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상피성 난소암 세포 (OVCAR3)에 대한 Zinc-Citrate Compound (CIZAR(R))의 증식 억제 및 세포자멸사에 미치는 영향
이용석 ( Yong Seok Lee ),김재동 ( Jae Dong Kim ),박래옥 ( Lae Ok Park ),배석년 ( Seog Nyeon Bae ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.7
목적: 인간의 정액은 세포독성 효과를 포함한 다양한 생물학적인 작용을 가지고 있다. 정액은 고농도의 아연과 citric acid를 포함하고 있으며 아연은 여러 종류의 암세포에서 성장을 억제하는 것으로 알려져 있다. 우리는 zinc-citrate compound (CIZAR(R))를 이용하여 정상 난소 상피세포 (NOSE)와 상피성 난소암 세포 (OVCAR-3)에서 세포의 성장과 생존에 어떤 작용을 나타내는 지 확인하고자 하였다. 연구 방법: NOSE와 OVCAR-3에 각각 다른 농도와 시간에 걸쳐 CIZAR(R)를 투여하였다. aconitase assay, flow cytometric assay와 DNA laddering, telomerase의 활성과 p53, Bcl-XL, Bcl-2, Bax protein과 caspase 활성을 측정하였다. 결과: CIZAR(R)의 투여 후 OVCAR-3 세포 수는 NOSE 세포에 비해 크게 감소하였으며 m-aconitase 활성이 감소하였다. CIZAR(R)는 OVCAR-3에서 p21wafl의 발현 증가와 telomerase 활성 감소, Bcl-2과 Bcl-xL 발현 감소와 Bax의 증가를 보였으며 caspase-3 pathway를 통해 세포자멸사를 유도하는 것으로 보인다. 결론: CIZAR(R)는 세포자멸사 관련 유전자를 통하여 OVCAR-3 세포 증식을 억제하는 것으로 보인다. CIZAR(R)의 작용은 상피성 난소암의 연구에 새로운 단서를 제공할 수 있을 것이다. Objective: Human seminal plasma has diverse biological activities including cytotoxic effect. It contains high concentrations of zinc and citric acid. Zinc inhibits several carcinoma cell growths through induction of cell cycle arrest and apoptosis. We tried to investigate the effects of zinc-citrate compound (CIZAR(R)) on normal human ovarian epithelial (NOSE) cells and human epithelial ovarian cancer cells, OVCAR-3. Methods: To investigate the potential effect of CIZAR(R) on cell growth and survival, cells were treated with different dose and exposed to different time. Mitochondrial(m)-aconitase activity was determined in cell extracts using aconitase assay. The flow cytometric assay, DNA laddering, telomerase activity and morphological analysis were done to investigate apoptosis of OVCAR-3 cells. Molecular mechanism of apoptosis was investigated by p53, Bcl-XL, Bcl-2, Bax protein, and caspase activity. Results: Treatment of OVCAR-3 cells with CIZAR(R) resulted in a time- and dose-dependent decrease in cell number in comparison with NOSE cells. M-aconitase activity was significantly decreased in OVCAR-3 cells but relatively constant in NOSE cells. The flow cytometric assay, DNA laddering and morphological analysis indicated apoptosis of OVCAR-3 cells. CIZAR(R) did not affect p53 but increased the expression of p21wafl upon the indicated times and induced reduction of telomerase activity. CIZAR(R) reduced expression of Bcl-2 and Bcl-xL proteins but induced expression of Bax protein. CIZAR(R) induced apoptosis of OVCAR-3 cells by activation of caspase-3 pathway. Conclusion: These results show that CIZAR(R) prevent the proliferation of OVCAR-3 cells by inactivation of m-aconitase activity and induce apoptosis by induction of apoptotic genes and repression of antiapoptotic genes without adverse effect on normal ovarian epithelial cells. These results will offer new window in prevention and treatment of epithelial ovarian cancer.
