NASA Scientific and Technical Aerospace Reports

factor-receptor and ligand expression as mechanism of prostate cancer prevention. To date, the offspring were evaluated for
transgene expression, and male TRAMP mice were subjected to these nutritional chemicals in AIN-76A diet or to control diet
(AIN-76A), starting at 5 weeks postpartum. Each group contains 30 TRAMP males. Necropsy is scheduled for April - June
2004. Aim 2 has been initiated.
DTIC
Cancer; Phenols; Prostate Gland
20040111587 Scripps Research Inst., La Jolla, CA
Novel Angiogenic Domains: Use in Identifying Unique Transforming and Tumor Promoting Pathways in Human
Breast Cancer
Deuel, Thomas F.; Oct. 2003; 18 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0151
Report No.(s): AD-A425651; No Copyright; Avail: CASI; A03, Hardcopy
Breast cancers in humans often grow slowly or even remain undetectable for long periods of time only to reappear in
discreet stages as progressively more malignant tumors. Recently, studies in both human cancers and experimental cancers in
animals have established that cancers become progressively more aggressive in incremental steps that result form genetic
mutations or ‘switches’ in the tumor cells themselves. We have found that the two growth/differentiation promoting cytokines
pleiotrophin (PTN) and midkine (MK) act as ‘switches’ when introduced into breast cancer cells to stimulate more aggressive
growth and induce new intratumor blood vessel formation, ie, an ‘angiogenic switch.’ Different studies have found constitutive
expression of either the PTN or MK genes in over 50% of human breast cancers, suggesting our data is very important and
relevant to human breast cancer. We now plan to pursue the mechanism of PTN signaling in both MMTV driven
pleiotrophin%gain of function mice and ‘knock-out’ pleiotrophin mice developed in the laboratory and the mechanisms of
downstream PTN signaling with different ‘chip technology-driven strategies available to us in the laboratory.
DTIC
Cancer; Identifying; Mammary Glands; Tumors
20040111589 Kansas Univ. Center for Research, Inc., Lawrence, KS
The Design, Synthesis, and Biological Evaluation of New Paclitaxel Analogs With the Ability to Evade Efflux by
P-Glycoprotein
Turunen, Brandon J.; Georg, Gunda I.; May 2004; 29 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0435
Report No.(s): AD-A425654; No Copyright; Avail: CASI; A03, Hardcopy
Paclitaxel, a cytotoxic agent originally isolated fro the bark of the Pacific Yew, has been developed as an effective
chemotherapeutic drug, Sadly however, the treatment of cancer with paclitaxel often results in the development of drug
resistance. Furthermore, few current chemotherapeutics are able to cross the blood brain barrier leaving victims of brain cancer
few viable treatment alternatives. P- glycoproteins are non-specific transmembrane transporter proteins that are associated
with specialized normal tissue barriers, for example the blood brain barrier, and are generally over expressed in tumor cells.
These transporter systems recognize a large variety of structurally and functionally diverse chemical entities and are
responsible for increasing efflux and decreasing influx of lipophilic substances. This active efflux by P-glycoprotein is believed
to be responsible for the development of drug resistance and also the lack of brain uptake. This research focuses on strategies
to by-pass P-glycoprotein efflux in order to deliver active, structurally modified paclitaxel analogues to the drug resistant
breast cancer cells and/or brain cancer cells.
DTIC
Cancer; Efflux; Mammary Glands; Metastasis
20040111590 Massachusetts General Hospital, Boston, MA
Ovarian Cancer Training Program at the Dana Farber/Harvard Cancer Center
Seiden, Michael V.; Apr. 2004; 40 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0161
Report No.(s): AD-A425655; No Copyright; Avail: CASI; A03, Hardcopy
This Award funded the initiation of a mentored research experience in ovarian cancer biology at the Dana Farber/Harvard
Cancer Center. The primary aims, articulated in the Statement of Work, included creating a mechanism to identify and select
outstanding postdoctoral fellows who had a commitment to serous multi-year experience in research that was directly related
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