| Malignant tumors appear most frequently in gallbladder in the bile duct system. In recent years, there has been a sharp increase in incidence of bile duct carcinoma. Carrying few if any typical signs and symptoms, the tumor is often diagnosed in its late stage with poor prognosis. Few effective therapies can be applied. Pity that there has been no breakthrough lately. It is very urgent to improve the early diagnosis and cure rate of gallbladder carcinoma, which requires a deep experimental and clinical research. Tumor metastasis is one of the main reasons that affect prognosis. Finding the molecular mechanisms through proper experimental models may be an effective way to provide remedy to intervene the metastasis of GBC. In China, for the short of good research models, experimental and clinical prospective studies on GBC are neither comprehensive nor thorough. Understanding of this tumor is far less than that of other tumors in depth and extension.All in all, it's the poor prognosis and increasing incidence rate of GBC may deserve more attention and study. Those key topics are on malignant invasion and metastasis. To establish good models in vivo and vitro, to find molecular mechanisms in cancer progression and to develop effective chemotherapy are visible directions to explore in the field of bile duct oncology.Part Ι Compare of several experimental models of GBCAnimal models and cell lines are necessary to start experimental research of cancer. As to GBC the need is more pressing. We have tried establishing an xenograft of GBC and introducing three GBC cell lines into our laboratory. In order to know their biological characteristic similarities and differences, we have compared these models in several aspects, including morphology, growing potential, xenograft forming, and expression of some oncogenic protein. As a result, those models can grow steadily both in vitro and in vivo. They are excellent research tools. The proteins of Met, P53, erbB2 and TERT are positively expressed in the grafts in the four xenografts. In their cell lines, G grows fastest and has the best migration and invasion ability. T1 and T2 come from the same tumor but different original site. T2 originates from the primary tumor, but T1 is from lymph node metastasis. T2 can migrate faster and invade deeper than T1. Cancer cell lines have less heterogeneity than that of original tumor tissue. For they have same heredity background, T1 and T2 are suitable for comparison. Two genetic microchips including 17000 human clones are used for profiling gene expression. Those genes can be sorted into 15 different categories according to their functions. As a result, 261 genes have the alteration of transcription level. 81 genes have more than 2 times higher transcription level in T2, 17 are 3 times higher. 69 genes transcript in 2 times lower level in T2, 14 have 3times lower level. Two genes are selected for further reverse transcriptase–PCR analysis. We conclude that the result of microarry is credible. The metastasis of GBC concerns a great deal of genetic alternations in a complex network. The result of microarray provides some clues for further investigation in metastasis mechanisms of GBC.Part ΙΙ Role of HGF/SF-c-Met in the development of GBCThe combination of Met protein and HGF/SF can activate the downstream signal pathway, which are relevant to the invasion and metastasis of several different cancers. The pathway activation can facilitate almost every step in the course of metastasis. The expression of Met protein in GBC tissues are tested with immunohistochemical staining ( En Vison). Paraffin-embedded tissue blocks of chronic cholecystitis, adenomatous polyps and gallbladders of liver transplation donor are used as the control. C- Met are expressed in GBC, benign disease and normal tissue. But the expression levels are statistically different. They are stronger in GBC. Then we stimulate GBC cells with HGF in concentration grads. In our designed concentration range, HGF cannot inspire proliferation. But HGF can...
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