NASA Scientific and Technical Aerospace Reports

20040111546 Texas Univ., Houston, TX
Functional Characterization of the Murine Homologue of PLAB a Novel TGF-B Member in Placental and Mammary
Tissues
Eakin, Guy S.; Jun. 2003; 39 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-00-1-0311
Report No.(s): AD-A425574; No Copyright; Avail: CASI; A03, Hardcopy
Primate and mouse display marked morphological differences upon their entrance to gastrulation. The most overt of these
are topological dissimilarities of the gross embryos. While primate embryos develop as a planar epiblast within a spheroidal
cytotrophoblastic shell, mouse epiblast develops in a cup shape, surrounded principally by a cylindrical endoderm shell. At
this stage, the bulk of the murine trophoblast is limited to the mesometrial pole of the cylinder, rather than encapsulated by
the cytotrophoblast as in the primate embryo. Additionally, the appearance of the primate mesoderm is precocious with respect
to that of the mouse. Primate extraembryonic mesoderm is evident in sectioned tissues prior to the established of a primitive
streak or node. In the mouse, such mesoderm appears only after establishment of these structures. We are developing a new
model of non- human primate biology using interspecific chimeras produced within tetraploid mouse blastocysts. By using
tetraploid blastocysts in...
DTIC
Mammary Glands; Rodents; Tissues (Biology)
20040111547 Pennsylvania Univ., Philadelphia, PA
Mechanism of Regression of c-MYC-Induced Mammary Tumors in a Conditional Transgenic Model
Moody, Susan E.; Jul. 2003; 23 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0401
Report No.(s): AD-A425575; No Copyright; Avail: CASI; A03, Hardcopy
The pathways stimulated by the oncogenes HER2/Neu/ErbB2, Wnt-l, and H-ras are aberrantly activated in many human
cancers, including breast cancer, and have been shown to play a role in carcinogenesis. In order to better investigate the role
these genes play in breast cancer, we generated mouse models that inducibly express activated forms of these oncogenes in
the mammary gland. This system allows us to activate these oncogenic pathways during specific windows of mammary gland
development, as well as to remove the initiating oncogenic stimulus after the development of a tumor or during later stages
of tumor progression. As such, we anticipate that the study of these models will provide valuable insights into the mechanisms
by which activation of these pathways contributes to breast cancer development or progression, and will ultimately aid in the
generation of therapeutic strategies that specifically target these pathways. We have found that expression of Neu in the
mammary glands of transgenic mice results in the development of both invasive adenocarcinomas and pulmonary metastases
that remain dependent upon Neu expression for maintenance of the transformed state. We have also determined that both Wnt-l
and c-Myc synergize with Neu in mammary tumorigenesis.
DTIC
Cancer; Genes; Mammary Glands; Tumors
20040111551 Duke Univ., Durham, NC
Nitric Oxide and CNS O2 Toxicity Biochemical Modeling and Risk Prediction
Piantadosi, Claude A.; Allen, B. W.; Demchenko, I. T.; Jan. 2004; 5 pp.; In English
Contract(s)/Grant(s): N00014-01-1-0240
Report No.(s): AD-A425587; No Copyright; Avail: CASI; A01, Hardcopy
The objective of this project was to elucidate the biological mechanisms and specific pathways that implicate the gaseous
signaling molecule nitric oxide (NO) as a critical factor in producing the convulsions of central nervous system (CNS) oxygen
(O2) toxicity, and to obtain data that could be the basis for mathematical risk predictions of O2 convulsions. For the past 3
years, data obtained in this project have supported the hypothesis that NO contributes to CNS O2 toxicity through several
mechanisms: (1) by increasing the availability of NO in the brain, which in turn eliminates cerebral vasoconstriction, leading
to hyperemia and the delivery of a toxic dose of oxygen; (2) by stimulating NO production and O2 generation, both of which
are implicated in the formation of ONOO, a potent neurotoxic agent; and (3) by altering the excitatory/inhibitory balance in
vulnerable brain regions during the early stage of extreme hyperoxia, prior to the appearance of O2 seizures. In rats protected
with the inhibitor of NO production (L-NAME), no significant changes were observed in the excitotoxic index. A bibliography
of 9 papers and 5 abstracts is included.
DTIC
Biochemistry; Central Nervous System; Convulsions; Hyperoxia; Nitric Oxide; Oxygen; Risk; Toxicity; Vasodilation
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