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NASA Scientific and Technical Aerospace Reports

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20040111607 Texas Univ., Houston, TX<br />

The Role of Sigma Receptor in Breast Cancer<br />

Pusztai, Lajos; Apr. 2004; 34 pp.; In English; Original contains color illustrations<br />

Contract(s)/Grant(s): DAMD17-02-1-0456<br />

Report No.(s): AD-A425685; No Copyright; Avail: CASI; A03, Hardcopy<br />

We have completed specific tasks #1 <strong>and</strong> #2. Sigma 1 receptor (Sig 1 R) mRNA expression was examined in 109 human<br />

tissue specimens including normal breast, hyperplasia, ductal carcinoma in situ, <strong>and</strong> invasive cancer. We have also screened<br />

breast cancer cell lines for expression of Sig 1 <strong>and</strong> examined the effect of sigma lig<strong>and</strong>s on cell growth <strong>and</strong> sensitivity to<br />

chemotherapy. These findings are presented in the manuscript, Expression of sigma 1 Receptor in Human Breast Cancer.<br />

DTIC<br />

Cancer; Mammary Gl<strong>and</strong>s<br />

20040111608 Harvard Medical School, Boston, MA<br />

Isolation <strong>and</strong> Analysis of Human Kekkon-Like Molecules a Family of Potential Inhibitors of ERbB Receptor Tyrosine<br />

Kinases<br />

Kockel, Lutz R.; Perrimon, Norbert; Apr. 2004; 12 pp.; In English<br />

Contract(s)/Grant(s): DAMD17-02-1-0401<br />

Report No.(s): AD-A425686; No Copyright; Avail: CASI; A03, Hardcopy<br />

Identification <strong>and</strong> characterization of proteins involved in intrinsic negative feedback loops autoregulating the<br />

transforming c-ErbB2/EGF Receptor activity in vivo. Scope: Receptor Tyronsine Kinase (RTK) activation trigger two distinct<br />

signal transduction cascades: Mitogenic Ras dependent NAP Kinase activation <strong>and</strong> P13 Kinase dependent Akt/PKB survival<br />

signaling. To date, the regulatory circuits in the Ras signaling pathway are well described. In contrast, no genes involved in<br />

the feedback regulating of the PI3K - Akt/PKB signaling branch are known so far. To this end, a cell based genome wide screen<br />

employing double str<strong>and</strong>ed RNA interference (dsRNAi) as well as an analysis of Akt mediated transcriptional response using<br />

DNA microarrays covering the whole genome have been initiated. Progress: A cuantitative assay to measure amounts of<br />

phosphorylated (&quot;active&quot;) Akt has been established. The description <strong>and</strong> analysis of regulatory feedback regulation<br />

within the Akt signal transduction pathway using dsRNAi, chemical inhibitors <strong>and</strong> metabolic perturbation ahs been<br />

accomplished. The first genome wide dsRNAi screen for activators of Akt has been completed in replicates. Secondary screens<br />

to retest the results form the high-throughput efforts are developed. The data analysis is ongoing.<br />

DTIC<br />

Inhibitors; Isolation; Molecules; Transcription (Genetics); Tyrosine<br />

20040111609 Massachusetts General Hospital, Boston, MA<br />

Research to Develop Biomedical Applications of Free Electron Laser Technology<br />

Parrish, John A.; Mar. 2004; 27 pp.; In English<br />

Contract(s)/Grant(s): F49620-01-1-0014; Proj-0483<br />

Report No.(s): AD-A425688; AFRL-SR-AR-TR-04-0432; No Copyright; Avail: CASI; A03, Hardcopy<br />

Specific Aim 1: Develop <strong>and</strong> test plaque characterization criteria based on bireftingence. Coronary artenes were obtained<br />

at autopsy <strong>and</strong> imaged with the existing OCT system in our laboratory. The specimens were opened <strong>and</strong> imaged at normal<br />

body temperature (37-C) in saline. To ensure proper registration of OCT images with histolog the image location was marked<br />

with ink viewable on the OCT image <strong>and</strong> in the histology section. Routine histologic processing was performed using H&E,<br />

Elastic <strong>and</strong> Movat’s pentachrome stains. Trichrome was used for fibrous tissue identification. Individual images were oriented<br />

<strong>and</strong> scaled to match histology. In the OCT images, the axial periodicity of the birefringence b<strong>and</strong>ing was measured using<br />

image processing software. A set of 20 correlated OCT <strong>and</strong> histology pairs were used to identify characterization criteria basal<br />

on birefringence. Our results indicated that fibrous plaque provides a strong birefringence as measured by OCT while lipid<br />

rich <strong>and</strong> calcific plaques can be identified by a complete loss of birefringenee.<br />

DTIC<br />

Biomedical Data; Birefringence; Free Electron Lasers; Laser Applications; Medical Science<br />

20040111612 Yale Univ., New Haven, CT<br />

Tissue Microarray Based Investigation of Stat3 Signaling Pathway in Breast Cancer<br />

Dolled-Filhart, Marisa; May 2004; 47 pp.; In English<br />

Contract(s)/Grant(s): DAMD17-03-1-0349<br />

Report No.(s): AD-A425703; No Copyright; Avail: CASI; A03, Hardcopy<br />

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