AIM: HI01, an EIB 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumo...AIM: HI01, an EIB 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumor activity and toxicity in combination with chemotherapy in patients with late stage cancers.METHODS: H101 5.0×10^11 virus particles were given by intra-tumor injection daily for five consecutive days at every three-week cycle, combined with routine chemotherapy,to one of the tumor lesions of 50 patients with different malignant tumors. Tumor lesions without H101 injection in the same individuals were used as controls. The efficacy and toxicity were recorded.RESULTS: Forty-six patients were evaluable with a 30.4% response rate. H101 injection in combination with chemotherapy induced three complete response (CR) and 11 partial response (PR), giving an overall response rate of 28.0% (14/50) among intention-to-treat patients. The response rate for the control lesions was 13.0%, including one case with CR and five cases with PR, which was significantly lower than that for the injected lesions (P<0.05).Main side effects were fever (30.2%) and pain at the injected sites (26.9%). Grade 1 hepatic dysfunction was found in four patients, grade 2 in one patient, and grade 4 in one patient. Hematological toxicity (grade 4) was found in four patients.CONCLUSION: Intra-tumor injection of the genetically engineered adenovirus H101 exhibits potential anti-tumor activity to refractory malignant tumors in combination with chemotherapy. Low toxicity and good tolerance of patients to H101were observed.展开更多
背景溶瘤病毒作为治疗癌症的新手段,具有疗效快,靶向性强,无细胞毒性等特点,H101作为商品化上市的溶瘤病毒表现出了稳定的抗癌特效,为中晚期胃癌患者的腹膜转移治疗提供了可能.目的探讨H101对胃癌细胞增殖、迁移、凋亡的调控作用及其相...背景溶瘤病毒作为治疗癌症的新手段,具有疗效快,靶向性强,无细胞毒性等特点,H101作为商品化上市的溶瘤病毒表现出了稳定的抗癌特效,为中晚期胃癌患者的腹膜转移治疗提供了可能.目的探讨H101对胃癌细胞增殖、迁移、凋亡的调控作用及其相关机制研究.方法将BGC-823和SGC-7901两种胃癌细胞系培养在6孔板中,分别加入感染复数(multiplicity of infection,MOI)值为1、5、10、15的H101,作用48 h后,用MTS法检测细胞的存活率,免疫印迹法(western blot,WB)检测腺病毒早期区1(adenovirus early region 1,E1A)的表达.选取SGC-7901细胞,用划痕法检测各组细胞48 h的迁移率,Hoechst33342染液,观察H101作用48 h后凋亡小体的形成情况.Western blot检测细胞凋亡相关蛋白的表达.结果WB结果显示,H101中的EIA表达量比对照组更高,差异具有统计学意义(P<0.05).MTS结果显示与MOI值为1时相比,MOI值为15的时候,H101在体外可以明显杀伤BGC-823和SGC-79012种胃癌肿瘤细胞(P<0.05).在增殖实验中发现相对于BGC-823细胞,SGC-7901细胞对H101的敏感性更差,因此选取敏感性相对较差的SGC-7901细胞作为研究重点.48 h后,与对照组和MOI=1组的迁移距离相比,MOI=5组,MOI=10组和MOI=15组的迁移距离明显更低,(P均<0.05).与MOI=1组相比,MOI=5、MOI=10和MOI=15组的凋亡小体数量更多(P均<0.05),与对照组和MOI=1组相比,MOI=5、MOI=5和MOI=10组的B淋巴细胞瘤-2蛋白(B-cell lymphoma-2,Bcl-2)表达量较低(P均<0.05),而凋亡蛋白(BCL2-associated X,Bax)、半胱氨酸蛋白酶-3(cysteinyl aspartate specific proteinase-3,Caspase-3)表达量均更高(P均<0.05).结论H101能够抑制胃癌细胞的增殖、迁移,提高细胞凋亡相关蛋白的表达量,加速细胞的凋亡.展开更多
Transcatheter arterial chemoembolization (TACE) has become the standard treatment modality for unresectable hepatocellular carcinoma (HCC). Nonetheless, the clinical outcomes in patients with unresectable HCC are ofte...Transcatheter arterial chemoembolization (TACE) has become the standard treatment modality for unresectable hepatocellular carcinoma (HCC). Nonetheless, the clinical outcomes in patients with unresectable HCC are often unsatisfactory, especially in those with recurrent HCC. H101, an E1B gene deleted adenovirus, is known to have a significant antitumor activity. In addition, local injection of H101 can enhance the effect of antitumor therapies (chemotherapy and radiotherapy). Transarterial H101 gene injection in combination with TACE may help to control refractory and recurrent HCC. In this study, we report a 55-year-old patient with recurrent HCC which was treated with transarterial injection of H101 in combination with TACE, leading to a good clinical prognosis of the patient.展开更多
