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Establishment of an Implanted Model of Human Gastrointestinal Stromal Tumors in Nude Mice and Observation Their Biological Characters

Author: ShengShuJuan
Tutor: HuaYaWei
School: Zhengzhou University
Course: Surgery
Keywords: Gastrointestinal stromal tumors Nude mice Animal models Transplant Immunohistochemistry CD117
CLC: R735
Type: Master's thesis
Year: 2009
Downloads: 32
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Abstract

Background and Purpose: gastrointestinal stromal tumor (gastrointestinal stromal tumor, GIST) is the most common gastrointestinal mesenchymal tumors often difficult to predict their biological behavior and poor prognosis. GIST pathogenesis mechanism of the formation of the proto-oncogene c-kit mutations activate causing mutations uncontrolled cell proliferation. GIST, c-kit gene mutation rate over 85%, the mutation occurs mainly in exon of 11,9,13 and the 17; small part can not be detected in GIST, c-kit gene mutations in these GIST, about 7% of the platelet-derived growth factor receptor A (PDGFRA) gene mutations; of GIST is not sensitive to radiotherapy and ordinary chemotherapy, rely mainly on surgery, but after 50% of patients will relapse and metastasis. For tyrosine kinase molecularly targeted drugs - imatinib emergence of GIST treatment and prognosis has improved remarkably. Of imatinib treatment complex, metastases, unresectable GIST of first-line drugs. Recently, however, imatinib Nepal in the process of treatment of GIST secondary resistance phenomenon growing, to produce resistant GIST patients treatment of major challenges, but the specific mechanism of resistance is not clear; relative gastric cancer, colon cancer, GIST incidence is relatively low, so that the GIST's disease information is not easy to collect, in addition the primary GIST vitro cell culture is more difficult, largely limiting GIST basic and clinical research. GIST pathogenesis and treatment has been a hot research Therefore, the purpose of this study is to establish nude mouse model of human gastrointestinal stromal tumors, investigate its biological characteristics, research in different parts of the nude mice model for further study of GIST pathogenesis, GIST of STI571 resistance mechanisms, and provides an ideal experimental platform for the design of new drugs to prevent and overcome STI571 resistance. MATERIALS AND METHODS: Fresh tumor tissue collected surgical resection human gastrointestinal stromal tumors, whichever part of the fresh tumor tissue, quickly prepared into about 1mm ~ 3 the size of the tumor tissue blocks, 103 nude mice were divided into two groups: the right axillary subcutaneous group (n = 50) the the left buttocks subcutaneous group of 53 subcutaneous the inoculated tumor tissue block after subcutaneously in nude mice right axillary and left hips, transplanted tumors were established animal models, and to observe, every six days measuring tumor volume According to the measured volume, draw a graph of tumor growth; observed tumor appearance, nude mice diet, mental state; killed tumor-bearing nude mice to observe whether the liver, peritoneal metastasis, parallel histopathological and immunohistochemical detection with human gastric intestinal stromal tumor specimens compared; immunohistochemical SP method for the determination of CD117 expression in the transplanted tumor cells. The analyzes were run SPSS10.0 package testing standards for α = 0.05, P <0.05 difference was statistically significant. Results: transplanted tumors generally Appearance: round or oval tumor boundary is clear, smooth surface. Anatomical see tumor nude mouse skin adhesions, easily separated, encapsulated visible capillaries with tumor connected, HE staining showed that the majority of GIST tumor cells are spindle-shaped cells, a small amount of epithelioid cells. Most of the spindle-shaped tumor cells ill-defined, no metastasis of the liver and intra-abdominal spread. The late part of the transplanted tumor visible and cachexia, SP immunohistochemistry: CD117 high expression in model tumor tissues. 103 nude mice, tumor-bearing success 70, 67.96% of the rate of tumor; tumor growth curve can be seen, the tissue blocks of the human gastrointestinal stromal tumors inoculated in nude mice after 6 days to 30 days of steady growth, after rapid growth. Axillary the subcutaneous group of 50 cases in the tumor-bearing winner of 40 patients, tumor formation rate was 80%, 90% of the cases, the positive rate of CD117-positive cases number 36; successful in 53 cases of tumor-bearing hips subcutaneous group of 30 patients, tumor formation rate of 56.6%, CD117 positive cases, 24 cases positive rate of 80%. Conclusion: This experiment established nude mouse model of gastrointestinal stromal tumors from tissue morphology, immunohistochemistry, etc., are consistent with the biological characteristics of the human gastrointestinal stromal tumors. That it is a stable biological characteristics of the human gastrointestinal stromal tumor xenografts in nude mice, human gastrointestinal stromal tumors, basic research and clinical treatment of the experimental platform. Xenograft model established in this study, tissue morphology, immunohistochemistry, and biological characteristics are maintained to the characteristics of the human gastrointestinal stromal tumors, this study directly using fresh human gastrointestinal stromal tumor tissue modeling feasible and successful. 2 subcutaneous xenograft model established in this study, the rate of tumor formation of the different parts of the nude mice model have significant differences: near the rostral part of the success rate is higher, the experimental results show that the composition of subcutaneous inoculation in the right posterior axillary The tumor is higher in the left buttocks subcutaneous inoculation group; CD117-positive expression rate of the different parts of transplantation model tumor tissue was no significant difference.

Establishment of an Implanted Model of Human Gastrointestinal Stromal Tumors in Nude Mice and Observation Their Biological Characters

Abstract

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