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Chronic inflammation and dietary fat consumption correlates with an increase in prostate cancer. Our previous studies in the colon have demonstrated that -tocopherol treatment could upregulate the expression of peroxisome proliferator-activated preceptors (PPAR) , a nuclear receptor involved in fatty acid metabolism as well modulation of cell proliferation and differentiation. In this study, we explored the possibility that -tocopherol could induce growth arrest in PC-3 prostate cancer cells through the regulation of fatty acid metabolism. Growth arrest (40%) and PPAR mRNA and protein upregulation was achieved with -tocopherol within 6 h. -Tocopherol-mediated growth arrest was demonstrated to be PPAR dependent using the agonist GW9662 and a PPAR dominant negative vector. -tocopherol was shown not to be a direct PPAR ligand, but rather 15-S-HETE (an endogenous PPAR ligand) was upregulated by -tocopherol treatment. 15-Lipoxygenase-2, a tumor suppressor and the enzyme that converts arachidonic acid to 15-S-HETE, was upregulated at 3 h following -tocopherol treatment. Expression of proteins downstream of the PPAR pathway were examined. Cyclin D1, cyclin D3, bcl-2, and NF B proteins were found to be downregulated following -tocopherol treatment. These data demonstrate that the growth arrest mediated by -tocopherol follows a PPAR - dependent mechanism.

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Background: Esterases are often overexpressed in cancer cells and can have chiral specificities different from that of the corresponding normal tissues. For this reason, ester prodrugs could be a promising approach in chemotherapy. In this study, we focused on the identification and characterization of differentially expressed esterases between non-tumorigenic and tumorigenic prostate epithelial cells.Methods: Cellular lysates from LNCaP, DU 145, and PC3 prostate cancer cell lines, tumorigenic RWPE-2 prostate epithelial cells, and non-tumorigenic RWPE-1 prostate epithelial cells were separated by native polyacrylamide gel electrophoresis (n-PAGE) and the esterase activity bands visualized using α-naphthyl acetate or α-naphthyl-N-acetylalaninate (ANAA) chiral esters and Fast Blue RR salt. The esterases were identified using nanospray LC/MS-MS tandem mass spectrometry and confirmed by Western blotting, native electroblotting, inhibition assays, and activity towards a known specific substrate. The serine protease/esterase oxidized protein hydrolase (OPH) was overexpressed in COS-7 cells to verify our results.Results: The major esterase observed with the ANAA substrates within the n-PAGE activity bands was identified as OPH. OPH (EC 3.4.19.1) is a serine protease/esterase and a member of the prolyl oligopeptidase family. We found that LNCaP lysates contained approximately 40% more OPH compared to RWPE-1 lysates. RWPE-2, DU145 and PC3 cell lysates had similar levels of OPH activity. OPH within all of the cell lysates tested had a chiral preference for the S-isomer of ANAA. LNCaP cells were stained more intensely with ANAA substrates than RWPE-1 cells and COS-7 cells overexpressing OPH were found to have a higher activity towards the ANAA and AcApNA than parent COS-7 cells.Conclusions: These data suggest that prodrug derivatives of ANAA and AcApNA could have potential as chemotherapeutic agents for the treatment of prostate cancer tumors that overexpress OPH.

In this chapter, we examine the feasibility of adapting the Family Check Up (FCU), an evidence-based program to identify and manage behavioral concerns in children ages 4 and 5 years, within a pediatric primary care clinic with an integrated mental health professional. Methods: Caregivers attending their child’s 4 and 5 year-old well child visit were asked to complete a screening tool (Pediatric Symptom Checklist-17; PSC-17) measuring behavioral concerns as part of routine care. Families who screened positively, were referred to the FCU and asked to participate in a study evaluating the intervention. The FCU is a 2-session intervention during which information on home environment and parenting style was collected through tailored questionnaires, videotaped interactions, and a clinical interview. Feasibility was examined using portions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (REAIM) framework from the Dissemination and Implementation Science field. This study presents preliminary data on the domains of Reach and Adoption over the first 5 months of the FCU. Results: The number of families referred who attended at least one session (Reach) was 77.2%. Current data shows that use of the PSC-17 screening instrument (Adoption) is 91.4% for well child checks and 25% for acute visits. Adoption of those referred to the FCU is 84%, indicating most families screening positively for behavioral concerns were successfully referred to the FCU. Conclusion: Initial results suggest Reach and Adoption rates support the feasibility of adapting a behavioral intervention for delivery in the pediatric clinic. Notably, having an existing integrated care delivery model is a critical piece to this early success. Future directions will continue to explore feasibility of the remaining REAIM domains.

Abstract available through the Journal of Investigative Medicine.

Abstract available through the Journal of Investigative Medicine.

Identify the signs and symptoms ofcommon perinatal mood disorders Identify local and national resources tosupport those with perinatal mentalhealth concerns

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