The Effect of Exogenous Superoxide Dismutase (SOD) on Caspase-3 Activation and Apoptosis Induction in Pc-3 Prostate Cancer Cells.

BACKGROUND: This study aimed to assess the effects of exogenous SOD administration on prostate cancer cell line (PC-3) apoptosis via the intrinsic pathway by examining the expression of manganese superoxide dismutase (MnSOD), caspase-3, and apoptosis index of the PC-3 cell line. METHODS: We used the prostate cancer cells from secondary prostate cancer cell lines (PC-3) derived from castration refractory prostate cancer (CRPC), cell differentiation grade IV, and had metastasized to the bone from the American Type Culture Collection (ATCC, Rockville, MD, USA). Superoxide dismutase (SOD) is derived from extracts of melon seeds and wheat gliadin biopolymer, and divided into 62.5 mg/mL, 83 mg/mL, 125 mg/mL, and 250 mg/mL doses. Expression of MnSOD was measured by immunohistochemistry (IHC). Expression of caspase-3 was measured using Western Blot method. Apoptotic index is calculated based on the reaction introduction 3OH end of fragmentation of DNA by the enzyme terminal transferase in preparations with TUNEL staining reagents. A one-way ANOVA test and Pearson correlation test were used to determine the relationship between SOD with expression of caspase-3 and apoptotic index. RESULTS: SOD extract significantly increased the expression of caspase-3 (P=0.016) and the apoptotic index (P=0.000) (P<0.05). There was a correlation between the increased doses of SOD extract and the apoptosis index (P=0.015; r=0.679) and between the increased caspase-3 expression and the apoptosis index (P=0.015; r=0.682). CONCLUSION: Administration of superoxide dismutase (SOD) increased apoptosis in a prostate cancer cell line (PC-3) through the increased expression of caspase-3. Superoxide dismutase (SOD) can be considered as a therapy for late-stage prostate cancer that had been progressed to hormone resistant and metastasized and promote apoptosis in those prostate cancer cells.

Indonesian prostate cancer risk calculator (IPCRC): an application for predicting prostate cancer risk (a multicenter study).

AIM: to develop a prediction risk model of prostate cancer based on Indonesia population. METHODS: we included all benign prostate hyperthrophy (BPH) and PCa patients who had prostate biopsy and prostatectomy between January 2009 and December 2013 from 5 urology centers in Indonesia. The relationship between the possibility of PCa with the following variables including: age; PSA level, prostate volume (by transabdominal ultrasound or transrectal ultrasound) and digital rectal examination (DRE) finding. We calculated a predictive scoring equation to predict the possibility of PCa using chi-square analysis, Kolmogorov-Smirnov test, multiple logistic regression and ROC curve. Then, we designed an application for predicting prostate cancer risk called Indonesian Prostate Cancer Risk Calculator (IPCRC). RESULTS: there were 784 PCa and 1173 BPH patients were used for developing the risk calculator in our study. The mean ages, PSA and prostate volume are 66.9±8.1 years old; 72.4±248.9 ng/ml and 49.6±28.2 ml, respectively. Abnormal DRE was found in 637 PCa and 56 BPH. We included age, PSA level, abnormal DRE finding (all showed significant p<0.05 in univariate model). Additionally, although not significant, we included prostate volume (p=0.157) due to its clinical importance. The corrected ROC analysis showed AUC 0.935, sensitivity of 90.1% and specificity 80% in predicting the prostate cancer in our population. CONCLUSION: we have developed the Indonesian Prostate Cancer Risk Calculator which includes age, PSA, DRE, and prostate volume as its variables. Future prospective study to validate the risk calculator is needed.

Prostate-specific antigen and prostate-specific antigen density cutoff points among Indonesian population suspected for prostate cancer.

PURPOSE: Racial differences exist in the incidence of prostate cancer (PCa). Although many studies have looked at the performance of prostate-specific antigen (PSA) and PSA density (PSAD) in the detection of PCa, only a few have looked at it in relation to Indonesian men. The objective of this study is to find out better PSA and PSAD cutoff point in the detection of PCa in Indonesian men. METHODS: A total of 404 consecutive Indonesian men underwent prostate biopsy for suspicion of PCa from 2008 to 2011. The biopsy criteria include one or more of the following: serum PSA more than 10 ng/mL, PSAD more than 0.15 if PSA 4-10 ng/mL, hypoechoic lesion during transrectal sonography and/or abnormal digital rectal examination. RESULTS: Forty five out of 404 (11.1%) had positive biopsies. The mean age, prostate volume, PSA and PSAD were respectively 64.06 years, 43.03 mL, 45.59 ng/mL and 1.15. Of the 404, 131 cases (32.4%) were confirmed to be urinary retention. Positive urine culture found in 182 cases (45%). The cutoff point to detect PCa as estimated by the receiver operating characteristics was 6.95 ng/mL for PSA (sensitivity 97.8%, specificity 19.6%) and 0.7072 for PSAD (sensitivity 62.2%, specificity 78.7%). Positive predictive value for this PSA and PSAD cutoff point were 11.6% and 27.5% respectively (P=0.004 and P=0.000). There was a significant correlation between hypoechoic lesion and positive biopsy results (P =0.000). Urinary retention elevates PSA cutoff point to 14.55 (sensitivity 90.9%, specificity 50%), while positive urine culture alters almost no PSA cutoff elevation. CONCLUSIONS: PSA and PSAD cutoff point for Indonesian men in this series is relatively different from international consensus. Furthermore, these data show that PSA and PSAD cutoff point must be adjusted to racial variation to discriminate between malignant and benign disease. Urinary retention is a significant factor for PSA cutoff increase.

Test - retest reliability of the Indonesian version of the Overactive Bladder Symptom Score (OABSS) and its correlation with standard assessment tools.

AIM: to evaluate the test-retest reliability of the Indonesian version of OABSS and its correlation with other validated assessment tools for OAB. METHODS: eligible patients aged 18 years with established OAB were instructed to complete 3-day micturition diaries and the OABSS, International Prostate Symptom Score (IPSS) and Patient Perception of Bladder Condition (PPBC) on two separate visits: Week 0 and Week 2. Test-retest reliability was examined using the internal correlation coefficient (ICC) and weighted Kappa coefficients between first and second applications of the OABSS. Pearson or Spearman correlation coefficients were calculated to test the correlation of OABSS with IPSS, IPSS Quality of Life (QOL) item, PPBC and clinical variables of the 3-day voiding diary. RESULTS: ICC for the OABSS total score was 0.83. The weighted Kappa coefficients of individual scores in OABSS were 0.55-0.66. In the first and second applications of OABSS, the Pearson correlation coefficients were 0.46-0.56 and 0.36-0.53 between OABSS and three clinical variables of the 3-day voiding diary (frequencies of micturition, urgency and urge incontinence). At Visit 1, the Spearman correlation coefficients were 0.41 between OABSS and IPSS total score, 0.47 between OABSS and IPSS QOL, and 0.34 between OABSS and PPBC. At Visit 2, the Spearman correlation coefficients were 0.45 between OABSS and IPSS total score, 0.55 between OABSS and IPSS QOL, and 0.44 between OABSS and PPBC. CONCLUSION: the Indonesian version of OABSS showed excellent test-retest reliability in Indonesian OAB patients. A satisfactory correlation with IPSS total and QOL scores, PPBC and several clinical variables of the 3-day voiding diary was obtained, particularly with urgency frequency.