Tumor Necrosis Factor Alpha 촉진자의 유전형이 방광암의 분화도에 미치는 효과

정필두,김원재,김은정,김종석,엄민식,이상철 대한비뇨의학회 2002 Investigative and Clinical Urology Vol.43 No.3

TNF-α 유전자형과 방광암과의 관계

정필두,김은정,엄민식,서정원,윤석중,김종석,이상철,김원재 충북대학교 의학연구소 2001 忠北醫大學術誌 Vol.11 No.2

연구목적: TNF-α는 일부 종양의 종양화 과정과 관련이 있는 것으로 알려져 있다. 본 연구는 TNF-α 발현에 영향을 미치는 TNF-α 촉진자 -308 부위의 유전적 다형성이 방광암과 관련이 있는지 유무를 알고자 시행하였다. 대상 및 방법: 유전자 분석을 위하여 환자 113명 및 대조군 109명으로부터 혈액을 채취하여 genomic DNA를 분리한 후 PCR-RFLP 및 direct DNA sequencing을 통하여 TNF-α유전자의 다형성을 조사하여 방광암의 발생, 병기 및 분화도와 비교 검토하였다. 결과: TNF-α 촉진자 -308 부위의 유전형은 대조군에서는 GG형이 83.5%(90례 및 GA형이 16.5%(19례)로 관찰되었으며 AA형은 없었다. 환자군에서는 GG 형이 85.4%(97례), GA형 및 AA형은 각각 13.1%(15례)및 0.8%(1례)에서 관찰되었다. 두 군 모두에서 GG형이 가장 많이 나타났으며 다음으로 GA형을 보이고 AA형은 1례의 방광암 환자에서만 관찰되었다. -308부위의 경우도 두 군 사이에 유전자형의 차이는 없었다(p=0.259) 분화도별 분포를 보면 grade I이 20례, grade II가 49례, grade Ⅲ은 34례였고 병기별로 표재성인 경우가 90례였으며 침윤성은 14례였다. 분화도가 나빠질수록 GA형이 증가하였다(p=0.04). 그러나 병기와 TNF-α promoter -308부위의 유전자형 사이에는 유의한 상관 관계가 없었다(p=0.123). 결론: 방광암 환자의 혈액에서 GA genotype이 관찰되는 경우, 분화도가 나쁠 가능성이 매우 높기 때문에 좀 더 적극적인 치료와 세밀한 추적관찰을 함으로써 방광암으로 인한 사망과 암의 진행을 예방할 수 있을 것으로 기대한다. Purpose : Tumor necrosis factor-alpha (TNF-α) is involved in tumorigenesis of several cancers as an endogenous tumor promoter. The purpose of this study was to investigate whether genetic polymorphism of TNF-α promoter region (-308) was associated with human bladder tumor. Materials and Methods: The DNA from 113 and 109 respective blood samples of bladder tumor Patients and control group was analyzed by PCR-based restriction fragment length polymorphism (RFLP) and direct DNA sequencing methods to characterize the genetic polymorphism of -308 promoter region of the TNF-α gene in bladder tumor patients. We compared the association of bladder tumor with genetic Polymorphism of TNF-α promoter region(-308) in relation to the stage, grade, recurrence and progressio. Results : Eighty-six percents(97/113) of bladder tumor patients and 83.5% (90/109) of control group showed genotype GG at -308 region of TNF-α. Difference in genetic variations of TNF-α promoter (-308) did not exist between bladder tumor patients and control group(p=0.259). Tumor grade was significantly related to the GA genotype (p=0.04). The higher is the grade in bladder tumor, the more frequent was the GA genotype. Tumor stage, recurrence and progression were not significantly associated with genetic polymorphism of TNF-α promoter region (-308). Conclusion: The GA genotype of TNF-a promoter region (-308) had a significant impact on TNF-α production and was related to higher grade tumor compared to GG genotype. TNF-α serum levels in bladder tumor patients were significantly higher than controls. These data suggested that TNF-α might involve the tumorigenesis of the bladder rather than treatment or prevention of bladder tumor.

Tumor Necrosis Factor Alpha 촉진자의 유전형이 방광암의 분화도에 미치는 효과

정필두,김원재,김은정,김종석,엄민식,이상철 大韓泌尿器科學會 2002 Korean Journal of Urology Vol.43 No.3

방광암에서 NF-κB와 Apoptosis 유발 유전자들에 관한 분석

정필두,한광희,윤석중,김용준,이상철,이형래,김원재 대한비뇨의학회 2007 Investigative and Clinical Urology Vol.48 No.5

NF-κB의 발현이 인체 방광암에 미치는 영향

정필두(Pildu Jeong),이영숙(Young-Suk Lee),박문선(Moonseon Park),조성환(Sunghwan Jo),김원재(Wun-Jae Kim) 대한비뇨기종양학회 2005 대한비뇨기종양학회지 Vol.3 No.1

N-butyl-N-(4-hydroxybutyl) Nitrosamine으로 유발시킨 쥐의 방광암에서 Magnolia officinalis 추출물의 항암효과

