Antiobesity and Hepatoprotective Effects of Protein Hydrolysates Derived from Protaetia brevitarsis in an Obese Mouse Model.

Background: Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. Methods: For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(-)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. Results: The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(-) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(-) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, ß3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. Conclusions: Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.

Renal Protective Effect of Beluga Lentil Pretreatment for Ischemia-Reperfusion Injury.

MATERIALS AND METHODS: Mice were divided into four groups: normal, untreated, low- (2 mg), and high-dose (8 mg) beluga lentil treatment groups. Beluga lentil was orally administered for 2 weeks, followed by bilateral renal ischemia for 20 min and reperfusion for 30 min. Blood samples and kidney tissues were collected and analyzed to investigate renal function, histopathology, epithelial and endothelial cell damage, apoptosis, oxidative stress, and inflammatory responses. RESULTS: The pretreated groups maintained renal function, with significantly lower blood urea nitrogen (BUN) and creatinine levels, compared with the other groups. The histopathological analysis showed reduced proximal tubule injury and decreased injury-related molecule (kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) secretion in the pretreated groups compared with the other groups. Terminal deoxynucleotidyl transferase dUTP nick-end labeling- (TUNEL-) positive cells and the secretion of apoptosis-related molecules (Fas and caspase 3) were significantly reduced in the pretreated groups compared with the other groups. The pretreated groups showed positive microvessel-associated gene (cluster of differentiation (CD31)) expression and negative adhesion molecule (intracellular adhesion molecule 1 (ICAM-1)) expression. An antioxidant effect was observed in the pretreatment groups, with reduced malonaldehyde (MDA) expression and increased antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx)) secretion. In the pretreated groups, F4/80+ macrophages and CD4+ T cell infiltration were inhibited and proinflammatory cytokine (interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor- (TNF-) α) levels decreased; however, the levels of anti-inflammatory cytokines (transforming growth factor- (TGF-) ß, IL-10, and IL-22) increased. CONCLUSIONS: Beluga lentil pretreatment demonstrated protective effects against I/R-induced renal damage, via antiapoptotic, anti-inflammatory, and antioxidant activities.

Efficacy of combination therapy with pentosan polysulfate sodium and adipose tissue-derived stem cells for the management of interstitial cystitis in a rat model.

We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation of the IC rat model, the rats were divided into 4 groups according to the treatment they received: phosphate-buffered saline injection into bladder submucosa, daily oral PPS feeding, MSC injection into bladder submucosa, or MSC injection into bladder submucosa with daily oral PPS feeding. After treatment, conscious cystometry and pain scale measurement were performed and their bladders were obtained for histological and proinflammatory-related gene expression analysis. On cystometric analysis, all treatment groups showed significantly increased intercontraction intervals and lower pain scores compared to those of the control group. Histological analysis revealed regenerated urothelium, less fibrosis, and decreased mast cell infiltration in all treatment groups compared to the control group. Significantly lower expression of TNF-α, IFN-γ, MCP, IL-6, TLR2, and TLR11 was observed in the PPS with MSC group compared to the other groups. Combination therapy with PPS and MSCs showed histological and functional effects in an IC rat model, including synergistic effects leading to increased intercontraction interval and decreased inflammatory reactions.

National practice patterns and direct medical costs for prostate cancer in Korea across a 10 year period: a nationwide population-based study using a national health insurance database.

BACKGROUND: A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. METHODS: Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. RESULTS: From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. CONCLUSIONS: Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Medical Travel among Non-Seoul Residents to Seek Prostate Cancer Treatment in Medical Facilities of Seoul.

PURPOSE: This study aims to investigate the trend in medical travel by non-Seoul residents to Seoul for treatment of prostate cancer and also to investigate the possible factors affecting the trend. MATERIALS AND METHODS: This study represents a retrospective cohort study using data from theKoreanNationalHealth Insurance System from 2002 to 2015. Annual trends were produced for proportions of patients who traveled according to the age group, economic status and types of treatment. Multiple logistic analysiswas used to determine factors affecting surgeries at medical facilities in Seoul among the non-Seoul residents. RESULTS: A total of 68,543 patients were defined as newly diagnosed prostate cancer cohorts from 2005 to 2014. The proportion of patients who traveled to Seoul for treatment, estimated from cases with prostate cancer-related claims, decreased slightly over 9 years (28.0 at 2005 and 27.0 at 2014, p=0.02). The average proportion of medical travelers seeking radical prostatectomy increased slightly but the increase was not statistically significant (43.1 at 2005 and 45.4 at 2014, p=0.26). Income level and performance ofrobot-assisted radical prostatectomy were significant positive factors for medical travel to medical facilities in Seoul. Combined comorbidity diseases and year undergoing surgery were significant negative factors for medical travel to medical facilities in Seoul. CONCLUSION: The general trend of patients travelling from outside Seoul for prostate cancer treatment decreased from 2005 to 2014. However, a large proportion of traveling remained irrespective of direct distance from Seoul.

The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M.

