DKK-1 与肝脏恶性肿瘤的相关研究进展

肝脏恶性肿瘤包括原发性肝癌、继发性肝癌、肝母细胞瘤、肝脏淋巴瘤、肝脏血管内皮细胞肉瘤、纤维板层肝细胞癌、肝脏未分化胚胎肉瘤等发生在肝脏的恶性病变。其中原发性肝癌(primary liver cancer,PLC)是临床上最常见的恶性肿瘤之一。PLC在我国的发病人数占全球的55%,是我国第二个最常见的癌症死亡原因。由于肝脏恶性肿瘤具有隐匿性强、恶性程度高,病情进展快的特点,很多患者就诊时已到疾病中晚期,即使采取多学科综合治疗,预后也很不理想。因此,美国肝病研究学会(AASLD)和卫生部制定的《原发性肝癌诊疗规范(2011年版)》特别强调了早期筛查和早期监测对提高患者生存时间和生存质量的作用。甲胎蛋白(AFP)联合影像学检查是目前筛查肝脏恶性肿瘤的主要方法,但是AFP和影像学检查尚缺乏足够的敏感性和特异性,尤其对于早期癌症的诊断而言。DKK-1(dickkopf-1)是近年来由德国科学家新发现的一种分泌型糖蛋白。DKK-1与肝脏恶性肿瘤,尤其与原发性肝癌的早期诊断和预后判断关系密切,是最值得期待的肿瘤诊断标志物之一。本文谨对DKK-1的分子生物学特点、在恶性肿瘤中的表达以及与肝脏恶性肿瘤的关系进行综述,探讨其作为肝癌诊断蛋白标志物的研究现状及临床应用前景。     

Maintaining viability and characteristics of cholangiocarcinoma tissue by vitrification-based cryopreservation

Tumor tissue has great clinical and scientific value which relies highly on the proper preservation of primary materials. Conventional tumor tissue cryopreservation using slow-freezing method has yielded limited success, leading to significant cell loss and morphological damage. Here we report a standardized vitrification-based cryopreservation method, by which we have successfully vitrified and warmed 35 intrahepatic cholangiocarcinoma (ICC) tissues with up to 80% viability of the fresh tumor tissues. Cryopreserved ICC tissue could generate patient-derived xenografts (PDXs) with take rates of 68.2% compared to 72.7% using fresh tumor tissues. Histological and genetic analyses showed that no significant alterations in morphology and gene expression were introduced by this cryopreservation method. Our procedure may facilitate collection, long-time storage and propagation of cholangiocarcinoma or other tumor specimens for (pre)clinical studies of novel therapies or for basic research.