Delayed graft function is correlated with graft loss in recipients of expanded-criteria rather than standard-criteria donor kidneys: a retrospective, multicenter, observation cohort study.

BACKGROUND: Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival. METHODS: We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss. RESULTS: Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P = 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305-7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio = 0.359; 95% CI = 0.197-0.652; P = 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130-0.728; P = 0.007) with ECD kidneys. CONCLUSION: DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys.

Molecular characterization of the major histocompatibility complex class Ia gene in the black-spotted frog, Pelophylax nigromaculata.

The genes of the major histocompatibility complex (MHC) are attractive candidates for investigating the link between adaptive variation and individual fitness. We improved rapid amplification of cDNA ends to obtain the whole coding sequence of the MHC class Ia gene of the black-spotted frog (Pelophylax nigromaculata), the most common amphibian in China. We also used genome walking to characterize the partial introns adjacent to exon 3 of the MHC Ia gene. Based on the sequences obtained, we designed locus-specific primers to investigate the molecular polymorphisms of this species in southeast China. The MHC class Ia gene showed a high level of genetic diversity, indicating that this species retains a relatively high potential for survival, despite a population decline among frog species in general and many other amphibians.

Laparoscopic radical prostatectomy plus extended lymph nodes dissection for cases with non-extra node metastatic prostate cancer: 5-year experience in a single Chinese institution.

OBJECTIVE: To investigate the functional and oncologic outcomes of patients with locally advanced or lymph node metastatic prostate cancer (PCa) treated by laparoscopic radical prostatectomy (LRP) in a single Chinese institution. METHODS: From June 2004 to June 2011, a total of 152 cases including 105 locally advanced PCa and 47 lymph node metastatic PCa who were treated by LRP with extended lymph node dissection (ePLND) were enrolled in this study. Surgical records, urinary continence, complications, and oncologic outcomes were presented. RESULTS: The mean operation time and bleeding were 240 min and 110 ml, respectively. After 12-87 months (median 48 m) of follow-up, 91.4 and 94.7 % of the patients were urinary continence at 6 and 12 m, respectively. Eighty biochemical recurrent diseases were observed. The 3- and 5-year biochemical progression-free survival rates were 59.2 and 47.3 %, respectively. Multivariate analysis showed that Gleason score (HR: 1.66, 95 % CI: 1.05-2.64, P = 0.031), pathological stage (HR: 1.64, 95 % CI: 1.2-2.23, P = 0.002), and surgical margin status (HR: 1.75, 95 % CI: 1.04-2.95, P = 0.035) were independent predictive factors for subsequent biochemical relapse. The 3- and 5-year overall and cancer-specific survival rates were 90.2, 86.0 and 95.8, 92.3 %, respectively. There were no significant differences in biochemical recurrence-free (42.6 vs. 49.5 %, P = 0.491), overall (83.4 vs. 87.3 % P = 0.503), and cancer-specific survival rates (92.3 vs. 94.9 %, P = 0.801) between lymph node-positive and -negative PCa. CONCLUSION: With favorable functional and oncologic outcomes in this cohort of 152 patients, we concluded that LRP plus ePLND is feasible for patients with locally advanced non-extra node metastatic PCa.

ERG rearrangement for predicting subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia and lymph node metastasis.

PURPOSE: We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer. EXPERIMENTAL DESIGN: Samples from 523 patients (361 with early prostate cancer and 162 with HGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n = 59) and the other with an ERG rearrangements rate <1.6% (n = 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n = 56 and node-negative, n = 87). All ERG rearrangement FISH data were validated with ERG immunohistochemistry. RESULTS: A total of 56 (of 59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). There were significant differences in ERG rearrangement rates between lymph node-positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6-89.8] and a specificity at 85.1% (95% CI, 75.8-91.8). ERG protein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH. CONCLUSIONS: The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer.

Detection of TMPRSS2-ETS fusions by a multiprobe fluorescence in situ hybridization assay for the early diagnosis of prostate cancer: a pilot study.

