암 미세환경 생체 인쇄의 현재와 미래

지병훈,조민지,김명주,황영미,장인호 대한비뇨기종양학회 2017 대한비뇨기종양학회지 Vol.15 No.3

Cancer is the tissue complex consisted with heterogeneous cellular compositions, and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell−cell interactions as well as cell-extracellular matrix play major roles. Conventional cancer models both 2-dimensional and 3-dimensional (3D) present numerous limitations, which restrict their use as biomimetic models for drug screening and fundamental cancer biology studies. Recently, bioprinting biofabrication platform enables the creation of high-resolution 3D structures. Moreover this platform has been extensively used to model multiple organs and diseases, and this versatile technique has further found its creation of accurate models that figure out the complexity of the cancer microenvironment. In this review we will focus on cancer biology and limitations with current cancer models and we discuss vascular structures bioprinting that are critical to the construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinting cancer models and propose future perspectives.

S-38 : 위에서 발견된 여포 림프종 1예

지병훈,박수범,홍정범,김동준,이창석,박승제,고경원 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

P70S6K and Elf4E Dual Inhibition Is Essential to Control Bladder Tumor Growth and Progression in Orthotopic Mouse Non-muscle Invasive Bladder Tumor Model

지병훈,김순자,서호경,서혜현,이상진,권종규,이태진,장인호 대한의학회 2015 Journal of Korean medical science Vol.30 No.3

We investigated how the dual inhibition of the molecular mechanism of the mammaliantarget of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryoticinitiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression ofurothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor(NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model wasmonitored using bioluminescence imaging (BLI) in vivo by interfering with differentmolecular components using rapamycin and siRNA technology. We then analyzed theeffects on molecular activation status, cell growth, proliferation, and progression. A highconcentration of rapamycin (10 μM) blocked both P70S6K and elF4E phosphorylation andinhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability andproliferation more than the transfection of siRNA against p70S6K or elF4E. The groups withdual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propriainvasion more than the groups with p70S6K or elF4E siRNA instillation, although all groupsreduced photon density compared to the control. These findings suggest that both themTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by highdose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladdertumor growth and progression.

Changes in Sexual Function in Benign Prostatic Hyperplasia Patients Taking Dutasteride: 1-Year Follow-Up Results

지병훈,김세철 대한비뇨의학회 2011 Investigative and Clinical Urology Vol.52 No.9

Purpose: Sexual adverse events (AEs), a major cause for discontinuing 5a-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. Materials and Methods: 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. Results: 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. Conclusions: 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.

Daily Mean Temperature and Urolithiasis Presentation in Six Cities in Korea: Time-Series Analysis

지병훈,장인호,최세영,서동철,장종원,최윤정,이소연 대한의학회 2017 Journal of Korean medical science Vol.32 No.6

Seasonal variation in urinary stone presentation is well described in the literature. However, previous studies have some limitations. To explore overall cumulative exposure-response and the heterogeneity in the relationships between daily meteorological factors and urolithiasis incidence in 6 major Korean cities, we analyzed data on 687,833 urolithiasis patients from 2009 to 2013 for 6 large cities in Korea: Seoul, Incheon, Daejeon, Gwangju, Daegu, and Busan. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of mean daily urolithiasis incidence (MDUI) associated with mean daily meteorological factors, including the cumulative RR for a 20-day period. The estimated location-specific associations were then pooled using multivariate meta-regression models. A positive association was confirmed between MDUI and mean daily temperature (MDT), and a negative association was shown between MDUI and mean daily relative humidity (MDRH) in all cities. The lag effect was within 5 days. The multivariate Cochran Q test for heterogeneity at MDT was 12.35 (P = 0.136), and the related I2 statistic accounted for 35.2% of the variability. Additionally, the Cochran Q test for heterogeneity and I2 statistic at MDHR were 26.73 (P value = 0.148) and 24.7% of variability in the total group. Association was confirmed between daily temperature, relative humidity and urolithiasis incidence, and the differences in urolithiasis incidence might have been partially attributable to the different frequencies and the ranges in temperature and humidity between cities in Korea.

이물질에 의한 십이지장벽 농양 1예

지병훈,윤지훈,이진호,이희룡,유성민,김민대,최영일,이일선 대한소화기내시경학회 2011 Clinical Endoscopy Vol.42 No.6

Duodenal abscess is a form of phlegmonous enterocolitis and is a rarely reported disease throughout the entire world. Duodenal abscess mostly develops from complications of duodenal ulcer perforation, and may result in a clinically fatal course because it is difficult to differentiate from some diseases such as gastric ulcer, gastric cancer, hepatobiliary disorders etc.. The therapeutic gold standard is surgical intervention including abscess removal and drainage. We experienced a case of duodenal abscess that expressed non-specific symptoms, weight loss and epigastric pain, and diagnosed by gastrointestinal endoscopy, abdominal computed tomography. We successfully treated it through surgical intervention with intravenous antibiotics. 십이지장 농양은 장관에서 발생하는 농양의 한 형태로 드물게 발생하는 질환으로 알려져 있으며, 상복부 통증, 식욕부진과 같은 비특이적인 증상을 보이는 경우가 많고 위궤양, 위암, 담도계 질환과의 감별이 어려워 진단과 치료가 늦어져서 치명적인 임상경과로 진행할 수 있다. 본 증례는 알코올 남용, 흡연, 스테로이드 제제 및 비스테로이드성 항염증약물의 복용과 같은 위장관 점막 손상의 복합적인 위험 인자를 가진 59세 남자환자에게서 체중감소 및 심와부 통증 등의 비특이적인 증상으로 발현된 십이지장벽 농양의 예이다. 저자들은 병리소견과 병변부 세균배양검사 결과를 종합하여 이물질로 인해 발생한 십이지장 농양으로 결론을 내렸고 수술적 치료와 경피적배농술 및 항생제 투여를 통해 임상경과의 호전을 경험하여 문헌고찰과 함께 보고한다.

