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      • KCI등재SCOPUS

        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.

      • KCI등재SCOPUS

        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

        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.

      • SCIESCOPUSKCI등재

        괴사 유도를 통한 정장의 상피성 난소암 세포의 파괴

        박래옥,김재훈,이성종,서주태,김재동,이연수,김병기,배석년 대한부인종양 콜포스코피학회 2002 Journal of Gynecologic Oncology Vol.13 No.3

        목적 : 난소암의 발생 위험인자를 토대로 배란 기간동안 인간 정장(human seminal plasma, hSP)에 노출이 감소되었을 경우 상피성 난소암이 증가할 수 있다는 가설을 검증하기 위해 난소암 세포주에 대한 정장의 효과를 실험하였다. 연구 방법 : 난소암 세포로 SK-OY-3, OYCAR-3을 이용하였고, 대조군으로 자궁경부암 세포인 Caski, 섬유모세포인 Wl-38을 사용하였다. 결과 ; MTT 정 량 실험에서 1:50으로 희석된 hSP는 난소암 세포 괴사를 유발하였으나 자궁경부암세포와 섬유모세포에서는 반응이 없었다. Flow cytometry, DNA laddering, 생화학적 정량 실험, 형태학적 관찰을 통하여, hSP는난소암 세포주에서 세포고사(apoptosis)보다는 세포괴사(necrosis)를 유도한다는 것을 관찰하였다. nude mice (Balb-C)에 SK-OY-3 난소암 세포를 주사한 in vivo 실험에서 hSP는 주요 장기에 영향없이 종양 세포괴사를 유도했다. 결론 : 본 연구는 hSP가 상피성 난소암 세포에 세포독성 효과가 있음을 증명하는 실험이었으며, 따라서 hSP는상피성 난소암에 대한 안전한 치료적 방법으로 사용될 수 있는 과학적 기초를 제공할 것이다. Objective : From knowledge of risk factors of epithelial ovarian cancer, we deduced a hypothesis that a reduced exposure to human seminal plasma (hSP) during the period of ovulation is one of etiological risk factors in the development of epithelial ovarian cancer and hSP contribute to eliminate maltransformed epithelial cells. Materials & Methods : To examine whether hSP directly influence the growth of ovarian cancer, we have been investigated the in vivo and in vitro effects of hSP on epithelial ovarian cancer cells (SK-OV-3, OVCAR-3) and, as a control, we also tested its effect in cervical cancer cell (CaSki) and fibroblast cell (WI-38). In in vitro MTT assays of varian cancer cells, we found hSP induces necrosis at a final concentration of 1:50 dilution, whereas cervical cancer cell and fibroblast cell were not affected. The flowcytometric assay, DNA laddering, biochemical assay and morphological analysis indicated that hSP induced necrosis rather than apoptosis of both ovarian adenocarcinoma cell lines. The morphological alterations of hSP-treated SK-OV-3 cells were confirmed by transmission electron microscopy that demonstrated swollen mitochondrias with partially or completely destroyed cristae and shrinkage of nucleus with margination and condensation of chromatin, and intranuclear vesiculation. These findings strongly suggest that hSP induced necrosis of ovarian cancer cell lines through destruction of mitochondria. In in vivo experiments that used the nude mice (Balb-C) with tumor by inoculation of SK-OV-3 ovarian cancer cell line, hSP induced necrosis of tumor with no detectable toxic effects on the major organs. Conclusion : Our study supported the hypothesis that hSP has a potent cytotoxic effect on epithelial ovarian cancer cells. Therefore, hSP can be used as a safe, promising therapeutic agent for the epithelial ovarian cancer and may provide a scientific basis for preventing epithelial ovarian cancer by direct exposure to seminal plasma without barrier and withdrawal method for contraception.

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