자궁경부암을 유발하는 HPV E6 단백질에 의한 p73 단백질의 불활성화 : p53과 무관한 E6의 새로운 기능

남궁성은(Sung Eun Namkoong),김승조(Seung Jo Kim),김은주(Eun Joo Kim),엄수종(Soo Jong Um),박종섭(Jong Sup Park) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

N/A Objective: Human papillomavirus (HPV) is strongly implicated as a causative agent in the etiology of cervical cancer. Of its gene products, E6 and E7 oncoproteins play major roles by inactivation of cellular p53 and pRb tumor suppressor proteins, respectively. However, it has been recently suggested that p53 and/or pRb-independent functions of E6 and E7 are involved in cervical carcinogenesis. The purpose of this study is to identify novel a cellular target, p73, of E6 and to determine how E6 inactivates p73 function, Methods: The interaction between E6 and p73 were identified by the yeast two-hybrid assay in vivo and the GST pull-down assay in vitro. The function of the interaction was determined by transient transfections using p21 promoter-CAT reporter plasmid. The molecular mechanism underlying the functional significance of the interaction was further assessed by in vivo and in vitro protein degradation assays, and gel mobility shift assays. Results: Yeast two-hybrid and GST pull-down assays indicate a physical interaction between p73 and either HPV-16 or HPV-11 E6 proteins in vivo and in vitro, respectively. Transactivation domain (amino acid residues 1-49) is found to be absolutely required for this interaction. Transient co-expression of E6 significantly inhibits the p73-mediated activation of p21 promoter in a p53-defective C33A cell line. Using Ga14-p73 fusion protein, we demonstrate that E6 inhibition of p73 transactivation function is independent of sequence-specific DNA binding, which is confirmed by direct electrophoretic mobility shift assay. Moreover, E6 inhibits p73 function by interfering with the activity of the amino-terminal activation domain. The protein degradation assays in vivo and in vitro indicate that p73, unlike p53, is not susceptible to E6-dependent proteolysis. Conclusion: Throughout this study, we identified p73 as a novel cellular target of HPV-E6 protein and found that E6 binds p73 through the amino-terminal transactivation domain, and inhibits its transactivation function independent of the protein degradation and DNA binding. These overall results, consequently, suggest that in addition to the inactivation of p53, the functional interference of p73 by HPV-E6 may, at least in part, contribute to E6-mediated cellular transformation.

자궁경부암 세포에서 retinoid / interferon 에 의한 성장 억제 조절의 새로운 분자생물학적 기전

김수평(Soo Pyung Kim),남궁성은(Sung Eun Namkoong),김승조(Seung Jo Kim),김은주(Eun Joo Kim),엄수종(Soo Jong Um),박종섭(Jong Sup Park),이근호(Keun Ho Lee),김찬주(Chan Joo Kim) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.3

