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甲胎蛋白生长抑制肽作为肿瘤生长和转移生物治疗药物的最新进展。

Update of alpha fetoprotein growth-inhibitory peptides as biotherapeutic agents for tumor growth and metastasis.

作者信息

Mizejewski G J, Muehlemann M, Dauphinee M

机构信息

Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.

出版信息

Chemotherapy. 2006;52(2):83-90. doi: 10.1159/000091728. Epub 2006 Feb 22.

Abstract

The present update describes the biological activities of an alpha fetoprotein (AFP)-derived peptide termed the growth-inhibitory peptide (GIP), which is a synthetic 34-amino acid segment produced from the native molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult cells. Even though its mechanism of action has not been completely elucidated, GIP has been shown to engage in cellular events such as endocytosis, cellular aggregation, hemagglution, and cytoskeleton-induced cell shape changes. The GIP was shown to be growth-suppressive in nine different human tumor types and to suppress the spread of tumor infiltrates and metastases in human and mouse mammary cancers. It was further found that the oligomeric state (cyclic vs. linear configuration) of the GIP determined its biological and anticancer efficacy. The combined properties of tumor growth suppression and reduction of tumor metastases represent promising areas for GIP as a chemotherapeutic agent. It was concluded that the GIP derived from full-length AFP represents a growth-inhibitory motif possessing intrinsic properties that allow it to interact in cell surface events such as tumor proliferation, progression, and metastasis.

摘要

本次更新描述了一种源自甲胎蛋白(AFP)的肽——生长抑制肽(GIP)的生物学活性,它是从天然分子中产生的一个34个氨基酸的合成片段。GIP已被证明在胎儿细胞和肿瘤细胞中具有生长抑制作用,但在成年细胞中则无此作用。尽管其作用机制尚未完全阐明,但GIP已被证明参与细胞内吞、细胞聚集、血细胞凝集和细胞骨架诱导的细胞形状变化等细胞事件。GIP在九种不同的人类肿瘤类型中显示出具有生长抑制作用,并能抑制人类和小鼠乳腺癌中肿瘤浸润和转移的扩散。进一步发现,GIP的寡聚状态(环状与线性构型)决定了其生物学和抗癌功效。肿瘤生长抑制和肿瘤转移减少的综合特性使GIP作为一种化疗药物具有广阔前景。得出的结论是,源自全长AFP的GIP代表一种具有内在特性的生长抑制基序,使其能够在肿瘤增殖、进展和转移等细胞表面事件中相互作用。

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