p53 gene therapy in combination with transcatheter arterial chemoembolization for HCC:One-year follow-up

AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC.

Antagonism between gene therapy and epigenetic therapy on human laryngeal carcinoma tumor-bearing mice

Background Gene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet. To study the mechanism and clinical application, human laryngeal carcinoma cell （Hep-2） tumor-bearing mice were used. Methods A xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice. The mice with well-formed tumor were randomly divided into six groups. Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor. Tumor growth was monitored by measuring tumor volume and growth rate. p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining. The mRNA levels were monitored with FQ-PCR. Results Gene therapy was much more effective than single epigenetic therapy and combined therapy. The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin. Conclusions The combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma, because gene therapy shows an antagonistic effect to epigenetic therapy. However, the mechanisms of action are still unclear.