Fusion of the prostate-specific and androgen-regulated transmembrane-serine protease gene (TMPRSS2) with the erythroblast transformation-specific (ETS) family members is the most common genetic alteration in prostate cancer. However, the biological and clinical role of TMPRSS2-ETS fusions in prostate cancer, especially in problematic prostate needle core biopsies, has not been rigorously evaluated. We randomly collected 85 specimens including 50 archival prostate cancer tissue blocks, 15 normal prostate specimens, and 20 benign prostatic hyperplasia specimens for TMPRSS2-ETS fusion analyses. Moreover, the fusion status in an additional 20 patients with initial negative biopsies who progressed to biopsy-positive prostate cancer at subsequent follow-ups was also characterized. Fluorescently labeled probes specific for ERG-related rearrangements involving the TMPRSS2-ERG fusion as well as TMPRSS2-ETV1 and TMPRSS2-ETV4 were used to assess samples for gene rearrangements indicative of malignancy under a design of sequential trial. Rearrangements involving TMPRSS2-ETS fusions were detected in 90.0% of the 50 postoperative prostate cancer samples. The positive rate for the rearrangements in the initial prostate cancer-negative biopsies of 20 patients who eventually progressed to prostate cancer was 60.0% (12/20). Our preliminary study demonstrates that the clinical utility of TMPRSS2-ETS fusion detection as a biomarker and ancillary diagnostic tool for the early diagnosis of prostate cancer is promising, given this approach shows significant high sensitivity and specificity in detection.

Toll-like receptor 9 agonists up-regulates the expression of cyclooxygenase-2 via activation of NF-kappaB in prostate cancer cells.

CpG-oligonucleotides (CpG-ODNs), mimicking bacterial DNA, have recently been shown to stimulate prostate cancer invasion in vitro via Toll-like receptor 9 (TLR9). Since cyclooxygenase 2 (COX-2), frequently overexpressed in multiple tumor types including prostate cancer, is a causal factor for tumor development, invasion and metastasis, an interesting question is raised whether TLR9 regulates COX-2 expression in prostate cancer cells. To address this question, herein we examined COX-2 expression in PC-3 cells stimulated with different doses and time courses of CpG-ODNs. The regulatory role of NF-kappaB in TLR9-mediated COX-2 expression was also investigated. CpG-ODN was found to up-regulate the expression of COX-2 in PC-3 cells in a dose- and time-dependent manner, but have little impact on COX-1 expression. Moreover, CpG-ODN also promoted nuclear translocation and activation of NF-kappaB, which appeared to be required for COX-2 induction by CpG-ODN. Overall, TLR9 up-regulates COX-2 expression in prostate cancer cells, at least partially through the activation of NF-kappaB, which may be implicated in tumor invasion and metastasis.

Profiling protein markers associated with lymph node metastasis in prostate cancer by DIGE-based proteomics analysis.

Current predictive tools and imaging modalities are not accurate enough for preoperative diagnosis of lymph node metastatic prostate cancer (LNM PCa). Proteomic analysis is introduced to screen potential biomarkers for early detection of LNM PCa. In our initial study, protein samples from localized and LNM PCa as well as benign prostatic hyperplasia tissues were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF MS. We identified 58 proteins that were differentially expressed in the LNM PCa group relative to the localized PCa group. Six of these proteins, e-FABP5, MCCC2, PPA2, Ezrin, SLP2, and SM22, are functionally relevant to cancer metastasis. Expression of these proteins was therefore further validated in tissue samples from the original cohort and also from a larger, independent cohort of patients using real time PCR, Western blotting, and immunohistochemistry staining. In addition, the serum levels of e-FABP5 were also examined by ELISA. Relative to localized PCa tissues, LNM PCa tissues had increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22. Patients with LNM PCa had significantly higher levels of serum e-FABP5. This study presents evidence that increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22 are useful diagnostic markers for the existence of LNM PCa.

Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-C and lymph node metastases in human prostate cancer.

BACKGROUND AND AIMS: Recent observations suggest an implication of cyclooxygenase-2 (COX-2) in tumor lymphangiogenesis through an upregulation of vascular endothelial growth factor-C (VEGF-C) expression. However, it is unclear whether COX-2 is also associated with VEGF-C expression, tumor lymphangiogenesis and lymph node metastasis in human prostate cancer. METHODS: COX-2 and VEGF-C expression were examined in tumor tissues from 58 prostate cancer patients using immunohistochemical staining. We also analyzed the association of COX-2 and VEGF-C expression with tumor lymphangiogenesis quantified as lymphatic vessel density (LVD), lymph node metastasis, and patients' biochemical progression-free survival (b-PFS). RESULTS: High expression of either COX-2 or VEGF-C was correlated with tumor lymphangiogenesis and lymph node metastasis, as well as poor b-PFS. Moreover, a strong correlation was found between expression of COX-2 and VEGF-C (r = 0.631, p <0.001). CONCLUSIONS: COX-2 is positively associated with VEGF-C expression, tumor lymphangiogenesis and lymphatic metastasis in prostate cancer. These findings suggest that COX-2 may play a pivotal role in lymphangiogenesis and lymph node metastasis of prostate cancer via the regulation of VEGF-C expression.