Although garlic induces apoptosis in cancer cells, it is unclear whether the effects are similar to those of cisplatin against bladder cancer (BC). Therefore, this study investigated whether garlic extracts and cisplatin show similar activity when used to treat BC. The effect of garlic on T24 BC cell line was examined in a BALB/C-nude mouse xenograft model and compared with that of cisplatin. Tissue microarray analysis and gene network analysis were performed to identify differences in gene expression by control tumors and tumors exposed to garlic extract or cisplatin. Investigation of gene expression based on tissues from 165 BC patients and normal controls was then performed to identify common targets of garlic and cisplatin. Tumor volume and tumor weight in cisplatin (0.05[Formula: see text]mg/kg)- and garlic-treated mice were significantly smaller than those in negative control mice. However, cisplatin-treated mice also showed a significant reduction in body weight. Microarray analysis of tumor tissue identified 515 common anticancer genes in the garlic and cisplatin groups ([Formula: see text]). Gene network analysis of 252 of these genes using the Cytoscape and ClueGo software packages mapped 17 genes and 9 gene ontologies to gene networks. BC (NMIBC and MIBC) patients with low expression of centromere protein M (CENPM) showed significantly better progression-free survival than those with high expression. Garlic extract shows anticancer activity in vivo similar to that of cisplatin, with no evident of side effects. Both appear to act by targeting protein-DNA complex assembly; in particular, expression of CENPM.

Prostate-specific antigen density toward a better cutoff to identify better candidates for active surveillance.

OBJECTIVE: To investigate the impact of prostate-specific antigen density (PSAD) on existing prostate cancer (PCa) active surveillance (AS) protocols. METHODS: Prospectively maintained database on men with PCa who underwent radical prostatectomy was reviewed retrospectively. Demographic data and pathologic characteristics of patients who fulfilled the AS inclusion criteria under the National Comprehensive Cancer Network (NCCN), Prostate Cancer Research International Active Surveillance (PRIAS), and University of California, San Francisco (UCSF) guidelines were examined. RESULTS: Of 930 patients, 231, 280, and 325 fulfilled the NCCN, PRIAS, and UCSF AS criteria, respectively. The frequencies of advanced disease on surgical pathology (upstaging and/or upgrading) were 31.6% (NCCN), 35.4% (PRIAS), and 34.2% (UCSF) of the study cohorts. PSAD was significantly higher in patients with advanced disease compared with that in patients with nonadvanced disease in all 3 AS schemas. Modifying the PRIAS and UCSF criteria using the NCCN's lower PSAD cutoff of 0.15 ng/mL(2) decreased the rates of the advanced disease significantly to 33.5% and 31.4%, respectively. Using the receiver operating characteristic curve analysis, the optimal PSAD cutoff level for the prediction of advanced disease was 0.085 ng/mL(2) (sensitivity/specificity of 76.7%/50.6% in NCCN and 75.6%/49.7% in PRIAS). CONCLUSION: Among patients with low-risk PCa who underwent radical prostatectomy, PSAD is a predictor of advanced disease at the time of surgery. Adopting a lower PSAD threshold of 0.085 ng/mL(2) decreased the risk of the advanced disease to 17.5%-21.7%. Therefore, PSAD should be part of all AS guidelines.

Enzalutamide: looking back at its preclinical discovery.

INTRODUCTION: In patients with metastatic prostate cancer (PCa), castration is the standard first-line therapy. However, all patients eventually develop castration-recurrent PCa (CRPC). In these patients who fail the first-line therapy, enzalutamide has emerged as a viable alternative. Enzalutamide is a second-generation small molecule androgen receptor (AR) antagonist that blocks the AR nuclear translocation and DNA binding without any known AR agonist activity. AREAS COVERED: This review provides an overview of the history of the oral selective AR modulator, enzalutamide, and discusses its discovery and current preclinical experimental results including resistance mechanisms. The article illustrates the history of discovery based on enzalutamide's mechanism of action. Furthermore, the authors highlight the drug's clinical development and post-launch developments. EXPERT OPINION: The landscape of CRPC has changed dramatically over the last few years, as new agents with proven benefit in overall survival have been approved. Compared to the average time of 10 - 15 years for a new drug to go from pre-clinical discovery to registration, enzalutamide obtained FDA approval in < 6 years after its initial characterization. Enzalutamide, a targeted agent of the androgen-AR axis, has shown promising results in CRPC and is generally well tolerated. However, drug resistance inevitably emerges is a severe limitation. The authors believe that further clinical studies that look at its use as either a combinational or sequential therapy could help to address these concerns.

Increased incidence of pathologically nonorgan confined prostate cancer in African-American men eligible for active surveillance.

OBJECTIVE: To compare the clinicopathologic findings of African-American (AA) and White-American (WA) men with prostate cancer (PCa) who were candidates for active surveillance (AS) and underwent radical prostatectomy (RP). METHODS: Prospectively maintained database of men who underwent RP from 2 academic centers were analyzed retrospectively. Postoperative pathologic characteristics of patients who met the AS inclusion criteria of the University of California, San Francisco (UCSF) and National Comprehensive Cancer Network (NCCN) were evaluated. After RP, the rate of pathological upstaging and Gleason upgrading were compared between AA and WA men. RESULTS: In the AA cohort, 196 and 124 men met the UCSF and NCCN criteria for AS, respectively. With respect to WA patients, 191 and 148 fulfilled the AS criteria for UCSF and NCCN, respectively. AA men had a higher percentage of maximum biopsy core than WA men (15.3%-20.4% vs 11.5%-15.0%, P <.05, respectively) in both cohorts. In addition, a greater proportion of AA men had multiple positive biopsy cores compared to WA men (45.2% vs 33.1%, P = .046) under the NCCN criteria. A higher proportion of AA men were upstaged (≥pT3) compared to WA men (19.4% vs 10.1%, P = .037). A multivariate regression test revealed that age, preoperative PSA, and number of positive cores were independent predictors of more advanced disease (upstaging and/or upgrading) in AA men. CONCLUSION: AA men who were candidates for AS criteria had worse clinicopathological features on final surgical pathology than WA men. These results suggest that a more stringent AS criteria should be considered in AA men with prostate cancer.