NASA Scientific and Technical Aerospace Reports

to a topic in or immediately applicable to ovarian cancer. The second aim was to provide a mentored experience for selected
fellows. The third aim specified the delivery of feedback to the trainees by mentors and the program PI. The final aim described
a rigorous review process for the program. These aims are all being addressed. The program has selected 3 talented senior post
doctoral fellows who are all assigned to work with Professors at Harvard Medical School in the fields of Medicine/
Oncogenesis, Surgery/Signal transduction, and Cell Biology/Signal transduction. These fellows conduct their research at 3
different institutions within the Dana Farber/Harvard Cancer Center. All the fellows are productive in their research and one
has already successfully competed for a faculty development grant. Formal review of the program is planned latter this spring
as is the second round of competition for fellows.
DTIC
Cancer; Education; Medical Science; Ovaries
20040111591 Texas Univ. Health Science Center, San Antonio, TX
BRCA1 Regulation of Estrogen Signaling in the Breast
Boyer, Thomas G.; May 2004; 41 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0272
Report No.(s): AD-A425657; No Copyright; Avail: CASI; A03, Hardcopy
Mutational inactivation of BRCAl confers a cumulative lifetime risk of breast and ovarian cancers. However, the
underlying basis for the tissue-specific tumor suppressor properties of BRCAl remains poorly defined. Previously, we
described a novel function for BRCAl in suppressing the ligand-independent transcriptional activity of the estrogen receptor
alpha (ER alpha), a principal determinant of the growth and differentiation of breasts and ovaries. Based on these observations,
we hypothesized that BRCAl represents a ligand-reversible barrier to transcriptional activation by unliganded ER alpha and,
further, that mutational inactivation of BRCAl promotes breast epithelial cell proliferation through aberrant expression of
estrogen-responsive genes, possibly contributing to tumorigenesis. To substantiate this hypothesis we have proposed the
following aims: (1) to biochemically reconstitute BRCAl-mediated ligand-independent repression of ER alpha in vitro; (2) to
examine the role of estrogen-induced site- specific BRCAl phosphorylation in the regulation of BRCAl- mediated
ligand-independent ER alpha repression; and (3) to determine the role of BRCA1 in the control of paracrine growth signaling
in the breast. Collectively, these studies should reveal novel insight into the tissue-specific tumor suppressor function of
BRCAl and provide defined molecular targets for future intervention in breast cancer.
DTIC
Cancer; Estrogens; Genes; Mammary Glands
20040111592 Florida Univ., Gainesville, FL
Biochemical Markers of Brain Injury: An Integrated Proteomics Based Approach
Hayes, Ronald L.; Feb. 2004; 112 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0066
Report No.(s): AD-A425658; No Copyright; Avail: CASI; A06, Hardcopy
In addition to being the leading cause of death for civilians under 45 years of age, recent studies have confirmed that
traumatic brain injury (TBI) is one of the most frequent causes of morbidity and mortality on the modern battlefield.
Specifically, 40% of battlefield fatalities in the Viet Nam war were due to head wounds. It has been reported that of patients
arriving alive at military field hospitals, 20% with extremely severe brain wounds die before surgery was performed, and 80%
received neurosurgical treatment, with a 10% surgical mortality rate. Penetrating head injury alone accounts for 25% of all
wartime casualties and approximately 40% of these injuries are fatal. Recently, studies of casualties during the Iraqi Conflict
suggest that as many as 2/3 of combat casualties have associated concussive brain injuries. Thus, the current proposal focuses
on development of non-invasive diagnostics of TBI that ultimately will be useful in a battlefield environment. The research
has been divided into 3 SOWs. The SOWs are as follows: SOW 1: To employ integrated proteomics-based technologies to
identify specific proteins or peptide fragments in brain released into CSF and/or blood of rats following experimental traumatic
brain injury (TBI) or focal cerebral ischemia (middle cerebral artery occlusion: MCAO).
DTIC
Biochemistry; Brain; Brain Damage; Injuries; Markers; Proteome
20040111593 Pittsburgh Univ., Pittsburgh, PA
TRAIL-Based Radio-Gene Therapy for Prostate Cancer
Song, Jae J.; Apr. 2004; 8 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0128
Report No.(s): AD-A425662; No Copyright; Avail: CASI; A02, Hardcopy
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