자궁경부 원추절제술 후 시행한 자궁경관내 세포진 검사의 역할에 관한 연구

윤만수(Man Soo Yoon),이규섭(Kyu Sup Lee),최욱환(Ook Hwan Choi),김원희(Won Whe Kim) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.6

Objective : To evaluate the impact of the cytologic smear of the endocervical canal immediately after cervical conization on the rate of residual cervical lesions. Method : A retrospective review of 229 patients who underwent cervical conization for high grade cervical intraepithelial neoplasia or microinvasive cancer followed by hysterectomy. Endocervical Papanicolaou smear with a cytologic brush performed immediately after cervical conization in all 229 patients. Results : Fifty-four of 229 patients undergoing cervical conization followed by hysterectomy had residual lesion in the hysterectomy specimen. The prevalence rate of residual lesion according to the margin status of conization specimen as well as the results of the postconization Papanicolaou smear of the endocervical canal was compared. Forty-one of 78 patients (52.6 %) with positive margins had residual lesion compared with thirteen of 151 patients (8.6 %) with negative margins. Twenty-six of 34 patients (76.5 %) with positive postcone cytology had residual lesion compared with twenty-eight of 195 patients (14.4 %) with negative postcone cytology.Conclusion : Postcone cytologic smear of the endocervical canal as well as margin status are useful in predicting residual lesion after conization.

상피성 난소종양에서 MTA1 발현에 관한 연구

윤만수 ( Man Soo Yoon ),장성규 ( Sung Kyu Jang ),이동형 ( Dong Hyung Lee ),김기형 ( Ki Hyung Kim ),나용진 ( Yong Jin Na ),김활웅 ( Hwal Woong Kim ),김지연 ( Jee Yeon Kim ),최경운 ( Kyung Un Choi ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.7

Objective: MTA1 has been identified as a metastasis-promiting gene, and its gene expression is correlated with invasion and metastasis in several cancers. We examined MTA1 expression levels in epithelial ovarian neoplasm. Methods: Expression of MTA1 was evaluated by immunohistochemistry and tissue array in 53 benign tumors, 27 borderline tumors and 68 malignant tumors. The data was analyzed in reference to various clinicopathological parameters. Results: Increased expression of MTA1 was significantly correlated with histologic grade and FIGO stage. There was no relationship between MTA1 expression and age, histologic type, tumor size. Conclusion: These results suggest that MTA1 is closely related to invasiveness and progression in epithelial ovarian neoplasm. The MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis.

가임기 여성의 골반종괴에 관한 임상적 고찰

윤만수(Man Soo Yoon),이영아(Young Ae Lee),배은지(Eun Jee Bae),김기형(Gee Hyung Kim),강기주(Gee Joo Kang) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.8

Objective : The purpose of this study was to review the types of pelvic masses, the incidence according to ages, the anatomic location and histology, the diagnostic and operative methods and the incidence of malignancy in reproductive ages. Methods : Retrospective review according to the medical records of 1,408 reproductive aged women with pelvic mass who visited and managed in the Department of Obstetrics and Gynecology of six University Hospitals from January 1997 to December 1998. Results : The results were as follows: 1. The case numbers of pelvic masses managed within 2 year period were 1,408. Among these, the most common was ovarian masses(52.4%) followed by uterine masses(44.7%). 2. The peak incidence age of ovarian masses was 20-29 years of age group(41.5%) and the uterine masses was 40-44 years of age group(49.0%). 3. Among 738 cases with ovarian masses, germ cell tumor was the most common(39.4%). Others were epithelial tumors(37.9%), endometriosis(31.9%), functional cysts(5.6%), and sex cord stromal tumors(2.1%). And the incidence rate of malignancy in ovarian masses is 10 %. 4. Among 630 cases with uterine masses, leiomyoma is the most common(87.0%) and adenomyosis is the next(12.4%). 5. The most frequently used diagnostic method was ultrasound(75%). The operation methods were somewhat different according to types of pelvic masses. In ovarian masses, 71.3% were managed by laparotomy and 28.7% were by laparoscopic surgery. Whereas in uterine masses, 94.4% were managed by laparotomy and 5.6% were by laparoscopic surgery. Conclusion : This study shows that benign ovarian mass and uterine myoma were common pelvic masses in reproductive ages. And correct diagnosis is needed and indication of surgical intervention should be considered cautiously in women who wish to preserve childbearing capacity.