이승찬,정필두,김용준,윤석중,이상철,김원재 대한비뇨의학회 2008 Investigative and Clinical Urology Vol.49 No.8

Purpose: Magnolia officinalis has been used in traditional Chinese medicine to treat a variety of diseases. The main constituents of Magnolia officinalis are honokiol and magnolol, which have a variety of pharmacological effects, such as antitumor, antioxidant, antimicrobial, anti-inflammatory etc. This study examined the anticancer effect of a Magnolia officinalis' extract on urinary bladder cancer in vivo. Materials and Methods: Male mice C3H/He were used as the experimental animals. The mice were divided into ten groups. Normal drinking water was provided to group 1(5 mice) for 20 weeks and 0.05% N-butyl- N-(4-hydroxybutyl) nitrosamine(BBN) was added to in the drinking water of group 2(5 mice). 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract was added to groups 3, 4, 5 and 6, respectively(5 mice each), and 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract plus 0.05% BBN was added to groups 7, 8, 9 and 10, respectively(10 mice each) for the same period. All surviving mice were sacrificed at week 20 to investigate the occurrence of bladder cancer, stage and grade. Results: Bladder cancer was not observed in groups 1, 3, 4, 5 and 6 mice. The rates of bladder cancer occurrence were 57.1, 66.7, 44.4 and 20.0% in groups 7, 8, 9 and 10, respectively. The incidence decreased with increasing concentration of Magnolia officinalis (p=0.005). However, the stage and grade were not associated with the concentration of Magnolia officinalis(each p>0.05). Conclusions: This study showed that Magnolia officinalis has some protective effect against bladder cancer. In the future, Magnolia officinalis may be expected to play an important role as a chemo-preventive and therapeutic agent or as a complementary agent in bladder cancer. Purpose: Magnolia officinalis has been used in traditional Chinese medicine to treat a variety of diseases. The main constituents of Magnolia officinalis are honokiol and magnolol, which have a variety of pharmacological effects, such as antitumor, antioxidant, antimicrobial, anti-inflammatory etc. This study examined the anticancer effect of a Magnolia officinalis' extract on urinary bladder cancer in vivo. Materials and Methods: Male mice C3H/He were used as the experimental animals. The mice were divided into ten groups. Normal drinking water was provided to group 1(5 mice) for 20 weeks and 0.05% N-butyl- N-(4-hydroxybutyl) nitrosamine(BBN) was added to in the drinking water of group 2(5 mice). 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract was added to groups 3, 4, 5 and 6, respectively(5 mice each), and 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract plus 0.05% BBN was added to groups 7, 8, 9 and 10, respectively(10 mice each) for the same period. All surviving mice were sacrificed at week 20 to investigate the occurrence of bladder cancer, stage and grade. Results: Bladder cancer was not observed in groups 1, 3, 4, 5 and 6 mice. The rates of bladder cancer occurrence were 57.1, 66.7, 44.4 and 20.0% in groups 7, 8, 9 and 10, respectively. The incidence decreased with increasing concentration of Magnolia officinalis (p=0.005). However, the stage and grade were not associated with the concentration of Magnolia officinalis(each p>0.05). Conclusions: This study showed that Magnolia officinalis has some protective effect against bladder cancer. In the future, Magnolia officinalis may be expected to play an important role as a chemo-preventive and therapeutic agent or as a complementary agent in bladder cancer.

