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The Basic And Clinical Study Of Local Immune Status In Gastric Cancer And Costimulatory Molecules 4-1BBL

Posted on:2005-03-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z C SongFull Text:PDF
GTID:1104360125958243Subject:Surgery
Abstract/Summary:PDF Full Text Request
According to the published data of Sanitary Information Statistics Center of Ministry of Health, in 2001 the first cause of city death in our country is malignant tumor, and mortality rate is 135.59/100,000, of which gastric cancer is the third cause. There is no any significant break through in its treatment, although the gastric cancer has been adopted multi-method therapies and its survival rate has risen. The one cause of difficult to cure relates to tumor immune escape. In our experiment, by monitoring local and total immune status of gastric cancer patients we intend to farther study the mechanisms of tumor immune escape and to find a new efficient therapy to raise the survival rate of tumor patients.The human anti-tumor immune almost is cellular immunity by T cell mediated and the activation of T cell needs bisignal stimulation: the first signal is provided by the compound of TCR combined MHC; the second signal is provided by costimulatories on the APC and the corresponding ligands on T cell. Only when stimulated by two signals specific T cell can be activated to take cell immunity and kill tumor cell. A lot of studies show that tumor cell can escape body immune by absence of costimulatory. The costimulatory includes B lymphocyte activated antigen (B7), intercellular adhesion molecule (ICAMs), lymphocyte function associated antigen (LFA-3), vessel cellular adhesiveness (VCAM-1), heat stable antigen (HSA) and 4-1BB, which was found recently, et al. They bind to corresponding ligands to play costimulatory roles.From Know found 4-1BB in 1989, hu4-1BB was named as CD137 on the International CD Denomination Conference in Japan 1996. People have studied more about 4-1BB and its ligand (4-1BBL) and found 4-1BB belongs to ultra-family of tumor necrosis factor receptor (TNFR) and 4-1BBL belongs to ultra-family of tumor necrosis factor (TNF). 4-1BB is II form membrane glycoprotein, which exists on the cell membrane superficial, and it expresses on activated T cell, monocyt, granulocyte and dendrite cell. Its ligand 4-1BBL is II form membrane protein that exists on the cell membrane superficial. It expresses CD3 monoclonal antibody activated CD4+T cell clone PL11, EBV transfected B cell line MP1, monocyte line THP1 and MOTE, neuroblastoma SKNSH, brain, placenta, lung, bone, heart, liver, pancreas. Besides CD28/B7, 4-1BB/4-1BBL is a pair of important costimulatory signal, which plays various roles on cell-to-cell interaction, cell adhesiveness, antigen present, T cell costimulation and signal transmission. Although 4-1BB was found only 15 years, the role in complex cell immunological network is more and more important. Nowadays the study of costimulatory molecules in gastric cancer is one of study focus; especially B7, ICAMs, VCAM-1 and HAS, have reported more in home, but the study of 4-1BBL is rare reported in home, which only in the field of liver cancer but never seen in gastric cancer. The immunity in gastric cancer patients is by assaying the cell contents in peri-blood, but in our study to farther illustrate gastric cancer local immunity we detected the expressions of 4-1BBL and IL-18 in gastric cancer and peri-cancer tissues with RT-PCR, meanwhile the contents of CD4+, CD8+ and NK cells were also examined with flow cytometry, which has not yet been reported in the world.To increase immunogenicity of tumor cells and activate anti-tumor immune effect in body, various cytokine genes or MHCI, II genes have been transferred into various tumor cells by genetic engineering. Studies show that it can significantly enlarge T cell induced anti-tumor effect to increase 4-1BBL/4-1BB interactions by the method of gene transfection, which displays satisfactory application prospect. In our study we firstly transferred 4-1BBL gene into mouse gastric cancer MFC cells with liposomes, to investigate the 4-1BBL gene affection on gastric tumor formation, growth and body immunological function, which may settle theory and experiment foundation of gene therapy in future. PART IDistribution of T Cell Subgroup...
Keywords/Search Tags:gastric cancer, T lymphocytes subgroup, nature killer cells, flow cytometry
PDF Full Text Request
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