N/A Objective: Retinoic acids (RAs) and interferons (IFNs) have been implicated in the growth regulation of cervical cancer cells, which was suggested by clinical trials and in vitro experiments. However, the molecular mechanisms of growth regulation are not fully defined, The purpose of this study is to assess the effect of RA and/or IFN on human cervical carcinoma cells in vitro and to analyze their action mechanisms in HPV-positive cervical carcinoma cells by molecular biologic studies. Methods: HPV-positive (CaSki, HeLa), HPV-negative (C33A, HT-3), and non-cervical cancer Cos-1 cell lines were treated with RA and/ar IFN. Their effects on cell growth were evaluated by the cell pmliferation assay and the following BrdU DNA incorporation assay. The molecular mechanism was further investigated by a series of immunoblottings and transient cotransfection assays, which were conducted in HeLa cells and C33A cells using the CAT reporter gene assay. To observe the down regulation of HPV E6/E7 gene expression by RA/IFN, reverse transcription-polymerase chain reaction (RT-PCR) was perforned. Results: The powth of RA-treated cells was less suppressed than that of IFN-treated cells. Combined treatment of RA and IFN leads to additive effect on the growth suppression of HeLa and CaSki cells. The proliferation activity was most severely reduced in Hela cells by treatment of both all-trans-RA (AtRA) and IFN-r. Combined treatment of AtRA/IFN-r causes a great increase in the level of interferon regulatory factor-1 (IRF-1) protein in HeLa cells, whereas no induction of IRF-1 was observed in C33A cells. The CAT gene expression for IRF-1 was greatly induced by IFN-r in HeLa cells. Immunoblotting assays shows the concurrent induction of p21 CDK inhibitor and dephosphorylation of Rb protein in HeLa cells. In RT-PCR, an individual treatment of either RA or IFN reduced HPV E6/E7 mRNA levels and significantly cooperative when both RA and IFN were treated. By deaeasing E6 levels, the p53 level was increased in HeLs cells treated with RA and/or IFN. Transient cotransfection of IRF-1 and p53 as the transcription factors leads to the cooperative activation of a common p21 promoter to regulate the cell cycle. Conclusion: RA/IFN suppressed the growth of HPV-positive cervical cancer cells. When they were both #treated, additive suppressive effects were observed in cellular proliferation as well as DNA synthesis. The growth suppressive effect is likely to be related to the increased expression of IRF-1 and p21 (antitumoral effect; p53-independent). The down regulation of HPV E6 gene suppression may account for the resultant increase of p53 levels (antiviral effect; p53-dependent). Both induced IRF-1 and p53 cooperatively augument tbe suppession of p21 CDK inhibitor, which results in dephosphorylation of pRb. Although clinical effects are likely complex and may include interactions of in vitro growth inhibitory effects with immunomodulatory and antiangiogeaetic effect, tbese results suggest the optimal clinical role for the combination of RA/IFN in the treatment of cervical canccers.

임신시에 발생한 급성호흡곤란증후군을 동반한 한국형 출혈열 1 예

김용욱(Yong Yook Kim),남궁성은(Sung Eun NamKoong),최은(Eun Choi),김미란(Mee Ran Kim),노덕영(Duck Yeong Ro),최옥춘(Ok Choon Choi),노승혜(Seung Hye Rho),김태응(Tae Eung Kim),정재근(Jae Keun Jung) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.7

Hantavirus infection occuring during pregnancy is rarely progressing to adult respiratory distress syndrome (ARDS), which is accompanied by thrombocytopenia, leukocytosis, fever, oliguria, aggravation of bleeding, hematuria, lactacedemia. Pregnancy may have an unfavorable impact on the pathophysiologic characteristics of ARDS. The high oxygen demands of pregnancy are unable to be matched by oxygen delivery in ARDS and may predispose the patient to multiple organ failure, as well as fetal oxygen deprivation. We present the case with hantavirus pulmonary syndrome complicating pregnancy.

The Results of Curative Radiotherapy for Carcinoma of Uterine cervix

강기문,유미령,장지영,서태석,윤세철,박용휘,신경섭,남궁성은,김승조,Kang Ki Mun,Ryu Mi Ryeong,Chang Gee Young,Suh Tae Suk,Yoon Sei Chul,Bahk Yong Whee,Shinn Kyung Sub,Namkoong Sung Eun,Kim Seung Jo The Korean Society for Radiation Oncology 1993 Radiation Oncology Journal Vol.11 No.1