최지향 ( Ji Hyang Choi ),허수영 ( Soo Young Hur ),배석년 ( Seog Nyeon Bae ),박종섭 ( Seong Sup Park ),남궁성은 ( Sung Eun Namkoong ),이준모 ( Joon Mo Lee ) 대한산부인과학회 2008 Obstetrics & Gynecology Science Vol.51 No.8
목적: 상피성 난소암은 성인에서 사망에 이르는 주요한 여성암 중 하나이지만, 어린이 및 사춘기에는 매우 드물다. 이러한 20세 이하의 상피성 난소암 환자의 일반적인 특징에 대해 알아보고자 한다. 방법: 1990년 1월부터 2005년 12월까지 가톨릭대학교 의과대학 강남성모병원 산부인과에서 상피성 난소암으로 진단받은 20세 이하의 환자 21명으로 대상으로 의무기록 및 수술기록, 병리 결과를 검토하였다. 결과: 전체 난소암 환자 중 20세 이하의 상피성 난소암으로 진단받은 환자는 2.2%이고, 20세 이하에서 난소암으로 진단받은 50명 중 상피성 난소암 환자는 42.0%였으며, 가장 흔한 조직학적 형태인 배아세포종양은 54%였다. 진단 시 평균 나이는 17.6세 (범위 13~20세)였으며, 추적 관찰 기간은 4~175개월이었다 (median 87개월). 조직학적 분류상 점액성 난소암 환자는 81% (10/21), 장액성 난소암 환자는 19% (4/21)였다. 경계성 난소암 환자는 8명으로 38.1%에 해당하였으며, 수술 병기상 병기I기는 85.7% (18/21)이고, 병기 III기는 14.3% (3/21)였다. 수술은 생식력을 보존하기 위한 보존적 수술을 85.7% (18/21), 광범위 수술은 14.3% (3/21)에서 시행하였다. 결론: 상피성 난소암은 어린이 및 사춘기에는 매우 드물다. 대부분의 환자는 성인에 비해 점액성 난소암의 비율이 높으며, 높은 빈도의 경계성 난소암과 낮은 분화도 및 낮은 수술적 병기에 의해 비교적 예후가 좋다. 이러한 환자에서 생식력을 보존하기 위해 보존적 수술을 시행하는 것이 받아들일 만하다. Objective: Epithelial ovarian cancer is the most common cause of death due to gynecologic malignancies in adults, but is rare in children and adolescents. This is a report of series of such patients under 20 years of age documenting their presentation, histologic type, stage of disease, treatment, and outcome. Methods: We collected data on 21 patients with epithelial ovarian cancer under 20 years of age between January 1990 and December 2005. Patient records and pathology were reviewed. Results: Epithelial ovarian cancer under 20 years of age was 2.2% in overall ovarian cancer. Epithelial ovarian cancer was 42.0% among 50 patients under 20 years of age and the most common histologic type was germ cell tumors (54%). The median age at the time of diagnosis was 17.6 years (range, 13-20 years), and the median follow-up was 87 months (range, 4-175 months). There were seventeen (81.0%) mucinous tumors, four (19.0%) serous tumors. About thirty-eight percent were low malignant potential or borderline tumors. About Eighty-five percent (18 patients) of tumors were stage I disease and about fourteen percent (3 patients) were stage III disease at the time of diagnosis. Surgical treatment included conservative surgery in 18 patients (85.7%), total abdominal hysterectomy and bilateral salpingo-oophorectomy in 3 patients (14.3%). Conclusion: Epithelial ovarian cancers are rare in patients in children and adolescents. The majority of ovarian cancers in this age group are mucinous tumors, stage I at diagnosis and borderline ovarian tumor. Conservative management is feasible to achieve preservation of fertility.
