Dissertation
Dissertation > Medicine, health > Oncology > Gastrointestinal Cancer > Gallbladder, bile duct cancer

Experimental Research of the Diagnosis and Treatment of Human Bile Duct Carcinoma by Targeting Against Integrin αvβ3

Author ZhengXiuHai
Tutor WangShuGuang
School Third Military Medical University
Course Surgery
Keywords Integrins Monoclonal antibody Bile duct carcinoma RGD peptides Molecular design Radionuclide imaging
CLC R735.8
Type Master's thesis
Year 2002
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The invasion and metastasis of the malignant tumor involve a lot of complicated steps. Among these steps, many different molecules are presented on the surface of the tumor cells and the endotheliocytes of the new blood vessels induced by tumor cells. It has been found that integrin αVβ3 not only has a high expression on the surface of the solid tumor cells, but also has a strong expression in the endotheliocytes of the new blood vessels in the tumor tissue. On the other hand, integrin αVβ3 receptor is deficient or can not be detected in the endotheliocytes of the mature blood vessels and most of the normal organs. For these reasons, it has become a focal point in recent years that cross-links corresponding radionuclide or chemical medicine to the monoclonal antibody or antagonist peptide against integrin αVβ3 to carry out targeting diagnosis or treatment on the tumor.The incidence of the bile duct carcinoma is rising in recent years. Up to now, surgery is still the main treatment. However, the resection rate of these patients is very low because there is a special anatomy in the porta hepatis. The short-term tumor recurrence rate is also very high in most of the patients who undergo tumor resection. Besides the special anatomy of the bile duct, there are other reasons for this difficulty in the treatment of the bile duct carcinoma and poor clinical effects. It includes the biological character of the bile duct carcinoma. Metastasis of the bile duct carcinoma appears easily in the early stage via many pathways. The tumor always invades the adjacent important<WP=6>organs when the symptoms appear and the patient comes to hospital. In order to improve the clinical effect of the bile duct carcinoma, it is important to find a molecule receptor that is correlated specially to the invasion and metastasis of the bile duct carcinoma and continued growth. After that, it may be possible to inhabit the invasion, metastasis, and continued growth via the receptor.In this study, we examined the expression of the integrin αVβ3 receptor in the bile duct carcinoma line QBC939 and 16 cases of bile duct carcinoma by immunocytochemical method firstly. We find that there is plenty of integrin αVβ3 expression in the cell line QBC939. In the specimens of the human bile duct carcinoma, the expression of the integrin αVβ3 is also abundant. Part of them are expressed by the tumor cells, others are expressed by the endotheliocytes of the new blood vessels in the tumor. The intensity of the expression of the integrin αVβ3 has no relation to the sex, age and the differentiation of the tumor cells, but there is a remarkable difference between the group with metastasis and the group with no metastasis(P<0.05). It prompts that integrin αVβ3 may play an important role in the malignant biological behavior of the bile duct carcinoma. Blocking or inhabiting the integrin αVβ3 receptor may be an effective way to change the malignant behavior of the bile duct carcinoma. It is hoped that the integrin αVβ3 examining may be one of the indicators of the prognosis of the bile duct carcinoma. After that, using the human bile duct carcinoma CAM model, we observed that the implanted tumor was inhibited by the monoclonal antibody of the integrin αVβ3 receptor. It is found that the monoclonal antibody of the integrin αVβ3 receptor can inhibit the growth and the angiogenesis of the implanted tumor remarkably. It is also found that there was a great difference between the weight in experiment group and in PBS-control group. Additionally, the monoclonal antibody inhibited angiogenesis apparently in the experiment group. Under the microscope, the tumor tissue is loose and the new blood<WP=7>vessels are less. These results show that integrin αVβ3 receptor play an important role in the growth of the bile duct carcinoma and can be regarded as a targeting receptor in the anti-tumor treatment of the bile duct carcinoma.On the basis of the afore mentioned research, we designed and synthesized an antagonist molecule against inte

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