한국형 자궁경부 촬영진 ( New Cervicography ) , 세포검사 그리고 HPV-DNA 검사를 이용한 새로운 자궁경부암 검진 모델 ( Model ) 개발

김승조(SJ Kim),박찬규(CK Park),이효표(HP Lee),남궁성은(SE Namkoong),강순범(SB Kang),서호석(HS Saw),이재관(JK Lee),김수녕(SN Kim),김재원(JW Kim),배석년(SN Bae),김찬주(CJ Kim),이근호(KH Lee),이선영(SY Lee),김인호(IH Kim),이찬(C Lee),이정노(JN Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Objective : The false negative rate of conventional cytology is reported to range from 18 to 45%. It is necessary to develop more effective screening strategies that would ideally be more accurate than conventional cytology. This study is designed to investigate the potential of conventional cytology, cervicography, HPV-DNA testing and their combinations as primary screening techniques for cervical neoplasia. The purpose of this project is to develop the models and guidelines for screening tools of cervical cancer of the uterus by evaluating sensitivity, specificity and cost-effectiveness of all the screening methods. Study design : We conducted a screening of random sample of women who visited the department of OB-Gyn. of five different major university hospitals such as Catholic University Hospital, Korea University Hospital, Seoul National University Hospital, Yeonsei University Hospital and Pochon CHA University Bundang CHA Hospital, from May 1, 1996 to April 30, 1999. In a cohort women with an age range of 20 to 70 who underwent routine cytologic screening at Catholic University, Hospital Bundang CHA General Hospital and local clinics from April 1, 1996 to Decomber 31, 2000. cervicography (n=417,125) and testing for HPV-DNA (n=1,347) by the hybrid capture assay were studied for the ability of the cervical cancer screeuing. A new cervicography system with Kim's classification which was developed by Prof. Kim Seung Jo as an adjunctive method for the cervical cancer screening was applied in this cohort study. And then, accuracy, effectivencess, cost-effectiveness of the single or combined screening method were analysed. Result : Sensitivity and specificity of Pap smear were ranged from 55.6% to 83.1% and 72.8% to 88.3% respectively. The combination of Pap smear and cervicography had sensitivity from 89.7% to 98.6%, specificity from 68.2% to 93.2%. With combination of Pap smear, HPV DNA test and cervicography, sensitivity became also highest accuracy among all screening methods from 92.8% to 98.8%. Considering medical charges for diagnosis and social cost occurred by false positive and false negative results, the most cost-effective diagnostic modality was thought to be the combination of Pap smear and cervicography(91,433 won). In patients who were diagnosed as LSIL, colposcopic examination confirmed progression to high grade intraepithelial lesion(HSIL) in 10.7% patients, persistence of LSIL in 55% patients during the 3 year follow-up period. Accuracy of the screening for cervical cancer and CIN can significantly be improved by cytology with new cervicography rather than cytology alone. We concluded that cervicography can be important adjunctive tests for cervical cytology, improving the effectiveness of cervical screening by allowing a more sensitive detection of cervical neoplasia.

자미꾸리 ( 추어 - Misgurnus Anguillicaudatus CANTOR ) 를 사용한 포상기태 뇨반응 및 임신뇨반응에 관한 연구 ( 제1보 )

김정완(JW Kim) 대한산부인과학회 1961 Obstetrics & Gynecology Science Vol.4 No.2

1. 저자는 자미꾸리 성어를 실험동물로서 사용하는 새로운 포상기태뇨반응 및 임신뇨반응의 시험법을 고안하여 잠정적으로 『김씨반응』(Kim`s test)이라고 명명하였다. 2. 저자는 자미꾸리 성어에 산란현상을 일으켜 양성으로 반응시킬 Gonadotrophin의 최소량을 1미꾸리 단위(L.U)라고 정하였다. 3. 이 반응을 포상기태뇨 21예 및 악성융모상피종뇨 2예에 시험한 결과 100%의 양성율을 얻어 임신과 감별되었고, 위반응은 대조뇨 즉 46일~100일 임뇨 165예중 8예 즉 4.84%였다. 4. 임부뇨 260예중 234예가 양성으로 반응하여 90.00%이었으며 위반응은 대조인 비임부뇨 229예중 16예 양성으로서 6.98%였다. 5. 이 반응은 단 1회의 시험만으로서 포상기태, 임신 및 비임신을 감별할 수 있었다. The author`s attention was called to the fact that adult female loaches do not spawn until they copulate in spite of carrying a large quantity of eggs around the year, and there is the possibility that an artificial spawning might be brought about by the administration of urine rich in gonadotrophin. In the light of this, the author developed a new test by administering patient`s urine to a loach for the diagnosis of hydatidiform mole and pregnancy, and its value was confirmed by various preliminary studies. The test was applied to 21 cases of hydatidiform mole and two cases of chorionepithelioma malignum, obtaining strongly positive reactions (++) in all cases it made the differentiaion of these conditions from pregnancy possible. In another study, 165 urine specimens from women of 46 to 100 day gestation were tested obtaining trongly positive reactions (++) in only eight specimens, resulting in 4.84% false positivity. Similar test was done utilizing 260 specimens of pregnant women in which 234 specimens (90%) were found to be positive (+) whereas out of 229 specimens of urine of nonpregnant women only 16 (6.98%) reacted positively (+). It was found that one of the most prominent features of this that is test it enabled us to differentiate between pregnancy, non-pregnancy and hydatidiform mole by a single test. In addition, this test is highly reliable and practical in diagnosing early pregnancy. The author temporarily named this test as Kim`s Test.

