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The Study Of Photochemical Gene Transfection And Differentiation Induction On Human Colon Carcinoma Cells

Posted on:2007-06-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:W D XiaoFull Text:PDF
GTID:1104360185970443Subject:Department of General Surgery
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ObjectiveDespite exciting progress in the development of gene therapy,the development of appropriate gene therapy strategies,allowing a specific therapeutic molecule to reach the target exactly and express a therapeutic function,remains to be one of the most important issues for cancer therapy.The present study was designed not only to investigate the technology of photochemical gene transfection(PCGT) for delivering gene vectors efficiently,but also to search the target gene for differentiation induction which may help the researchers to overcome these obestacles in cancer gene therapy.Most gene therapy vectors are taken into the cell by endocytosis and,hence,are located in the endocytic vesicles.Poor endosomal release is one of the major obstacles for non-viral gene vectors.PCGT is a novel technology for specific delivery of gene vectors and macromolecules.The technology is based on photosensitisers that localise specifically in the membranes of endocytic vesicles and,following activation by light,induce the rupture of the vesicular membranes.The present study is focused on transfection efficiency of PCGT compared with polycation,endocytic release mechanism of PCGT,and optimization of the technology by investigating the influence of light dose,photosensitizers,cell type and so on.The relationship among tumor cell differentiation,photosensitizer accumulation in cell,and photodynamic cytotoxicity is poor defined.In present work,specific cell differentiation of colon carcinoma cell was induced by sodium butyrate(NaBt) and all-trans retinoic acid(ATRA).The study was designed to invetigate the effect of differentiation therapy(DT) on photosensitizer accumulation and photodynamic therapy(PDT) on colon carcinoma cells.As compared to more traditonal anti-cancer drugs, DT has the potential advantage in gene therapy against cancer which could induce a more normal or benign phenotype in...
Keywords/Search Tags:photodynamic therapy, photochemical gene transfection, photosensitizer, polycation, sodium butyrate, all-trans retinoic acid, colorectal carcinoma, differentiation, histone acetylation
PDF Full Text Request
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