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细胞色素 P450 酶在儿科非横纹肌肉瘤软组织肉瘤中的表达:在致癌作用和治疗反应中的可能作用。

Expression of Cytochrome P450 Enzymes in Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Possible Role in Carcinogenesis and Treatment Response.

机构信息

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Mexico City, Mexico.

Instituto de Investigaciones Biomédicas, Universidad Autónoma de México, Mexico City, Mexico.

出版信息

Int J Toxicol. 2022 May-Jun;41(3):234-242. doi: 10.1177/10915818221085909. Epub 2022 Apr 19.

DOI:10.1177/10915818221085909
PMID:35437033
Abstract

The 5-year relative survival rate estimate of treated patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is ∼50% since they generally present with tumor progression, relapse, metastasis, and/or chemoresistance. The expression of cytochrome P450 (CYP) enzymes in malignancies can affect the pharmacology of drugs commonly used in chemotherapy or confer susceptibility to development of chemical carcinogenesis; in addition, their specific tumor expression can be used as a therapeutic target. Using qPCR and Western blot assays, the expression of CYP1B1, CYP2E1, CYP3A4, and CYP3A5 were analyzed in a cohort of tumor tissue paired with non-malignant adjacent tissue of patients with NRSTS. The mRNA and protein expression of CYP1B1, CYP2E1, and CYP3A4 were significantly increased in tumor tissue. We propose that the expression of these isoforms is related to carcinogenesis and chemoresistance frequently observed in these neoplasms.

摘要

经治疗的非横纹肌肉瘤软组织肉瘤(NRSTS)患者的 5 年相对生存率估计约为 50%,因为它们通常表现为肿瘤进展、复发、转移和/或化疗耐药。细胞色素 P450(CYP)酶在恶性肿瘤中的表达会影响化疗中常用药物的药理学,或者易发生化学致癌作用;此外,它们在特定肿瘤中的表达可以用作治疗靶点。本研究使用 qPCR 和 Western blot 分析了 NRSTS 患者肿瘤组织及其配对的非恶性邻近组织中 CYP1B1、CYP2E1、CYP3A4 和 CYP3A5 的表达。CYP1B1、CYP2E1 和 CYP3A4 的 mRNA 和蛋白表达在肿瘤组织中显著增加。我们提出这些同工酶的表达与这些肿瘤中经常观察到的癌变和化疗耐药有关。

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