Abstract. Early detection and treatment are critical in the management of renal cell carcinoma (RCC). However, there is no standard serum biomarker to facilitate early diagnosis or prognostic stratification in patients with RCC. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for diagnosis and prognosis in patients with several types of cancers. Further, many studies using miRNA microarray analysis demonstrated that miR-210 expression in clear cell carcinoma (CCC), which is the largest subtype of RCC, was significantly upregulated in tumor tissue. Therefore, we investigated whether serum miR-210 could be a useful biomarker for the diagnosis and progression of CCC. This study included 34 CCC patients and 23 healthy controls (HC). First, we analyzed tissue miR-210 levels in tumor tissues and matched normal tissues from the 34 CCC patients. Second, we investigated the serum miR-210 levels in the 34 CCC patients and the 23 HC patients. Real-time polymerase chain reaction (PCR) was used to measure miRNA levels. Moreover, we examined the correlation between serum miR-210 levels and the clinicopathological parameters. Among patients with CCC, expression of miR-210 was higher in tumor tissues compared to normal tissues (P<0.001). Serum miR-210 levels were higher in CCC patients compared to HCs (P=0.001). Receiver operating characteristic (ROC) curve analysis showed an area under the ROC curve (AUC) of 0.77 (95% confidence interval, 0.65-0.89) and a sensitivity and specificity of 65 and 83%, respectively. In addition, there was no significant association between serum miR-210 levels and age, sex, tumor size or existence of metastasis at diagnosis among the 34 CCC patients. In conclusion, serum miR-210 upregulation may occur in the early stage of CCC and serum miR-210 can be a useful biomarker for early CCC in humans.

In the light of increasing evidence that benign prostatic hyperplasia is associated with cardiovascular disease, we have investigated the relationship between prostatic blood flow and prostatic hyperplasia in the spontaneously-hypertensive-rat (SHR). Twelve-week-old male SHRs were treated with nicorandil for six weeks. Wistar-Kyoto rats were used as controls. Six weeks after nicorandil treatment, blood pressure and the prostatic blood flow were estimated, and tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, dihydrotestosterone, and α-SMA were measured. SHRs showed significant increases in blood pressure, tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, α-SMA and a significant decrease in the prostatic blood flow. Although treatment with nicorandil failed to alter the blood-pressure and α-SMA, it significantly ameliorated the increased levels of malondialdehyde, HIF-1α, TGF-β1, and bFGF. There were no significant differences in tissue levels of dihydrotestosterone among any groups. These data indicate that development of prostatic hyperplasia may be associated with prostatic hypoxia, which nicorandil prevents via its effect to increase the blood flow.

These miRNAs may contribute to sunitinib resistance in humans.

Abbreviations & Acronyms ASA = American Society of Anesthesiologists BCa = bladder cancer BMI = body mass index CCI = Charlson Comorbidity Index CI = confidential interval CRP = C-reactive protein DSS = disease-specific survival ECOG = Eastern Cooperative Oncology Group eGFR = estimated glomerular filtration rate HB = hemoglobin HR = hazard ratio LDH = lactate dehydrogenase LNM = lymph node metastasis LVI = lympho-vascular invasion NA = not available PS = performance status PSM = positive surgical margin RC = radical cystectomy SD = standard deviation Objectives: The present study investigated prognostic indicators, including clinicopathological and preoperative hematological factors, and developed a prognostic factorbased risk stratification model in bladder cancer patients treated with radical cystectomy. Methods: Data were collected from 249 consecutive bladder cancer patients treated with radical cystectomy without neoadjuvant therapy. Prognostic values of the preoperative hematological parameters, along with the patients' clinicopathological parameters were evaluated. A risk stratification model was developed to predict disease-specific survival after radical cystectomy using the regression coefficients of multivariate analysis. Results: In the multivariate analysis, preoperative hemoglobin and C-reactive protein levels, as well as the pathological factors of T stage, positive surgical margin and lymph node metastasis, were independently predictive of disease-specific survival. Low hemoglobin (<10.5 g/dL), a high C-reactive protein (>0.5 mg/dL), extravesical T stage (≥pT3a) and positive surgical margin were independent predictors of poor disease-specific survival. The risk stratification model showed significant differences in disease-specific survival between the three subgroups. Conclusions: This is the first report to show the significance of combining preoperative hemoglobin with the pathology of radical cystectomy specimens as an independent predictor for disease-specific survival, and it also represents the largest contemporary series to date demonstrating that two types of preoperative hematological disorders, assessed by hemoglobin and C-reactive protein, are independent predictors in bladder cancer patients treated with radical cystectomy. Our risk stratification model could provide physicians with useful prognostic information for identifying patients who might be candidates for multimodal treatments.

Objective: To evaluate the prognostic significance of the neutrophil-to-lymphocyte ratio in patients receiving chemotherapy with docetaxel for castration-resistant prostate cancer. Methods: A total of 57 castration-resistant prostate cancer patients treated between 2009 and 2014 were included in the present retrospective study. All patient data, including clinicopathological factors, were assessed. Univariate and multivariate Cox regression models were used to predict overall survival and progression-free survival after chemotherapy initiation. Results: The median overall survival and progression-free survival were determined as 19.0 months (range 1-61 months) and 10.0 months (range 1-56 months), respectively. The cut-off level of the neutrophil-to-lymphocyte ratio was set as the median value of 3.5 among all patients in this study. In Kaplan-Meier analysis, the median overall survival and progression-free survival were shorter in patients with a high neutrophil-to-lymphocyte ratio compared with those with a low neutrophil-to-lymphocyte ratio (15 vs 20 months, P = 0.0125; and 9.5 vs 15 months, P = 0.0132, respectively). The overall survival and progression-free survival periods in patients with a high neutrophil-to-lymphocyte ratio were significantly shorter than those of patients with a low neutrophil-to-lymphocyte ratio (P = 0.0178 and 0.0176, respectively). In the multivariate analysis, a high neutrophilto-lymphocyte ratio was an independent predictor of overall survival and progressionfree survival (hazard ratio 2.728, 95% confidence interval 1.05-7.09, P = 0.039; and hazard ratio 2.376, 95% confidence interval 1.12-5.06, P = 0.024, respectively). Conclusion: The present study results suggest that the neutrophil-to-lymphocyte ratio is a useful prognostic factor in patients with castration-resistant prostate cancer treated by docetaxel chemotherapy. These findings might be useful in determining treatment strategies in the future.