가톨릭의과대학 강남성모병원 치료방사선과에서 1983년 3월부터 1989년 10월까지 79개월 동안에 자궁경부암으로 근치적 방사선치료를 받았던 135명의 환자들 중에서 추적이 가능하였던 120명의 환자들을 대상으로 치료결과및 예후에 영향을 미치는 인자에 대하여 후향적 분석을 하였다. 방사선 단독으로 치료한 환자는 78명이었고 유도 화학요법을 방사선 치료전에 시행한 환자는 42명이었다. 대상 환자들의 추적 조사기간은,2개월에서 106개월이었고 중간 추적조사 기간은 62개월이었다. 환자들의 나이는 32세부터 79세까지의 분포를 보였다(중앙값, 59세). FIGO 병기별 분류에 의하면, IB 기가 20명 ($16.7{\%}$), IIA 기가 19명 ($15.8{\%}$), IIB기가 49명 ($40.8{\%}$), IIIA 기가 5명 ($4.2{\%}$), IIIB기가 13명 ($10.8{\%}$), IVA 기가 14명 ($11.7{\%}$)이었다. 전체환자의 5년 생존율은 $50.8{\%}$였다. 병기별 5년 생존율은 IB 기가 $47.7{\%}$ IIA 기가 $70.2{\%}$, IIB 기가 $64.1{\%}$, IIIA 기가 $40.0{\%}$, IIIB 기가 $23.1{\%}$, IVA 기가 $14.3{\%}$였다. 치료방법에 따른 5년 생존율은 방사선 단독으로 치료한 환자가 $51.2{\%}$였고, 유도화학요법을 방사선 치료전에 시행한 환자는 $54.0{\%}$였다. 치료후 재발은 22명 ($18.3{\%}$,)에서 관찰되었고, 이중 14명 ($11.7{\%}$)에서 국소재발이, 7명 ($5.8{\%}$)에서 원격전이가, 1명 ($0.8{\%}$)에서 국소재발과 원격전이가 함께 발생하였다. 그리고, 치료에 의한 합병증은 41명 ($34.2{\%}$)에서 관찰되었으며 9명 ($7.5{\%}$)에서 습낙설, 8명 ($7.5{\%}$)에서 설사, 7명 ($5.8{\%}$)에서 방사선 직장염의 순으로 발생하였다. 예후와 관련된 생존율에 영향을 주었던 인자로는 나이 (p<0.0291), 병기(p<0.0001), 전신상태(p<0.0041), 초기 혈색소 수치 (p<0.0001), 강내 조사(p<0.0004)였고, 조직학적 소견(p<0.29), 유도 화학요법과의 병행치료(p<0.87)는 통계학적으로 유의하지 않았다. This is a retrospective analysis of 135 patients with invasive carcinoma of the uterine cervix treated with curative radiotherapy from March 1983 through October 1989 at the Department of Therapeutic Radiology, Kang-Nam 51. Mary's Hospital. Among them, 78 patients received radiotherapy alone and 42 patients treated with neoadjuvant chemotherapy followed by radiotherapy and 15 patients were lost to follow up. All patients had follow up from 2 to 106 months (median; 62 months). Age of the patients ranged from 32 to 79 years at presentation (median; 59 years). According to FIGO classification, there were 20 ($16.7{\%}$) in stage IB, 19 ($15.8{\%}$) in stage IIA,49 ($40.8{\%}$) in stage IIB, 5 ($4.2{\%}$) in stage IIIA, 13 ($10.8{\%}$,) in stage IIIB,14 ($11.7{\%}$) in stage IVA. The pathological classification showed 96 ($80.0{\%}$) squamous cell carcinomas, 5 ($4.2{\%}$) adenocarcinomas and 19 ($15.8{\%}$) proven by cytology. The overall 5-year survival rates was $50.8{\%}$, and the 5-year survival rates by stage IB, IIA, IIB, IIIA, IIIB, IVA was $47.7{\%},\;70.2{\%},\;64.1{\%},\;40.0{\%},\;23.1{\%},\;14.3{\%}$, respectively. The 5-year survival rates was noted $51.2{\%}$ of radiotherapy alone and $50.4{\%}$of neoadjuvant chemotherapy followed by radiotherapy. The overall failure rate was $18.3{\%}$(22/120) including $11.7{\%}$ (14/120) locoregional failure, $5.8{\%}$ (7/120) distant metastasis and $0.8{\%}$(1/120) locoregional failure with distant metastasis. Treatment failure rates by the stages were $15{\%}$ (3/20) in stage IB. $10.5{\%}$ (2/19) in stage IIA, $10.2{\%}$, (5/49) in stage IIB, $20{\%}$ (1/5) in stage IIIA, $61.5{\%}$(8/13) in stage IIB, and $28.6{\%}$ (4/14) in stage IVA. The overall complication rate was $34.2{\%}$(41/120) including wet desquamation $7.5{\%}$, (9/120), diarrhea $6.7{\%}(8/120), radiation proctitis $5.8{\%}$(7/120) in decreasing order. A multivariate analysis of factors influencing the survival showed patient age (p < 0.0291), FIGO stage (p<0.0001), Karnofsky performance status (p<0.0043), initial hemoglobin level (p<0.0001), and intracavitary radiation (p<0.0004), but, no significancy in histology (p<0.29) and treatment method (p < 0.87).