폐경 여성에서 타목시펜 사용 후 발견된 거대 자궁내막용종

문수현 ( Soo Hyeon Moon ),이성의 ( Seong Eui Lee ),정인국 ( In Kook Jung ),정주은 ( Ju Eun Jeong ),박원영 ( Won Young Park ),이우희 ( Woo Hee Yi ),서동수 ( Dong Soo Suh ),윤만수 ( Man Soo Yoon ),김기형 ( Ki Hyung Kim ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.12

Tamoxifen is a synthetic non-steroid anti-estrogen that has been used effectively for several years in the adjuvant treatment of breast cancer. But, the drug has been associated with development of endometrial poylp, hyperplasia and adenocarcinoma possibly mediated through its agonistic estrogen properties during the menopausal period in which estrogens are at a low level. Endometrial polyp has been described as the most common endometrial pathology in association with postmenopausal tamoxifen treatment. We present the case of woman with a giant endometrial polyp of uncommon dimension who was receiving adjuvant tamoxifen for 5 years after breast cancer surgery.

상피성 난소암세포에서 이소플라본 유도체 NV-196의 세포고사 유도 효과

서동수 ( Dong Soo Suh ),주종길 ( Jong Kil Joo ),김승철 ( Seung Chul Kim ),이동형 ( Dong Hyung Lee ),이우희 ( Woo Hee Yi ),윤만수 ( Man Soo Yoon ),김기형 ( Ki Hyung Kim ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.2

Objective: The objectives of this study were to determine the efficacy of NV-196, a synthetic isoflavone derivative, as a chemosensitizer in chemoresistant CP70 and R182 epithelial ovarian cancer (EOC) cells and to characterize the mechanism behind its sensitizing effect. Methods: EOC cells were treated with tenfold dilutions of NV-196 (0.1 to 10 μg/mL) for 24 and 48 hours. Cell viability was determined by the CellTiter 96 AQueous One Solution Cell Proliferation Assay. Apoptosis was assessed by Caspase-Glo assays and apoptotic cascade X-linked inhibitor of apoptosis protein (XIAP), caspase-2 and Bid were characterized by Western blot analyses. Results: As a monotherapy, NV-196 showed decreased cell viability in a time- and dose-dependent manner in both CP70 and R182 cells. A significant increase in caspase-3 activity was observed in both cells. Caspase-8 and -9 activation were also observed. Western blots demonstrated Bid and caspase-2 activation and cleavage of XIAP. NV-196 enhances the cytotoxic effects of carboplatin and paclitaxel. Conclusion: NV-196 induces cell death through the induction of apoptosis. Pretreatment with NV-196 may sensitize the ovarian cancer cells to carboplatin or paclitaxel. NV-196 may act as a chemosensitizing agent in epithelial ovarian cancer cells.

상피성 난소암 세포에서 MyD88 발현과 paclitaxel의 항세포고사 신호

서동수 ( Dong Soo Suh ),조무성 ( Moo Sung Jo ),유신애 ( Shin Ae Yu ),김기형 ( Ki Hyung Kim ),윤만수 ( Man Soo Yoon ) 대한산부인과학회 2010 Obstetrics & Gynecology Science Vol.53 No.4

Objective: The objectives of this study was to evaluate the correlation between myeloid differentiation protein 88 (MyD88) expression and paclitaxel effects on epithelial ovarian cancer cells and to evaluate whether paclitaxel had anti-apoptotic signals. Methods: Epithelial ovarian cancer cells isolated from ascites and established cell lines were treated with increasing concentrations of paclitaxel (0.2 to 20 μM) for 24 and 48 hours and cell viability was determined using the CellTiter 96 AQueous One Solution Cell Proliferation Assay. Cytokine profiling was performed from culture supernatants using the Luminex 200 system. Nuclear factor-kappaB (NF-κB) activity was determined using a Luciferase reporter system. Levels of phospho-extracellular signal-regulated kinase (p-ERK) were measured by Western blot analysis. Results: A strong signal for MyD88 expression was observed in R182, 01-19b and SKOV3 cells (MyD88-positive). A2780, R454 and 01-28 cells showed low levels of MyD88 (MyD88-negative). Paclitaxel effectively decreased cell viability in MyD88-negative A2780, R454, 01-28 cells after 24 and 48 hours (57%, 49%, 42% and 35%, 28%, 29%, respectively). MyD88-positive cells were resistant to paclitaxel. There was a significant increase in caspase-3/7 activity following paclitaxel treatment in MyD88-negative cells. No significant change in caspase-3/7 activity was detected in MyD88-positive cells. Paclitaxel induced NF-κB activation and enhanced the secretion of interleukin-6 (IL-6) and IL-8 in a dose dependent manner and induced ERK phosphorylation on MyD88-positive cells. Conclusion: Paclitaxel treatment for MyD88-positive ovarian cancer could have detrimental effects due to the paclitaxel-induced enhancement of NF-κB, ERK activities and pro-inflammatory cytokine production, which promote chemoresistance and tumor progression.

