Establishment Of An Implanted Model Of Human Gastrointestinal Stromal Tumors In Nude Mice And Observation Their Biological Characters

Background and ObjectiveGastrointestinal stromal tumour(GIST) are the most common mesenchymal neoplasms of gastrointestinal tract,the clinical behavior of GIST is varied,which poses difficulties in determining the degree of aggressiveness and prognosis.The major nosogenesis of GIST is gain-of function mutations of c-kit gene.Mutations of the c-kit gene are known to be persent more 85%of GIST,most commonly in exon11,exong9,exon13 and exon17.some GISTs do not have c-kit tmutations,and about 7%of GISTs have PDGFRA gene mutations.GIST is not sensitive to radiotherapy and common chemotherapy,and the major therapy device is operation, but 50%of GISTs would relapse and metastasize after operation.Imatinib mesylate is a specific tyrosine kinase inhibitor that acts with BCR-ABL,PDGFRA and c-kit.It has been used successufully in unresectable or metastatic GISTs patients.But secondary resistanse to STI571 in GIST patients has been reported recentiy,the cellular mechanisms of resistance to STI571 have not been identified.In addition to this,the morbility of GIST is more low than gastric cancer or cancer of colon. Accordingly,it is difficult to gather the information of GIST.It is not very easy to culture GIST cells in vitro.So the investigation of GIST was restricted to some extent.The nosogenesis and treatment of GIST are researched priority all the time. Therefore,the study aimed at established a satisfactory animal model of GIST by subcutaneous inoculation of human gastrointestinal stromal tumors tissue piece.Then we approached the biological behaviour of GIST and study on method of establishment of laboratory animal model of GIST in different subcutaneous parts of nude mice.At the same time,model of human gastrointestinal stromal tumors in nude mice make for reresearh nosogenesis of GIST,mechanisms of resistance to STI571 and designing new drug to overcome resistance.It can be useful for further investigation bionomics of GISTMaterials and MethodsA fresh human GIST specimen was obtained from a patient under aseptic condition during operation,Using parts of primary tissue,quickly cutting these into 1mm3 small pieces,with small pieces to established animal model of human gastrointestinal stromal tumors and divided it into subcutaneous transplantation tumor of armpit and haunch two groups,respectively 50 mice and 53 mice.The mice were observed every 6 days.the growth of tumor was recorded and growth curve were figured.The mice were sacrificed when they showed serious illness and laparotomized to exminemetastatic tumors in liver and peritoneum.Then CD117 level in tumor cell surface of transplantation tumor was evaluated by SP immunohistochemistry.The difference of enumeration datas were detected by the x~2 test.All the datas were processed on SPSS11.0 package.Differences were considered statistically significant if P-values were＜0.05.Resultsgross appearance of subcutaneous transplantation tumors:The tumor was elliptical and mobile.It has smooth and glossy surface.Its cellular membrane is intact. HE staining showed GISTS cells of spindle shape.some are epithelioid cells.just like the human gastrointestinal stromal tumors specimen.No liver or peritoneum metastatic tumors were observed in all the mice.a few transplantation tumors manifested cachexia.CD117 in tumor cell surface was heavily expressed.70(67.96%) nude mice were successfully transplanted with the tumor.The features of transplanted tumors were the same as the primary tumor in histopathologic and immunohistochemical assays.We cound discern thant transplantation tumors grow steadily from the sixth day to the thirtieth day from the growth curves.Then transplantation tumors grow quickly.In subcutaneous transplantation tumor of armpit group,40(80%) nude mice were successfully transplanted with the tumor,The positive expression rate of CD117 in 40 specimens GISTs reaches 36(90%).another group,30(56.6%) nude mice were successfully transplanted with the tumor,The positive expression rate of CD117 in 30 specimens GISTs reaches 24(80%).ConclusionThe features of transplanted tumors were the same as the primary tumor in histopathologic and immunohistochemical assays.Its bionomics was rather steady.The animal model of human gastrointestinal stromal tumors was established successfully. It can be helpful for us further study the bionomics,course of disease,invasive growth and therapy of GISTs.1.The features of transplanted tumors were the same as the primary tumor in histopathologic and immunohistochemical assays.The outcome indicated that we utilize fresh human GIST tissue for constructing model of human gastrointestinal stromal tumor in nude mice was feasible and successful.2.In two groups,the differences of transplantation achievement ratio in different subcutaneous parts of nude mice were consideredstatistically significant.The positive expression rate of CD117 were no significant difference in two groups.