자궁경부암 치료에서 p53 종양억제유전자의 플라스미드와 아데노바이러스를 이용한 유전자 치료법의 개발

이준모(Jun Mo Lee),김승조(Seung Jo Kim),남궁성은(Sung Eun NamKoong),조성대(Sung Dae Cho),황성진(Seong Jin Hwang),박현라(Hyun Ra Park),한유진(You Jin Han),김상태(Sang Tae Kim),이헌영(Hun Young Lee),김동재(Dong Jae Kim),박용석(Yong Serk 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.9

연구배경: 악성종양의 치료법에서 근간을 이루고 있는 방법은 수술, 방사선과 항암요법이다. 이와같은 치료에도 불구하고 종양세포의 파괴를 주 목표로 하고 있는 현재의 치료법은 그 한계에 도달하고 있다. 따라서 앞으로 종양치료의 방향은 이미 언급한 고식적인 방법과 아울러 종양에 대한 인체의 면역 반응을 항진시켜 종양세포 손상을 유도하는 유전자 치료쪽으로 연구가 진행되어야 할 것으로 사료되어 연구를 시작하였다. 연구목적: 자궁경부암의 유전자 치료를 위하여 자궁경부암 세포주들에 리포솜을 이용한 종양억제 유전자의 직접 이입법 (pRcCMVp53/ lipofectin)과 아데노 바이러스 (AdCMVp53)를 이용한 간접이입법에 의한 종양세포의 성장억제효과를 보고자 하였다. 연구방법: 이 연구에 사용한 자궁경부암 세포주들은 억제 유전자인 야생형 p53유전자를 가지고 있고 인유두종 바이러스 (human papilloma virus : HPV) 16 양성을 나타내는 CaSki, SiHa 세포주, HPV 18 양성을 나타내는 HeLa, HeLaS3 세포주와 HPV 음성을 나타내는 C33A, HT3 세포주이었다. LacZ를 표지유전자로 사용하여 그 이입효율을 확인 하였으며 인체 자궁경부암세포주로의 유전자의 직접 이입법으로는 lipofectin을 매개로 한 방법(pRcCMVp53/lipofectin)을 사용하였고 간접이입법으로는 바이러스를 사용한 AdCMVp53를 사용하였다. 암세포 성장억제 효과는 세포수 측정을 통해 확인하였다. 결과: p53 유전자의 이입에의한 자궁경부암 세포주의 성장억제는 직접이입법에의한 (pRcCMVp53/lipofectin) 경우 CaSki에서는 88.5%, SiHa는 59.1%, HeLa는86.0%, HeLaS3는 78.0%, C33A는 91.3%, 그리고 HT3에서는 74.0%의 성장억제를 나타냈다. 간접이입법 (AdCMVp53)에 의한 세포수 측정에서 CaSki인 경우에는 97.4%, SiHa는 91.6%, HeLa는 95.8%, HeLaS3는 99.7%, C33A는 97.3%, 그리고 HT3에서는 87.4%의 성장억제를 나타냈다. 결론: 자궁경부암 세포주에 직, 간접 이입법을 통한 억제유전자 전달 후 세포성장 억제는 HPV 양, 음성 모든세포주에서 매우 유의하게 감소되었으며 CaSki, HeLa세포주인 경우 직·간접 이입법에서는 유의한 차이가 없었으나 SiHa, HeLaS3, C33A세포주에서는 간접법 HT3세포주에서는 직접법이 좋은 것으로 나타났다. 이와같은 결과는 향후 자궁경부암 환자에 있어서 억제유전자의 직·간접이입법에 의한 유전자 치료를 실시할 수 있는 새로운 장으로 그 의의가 클것으로 생각 되어진다. Background: The basic treatment of malignant tumors is surgery, radiotherapy, chemotherapy. Even though, the object of these treatments is to kill cancer cells, they have limitations. So, in future studies of treatment of cancer, we should look into increasing human immune response using gene therapy in order to induce damage to tumor cells. Objective: The cell growth inhibitory effect of cervical cancer cells was investigated by direct transfection using liposome(pRcCMVp53/lipofectin). and by indirect transfection using Adenovirus(AdCMVp53). Methods: The cervical cancer cell lines we used in this study were HPV16 positive, having inhibitory gene, wild p53 gene, CaSki, SiHa, HPV18 positive HeLa, HeLaS3 and HPV negative C33A, HT3, LacZ gene was used as the marker gene for the transfection efficacy. Direct transfection was done by using lipofectin (pRcCMVp53/lipofectin) and indirect transfection was done by using virus, AdCMVp53. The effect of tumor cell growth inhibition was measured by cell counting assay. Result: Inhibition of growth of cervical cancer cells in cell counts of direct transfection was CaSki(88.5%), SiHa(59.1%), HeLa(86.0%), HeLaS3(78.0%), C33A(91.3%) and HT3(74.0%). Inhibition of growth of cervical cancer cells in cell counts of indirect transfection was CaSki(97.4%), SiHa(91.6%), HeLa(95.8%), HeLaS3(99.7%), C33A(97.3%) and HT3(87.4%). Conclusion : The inhibition of cell growth of cervical cancer cells by direct and indirect transfection was significantly reduced, and showed little differences depending on the type of cells. These results will have a great meaning in treating cervical cancer patients using gene therapy by direct or indirect transfection

