NASA Scientific and Technical Aerospace Reports

20040111561 McMaster Univ., Hamilton, Ontario
A Research Program of Weight and Body Composition Management for Women with Breast Cancer
Ingram, Caroyln; May 2004; 17 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0301
Report No.(s): AD-A425604; No Copyright; Avail: CASI; A03, Hardcopy
The objectives of this award are to establish a viable -program of research focusing on weight and body composition
management in breast cancer, and to lay the groundwork for a feasibility study of a home-based exercise intervention for
weight and body composition management. The specific aims of the award are: 1) to develop a systematic literature review
of studies on exercise and breast cancer that include the outcomes of weight and/or body composition, 2) to examine the
relationships between physical activity and body composition changes during adjuvant chemotherapy, and the changes in
proportions of body water and lean tissue underlying changes in body composition that were suggested in the Pi’s dissertation
research, 3) to acquire skills in designing and applying tailored exercise programs, measuring fitness and weight-related
outcomes, managing clinical trials research, and designing exercise intervention trials, and 5) to develop multidisciplinary
teambuilding and grantsmanship capabilities. All tasks outlined in the Statement of Work have been addressed and all are
completed or nearing completion. One manuscript has been accepted for publication thus far, and a systematic literature review
has been carried out. The major differences for the original submission are in-the timeline first proposed.
DTIC
Cancer; Exercise Physiology; Females; Human Body; Mammary Glands
20040111562 Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec
Investigating the Role of Celecoxib as a Chemopreventive and Chemotherapeutic Agent for Breast Cancer
Levitt, Randy; May 2004; 24 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0322
Report No.(s): AD-A425607; No Copyright; Avail: CASI; A03, Hardcopy
Experimental and epidemiological studies have suggested a role for the use of cyclooxygenase(COX)-2 inhibitors in the.
prevention of breast cancer. The relative lack of toxicity associated with these compounds favors their use as chemopreventive
agents, but the underlying mechanism of their chemopreventive effect remains unclear. We have observed that the COX-2
inhibitor celecoxib inhibits growth and induces apoptosis in the immortalized breast epithelial cell line 184htert. Microarray
gene expression analysis of 1 184htert cells treated with 50 micronmeter celecoxib revealed the modulation of several genes
of interest, including a significant induction of expression of the mRNA encoding insulin-like growth factor binding protein-3
(IGFBP-3). IGFBP- 3 is a potent pro-apoptotic protein and growth inhibitor of breast cancer cells, which acts mainly by
inhibiting the access of the mitogens IGF-I and IGF-II to their cell surface receptor, but also via IGF-independent effects.
Quantitative real-time RT PCR -demonstrated that 50 micronmeter celecoxib induced a ^3 fold increase in expression of
IGFBP-3 mRNA. Furthermore, ligand blot analysis revealed that celecoxib treatment was associated with the upregulation of
IGFBP-3 at the protein level. IGFBP-3 treatment of 184htert cells inhibited IGF-I and serum-induced proliferation, but had
no effect on cell growth under serum-free conditions, indicating that IGF-independent effects of IGFBP-3 are not observed in
this system. Our results suggest that celecoxib may decrease IGF-I associated breast cancer risk by a mechanism involving
induction of expression of IGFBP-3 and subsequent reduced proliferation of at-risk breast epithelial cells.
DTIC
Cancer; Cells (Biology); Chemotherapy; Drugs; Health; Mammary Glands; Toxicity
20040111565 Long Island Jewish Medical Center, New Hyde Park, NY
Omega-3 Fatty Acids and a Novel Mammary Derived Growth Inhibitor Fatty Acid Binding Protein MRG in
Suppression of Mammary Tumor
Liu, Yiliang E.; Jul. 2003; 11 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0309
Report No.(s): AD-A425613; No Copyright; Avail: CASI; A03, Hardcopy
A mammary derived growth inhibitor related gene (MRG) was previously identified and characterized. The present study
is to test the hypothesis that MRG is a candidate mediator of the differentiating effect of pregnancy and lactation of breast
epithelial cells and a candidate mediator of the tumor suppressing effect of n-3 fatty acid DHA on mammary tumors. MRG
induces differentiation of mammary epithelial cells in vitro and its expression is associated with mammary differentiation.
Overexpression of MRG in human breast cancer cells induced differentiation with changes in cellular morphology and a
significant increase in the production of lipid droplets. Treatment of mouse mammary gland in organ culture with MRG protein
resulted in a differentiated morphology and stimulation of beta-casein expression. While there was no lobulo-alveolar structure
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