NASA Scientific and Technical Aerospace Reports

child health clinic and construction is underway to extend the Kombewa clinical research facility. A pediatric wing and modem
research laboratory buildings will be ready for occupancy during the final year of the agreement. A 135 children dose and age
stratified Phase 1 clinical trial for MSP-1 and an epidemiological study involving 276 children is in progress at the Kombewa
field site. Both studies are in their follow-up phase. In Kericho, a retrospective economic impact study was completed and
published results demonstrate a significant decrease in earnings of both the infected worker and the employer. A prospective
comparison of ElA and Western blot testing with four rapid tests in 486 subjects enrolled in an HIV-l sero-incidence study was
undertaken in Kericho. The sensitivity of all four rapid tests was 100% and specificity ranged from 99.1% to 100% with high
positive and negative predictive values. Recruitment into the cohort development protocol in preparation for future HIV/AlDS
vaccine intervention studies also commenced this year. Over 2600 subjects have been enrolled with some groups already into
their first six month follow-up visit. Work in leishmaniasis was initiated with the arrival of Ellison Fellows to the unit under
a special new NRC program. A pathway for prostaglandin synthesis in the parasite has been described and published. A
potential role for this novel pathway in the life cycle or pathogenesis of the parasite is under investigation.
DTIC
Epidemiology; Immunology; Infectious Diseases; Parasitic Diseases; Prevention
20040111678 Baylor Coll. of Medicine, Houston, TX
The Role of Chk2 in Breast Cancer
Elledge, Stephan J.; Apr. 2004; 15 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0280
Report No.(s): AD-A425809; No Copyright; Avail: CASI; A03, Hardcopy
In the last progress report, I described our progress on the isolation of Chk2 mutant cells and their characterization. That
aim is essentially completed. In the last year we have concentrated on Aim 2, which includes finding Chk2 associated proteins
and potential Chk2 substrates. To identify Chk2 associated proteins, we took the FHA domain (Forked-Head Associated) of
Chk2 which is known to be involved in protein-Protein interaction and produced it in E. coli as a GST fusion. We then went
on to use this GST-FHA domain protein as an affinity column to purify associated proteins. In this way we identified a known
DNA damage regulated protein 53BP1. We provide the data for this experiment below in the Body section. 53BP1 was
originally identified through its ability to bind to the tumor suppressor protein p53 through 53BP1’s C- terminal BRCT (Brcal
carboxyl terminus) repeats (1,2) which are found in many DNA damage response proteins (3-8). 53BP1 responds to DNA
double strand breaks (9-12), quickly relocalizing to discrete nuclear foci upon exposure to IR. These foci colocalize with those
of the Mrel l/Nbsl/Rad50 complex and phosphorylated gamma-H2AX which are thought to facilitate recruitment of repair
factors to damaged DNA (9-11). In response to IR, 53BP1 is phosphorylated in an ATM (ataxia telangiectasia mutated)
dependent manner (10-12), but its role in the DNA damage response is unclear.
DTIC
Cancer; Mammary Glands
20040111681 California Univ., Berkeley, CA
Dietary Determinants of Prostate Cancer
Chu, Lisa W.; Mar. 2004; 8 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-03-1-0157
Report No.(s): AD-A425814; No Copyright; Avail: CASI; A02, Hardcopy
Prostate Cancer (PCa) accounts for nearly 30% of all newly diagnosed cancers among American men. Epidemiologic
studies suggest that dietary factors may be important in the etiology of PCa. The objectives of our research is to determine
how nutritional compounds genistein, betasitosterol, and omega-6 fatty acids function as modulators of PCa. In the first year,
we are developing the technical tools with which to investigate gene expression patterns that are altered by the 3 dietary
compounds. We have upgraded and optimized our microarrayer to allow for more efficient printing. The new microarrayer
setup will aid in preparing a custom microarray containing approximately 400 unique CDNAs that are relevant in pathways
of apoptosis and androgen receptor among others. In addition, we optimized our protocol for multicolor spectral transcript
analysis to accommodate up to 8 colors 50 as to maximize the number of different RNA species that can be detected. To test
the improved tools, we have initiated in vitro experiments using PCa cell lines and the three dietary compounds. In addition,
the fellow has learned xenograft techniques in the co-mentor’s laboratory as well as biostatistical analyses that will be applied
towards the in vivo studies for the second year of fellowship.
DTIC
Cancer; Diets; Prostate Gland
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