Zinc-citrate compound (SeLava(R))을 이용한 임신과 동반된 자궁경부 선암 치료
최지향 ( Ji Hyang Choi ),이용석 ( Yong Seok Lee ),정찬권 ( Chan Kwon Jung ),박래옥 ( Lae Ok Park ),배석년 ( Seog Nyeon Bae ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.12
Cervical carcinoma is the second leading cause of death from cancer in women worldwide. It is well known that human papillomaviruses (HPVs) is the etiologic agent of cervical neoplasia and cervical cancer. Zinc has been shown to inhibit the growth of malignant cell lines by inducing apoptosis and cell cycle arrest. Recently it was reported that zinc-citrate compound (CIZAR(R)) has a cytotoxic effect on choriocarcinoma cell line and ovarian adenocarcinoma cell line and suppresses its proliferation inducing apoptosis. CIZAR(R) prevents the proliferation by inactivation of m-aconitase activity and induces apoptosis by increasing Bax expression and reducing Bcl-2 expression and inactivation of telomerase. We report one patient of cervical adenocarcinoma with HPV infection, who desires to continue pregnancy, treated by daily topical application of SeLava(R) which contains zinc-citrate compound (CIZAR(R)). We followed up the cytologic, pathologic and coloposcopic changes of healing process.
융모성 성선자극호르몬과 태반 락토젠이 태반 영양배엽세포의 분화와 성장에 미치는 영향
김동주 ( Dong Joo Kim ),신종철 ( Jong Chul Shin ),안현영 ( Hyun Young Ahn ),남궁성은 ( Sung Eun Namkoong ),백은정 ( Eun Jeong Baik ),노성래 ( Sung Rae Roh ),강미지 ( Mi Ji Kang ),배석년 ( Seog Nyeon Bae ) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.7
N/A Background: There are many factors that influence the differentiation and growth of trophoblasts. During differentiation of trophoblasts, two major hormones are secreted; human chorionic gonadotropin (hCG) and human placental lactogen (hPL). These two hormones are secreted in a peculiar pattern during pregnancy and function of these hormones is not yet fully understood. Also, it is not known whether these hormones directly influence the differentiation and growth of trophoblasts. On the other hand, it is known that choriocarcinoma cells are undifferentiated, so they are unable to form syncytiotrophblasts. And many factors may be associated with this inhibitory potential. Objective :The purpose of this study was to observe whether the hCG and hPL are associated with differentiation and growth of early placental trophoblasts and becoming malignant. Method: The hCG, hPL, IL-6 and insulin were added to cytotrophoblasts isolated from normal 8 to 10 gestational weeks placental tissues by a degree of concentration, and observed the secreted hPL concentration and morphological change to syncytiotrophoblasts daily. And it was performed in Bewo cells in same manner. Result: The increased hPL secretion was noted in hCG, hPL, IL-6 and insulin were added normal trophoblasts and this may result from differentiation of cytotrophoblasts to syncytiotrophoblasts. Also, morphological changes to syncytiotrohoblasts was observed at the same time. But, Increased hPL secretion and syncytiotrophoblasts formation was not detected in Bewo cells. Conclusion .In this study, it seems that hCG, hPL, IL-6 and insulin had an influence on differentiation and growth of normal trophoblasts. On the other hand, no changes in hPL secretion and morphology at the choriocarcinoma cell line tells us that defects of differentiation in choriocarcinoma is due to abnormalities of the receptors on hCG and hPL or a differentiation associated gene, not a defect of these hormones themselves.
자궁경부 상피내종양 및 미세침윤암의 원추절제술 후 잔류병변에 관한 고찰
정선영 ( Sun Young Jeong ),이현정 ( Hyun Jeong Lee ),구남식 ( Nam Sik Ku ),오세정 ( Sae Jeong Oh ),황성진 ( Seong Jin Hwang ),배석년 ( Seog Nyeon Bae ) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.11
목적: 자궁 경부 상피내종양의 주된 치료인 원추절제술 시행 후 잔류 병변과 관련된 위험 인자에 대해 고찰해 보고자 하였다. 연구 방법: 1989년부터 2000년까지 11년간 강남성모병원에서 시행한 원추절제술 환자 중 자궁 적출술을 받은 경우에서 잔류병변에 관련된 위험인자를 설정하여 후향적 연구를 시행하였다. 결과: 환자의 연령이 많을수록, 원추절제술 조직의 내자궁 경부 변연부 혹은 외자궁경부 변연부에 침범이 있는 환자에서 잔류병변의 위험도가 높았고 원추 Objective: Conization is used for diagnosis and treatment of cervical neoplasia. Our purpose of this investigation is to determine the efficacy of loop conization for the treatment of cervical dysplasia and the significance of the clinical and histologica