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小鼠重组干扰素β、小鼠重组干扰素γ与人重组白细胞介素-2联合应用对荷 MethA 小鼠的抗肿瘤作用。

Antitumor effect of combination of murine recombinant interferon beta, murine recombinant interferon gamma and human recombinant interleukin-2 in MethA-bearing mice.

作者信息

Itoh T, Sakata Y, Yoshida Y, Tsushima K, Suzuki H, Saitoh S, Tamura Y, Ogasawara H, Sugimoto N, Takemori H

机构信息

First Department of Internal Medicine, Hirosaki University School of Medicine, Japan.

出版信息

Cancer Immunol Immunother. 1990;32(2):88-94. doi: 10.1007/BF01754204.

Abstract

We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.

摘要

我们之前曾报道,在携带MethA肿瘤的小鼠中,小鼠重组干扰素β(Mu-rIFNβ)与小鼠重组干扰素γ(Mu-rIFNγ)联合使用比单独使用其中任何一种对肿瘤生长的抑制作用更强。在本研究中,我们检测了在携带同基因MethA纤维肉瘤的BALB/c小鼠中,向Mu-rIFNβ与Mu-rIFNγ的联合用药中添加人重组白细胞介素-2(Hu-rIL-2)对肿瘤生长的影响。低剂量的Hu-rIL-2(5×10³ U或5×10⁴ U,间隔3天给药)未显示出抗肿瘤活性,而高剂量的Hu-rIL-2(5×10⁵ U)则显示出显著的生长抑制作用。除了IFNβ和IFNγ联合用药外,给予IL-2(剂量范围为5×10³ U至5×10⁵ U)显示出更强的抗肿瘤作用,且呈剂量依赖性。此外,与干扰素和IL-2的序贯给药相比,同时给予IL-2、IFNβ和IFNγ具有更有效的治疗活性。这些发现表明,IL-2与IFNβ和γ联合使用对癌症治疗有效。

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