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Recent studies have introduced prosaposin (PSAP) as a pleiotrophic growth factor for prostate cancer (PCa). We have previously reported that PSAP or one of its known active molecular derivatives, saposin C functions as an androgen-agonist and androgen-regulated gene (ARG) for androgen-sensitive (AS) PCa cell lines. Due to the potential significance of androgen receptor (AR)-expressing stroma in PCa, we evaluated a possible bi-directional paracrine regulatory interactions between DHT and PSAP in AR-positive prostate stromal (PrSt) cells. We report that saposin C in a ligand-independent manner increased AR expression, its nuclear content, and tyrosine phosphorylation. DHT treatment of PrSt cells increased PSAP expression. We also demonstrated both serum- and androgen-inducibility of a previously characterized hormone-responsive element (HRE) located in the proximal region of PSAP promoter. In addition, conditioned-media derived from PrSt cells and bone fibroblasts (i.e., MSF) differentially increased PSAP-promoter activity in androgen-independent (AI) PC-3 and AS LNCaP cells. Our data for the first time demonstrate that not only saposin C or PSAP regulates AR expression/activity, but also function as an ARG in PrSt. Ligand-independent activation of AR by PSAP or saposin C in PCa and stromal cells may contribute not only to prostate carcinogenesis at an early stage, but also in AI progression of the disease in an androgen-deprived tumor microenvironment.

Androgen-regulated genes (ARG) are implicated in normal and neoplastic growth of the prostate. Recently, we reported genomic amplification and/or overexpression of a previously known neurotrophic factor, prosaposin, in androgen-independent (AI) or metastatic prostate cancer (PCa) cells and tissues. Prosaposin and/or its known active molecular derivatives (e.g., saposin C) function as a pluripotent growth factor with diverse biological activities that favor malignant phenotypes in PCa cells. In addition, prosaposin or saposin C upregulates androgen receptor (AR) and AR-target genes (i.e., prostate-specific antigen, Probasin) expression and activity in LNCaP cells. Here, we examined prosaposin as an ARG. We report that DHT treatment of LNCaP cells increases prosaposin expression. In addition, we demonstrate androgen-responsiveness of prosaposin promoter and AR occupancy to a hormone-responsive element located in the proximal region of the prosaposin promoter. Our data for the first time identify prosaposin as an ARG. This observation, together with the pleiotropic growth factor activity of prosaposin, might suggest a role for this molecule in AR-dependent progression of prostate cancer at its early or late AI-state. J. Cell. Biochem. 101: 631–641, 2007. © 2006 Wiley-Liss, Inc.

Summary Background : Proton-pump inhibitors are often recommended for continuous use in gastro-oesophageal reflux disease, but this may not be necessary in all patients. Aim : To ascertain the level of evidence for alternative strategies for proton-pump inhibitor treatment in gastro-oesophageal reflux disease. Methods : We searched for observational or interventional studies examining alternatives to continuous proton-pump inhibitor treatment in gastro-oesophageal reflux disease. Results : Non-randomized studies suggest that some patients with gastro-oesophageal reflux disease, including some with erosive oesophagitis, may be adequately maintained on proton-pump inhibitor therapy given less frequently than once daily. However, the results may not be generalizable. Four high quality randomized-controlled trials compared ‘on-demand’ proton-pump inhibitor and placebo treatment in endoscopy-negative reflux disease; all found this effective for most patients. One high quality randomized-controlled trial found intermittent courses of a proton-pump inhibitor or H2-receptor antagonist in erosive oesophagitis or endoscopy-negative reflux disease adequate for almost half of the patients studied. Up to 80% of patients on continuous high-dose proton-pump inhibitor treatment for gastro-oesophageal reflux disease can be ‘stepped down’ to less intensive therapy. Conclusions : On-demand proton-pump inhibitor treatment may be appropriate in endoscopy-negative reflux disease. In gastro-oesophageal reflux disease, patients taking more than once daily or high-dose proton-pump inhibitor treatment, a step down to once daily or standard dose therapy should be attempted.

BACKGROUND Establishment of human prostate cancer cell lines is essential to advance our understanding of complex processes associated with the initiation and progression of the disease. In the present study, we report the establishment of a primary African-American prostate cancer cell line (E006AA) as well as its associated stromal cells (S006AA). METHODS E006AA cell line was established as a spontaneously immortalized cells from a patient with a clinically localized prostate cancer. Extensive characterization of the cells was accomplished using androgen-dependent growth and sensitivity assays, Western analyses, RT-PCR/real-time PCR, cytogenetic analyses, and tumorigenicity in nude mice. RESULTS E006AA cell line shows androgen-dependent growth, expresses PSA and the androgen receptor (AR) with 26 CAG repeats in exon 1 of AR. Cytogenetic analyses revealed a hypertriploid karyotype with additional numerical gains in chromosomes 5, 6, 8, 10, 17, 20, 21 and a marker chromosome of unknown origin as well as structural abnormalities in chromosomes 4, 5, 8, 9, 11–14, 18, and 20. This cell line is not tumorigenic in nude mice. S006AA cell line, isolated from the same tumor specimen, also expresses AR and shows the morphological characteristics of smooth muscle cells of prostatic stroma. CONCLUSIONS These cell lines are the first available primary epithelial and stromal cells derived from an African-American patient with organ-confined prostate cancer and in conjunction with other established cell lines, could provide an in vitro model system to investigate early transforming events in prostate cancer. © 2004 Wiley-Liss, Inc.

This paper utilizes United States Geological Survey (USGS) data to investigate the influence of landscape structure on atmospheric circulations. The procedure to insert this data in the Regional Atmospheric Modeling System (RAMS) is described. Simulations are presented for a monthly simulation of summer weather in the United States, for case studies of cumulonimbus convection along a dryline in the Great Plains of the U.S. and over northern Georgia, and for pollutant dispersal in South Carolina. These results demonstrate the significant role that landscape, including its spatial heterogeneity, has on weather and climate. Environmental policy-makers need to consider this feedback to weather and climate, rather than just assuming the atmosphere is an external factor to such issues as ecosystem management and water resource management. This feedback between the atmosphere and the land surface needs to be considered on all spatial scales from the plot scale to the global scale. This includes studies being per...

Liquid composition-total pressure and liquid composition-liquid density data for the carbon dioxide-ethane system were measured at −31.7°, −17.8°, −3.9°, and 10.0°C (−25°, 0°, 25°, and 50°F ± 0.02°F), from 0 to 80 mole % CO2 at 10°C and 0 to 100% CO2 for the other isotherms. The Benedict-Webb-Rubin equation of state with a modified A0 mixing rule was used to correlate the composition-pressure data, with deviations in predicted pressures of only 0.8% average and 2% maximum. Vapor-liquid equilibrium compositions and component K values y/x were then predicted for this minimum boiling azeotrope system from 10° down to −56.7°C (50° to −70°F).