These data showed that an ARB had potential biological effects on prostate cancer, suggesting the usefulness of the cytostatic activity of such agents on recurrent prostate cancer.

The present data suggest that prostatic RAS is overexpressed in HRPC tissue, and expression of its components is influenced by several kinds of hormonal stimulation.

Introduction. Gemcitabine and cisplatin (GC) is a gold-standard first-line systemic chemotherapy for advanced urothelial carcinoma (UC). However, it may cause severe adverse effects such as renal toxicity, gastrointestinal toxicity, and neurotoxicity. Sarcopenia is the age-related loss of skeletal muscle mass. A correlation between sarcopenia and the oncological prognosis has been reported. In UC, several studies have noted that patients with sarcopenia had a greater incidence of complications and worse survival after radical cystectomy or chemotherapy. Our institute introduced gemcitabine and nedaplatin (GN) for UC patients with renal failure. We investigated whether the presence of sarcopenia predicted the prognosis of patients with advanced UC who were treated by GN chemotherapy. Methods. A total of 27 patients (male, n = 21; female, n = 6) received GN therapy for metastatic UC from 2005 to 2016. The institutional review board of Yokohama City University Hospital approved this study. The psoas muscle index (PMI, cm2/m2) was calculated using this formula: right psoas muscle area (cm2)/the square of the body height (m2). The overall survival (OS) of the high PMI group (male: ≥2.49, female: ≥2.07) and low PMI group (male: <2.49, female: <2.07) was compared. Results. Kaplan-Meier survival curves and a log-rank test revealed that the high PMI group had significantly better OS than the low PMI group (p = 0.015). The mean survival of the high and low PMI groups was 561 days and 223 days, respectively. Conclusions. In the present study, we revealed that sarcopenia (a low psoas muscle volume) might be a predictive factor for poorer overall survival in patients with advanced urothelial carcinoma who are undergoing GN chemotherapy.

BackgroundBladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression.MethodsWe examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively.ResultsThere were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001).ConclusionsPD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.Electronic supplementary materialThe online version of this article (10.1186/s12894-018-0414-8) contains supplementary material, which is available to authorized users.

BackgroundThe bone scan index (BSI), which is obtained using a computer-aided bone scan evaluation system, is anticipated to become an objective and quantitative clinical tool for evaluating bone metastases in prostate cancer. Here, we assessed the usefulness of the BSI as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated using docetaxel.MethodsWe analyzed 41 patients who received docetaxel for mCRPC. The Bonenavi system was used as the calculation program for the BSI. The utility of the BSI as a predictor of overall survival (OS) after docetaxel was evaluated. The Cox proportional hazards model was used to investigate the association between clinical variables obtained at docetaxel treatment, namely PSA, patient age, liver metastasis, local therapy, hemoglobin (Hb), lactase dehydrogenase (LDH), albumin (Alb), PSA doubling time, and BSI and OS.ResultsThe median OS after docetaxel therapy was 17.7 months. Death occurred in 22 (53.7 %) patients; all deaths were caused by prostate cancer. In multivariate analysis, three factors were identified as significant independent prognostic biomarkers for OS after docetaxel; these were liver metastases (yes vs no; HR, 3.681; p = 0.026), Alb (<3.9 vs ≥3.9; HR, 3.776; p = 0.020), and BSI (>1 % vs ≤1 %; HR, 3.356; p = 0.037). We evaluated the discriminatory ability of our models including or excluding the BSI by quantifying the c-index. The BSI improved the c-index from 0.758 to 0.769 for OS after docetaxel. CRPC patients with a BSI >1 had a significantly shorter OS than patients with a BSI ≤1 (p = 0.029).ConclusionsThe BSI, liver metastases and Alb were independent prognostic factors for OS after docetaxel. The BSI might be a useful tool for risk stratification of mCRPC patients undergoing docetaxel treatment.

