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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.
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.
김명주(Myeong Joo Kim),지병훈(Byung Hoon Chi),조민지(Min Ji Cho),황영미(Young Mi Whang),장인호(In Ho Chang) 대한비뇨기종양학회 2017 대한비뇨기종양학회지 Vol.15 No.2
Tissue engineering is limited by our inability to adequately vascularize tissues post implantation because all tissue-engineered substitutes (with the exception of cornea and cartilage) require a vascular network to provide the nutrient and oxygen supply needed for their survival. This review gives a brief overview of the processes and factors involved in the vascularization and angiogenesis and summarizes the different strategies to overcome the issue of slow vascularization and angiogenesis in a range of tissue-engineered substitutes. Moreover, we will announce some potential future plans.
조민지(Min Ji Cho),지병훈(Byung Hoon Chi),김명주(Myeong Joo Kim),황영미(Young Mi Whang),장인호(In Ho Chang) 대한비뇨기종양학회 2018 대한비뇨기종양학회지 Vol.16 No.2
Three-dimensional (3D) printing is an additive manufacturing process by which precursor materials are deposited layer by layer to form complex 3D geometries from computer-aided designs, and bioprinting offers the ability to create 3D architecture living cells. Bioprinting methods have been developed rapidly pattern living cells, biological macromolecules, and biomaterials, and an advantage of the 3D microenviroment over traditional 2-dimensional cell culture is the ability to obtain more accurate and reliable data from model about tumor formation, progression, and response to anticancer therapies. This review focuses on recent advances in the use of biopriniting technologies for cancer research, bioprinting physiologically relevant testing platforms for anticancer drug development, and computational modeling for improvement bioprinting technique.
이정우(Jung Woo Lee),김지아(Jia Kim),신영재(Youngjae Shin),지병훈(Byung Hoon Chi),김정훈(Jung Hoon Kim),최세영(Se Young Choi) 대한비뇨기종양학회 2021 대한비뇨기종양학회지 Vol.19 No.4
The heterogeneity of cancer makes it difficult to predict the prognosis of treatment. There is still a lack of preclinical model systems that reflect the clinical characteristics of patients who have heterogenetic tumors. Advances in 3-dimentional (3D) cell culture are leading to discoveries that occur in the development and progression of cancer that has not been known. There are many models including patient-derived xenograft, patient-derived organoid and spheroid, patient-derived explant, scaffold-based model, and system-based model. Each 3D model has its strengths and limitations. One model cannot answer every question, so it seems most reasonable to approach multiple models when studying cancer heterogeneity. Hopefully, 3D tumor modeling will make tremendous progress on this path by fusion of innovative biomaterials and advanced modeling techniques that can partially mimic the heterogeneous environment of real tumors.
마우스 정위성 방광암 모델에서 항미생물 펩타이드의 저항성을 지닌 재조합 Bacillus Calmette-Guérin의 효과
홍석주(Seok Ju Hong),황광용(Gwang Yong Hwang),강수정(Su Jeong Kang),최세영(Se Young Choi),지병훈(Byung Hoon Chi),장인호(In Ho Chang) 대한비뇨기종양학회 2021 대한비뇨기종양학회지 Vol.19 No.1
Purpose: Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure. Here, we developed genetically modified recombinant BCG (rBCG) strains which escape AMPs and evaluate the efficacy and effects of rBCG. Materials and Methods: We constructed rBCG strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. The efficacy of the Sic and dltA gene electroporation into BCG was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The internalization rates and anticancer effects of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA) was evaluated by the orthotopic bladder cancer mouse model. Results: The cycle quantification (Cq) values of rBCG-Sic (y=-4.8823x+13.645, R²=0.9996) and rBCG-dltA (y=-5.438x+11.641, R²=0.9995) were inverse correlations to the amount of Sic and dltA genes dose dependently. The mean introduction proportions of Sic and dltA genes into BCG by electroporation were 22.2%, 27.5% and showed constant efficacy. In the orthotopic bladder cancer mouse model, the relative internalization number of rBCG-Sic, and rBCG-dltA into bladder cell in mouse bladder were higher than that of BCG and the tumor volume at rBCG-Sic were lower than at BCG and rBCG-dltA at 11, 14 and 18 days. Conclusions: Our results showed that constructed rBCG-Sic and rBCG-dltA by electroporation and the rBCG-Sic and rBCG-dltA can effectively escape BCG-stimulated AMPs, and significantly improved immunotherapeutic tools to treat bladder cancer in orthotopic bladder cancer mouse model.
심재헌(Jae Hun Shim),국준희(Joon Hee Gook),장인호(In Ho Chang),손정민(Jung Min Sohn),성신우(Sin Woo Seong),지병훈(Byung Hoon Chi) 대한비뇨기종양학회 2021 대한비뇨기종양학회지 Vol.19 No.2
Microbiomes are known to have a beneficial effect on human health by promoting the effective removal of improperly functioning immune cells and protecting the host from pathogen infection. On the other hand, these microbiomes are also known as the causative agent of numerous malignant tumors. Until now, the bladder has been regarded as aseptic, but the concept of the “sterile bladder” has been changed with the discovery of living bacteria embedded in the bladder with the recent development of polymerase chain reaction and culture techniques. This paper referred to the relationship between microbiome and bladder cancer. Microbiome will be able to be seen as a non-invasive biomarker to predict the success rate of intravesical bacillus Calmette-Guerin instillation treatment in patients of bladder cancer.