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Anticancer Res. 2013 Aug;33(8):3047-52.
Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide (NAD(+)) synthesis. NAMPT expression promotes angiogenesis, DNA synthesis, cell growth and survival, and mitochondrial biogenesis and function. Sirtuin-3 (SIRT3) is an NAD(+)-dependent deacetylase which functions in conjunction with mitochondrial NAMPT to promote cell survival following genotoxic stress. NAMPT expression is increased in several human malignancies, while SIRT3 levels are increased in some malignancies and suppressed in others. Based on this, we hypothesized that NAMPT and SIRT3 expression might be increased in well-differentiated thyroid carcinomas (TCs), follicular carcinomas (FC) and papillary thyroid carcinomas (PTC). Immunohistochemical analysis for NAMPT and SIRT3 staining was performed on these tumors using tissue microarrays. NAMPT and SIRT3 expression was low in benign thyroid tissues, moderately increased in FC, and more highly expressed in PTC. Specifically we observed both NAMPT and SIRT3 to be highly expressed in well-differentiated TCs. The data suggest that mitochondrial alterations play a role in the development and maintenance of well-differentiated TC. Since an effective pharmacological NAMPT inhibitor is currently in clinical use, further studies of NAMPT overexpression in well-differentiated TCs may be useful in selecting patients for NAMPT inhibitor therapy, particularly for metastatic well-differentiated thyroid carcinomas refractory to other treatments.
烟酰胺磷酸核糖基转移酶（NAMPT）催化烟酰胺腺嘌呤二核苷酸（NAD(+)）合成的限速步骤。NAMPT 的表达促进血管生成、DNA 合成、细胞生长和存活以及线粒体生物发生和功能。Sirtuin-3（SIRT3）是一种 NAD(+)依赖性去乙酰化酶，与线粒体 NAMPT 一起在遗传毒性应激后促进细胞存活。几种人类恶性肿瘤中 NAMPT 的表达增加，而 SIRT3 水平在一些恶性肿瘤中增加，而在另一些恶性肿瘤中则降低。基于此，我们假设 NAMPT 和 SIRT3 的表达可能在分化良好的甲状腺癌（TC）、滤泡状癌（FC）和甲状腺乳头状癌（PTC）中增加。使用组织微阵列对这些肿瘤进行了 NAMPT 和 SIRT3 染色的免疫组织化学分析。良性甲状腺组织中 NAMPT 和 SIRT3 的表达较低，FC 中度增加，PTC 表达更高。具体来说，我们观察到 NAMPT 和 SIRT3 在分化良好的 TC 中均高度表达。数据表明，线粒体改变在分化良好的 TC 的发生和维持中起作用。由于有效的药理学 NAMPT 抑制剂目前正在临床使用，因此对分化良好的 TC 中 NAMPT 过表达的进一步研究可能有助于选择接受 NAMPT 抑制剂治疗的患者，特别是对其他治疗方法耐药的转移性分化良好的甲状腺癌患者。
