Byung Hoon Chi

Chung-Ang University Hospital, Sŏul, Seoul, South Korea

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Publications (9)17.91 Total impact

  • The Journal of Urology 04/2015; 193(4):e1101. DOI:10.1016/j.juro.2015.02.1804
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    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. Graphical Abstract
    Journal of Korean Medical Science 03/2015; 30(3):308-16. DOI:10.3346/jkms.2015.30.3.308
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    ABSTRACT: To confirm the role of cathelicidin (LL-37) in the internalization of bacille Calmette-Guérin (BCG) into bladder cancer cells. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction analysis evaluated the changes in protein and messenger ribonucleic acid (RNA) expression with BCG incubation after LL-37 pretreatment in 5637 and T24 human bladder cancer cells. The internalization rate was evaluated by a double immunofluorescence assay, and confocal microscopy confirmed the function of LL-37 in BCG internalization. We also investigated the difference in internalization rates and cell viability between LL-37, anti-LL-37 antibody, and LL-37 plus anti-LL-37 antibody. The levels of LL-37 increased after BCG exposure in bladder cancer cells in dose- and time-dependent manners. Increasing LL-37 levels using recombinant LL-37 protein further dose dependently decreased BCG internalization in both cell lines. The internalization rates of BCG after LL-37 instillation were lower compared with the controls, and the internalization rate of BCG after anti-LL-37 antibody instillation was significantly higher compared with the controls in both cell lines (P <.05). Viability of LL-37 plus BCG group was higher compared with the BCG-alone group. The anti-LL-37 antibody plus BCG group had decreased cell viability compared with the BCG-alone group in both cell lines. Bladder cancer cells produce cathelicidin when infected with BCG and upregulate cathelicidin to defend against BCG by inhibiting its internalization. Blocking the action of cathelicidin may increase the internalization and effectiveness of BCG in reducing bladder cancer cell proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urology 02/2015; 85(4). DOI:10.1016/j.urology.2014.12.028
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    ABSTRACT: We investigated whether bacillus Calmette-Guérin (BCG)-induced secretion of murine β-defensin-2 (mBD2) and determined whether mBD2 regulated BCG effects in the normal mouse bladder. A total of 140 C57BL/6 female mice were divided into 28 groups, and the experiment was performed over 3 steps. In the first step (20 groups), mice bladders were stimulated with different doses of BCG (multiplicity of infection [MOI] 0, 1, 10, 30, and 100) and histological analysis was conducted in bladder specimens isolated at different times (0, 4, 8, and 24h after instillation) to determine optimal dose and time point of BCG internalization and urine mBD2 and cytokine concentration. In the second step (4 groups), BCG internalization and urine cytokine levels were measured after pretreatment of different recombinant mBD2 (rmBD2) (0, 1, 2.5, and 5ng/ml) at optimal dose and time point. In the third step (4 groups), BCG internalization and urine cytokine levels were compared between pretreatment conditions (control, rmBD2, anti-mBD2 Ab, and rmBD2+anti-mBD2 Ab). Urine was collected for estimating mBD2 levels and a multiplex analysis for 9 cytokines. Real-time polymerase chain reaction assay was used for estimating the relative BCG cell number in mice bladder tissue. Bladder edema was induced by BCG (MOI 30 and 100), which progressed to an inflammatory infiltrate composed primarily of neutrophils and increased mBD2 secretion at 4 hours after instillation. Relative BCG cell number and urinary cytokine levels (interferon-γ and interleukins [IL]-2, -4, -6, and -10) response pattern was characterized by a peak at 4 hours after instillation followed by rapid decline. The levels of interferon-γ, and IL-1β, -2, -4, -6, and -10 and relative BCG cell numbers decreased in a dose-dependent manner according to pretreatment with rmBD2 protein, and the responses were potentiated in the anti-mBD2 pretreatment group at 4 hours after BCG (MOI 30) instillation. The present results suggest that the mouse urothelium produces mBD2 in response to intravesicular BCG as a defense mechanism against BCG, and blocking mBD2 by an anti-mBD2 antibody increased the effectiveness of BCG. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urologic Oncology 01/2015; 33(3). DOI:10.1016/j.urolonc.2014.10.015
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    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
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    Byung Hoon Chi, Sae Chul Kim
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    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
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    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
  • The Journal of Urology 04/2010; 183(4):e652. DOI:10.1016/j.juro.2010.02.1513
  • Byung Hoon Chi, In Ho Chang
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    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

Publication Stats

10 Citations
17.91 Total Impact Points


  • 2011–2015
    • Chung-Ang University Hospital
      Sŏul, Seoul, South Korea
  • 2010–2014
    • Chung-Ang University
      Sŏul, Seoul, South Korea