| Background/Aim: Cholangiocarcinoma is a malignancy that is resistant to current therapy. Cholangiocarcinorna is a virtually incurable tumor, resistant to current surgical, chemotherapy, and radiotherapy interventions. Cholangiocarcinoma represents a challenging primary malignancy of the liver with no effective medical therapy and a poor prognosis. Nevertheless effects of all is not sufficient ideal As well many patiens's Death cause is not Neoplasn- recurring and metastasis, but obstruction of biliary tract.for this reason rising Local efficiency of Tumor therapy. Assurancing Biliary tract to be unobstructed at present is utility Methods rising Cholangiocarcinoma survival rate. Suicide Gene therapy is one of utility Tumor therapy and potentia of clinical application therapy strategy. β -Glucuronidiase is a acidity hydrolytic enzyme in Lysosome of body,taking part in body's physio.. Illness and drug metabolism Process. It can specificly Hydrolysis glucuronic acid Glycoside, release toglucuronic acid and ligand. Applied investigation of ADEPT, 13 0 was already confirmed that its prosoma Drug can selective kill Tumor cell Role. Conjugating with gene therapy and ADEPT, will develop Newly practiced Method of molecul treatmeet, treat with 13 0 corresponding prosoma Drug, opportunitly prevent Neoplastic abnormily proliferation about 13 0 Expression of Neoplasm, in order to ques a New Strip utility Pathway in therapy of Bile duct carcinoma. We applied the toxin gene therapy strategy of 13 -glucronidase conversion of the nontoxic producing β -G prodrug to ADM combined with bystander effect to cholangiocarcinoma. Cholangiocarcinoi-na cells were transduced by recombinant adenoviral vectors and were killed by β -G Gene! β -G prodrug system . Enhanced cytotoxicity was seen with the addition of external bystander effect. These results provide a foundation for multirnodality therapy for human cholangiocarcinoma that combines gene therapy technology with prosoma Drug therapy. Aim To establish a β-glucronidase expressing bile duct carcinoma model and to localize the transfected β-G gene and its expression product in the bile duct carcinoma cell ultrastructurally, And to investigate the growth inhibitory effect of β -G gene and β-G prodrug on human bile duct carcinoma cell line(QBC939). Methods: virus vector was used to transfect the PDOR- J3 G gene into .the bile duct carcinoma cell line(QBC939)by cation lipofectin. The expression of PDOR- β G gene was examined by immunohistochemistry and immuno-electron microscopy and ultrastructurally morphological features of the transfected cells were also observed. We applied the gene therapy strategy of toxin gene conversion of nontoxic prodrug to chemotherapeutic drug in combination with bystand effect therapy to the treatment of cholangiocarcinoma. In this regard, β -G prodrug system is an accepted chemotherapeutic agent presently used in cancer therapy. Therefore, our goal was to express the β 6 gene in the human cholangiocarcinoma cell line, assess the cytotoxicity of intracellular production of β -G prodrug system, and determine any enhanced cell killing by the addition of external bystander effect. The susceptibility of cells to recombinant adenoviral infection was determined by fluorescence-activated cell sorting analysis. Cell proliferation assays (tetrazoliurn salt conversion to formazan colorimetric assay) were performed beginning 10-14 days after plating. Results: The selected positive cell clone by G418 system was confirmed to be P -G highly... |
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