뇌혈관질환 환자의 후유증의 개선에 대한 Propentofylline(HWA 285)의 임상 연구

최영빈,박정욱,한시령,양동원,나정호,김범생 최신의학사 1994 最新醫學 Vol.37 No.6

인간 상피성 자궁경부암 세포주 (CUMC-6) 의 확립 및 특징화

김승조,정재근,김진우,남궁성은,박태철,김흥기,김수평,김사진,김태웅,김재훈 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.1

본 연구진은 31세된 한국여성의 자궁경부암 종양조직을 채취한 후 세포배양을 통하여 자궁경부의 편평상피암 세포주(CUMC-6)를 새로이 확립하여 시험관내 성장특성, 세포의 형태학적 특성, 세포의 초미세 구조, 생체내 종양형성 능력, 동위효소 발현, 염색체 특성, 호르몬 및 태반단백 분비, 종양표지물질분비, 스테로이드 호르몬 수용체 여부, 인체 백혈구 항원의 규명, 인유두종 바이러스(HPV) 감염,c-myc및 L-myc 발암유전자들의 변이, 및 p53 종양 억제 유전자의 변이여부를 검색하여 다음과 같은 결과를 얻었다. 1. 자궁경부암 세포주는 현재 61개월간 배양중에 있으며 지속적인 성장을 보였고 현재까지 연속적으로 300계대까지 수행되었다. 2. 배양중인 종양세포의 성장특성을 분석한 결과 population doubling time은 약 36시간이었으며 plating efficiency는 32%로 나타났다. 3. 배양세포주의 형태학적 특성을 규명하고자 위상차 현미경 소견, H & E 염색, Papanicolaou`s 염색 및 전자현미경적 방법 등을 이용한 결과 인간 상피세포 유래 종양임을 확인할 수 있다. 4. 배양세포주를 누드마우스에 이종이식시켜 종양의 형태학적 변화를 분석한 결과 형성된 종양조직은 본래의 조직소견과 유사하였으나 분화정도는 나빴다. 또한, 종양형성 능력을 파악한 결과 2주 이내에 96%의 높은 종양형성 능력을 보였다. 5. 자궁암 세포주의 glucose-6-phosphate dehydrogenase 동위효소 분석시 type B pattern을 보여 기존의 HeLa 세포주와의 실험실내 오염이 아닌것으로 판명되었다. 6. CUMC-6 종양세포주들의 염색체 분석시 대부분의 세포들은 이배수성(2n-46)을 나타내었으며 약 20%의 세포들에서 7번 염색체 하나가 더 많은 삼배수성(trisomy)을 보였다. 7. 태반단백, 호르몬 및 종양표지물질 분비여부를 검색한 결과 태반단백으로서는 B-HCG 분비를 확인하였고, 또한 종양표지물질로서는 AFP분비를 확인하였다. 8. 종양세포주의 에스트로겐 및 프로게스테론 수용체 존재여부를 분석한 결과 각각 음성으로 판정되었다. 9. 종양세포주의 인체 백혈구항원(human leukocyte antigen) 검색 결과 HLA class II phenotype 들은 DR12와 DQw3로 나타났으며, HLA class II allele specificity들은 DRB1*1202, DQA1*0601 , 및DQB1*03*들로 판명되었다. 10. 배양된 CUMC-6 세포주에서 HPV 감염여부를 검색하기 위하여 polymerase chain reaction(PCR) 을 실시한 결과 HVP 16과 HVP 18이 동시에 감염되어 있는것을 확인할 수 있었다. 11. CUMC-6 세포주에서 c-myc 유전자는 재배열 및 증폭소견들을 보여주었으나 L-myc 유전자의 재배열 및 증폭 소견들은 발견되지 않았다. 12. Polymerase chain reaction-signle strand conformation polymorphism(PCR-SSCP)방법으로 배양된 CUMC-6 세포주에서 p53 종양억제 유전자의 변이는 관찰되지 않았다. 이와같이 특징화 과정이 완료된 CUMC-6 자궁경부 상피암 세포주는 향후 한국 여성의 자궁경부암 치료와 생물학적 연구에 적절한 실험 모델이 될것으로 사료되며 자궁경부 상피암의 발생기전에 염색체 1번의 이상, c-myc 발암유전자의 변이, 및 HVP 감염등이 복합적으로 관여하는 것을 파악할 수 있었다. A new cell line, CUMC-6, has been derived from an invasive non-keratinizing squamous cell carcinoma of the uterine cervix in a 31-year-old patient. It has been maintained in long term culture for 61 months, and passaged over 300 times. The results were as follows; 1. Monolayer-cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. 2. The epithelial nature of the cultured CUMC-6 cells was confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. 3. The sbucutaneous injection of cultured cells into nude mice gave rise to fast growing tumor. The transplanted tumor showed similar histological features, but poor differentiation than the original tumor. 4. Repeated chromosome analysis revealed that most metaphases of this cell line contained diploid number of chromosomes. The consistently observed structural abnormality in this cell line was elongation of short arm of chromosome 1. The G-banded pattern of this chromosome was inv dup (1)(1pter-$gt;1p34:: 1p21-$gt;34:: 1p34-$gt;1qter). 5. The results of isozyme analyses were distinct from the HeLa cell line. 6. Cultured CUMC-6 cells produced human chorionic gonadotropin B-subunit(B-HCG),and a-fetoprotein(AFP). 7. Cytosol estrogen and progesterone receptors were not measured in this cell line. 8. Human leukocyte antigen(HLA) typing of CUMC-6 cells indicated the presence of DR12 and DQw3. 9. Analysis of the DNA extracted from the CUMC-6 cells showed the presence of human papillomavirus(HPV) type 16 and 18 DNAs. 10. Southern blotting technique revealed ampification and rearrangement of oncogene c-myc and no amplification of L-myc. 11. Using the polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) technique, we have screened CUMC-6 cells for p53 mutation in exons 4 to 9. No mobility shift was observed in this cell cline. This cell line will be a valuable tool in studying the in vitro and in vivo properties of human cervical carcinoma.

