Suchergebnisse

Ziheng Ye,1,* Su Zeng,1,* Peipei Xu,1 Wenfei Liu,1 Shoufei Wang,1 Xiaotian Xia,1 Changqing Su,2 Minggao Guo1 1Center of Thyroid and Parathyroid, Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Afï¬liated Sixth People's Hospital, Shanghai, People's Republic of China; 2Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital and Institute, The Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workCorrespondence: Minggao Guo Email guominggao203@163.comChangqing Su Email suchangqing@gmail.comAim: To investigate the inhibitory effect of hepatitis B virus (HBV) preS2 mini-antibody (mPreS2) against HBV infection, HBV-associated liver injury and HBV-associated hepatic carcinogenesis.Methods: A recombinant adenovirus vector with the human survivin promoter and mPreS2 gene, Ad5SVP-mPreS2, was constructed. Fluorescence microscopy examination and TCID 50 analysis were utilized to determine the specific proliferation of recombinant adenovirus in liver cancer cells. Western blot analysis was used to determine the mPreS2 expression levels. Enzyme-linked immunosorbent assay (ELISA) was used to examine HBsAg levels to evaluate the inhibitory effect of mPreS2 against HBV infection. The protective effects on hepatic function and preventive effects against hepatic carcinogenesis of Ad5SVP-mPreS2 were studied in diethylnitrosamine (DEN)-treated HBV transgenic Imprinting Control Region mice.Results: The recombinant adenovirus regulated by the human survivin promoter proliferated exclusively in liver cancer cells rather than normal liver cells. The expression levels of mPreS2 were increased in liver cancer cells compared with normal liver cells, and mPreS2 could be used to recognize liver cells from HBV transgenic mice. ELISA showed that HBsAg levels were decreased in the group treated with Ad5SVP-mPreS2. Ad5SVP-mPreS2 had a protective effect on hepatic function in a DEN-induced liver injury model because of lower serum levels of alanine transaminase and aspartate transaminase. Additionally, HBV transgenic mice treated with Ad5SVP-mPreS2 had fewer and smaller cancerous nodes after induction with DEN than untreated mice.Conclusion: Conditionally replicating adenovirus-mediated mPreS2 expression inhibited HBV infection and had an inhibitory effect on liver injury and hepatocellular carcinogenesis in HBV transgenic mice.Keywords: hepatitis B virus, hepatocellular carcinoma, conditionally replicating adenovirus

Shu-De Feng,1,* Ziming Mao,2,* Chunying Liu,2,* Yu-Song Nie,1 Bin Sun,2 Minggao Guo,3 Changqing Su2 1Department of General Surgery, Jiangsu Armed Police General Hospital, Yangzhou, Jiangsu, China; 2Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Center of Liver Cancer, Second Military Medical University, Shanghai, China; 3Department of General Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China *These authors contributed equally to this work Background: Pancreatic adenocarcinoma (PAC) is one of the most fatal cancers due to its high degree of malignancy, increasing incidence, high mortality, and unsatisfactory treatment efficacy. Evidence has suggested that numerous microRNAs (miRNAs), including miR-126 and miR-34a, have potent tumor-suppressing effects on PAC, implicating a possible application of miRNA in tumor therapy. However, the therapeutic effect of a single miRNA on pancreatic cancer is limited.Methods: We simultaneously delivered miR-126 and miR-34a into PAC cells by a carcinoem­bryonic antigen promoter-driven oncolytic adenovirus (AdCEAp-miR126/34a), and examined the antitumor efficacy of the therapeutic system in in vitro and in vivo experiments.Results: In vitro cytological experiments found that the expression levels of miR-126 and miR-34a were specifically increased in the AdCEAp-miR126/34a-infected PAC cells, and the antitumor efficacy was enhanced in aspects of cancer cell viability, migration, invasion, and apoptosis, by synergistically combining the antitumor effects of overexpressed miR-126 and miR-34a and the oncolytic effect of viral replication specifically in PAC cells. The expression levels of miR-126 target genes (vascular endothelial growth factor-A and SOX2) and miR-34a target genes (cyclin D1, E2F1, and Bcl-2) were markedly decreased in the PAC cells after being infected with AdCEAp-miR126/34a. Notable suppression of the therapeutic system on tumor growth was also proven in established PAC xenograft tumor models in nude mice, which demonstrated that the combination of miR-126 and miR-34a exerts more effective antitumor outcomes than a single miRNA.Conclusion: The therapeutic system co-expressing miR-126 and miR-34a mediated by oncolytic adenovirus is a promising system for PAC target therapy. Keywords: pancreatic cancer, miR-126, miR-34a, oncolytic adenovirus, target therapy

AbstractTo realize the integrated remediation of SW/GW and soil in the rural river network area, the integrated remediation in rural river network area project (IR-RRNA), funded by the Ministry of Science and Technology of the People's Republic of China, has been launched. In eastern China, the rural river network area (RRNA) is an anthropic active area characterized by its rapid economic development and high gross national product. However, the water environmental pollution in these areas is increasingly severe, which has greatly hindered their sustainable development. Especially, the frequent interactions between surface/groundwater (SW–GW) have intensified the pollution migration and transformation in RRNA. The IR-RRNA (2019–2022) will apply the related interdisciplinary and methodological knowledge to elucidate the transportation and transformation of pollutants in water and soil during SW–GW interaction and develop remediation technologies of surface water, groundwater, and soil suitable for the RRNA. In this way, to realize the remediation technologies integration for surface/groundwater and soil in RRNA and implementing application demonstration. Meanwhile, a technical guideline will be compiled for the integrated remediation suitable for the RRNA. This project is conducive to addressing the urgent environmental problems as well as promoting rural economic revitalization and ecological environment optimization.