Germline mutations of the VHL gene are responsible for VHL. Approximately 70% of VHL families display small intragenic mutations detectable by sequencing, whereas partial-or whole-gene deletions have been described in the majority of the remaining families. For such large deletions, complex genetic techniques other than sequencing might have to be used. In this study, we describe an RQ-PCR assay with TaqMan fluorescent probes to detect germline VHL deletions. The RQ-PCR primer/ probe sets were designed for the three VHL coding exons as well as for the 5′ ′ ′ ′ promoter and 3′ ′ ′ ′ untranslated regions. The RQ-PCR assay for 30 normal and 10 known VHL deletion control samples demonstrated high sensitivity and specificity. We then screened 29 individuals from 19 classical VHL families (16 type 1, 2 type 2A, and one type 2B) and one PHEO family, as well as four solitary suspected cases, none displaying any sequence changes, for VHL deletions by the RQ-PCR assay. We detected germline deletions in 17 (89%) classical families including 15 type 1, one type 2A, and one type 2B. We also identified two mutation carriers and two non-carriers in our family cohort. The one PHEO family and four solitary cases did not display any deletion patterns. These findings indicated that the TaqMan-based RQ-PCR assay is a simple and potent technique for the rapid, sensitive, and specific investigation of VHL genetic diagnoses that could be used profitably before more complex large-deletion detection techniques. (Cancer Sci 2006; 97: 400-405) V HL (MIM 193300) is an autosomal dominantly inherited disorder characterized by a predisposition to multiple neoplastic lesions, including retinal angiomas, central nervous system hemangioblastomas, pancreatic tumors, clear-cell renal carcinomas, PHEO, endolymphatic sac tumors, epididymal cystadenomas, and cystic lesions in various organs. (1,2) The gene responsible for VHL is located on chromosome 3p25 and was cloned as a VHL tumor suppressor. (3) Subsequently, the detection of germline VHL alterations as well as genotype-phenotype correlation analyses have been carried out extensively in various countries, and genetic testing based on the detection of germline alterations is now widely applied as a standard diagnostic procedure. (4-7) Previous studies demonstrated that approximately 70% of VHL families have relatively small intragenic mutations affecting nucleotides of up to 30 bp; such mutations are detectable by routine PCR-based sequencing of the three VHL coding exons. (4) However, standard sequencing analysis failed to detect germline alteration in the rest of the families. As the majority of these cases have been demonstrated to possess relatively large (Kb-Mb order) deletions involving the partial or whole VHL gene, various molecular genetic techniques other than sequencing, including pulsed-field gel electrophoresis, standard or quantitative Southern blot analysis, long-range or quantitative PCR, and fluorescence in situ hybri-dization, have been applied to identify such large deletions. ...

BackgroundRecently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy.MethodsA total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery.ResultsThe median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p < 0.001). Based on the differences in gender, we analyzed 63 male patients for a further analysis. In male patients, those hospitalized longer showed a significantly smaller PMI than those normally discharged (377 ± 93.1 vs. 425 ± 83.4; p = 0.04). Similarly, male patients with a small PMI (<400) had a significantly worse overall survival (p = 0.02) than those with a large PMI (≥400).ConclusionsThe presence of sarcopenia was found to be associated with significantly longer hospitalization after radical cystectomy in male patients. Furthermore, in men, a PMI <400 may suggest a significantly worse prognosis.

Introduction and Objectives An elevated neutrophil-to-lymphocyte ratio (NLR) has been suggested to be associated with a poor prognosis in several cancers. We evaluated the utility of an elevated NLR as a biomarker to predict the prognosis of metastatic castration-resistant prostate cancer (mCRPC) patients treated with cabazitaxel (CBZ). Methods We analyzed 47 patients who received CBZ chemotherapy for mCRPC in our institutions. The NLR was calculated using the neutrophil and lymphocyte counts before CBZ chemotherapy. We determined the NLR cut-off value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. A multivariate analysis was performed to investigate the association between the NLR and the prognosis. Results The median overall survival (OS) after CBZ was 10.0 months (range: 6.3–13.2). The median OS was shorter in patients with a high NLR (≥3.83) than in those with a low NLR (<3.83) (5.8 versus 13.2 months, p = 0.018). In the multivariate analysis, the NLR, patient age, and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.01, p = 0.030; hazard ratio 3.10, p = 0.029; hazard ratio 12.38, p = 0.001, resp.). Conclusions NLR might be a useful prognostic biomarker in mCRPC patients treated with CBZ.