Showing papers by "In Ho Chang published in 2011"

Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation.

Abstract: What’s known on the subject? and What does the study add? We found that resistin, a member of adipokine family, is expressed in human prostate cancers and induces prostate cancer cell proliferation through PI3K/Akt signaling pathways We are studying the effect of resistin on other urogenital tract diseases besides prostate cancer, and the relationship between other adipokines and the urogenital tract diseases OBJECTIVES • To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation • To identify the mechanisms underlying the activation of prostate cancer cells by resistin MATERIALS AND METHODS • Semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression • Human full-length resistin gene (RETN) was transfected into the PC-3 cells using the pEGFP-N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC-3 • Various concentrations of human recombinant protein resistin were added to the hormone-insensitive prostate cancer cell lines PC-3 and DU-145 for 48 h, and cell proliferation was assessed by a water-soluble tetrazolium salt assay RESULTS • Human prostate cancer cell lines PC-3 and DU-145 were found to express the human resistin mRNA • Resistin protein was strongly detected in high-grade prostate cancer tissue, whereas BPH or low-grade prostate cancer tissue revealed fainter expression of resistin • Cell proliferation was stimulated by both the full-length resistin gene overexpression and resistin treatment • Akt phosphorylation occurred after addition of resistin to PC-3 and DU-145 cells LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited PC-3 and DU-145 cell proliferation after resistin treatment CONCLUSIONS • Resistin is expressed in human prostate cancers • Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways • The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression

Role of the mTOR Pathway in the Progression and Recurrence of Bladder Cancer: An Immunohistochemical Tissue Microarray Study

Abstract: Purpose: Numerous trials have been conducted to develop new treatment regimens for superficial and invasive bladder cancer, because there is an urgent need to identify novel agents to prevent the recurrence and progression of these cancers. We evaluated the prognostic and biological significance of mTOR pathway-related markers in patients with bladder cancer who had undergone transurethral resection of their bladder tumors and radical cystectomy. Materials and Methods: We retrieved 208 bladder cancer specimens collected from patients between 1989 and 2007 and constructed a tissue microarray comprising 208 tumor samples and 25 benign urothelium samples. Immunohistochemical staining was performed for mTOR, phosphorylated (phos) S6, and phos4E-BP1. The pattern, percentage, and intensity of staining for all three markers were evaluated. Results: The median age at diagnosis of the patient cohort was 67 years (range: 29-87 years), and the median follow-up was 72 months (range: 1-257 months). The expression of phos4E-BP1 was higher in the bladder cancer cohort than in the benign cohort, whereas phosS6 expression was lower in the bladder cancer cohort than in the benign cohort. The expression of phosS6 was significantly higher in high-grade bladder cancer (p ＜0.01). There was a significant positive correlation between the H-scores of mTOR and phos4E-BP1 (coefficient of correlation, r=0.37, p＜0.01) as well as between the H-scores of mTOR and phosS6 (r=0.17, p＜0.05). In the multivariate analysis, strong phosS6 expression predicted shorter progression (p＜0.01; hazard ratio [HR], 2.516) and disease-specific survival (p＜0.01; HR, 2.396) but not overall survival (p=0.112), whereas strong phos4E-BP1 expression was a predictor of disease-specific survival (p＜0.05; HR, 2.105). Moreover, strong phosS6 expression predicted shorter recurrence-free (p ＜0.05) and progression-free (p＜0.05) survival in the superficial bladder cancer cohort. Conclusions: Our results demonstrate that mTOR pathway activation, as assessed by phos4E-BP1 phosphorylation, is related to bladder cancer tumorigenesis and that S6 protein phosphorylation is associated with a high level of disease recurrence and progression and poor cancer-specific survival.

Possible Relationship between Metabolic Syndrome Traits and Nephrolithiasis: Incidence for 15 Years According to Gender.

Abstract: Purpose: To analyze the independent effect of metabolic syndrome (MS) on nephrolithiasis (NL) despite differences in gender compared with the known lithogenic factors. Materials and Methods: From 1995 to 2009, 40,687 Koreans were enrolled in the study and observed for the development of NL at a health promotion center. The examination included anthropometric and biochemical measurements as well as kidney ultrasonography. A student’s t-test or chi-square test was used to characterize the participants and a standard Cox proportional hazards model was used to calculate the adjusted odds ratio of lithogenic risk factors in the NL model. Results: The mean age of the study cohort was 44.9 years (range, 13-100 years), and 22,540 (55.4%) of the cohort was male. The incidence of NL was 1.5% (609 participants), with males exhibiting a higher incidence than females (1.9% vs 1.0%, p＜0.01). Among the total cohort, MS as well as each trait of MS were risk factors for NL. In males, high body mass index (BMI), high blood pressure, and abnormal glucose metabolism were significant lithogenic factors, whereas in females, lithogenic factors included only high BMI and abnormal glucose metabolism. Conclusions: MS is a significant lithogenic factor compared with other lithogenic factors. There was a correlated change in the prevalence of MS and NL and MS traits

Expression of human β-defensin-2 in the prostate.

