グリオーマ血管新生に対するデキサメタゾンの抑制効果の検討

Inhibition of Neovascularization and Tumor Growth by Dexamethasone

　腫瘍の増大には，腫瘍血管新生因子（TAF）により誘導された腫瘍血管網の発達が不可欠と考えられており，この腫瘍血管新生を抑制する事により腫瘍増殖を抑制しうるとの概念に基づき，種々の血管新生抑制剤が報告されている。

　今回我々は，血管新生抑制作用を有すると考えられているステロイド剤のうち，脳神経外科領域で広く使用されているデキサメタゾン（DEX）の血管新生抑制効果を，ウサギ角膜移植法（角膜法），孵化鶏卵漿尿膜移植法（CAM法）を用いて検討すると同時に，これら検索法の有用性についても検討した。

　角膜法は総体としての血管新生抑制効果を観察する上では最も確実な方法と考えられた。一方，CAM法は定量性には乏しいものの，習熟すれば，多数の検体を簡便に検索する事が可能であり，実用的な検索法と考えられた。デキサメタゾンは，角膜法，CAM法のいずれにおいても，血管新生抑制効果を有する事が確認された。

It has been proposed that angiogenesis inhibitors should be used for the treatment of diseases ac-companied by an uncontrolled angiogenic response, particularly such disease occuring during progres-sive growth of solid tumors.

In this study, the antiangiogenic effect of dex-amethasone (DEX) was studied in a system usingchorioallantoic membranes (CAM) of fertilized eggs and rabbit corneas.

First, DEX was examined for its effect on embry-onic angiogenesis using 4, 5 day old CAMs of chick embryos. After the shell and shell membrane was removed, an EV pellet with or without DEX was placed within a silicon ring. Two days later, the antiangiogenic response was evaluated by measur-ing the avascular zone of the CAM beneath the pellet. When the CAM showed an avascular zone of 3 mm or more in diameter, the response was scored as positive. DEX showed potent antiangogenic activity and produced an avascular zone in 100 % of CAMs at the highest dose tested. (250 ng/egg)

Next, inhibitory effect of vascularization and tumor growth by local implant of DEX was obser-ved in a rabbit cornea assay. An intra-corneal pocket extending to within 1 mm of the limbus was used to house a 1-mm³ piece of glioma. In the treatment group, DEX-containing EV pellet was inserted between the limbus and glioma. Ten days after the implantation of glioma and EV pellet, vascular response and tumor growth was evaluated. For morphologic studies, the excised corneas were fixed with formaldehyde fixative and sectioned for light microscopy. In all corneas that were implanted with tumor fragments, capillary growth from the limbus closest to the implanted glioma was recog-nized. And in all corneas that were implanted with tumor fragments and DEX pellets, neovasculariza-tion was limited.

In conclusion, DEX was confirmed to be a potent inhibitor of vascularization and tumor growth in both CAM assay and rabbit cornea assay.