strong> therefore may enhance tamoxifen sensitivity in breast cancer cells. Purpose: The<br />
objective of this proposal is to thoroughly evaluate the effects of Herstatin on hormonal responsiveness of ER positive breast<br />
cancer cells. Scope: The proposed research will evaluate the potential therapeutic efficacy of Herstatin combined with<br />
tamoxifen in the treatment of breast cancer.<br />
DTIC<br />
Cancer; Estrogens; Hormones; Mammary Gl<strong>and</strong>s<br />
20040111645 Texas Univ., Houston, TX<br />
Investigation of Alpha6 Integrins <strong>and</strong> Their Signaling Intermediates as Prognostic Markers for Breast Cancer<br />
Gilcrease, Michael Z.; May 2004; 8 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-01-1-0298<br />
Report No.(s): AD-A425749; No Copyright; Avail: CASI; A02, Hardcopy<br />
Our goal was to evaluate the expression of alpha6beta4 integrin in breast carcinoma <strong>and</strong> to test whether increased<br />
alpha6beta4-mediated signaling correlates with poor prognosis in breast cancers that overexpress alpha6beta4. We found that<br />
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