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Development of Antiangiogenic Recombinant human apolipoprotein(a) kringle V(Greenstatin)
Yoon, Yeup 이화여자대학교 세포신호전달연구센터 2009 고사리 세포신호전달 심포지움 Vol. No.11
Anti-angiogenic therapy is regarded as a promising strategy for cancer treatment, reflecting the fact that the growth of most tumors and their metastasis are angiogenesis-dependent. Apolipoprotein(a) [apo(a)] contains the largest numbers of kringle domains identified to date. Of these, apo(a) kringle V shows significant sequence homology with plasminogen kringle 5, which is reported to be a potent inhibitor of endothelial cell proliferation and migration. The present study was performed to determine the potential anti-angiogenic and anti-tumor activities of apo(a) kringle V. Apo(a) kringle V was expressed as a recombinant protein(termed rhLK8) in Saccharomyces cerevisiae and its in vitro and in vivo anti-angiogenic properties were examined. rhLK8 inhibited endothelial cell migration in vitro in a dose-dependent manner. To evaluate the therapeutic potential of rhLK8 for the treatment of tumor growth and metastasis, the effects of LK8 on tumor growth and metastasis were determined in several human tumor xenograft models as well as in orthotopically transplanted cancer model. In addition, the experimental model of colon cancer liver metastasis established by injecting LS174T human colorectal cancer cells into the spleens of Balb/c nu/nu nude mice. Systemic treatment with rhLK8 significantly suppressed the growth of subcutaneously implanted human lung(A549), human prostate(PC-3), and human colorectal(LS174T) cancer cells in nude mice. rhLK8 treatment exhibits a significant extension of host survival in animals that have been injected with KM12SM human colon cancer cells into the cecal wall of nude mice. The treated tumors showed reduced microvessel density, lower expression of vascular endothelial growth factor, and increased tumor cell apoptosis, while proliferation was not affected. From the immuno-histological analysis, it is observed that rhLK8 suppresses tumor growth by interfering with tumor angiogenesis associated with its ability to stimulate apoptotic turnover in endothelial cells. In conclusion, these observations suggest that rhLK8 may be an effective angiogenesis inhibitor both in vitro and in vivo and a promising candidate for the treatment of cancer. Currently, the clinical developments are in preparation for the indication of anti-angiogenic therapies for the metastastic cancers.
비면역성 태아수종: 임상양상과 신생아의 생존과 관련된 예후인자
이중엽 ( Joong Yeup Lee ),손유경 ( Yoo Kyung Sohn ),심순섭 ( Soon Sup Shim ),임준희 ( June Hee Im ),심재윤 ( Jae Yoon Shim ),박중신 ( Joong Shin Park ),전종관 ( Jong Kwan Jun ),윤보현 ( Bo Hyun Yoon ),신희철 ( Hee Chul Syn ) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.12
목적 : 비면역성 태아수종의 발생빈도, 관련조건 (혹은 원인), 주산기 결과를 확인하고, 신생아 생존과 관련있는 예후인자를 밝혀내고자 하였다. 연구 방법 : 1988년 10월부터 2001년 2월까지 서울대학교병원 산부인과에서 진단된 54예의 비면역성 태아수종의 후향적 고찰을 통하여 발생빈도, 관련조건, 주산기 결과를 확인하였다. 아울러 생존하여 출산된 20예의 신생아를 28일 초과 생존한 군과 28일 이하에 사망한 군으로 구분하여 신생아 생존과 관련된 Objective : We undertook this study to find out clinical characteristics and prognostic factors of neonatal survival in nonimmune hydrops fetalis (NIHF). Methods : From Oct. 1988 to Feb. 2001, 54 cases of nonimmune hydrops fetalis diagnosed at Seoul Natio
Nuclear Remodeling and In Vitro Development Following Somatic Cell Nuclear Transfer in Swine
Yoon, Jong-Taek,Kim, Yong-Yeup,Lee, Jong-Wan,Min, Kwan-Sil,Hwang, Seongsoo 한국동물번식학회 2004 Reproductive & developmental biology Vol.28 No.4
This study was conducted to investigate nuclear remodeling and developmental rate following nuclear transfer of fetal fibroblast cells, ear skin cells and oviduct epithelial cells into porcine recipient oocytes. To test par-thenogenetic activation, oocytes were treated with a 6-dimethylaminopurine (6-DMAP), a single DC-pulse (DC), calcium ionomycin (ionomycin), DC+6-DMAP and ionomycin + 6-DMAP after in vitro maturation. For nuclear transfer, in vitro matured oocytes were enucleated, and donor cells were transferred into oocytes. Cloned embryos were fused and stimulated with 6-DMAP for 4 h and cultured in vitro for 6 days. Among treatments for parthenogenesis, the activation rate of DC +6-DMAP treatment was significantly higher than that of single treatment roups (p<0.01), except for DC treatment group. However, the difference was not significant in activation rate compared to other complex treatment groups. Nuclear swelling of the cloned embryos was initiated at 60 min after stimulation and increased afterwards. Fusion rates were not different among different donor cells. Cleavage rates of DC treatment groups were significantly higher than those of DC+6-DMAP treatment groups (p<0.05) in case that fetal fibroblast and ear cells were used for nuclear donor. The cloned embryos from developed to blastocysts in oviduct epithelial cell nuclear transfer with DC+6-DMAP treatment was significantly higher compared to those with DC only treatment (p<0.05). However, no blastocyst was developed from nuclear transfer of fetal fibroblast and ear cells regardless of activation treatments. Based on these results, a proper activation stimulation may be necessary to increase the activation rate and the development to blastocyst in cloned porcine embryos.
