Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2) could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy.
Three metal-salen (Ni, Cu, Zn) complexes were firstly introduced into homogeneous photocatalytic hydrogen-evolution systems. Based on these complexes, we developed noble-metal-free hydrogen production systems using disodium salts of Eosin Y (EY 2À ) as photosensitizers and trimethylamine (TEA) as sacrificial donors. In a Ni(II)-salen/EY 2À /TEA system, a TON of 362 based on Ni(II)-salen was achieved in 5.5 h with one time complement for EY 2À . The stability study revealed the quick photodecomposition of EY 2À in the presence of ether Ni(II)-salen, TEA or both chemicals, and quick dehalogenation of EY 2À was observed in the presence of TEA under irradiation. Besides, relatively slower photodecomposition of Ni(II)-salen was also found. These factors should be responsible for the deactivation of the photolysis system. Investigation of electrocatalytic proton reduction by Ni(II)-salen showed a CECE mechanism. An overall catalytic rate constant of 7.62 × 10 6 M À 2 s À 1 was achieved. Combined with the stability analysis, photo-induced electron transfer and electrochemistry investigation, for the first time, the photocatalytic hydrogen production mechanism for metalsalen complexes (e. g. Ni(II)-salen) was proposed.[a] Dr.
BackgroundNumerous studies have demonstrated that the NDV-mediated gene therapy is a promising new approach for treatment of cancers. P53 plays a vital role in tumor suppression and surveillance. Therefore, we hypothesize that a recombinant NDV expressing P53 would be an ideal agent for the hepatoma therapy.ResultsIn the essay, the human P53 gene was incorporated into the genome of a lentogenic strain (named rNDV-P53), which did not affect viral replication kinetics and magnitude in HepG2 cells. Compared to the vehicle virus, rNDV-P53 increased cell growth suppressor ratio and early apoptosis by 2 folds, and decreased the mitochondrial membrane potential in HepG2 cells. In vivo studies, treatment with rNDV-P53 reduced tumor volume of tumor-bearing mice by more than 4 folds, tumor weight by more than 5 folds comparing with rNDV. The 120-day survival rate of rNDV-P53-treated mice was 75 %, survival rate of rNDV-treated mice was 12.5 %. TUNEL analysis showed a significant increase in the apoptosis rate in the tumor tissues of rNDV-P53-treated mice than that of rNDV-treated mice. Moreover, serum chemistries revealed an insignificant change of blood urea nitrogen (BUN), creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST) in rNDV-P53-treated group compared to normal mice, suggesting treatment with the recombinant virus was not toxic.ConclusionrNDV-P53 is a potent candidate for carcinoma therapy especially for hepatocarcinoma.
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