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免疫相关基因多态性对曲妥珠单抗靶向乳腺癌细胞的影响。

Effects of immunorelated gene polymorphisms on trastuzumab targeting breast cancer cell .

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.

Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, China.

出版信息

Pharmacogenomics. 2024;25(10-11):461-468. doi: 10.1080/14622416.2024.2404819. Epub 2024 Oct 11.

DOI:10.1080/14622416.2024.2404819
PMID:39392082
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11492633/
Abstract

To investigate the associations between genetic polymorphisms in immunorelated genes and PBMC-induced cytotoxicity to breast cancer cell with the treatment of trastuzumab . Trastuzumab-mediated cytotoxicity of peripheral blood mononuclear cells (PBMC) from 148 healthy donors and 13 BC patients was analyzed by flow cytometry. 16 SNPs in 7 immunorelated genes were genotyped by Sequenom Mass Array Genotype Platform. Cytotoxicity in the trastuzumab treated PBMCs were significantly higher than those of the basal group. A wide variability in trastuzumab-mediated cytotoxicity was observed, and PBMC from individuals with the rs16859030 T genotype generated increased cytotoxicity than those with the CC genotype. The rs16859030 polymorphism affects trastuzumab-mediated cytotoxicity .

摘要

为了研究免疫相关基因的遗传多态性与曲妥珠单抗治疗乳腺癌细胞的外周血单个核细胞(PBMC)诱导细胞毒性之间的关系。通过流式细胞术分析了 148 名健康供体和 13 名 BC 患者的 PBMC 对曲妥珠单抗的细胞毒性。通过 Sequenom MassArray Genotype 平台对 7 个免疫相关基因中的 16 个 SNP 进行了基因分型。与基础组相比,曲妥珠单抗处理的 PBMC 的细胞毒性明显更高。曲妥珠单抗介导的细胞毒性存在广泛的可变性,并且具有 rs16859030T 基因型的个体的 PBMC 产生的细胞毒性比具有 CC 基因型的个体更高。rs16859030 多态性影响曲妥珠单抗介导的细胞毒性。

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本文引用的文献

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PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival.PTEN rs701848 多态性与曲妥珠单抗耐药的 HER2 阳性转移性乳腺癌相关,并预测无进展生存期。
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The combination of trastuzumab and pertuzumab administered at approved doses may delay development of trastuzumab resistance by additively enhancing antibody-dependent cell-mediated cytotoxicity.以批准剂量给予曲妥珠单抗和帕妥珠单抗联合用药,可通过累加增强抗体依赖性细胞介导的细胞毒性来延缓曲妥珠单抗耐药性的发展。
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