수술 후 국소재발한 자궁경부암에서의 방사선치료 성적

유미령(Mi Ryeong Ryu),계철승(Chul Seung Kay),강기문(Ki Moon Kang),김연실(Yeon Shil Kim),정수미(Su Mi Chung),남궁성은(Sung Eun Namkoong),윤세철(Sei Chul Yoon) 대한방사선종양학회 1999 Radiation Oncology Journal Vol.17 No.3

목 적 : 근치적 수술 후 국소재발한 자궁경부암 치료에 있어서 방사선치료의 역할 및 치료 결과에 영향을 미치는 인자들을 분석하고자 본 연구를 시행하였다. 대상 및 방법 : 1983년 10월부터 1996년 7월까지 가톨릭대학교 강남성모병원 치료방사선과에서 FIGO병기 I, II 자궁경부암의 근치적 수술 후 국소재발한 환자 중 방사선치료를 받았던 53명을 대상으로 치료결과에 대한 후향적 분석을 시행하였다. 환자의 연령은 33세에서 69세 사이(중앙값 53세)였으며, 병리조직학적 분류로는 편평상피암이 45명(84.9%), 선암이 7명(13.2%), 편평상피선암이 1명(1.9%)이었다. 수술 후 재발까지의 기간은 2 개월에서 25년 사이로 평균 34.4 개월이었다. 재발한 병소의 위치에 따라서 질 절제단(vaginal stump )이 41명(77.4%), 골반외벽(pelvic side wall)이 12명(22.6%)이었고, 재발한 병소를 크기에 따라 나누었을 때 3cm 이하인 경우가 43명(81.1%), 3 cm보다 큰 경우가 10명(18.9%)이었다. 방사선치료는 대부분 환자에서 전골반에 외부 방사선치료를 하루 1.8 Gy 의 양으로 주 5회씩 치료하여 46.8∼50.4 Gy 까지 치료한 후, 18명(34%)에서는 병소부위에 외 부방사선치료를, 24명(45.3%)의 환자에서는 강내근접치료를 각각 추가하여 총방사선량 46.8∼111 Gy(중앙값 70.2 Gy)까지 치료하였다. 추적조사 기간은 2 개월에서 153 개월 사이(중앙값 35 개월)였다. 결 과 : 방사선치료후 초기관해율은 66% (35/53) 이었고, 이 중 6명(17.1%)에서 방사선치료후 7 개월에서 116 개월사이(평균 47.7 개월)에 다시 국소재발하여 전체환자의 국소재발율은 45.3%였다. 전체환자의 5년 생존율은 78.9%였으며, 원격전이율은 10% (5/50)로 발생부위별로는 폐 2명, 뇌 1명, 원격 임파절 2명이었다. 생존율에 영향을 미치는 인자로는 수술후 재발까지의 기간( p=0.0055), 재발 병소의 크기( p=0.0039), 방사선치료에 대한 초기반응 유무( p=0.0428) 등으로 분석되었으며, 그 외에 초기 병기, 연령, 조직학적 유형, 재발병소의 위치, 방사선 조사량, 약물치료 유무 등은 영향이 없는 것으로 나타났다( p>0.05). 방사선치료의 합병증은 10명(20%)에서 발생하였으나, 대부분 경미하거나 중등도의 하부위장관 또는 비뇨기계, 피부 합병 증이었고, 한명이 강내 방사선치료 직후 폐전색증으로 사망하였다. 결 론 : 근치적 수술 후 국소재발한 자궁경부암 환자에서 방사선치료는 매우 효과적이며, 수술 후 재발까지의 기간, 재발병소의 크기, 방사선치료에 대한 초기반응 등이 예후에 영향을 미치는 인자로 나타났다. Purpose : To evaluate prognostic factors and survival rates of the patients who received radiation therapy for locally recurrent uterine cervical cancer after curative surgery. Materials and Methods : Between October 1983 and July 1996, fifty three patients who received radiation therapy for locally recurrent cervical cancer after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, The Catholic University of Korea were analysed retrospectively. Age at diagn osis ranged from 33 to 69 years (median 53 years). Pathological analysis showed that forty five (84.9%) patients had squamous cell carcinoma, seven (13.2%) patients had adenocarcinoma, and one (1.9%) patient had adenosquamous cell carcinoma. The interval between hysterectomy and tumor recurrence ranged from 2 months to 25 years (mean 34.4 months). The recurrent sites were vaginal stump in 41 patients (77.4%) and pelvic side wall in 12 patients (22.6%). Recurrent tumor size was devided into two groups : less than 3 cm in 43 patients (81.1%) and more than 3cm in 10 patients (18.9%). External beam irradiation of whole pelvis was done first up to 46.8 Gy to 50.4 Gy in 5 weeks to 6 weeks, followed by either external beam boost to the recurrent site in 18 patient s (34%) or intracavitary irradiation in 24 patients (45.3%). Total dose of radiation ranged from 46.8 Gy to 111 Gy (median 70.2 Gy). Follow up period ranged from 2 to 153 months with a median of 35 months. Results : Overall response rate was 66% (35/53). Among them, six patients (17.1%) relapsed between 7 months and 116 months after radiation therapy (mean 47.7 months). Therefore overall recurrence rate was 45.3%. Overall five-year actuarial survival rate was 78.9% and distant failure rate was 10% (5/50). The significant prognostic factors affecting survival rate were interval between primary surgery and tumor recurrence ( p=0.0055), recurrent tumor size (p=0.0039), and initial response to radiation therapy (p=0.0428). Complications were observed in 10 (20%) patients, which included mild to moderate lower gastrointestinal, genitourinary, or skin manifestations. One patient died of pulmonary embolism just after intracavitary irradiation. Conclusion : Radiation therapy is the effective treatment for the patients with locally recurrent cervical cancer after curative surgery. These results suggest that interval between primary surgery and tumor recurrence, recurrrent tumor size, and initial response to radiation therapy were significant prognostic factors for recur rent cervical cancer.

