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人嘧啶核苷转运蛋白-1 和脱氧胞苷激酶可预测埃及肝细胞癌患者吉西他滨的疗效。

Human equilibrative nucleoside transporter-1 and deoxycytidine kinase can predict gemcitabine effectiveness in Egyptian patients with Hepatocellular carcinoma.

机构信息

Departments of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

出版信息

J Clin Lab Anal. 2020 Nov;34(11):e23457. doi: 10.1002/jcla.23457. Epub 2020 Jul 16.

Abstract

BACKGROUND

Several biomarkers of gemcitabine effectiveness have been studied in cancers, but less so in hepatocellular carcinoma (HCC), which is identified as the fifth most common cancer worldwide. Investigation of human equilibrative nucleoside transporter-1 (HENT-1) and deoxycytidine kinase (DCK), genes involved in gemcitabine uptake and metabolism, can be beneficial in the selection of potential cancer patients who could be responding to the treatment.

AIM

To study HENT-1 and DCK gene expression in HCC patients with different protocols of treatment.

METHODS

Using real-time PCR, we analyzed expression levels of HENT-1 and DCK genes from peripheral blood samples of 109 patients (20 controls & 89 HCC patients) between March 2015 and March 2017. All the 89 HCC patients received the antioxidants selenium (Se) and vitamin E (Vit.E) either alone (45 patients) or in combination with gemcitabine (24 patients) or radiofrequency ablation (RFA) (20 patients).

RESULTS

There was a significant increase in HENT-1 expression levels in HCC patients treated with Se and Vit.E alone as compared to controls (P ˂ .0001), while there was no significant difference between HCC patients treated with gemcitabine or RFA as compared to controls. In contrast, expression of DCK was significantly increased in all groups of HCC patients as compared to controls (P ˂ .0001).

CONCLUSIONS

HENT-1 and DCK mRNA expressions are important markers of HCC and for GEM effect and GEM sensitivity in patients with HCC. This could be beneficial in the selection of HCC patients sensitive to gemcitabine to avoid subjecting resistant patients to unnecessary chemotherapy.

摘要

背景

已有多项研究探讨了吉西他滨疗效的生物标志物,然而在肝癌(HCC)中研究较少,HCC 是全球第五大常见癌症。研究人类核苷转运蛋白-1(HENT-1)和脱氧胞苷激酶(DCK)基因,这两种基因与吉西他滨摄取和代谢有关,可能有助于筛选出对治疗有反应的潜在癌症患者。

目的

研究不同治疗方案的 HCC 患者中 HENT-1 和 DCK 基因的表达。

方法

使用实时 PCR 技术,我们分析了 2015 年 3 月至 2017 年 3 月期间 109 名患者(20 名对照和 89 名 HCC 患者)外周血样本中 HENT-1 和 DCK 基因的表达水平。89 名 HCC 患者均接受了抗氧化剂硒(Se)和维生素 E(Vit.E)单独治疗(45 名患者)或联合吉西他滨(24 名患者)或射频消融(RFA)(20 名患者)治疗。

结果

与对照组相比,单独接受 Se 和 Vit.E 治疗的 HCC 患者 HENT-1 表达水平显著升高(P ˂ 0.0001),而接受吉西他滨或 RFA 治疗的 HCC 患者与对照组之间无显著差异。相比之下,所有 HCC 患者组的 DCK 表达均显著高于对照组(P ˂ 0.0001)。

结论

HCC 患者的 HENT-1 和 DCK mRNA 表达是 HCC 的重要标志物,也是吉西他滨效果和 HCC 患者吉西他滨敏感性的标志物。这有助于筛选对吉西他滨敏感的 HCC 患者,避免将耐药患者置于不必要的化疗中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37e4/7676182/0dce89d6d826/JCLA-34-e23457-g001.jpg

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