Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ₃ integrin-dependent migration in vitro. Furthermore, αVβ₃ integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ₃ integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ₃ integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.     

Comparison of oncological outcomes between retropubic radical prostatectomy and robot-assisted radical prostatectomy: an analysis stratified by surgical experience

Objectives

To compare oncological outcomes of a consecutive retropubic radical prostatectomy (RRP) and robot-assisted radical prostatectomy (RARP) series performed by a single surgeon who had performed >750 prior RRPs and was starting to perform RARPs.

Materials and methods

Prospectively collected longitudinal data of 277 RRP and 730 RARP cases over a 5-year period were retrospectively analyzed. The RARP series were divided into 3 subgroups (1st, <250 cases; 2nd, 250–500; and 3rd, >500) according to the surgical period. The positive surgical margin (PSM) and biochemical recurrence-free survival (BCRFS) rates were compared at each pathological stage.

Results

The pT2 PSM rates showed no significant difference between the RRP (7.8 %) and RARP series (1st, 9.5 %; 2nd, 14.1 %; and 3rd, 9.8 %) throughout the study period (P = 0.689, 0.079, and 0.688, respectively). Although the pT3 PSM rates of the 1st (50.6 %) and 2nd RARP series (50.0 %) were higher than that of the RRP series (36.0 %; P = 0.044 and P = 0.069, respectively), the 3rd RARP series had a comparable pT3 PSM rate (32.4 %, P = 0.641). The 3-year BCRFS rates of the RRP and RARP series were similar at each pathological stage (pT2, 92.1 vs. 96.8 %, P = 0.517; pT3, 60.0 vs. 67.3 %, P = 0.265, respectively).

Conclusions

The pT2 PSM and short-term BCRFS rates were similar between RRP and RARP, and RARP showed comparable pT3 PSM rate with RRP after >500 cases of surgical experience. Our data suggest that an experienced robotic surgeon at a high-volume center may achieve comparable oncological outcomes with open prostatectomy even in locally advanced disease.     

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.     

Intake of Soy Products and Other Foods and Gastric Cancer Risk: A Prospective Study

Background

Gastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC).

Methods

The KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs.

Results

Frequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22–0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52–1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268).

Conclusions

Frequent soybean/tofu intake was associated with lower risk of gastric cancer.Key words: soybean, dietary intake, gastric cancer     

Cigarette smoking and gastric cancer risk in a community-based cohort study in Korea]

OBJECTIVES: Gastric cancer is the most common incident cancer in Korea. Although Helicobacter pylori infection is the most important risk factor for the development of gastric cancer, cigarette smoking has also been suggested to play an important role in the development of gastric cancer. The objective of this study is to evaluate the relationship between cigarette smoking and gastric cancer risk in a Korean population. METHODS: The study population consisted of 13,785 subjects who had been enrolled in the Korean Multi-Center Cancer Cohort between 1993 and 2002. As of December 2002, 139 incident gastric cancer cases were ascertained through the Korea Central Cancer Registry and the National Death Certificate Database. Relative risks (RR) and 95% confidence intervals (CI) for gastric cancer were estimated using Cox's proportional hazard model adjusted for age, education, alcohol drinking status and history of gastritis or ulcer. RESULTS: Significant dose-response relationships were observed between the duration of smoking and the risk of gastric cancer among the male subjects in comparison to non-smokers: men who smoked for 20-39 years had a 2.09- fold (95% CI 1.00-4.38) increase, and those who smoked for more than 40 years had a 3.13-fold (95% CI 1.59-6.17) increase in the risk of gastric cancer (P trend<0.01). CONCLUSIONS: This study suggests that a longer duration of cigarette smoking may increase the risk of gastric cancer development in a dose-response manner in Korean men. The association between smoking and gastric cancer risk in women should be verified in future studies with a larger number of cases.     

Multimodal treatment including tandem high‐dose chemotherapy and autologous stem cell transplantation in children with anaplastic ependymomas

In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas.