Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects:: A phase I clinical trial
Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects:: A phase I clinical trial
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DOI：
10.1200/jco.2001.19.14.3422
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发表时间：
2001-07-15
影响因子：
45.3
通讯作者：
Hung, MC
中科院分区：
文献类型：
--
作者：
Hortobagyi, GN;Ueno, NT;Hung, MC
目的：临床前研究已经证明，5型腺病毒EIA基因通过HER-2/neu的转录抑制和细胞凋亡的诱导与抗肿瘤活性相关。事实上，已知E1 A基因治疗可诱导HER-2/neu过表达的乳腺癌和卵巢癌在裸鼠中消退。因此，我们在I期临床试验中评估了在HER-2/neu过表达和HER-2/neu低表达的乳腺癌和卵巢癌患者中腔内注射EIA基因与DC-Chol阳离子脂质体（DCC-E1 A）复合物的可行性。将与DCC-E1 A阳离子脂质体复合的EIA基因每周一次注射到18名晚期癌症患者的胸腔或腹腔中：结果：免疫组化和逆转录-聚合酶链反应（RT-PCR）均检测到肿瘤细胞中ETA基因的表达。E1 A基因表达伴随HER-2/neu下调、凋亡增加和增殖减少。最常见的治疗相关的毒性是发热，恶心，呕吐，和/或不适的注射situation.Conclusion：这些结果认为腔内DCC-E1 A管理的可行性，提供了一个明确的证明临床前的概念，并保证II期试验，以确定EIA基因的抗肿瘤活性。(C)2001年，美国临床肿瘤学会。
Purpose: preclinical studies have demonstrated that the adenovirus type 5 EIA gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of EIA gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial.Patients and Methods: An EIA gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of:the breast (n = 6) or ovary(n = 12).Results: ETA gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression wets accompanied by HER-2/neu down-regulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites.Conclusion: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the EIA gene. (C) 2001 by American Society of Clinical Oncology.