Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer.
Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer.
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DOI：
10.3390/v15040901
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发表时间：
2023-03-31
期刊：
影响因子：
--
通讯作者：
Yamamoto M
中科院分区：
文献类型：
--
作者：
Gavrikova T;Nakamura N;Davydova J;Antonarakis ES;Yamamoto M
背景资料：用于去势抵抗性前列腺癌（CRPC），特别是神经内分泌前列腺癌（NEPC）的条件复制型腺病毒（CRAds）的开发有两个主要障碍：控制元件的选择和差的感染性。我们应用基于纤维修饰的感染性增强和雄激素非依赖性启动子（环氧合酶-2，考克斯-2）来克服这些问题。方法：在两种CRPC细胞系（Du-145和PC 3）中检测考克斯-2启动子的特性和纤维修饰的效果。在体外测试纤维修饰的考克斯-2 CRAd的杀细胞作用以及在体内测试皮下CRPC异种移植物的抗肿瘤作用。结果如下：在两种CRPC细胞系中，考克斯-2启动子显示出高活性，Ad 5/Ad 3纤维修饰显著增强腺病毒感染性。考克斯-2 CRAds在CRPC细胞中显示出有效的细胞杀伤作用，并通过纤维修饰显着增强。在体内，考克斯-2 CRAd在Du-145中显示出抗肿瘤作用，而只有Ad 5/Ad 3 CRAd在PC 3中显示出最强的抗肿瘤作用。结论：基于考克斯-2启动子的感染性增强CRAds对CRPC/NEPC细胞具有较强的抗肿瘤作用。
Background: The development of conditionally replicative adenoviruses (CRAds) for castration-resistant prostate cancer (CRPC), particularly neuroendocrine prostate cancer (NEPC), has two major obstacles: choice of control element and poor infectivity. We applied fiber-modification-based infectivity enhancement and an androgen-independent promoter (cyclooxynegase-2, COX-2) to overcome these issues. Methods: The properties of the COX-2 promoter and the effect of fiber modification were tested in two CRPC cell lines (Du-145 and PC3). Fiber-modified COX-2 CRAds were tested in vitro for cytocidal effect as well as in vivo for antitumor effect with subcutaneous CRPC xenografts. Results: In both CRPC cell lines, the COX-2 promoter showed high activity, and Ad5/Ad3 fiber modification significantly enhanced adenoviral infectivity. COX-2 CRAds showed a potent cytocidal effect in CRPC cells with remarkable augmentation by fiber modification. In vivo, COX-2 CRAds showed an antitumor effect in Du-145 while only Ad5/Ad3 CRAd showed the strongest antitumor effect in PC3. Conclusion: COX-2 promoter–based, infectivity-enhanced CRAds showed a potent antitumor effect in CRPC/NEPC cells.
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影响因子：
82.9
作者：
Gaggar, A;Shayakhmetov, DM;Lieber, A
通讯作者：
Lieber, A
影响因子：
51.1
作者：
Khor, Li-Yan;Bae, Kyounghwa;Dicker, Adam P.
通讯作者：
Dicker, Adam P.
影响因子：
4.6
作者：
Hsu EC;Shen M;Aslan M;Liu S;Kumar M;Garcia-Marques F;Nguyen HM;Nolley R;Pitteri SJ;Corey E;Brooks JD;Stoyanova T
通讯作者：
Stoyanova T
DOI：
10.1158/1078-0432.ccr-12-3791
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Aparicio AM;Harzstark AL;Corn PG;Wen S;Araujo JC;Tu SM;Pagliaro LC;Kim J;Millikan RE;Ryan C;Tannir NM;Zurita AJ;Mathew P;Arap W;Troncoso P;Thall PF;Logothetis CJ
通讯作者：
Logothetis CJ
DOI：
10.1158/1078-0432.ccr-13-3309
发表时间：
2014-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beltran H;Tomlins S;Aparicio A;Arora V;Rickman D;Ayala G;Huang J;True L;Gleave ME;Soule H;Logothetis C;Rubin MA
通讯作者：
Rubin MA