Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization

被引：384

作者：

Kenyon, BM ^{[1
]}

Browne, F ^{[1
]}

DAmato, RJ ^{[1
]}

机构：

[1] HARVARD UNIV,CHILDRENS HOSP,DEPT SURG,SCH MED,BOSTON,MA 02115

来源：

EXPERIMENTAL EYE RESEARCH | 1997年 / 64卷 / 06期

关键词：

thalidomide; angiogenesis; neovascularization; tumor necrosis factor-alpha; growth factor; cornea;

D O I：

10.1006/exer.1997.0292

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Thalidomide, when administered orally, is an inhibitor of angiogenesis in the basic fibroblast growth factor (bFGF)-induced rabbit cornea micropocket assay. We now show in the mouse that thalidomide given intraperitoneally but not orally significantly inhibits bFGF-induced and vascular endothelial growth factor (VEGF)-induced corneal neovascularization, We further demonstrate that this inhibition is independent from thalidomide's ability to suppress tumor necrosis factor-alpha (TNF-alpha) production. Experiments examining thalidomide's enantiomers reveal that the S(-)-enantiomer has the strongest antiangiogenic activity in VEGF-induced and bFGF-induced corneal neovascularization. Structure activity studies suggest that thalidomide's anti-angiogenic activity is related to the open ring metabolites resulting from hydrolysis. Together these data support a correlation between thalidomide's antiangiogenic and teratogenic activities. (C) 1997 Academic Press Limited.

引用

页码：971 / 978

页数：8

共 41 条

[1] BLASCHKE G, 1979, ARZNEIMITTEL-FORSCH, V29-2, P1640
[2] CAHEN RL, 1964, CLIN PHARMACOL THER, V5, P480
[3] TREATMENT OF CUTANEOUS AND PULMONARY SARCOIDOSIS WITH THALIDOMIDE
CARLESIMO, M
GIUSTINI, S
ROSSI, A
BONACCORSI, P
CALVIERI, S
[J]. JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1995, 32 (05) : 866 - 869
[4] THALIDOMIDE IS AN INHIBITOR OF ANGIOGENESIS
DAMATO, RJ
LOUGHNAN, MS
FLYNN, E
FOLKMAN, J
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) : 4082 - 4085
[5] TOXICITY AND TERATOGENICITY OF OPTICAL ISOMERS OF THALIDOMIDE
FABRO, S
SMITH, RL
WILLIAMS, RT
[J]. NATURE, 1967, 215 (5098) : 296 - &
[6] FABRO S, 1967, BIOCHEM J, V1045, P565
[7] FERRAR N, 1989, BIOCHEM BIOPH RES CO, V162, P851
[8] FIEDLANDER M, 1995, SCIENCE, V70, P1500
[9] EFFECT OF THALIDOMIDE ON GRAFT VERSUS HOST REACTION
FIELD, EO
GIBBS, JE
TUCKER, DF
HELLMANN, K
[J]. NATURE, 1966, 211 (5055) : 1308 - &
[10] CLINICAL-EXPERIENCE WITH THALIDOMIDE IN THE MANAGEMENT OF SEVERE ORAL AND GENITAL ULCERATION IN CONDITIONS SUCH AS BEHCETS-DISEASE - USE OF NEUROPHYSIOLOGICAL STUDIES TO DETECT THALIDOMIDE NEUROPATHY
GARDNERMEDWIN, JMM
SMITH, NJ
POWELL, RJ
[J]. ANNALS OF THE RHEUMATIC DISEASES, 1994, 53 (12) : 828 - 832

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