Expression of DNA-dependent Protein Kinase and Its Relationship with Epidermal Growth Factor Receptor Signaling in Metastatic Cancer Cell Lines

황지영,김선희,강치덕,윤만수,Hwang Jee Young,Kim Sun Hee,Kang Chi Dug,Yoon Man Soo Korean Society of Life Science 2005 생명과학회지 Vol.15 No.3

암세포의 유전적 불안정성은 부적절하게 활성화된 DNA수복경로와 관련되어 있다. 전이성 암은 높은 유전적 불안정성을 나타내는데, 이와 관련하여 본 연구에서는 전이성 암세포에서의 중요한 DNA수복 단백질의 하나인 DN의존성 단백질 키나아제(DNA-PK)의 발현 변화를 조사하였다. 여러 종류의 전이도가 다른 암세포들을 대상으로 한 실험에서 전이성 암세포들은 각각의 모세포에 비하여 DNA-PK 성분의 조절 소단위인 Ku70/80의 발현 및 Ku의 DNA 결합 활성이 증강되어 있었다. 또한 DNA-PK의 촉매 소단위인 DNA-PKcs의 발현 및 whole DNA-PK복합체의 kinase의 활성도 전이도가 큰 암세포에서 그 모세포보다 증강되어 있음을 알 수 있어, 전이성 암세포의 증강된 DNA수복능은 부적절한 DNA수복을 일으켜 암의 진행 및 전이를 촉진시키는 원인이 될 수 있음을 시사하였다. 한편 암세포의 표피성장인자수용체의 신호전달의 증강은 암의 침윤과 전이에 관련되어 있으며, DNA-PK의 기 기능에도 영향을 줄 수 있는 가능성이 보고 된 바 있는데, 본 연구에서는 표피성장인자수용체의 신호전달과 DNA-PK의 관련성을 명확히 밝히기 위하여 새로 개발된 EGFR tyrosine kinase inhibitor인 PKI166의 DNA-PK의 활성에 미치는 영향을 조사하였다. PKI166는 Ku70/80 및 DNA-PKcs의 발현을 억제하였고 이와 관련하여 전이성 및 항암제 다제내성 암세포에서 PKI166에 의하여 항암제에 대한 감수성을 증가시켜 항암제 내성을 나타내는 전이성 암세포 대한 치료법 연구에 DNA-PK가 분자적 표적이 될 수 있음을 밝혔다. The genetic instability of cancer cells may be related to inappropriately activated DNA repair pathways. In present study, the modulated expression of DNA-dependent protein kinase (DNA-PK), a major DNA repair protein, in human cancer metastatic cells was tested. The expressions of Ku70/80, regulatory subunit of DNA-PK, and the Ku DNA-binding activity in various highly metastatic cell lines were higher than those in each parental cell line. Also, the expression of DNA-PKcs, catalytic subunit of DNA-PK, and the kinase activity of the whole DNA-PK complex in highly metastatic cells were significantly increased as compared to those of parental cells, suggesting that the enhanced DNA repair capacity of metastatic cells could be associated with aberrant use of DNA repair, which may mediate tumor progression and metastatic potential. Increased EGFR (epidermal growth factor receptor) signaling has been associated with tumor invasion and metastasis, and the linkage between EGFR-mediated signaling and DNA-PK has been suggested. This study showed that PKI166, the new EGFR tyrosine kinase inhibitor, modulated the expressions of Ku70/80 and DNA-PKcs and also revealed the chemosensitization effect of PKI166 against metastatic cells may be in part due to inhibition of Ku70/80. These results suggest that interference in EGFR signaling by EGFR inhibitor resulted in the impairment of DNA repair activity, and thus DNA-PK could be possible molecular targets for therapy against metastatic cancer cells.

자궁 경부암에서 골반 임파절 전이의 예측 인자로서 SCC ( squamous cell carcinoma antigen ) 의 가치에 대한 연구

박창수,박창수(Chang Soo Park),고형권(Hyeong Kweon Ko),강기주(Gi Joo Kang),윤만수(Man Soo Yoon),설미영(Mee Young Sol) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.3

Objective: The clinical value of preoperative serum squamous cell carcinoma antigen(SCC) in relation to clinical stage, tumor volume, disease extent and prognosis has already reported in many papers. The aim of this study is to analyse the relationship between preoperative SCC level and pelvic lymph node metastasis. Matrials and Methods: From March 1995 to December 1998, 157 patients who examined pretreatment SCC levels before undergoing radical hysterectomy for squamous cell carcinoma of uterine cervix were included. The effect of pelvic lymph node status on the SCC level was examined by comparing 125 cases with cancer limited uterus or upper vagina and 32 cases with cancer confined to the uterus (including upper vagina) and pelvic lymph node using multivariate analysis. Results: 90% of patients without pelvic lymph node metastasis showed SCC levels of 2.9ng/ml or below. 60.7% of patients with serum SCC level more than 2.9ng/ml exhibited pelvic lymph node metastasis. The marker values exceeding 2.9ng/ml increased risk of nodal metastasis 5 times compared with serum level 2.9ng/ml or below. Multivariate analysis confirmed that the pelvic lymph node metastasis had a large impact on the marker level than did tumor size or depth of stromal infilteration. Conclusion: SCC levels greater than 2.9ng/ml can be considered a high risk zone for nodal metastasis