基金Supported by China "863" Hi-tech R&D Program,No.2002AA2Z3304
文摘AIM: HI01, an EIB 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumor activity and toxicity in combination with chemotherapy in patients with late stage cancers.METHODS: H101 5.0×10^11 virus particles were given by intra-tumor injection daily for five consecutive days at every three-week cycle, combined with routine chemotherapy,to one of the tumor lesions of 50 patients with different malignant tumors. Tumor lesions without H101 injection in the same individuals were used as controls. The efficacy and toxicity were recorded.RESULTS: Forty-six patients were evaluable with a 30.4% response rate. H101 injection in combination with chemotherapy induced three complete response (CR) and 11 partial response (PR), giving an overall response rate of 28.0% (14/50) among intention-to-treat patients. The response rate for the control lesions was 13.0%, including one case with CR and five cases with PR, which was significantly lower than that for the injected lesions (P<0.05).Main side effects were fever (30.2%) and pain at the injected sites (26.9%). Grade 1 hepatic dysfunction was found in four patients, grade 2 in one patient, and grade 4 in one patient. Hematological toxicity (grade 4) was found in four patients.CONCLUSION: Intra-tumor injection of the genetically engineered adenovirus H101 exhibits potential anti-tumor activity to refractory malignant tumors in combination with chemotherapy. Low toxicity and good tolerance of patients to H101were observed.
文摘背景溶瘤病毒作为治疗癌症的新手段,具有疗效快,靶向性强,无细胞毒性等特点,H101作为商品化上市的溶瘤病毒表现出了稳定的抗癌特效,为中晚期胃癌患者的腹膜转移治疗提供了可能.目的探讨H101对胃癌细胞增殖、迁移、凋亡的调控作用及其相关机制研究.方法将BGC-823和SGC-7901两种胃癌细胞系培养在6孔板中,分别加入感染复数(multiplicity of infection,MOI)值为1、5、10、15的H101,作用48 h后,用MTS法检测细胞的存活率,免疫印迹法(western blot,WB)检测腺病毒早期区1(adenovirus early region 1,E1A)的表达.选取SGC-7901细胞,用划痕法检测各组细胞48 h的迁移率,Hoechst33342染液,观察H101作用48 h后凋亡小体的形成情况.Western blot检测细胞凋亡相关蛋白的表达.结果WB结果显示,H101中的EIA表达量比对照组更高,差异具有统计学意义(P<0.05).MTS结果显示与MOI值为1时相比,MOI值为15的时候,H101在体外可以明显杀伤BGC-823和SGC-79012种胃癌肿瘤细胞(P<0.05).在增殖实验中发现相对于BGC-823细胞,SGC-7901细胞对H101的敏感性更差,因此选取敏感性相对较差的SGC-7901细胞作为研究重点.48 h后,与对照组和MOI=1组的迁移距离相比,MOI=5组,MOI=10组和MOI=15组的迁移距离明显更低,(P均<0.05).与MOI=1组相比,MOI=5、MOI=10和MOI=15组的凋亡小体数量更多(P均<0.05),与对照组和MOI=1组相比,MOI=5、MOI=5和MOI=10组的B淋巴细胞瘤-2蛋白(B-cell lymphoma-2,Bcl-2)表达量较低(P均<0.05),而凋亡蛋白(BCL2-associated X,Bax)、半胱氨酸蛋白酶-3(cysteinyl aspartate specific proteinase-3,Caspase-3)表达量均更高(P均<0.05).结论H101能够抑制胃癌细胞的增殖、迁移,提高细胞凋亡相关蛋白的表达量,加速细胞的凋亡.
文摘Transcatheter arterial chemoembolization (TACE) has become the standard treatment modality for unresectable hepatocellular carcinoma (HCC). Nonetheless, the clinical outcomes in patients with unresectable HCC are often unsatisfactory, especially in those with recurrent HCC. H101, an E1B gene deleted adenovirus, is known to have a significant antitumor activity. In addition, local injection of H101 can enhance the effect of antitumor therapies (chemotherapy and radiotherapy). Transarterial H101 gene injection in combination with TACE may help to control refractory and recurrent HCC. In this study, we report a 55-year-old patient with recurrent HCC which was treated with transarterial injection of H101 in combination with TACE, leading to a good clinical prognosis of the patient.
