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Expression of apoptosis- and vitamin D pathway-related genes in hepatocellular carcinoma

机译:凋亡和维生素D途径相关基因在肝细胞癌中的表达

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Background/Aims: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and therapeutic options are scarce. As they might represent future targets for cancer therapy, the expression of apoptosis-related genes in HCC is of particular interest. In this pilot study, we further examined apoptosis-related genes in human HCC and also focused on vitamin D signaling as this might be a regulator of HCC cell apoptosis. Methods: We employed tumor tissue and serum samples from 62 HCC patients as well as 62 healthy controls for these studies. Tissue and serum specimens were analyzed by quantitative RT-PCR, immunohistochemistry and ELISA. Results: In HCC patients the apoptosis marker M30 was found to be elevated and several pro-apoptotic (TRAIL, FasL and FasR) as well as anti-apoptotic genes (Mcl-1 and Bcl-2) were simultaneously upregulated in tumor tissue and especially tumor-surrounding tissue as compared to healthy control livers. Moreover, vitamin D serum levels were decreased in HCC patients whereas vitamin D receptor mRNA expression was increased in tumor tissue and tumor-surrounding tissue as compared to healthy livers. Conclusions: In human HCC, M30 serum levels are elevated indicating an increased cell turnover. Modulation of the vitamin D pathway might be a supportive, pro-apoptotic HCC therapy.
机译:背景/目的:肝细胞癌(HCC)是全球第六大最常见的恶性肿瘤,治疗选择稀缺。由于它们可能代表癌症治疗的未来目标,因此引起肝癌中凋亡相关基因的表达特别令人关注。在这项前期研究中,我们进一步检查了人类HCC中与凋亡相关的基因,并且还关注维生素D信号传导,因为这可能是HCC细胞凋亡的调节剂。方法:我们采用了62例HCC患者的肿瘤组织和血清样本以及62例健康对照者进行这些研究。通过定量RT-PCR,免疫组织化学和ELISA分析组织和血清标本。结果:在肝癌患者中,发现凋亡标记物M30升高,并且在肿瘤组织中,尤其是在肿瘤组织中同时上调了一些促凋亡基因(TRAIL,FasL和FasR)以及抗凋亡基因(Mcl-1和Bcl-2)。与健康对照肝脏相比,肿瘤周围组织。此外,与健康肝脏相比,HCC患者的维生素D血清水平降低,而肿瘤组织和肿瘤周围组织中的维生素D受体mRNA表达增加。结论:在人类肝癌中,M30血清水平升高,表明细胞更新增加。调节维生素D途径可能是支持性的促凋亡HCC治疗。

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