Nuclear Remodeling and In Vitro Development Following Somatic Cell Nuclear Transfer in Swine
Yoon, Jong-Taek,Kim, Yong-Yeup,Lee, Jong-Wan,Min, Kwan-Sil,Hwang, Seongsoo 한국동물생명공학회(구 한국동물번식학회) 2004 Reproductive & developmental biology Vol.28 No.4
This study was conducted to investigate nuclear remodeling and developmental rate following nuclear transfer of fetal fibroblast cells, ear skin cells and oviduct epithelial cells into porcine recipient oocytes. To test par-thenogenetic activation, oocytes were treated with a 6-dimethylaminopurine (6-DMAP), a single DC-pulse (DC), calcium ionomycin (ionomycin), DC+6-DMAP and ionomycin + 6-DMAP after in vitro maturation. For nuclear transfer, in vitro matured oocytes were enucleated, and donor cells were transferred into oocytes. Cloned embryos were fused and stimulated with 6-DMAP for 4 h and cultured in vitro for 6 days. Among treatments for parthenogenesis, the activation rate of DC +6-DMAP treatment was significantly higher than that of single treatment roups (p<0.01), except for DC treatment group. However, the difference was not significant in activation rate compared to other complex treatment groups. Nuclear swelling of the cloned embryos was initiated at 60 min after stimulation and increased afterwards. Fusion rates were not different among different donor cells. Cleavage rates of DC treatment groups were significantly higher than those of DC+6-DMAP treatment groups (p<0.05) in case that fetal fibroblast and ear cells were used for nuclear donor. The cloned embryos from developed to blastocysts in oviduct epithelial cell nuclear transfer with DC+6-DMAP treatment was significantly higher compared to those with DC only treatment (p<0.05). However, no blastocyst was developed from nuclear transfer of fetal fibroblast and ear cells regardless of activation treatments. Based on these results, a proper activation stimulation may be necessary to increase the activation rate and the development to blastocyst in cloned porcine embryos.
이중엽(Joong Yeup Lee),심순섭(Soon Sup Shim),한수연(Soo Yeon Han),고은미(Eun Mi Ko),박중신(Joong Shin Park),전종관(Jong Kwan Jun),윤보현(Bo Hyun Yoon),신희철(Hee Chul Syn) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.8
Acardiac twin is a rare complication of multifetal pregnancy. The literatures report an incidence of 1% among monochorionic twin pregnancies, I. E. 1 of 35,000 pregnancies. The absence of identifiable fetal heart structures in one twin and reduction anomalies in many organ systems suggest the diagnosis. It has been hypothesized that in the presence of artery-to-artery and vein-to-vein anastomoses in a monozygotic placenta, blood is perfused by hemodynamically advantaged pump-twin to the recipient twin by retrograde flow. The principal perinatal problems associated with acardiac twinning are congestive heart failure of pump-twin, maternal polyhydramnios, preterm delivery and intrauterine death. The outcome is invariably fatal for the acardiac twin and 50-75% of the normal twin. Management options include observation, medical therapy, and selective termination of acardiac twin. The most appropriate intervention for the various clinical presentations of this disorder is undetermined, and conservative nonintervention is often appropriate. Long-term follow-up data on surviving pump twins are lacking. We experienced a case of acardiac twin gestation which showed satisfactory outcome with conservative management, so we present the case with a brief review of the literature.