동결 전 단계적 노출처리방법이 유리화동결 및 초급속동결-융해 후 생쥐 성숙난자의 생존력에 미치는 영향에 관한 연구

김상우,이재익,김미경,이영아,이규섭,윤만수,Kim, Sang-Woo,Lee, Jae-Ik,Kim, Mi-Kyung,Lee, Young-Ah,Lee, Kyu-Sup,Yoon, Man-Soo 대한생식의학회 2000 Clinical and Experimental Reproductive Medicine Vol.27 No.2

Objective: This study was carried out to compare the effects of the stepwise exposure treatments on the morphological normality, fertilization and blastocyst formation rate of the frozen-thawed mouse mature oocytes by vitrification or ultra-rapid freezing and to use as a fundamental data for the cryopreservation of human oocytes. Materials and Methods: The morphological normality and fertilization rates of the vitrified and ultra-rapid frozen mouse mature oocytes after three-stepwise exposure treatments (1step, 3step and 5step) were observed. After choosing the 3step exposure treatment groups, we observed the morphological normality and fertilization, blastocyst formation rate of the vitrified and ultra-rapid frozen mouse mature oocytes. Results: The morphological normality and fertilization rates of the vitrified mouse mature oocytes after three-stepwise exposure treatments (1step, 3step and 5step) were 75%, 85%, 88% and 58%, 61 %, 54% respectively. There were no significant differences among treatments(p>0.05). The morphological normality and fertilization rate of the control was 92% and 65%. There were no significant differences in fertilization rate among control and treatments (p>0.05). The morphological normality and fertilization rates of the ultra-rapid frozen mouse mature oocytes after three-stepwise exposure treatments (1step, 3step and 5step) were 83%, 83%, 84% and 75%, 63%, 56% respectively. There were no significant differences among treatments (p>0.05). The morphological normality and fertilization rate of the control was 95% and 67%. There were no significant differences among control and treatments (p>0.05). The morphological normality and fertilization rate of the vitrified or ultra-rapid frozen mouse mature oocytes after 3step exposure treatment were 69% and 75%, respectively. The blastocyst formation rate was 60% and 57%. The results did not differ significantly between vitrification and ultra-rapid freezing (p>0.05). Conclusion: As known in the above results, there were no significant differences in the fertilization and blastocyst formation rate of the frozen-thawed mouse mature oocytes by vitrification or ultra-rapid freezing among the control and treatments. It is suggested that vitrification and ultra-rapid freezing method were effective for the cryopreservation of mouse mature oocytes.

상피성 난소종양에서 SPARC 발현과 임상병리학적 연관성에 관한 연구

박상일 ( Sang Il Park ),이의돈 ( Eui Don Lee ),서동수 ( Dong Soo Suh ),김기형 ( Ki Hyung Kim ),윤만수 ( Man Soo Yoon ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.12

Objective Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein implicated in the modulation of cell adhesion, migration, cell cycle regulation, and angiogenesis. It has been associated with the progression or suppression of various cancers. This study was aimed at correlating SPARC protein expression with tumor progression and clinicopathological features in ovarian epithelial tumors. Methods Epithelial ovarian cancer (n=69), borderline tumor (n=18), benign tumor (n=10) and normal ovary tissues were obtained after operation. SPARC protein expression was examined using immunohistochemistry. With a retrospective review, patients` characteristics and slide samples were analyzed. Results Cytoplasmic SPARC immunoreactivity was observed in stromal cells in nearly all cases of normal ovary, benign and borderline tumors (100%, 94.7%, and 100%). In contrast, SPARC was detected in the stroma of 63.8% (44/69) and the score of immunoreactivity was significantly reduced in malignant tumors (P<0.001). SPARC expression in ovarian epithelial cancers was significantly associated with International Federation of Gynecology and Obstetrics stage. However, it was not correlated with other clinicopathologic parameters, including histologic type, tumor grade, nuclear grade, mitosis, tumor size, local recurrence, distant metastasis, and survival. Conclusion This study showed that reduction of SPARC expression in ovarian epithelial tumors is significantly correlated with tumor invasiveness and SPARC may act as tumor suppressor.