Paraneoplastic hormones: parathyroid hormone-related protein (PTHrP) and erythropoietin (EPO) are related to vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma.

To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3% and 2.0% respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P < 0.0001 respectively). PTHrP was not related to tumour grade. Expressions of EPO and VEGF were correlated to tumour grade significantly. All factors were expressed higher in hypercalcaemic patients. PTHrP, EPO, and VEGF were positively correlated with each other in non-hypercalcaemic patients yet not in hypercalcaemic ones. PTHrP and EPO are related to VEGF expression and to the progression of ccRCC. This finding offers us new insight on the behaviour of ccRCC and offers possible targets in RCC treatment.

Diabetes mellitus reduces prostate cancer risk - no function of age at diagnosis or duration of disease.

BACKGROUND: Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature. METHODS: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to November, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0. Dose-response regression was conducted with SPSS 19.0. RESULTS: We included 29 studies in the meta-analysis (13 case-control studies, 16 cohort studies), and found an inverse association between DM and prostate cancer (relative risk (RR) 0.84, 95% confidence interval (CI), 0.78-0.91). An inverse association was also observed in non-Asian populations (RR 0.81, 95% CI 0.76-0.87) and population-based studies (RR 0.80, 95% CI 0.77-0.91). No statistical significance was found of the association between prostate cancer risk and the duration of DM (p=0.338), and risk seemed not related with the age of DM diagnosis. CONCLUSIONS: This study suggested an inverse relationship between DM and prostate cancer, but without links to duration of disease or age of diagnosis.

The association between overall survival of prostate cancer patients and hypertension, hyperglycemia, and overweight in Southern China: a prospective cohort study.

PURPOSE: Hypertension, hyperglycemia, and overweight are considered associated with the development and prognosis of prostate cancer (PCa). This study is aimed at investigating the association between pre-existing hypertension, hyperglycemia, and overweight and the overall survival (OS) of PCa patients receiving androgen deprivation therapy (ADT). METHODS: We studied the clinical data of 323 patients of PCa receiving ADT in our hospital from January 2003 to August 2012 aged 50-91. The association between OS and hypertension, hyperglycemia, or overweight, both separately and together, was analyzed via Kaplan-Meier method. The distributions of clinicopathological features among groups were evaluated using Fisher's exact or chi-square test. RESULTS: 23 men (7.12 %) were lost to follow-up during this study. During a median follow-up for 43 months (range 3-119 months), 122 deaths (40.67 %) were confirmed. The five-year OS rate of men with both hypertension and overweight (28.57 %) was significantly lower than that of control group (48.33 %, P = 0.024). It was also moderately lower than that of men just with hypertension (50.00 %, P = 0.095) or overweight (55.56 %, P = 0.088). Men with both hyperglycemia and overweight had significantly shorter survival time than control group (P = 0.037). The distributions of clinical information were similar among all the groups except that overweight patients had a lower proportion of PSA level over 20 ng/mL (65.38 %) than control group (84.95 %, P = 0.026). CONCLUSIONS: Pre-existing hypertension, hyperglycemia, and overweight were associated with poor prognosis of PCa patients. Men with both hypertension and overweight, or with both hyperglycemia and overweight had significantly shorter survival time.

Diabetes mellitus and prostate cancer risk of different grade or stage: a systematic review and meta-analysis.

AIM: Prior studies have reported that diabetes mellitus might reduce the overall prostate cancer risk. We examined this association by conducting a detailed meta-analysis of the studies published in peer-reviewed literature on the association between diabetes mellitus and prostate cancer risk of different stage or grade. METHODS: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to October 23, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scale. Meta-analysis was performed using STATA 12.0. RESULTS: We included 9 studies in the meta-analysis (5 studies examining the relation of different stage only, 2 studies for grade only, and 2 studies for both grade and stage), and found an inverse association between diabetes mellitus and prostate cancer of different stage or grade. The relative risk (RRs) was moderately stronger for low grade (RR 0.74, 95% confidence interval (CI), 0.64-0.86) and localized disease (RR 0.72, 95% CI 0.67-0.76) compared with high grade (RR 0.78, 95% CI 0.67-0.90) and advanced disease (RR 0.85, 95% CI 0.75-0.97). CONCLUSION: This study suggests an inverse relationship between diabetes mellitus and prostate cancer of different stage or grade. Possible biases underlying this association are discussed.

Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2.

