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[用于治疗卡波西肉瘤的HIV蛋白酶抑制剂]

[HIV protease inhibitors for the treatment of Kaposi's sarcoma].

作者信息

Grosso Gabriella, Sgadari Cecilia, Barillari Giovanni, Toschi Elena, Bacigalupo Ilaria, Carlei Davide, Palladino Clelia, Baccarini Sara, Malavasi Laura, Moracci Gabriele, Leone Patrizia, Chiozzini Chiara, Monini Paolo, Ensoli Barbara

机构信息

Reparto Infezioni da Retrovirus Laboratorio di Virologia, Istituto Superiore di Sanità, Roma.

出版信息

Recenti Prog Med. 2003 Feb;94(2):69-74.

Abstract

A reduced incidence or the regression of Kaposi's sarcoma (KS) has been described in HIV-infected patients treated with HIV-protease inhibitors (PI). We have recently demonstrated that PI block the angiogenesis and the development of KS lesions induced experimentally in vivo by the inoculation of angiogenic factors or human primary KS cells. These effects of PI occur at the same drug concentrations in plasma of treated individuals, and they are due to the inhibition of cell invasion and of the activation of matrix metalloprotease-2, an enzyme that is key to angiogenesis and tumor growth and invasion. Since PI also block the production of cytokines involved in KS initiation and maintenance, this anti-inflammatory activity of PI may also contribute to the anti-KS effects observed in treated individuals. Thus, by direct and indirect activities PI can simultaneously block several pathways involved in tumor growth, invasion or metastasis. These data indicate that PI should also be investigated and exploited for the therapy of KS and tumors of different histology occurring in non infected individuals.

摘要

在接受HIV蛋白酶抑制剂(PI)治疗的HIV感染患者中,已观察到卡波西肉瘤(KS)的发病率降低或病情消退。我们最近证明,PI可阻断通过接种血管生成因子或人原发性KS细胞在体内实验诱导的KS病变的血管生成和发展。PI的这些作用在接受治疗个体的血浆中以相同的药物浓度出现,这是由于细胞侵袭受到抑制以及基质金属蛋白酶-2(一种对血管生成、肿瘤生长和侵袭至关重要的酶)的激活受到抑制。由于PI还可阻断参与KS起始和维持的细胞因子的产生,PI的这种抗炎活性也可能有助于在接受治疗的个体中观察到的抗KS效应。因此,通过直接和间接作用,PI可同时阻断参与肿瘤生长、侵袭或转移的多种途径。这些数据表明,PI也应针对KS以及非感染个体中发生的不同组织学类型的肿瘤的治疗进行研究和开发。

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