Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207
Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207
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DOI：
10.1089/10430349950017211
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发表时间：
1999-09-01
影响因子：
4.2
通讯作者：
Martuza, RL
中科院分区：
文献类型：
--
作者：
Walker, JR;McGeagh, KG;Martuza, RL
前列腺癌是男性中最常见的非皮肤恶性肿瘤，并且是美国癌症死亡的第二常见原因（Landis等人，1998年）。手术或放射疗法的初始治疗可能由于神经损伤而导致阳痿和/或失禁（Eastham和Scardino，1998; Porter等人，1998年）。当发生前列腺外或转移性疾病时，可采用去势或药物雄激素消融（Catalona，1994）。雄激素抵抗复发表明预后差，并证明实验性化疗是合理的（Oh和Kantoff，1998）。G207（Mineta等人，1995; Yazaki等人，1995）是一种多突变的单纯疱疹病毒1（HSV）载体，其在癌细胞内复制，导致细胞死亡;然而，复制在正常细胞中受到限制，包括神经系统的细胞。在体外，G207在低感染复数（MOI为0.01）下对多种人前列腺癌细胞具有溶瘤作用。在无胸腺小鼠中，单次瘤内接种G207完全根除>22%的已建立的皮下人前列腺癌肿瘤，而与激素反应性无关。两次肿瘤内接种G207完全根除了三个复发的先前照射的肿瘤中的两个，两次静脉注射G207诱导远处皮下肿瘤的肿瘤消退，并完全根除了四分之一的肿瘤。
Prostate adenocarcinoma is the most common nonskin malignancy in males and the second most common cause of cancer death in the United States (Landis et al., 1998). Initial treatments of surgery or radiotherapy may cause impotence and/or incontinence from neural damage (Eastham and Scardino, 1998; Porter et al., 1998). When extraprostatic or metastatic disease develops, castration or pharmaceutical androgen ablation is utilized (Catalona, 1994). Androgen-resistant recurrence indicates a poor prognosis and justifies experimental chemotherapy (Oh and Kantoff, 1998). G207 (Mineta et al., 1995; Yazaki et al., 1995) is a multimutated herpes simplex virus 1 (HSV) vector that replicates within cancer cells, causing cellular death; however, replication is limited in normal cells, including those of the nervous system. In vitro, G207 at a low multiplicity of infection (MOI of 0.01) is oncolytic for multiple human prostate cancer cells. In athymic mice, a single intraneoplastic inoculation of G207 completely eradicates >22% of established subcutaneous human prostate cancer tumors irrespective of hormonal responsiveness. Two intraneoplastic inoculations of G207 completely eradicated two of three recurrent previously irradiated tumors and two intravenous administration of G207 induced tumor regression in distant subcutaneous tumors and completely eradicated one-fourth of the tumors.