NASA Scientific and Technical Aerospace Reports

A recombinant gene was constructed, encoding the soluble form of the human Flt3L gene (hFlex) at the 5’ end and the
human TRAIL gene at the 3’ end. This plasmid (phFlex/TRAIL) was administrated by the hydrodynamic-based gene delivery.
As a result, tumor growth was significantly delayed by hFlex/TRAIL plasmid administration. For the expression of GOD,
hybrid yeast promoter-containing vector was constructed, confirming the GOD expression. In vivo studies were conducted to
examine the effects of intratumoral GOD-IT administration on nude mice. As a result, tumor growth was delayed by GOD-IT
administration.
DTIC
Cancer; Gene Therapy; Prostate Gland
20040111594 Nebraska Univ., Omaha, NE
Nanoparticle-Mediated p53 Gene Therapy for Breast Cancer
Prabha, Swayam; Apr. 2004; 33 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0506
Report No.(s): AD-A425664; No Copyright; Avail: CASI; A03, Hardcopy
Gene expression with non-viral vectors is usually transient and lasts only for few days. Therefore, repeated injection of
the expression vector is required to maintain a therapeutic protein concentration in the target tissue. Biodegradable
nanoparticles ( 200 nm diameter) formulated using biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA) have the
potential for sustained gene delivery. Our hypothesis is that the nanoparticle-mediated gene delivery would resuft in sustained
gene expression, and hence better efficacy with a therapeutic gene. Nanoparticles loaded with wt- p53 DNA demonstrated
greater and sustained antiproliperative activity in vitro as compared to that with naked DNA and DNA- liposome complex.
The greater efficacy of wt-p53 DNA-loaded nanoparticles was attributed to sustained intracellular DNA delivery and gene
expression. A single-dose intratumoral administration of wt-p53 DNA-loaded nanoparticles demonstrated significant
inhibition of tumor growth in MDAMB-435-induced subcutaneous breast cancer mouse model that also resulted in prolonged
animal survival than controls. The mechanism of inhibition of tumor growth with wt-p53- DNA-loaded nanoparticles was
attributed to higher apoptosis of tumor cells than that in controls, and also the induction of antiangiogenic protein,
thrombospondin-I that inhibited tumor angiogenesis. The studies thus demonstrate the efficacy of nanoparticles as a non-viral
gene expression vector and their potential application in breast cancer therapy.
DTIC
Cancer; Gene Therapy; Mammary Glands; Nanoparticles
20040111596 Virginia Commonwealth Univ., Richmond, VA
Feasibility Studies in Development of a Temporary Implantable Lactate Sensor Biochip for Monitoring During
Hemorrhage
Guiseppi-Elie, Anthony; Apr. 2004; 46 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0172
Report No.(s): AD-A425666; No Copyright; Avail: CASI; A03, Hardcopy
Lactate levels have been found to correlate with the severity of injury, including hemorrhage and whole body hypoxia.
The ability to monitor in vivo lactate in the interstitium is possible but current methods are either not clinically feasible for
prolonged measurement or are unreliable because they suffer from deleterious effects of endogenous interference and fouling.
DTIC
Feasibility; Hemorrhages; Implantation; In Vivo Methods and Tests; Injuries; Lactates
20040111597 New Mexico Univ., Albuquerque, NM
Regulation of Cell Cycle by BCCIP a BRCA2 and CDKN1(p21) Interacting Protein
Shen, Zhiyuan; Jun. 2004; 11 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0317
Report No.(s): AD-A425667; No Copyright; Avail: CASI; A03, Hardcopy
DAMD17-03-1-0317 is an IDEA award that focuses on the roles of BCCIP in cell cycle regulation. The approaches are
over-expression and down-regulation of BCCIP by RNAi. The project has been moving on smoothly in the first 12 months.
We have accomplished the scientific objectives of tasks 1-3, and 50% of tasks 4-5. We have published one paper based on this
study. As an un-anticipated discovery, we have found that BCCIP also regulates p2l expression. This finding further
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