관상동맥 스텐트 재협착 치료를 위한 “커팅 벌룬” 혈관성형술 후 혈관조영술상 성적 및 재발성 재협착의 예측인자

이수훈,김두일,김진우,차광수,이성윤,김상곤,조길현,오주현,김원,김무현,김영대,안태훈,정명호,김동수,강정채,신익균,김종성 대한순환기학회 2003 Korean Circulation Journal Vol.33 No.3

p16 유전자가 삽입된 재조합 아데노 바이러스에 의한 난소암 세포주의 시험관내 성작 억제

김승조,김진우,남궁성은,김장흡,김수평,김용욱,김태웅,신재인,Judith K. Wolf 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.4

암억제유전자로 알려진 p16 유전자를 재조합 아데노바이러스를 사용하여 난소암 세포주에 이입시킨 후 발생하는 변화를 관찰하였다. 아데노바이러스의 난소암 세포주 이입률은 폐암의 경우보다 낮았지만, p16 유전자 이입 후 24시간부터 6일간의 관찰기간 동안 고농도의 p16 단백질이 난소암 세포주에서 발현되었다. 난소암 세포주의 성장억제는 SKOV3 세포주의 경우 78%, OVCA420 세포주의 경우 77%이었고, 동시에 세포 변성의 형태학적 소견을 보였으며, 세포주기 분석에서 두 세포주 모두 G1상에 정지되는 세포의 수가 증가하는 것을 확인하였다. 난소암 세포주에 p16 유전자를 이입 후 성장억제가 확인되었으므로, 기존 항암요법의 보조요법으로 암억제유전자를 사용할 수 있을 것으로 사료된다. Objective: The cell cycle regulatory p16 protein (the product of the CDKN2A gene also called p16INK4A, CDK4I, and MTS-1) causes cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D and CDK4/6 complexes. The purpose of this study is to assess the growth suppressive effect by introduction of the p16 gene into two ovarian cancer cell lines via a recombinant adenoviral vector (Ad5CMV-p16). Methods: The cell lines used for this study are: SKOV3 (deletion of the p16 gene) and OVCA 420 (no mutation along the coding region of the p16 gene by SSCP). To assess the transduction efficiency, cells were with an adenovirus containing Escherichia coli -galactosidase gene (Ad5CMV-LacZ) at different multiplicity of infection (MOI) from 0-500; then stained for X-gal. To assess the effects on cell growth, cells were infected with Ad5CMV-p16 then counted every other day up to 7 days. Controls were mock-infected cells and cells infected with Ad5CMV-LacZ. Western blot and cell cycle analysis were done to assess expression of the p16 gene. Results: The transduction efficiencies were 80% with an MOI of 100 in SKOV3 cells and 75% with an MOI of 250 in OVCA 420 cells. Growth of the Ad5CMV-p16 infected cells was suppressed over 75% by cell count in both cell lines with significant morphological changes of cells. The p16 protein was detected in both cell lines by Western blot analysis 24 hours after introduction of the p16 gene and expressed for at least 6 days. A clear shift to G1 phase was found in Ad5CMV-p16 infected cells of both cell lines by cell cycle analysis. Conclusion: These results suggest that Ad5CMV-p16 may be further studied as a potential therapeutic agent for ovarian cancer since introduction of the p16 gene into two ovarian cancer cell lines attenuates their growth.

