NASA Scientific and Technical Aerospace Reports

Early detection and intervention is key to a favorable prognosis in prostate cancer. Despite advances in the detection and
treatment of prostate cancer, the mortality rate remains high. To improve survival, early detection and treatment strategies
tailored to pre-invasive prostate cancer are required. We propose to catalog genetic alterations associated with the
developmental stages of disease for use as diagnostic tools and to identify the critical genes that drive the transformation of
premalignant lesions to tumors for use as molecular targets for novel treatment design. The combination of laser capture
microdissection (efficient isolation of specific cell types form hundreds of specimens) and SMAL DNA fingerprinting
technology (high-through put analysis of genomic targets using minute quantities of DNA yielded form the microdissected
cells) will facilitate systematic comparison of samples in various stages of disease development. By the end of this work, we
will have identified a set of genetic loci (and genes) by virtues of their frequency of alteration in premalignant lesions and
subsequent in low-grade tumors. We will have established a publicly accessible ‘genetic alterations in prostate cancer database
which catalogs somatic changes present in the various stages of cancer progression. Such information contribute to the
fundamental understanding of prostate cancer pathogenesis.
DTIC
Cancer; Detection; Genome; Identifying; Prostate Gland; Targets
20040111742 Case Western Reserve Univ., Cleveland, OH
Molecular Imaging for IMRI-Guided Minimally Invasive Treatment of Prostate Cancer
Fei, Baowei; Wilson, David L.; Duerk, Jeffrey L.; Sodee, D. B.; Mar. 2004; 175 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0230
Report No.(s): AD-A425929; No Copyright; Avail: CASI; A08, Hardcopy
Our long-range goal is to develop an image-guided, minimally invasive thermal ablation treatment method for the prostate
cancer. Before this method can be achieved, significant engineering developments are required. Since MRI does not reliably
show prostate tumors, we intend to incorporate nuclear medicine images with higher sensitivity for detecting and localizing
prostate tumors. We investigated image registration techniques to incorporate other imaging modalities into interventional
MRI (iMRI)-guided treatment for improved tumor targeting. MR imaging techniques were developed for the prostate that
could possibly be used for prostate cancer diagnosis and treatment. High resolution MRI and SPECT images were combined
and included into interventional MRI- guided procedures such as the applications of thermal ablation treatment for the prostate
cancer. We created three image registration techniques that could be used to combine high resolution MRI and SPECT images
with iMRI images. We demonstrated the feasibility of combining the three modalities for iMRI-guided thermal ablation
treatment. With this research, we create a potential minimally invasive treatment method for prostate cancer that requires no
radiation, surgery, or hospitalization. We achieved the goals of training and research in the two years.
DTIC
Cancer; Image Processing; Imaging Techniques; Magnetic Resonance; Pattern Registration; Prostate Gland
20040111747 Cold Spring Harbor Lab., New York, NY
Determine the Mechanism by which Specific ERbB Receptor Dimers Differ in Their Ability to Disrupt Epithelial Cell
Polarity
Luca, Alexandra V.; Apr. 2004; 7 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0196
Report No.(s): AD-A425954; No Copyright; Avail: CASI; A02, Hardcopy
ErbB2 is overexpressed in approximately 25% of breast cancers. ErbB2 homodimers can cause an increase in cell
proliferation and a disruption of cell polarity, both characteristics of early cancer stages. In order to dissect the role of ErbB2
biochemistry on cell polarity we have constructed two series of mutations in the autophosphorylation sites of chimeric Neu
(rat ErbB2). The chimeric receptor is used in order to create an inducible system of Neu homodimers. In one series 4 of the
5 autophosphorylated tyrosines are active. In the other only one of these tyrosines is active (Y mutants). Preliminary results
suggest that different Y mutations can cause distinct cell polarity disruption phenotypes. More in depth studies of these
phenotypes are planned for the near future, including some preliminary studies to look at possible changes in the three major
polarity complexes - Par, Crumbs and Lgl. In order to investigate the role localization plays in ErbB2’s ability to promote
proliferation and disrupt polarity, we have also constructed a series of mutations that cause mislocalization of chimeric ErbB2.
Preliminary data suggests that ErbB2 cannot phosphorylate from the apical surface, but must be located on the lateral
surface-where wild type ErbB2 normally localizes - or in a non-polarized cell. After more in depth testing of this hypothesis,
we shall attempt to find the factor(s) responsible for the inability of ErbB2 to phosphorylate from the apical surface.
DTIC
Cancer; Cells (Biology); Dimers; Disrupting; Mammary Glands; Polarity
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