| Intrahepatic cholangiocarcinoma (ICC) is the second most common intrahepatic neoplasm and comprises nearly 5% of primary liver neoplasm in most large series. ICC presents differently form extrahepatic cholangio- carcinoma, in that jaundice and biliary obstruction are uncommon. Symptoms tend to be vague and insidious in the early stage of this carcinoma. Once the distinct symptoms were given, it was meant that patients suffered from advanced ICC and lost the chance of curative surgery. The prognosis of the patients with ICC is poor. Although much is known about extrapatic cholangiocarcinoma, knowledge of ICC is far less complete. To make a correct diagnosis in the early stage and to perform an effective therapy, it is necessary to understand the biologic nature of this carcinoma. On the base of the animal model which we copied, the expression of Vascular endothelial growth factor (VEGF) and its receptor flk-1 were detected by immunohistochemistry and microvessel was observated by combining with histoloy and blood vessel transformation and scanning electron microscope during the ICC carcinogenesis of syrian hamsters. The effects of VEGF and its receptor flk-1 in ICC carcinogenesis and angiogenesis were investigated in order to provide the testing foundation to diagnosis, treatment and prevention of this carcinoma. The main results and conclusion are as follow:1. ICC was successfully induced in syrian hamsters by aminopyrine and sodium nitrite. The incidence of ICC was 58%(11/19) in 21~26 weeks ofcarcinoma induction and the hisologic type of all carcinoma induced was tubular adenocarcinoma. 2. No expression of VEGF and Flk-1 protein was found in the normal intrahepatic bile duct, weak expression or no expression of VEGF protein was found in intrahepatic bile duct hyperplasia, the overexpression of VEGF protein was found in the intrahepatic bile duct atypical hyperplasia, adenoma, and ICC. The expression of VEGF receptor flk-1, on the hand, was found in the vascular endothelial cell, the positive rates gradually increased along with the expression of VEGF and close related to the expression of VEGF during carcinogenesis, this indicated that VEGF/ flk-1 paracrine loop accelerated endothelial cell proliferation and vascularization; on the other hand, The expression of flk-1 protein was found in the different bile duct lesion cell, no expression of flk-1 protein was found in the normal intrahepatic bile duct and hyperplasia, the overexpression of flk-1 protein was found in the majority of atypical hyperplasia, adenoma, and ICC. This indicated that VEGF/ flk-1 autocrine loop might be close related to intrahepatic bile duct cell proliferation and malignant transforming. The aberrant VEGF/ flk-1 autocrine/ paracrine loop may play an important role in ICC carcinogenesis of syrian hamsters. 3. In the normal intrahepatic bile duct, blood capillary regularily arraied, formed integrated capillary network, the shape of blood capillary was regular and smooth, the caliber of blood capillary was fairly even, the courser of blood capillary was natural and had integrated basement membrane. In the hyperplasia bile duct, the quantity of blood capillary moderly increased, blood capillary had basement membrane. In adenoma, the quantity of blood capillary obviously increased, its basement membrane was no integrity. In atypical hyperplasia bile duct, the quantity of blood capillary also obviously increased, blood capillary became wrench and no regularity, its basement membrane became no integrity. In the bile duct adenocarcinoma, the quantity of bloodcapillary significantly increased and angiectasia, pip cava became big and dissepiment became frail, the structure of blood capillary was absence integrity, only arrayed one layer endothelial cell, its basement membrane became gracile or deficiency, the arrangement of blood capillary had no regularity, there were rich capillary network was formed, bubble shape matter was found in many blood capillary surface and resin aggregation was found in many area of c...
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