NASA Scientific and Technical Aerospace Reports

The proposal entitled "Effects of moderate aerobic exercise combined with caloric restriction on circulating
estrogens and IGF-I in premenopausal women will provide important scientific contributions with respect to the primary
prevention of breast cancer in women. Specifically, this study will examine potential mechanisms relating to the role of
physical activity in the reduction of the risk of breast cancer by testing whether moderate aerobic exercise can reduce the levels
of two hormonal biomarkers, circulating estrogens and insulin-like growth factor I (IGF-I). as expected caloric restriction
combined with aerobic exercise training occurring 4 times per week has resulted in increases in aerobic capacity, weight loss
ranging from 2.5-7.5 kg and loss of body fat raging form 3% to 7% over four months. Results for T3, IGF-1, and estrone look
promising, although the number of subjects who have completed the study thus far is too low to test these changes statistically.
Compliance to our dietary and exercise protocols has been excellent, with subjects completed 3.8/4 workouts per week, and
meeting or exceeding their caloric intake goals. In conclusion, we are making good progress toward completion of this study.
DTIC
Aerobes; Circulation; Diets; Estrogens; Exercise Physiology; Females; Menstruation; Physical Exercise
20040073750 AMC Cancer Research Center, Lakewood, CO
Methylselenium and Prostate Cancer Apoptosis
Lu, Junxuan; Feb. 2004; 7 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0007
Report No.(s): AD-A422674; No Copyright; Avail: CASI; A02, Hardcopy
The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the
selective induction of apoptosis signaling and execution of PCa cells by methyl selenium (Se)/selenol. We hypothesized that
methyl selenium inhibits PI3K-AKT survival pathway leading to the activation of caspase-dependent apoptosis execution in
PCa cells. We have so far refined a methylselenol generation system based on methioninase with selenomethionine as substrate
(Wang et al, Mol. Carcinogenesis, 2002) and studied the association of protein kinases and effects of PI3K inhibitors for
apoptosis induction in DU145 cells by methyl Se and selenite (Jiang et al, Mol. Cancer Therapeutics, 2002). We compared
the apoptosis responses of DU145 (androgen independent and mutant p53) and LnCaP (androgen dependent, wild type p53)
PCa cell lines to methyl Se/selenol and to selenite. The LNCaP cells are PTEN mutant and possess high basal AKT activity
and are more resistant to apoptosis induction by methyl Se, but was not cross resistant to cell death induction by selenite
(AACR abstract, 2003). These studies lend additional credence to the role of PI3K-AKT in apoptosis signaling induction by
the methyl Se pool. Furthermore, we have discovered a caspase-dependent apoptosis response induced by selenite in LNCaP
cells, which is distinct from the lack of caspase involvement in DU145 cells after selenite exposure. This led to a hypothesis
that p53 phosphorylation may play a crucial role in mediating apoptosis induced by a genotoxic Se agent through caspasemediated
execution (AACR Abstract, 2003). With the anticipation of fund transferred in 2004, we will initiate studies with
transfections of mutant kinases/proteins to specifically address their roles in signaling pathways for apoptosis induction by
selenium agents.
DTIC
Apoptosis; Cancer; Prostate Gland
20040073752 Pennsylvania State Univ., University Park, PA
Effects of Moderate Aerobic Exercise Combined with Caloric Restriction on Circulating Estrogens and IGF-I in
Premenopausal Women
Williams, Nancy I.; Oct. 2003; 46 pp.; In English
Contract(s)/Grant(s): DAMD17-01-1-0360
Report No.(s): AD-A422676; No Copyright; Avail: CASI; A03, Hardcopy
The proposal entitled "Effects of moderate aerobic exercise combined with caloric restriction on circulating
estrogens and IGF-I in premenopausal women% will provide important scientific contributions with respect to the primary
prevention of breast cancer in women. Specifically, this study will examine potential mechanisms relating to the role of
physical activity in the reduction of the risk of breast cancer by testing whether moderate aerobic exercise can reduce the levels
of two hormonal biomarkers, circulating estrogens and insulin-like growth factor I (IGF-I). as expected caloric restriction
combined with aerobic exercise training occurring 4 times per week has resulted in increases in aerobic capacity, weight loss
ranging from 2.5-7.5 kg and loss of body fat raging form 3% to 7% over four months. Results for T3, IGF-1, and estrone look
promising, although the number of subjects who have completed the study thus far is too low to test these changes statistically.
Compliance to our dietary and exercise protocols has been excellent, with subjects completed 3.8/4 workouts per week, and
171