Physical and functional mapping of a novel tumor suppressor locus for prostate cancer within chromosome 10p12.31-q11

Prostate cancer remains the second leading cause of male cancer deaths in the United States, yet the molecular mechanisms underlying this disease remain largely unknown. Cytogenetic and molecular analyses of prostate tumors suggest a consistent association with the loss of chromosome 10. Previously, we have defined a novel tumor suppressor locus PAC-1 within chromosome 10pter-q11. Introduction of the short arm of chromosome 10 into a prostatic adenocarcinoma cell line PC-3H resulted in dramatic tumor suppression and restoration of a programmed cell death pathway. Using a combined approach of comparative genomic hybridization and microsatellite analysis of PC-3H, I have identified a region of hemizygosity within 10p12-p15. This region has been shown to be involved in frequent loss of heterozygosity in gliomas and melanoma. To functionally dissect the region within chromosome 10p containing PAC-1, we developed a strategy of serial microcell fusion, a technique that allows the transfer of defined fragments of chromosome 10p into PC-3H. Serial microcell fusion was used to transfer defined 10p fragments into a mouse A9 fibrosarcoma cell line. Once characterized by FISH and microsatellite analyses, the 10p fragments were subsequently transferred into PC-3H to generate a panel of microcell hybrid clones containing overlapping deletions of chromosome 10p. In vivo and microsatellite analyses of these PC hybrids identified a small chromosome 10p fragment (an estimated 31 Mb in size inclusive of the centromere) that when transferred into the PC-3H background, resulted in significant tumor suppression and limited a region of functional tumor suppressor activity to chromosome 10p12.31-q11. This region coincides with a region of LOH demonstrated in prostate cancer. These studies demonstrate the utility of this approach as a powerful tool to limit regions of functional tumor suppressor activity. Furthermore, these data used in conjunction with data generated by the Human Genome Project lent a focused approach to identify candidate tumor suppressor genes involved in prostate cancer. ^

Dietary intake patterns and relationships to polybrominated diphenyl ether (PBDE) and phthalate body burden

Polybrominated diphenyl ethers (PBDEs) and phthalates are chemicals of concern because of high levels measured in people and the environment as well as the demonstrated toxicity in animal studies and limited epidemiological studies. Exposure to these chemicals has been associated with a range of toxicological outcomes, including developmental effects, behavioral changes, endocrine disruption, effects on sexual health, and cancer. Previous research has shown that both of these classes of chemicals contaminate food in the United States and worldwide. However, how large a role diet plays in exposure to these chemicals is currently unknown. To address this question, an exploratory analysis of data collected as part of the 2003-04 National Health and Nutrition Examination Survey (NHANES) was conducted. Associations between dietary intake (assessed by 24-hour dietary recalls) for a range of food types (meat, poultry, fish, and dairy) and levels PBDEs and phthalate metabolites were analyzed using multiple linear regression modeling. Levels of individual PBDE congeners 28, 47, 99, 100 as well as total PBDEs were found to be significantly associated with the consumption of poultry. Metabolites of di-(2-ethylhexyl) phthalate (DEHP) were found to be associated with the consumption of poultry, as well as with an increased consumption of fat of animal origin. These results, combined with results from previous studies, suggest that diet is an important route of intake for both PBDEs and phthalates. Further research needs to be conducted to determine the sources of food contamination with these toxic chemicals as well as to describe the levels of contamination of US food in a large, representative sample.^

Food intake in nonpurging obese women who binge eat before and after a behavioral weight loss program

Little is known about the impact of behavioral programs to decrease binge eating in obese persons who do not purge. This study was conducted to compare the amount of change in the reduction of binge days and selected nutrients in women who had joined a behavioral weight loss program. Forty-six women in the behavioral self management (BSM) group and thirty-six women in the Wait List Control (WLC) groups completed seven day food records at baseline and six months. These records were analyzed for calories, percentage of calories from protein, carbohydrate, fat and dietary fiber/ 1000 calories and were marked as "binge" or "nonbinge" days. Foods were also divided into 12 food groups but only six contributing to fat intake were chosen for analysis: dairy; fat; grains and starchy vegetables; meat, fish, and poultry; meat, fish, and poultry combinations; snacks and desserts. At six months, there was no difference in the amount of change in any of the selected nutrients between the BSM and WLC groups or in the amount of change within each food group except in the meat, fish, and poultry combination and in the snacks and desserts groups because both groups experienced similar changes at six months. Binge and nonbinge day nutrient analysis by BSM and WLC showed that at baseline and six months within the BSM group, calories increased significantly on binge days. Within the WLC group at six months, percentage of calories from protein was significantly decreased on binge days.^ The significant finding of this study was the reduction in the amount of change in the number of binge days at six months between the BSM and WLC groups ($-$2.2 versus $-$1.1 respectively). These data suggest that behavioral programs can successful reduce binge days, but that significant change in food intake may require more intensive treatment. ^

The effects of omega -3 fatty acid -enriched fish on C -reactive protein levels in postmenopausal women

Coronary heart disease (CHD) is the leading cause of death in women and rates markedly increase among women after 65 years of age. C-reactive protein (CRP) is a new clinical indicator of atherosclerotic-related inflammation with a direct pathogenic role. Studies show lifestyle factors can modulate CRP. Omega-3 fatty acids have anti-inflammatory properties and studies suggest that eating fish high in omega-3 fatty acids may lower CHD risk in women. This study sought to assess the possible role of omega-3 fatty acids in the reduction of CHD-related inflammation by investigating the effect of fish consumption on CRP levels. Methods. Twenty-four healthy postmenopausal women were randomly assigned to a fish group (usual diet plus two servings per week of enriched fish) or control group (usual diet with no fatty fish) for eight weeks. Omega-3 fatty acid-enriched fish developed by the West Virginia University Aquaculture Division was used. Serum CRP, serum interleukin-6 (IL-6), and the fatty acid content of red blood cells (RBC) were measured before and after the study. Women also completed food records. RESULTS: Baseline levels of CRP were low (85% of the fish group had normal levels) and few changes in CRP risk category were observed. Mean IL-6 levels were reduced by 27% and 35% in the fish and control groups, respectively (p for between-group difference = 0.60). Changes in RBC fatty acid composition were not statistically significant. Compared to control women, women in the fish group had greater reductions in mean triglycerides (p = 0.08), total cholesterol (P = 0.04), and LDL cholesterol levels (p = 0.06). Baseline dietary intake of total and monounsaturated fatty acids tended to be positively associated with baseline CRP, while vitamin E intake was inversely related. Saturated fat intake tended to have a positive association with IL-6. Conclusions. Findings regarding the effect of two servings of fish on CRP and IL-6 levels are inconclusive due to low baseline levels of CRP and IL-6. However, results indicate two servings of fatty fish have favorable effects on blood lipids. The relationship of dietary components with CRP and IL-6 is complex and further research is needed to determine the varying roles of diet on the inflammatory process. ^