NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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educe the acidosis that forms with hypoxia <strong>and</strong> to reduce damage to liver <strong>and</strong> kidney.<br />
DTIC<br />
Blood Plasma; Oxygen Consumption; Pathology<br />
20040073786 Alabama Univ., Birmingham, AL<br />
Genetic Radiotherapy of Prostate Cancer<br />
Buchsbaum, Donald J.; Dec. 2003; 14 pp.; In English; Original contains color illustrations<br />
Contract(s)/Grant(s): DAMD17-02-1-0001<br />
Report No.(s): AD-A422767; No Copyright; Avail: CASI; A03, Hardcopy<br />
A goal of this proposal is to achieve a high intratumoral concentration of 5-fluorouracil (5-FU) via molecular<br />
chemotherapy employing genetically modified adenoviral (Ad) vectors encoding the genes for somatostatin receptor subtype<br />
2 (SSTr2) <strong>and</strong> cytosine deaminase (CD) which converts the prodrug 5-fluorocytosine (5-FC) to 5-FU under control of the<br />
cyclooxygenase-2 (Cox-2) tumor-specific promoter. The purpose of Specific Aim 1 was to develop, validate, <strong>and</strong> evaluate<br />
genetically modified Ad vectors that will increase expression levels of both SSTr2 <strong>and</strong> CD. We proposed to initially evaluate<br />
two novel two-gene Ad vectors: (1) a native fiber Ad (AdCMVCDCMVSSTr2) <strong>and</strong> (2) Ad under control of the Cox-2<br />
promoter expressing CD <strong>and</strong> SSTr2. We have produced several vectors including AdCox-2LCDCox-2LS STr2, AdCox-2LS<br />
STr2Cox-2LCD, AdRGDCox- 2LCDCox-2LSSTr2, <strong>and</strong> AdRGDCox-2LCDCox-2LSSTr2. The vectors we developed were<br />
tested for SSTr2 <strong>and</strong> CD expression employing membrane receptor binding in vitro with 125I-somatostatin <strong>and</strong> 99mTc-P2O45<br />
that binds to SSTr2, conversion of 5-FC to 5-FU, <strong>and</strong> cytotoxicity against Ad infected cells in the presence of 5-FC. The<br />
vectors were evaluated in vivo for SSTr2 expression <strong>and</strong> CD expression. Efforts are continuing to produce ROD modified<br />
vectors expressing CD <strong>and</strong> SSTr2 under control of the Cox-2L promoter to be used for therapy in local <strong>and</strong> metastatic models.<br />
DTIC<br />
Cancer; Genetics; Prostate Gl<strong>and</strong>; Radiation Therapy<br />
20040073787 California Univ., Irvine, CA<br />
The Role of a LIM Only Factor, LMO-4 in Breast Cancer<br />
Anderson, Bogi; Oct. 2003; 42 pp.; In English; Original contains color illustrations<br />
Contract(s)/Grant(s): DAMD17-00-1-0182<br />
Report No.(s): AD-A422769; No Copyright; Avail: CASI; A03, Hardcopy<br />
LMO-4 is a transcription factor, which exhibits prominent expression in epithelial cells, including that of the breast. Since<br />
previous members of the LIM only (LMO) gene family are oncogenes in lymphocytes, we hypothesized that LMO- 4 may<br />
play a role in mammary gl<strong>and</strong> development <strong>and</strong> cancer. We have now shown that expression of LMO-4 is associated with<br />
undifferentiated cellular stage of breast epithelial cells, such as that found during lobuloalveolar development in pregnancy <strong>and</strong><br />
in breast cancer. Furthermore, the ErbB2 activator heregulin stimulates LMO4 expression in MCF-7 breast cancer cells,<br />
suggesting that LMO4 plays a role in this important oncogenic pathway. In protein interactions studies, we have found that<br />
LMO4 interacts with DNA-binding proteins, including GATA3. We have created transgenic mice in which we overexpress a<br />
dominant negative LMO-4 under the MMTV promoter (MMTV-engrailed-LMO4) to test the role of LMO4 in mammary gl<strong>and</strong><br />
development. Our results show significant inhibition of lobuloalveolar development in these MMTV-engrailed-LMO4<br />
transgenic mice, indicating that LMO-4 plays roles in proliferation <strong>and</strong>/or invasion of breast epithelial cells. Because these<br />
cellular features are associated with breast carcinogenesis <strong>and</strong> because LMO4 is overexpressed in a subset of breast cancers,<br />
our studies implicate LMO4 as a possible oncogene in breast cancer.<br />
DTIC<br />
Cancer; Lymphocytes; Mammary Gl<strong>and</strong>s; Transcription (Genetics)<br />
20040073788 Ohio State Univ., Columbus, OH<br />
Alteration of the Endothelial Barrier by Breast Cancer Cells as a Mechanism of Tumor Resistance<br />
Jones, Carleton B.; May 2002; 8 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-01-1-0588<br />
Report No.(s): AD-A422770; No Copyright; Avail: CASI; A02, Hardcopy<br />
The endothelial cells lining blood vessels that perfuse breast tumors present a barrier that antineoplastic agents must cross<br />
to reach the tumor cells. The purpose of this award was to provide preliminary data to support the hypothesis that tumor cells<br />
can modulate this barrier by secreting soluble factors, by affecting extracellular matrix, or by a combination of these factors.<br />
The specific aims of this project were to 1) determine tumor cell induced expression of multi-drug-resistance proteins in<br />
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