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The Experiment Study On Treatment Cancer By Microencapsulated Cells Modified With Maspin, IL-12 Gene

Posted on:2004-10-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y L PanFull Text:PDF
GTID:1104360092990621Subject:Oncology
Abstract/Summary:PDF Full Text Request
The cytokine therapy has being utilized and accepted in clinic, for instance interleukin-2 (IL-2), interferon (INF), clone stimulating factor (CSF). But the clinic effect still could not be satisfactory, duing to the following factors. (1)The half life was shorter, only 5~7 minutes in veins, and they were almost exhausted among 24 hours. The utility concentration was kept by the big dosage cytokine continuously given intravenously or subcutaneously. When large dosage cytokine was given to patients, the serious side effects, for example vascular leak syndrome, orthostatic hypotension and hidden severity upset, would be occurrence. Repeatedly injected subcutaneously cytokine for long-term, patients could not persist. (2)The purity and activity of recombinant cytokines still were not satisfact the clinic needed, the recombinant cytokines being applied in clinic at present were yielded by prokaryocyte, the bacteria protein, lipopolysaccharide and organo-solvent for purification were very difficult cleared thoroughly. So Influenza-like symptom (for example fever) would occur easily, some other recessive harmful still was not understood. It was difficult that the activity of recombinant cytokines was assured, because being influenced by production, storage and traffic.The gene therapy is the target gene was modified with artificial methods, including gene transfer and gene being inactivated. The gene transfer being a capital one now that the foreign aim gene (cytokine, MHC molecule, costimulatory molecules, antioncogene, anti-nucleic acid, correlation gene of anti-cancer agent and virus gene) was transferred into lesion or other cells. The production of target gene changed the function of defect cells or made the function of cells stronger. The program included immuno-gene therapy, target chemotherapy, enhancing body's tolerance to chemotherapy and the expression level of antioncogene being rised. The operation program was very complicated including gene cloning, plasmid constructed, transfection, cell culture and cell transplantation. (1) If autogenic cell was target cell, the immunological rejection was not occurred after the cell transplantation, but these operations must be repeated in every one. the worker was hard, the fee was very much and the quality could not assured, so it was very difficult for this method being wide used in clinic. (2) If xenogenic cell was target cell, the immunological rejection was the most disorder for transplantation. (3) If the naked gene was injected into body, they might be intergraded to host's gene, and there was hidden danger.The genetic enginnering cells were that the exogenous genes were transferred into target cells by every methods for gene transfection, the aim protein was expressed and excreted. The advantage of genetic enginnering cells was that the DNA molecules might be cut and spliced according to some aim, the new DNA molecules would be made, and they were transferred into the cells, the aim gene expressed in the target cells.The main behavior of microcapsules was that the membrane allows the free exchange of nutrients, oxygen, and biotherapeutic substances between the blood or plasma and the encapsulated cells, whereas high-molecular-weight substances such as immunocytes, antibodies, and other transplant rejection effector mechanisms, are excluded. Encapsulated cell technology offers a solution to the problem of donor organ supply, not only by potentially allowing the transplantation of cell and tissues without immunosuppression, but also by permitting use of materials isolated from animals. The expression protein of immortalized target cells might effect for all the patients with same ill. The encapsulated cells might expressed aim protein in host for long-term. The advantages of this nonautologous method of gene delivery are: (l)it does not require chemical purification of the gene product, an ofen daunting task in terms of labor and cost; (2)it does not require modification of the host's genome, thus providing additional measures of safety and cost sav...
Keywords/Search Tags:Microcapsulation, Maspin, IL-12, Genetic enginnering, Cancer/Tumor
PDF Full Text Request
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