랫드 각막에서 Vascular Endothelial Growth Factor(VEGF)로 유발시킨 신생혈관에 대한 $As_4O_6$의 혈관신생 억제효과 Antiangiogenic Effect of $As_4O_6$ on the Angiogenesis Induced by Vascular Endothelial Growth Factor (VEGF) in the Rat Cornea원문보기
본 연구는 VEGF로 유발된 랫드 각막 미세낭 모델에서 As₄O/sub 6/와 As₂O₃ 혈관신생 억제효과를 비교하기 위해 실시하였다. 20ng VEGF가 함유된 펠렛을 이식하여 혈관신생을 유도하였다. 안과 검사후 정상적인 각막을 가진 Sprague-Dawley 랫드의 안구 60안을 이용하여 각 20안씩 무작위로 선정하여 대조군(비투약군), As₂O₃군(50mg/kg As₂O₃, 경구투여, 1일 1회), 그리고 As₄O/sub 6/군(50mg/kg As₄O/sub 6/, 경구투여, 1일 1회)으로 나누어 실시하였다. 이식이 완료된 후, 신생혈관의 개수, 길이 및 신생혈관의 각도를 미세수술현미경하에서 이식 3일째부터 9일째까지 매일 검사하였다. 신생혈관의 넓이는 신생혈관의 길이와 각도를 수학적인 공식에 적용하여 계산하였다. 실험 기간동안 As₄O/sub 6/군의 신생혈관 개수, 길이, 각도 및 넓이가 대조군과 As₂O₃군에 비하여 유의성 있게 억압되었다. (P<0.05). 이러한 결과 As₄O/sub 6/는 랫드 각막에서 VEGF에 의해 유도된 신생혈관에 As₂O₃보다 더 뛰어난 억제효과를 가지고 있음을 보여주었다.
본 연구는 VEGF로 유발된 랫드 각막 미세낭 모델에서 As₄O/sub 6/와 As₂O₃ 혈관신생 억제효과를 비교하기 위해 실시하였다. 20ng VEGF가 함유된 펠렛을 이식하여 혈관신생을 유도하였다. 안과 검사후 정상적인 각막을 가진 Sprague-Dawley 랫드의 안구 60안을 이용하여 각 20안씩 무작위로 선정하여 대조군(비투약군), As₂O₃군(50mg/kg As₂O₃, 경구투여, 1일 1회), 그리고 As₄O/sub 6/군(50mg/kg As₄O/sub 6/, 경구투여, 1일 1회)으로 나누어 실시하였다. 이식이 완료된 후, 신생혈관의 개수, 길이 및 신생혈관의 각도를 미세수술현미경하에서 이식 3일째부터 9일째까지 매일 검사하였다. 신생혈관의 넓이는 신생혈관의 길이와 각도를 수학적인 공식에 적용하여 계산하였다. 실험 기간동안 As₄O/sub 6/군의 신생혈관 개수, 길이, 각도 및 넓이가 대조군과 As₂O₃군에 비하여 유의성 있게 억압되었다. (P<0.05). 이러한 결과 As₄O/sub 6/는 랫드 각막에서 VEGF에 의해 유도된 신생혈관에 As₂O₃보다 더 뛰어난 억제효과를 가지고 있음을 보여주었다.
The purpose of this study was to compare the antiangiogenic effects of As₄O/sub 6/ to those of As₂O₃ on the rat corneal micropocket model induced by VEGF. 20 ng VEGF impregnated pellets were used for angiogenic inducer on the rat cornea micropocket assay in this study. After ophthalmoscopic examinat...
The purpose of this study was to compare the antiangiogenic effects of As₄O/sub 6/ to those of As₂O₃ on the rat corneal micropocket model induced by VEGF. 20 ng VEGF impregnated pellets were used for angiogenic inducer on the rat cornea micropocket assay in this study. After ophthalmoscopic examination, Sprague-Dawley rats with normal cornea were implanted VEGF pellet. Total 60 eyes were used in this study. Control group only received VEGF pellet, As₂O₃ group followed oral administration of As₂O₃ at a dose of 50 mg/kg per day after VEGF pellet implantation and As₄O/sub 6/ group followed oral administration of As₄O/sub 6/ at a dose of 50 mg/kg per day after VEGF pellet implantation were classified. The eyes were examined under a surgical microscope daily on postoperative from day 3 to day 9 after pellet implantation. The number, length, clock hour of vascularization, and area of vessels in As₄O/sub 6/ group were significantly less evident than those of control group and As₂O₃ group (P < 0.05). In conclusion, As₄O/sub 6/ had better antiangiogenic effects on the new vessel induced by VEGF in the rat cornea.
The purpose of this study was to compare the antiangiogenic effects of As₄O/sub 6/ to those of As₂O₃ on the rat corneal micropocket model induced by VEGF. 20 ng VEGF impregnated pellets were used for angiogenic inducer on the rat cornea micropocket assay in this study. After ophthalmoscopic examination, Sprague-Dawley rats with normal cornea were implanted VEGF pellet. Total 60 eyes were used in this study. Control group only received VEGF pellet, As₂O₃ group followed oral administration of As₂O₃ at a dose of 50 mg/kg per day after VEGF pellet implantation and As₄O/sub 6/ group followed oral administration of As₄O/sub 6/ at a dose of 50 mg/kg per day after VEGF pellet implantation were classified. The eyes were examined under a surgical microscope daily on postoperative from day 3 to day 9 after pellet implantation. The number, length, clock hour of vascularization, and area of vessels in As₄O/sub 6/ group were significantly less evident than those of control group and As₂O₃ group (P < 0.05). In conclusion, As₄O/sub 6/ had better antiangiogenic effects on the new vessel induced by VEGF in the rat cornea.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
문제 정의
The aim of this study was to compare the antiangiogenic effects between the new arsenic compound As4O6 and the existing As2O3 on neovascularization induced by VEGF in the rat micropoket cornea.
