NASA Scientific and Technical Aerospace Reports

endothelial cells express two EG-1 RNA species (1.2 kb and 2.4 kb). The expression of either transcripts is upregulated by
endothelial cells when exposed to tumor conditioned media. This phenomenon is observed only in sparse conditions (50%
confluency). Transcripts are present abundantly in highly vascular tissues such as placenta, testis, and liver. Interestingly, both
Northern analysis and in situ hybridization studies show that this gene is expressed in other cell types as well, predominantly
the epithelial type. Breast cancer, prostate cancer, and colon cancer cells show elevated expression of the higher 2.4 kb RNA
form. Our data suggest that EG-1 is associated with a stimulated state in endothelial and epithelial cells, and may have a role
in tumor angiogenesis.
DTIC
Cancer; Deoxyribonucleic Acid; Diagnosis; Endothelium; Genes; Intestines; Mammary Glands; Prostate Gland; Ribonucleic
Acids
20040111636 Sloan-Kettering Inst. for Cancer Research, New York, NY
Toward a Diagnostic Immunoassay Specific for Prostate Cancer: Chemical Synthesis of Homogeneous N-Linked
Prostate Specific Antigen Glycopeptides
Miller, Justin S.; Mar. 2004; 17 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-03-1-0016
Report No.(s): AD-A425738; No Copyright; Avail: CASI; A03, Hardcopy
Current prostate cancer (PCa) diagnostic tools are unsatisfactory because of their inability to determine the root cause of
elevated levels of prostate specific antigen (PSA), which can arise from benign or malignant conditions. The purpose of the
research described is the development of an improved PCa immunoassay based on errant PSA glycoform expression in
prostatic cancer cells. Specifically, the aim is to define and implement a strategy for the synthesis of normal and transformed
PSA glycopeptides, and to employ the PSA glycopeptides in immunological studies targeting the generation of antibodies that
differentiate between normal and cancerous PSA. Such differentiating antibodies would comprise the sought-after improved
PCa diagnostic. The first round of synthetic studies is complete: a strategy has been defined for the chemical synthesis of
complex glycans and glycopeptides, including PSA-based glycopeptides. The synthetic strategy has been applied successfully
to the syntheses of normal and transformed fragments of PSA. A collaboration is currently underway, during which the PSA
glycopeptides will be conjugated with a carrier protein (keyhole limpet hemocyanin, KLH), and attempts will be made to
generate antibodies that can differentiate between normal and transformed glycoforms of PSA.
DTIC
Antigens; Cancer; Immunoassay; Prostate Gland; Synthesis (Chemistry)
20040111637 Baylor Coll. of Medicine, Houston, TX
Inhibition of Her2 Transcription by Small Organic Molecules
Choi, Yongmun; Uesugi, Motonari; Apr. 2004; 17 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0277
Report No.(s): AD-A425740; No Copyright; Avail: CASI; A03, Hardcopy
Overexpression of the Her2 protein has been found in -30% of breast tumors, and the inhibition of Her2 expression may
be an effective way to treat Her2-positive patients. In the first year, the P.I. and co-workers discovered adamanolol, a drug-like
compound that impairs the viability of Her2 positive breast cancer cell lines by reducing the expression of Her2. In the second
year of funding, we conducted structure-activity relationship studies of adamanolol derivatives and designed a secondgeneration
compound we named ‘wrenchnolol.’ The wrench-shaped structure of wrenchnolol permitted detailed biochemical
and biophysical analysis of the compound including evaluation of dissociation constants, subcellular localization, binding
selectivity in cells. Wrenchnolol is a chemically tractable compound that is suited for mechanistic analysis and for further
application.
DTIC
Cancer; Mammary Glands; Molecules; Organic Compounds; Transcription (Genetics)
20040111638 Baylor Coll. of Medicine, Houston, TX
Molecular Dissection of the 8 Phase Transcriptional Program Controlled by Cyclin E/P220 NPAT Signaling Pathway
Nalepa, Grzegorz; Harper, Jeffrey; Apr. 2004; 23 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0292
Report No.(s): AD-A425741; No Copyright; Avail: CASI; A03, Hardcopy
Deregulation of the cyclin E pathway is associated with breast cancer. p220 links cyclin E to important S-phase events
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