자궁경관에 발생한 최소이탈 선종 1 예

최원석(Won Suk Choi),임채춘(Chae Chun Rhim),이성종(Sung Jong Lee),진기홍(Ki Hong Jin),홍승표(Seung Pyo Hong),김동주(Dong Joo Kim),이연수(Youn Soo Lee),남궁성은(Sung Eun Namkoong) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.2

Minimal deviation adenocarcinoma (adenoma malignum) is a variant of adenocarcinoma and is expressed from uterine endocervix. As a result of ever reported cases in the world, it is rare enough to occur in 1 to 2% of invasive cervical adenocarcinoma. Minimal deviation adenocarcinoma is well-differentiated form of adenocarcinoma in which the cytoplasmic mucin is rich and the glandular pattern simulates that of normal endocervical glands. Because of this, the tumor may not be recognized as malignant in small specimens, thereby causing delay in diagnosis. But recent studies have found a favorable prognosis if the disease is detected early. We experienced a case of minimal deviation adenocarcinoma, rare disease in the world, so we report with a brief review of literature.

AGUS 세포진을 가진 여성의 평가에 있어서 HPV test의 의의

김찬주(Chan Joo Kim),박태철(Tae Chul Park),박종섭(Jong Sup Park),이준모(Jun Mo Lee),김승조(Seung Jo Kim),남궁성은(Sung Eun NamKoong) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.7

목적 : AGUS는 자궁 경부의 선조직에서 발생한 HSIL같은 자궁암을 종종 반영한다. 이에 저자들은 세포진 검사상 AGUS로 진단된 여성의 임상적 중요성을 알아보고, AGUS의 관리와 평가에 있어 HPV 검사가 가지는 의의를 알아보기 위함이다. 연구 방법 : 1994년에서 1998년 기간에 강남 성모 병원과 의정부 성모 병원에서 시행된 67,730 예의 세포진 검사에서 AGUS로 진단된 87 명 (0.13%) 에 대하여 그 최종 진단과 평가 방법에 대하여 조사하였다. HPV 검사를 시행한 11명의 환자에 대하여 그 예민도를 알아보앗다. 결과 : 대상 환자의 평균 연령은 45.8세였다. AGUS 조직생검에 의하면 kolocytosis와 CIN-I 병변이 6명에서 발견되었고 (6.9%), CIS가 1명 (1.1%), 자궁 내막 증식증이 2명 (2.3%), 자궁내막의 선암이 7명 (8.0%)에서 발견되었고, 자궁 경부의 선암이 14명 (16.1%), 자궁 경부의 편평상피세포암이 2명(2.3%)에서 발견되었다. 평균 연령인 46세 미만에서 자궁내막증은 8.9%였고, 46세 이상에서는 없었다. CIN 병변은 46세 미만에서는 8.9%, 46세 이상에서는 7.2%였으며, 자궁 경부 선암은 46세 미만과 이상에서 각각 6.7%, 19.1%였다. 자궁 내막암은 4.4%와 11.9%로 46세 이상의 연령에서 자궁 경부암과 자궁내막암에 대한 주의가 필요한 것으로 생각된다. HPV 검사는 CIN 이상의 자궁 경부 병변에 대한 예민도는 AGUS 환자에서 75% 였으며, 음성 예측률은 87.5%였다. 결론 : AGUS로 진단된 상당수의 여성이 임상적으로 의미있는 CIN이상의 병변을 가지고 있었으며, HPV 검사는 AGUS 진단의 평가와 관리에 유용한 방법이 될 것으로 생각된다. Objectives : AGUS often reflects an immediate cervical cancer precursor such as a HSIL mimicking an endocervical glandular lesion. In this study, we attempted to assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the usefulness of the human papillomavirus (HPV) DNA testing as the triage strategies in evaluating AGUS. Methods : Between 1994 and 1998, 67,730 Papanicolaou smears were evaluated at Kangnam and Uijongbu St Mary's Hospital. There were 87 (0.13%) cases of AGUS smears during that time. Colposcopy was performed on all women, and HPV DNA testing was performed on 11 persons. Results : Mean age of these patients was 45.8 years. Histologic diagnosis of AGUS were kolocytosis and CIN-I in 6 (6.9%), CIS in one, endometrial hyperplasia in 2 (2.3%), endometrial adenocarcinoma in 7 (8.0%), cervical adenocarcinoma in 14 (16.1%) and cervical squamous cell carcinoma in 2 (2.3%) cases. Endometriosis was 8.9% under 46 years old and none in over 46. CIN was 8.9% and 7.2%, respectively. Cervical adenocarcinoma was 6.7% under 46 and 19.1% over 46. Endometrial cancer was 4.4% and 11.9%, respectively. The risk of cervical cancer and endometrial cancer was high in the AGUS with >= 46 years old. The sensitivity for the prediction of CIN and cervical cancer by Hybrid Capture HPV testing was 75% and negative predictive value was 87.5%. Conclusion : A significant proportion of women with a cytologic diagnosis of AGUS have abnormal histopathology. Use of HPV DNA testing in patients with AGUS may provide improvements in the management of woman with AGUS.

