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