Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades.

OBJECTIVES: Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post-transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long-term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors. METHODS: A total of 443 grafts recovered using an in situ regional cooling technique from 1983 to 2011 were assessed. To assess the combined predictive value of the significant expanded criteria donor risk criteria, the patients were divided into three groups: those with no expanded criteria donor risk factors (no risk), one expanded criteria donor risk factor (single-risk) and two or more expanded criteria donor risk factors (multiple-risk). RESULTS: Among the donor factors, age ≥50 years, hypertension, maximum serum creatinine level ≥1.5 mg/dL and a warm ischemia time ≥30 min were identified as independent predictors of long-term graft failure on multivariate analysis. Regarding the expanded criteria donors criteria for marginal donors, cerebrovascular disease, hypertension and maximum serum creatinine level ≥1.5 mg/dL were identified as significant predictors on univariate analysis. The single- and multiple-risk groups showed 2.01- and 2.40-fold higher risks of graft loss, respectively. CONCLUSIONS: Renal grafts recovered from donors after cardiac death donors have a good renal function with an excellent long-term graft survival. However, an increased number of expanded criteria donors risk factors increase the risk of graft loss.

Associations of coronary artery calcification and carotid intima-media thickness with plasma concentrations of vascular calcification inhibitors in type 2 diabetic patients.

Vascular calcification is frequently accompanied by intima-media thickening, but the associations among these atherosclerotic features and bone-related peptides in diabetic patients are unclear. We enrolled 168 type 2 diabetic patients and 40 non-diabetic subjects consecutively admitted to our hospital. Mean intima-media thickness (mean-IMT) in common carotid arteries was measured by B-mode ultrasonography. Agatston coronary artery calcium score (CACS) was obtained using multidetector-row computed tomography (MDCT). Plasma bone-related peptides osteopontin and osteoprotegerin levels were measured. Diabetic patients had higher mean-IMT (p=0.0002) and log(CACS+1) (p<0.0001) and similar bone-related peptides compared to non-diabetic subjects. In diabetic patients classified into tertiles according to their CACS levels, those with the highest scores showed the highest mean-IMT (p=0.0004) and bone-related peptides (p<0.05) among the groups. log(CACS+1) and mean-IMT were associated (p<0.0001) and were positively correlated with osteopontin (p<0.01) and osteoprotegerin (p<0.01) in diabetic patients. Multivariate analyses revealed that the significant independent determinants of log(CACS+1) were age, duration of diabetes and osteopontin (p<0.0001) and those of mean-IMT were age, hypertension, osteopontin and osteoprotegerin (p<0.0001), respectively. We have demonstrated that vascular calcification in type 2 diabetic patients is frequently accompanied by intima-media thickening, and osteopontin may act as a vascular calcification inhibitor by increasing intima-media thickness.

Expression of prothymosin alpha is correlated with development and progression in human prostate cancers.

BACKGROUND: Our previous study clearly demonstrated that decreased expression of prothymosin alpha (PTMA) was associated with inhibition of rat prostate carcinogenesis by isoflavones. The purpose of the present investigation was to provide a better understanding of the role of PTMA in human prostate cancers. METHODS AND RESULTS: PTMA expression in 68 prostate cancer cases and in prostate cancer cell lines was examined by immunohistochemistry and immunoblotting, and its levels were increased with progression from normal epithelium, through prostatic intraepithelial neoplasia (PIN) to carcinomas, correlating with the Gleason's pattern. All cell lines studied (LNCaP, 22Rv1, DU145, and PC3) showed high PTMA expression compared with prostate epithelial cells (PrEC). Knockdown of PTMA expression in PC3 cells by RNAi resulted in the inhibition of both cell growth and invasion in vitro. CONCLUSIONS: The present study clearly demonstrated that PTMA expression is intimately involved in the differentiation and progression of human prostate cancers, and could be a target for therapy and diagnostic purposes.

Down-regulated expression of prostasin in high-grade or hormone-refractory human prostate cancers.

BACKGROUND: We previously conducted a search for genes which are differentially expressed in hormone-refractory prostate cancers using cDNA-representational difference analysis (RDA). The prostasin gene was isolated as one showing down-regulation in hormone-refractory cancers. In the present study, linkage to the stage in prostate neoplasia was examined. METHODS: Prostasin expressions in 54 prostate cancer cases were examined by mRNA in situ hybridization and immunohistochemistry as well as by northern blot analysis. RESULTS: Expression levels of prostasin in hormone-refractory cancers were approximately one-sixth of those in organ-confined cancers by northern blotting. Glandular components in benign prostatic hyperplasia and high-grade prostatic intraepithelial neoplasias tended to exhibit mild to moderate and relatively strong intensities, respectively. Expression levels of both prostasin mRNA and protein were inversely correlated with histological differentiation but not associated with clinical stage of human prostate cancer. Almost all cases of metastatic and hormone-refractory cancers demonstrated down-regulation of prostasin expression. CONCLUSIONS: These results suggest that prostasin cannot be regarded as a prognostic indicator for human prostate cancer although it may be a useful marker for tumor differentiation.

Down-regulation of human X-box binding protein 1 (hXBP-1) expression correlates with tumor progression in human prostate cancers.

BACKGROUND: In our previous study, the gene encoding the human X-box binding protein 1 (hXBP-1) was isolated as a down-regulated gene in advanced prostate cancers using cDNA-representational difference analysis (RDA). In the present investigation, we characterized alterations of hXBP-1 in prostate cancer specimens. METHODS: Expression patterns of hXBP-1 in a series of human prostate cancers were examined by Northern blotting, mRNA in situ hybridization or immunohistochemistry. Loss of heterozygosity (LOH) analysis using microsatellite markers and gene mutation analysis in the hXBP-1 region were also performed. RESULTS: Expression of hXBP-1 was localized in epithelial and adenocarcinoma cells of the prostate. An inverse correlation between hXBP-1 expression and histological differentiation was found in a series of prostate cancers without hormonal therapy. Majority of refractory cancer cases exhibited weak hXBP-1 expression. No allelic loss or gene mutations were found in the hXBP-1 region and its open reading frame, respectively, in the prostate cancer examined. CONCLUSIONS: These results suggest that reduction of hXBP-1 expression may be a useful marker for prostate adenocarcinoma differentiation and progression.