동시에 발견된 원발성 부인암에 대한 임상적 분석

동서연 ( Seo Yun Tong ),이용석 ( Yong Sek Lee ),박종섭 ( Jong Sup Park ),이준모 ( Jun Mo Lee ),남궁성은 ( Seung Eun Namkoong ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.9

목적: 부인과 영역에서 동시에 발생하는 원발암에 대한 임상적 분석을 통해 발생 빈도, 임상적 특징 및 예후를 알아보고자 한다. 연구 방법: 2000년 2월부터 2005년 1월까지 부인암을 진단 받은 환자 중 다발성 일차암으로 진단된 환자를 대상으로 임상병리적 특징, 치료 및 치료 후 결과에 대해 후향적으로 고찰하였다. 결과: 같은 기간에 부인암을 진단 받은 환자는 모두 3164명으로 그 중 20명이 동시성 일차암으로 진단되어 0.63%의 빈도를 나타내었다. 이중 생식기에 다발성 종양은 13명이었고 가장 많은 동시성 일차암은 자궁내막암과 난소암으로 20명 중 8명이었다 (40%). 자궁내막암과 난소암이 동시에 발생한 경우는 평균연령이 45.2세로 각각 종양이 발생한 경우보다 비교적 빠른 나이에 발생하였고, 조직학적으로는 자궁내막선암과 난소의 자궁내막양 선암이 동반된 경우가 5예로 빈도가 높았다. 수술 후 추적관찰기간 동안 2명의 환자가 사망하였고, 평균 생존 기간은 57개월 (SE 10.0, 95% Confidence interval 37-77)이었다. 결론: 부인암과 동시에 발생하는 원발암은 비교적 드문 질환이다. 그 중 자궁내막암과 난소암의 빈도가 가장 높고 일반적으로 단일암보다 젊은 나이에 발생하며, 수술과 보조적 치료로 비교적 좋은 예후를 기대할 수 있다. Objective: A histopathologic review of synchronous primary neoplasms of the female reproductive tract was presented and the possible correlation among discrete tumor subsets, natural history, and survival was evaluated. Methods: Between 2000 and 2005, 20 patients with synchronous primary cancers of the gynecologic malignancy were identified. Clinical and pathologic informations were obtained from medical records. Kaplan-Meier survival analysis was performed. Results: The patients with Synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasms were those of the ovary with the endometrium (40%). The mean age of patient with synchronous ovarian and endometrial cancer was 45.2 years. 8 patients underwent the hysterectomy with bilateral salpingo-oophorectomy and adjuvant therapy. The mean survival is 57 months (SE 10.0, 95% Confidence interval 37-77). Conclusion: Synchronous ovarian and endometrial cancers were detected in relatively early age and the prognosis was favorable.

ATP에 의한 자궁경부암 세포내 NF-κB와 칼슘이온의 변화

임대석 ( Dae Seog Lim ),배수미 ( Su Mi Bae ),곽선영 ( Sun Young Kwak ),정국화 ( Guo Hua Ding ),김정 ( Jeong Kim ),김용욱 ( Yong Wook Kim ),노덕영 ( Duck Yeong Ro ),이준모 ( Joon Mo Lee ),남궁성은 ( Seung Eun Namkoong ),조영래 ( Yo 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.12