Abstract: OBJECTIVE To investigate the expression and regulation of human β-defensin-2 (HBD-2) in the prostate PATIENTS AND METHODS Normal human prostate epithelial cell line (RWPE-1), human prostate cancer cell lines (DU-145, PC-3), and paraffin-embedded prostate tissue from patients with benign prostatic hyperplasia (BPH) were analysed by RT-PCR and immunohistochemical staining HBD-2 expression was also analysed by RT-PCR and ELISA in RWPE-1 cells treated with lipopolysaccharide (LPS) Nuclear factor-κB (NF-κB) activation was assessed by IκBα immunoblotting and electrophoretic mobility shift assay (EMSA) RESULTS BPH tissue and all of the tested prostate cell lines other than PC-3 constitutively express HBD-2 mRNA HBD-2 protein was strongly detected in prostate gland tissue surrounded by inflammatory cells including macrophages Exposure to LPS induced HBD-2 upregulation and NF-κB activation, as assessed by IκBα phosphorylation and degradation in RWPE-1 cells Bay11-7082, an NF-κB inhibitor prevented LPS-induced HBD-2 production in RWPE-1 cells CONCLUSIONS Prostate epithelial cells may constitutively express HBD-2, and its expression was upregulated by LPS Our data indicate that HBD-2 may be an important immunomodulatory factor in prostate function Expression of HBD-2 in normal prostates and the potential role of HBD-2 in prostatitis and BPH should be addressed in the future

Effect of Prostate Biopsy Hemorrhage on MRDW and MRS Imaging

Abstract: Purpose: To retrospectively evaluate the effect of post-prostate-biopsy hemorrhage on the interpretation of magnetic resonance diffusion-weighted (MRDW) and magnetic resonance spectroscopic (MRS) imaging in the detection of prostate cancer. We also investigated the optimal timing for magnetic resonance examination after prostate biopsy. Materials and Methods: We reviewed the records of 135 men. All patients underwent prostate magnetic resonance imaging (MRI). The prostate was divided into eight regions according to the biopsy site. Subsequently, we measured hemorrhage on apparent diffusion coefficient (ADC) values and (choline+creatinine)/citrate ([Cho+Cr]/Cit) ratios in the same regions on the MRI. We investigated the effect of hemorrhage at ADC values and (Cho+Cr)/Cit ratios on MRI and the relationship between prostate biopsy results and MRI findings. Results: The mean patient age was 68.7 years and the mean time between biopsy and MRI was 23.5 days. The total hemorrhagic score demonstrated no significant associations with intervals from biopsy to MRI. Higher hemorrhagic scores were associated with higher ADC values, prostate cancer, and noncancer groups, respectively (p ＜0.001). ADC values were lower in tumors than in normal tissue (p＜0.001), and ADC values were inversely correlated with tumor Gleason score in biopsy cores (p＜0.001). However, (Cho+Cr)/Cit ratios did not exhibit any association with prostate biopsy results and hemorrhage. Conclusions: Hemorrhage had no significant associations with the interval from biopsy to MRI. ADC values may help to detect prostate cancer and predict the aggressiveness of cancer; however, it is important to consider the bias effect of hemorrhage on the interpretation of MRDW imaging given that hemorrhage affects ADC values.

Association between LEP Gene Polymorphisms and Prostate Cancer Susceptibility in Korean Men

Abstract: Purpose: Obesity is thought to influence prostate carcinogenesis. Thus, variants in the leptin (LEP) gene could be associated with prostate cancer (PC) risk. Sequence variants in the LEP gene were investigated to determine whether they were associated with PC risk in a Korean study cohort. Materials and Methods: We evaluated the association between 14 single nucleotide polymorphisms (SNPs) in the LEP gene and PC risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects). Results: We observed significantly lower frequencies of rs2278815 and rs4731426 in the patients with PC (18.1%) compared to those in the control group (23.5%) (odds ratio, 0.70; 95% confidence interval, 0.50-0.98, p=0.04). These SNPs were not correlated with clinical stage, prostate specific antigen level, Gleason biopsy score, or age at diagnosis. Our results indicate that the frequencies of rs2278815 and rs4731426 in the LEP gene were significantly lower in Korean patients with PC. Conclusions: These results suggest that polymorphisms or haplotypes in the LEP gene may influence the risk for PC.