Comparison Of Expression Abundance Of HIF-1α And Glut1 In Hepatocellular Carcinoma And Pancreatic Ductal Carcinoma And Its Significance

Pancreatic Ductal Adenocarcinoam (PDAC) is a malignant gastrointestinal cancer with extremely poor prognosis. The mortality of PDAC is almost the same with the incidence with median survival time of just six months and less than1%five-year survival.By westernblot we find that HIF-la is not expressed in PDAC and adjecent tissue, while is expressed in hepatocarcinoma (HCC) and its adjecent tissue. By tissue immunofluorescent branched microvascular is obversed in HCC is rich in while PDAC is very limited in microvascular. This results indicate that there maybe some differences in energy intaking between HCC and PDAC. Most tumors rely on VEGF which is induced by hypoxia to form large amount of neovascular. Then we analysed the tissue array of HCC and PDAC to find out the relashionship between HIF-la and neovascular, the result shows in HCC, HIF-la is significantly correlated with the density and size of neovascular, however, in PDAC this correlation doesn’t exist. Most of the neovascular induced by HIF-1a is swelling, so we infer that HIF-a may not involve in neovascular formation in PDAC. The Kaplan-Meier survival curve analysis shows that there’s no significant correlation between HIF-la and PDAC patients(Log rank P=0.585). All these results indicate that PDAC is independent on the neovascular formation controled by HIF-la. Some of cancer cells rely on glycolysis for energy which need a large amount of glucose, it is through Glutl that most of cells intake glucose, so we then compared the expression level of Glut land its distribution as well as their relative position with vascular in HCC, PDAC and Pancreas by utinilizing tissue immunoflorecent array. We find that HCC and Pancrease are rich in microvascular but poor in Glutl and the distribution between Glutl and vascular is almost the same, however, in PDAC there’s very little microvascular, but the expression of Glutl is extremely high, and the most interesting thing is where there is more Glutl there’s less microvascular. So, we can see that Glutl maybe the most important tool for cells to intake glucose, also, HCC and PDAC may utilize totally different way for energy intaking. We then use different HCC and PDAC cell lines to verify the hypothesis that HCC and PDAC have totally different way for energy intaking. The most special feature of PDAC is the mutation of the12th codon of K-ras, so we first find out the mutation of the cell lines we used, the result shows thej mutation of MiaPaCa-2which expresses high amount of Glut1as well as HIF-la. To elucidate that PDAC is mainly dependent on the glucose transporting for energy, we unilized FACS to compare the apoptosis of HCC and PDAC cell lines. The results show that under hypoxia, a large amount of HCC cell die while only a few PDAC cells die; however, when cultured without glucose, the number of PDAC dying cells increase greatly which indicate that PDAC cells are much more sensitive to glucose deprivation other than O2deprivation. So we conclude that PDAC is mainly dependent on the increase of Glutl to transport more glucose for malignant cells’surviving and proliferating.Based on all these results, we analysed the correlation between the pathological charicteristics of PDAC and the expression of Glutl, we also analysed the Kaplan-Meier survival curve of32PDAC tissues, the result shows Glutl is strongly correlated with PDAC patients’survival(Log rank P=0.033*).In conculsion, our research find out that, in contrast to the dependenc of HCC on neovascular formation, PDAC relies much more on the intaking of glucose for cell survival and proliferation. Which elucidate the reason why PDAC is resistant to anti-vascular therapy, and provide the evidence for bring forward new therapeutic approaches for PDAC. Based on the multi-epitope antigen PCXZ which is against the hepatitis C virus synthesized before, this research triplicate PCXZ into3PCXZ. The antigenic specificity of3PCXZ was determined by recognizing antibodies in serum samples from hepatitis C virus patients, but not from healthy subjects or subjects who had the hepatitis B virus. The characteristics of3PCXZ immunogenicity were evaluated in BALB/c mice. Strong antibody responses were generated in mice immunized with either naked3PCXZ or3PCXZ in Freund’s adjuvant. Analysis of antibody subtype shows this responses is mainly through the Th2pathway. It can also stimulate the CTL effects of specific CD4+T and CD8+T help cell. The synthesized multi-epitope antigen3PCXZ can not only induced high titer IgG antibody production of immunized BALB/c mice, but also significantly increased interferon-g secretion from CD4+T cell and enhanced the lytic activity of cytotoxic T lymphocytes.