[Show abstract][Hide abstract] ABSTRACT: We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 µM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.
Journal of Korean Medical Science 03/2015; 30(3):308-16. DOI:10.3346/jkms.2015.30.3.308 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We established an orthotopic non-muscle invasive bladder cancer (NMIBC) mouse model expressing the mammalian target of the rapamycin (mTOR) signaling pathway. After intravesical instillation of KU-7-lucs (day 0), animals were subsequently monitored by bioluminescence imaging (BLI) on days 4, 7, 14, and 21, and performed histopathological examination. We also validated the orthotopic mouse model expressing the mTOR signaling pathway immunohistochemically. In vitro BLI photon density was correlated with KU-7-luc cell number (r2 = 0.97, P < 0.01) and in vivo BLI photon densities increased steadily with time after intravesical instillation. The tumor take rate was 84.2%, formed initially on day 4 and remained NMIBC up to day 21. T1 photon densities were significantly higher than Ta (P < 0.01), and histological tumor volume was positively correlated with BLI photon density (r2 = 0.87, P < 0.01). The mTOR signaling pathway-related proteins were expressed in the bladder, and were correlated with the western blot results. Our results suggest successful establishment of an orthotopic mouse NMIBC model expressing the mTOR signaling pathway using KU-7-luc cells. This model is expected to be helpful to evaluate preclinical testing of intravesical therapy based on the mTOR signaling pathway against NMIBC.
Journal of Korean medical science 04/2014; 29(4):617. DOI:10.3346/jkms.2014.29.4.617 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sexual adverse events (AEs), a major cause for discontinuing 5α-reductase inhibitor (5ARI) therapy for benign prostatic hyperplasia (BPH), are known to occur most frequently early in therapy and appear to decline over time. The aim of this study was to investigate the changes in sexual function occurring with dutasteride treatment during a 1-year follow-up period in Korean men.
Using the International Index of Erectile Function, we prospectively evaluated, after 1, 3, 6, 9, and 12 months of treatment, the changes in sexual function of 55 outpatients (mean age 62.3±7.2 years) with BPH (mean volume 48.9±16.0 g) who had relatively good erectile function (EF) and were treated with dutasteride for at least 1 year.
EF scores showed the most significant decrease at 1 month (p<0.01). Function gradually recovered thereafter but was still significantly decreased after 12 months of treatment (p<0.05). The scores for orgasmic function and sexual desire also showed the most significant reduction at 1 month but were restored to the baseline level at 6 months. No significant correlation was observed between changes in sexual function and prostate-specific antigen level, prostate volume, or International Prostate Symptom Scores.
After 1 month of treatment, dutasteride therapy resulted in a significant reduction in all investigated sexual functions. Overall, recovery in sexual function was noted at 3 months, and orgasmic function and sexual desire were restored to baseline levels at 6 months. However, EF was still significantly reduced at 12 months.
Korean journal of urology 09/2011; 52(9):632-6. DOI:10.4111/kju.2011.52.9.632
[Show abstract][Hide abstract] ABSTRACT: A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531 x 10(9)/L. The patient was anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day, oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and LMWH was discontinued at third hospital day. On the third day of oral anticoagulation therapy, he complained of left leg swelling and prolonged painful penile erection of 24 hr-duration. His platelet count reached a nadir 164 x 10(9)/L at that time, and the patient had a deficiency of protein C and S, with an activity level of 16% and 20% of normal value. Warfarin was stopped and he underwent penile aspiration. The next day, left leg edema and penile erection was disappeared, but penile and glans penis necrosis was started. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis.
Journal of Korean medical science 09/2010; 25(9):1390-3. DOI:10.3346/jkms.2010.25.9.1390 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the yearly changes in the baseline prostate-specific antigen (PSA) levels and the incidence of prostate cancer in men screened at our health promotion center from 1995 to 2008 to determine the trends in prostate cancer in Korea.
The participants were 6,007 men, who had PSA screening for the first time at the health promotion center. Changes in the baseline PSA levels, age, body mass index (BMI), and cholesterol levels were investigated. We evaluated the percentage of participants with a PSA level >or=2.0 and 4.0 ng/ml; the men were stratified by a 5-year age range, over two calendar years. In addition, we reviewed the results of their prostate biopsies.
The median baseline PSA level and the percentage of participants with a PSA level >or=2.0 and 4.0 ng/ml was not increased. The univariate and multivariate analyses, controlled for age and BMI, showed that two calendar years was not an independent predictive factor of the PSA level. The biopsy compliance rate increased from 36% during 1997-1998 to 70% during 2005-2006.
The data from this study suggest that the increase in the incidence of prostate cancer might have been inaccurate in Korea.
Urologia Internationalis 01/2010; 85(1):88-93. DOI:10.1159/000318677 · 1.15 Impact Factor