Habib Nagy, Salama Hosny, Abd El Latif Abu Median Ahmed, Isac Anis Ilia, Abd Al Aziz Rasha Ahmed, Sarraf Catherine, Mitry Ragai, Havlik Roman, Seth Prem, Hartwigsen Jack, Bhushan Reva, Nicholls Joanna, Jensen Steen
Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital Campus, London W12 ONN, UK.
Cancer Gene Ther. 2002 Mar;9(3):254-9. doi: 10.1038/sj.cgt.7700431.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The prognosis of HCC is poor and current therapies are largely ineffective. Genetic abnormalities are commonly seen in HCC tumors particularly with inactivation of the p53 tumor suppressor. Gene therapy with E1B-deleted (dl1520) adenovirus could be of therapeutic value as it offers the potential of tumor growth control in patients with p53 mutation. Ten patients with posthepatitis cirrhosis and histologically proven HCC were enrolled into an open label, randomized prospective study. Randomization was to receive either percutaneous ethanol injection (control group) or dl1520. Toxicity and complications in the ethanol group were pain and fever, whereas in the gene therapy group complications were minimal. Grade I-II toxicity fever, stable performance status, and no significant rise in liver enzymes were observed in patients treated with dl1520. Analysis of patients' response to treatment in the gene therapy group showed one patient with a partial response and four patients with progressive disease. In the ethanol-treated group two patients had stable disease and three patients showed disease progression. In conclusion, this study showed that the adenovirus was well tolerated, but did not seem to offer significant tumor control. Although only a small number of patients were treated here it appears that more effective vectors are needed to achieve a useful clinical impact.
肝细胞癌（HCC）是全球最常见的癌症之一。HCC的预后很差，目前的治疗方法大多无效。基因异常在HCC肿瘤中很常见，尤其是p53肿瘤抑制基因失活。使用E1B缺失（dl1520）腺病毒进行基因治疗可能具有治疗价值，因为它为p53突变患者提供了控制肿瘤生长的潜力。十名患有肝炎后肝硬化且经组织学证实为HCC的患者被纳入一项开放标签、随机前瞻性研究。随机分组后，患者分别接受经皮乙醇注射（对照组）或dl1520治疗。乙醇组的毒性和并发症为疼痛和发热，而基因治疗组的并发症极少。接受dl1520治疗的患者出现了I-II级毒性发热、稳定的身体状况，且肝酶没有显著升高。对基因治疗组患者治疗反应的分析显示，一名患者部分缓解，四名患者疾病进展。在乙醇治疗组中，两名患者病情稳定，三名患者病情进展。总之，本研究表明腺病毒耐受性良好，但似乎无法有效控制肿瘤。尽管这里仅治疗了少数患者，但似乎需要更有效的载体才能产生有益的临床效果。
