Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma

AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.

Study of the Antitumor Activity of the Drug Dekoglitz on Two Tumors and Some Aspects of Its Mechanism of Action

Aim:Evaluation of the antitumor activity of the new drug Dekoglitz in animals with tumor strains of Sarcoma 45 in comparison with the drug dekocin,from which it was obtained,as well as with 5-fluorouracil and etoposide,and on ovarian tumors(OT)in comparison with the drug dekocin and identification of the effect of Dekoglitz on NA synthesis and internucleosomal DNA degradation.Methods:The study of preparations was carried out on 68 outbred rats with transplanted C-45 and OT tumors.The alkylating effect of the drugs was studied on cells tumor of Sarcoma 180.Results:The antitumor activity of dekoglitz on Sarcoma 45 was high,about 98/96%,with a remission rate of 80%.Its effect was 28-24%higher than that of dekocin.On OT,the effect of decoglitz with intraperitoneal administration reached 89/76%with a remission rate of 40%,with oral administration 96/86%with a remission rate of 60%.Conclusion:The study of the new drug Dekoglitz on animals with a tumor of Sarcoma 45 revealed its higher activity(by 20-27%)in comparison with the original Dekocin,5-fluorouracil and etoposide with a lower level of side effects.On OT,the effect of Dekoglitz was 35-40%higher,especially after oral administration.Apparently,the great ability to suppress the synthesis of NA and carry out internucleosomal degradation and fragmentation of tumor DNA by the new drugs dekoglitz explains its antitumor efficacy,which is greater than that of Dekocin(K-18)in experiments on tumors.