The purpose of this study was to compare the antiangiogenic effects of As4O6 to those of As2O3 on the rat corneal micropocket model induced by VEGF. With application of cornea micropocket assay, the confusion could be avoided between new vessels and previously exiting vessels 10, 14, 15, 23.
가설 설정
In this study, As4O6 had better antiangiogenic effect than As2O3 in length, and area of vessels. As As4O6 inhibited the angiogenesis induced by VEGF, it was hypothesized that As4O6 might suppress autocrine secretion.
제안 방법
20 ng VEGF impregnated pellets were used for angiogenic inducer on the rat cornea micropocket assay in this study. Park14 used the same dose as the optimal effective dose of VEGF, and reported that the dose did not induce side effects such as corneal edema or inflammation after operation.
The entire groups were randomly divided into three groups ; control group only received VEGF pellet, As2O3 group followed the trans-oral administration of As2O3 at a dose of 50 ㎎/㎏ per day after VEGF pellet implantation, and As4O6 group followed the trans-oral administration ofAs4O6 at a dose of 50 ㎎/㎏ per day after VEGF pellet implantation.
대상 데이터
Male Sprague-Dawley (SD) rats weighing 300-400 g were used in this study. Animals were housed in cages at a controlled temperature (22±2℃, 55±10% humidity) with a 12 h light/dark cycle, and fed with commercial rat pellet, and free access to water at all times throughout the study.
After ophthalmoscopic examination, rats with normal cornea only were performed VEGF pellet implantation. Total 60 eyes were used in this study.
데이터처리
For a intention verification of this study, all numerical variables (number of vessels, length of vessels, clock hour of neovascularization, and area of neovascularization) were assessed by use of repeated ANOVA test with two factors; time and treatment (control, As2O3, As4O6). And their interactions were examined.
And their interactions were examined. When significant difference was determined, multiple comparisons at each time point were made using Scheffe test. Values of P < 0.
참고문헌 (23)
Antman K. Introduction : The history of arsenic trioxide in cancer therapy. Oncologist 2001; 6: 1-2
D'Amato R, Loughnan M, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci 1994; 91: 4082-4085
Fokman J, D'Amore P. Blood vessel formation : what is its molecular basis? Cell 1996; 87: 1153-1155
Jin YJ, Lien WH, Tsai WC, Yang GW, Li C, Wu LW. Distinct regulation of genes by bFGF and VEGF-A in endothelial cells. Angiogenesis 2001; 4: 313-321
Jing Y, Dai J, Chalmers-Redman R. Tatton W, Waxman S. Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood 1999; 94: 2102-2111
Kenyon B, Browne F, D'Amato R. Effect of thalidomide and related metabolites in a mouse corneal model of neocvascularization. Exp Eye Res 1997; 64: 971-978
Kim K, Li B, Winer J, Armanini M, Gillett N, Phillips H, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993; 362: 841-844
Lee JB, Jung SE, Lee HC, Kwon HM, Hong BK, Park HY, Kim EK, Oh JH. Effect of vascular endothelial growth factor(VEGF) on the corneal neovascularization and expression of MMP-2,9,TIMP-1,2 and flk-1. J Korean Ophthalmol Soc 2001; 42: 1053-1062
Lew Y, Brown S, Griffin R, Song C, Kim J. Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown. Cancer Res 1999; 59: 6033-6037
Park CH. Angiogenic effect of vascular endothelial growth factor on the rat cornea. Kangwon national univerity. 2003
Park MJ, Park IC, Bae IJ, Seo KM, Lee SH, Hong SI, Eun CK, Zhang W, Rhee CH. Tetraarsenic oxide, a novel orally administrable angiogenesis inhibitor. International Journal of Oncology 2003; 22: 1271-1276
Roboz G, Dias S, Lam G, Lane W, Soignet S, Warrell Jr R, Rafii S. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 2000; 96: 1525-1530
Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY, Use of arsenic trioxde( $As_2O_3$ ) in the treatment of acute promyelocytic leukemia(APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997; 89: 3354-3360
Soignet S, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti L, Corso D, DeBlasio A, Garbrilove J, Scheinberg D, Pandolfi P, Warrell R. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. NEJM 1998; 339: 1341-1348
University of Tennessee, Department of EHS. 1997. Arsenic trioxide. http://web.utk.edu/~ehss/arsenic/arsenicb.htm
Waxman S, Anderson K. History of the development of arsenic derivatives in cancer therapy. Oncologist 2001; 6: 3-10
Wilson H. Miller, Jr., Hyman M. Schipper, Janet S. Lee, Jack Singer, and Samuel Waxman. Mechanisms of action of arsenic trioxide. Cancer Research 2002; 62: 3893-3903
Yoo MH, Kim JT, Rhee CH, Park MJ, Bae IJ, Yi NY, Jeong MB, Jeong SM, Nam TC, Seo KM. Reverse effects of tetraarsenic oxide on the angiogenesis induced by nerve growth factor in the rat cornea. J Vet Med Sci 2004; 66: 1091-1095
※ AI-Helper는 부적절한 답변을 할 수 있습니다.