不可切除和复发的头颈癌患者,以四组不同的剂量(15、30、6 0 和120 μg DNA/cm3 肿瘤)进行瘤体注射,未发现明显的毒性作用;评估的6例 患者中,4例肿瘤得到控制,1例部分缩小,1例有较小的改变。Kirn等[24]用在 p53功能丧失的肿瘤细胞中选择性复制的E1B缺失的5型腺病毒(ONYX-015),对复 发的、放化学治疗难以控制的21例头颈癌患者进行Ⅱ期临床试验,每天肿瘤内注射 ONYX-015(1010PFU),连续5天,每3周重复治疗一次,13例患者可以评估,其中 2例肿瘤缩小50%以上,2例完全消退,5例肿瘤稳定持续6~12周,3例症状(咬颌和 语言)得到改善,1例治疗前后无改变。以上结果均表明E1A基因对晚期头颈部肿瘤 的治疗是有效的。 目前大多数基因治疗的策略是基于肿瘤局部注射,该途径安全、简捷、易于观 察疗效。因此,头颈肿瘤应是E1A基因临床应用首选的肿瘤。E1A基因不仅局部注射 Ⅰ、Ⅱ期临床试验均取得了肯定的疗效,而且静脉注射在动物模型也取得了较好的 治疗效果,未见明显的毒副作用。因此,E1A基因通过多种途径,作用于不同的基 因,不仅可以治疗不可手术的和复发的头颈癌,而且对远处转移的头颈癌也可获得 同样的治疗效果。所以,E1A基因在头颈肿瘤治疗中的应用前景可能是光明的。 近年来,随着分子生物学技术的发展,基因治疗的研究在医学领域越来越活跃 。相信E1A基因的临床应用将有可能推动肿瘤的综合治疗,进一步改善患者的生存 质量,提高患者的生存率。 参 考 文 献 1 屠规益,韩德民.当前头颈肿瘤科研应着重临床实用.中华耳鼻咽喉科杂志,199 7,32: 131-132. 2 屠规益,唐平章.我国头颈肿瘤外科的发展轨迹.中华耳鼻咽喉科杂志,1998,33 :259-260. 3 Nakajima T,Morita K,Ohi N, et al.Degradation of topoisomerase Ⅱα d uring adenovirus E1A-induced apoptosis is mediated by the activation of the ubiquitin proteolysis system.J Biol Chem,1996,271:24842-24849. 4 Somasundaram K,El-Deiry WS.Inhibition ofp53 -mediated transactivatio n and cell cycle arrest by E1A through its p300/CBP-interacting region. Oncogene, 1997,14:1047-1057. 5 Yu D,Hung MC.The erbB2 gene as a cancer therapetic target and the tu mor- and metastasis-suppressing function of E1A .Cancer Metast Rev,1998 ;17:195-202. 6 Chang JY,Xia W,Shao R et al.Inhibition of intratracheal lung cancer development by systemic delivery of E1A .Oncogene,1996,13:1405-1412. 7 Tsai CM,Yu D,Chang KT,et al.Enhanced chemoresistance by elevation of p185neu Levels in HER-2/neu-transfected human lung cancer cell.J Natl Cancer Inst,1995,87:682-684. 8 Yu D,Suen TC,Yan DH,et al.Transcriptional repression of the neu prot ooncogene by the adenovirus 5 E1A gene products.Proc Natl Acad Sci U S A,1990,87:4499-4503. 9 Frisch SM,Dolter KE.Adenovirus E1A-mediated tumor suppression by a c -erbB-2/neu-independent mechanism.Cancer Res, 1995,55:5551-5555. 10 Ricardo SP,Quintanilla M,Cano A, et al.Cancinoma cell lines become sensitive to DNA-damaging agents by the expression of the adenovirus E1 A gene.Oncogene,1996,13:1083-1092. 11 Chen MJ,Holskin B,Strickler J, et al.Induction by E1A oncogene expr ession of cellular susceptibility to lysis by TNF.Nature,1987,330:581-5 84. 12 Steeg PS,Bevilacqa G,Pozzatti R, et al.Altered expression of nm23,a gene associated with low tumor metastatic potential,during adenovirus 2 E1A inhibition of experimental metastasis.Cancer Res,1988,48:6550-655 4. 13 Shao RP,Karunagaran D,Zhou BH, et al.Inhibition of nuclear factor-K B activity is involved in E1A-mediated sensitization ofradiation-induce d apoptosis.J Biol Chem,1997,272:32739-32742. 14 Xia W,Lan YK,Zhang HZ, et al.Strong correlation between c-erbB-2 ov erexpression and overall survival of patients with oral squamous cell c arcinoma.Clin Cancer Res,1997,3:3-9. 15 Hou L,Shi D,Tu SM, et al.Oral cancer progression and c-erbB-2/neu p roto-oncogene expression.Cancer Letters,1992,65:215-220. 16 Beckhardt RN,Kiyokawa N,Xi L, et al.HER-2/neu oncogene characteriza tion in head and neck squamous cell carcinoma.Arch Otolaryngol Head Nec k Surg, 1995, 121:1265-1270. 17 Karja V,Syrjanen S,Kataja V, et al.c-erbB-2 oncogene expression in salivary land tumors.ORL J Otorhinolaryngol Relat Spec, 1994,56:206-212 . 18 王琪,韩德民,刘鋋,等.头颈部肿瘤的P53基因研究进展.国外医学耳鼻咽喉 科学分册,1996,20:4-7. 19 Liu M,Lawson G,Delos M, et al. Expression of E-cadherin adhesion mo lecule in vocal cord carcinomas. Eur Arch Otorhinolaryngol,1997,254:417 -421. 20 王强,郭敏,孙连玉.nm23-H1基因在喉癌组织中表达的研究.中华耳鼻咽喉科 杂志,1996,31:198-200. 21 Yu D,Matin A,Xia W, et al.Liposome-mediated in vivo E1A gene tranfe r suppressed dissemination of ovarian cancer cells that overexpress HER -2/neu.Oncogene, 1995,11:1383-1388. 22 Ueno NT,Hung MC,Zhang S, et al.Phase I E1A gene therapy in patients with advanced breast and ovarian cancer.Proc AACR,1998,39:360-364. 23 Yoo GH,Ensley J,Jacobs J, et al.Intratumoral E1A gene therapy for p atients with unresectable and recurrent head and neck cancer.Proc AACR, 1998,39:322-324. 24 Kirn D,Nemunaitis J,Ganly I, et al. A phase Ⅱ trial of intratumora l injection with an E1B-deleted adenovirus, ONYX-015,in patients with r ecurrent,refractory head and neck cancer.Proc ASCO,1998,17:391-394.
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