The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.

Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2. We evaluated the transcript abundance for FOLH1 and SSTR2 genes as well as NE markers across 909 tumors. A significant suppression of FOLH1 in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression of FOLH1 and amplification of SSTR2 expression. Due to the observed FOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation of SSTR2 in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development.

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis (3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radicalscavenging activities against the xanthine/xanthine oxidaseinduced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m-and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthaseNeither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NO-ARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.Endothelium-derived nitric oxide (NO) is a potent vasodilator. NO synthesized by endothelial NO synthase (eNOS) diffuses into the smooth muscle cells and stimulates the soluble guanylate cyclase (sGC), leading to increased cGMP production and smooth muscle relaxation (Moncada and Higgs, 1993). Several findings have suggested that excess superoxide (O 2 . ) produced in vascular cells interacts with NO, induces the abnormality of vascular tonus regulation, and results in the development of hypertension (Rajagopalan et al., 1996;Jung et al., 2004). In addition, Laursen et al. (1997) reported that both the development of hypertension and the altered endothelium-dependent vascular relaxation were improved by the treatment with membrane-targeted forms of superoxide dismutase in angiotensin II-induced hypertensive rats. Thus, it seems likely that the suppression of oxidative stress improves the NO bioavailability and prevents the development of hypertension and end-organ damage (Zhou et al., 2003;Schmieder, 2005). Sesamin ( Fig. 1) is one of the lignans found in high concentration in sesame seeds and oil. We have obtained evidence that dietary sesamin efficiently suppressed the development and maintenance of hypertension in deoxycorticoArticle, publication date, and citation information can be found at

An elevated AST/ALT ratio was significantly associated with worse postoperative survival in patients surgically treated for localized clear-cell RCC. Further prospective studies are needed to understand the prognostic value of preoperative AST/ALT ratio.

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