Tumour Cannabinoid CB1 Receptor and Phosphorylated Epidermal Growth Factor Receptor Expression Are Additive Prognostic Markers for Prostate Cancer

BACKGROUND: In cultured prostate cancer cells, down-regulation of epidermal growth factor receptor (EGFR) has been implicated in mediating the antiproliferative effect of the endogenous cannabinoid (CB) ligand anandamide. Using a well-characterised cohort of prostate cancer patients, we have previously reported that expression levels of phosphorylated EGFR (pEGFR-IR) and CB(1) receptor (CB(1)IR) in tumour tissue at diagnosis are markers of disease-specific survival, but it is not known whether the two markers interact in terms of their influence on disease severity at diagnosis and disease outcome. METHODOLOGY/PRINCIPAL FINDINGS: Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for voiding difficulties was used. Scores for both tumour CB(1)IR and pEGFR-IR were available in the database. Of these, 235 had been followed by expectancy until the appearance of metastases. For patients scored for both parameters, Cox proportional-hazards regression analyses using optimal cut-off scores indicated that the two measures provided additional diagnostic information not only to each other, but to that provided by the tumour stage and the Gleason score. When the cases were divided into subgroups on the basis of these cut-off scores, the patients with both CB(1)IR and pEGFR-IR scores above their cut-off had a poorer disease-specific survival and showed a more severe pathology at diagnosis than patients with high pEGFR-IR scores but with CB(1)IR scores below the cut-off. CONCLUSIONS/SIGNIFICANCE: These data indicate that a high tumour CB(1) receptor expression at diagnosis augments the deleterious effects of a high pEGFR expression upon disease-specific survival

Holocene Cyclic Records of Ice-Rafted Debris and Sea Ice Variations on the East Greenland and Northwest Iceland Margins

The dynamics of the Greenland Ice Sheet and drift of sea ice from the Arctic Ocean reaching Denmark Strait are poorly constrained. We present data on the provenance of Fe oxide detrital grains from two cores in the Denmark Strait area and compare the Fe grain source data with other environmental proxies in order to document the variations and potential periodicities in ice-rafted debris delivery during the Holocene. Based on their Fe grain geochemistry, the sediments can be traced to East Greenland sources and to more distal sites around the Arctic Basin. On the Holocene time scales of the two cores, sea ice biomarker (IP25) data, and quartz weight percent reveal positive associations with T°C and inverse associations with biogenic carbonate wt%. Trends in the data were obtained from Singular Spectrum Analysis (SSA), and residuals were tested for cyclicity. Trends on the environmental proxies explained between 15 and 90% of the variance. At both sites the primary Fe grain sources were from Greenland, but significant contributions were also noted from Banks Island and Svalbard. There is a prominent cyclicity of 800 yrs as well as other less prominent cycles for both Greenland and arctic sources. The Fe grain sources from Greenland and the circum-Arctic Ocean are in synchronization, suggesting that the forcings for these cycles are regional and not local ice sheet instabilities