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原发性肝癌是世界上最常见、最严重的10种恶性肿瘤之一,主要有3种组织学类型:肝细胞肝癌(hepatocellular carcinoma, HCC)、胆管细胞癌(cholangiocarcinoma, CCC)和混合细胞肝癌,其中HCC约占90%[1]。导致发生HCC的危险因素包括乙型肝炎病毒、丙型肝炎病毒、酒精性肝病和可能的非酒精性脂肪肝[2]。现阶段应用于临床的治疗方式主要有肝段切除术、局部消融术、肝移植术及分子靶向药物治疗等,但患者的预后仍不佳[3]。
早在1924年, Warburg发现癌细胞采用一种特殊的方式产生能量。大多数肿瘤细胞在有氧条件下仍通过产能率相对较低的糖酵解为自身供能,这就是著名的“Warburg效应”[4]。由于肿瘤细胞无限增殖的能力,肿瘤细胞内部常处于缺氧的状态,而糖酵解通路可以提高组织细胞对缺氧的耐受性[5]。此外,糖酵解途径导致的乳酸增加可以分解破坏肿瘤细胞周围的细胞基质,促进肿瘤细胞迁移[6],在恶性肿瘤的转移中也具有重要的作用。
18F-FDG是一种葡萄糖类似物,主要通过葡萄糖转运体(glucose transporters, Gluts)转运至细胞内,然后在己糖激酶(hexokinase, HK)的作用下生成18F-FDG-6-磷酸盐,后者不能自由进出细胞膜而被滞留在细胞内。早期研究显示,在大多数肿瘤细胞内均可观察到Glut-1和HK的高表达,因此,在肿瘤细胞内18F-FDG的摄取明显增高,这也是18F-FDG作为显像剂的原理之一。自20世纪80年代以来,18F-FDG PET显像被广泛应用于临床恶性肿瘤的诊断,但在HCC的18F-FDG PET显像研究中发现其灵敏度较低,仅为50%~70%[7-8],这可能与HCC葡萄糖代谢特点密切相关。本文回顾分析了国内外对HCC葡萄糖代谢的研究,并对其代谢机制及在PET显像中的应用价值进行综述。
肝细胞肝癌的葡萄糖代谢机制及在PET显像中的应用价值
Glycometabolism mechanism in hepatocellular carcinoma and its application in PET
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摘要: 目的 肝细胞肝癌(HCC)是最常见的恶性肿瘤之一,其恶性程度较高,患者预后较差。众所周知,恶性肿瘤和正常细胞之间的葡萄糖代谢方式存在显著差异,恶性肿瘤摄取葡萄糖明显高于正常组织。然而,不同分化程度的HCC其葡萄糖代谢变化很大。18F-FDG是一种葡萄糖类似物,作为一种非特异性的显像剂被广泛应用于临床恶性肿瘤(包括HCC)的显像。全面了解HCC的葡萄糖代谢特性及其机制有助于临床更好地掌握PET显像在HCC中的应用价值,寻找更为有效的肿瘤治疗药物及新的分子探针应用于HCC的疗效评价。笔者就HCC的葡萄糖代谢特点及在PET显像中的应用价值进行综述。
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关键词:
- 癌, 肝细胞 /
- 正电子发射断层显像术 /
- 糖代谢 /
- 转运蛋白
Abstract: Hepatocellular carcinoma (HCC) is one of the most lethal tumors and has high malignancy and low survival. Generally, the glucose metabolism in malignant tumors is significantly different from normal tissues, which show high uptake. However, it varies greatly in HCC. Low glucose metabolism is often observed in well- and moderately differentiated HCC. Furthermore, glycolysis has been widely confirmed to be a nonspecific biological phenomenon in malignant tumors, including HCC, by positron emission tomography (PET) combined with computed tomography using 18-fluorine-fluorodeoxyglucose (a glucose analogue). However, to determine the value of PET and develop new effective drugs and molecular probes, we need to comprehensively understand how hepatocellular cancer cells use glucose to supply energy. In this article, we reviewed and summarized the glycometabolism characteristics of HCC and their application in PET. -
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