자궁경부암 세포주들에서 Transforming Growth Factor-β1의 세포성장 및 c-myc암유전자 발현 억제효과

김승조,이헌영,김진우,김미란,남궁성은,박태철,김태웅,김재훈 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.1

Transforming growth factor-β1(TGF-β1) is known to be a potent growth inhibitor for many cell types, including most epithelial cells. In skin keratinocytes, TGF-β1 has been shown to inhibit growth and to rapidly reduce c-myc expression. However, the molecular mechanism of TGF-β1 action on cell growth of cervical carcinoma has not yet been elucidated. We thus assessed the effect of TGF-β1 on the growth of cervical carcinoma cell lines. Two cervical squamous carcinoma cell lines were incubated with varying concentration of TGF-β 1, and growth inhibition was evaluated with tetrazolium-based colorimetric assay. After culturing in concentrations of 0.1~10 ng/ml in both cell lines. Northern blot analysis revealed c-myc mRNA expression was suppressed by 10 ng/ml of TGF-β 1 following 6-hour of treatment in both cell lines. These results suggest that TGF-β1 inhibits the growth of cervical carcinoma cells by suppressing c-myc oncogene expression.

Discovery of Cathepsin K Inhibitors Using Fluorogenic Assay

NC Kim,YH Jung,JH Lee,HJ Hwang,YA Shin,SJ Lee,CH Lee,BY Lee,JW Lee,EJ Bae,MK Kim,MH Son,HT Shin,KJ Lim,SH Kim,WB Kim 대한약학회 1999 大韓藥學會 總會 및 學術大會 Vol.48 No.-

導入 機器의 效率的 活用을 위한 敎授-學習 敎材의 開發 : 8 個 學科 共同 硏究

李昌甲,孟琦錫,李載元,朴萬植,廷吉煥,金鍾悟,朴景采,李英浩,李東周,邕章祐,柳盛淵,趙澤東,姜理錫,李殷雄,李興浩,金健中,韓相玉,金良模,張錫明,朴俊灝,洪鳳植,金太均,金再韓,宋海永,盧載星 충남대학교 공업교육연구소 1982 論文集 Vol.5 No.1

In this study, through the combined effort and collaboration of 8 engineering education departments, teaching-learning processes and models were reviewed, and printed and bound student manuals developed on 120 different tasks and subjects. Audio-visual supportive material, already in use in laboratories, was added to form a complete teaching-learning package. In addition to promoting the maximum use of the newly acquired equipment, this study will also contribute to the development of laboratory practice, the in-service training of technical high schools teachers and help in the development of their own instructional program.

고콜레스테롤혈증 환자에 대한 아토바스타틴의 효과와 안전성을 검토하기 위한 다기관 공동 임상 연구

배종화,최경훈,전재은,박의현,김권배,김기식,이재우,이원로,박정의,최윤식,권영주,강정채,김종준,문용,홍순표,김태호,김영조,심봉섭,박승정,정진원,이건주,최규보,임종윤,이방헌 대한순환기학회 2001 Korean Circulation Journal Vol.31 No.4