한국인에서 신장암의 과잉 진단 및 작은 국소신장암에서 능동적 관찰의 의미

지병훈(Byung Hoon Chi),장인호(In Ho Chang) 대한비뇨기종양학회 2018 대한비뇨기종양학회지 Vol.16 No.1

While overtreatment in medical services had been the topic of interest among the medical community for a long time, there are numerous academic papers concerning over-diagnosis nowadays. The use of imaging studies for screening might lead to over-diagnosis of small renal masses (SRMs) therefore the incidence of kidney cancer increased 5 times higher than that of mortality in Korea between 2000 and 2011. The best treatment for SRMs had been debated and the present strategies include surgery, local treatment, and active surveillance. Competing risks to mortality should be considered to determine initial management strategies, and a period of initial active surveillance in patients with SRMs is safe. Tumor growth rate is the primary driver for delayed intervention of SRMs patients, and the risk of metastasis on active surveillance for SRMs is 1%–2% at 2-year follow-up.

BCG치료에서 방광의 면역 반응에 대한 이해

지병훈(Byung Hoon Chi),장인호(In Ho Chang) 대한비뇨기종양학회 2014 대한비뇨기종양학회지 Vol.12 No.1

Though BCG (bacille de Calmette-Guerin) therapy has been the standard of care for high-risk non-muscle invasive bladder cancer for more than 35 years, its precise mechanisms of action remain unclear. It is however well established that it involves an immune response from the tumor-bearing host and I review the current knowledge based on human observational trials and experimental studies in mice. Recent studies reported that the vast majority of BCG was voided after instillation, and, among the few bacteria that persist, their internalization by urothelial cells remained questionable and understudied. Knowledge about the mechanism of BCG internalization is scarce and controversial and there is no data about the fate of BCG following internalization by urothelial cells. Despite this low level of internalization, a strong immune response is triggered following repeated intravesical BCG. Through several in vitro and orthotopic mice model studies, it is suggested that BCG-mediated anti-tumor activity involves an immune response that is characterized by waves of inflammatory cells shortly after each repeated instillation, followed by the establishment of a Th1 polarized environment. Whether the effective eradication of tumor cells involves some tumor-specific killing or whether BCG therapy functions as a nonspecific immunotherapy is not yet clear.

지속성 외래 복막 투석 환자의 반코마이신 내성 장구균복막염 치료 1예

정정임,김수진,지병훈,오준석,김성민,신용훈,김중경 대한내과학회 2011 대한내과학회지 Vol.80 No.-

Peritonitis is one of the major complications of continuous ambulatory peritoneal dialysis (CAPD). Multidrug-resistant organisms, including vancomycin-resistant enterococci (VRE), have been reported as pathogens of CAPD-associated peritonitis. The incidence of hospital-associated infections caused by VRE has recently increased. Some drugs, such as linezolid and quinupristin/dalfopristin, have been introduced as treatments of VRE infection. However, there is limited information about the effects of VRE-associated CAPD peritonitis. We present a case of successful treatment of CAPD peritonitis caused by VRE with quinupristin/dalfopristin and include a review of the literature. (Korean J Med 2011;80:S245-S248) 본 증례를 통하여 VRE에 의한 복막투석 복막염에 대해 quinupristin-dalfopristin를 사용하여 치료한 효과는 확인하였다. 하지만 치료 방법에 대한 명확한 기준은 아직 미흡한 실정이다. VRE 감염이 확인된 후 2주간의 quinupristin-dalfopristin를 사용하여 치료에 성공한 경우로 다른 항생제의 투여가 병용된 점은 quinupristin-dalfopristin만의 단독 효과로 생각하기에는 제한점을 가진다. 하지만 균주가 동정된 후 항생제 내성 결과에 따라 투여된 약제가 효과를 나타냄에 따라 VRE 감염증을 도관제거 없이 quinupristin-dalfopristin를 정맥 투여하여 감염증을 치료하였다. 도관을 제거하지 않고 지속적인 관류함으로 감염된 상처를 열어 놓으면서 균주의 박멸을 시도하는 것도 한 가지 방법이 될 수 있음을 이번 증례를 통해 경험하여 보고하는 바이다[17]. 최근 반코마이신 내성 균주의 증가추세로 볼 때 향후 본 증례와 같은 VRE 복막염의 예가 증가할 것으로 예측되며 먼저 이를 줄이기 위해 VRE의 전파 방지를 위한 노력이 필요하다. 또한, VRE로 인한 복막염이 진단된 경우에는 quinupristin-dalfopristin의 사용이 효과적일 것으로 생각되나 향후 지속적 연구를 통해 적절한 용량 및 투여기간에 대한 연구 및 보고가 있어야 할 것이다.

Warfarin-Induced Penile Necrosis in a Patient with Heparin-Induced Thrombocytopenia

장인호,하문수,지병훈,권용욱,이상재 대한의학회 2010 Journal of Korean medical science Vol.25 No.9

A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531×109/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 164×109/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 warfarininduced skin necrosis.