Dissertation > Excellent graduate degree dissertation topics show

Killing-effect on Hepatocellular Carcinoma by AFP-regulated Oncolytic Adenvirus Carrying Manganese Superoxide Dismutase Gene

Author: KongYanPing
Tutor: LiuXinYuan
School: Zhejiang University of Technology
Course: Biochemistry and Molecular Biology
Keywords: hepatocellular carcinoma MnSOD AFP oncolytic virus
CLC: R735.7
Type: Master's thesis
Year: 2011
Downloads: 13
Quote: 0
Read: Download Dissertation

Abstract


High mortality, low survival rate, and poor treatment effect make cancer threpay become the current challenge for medical and biology. Cancer has become the ahead cause of death in worldwide. Among of which hepatocellular carcinoma is one of the most common malignant tumors, and its incidence is very high in China and even in some areas with the highest mortality rates among cancers. Traditionally the therapeutic methods of cancer include surgery, radiotherapy and chemotherapy. However, due to the metastasis easily, invasion, and uncurability et al for above, people are now being explored safer and effective anti-cancer treatment strategies, including cancer gene therapy.The occurrence of cancer is fundamentally the cause of multiple gene mutation. Cancer gene therapy is expected to become a novel treatment strategy for cancer. Manganese superoxide dismutase gene (MnSOD) is a new tumor suppressor gene. Studies showed that MnSOD can prevent normal cells to transform into cancer cells, inhibit tumor cell growth and promote the rapid apoptosis of tumor cells, exhibiting the potent anti-tumor effects. In addition the choice of vector is very important for successful gene therapy. Recently adenovirus vector has been widely used because of the large packaging capacity, stability and security, unaffected virus replication after the insertion of foreign genes. The modified oncolytic adenovirus Ad.enAFP-E1A-△E1B55Kd was constructed by us through deleting adenovirus E1B55Kd region and displacing adenovirus E1A gene promoter with the hepatoma-specific alpha-fetoprotein ( AFP) promoter, which can greatly improve the targeting of viral infection and the hepatoma-specific of virus-carried MnSOD gene. In this study, the therapeutic virus Ad.enAFP-E1A-△E1B55Kd-MnSOD was constructed by the modified oncolytic adenovirus Ad.enAFP-E1A-△E1B55Kd as vectors to carry therapeutic genes MnSOD. Subsequently, the identification of correct virus construction by PCR, cell morphology changes and cell apoptosis after infected by virus by microscope, the tumor-specific killing effect by MTT assay, the evaluation of liver normal cell security by crystal violet staining , and the detection of apoptosis mechanism by western blot assay were performed. The results indicate the obvious pathological changes and growth inhibition of hepatoma cells after infection of therapeutic viruses, while little impact on the liver normal cells with high security. Moreover, the treatment of therapeutic virus Ad.enAFP-E1A-△E1B55Kd-MnSOD significantly induced apoptosis of hepatoma cells through carrying the MnSOD gene, indicating the good targeting ability and the effect of inhibition of tumor cell growth.In conclusion, oncolytic adenovirus Ad.enAFP-E1A-△E1B55Kd-MnSOD was constructed under the control of hepatoma-specific AFP promoter. The studies show that the Ad.enAFP-E1A-△E1B55Kd-MnSOD exhibited liver cancer-specific killing effect and the inducement of apoptosis in hepatoma cells, while not for liver normal cells, which laid the preliminary foundation for further in vivo antitumor researches and clinical liver cancer treatment.

Related Dissertations

  1. Cloth and β- elemene combined administration of anti-tumor effect and mechanism of celecoxib,R96
  2. Clinical Significance of STAT3 and MMP-2 in Hepatocellular Carcinoma.,R735.7
  3. Assessment of Efficicy of Transarterial Chemoembolization by Gelfoam Particles Using DSCT Perfusion Imaging for Hepatocellular Carcinoma,R735.7
  4. Gelatin Sponge Particles Embolization of Hepatocellular Carcinoma after Regulatory T Cells and Its Significance,R735.7
  5. Quantiative Proteomics of Liver Immortalized Cell Line Chang Liver and Liver Cancer Cell Line HepG2,R735.7
  6. Expression and Functional Role of Proton-regulated Channels in Hepatic Carcinoma Cells,R735.7
  7. Dynamic Observation on the Plasma Level of Vascular Endothelial Growth Factor and Matrix Metalloproteinases in Advanced Hepatocellular Carcinoma Patients after Transarterial Chemoembolization Combined with Infusion of Endostar,R735.7
  8. Study of the Expression and Function of TC21/R-Ras2 in Hepatocellular Carcinoma,R735.7
  9. The Assocation of Hepatitis B Virus Genotype and Bascal Core Protmoer Mutations with Liver Cirrhosis and Hepatocellular Carcinoma Risks in Southern Shandong Province,R512.62
  10. The Transmembrane Fusion Protein of MnSOD Clone Expression and Function Study,Q78
  11. Qingdao region of hepatitis B virus the BCP gene mutation and hepatitis B virus associated with primary liver cancer,R512.62
  12. The Expression and Correlation of TGF-β1and E-cadherin in Hepatocellular Carcinoma,R735.7
  13. Significance of Protein and mRNA Expression of Tumor Suppressor Gene PLAGL1 in Human Hepatocellular Carcinoma,R735.7
  14. Expression of HMGB1 in Hepatocellular Carcinoma and Its Clinicopathologic Significance,R735.7
  15. The Mrna Expression of Unfolded Protein Response Genes Atf6, GRP78 and XBP1 in Human Hepatocellular Carcinoma and Its Clinical Implications,R735.7
  16. Clinical Research of Hot Lipiodol Ranscatheter Hepatic Arterial Chemoembolization Combined with Percutaneous Acetic Acid Interventional in Patients with Advanced Liver Cancer,R735.7
  17. Construction of Gene AFP、CBF2 Expression Vector and Transformation into Alfalfa Callus,S541.9
  18. Study on Targeting Oncolytic Adenovirus with E1B Gene Deletion and Mda-7/IL-24 for Hepatocellular Carcinoma Therapy,R735.7
  19. Effect of Curcumin on HIF-1α and VEGF Expression in Hepatocellular Carcinoma Hep1 Cells,R735.7
  20. The Expression and Significance of CD95 and JNK in Hepatocellular Carcinoma,R735.7
  21. Effects of Recombinant Plasmid pEGFP-AFP-TK Delivered by Nano-magnetic Fluids on Targeting Therapy for Implanted Liver Cancer in Nude Mice under Alternating Magnetic Field,R735.7

CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Liver tumors
© 2012 www.DissertationTopic.Net  Mobile