NASA Scientific and Technical Aerospace Reports

20040111552 Colorado State Univ., Fort Collins, CO
Evaluation of Intracavitary Chemotherapy Delivery for the Treatment of Mammary Carcinoma
Dernell, Wukkuan S.; Apr. 2004; 13 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0347; DAMD17-02-1-0348
Report No.(s): AD-A425589; No Copyright; Avail: CASI; A03, Hardcopy
This project will evaluate paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following
conservative (marginal) surgical removal of human breast cancers grown in nude mice. This delivery method is proposed to
control local tumor disease as well as assist in control of systemic metastasis. We have established 5 human breast cancer cell
lines within our laboratory. We have elected purchase and implement a unique (luciferase) imaging system which allows in
vivo imaging of tumor growth and metastasis (and subsequently decrease animal use) . Tumor cell lines have been transfected
with the luciferase gene. In vitro testing of cell lines has established paclitaxel sensitivity and shown a synergistic effect of
delivering paclitaxel by the poloxamer polymer for the chemotherapy resistant cell line, MCF-7-ADR. We have begun the
simultaneous evaluation of local and systemic toxicity, local, regional, and systemic distribution and local and systemic
efficacy of locally delivered paclitaxel chemotherapy following tumor removal using the MCF-7-ADR cell line in nude mice.
Intracavitary administration of taxol in poloxamer has been well tolerated and resulted in complete control of local tumor
regrowth and metastasis following marginal tumor removal. This compared to only marginal tumor control using systemically
delivered parent paclitaxel.
DTIC
Cancer; Chemotherapy; Enzymes; In Vivo Methods and Tests; Mammary Glands
20040111553 California Univ., Irvine, CA
SXR: A Target for Breast Cancer Prevention and Treatment
Blumberg, Bruce; Apr. 2004; 18 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0323
Report No.(s): AD-A425590; No Copyright; Avail: CASI; A03, Hardcopy
Anti-estrogens such as tamoxifen are important therapeutic agents in the treatment and chemoprevention of breast
cancers. Other compounds such as phytoestrogens, fatty acid amides and retinold X receptor (RxR) agonists are also effective
against breast cancer in cell lines and in animal models. Because these compounds are unrelated it has not been appreciated
that they might act through a common mechanism. These compounds all share the ability to activate a heterodimer of the
steroid and xenobiotic receptor (SxR) and RXR. Our hypothesis is that SXR serves as a common molecular target for some
of the anti-proliferative effects of these compounds and that activation of SXR is itself anti- proliferative. We have analyzed
mRNA from breast cancer cell lines treated with SXR activators by micorarray, and have validated some of the putative SXR
target genes found using quantitative real time RT-PCR. We have also analyzed the mechanism by which SXR activation stops
cell proliferation using assays for apoptosis and necrosis. Our preliminary results indicate that SXR activators may be inducing
caspase- dependent apoptosis to stop the apparent cell proliferation. Further experiments are underway to study SXR activatorinduced
apoptosis and link this effect back to the induced SXR target genes found by microarray.
DTIC
Cancer; Health; Mammary Glands; Prevention; Targets
20040111554 Naval Medical Research Center, Silver Spring, MD
Enhancing the Immunogenicity of a Dengue-2 DNA Vaccine with Adjuvants and Anti-FCgammaRI Antibodies
Porter, Kevin R.; Oct. 2003; 12 pp.; In English
Report No.(s): AD-A425592; No Copyright; Avail: CASI; A03, Hardcopy
The objective is to use adjuvants to enhance the immunogenicity of a dengue (DEN) DNA vaccine. The adjuvants to be
evaluated in this project include aluminum phosphate, tetanus toxoid and anti-FcyR monoclonal antibodies chemically linked
to the DNA vaccine. Initial attempts to link the anti- FcyR monoclonal antibody to the DNA vaccine resulted in a poor
efficiency in the linkage reaction. An alternative method of adding the thiol group (EndTag Nucleic Acid Labeling System)
to the linearized DNA should increase the reaction efficiency. Experiments were initiated to evaluate the ability of tetanus
toxoid (TT) to enhance the immunogenicity of the DEN DNA vaccine. The antibody responses to the vaccine given IM were
enhanced slightly by combining it with TT. However, the ELISA and neutralizing antibody levels were inferior to the levels
obtained with ID administration of the vaccine alone. Aluminum Phosphate was demonstrated to slightly enhance anti-dengue
neutralizing antibody responses, only when the DNA vaccine was given ID at sub optimal doses. There was essentially no
effect when the vaccine was administered IM.
DTIC
Antibodies; Deoxyribonucleic Acid; Infectious Diseases; Vaccines
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