Bladder cancer (BCa) remained a major health problem. Med19 was related to tumor growth of BCa. Bone morphogenetic proteins (BMPs) were reported to be critical in bone metastasis of cancer. We therefore investigated the relations between Med19 and BMPs in BCa and their effect on bone metastasis of BCa. Bladder cancer cell lines were cultured and interfered with Med19 shRNA and control. Expressions of BMP-1, BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-9, and BMP-15 were studied between 2 groups. Fifty-two BCa samples were included for immunohistochemical staining of Med19 and BMP-2. Expressions were scored and studied statistically. Invasiveness was studied with Transwell assay. Silencing or Med19 in BCa cells induced altered expressions of BMPs. Increased expressions of BMP-1, BMP-4, BMP-6, BMP-7, and BMP-15 and decreased expressions of BMP-2, BMP-5, and BMP-9 were noticed, but only BMP-2 reached statistical significance. Expressions of Med19 and BMP-2 were significantly higher in cases with bone metastasis and were positively correlated in cases with bone metastasis and muscle invasion. Med19 is a critical factor involved in the invasiveness and promotion of bone metastasis of BCa, possibly via BMP-2.

Paraneoplastic symptoms: cachexia, polycythemia, and hypercalcemia are, respectively, related to vascular endothelial growth factor (VEGF) expression in renal clear cell carcinoma.

OBJECTIVES: To evaluate whether there is a relation between expression of vascular endothelial growth factor (VEGF) and any of the paraneoplastic syndromes (PNS) in clear cell renal cell carcinoma (ccRCC) patients. MATERIALS AND METHODS: A total of 667 patients with ccRCC and at least one PNS were included. Thorough history taking, physical examinations, and laboratory tests were used to diagnose PNS. Immunohistochemistry was performed for VEGF evaluation. RESULTS: There were 10 different PNS identified in the population. Sixty patients had a single paraneoplastic presentation. In all patients, presence of cachexia (n = 267, P < 0.0001), polycythemia (n = 40, P = 0.0014), and hypercalcemia (n = 48, P = 0.0006) was correlated to VEGF expression. Correlation was neither acquired in Stauffer's syndrome, pyrexia, elevated erythrocyte sedimentation rate (ESR), anemia, thrombocytosis, hypertension, neuromyopathy nor obtained within patients with single PNS. CONCLUSIONS: Relations between PNS and VEGF expression in renal cell carcinoma (RCC) has not been studied yet. The results we gained hereby can help us further understand the mechanistic of PNS in RCC.

Is there an association between advanced stage of renal cell carcinoma and paraneoplastic syndrome?

OBJECTIVE: To investigate any association between renal cell carcinoma (RCC) and paraneoplastic syndromes (PNS). SUBJECTS AND METHODS: The retrospective analysis included 1,028 patients of Chinese Han nationality with resectable RCC and PNS. The PNS included elevated erythrocyte sedimentation rate (ESR), hypertension, cachexia, anemia, pyrexia, abnormal liver function, hypercalcemia, polycythemia, varicocele and neuromyopathy. Staging was categorized as local (T1-2N0M0) and locally advanced (T3-4NxM0). RESULTS: Among patients with at least one PNS, elevated ESR (p = 0.008), cachexia (p = 0.000), varicocele (p = 0.000) and pyrexia (p = 0.021) were related to advanced stage of RCC. Among patients with only one PNS, hypertension (p = 0.012) and hypercalcemia (p = 0.000) were related to advanced stage. The remaining PNS were not associated with tumor stage. CONCLUSION: Pyrexia, elevated ESR, cachexia and varicocele were related to advanced RCC. Hypertension and hypercalcemia occurring as single PNS, although also correlated with advanced stage, require further investigation.

AZF gene expression analysis in peripheral leukocytes and testicular cells from idiopathic infertility.

The aim of this study was to assess the frequency of AZF microdeletions in peripheral leukocytes and testicular cells in Chinese men with idiopathic infertility. Expression in testicular cells was also determined. In this study, we screened 62 idiopathic infertile patients, in whom karyotype, sperm count and hormonal parameters were evaluated. Genomic DNA was extracted from the peripheral leukocytes. Molecular analysis was performed by two multiplex polymerase chain reactions (PCR) using a set of eight sequence tagged sites (STS) from 3 different regions of the Y chromosome. Total cellular RNA was extracted from the testicular tissue using a Trizol-method. Reverse Transcription (RT) reactions were performed to synthesize cDNA. Amplification of DFFRY, RBM and DAZ genes was performed to analyze their expression in testicular cells. In this cohort, we found 12 submicroscopic deletions (12/62, 19.4%). Nine patients (9/33, 27.2%) were detected in the azoospermic group and three (3/29, 10.3%) in the severe oligozoospermic group. RT-PCR analysis from testicular cells gave normal amplifications for SRY and DFFRY mRNA in 62 idiopathic patients; two patients were negative for RBM expression; no RBM and DAZ were detected for a case; 12 patients had no expression in the AZFc region involving the DAZ gene. Of 12 cases, three patients with normal PCR analysis of DAZ gene on genomic DNA showed no RT-PCR amplification for DAZ mRNA. The use of RT-PCR of specific spermatid expressed genes in conjunction with examining microdeletions using peripheral leukocytes is suggested to avoid the transmission of the Y chromosomal microdeletions from a father to a son via testicular sperm aspiration (TESE), intracytoplasmic sperm injection (JCSI).