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白细胞介素-2:实体瘤治疗

Interleukin-2: solid-tumor therapy.

作者信息

Oppenheim M H, Lotze M T

机构信息

Section of Surgical Oncology, University of Pittsburgh Medical Center, Pa.

出版信息

Oncology. 1994 Mar-Apr;51(2):154-69. doi: 10.1159/000227330.

Abstract

Interleukin-2 (IL-2) is a soluble factor produced by T cells that stimulates growth and activity of lymphocytes and other immune cells. First noted in murine studies, the antitumor efficacy of IL-2 has been shown to induce partial and complete regression of some tumors in human clinical trials over the past decade. Although the initial clinical success of IL-2 was in combination with lymphokine-activated killer cells, IL-2 alone has subsequently been shown to be equally efficacious. Combinations of cytokines and chemotherapies with IL-2 have been generally inconclusive and disappointing with the possible exception of interferon-alpha. Toxicities of IL-2 are common and often dose limiting. Symptomatic therapy has allowed patients to tolerate somewhat higher doses, but has not addressed the underlying mechanisms of these toxicities which may involve mediators such as tumor necrosis factor, interferon-gamma, and nitric oxide. Clinical studies assessing these factors for their involvement in the antitumor effects of IL-2 as well as its toxicities may allow better understanding of IL-2, and perhaps lead to improved cancer therapies.

摘要

白细胞介素-2(IL-2)是一种由T细胞产生的可溶性因子,可刺激淋巴细胞和其他免疫细胞的生长与活性。IL-2最初在小鼠研究中被发现,在过去十年的人类临床试验中,其抗肿瘤功效已被证明能使某些肿瘤部分或完全消退。尽管IL-2最初的临床成功是与淋巴因子激活的杀伤细胞联合使用,但随后发现单独使用IL-2同样有效。除了α干扰素外,细胞因子与化疗药物和IL-2联合使用的效果通常尚无定论且令人失望。IL-2的毒性很常见,且常常限制剂量。对症治疗使患者能够耐受稍高的剂量,但并未解决这些毒性的潜在机制,这些机制可能涉及肿瘤坏死因子、γ干扰素和一氧化氮等介质。评估这些因子在IL-2抗肿瘤作用及其毒性中的作用的临床研究,可能有助于更好地理解IL-2,并可能带来改进的癌症治疗方法。

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