방광암에서 Human 8-Oxoguanine Glycosylase1(hOGG1) 유전자의 다형성

김은정,정필두,정춘구,김원재 대한비뇨의학회 2002 Investigative and Clinical Urology Vol.43 No.3

OGGI 유전자의 다형성이 방광암에 미치는 영향

김은정,정필두,정춘구,서정원,윤석중,김원재 충북대학교 의학연구소 2001 忠北醫大學術誌 Vol.11 No.2

연구목적 : 손상된 유전자의 회복은 암의 발생 및 예방에 중요한 역할을 한다. 잘못된 염기의 제거 및 회복에 중요한 역할을 하는 OGGI 유전자의 다형성이 방광암에 어떠한 작용을 하는지를 환자-대조군 연구를 통해서 조사하였다. 대상 및 방법: 방광암 환자 168명과 건강인 672명을 대조군으로 하여 genomic DNA를 이용하여 SSCP (single-stranded conformational polymorphism), direct DNA sequencing 및 restriction fragment length polymorphism (RFLP) 방법을 통해 환자 및 대조군사이의 OGGI 유전자의 다형성을 조사하였다. 결과: 건강 한국인에서 OGGI 유전자의 유전형을 조사한 결과 econ 6의 Pro324Pro 부위(lb type)와 exon 7의 Ser326Cys 부위 (la type)에 유전자의 다형성이 있음을 발견하였다. Codon 324는 silent polymorphic site였으나 codon 326은 C→G로 nucleotide가 바뀌어 amino acid가 serine→cysteine으로 바뀌는 polymorphic site였다. 대조군에서 codon 326은 Ser326Ser 형이 127례 (18.9%), Ser326Cys 형이 363례 (54.0%) 및 Cys326Cys 형이 182례 (27.1%)이었으며, 168명의 방광암 환자군에서는 Ser326Ser 형이 44례 (26.2%), Ser326Cys 형이 87례 (51.8%)이고 0ys3260ys 형이 37례 (22.0%) 이었다(p=0.034) 즉 Cys326Cys 형 및 Ser326cys 형에 비하여 Ser326Ser 형에서 방광암이 생길 확율이 1.52배 (95% CI=0.439-0.969) 높았다 특히 40세 미만의 남자의 경우 Ser326Ser 형에서 방광암 발생확률이 다른 유전형에 비하여 6.1배 높았다. 결론: OGGI 유전자의 유전형은 서구인과 판이하게 달랐으며 방광암에서는 이 유전자의 변이가 빈번할 뿐아니라 codon 326의 Ser326Ser 형에서는 다른 유전자형에 비하여 방광암이 발생할 확률이 1.5배 이상 높았다. 특히 한국인 40세 미만의 남자에서는 방광암 발생확률이 6배이상 높았다. 본 연구결과 OGGI codon 326의 유전적 다형성은 방광암의 종양화 과정과 관계가 있을 것으로 여겨지며 특히 40세 미만의 한국 남자의 경우는 더욱 밀접한 관계가 있을 것으로 사료된다. Purpose: A repair of damaged DNA has been shown to be involved in the susceptibility to cancer development and prevention. Therefore, it is worth investigating genetic polymorphisms of the OGGl gene associated with the gene repair mechanism. In this study, we examined a possible association of genetic ploymorphisms in OGGl with the risk of bladder tumor. Materials and Methods: Hospital based, case-control investigation was carried out in 168 primary bladder tumor patients and 672 control subjects. We performed the SSCP, PCR-based restriction fragment length polymorphism (RFLP) and direct DNA sequencing to characterize the genetic polymorphism of OGGI in both cases and oontrols. Results: We found two polymorphic sites in OGGl. A Ser/Cys polymorphism at codon 326 (la type) in exon 7 was associated with an exchange of amino acid. Another polymorphic site at codon 324 (1b type) in econ 6 was silent. The association between codon 326 Polymorphism and the risk of the bladder tumor was examined by a age-sex adjusted analysis. We found that the distribution of OGGl Ser326Cys genotypes of controls(Ser/Ser, 18.9% ; Ser/Cys, 54.0% ; Cys/Cys, 27.1%) was significantly different from that of bladder tumor patients (36.2%, 51.8% and 22.0%, respectively) (p = 0.034, adjusted OR = 0.652, 95% Cl = 0.44 - 0.97). Especially, bladder tumor risk in Korean male under 40 years old was approximately 6 times higher than over 40 years old males. Conclusion : Our data suggested that Ser326cys polymorphism at codon 326 of OGGl male below 40 years old in Korea significantly increased the risk of tumorigenesis in the urinary bladder (p = 0.015, adjusted OR = 0.165, 95% CI = 0.04 - 0.75) Our results suggest that the OGGl Ser326Cys Polymorphism might play a role in the tumorigenesis of the bladder.

방광암에서 Human 8-Oxoguanine Glycosylase1 (hOGG1) 유전자의 다형성

김은정,정필두,정춘구,김원재 大韓泌尿器科學會 2002 Korean Journal of Urology Vol.43 No.3

Urinary microRNA-1913 to microRNA-3659 expression ratio as a non-invasive diagnostic biomarker for prostate cancer

변영준,박현미,정필두,강호원,서성필,문성권,이종영,최영현,이희윤,김원태,이상철,차은종,윤석중,김원재 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.3

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs and are involved in the development, proliferation, and pathogenesis of prostate cancer (PCa). Urinary miRNAs are promising non-invasive biomarkers for PCa diagnosis because of their stability in urine. Here, we evaluated the diagnostic value of urinary miR-1913 to miR-3659 ratio in PCa patients and benign prostate hyperplasia (BPH) controls. Materials and Methods: Candidate miRNAs were identified from urinary microarray data and tested by real-time PCR. The urinary miR-1913 to miR-3659 expression ratio was selected and tested in 83 urine samples (44 PCa and 39 BPH) to confirm its validity as a non-invasive diagnostic biomarker for PCa. Results: The expression ratio of urinary miR-1913 to miR-3659 was significantly higher in PCa than in BPH (p=0.002) and showed a higher area under the receiver operating characteristic curve than prostate-specific antigen (PSA; 0.821 vs. 0.518) in patients within the PSA gray zone (tPSA: 3–10 ng/mL), with sensitivity of 75.0% and specificity of 78.6% (p=0.003). Conclusions: The urinary miR-1913 to miR-3659 expression ratio was increased in PCa and may serve as a useful supplemental biomarker to PSA for the diagnosis of PCa, particularly in patients within the PSA gray zone.