The Familial Adenoma Polyposis Adenoma Stem Cell's Research And The High Frequency Electricity Cut To The Familial Adenoma Polyposis's Therapeutic Action

BACKGROUDIt is always a focus in research on the carcinogenesis,development, invasion,metastasis and therapeutics of cancer.Generally it has been believed that tumor cells are mutated from mature cells and have homogeneous potential of proliferation.All tumor cells have the abilities to proliferate infinitely.Accordingly,it is an accepted standard for the curative effect in clinical tumor therapy that tumor volume could grown downwards or even vanish.However,some tumors recurred or even distantly metastasized and could not been cured completely after tumor removal by surgery or some others treatment and had been stable for some periods.Recent researches had discovered that there were some stem-like subpopulations in tumor tissues which had the potential to proliferate infinitely and played much crucial role in initiating carcinogenesis and develoment,while the other cells would die after transitory differentiation. It was thought that the tumor growth resulted from the proliferation of some tumor stem cells with special surface markers.For this reason,the tumor treatment must aim directly at the tumor stem cells but not at the bulk of tumor cells with little ability to proliferate and differentiate.This theory might bring about some revolutionary in tumor therapeutics.Familial adenomatous polyposis(FAP) is one of the two commonest familial syndromes that predispose to colorectal cancer and characterized by the occurrence of hundreds to thousands of colorectal polys.FAP accounts for about 1%of total colorectal cancers and was classified into three types,one is classical FAP(CFAP),the other two are attenuated FAP(AFAP) and MYH associated FAP(MAP).Under the guide of this theory,we believed that FAP possibly also originated from the adenoma stem cells.There were be great importance to study on identification,isolation,culture and the basic characteristics ofthem.However,the key point of the research on adenoma stem cells was how to establish the special surface marker of them.However,it was hope to achieve an efficient sorting scheme of adenoma stem cells by detecting the surface markers with some directing antigens,which would save a lots of time and research funds. ChapterⅠIdentification,Isolation and Cultivation of FAP stem cells by a novel stem cell marker DCAMKL-LObjective:Identification,Isolation and Cultivation of FAP stem cells by a novel stem cell marker DCAMKL-1.Some proteins that expressed in adenoma such as PCNA,β-catenin and COX-2 were studied.And the relationship between the proteins and development of FAP was studied.Methods:Immunohistochemistry was used to identify DCAMKL-1,PCNA,β-catenin and COX-2 expression in normal epithelium,FAP crypts and cancer cell.To study the effects of PCNA,β-catenin,COX-2 on the development of FAP.The cell position that expressed DCAMKL-1 was compared with the cell position 4 that express MSI-1.The cell expressed DCAMKL-1 was stained Hoechst.Results:In normal intestine,FAP intestine and malignant adenoma, the DCAMK-1 was immunoreactive in the cells in the cell position 4 that was considered as a stem cell position.And it showed a trend toward increaseed expression on villi.The nuclei of the cells positive for DCAMK-L could not been stained with Hoechst 33342.Conclusion:DCAMKL-1 is a noval putative stem cell marker.The cell expressed DCAMKL-1 could be gastrointestinal stem cell and adenoma stem cell.The key point to treat the FAP is to cut the adenoma especially the adenoma stem cell.And and selective inhibition of COX-2 is expected to be an effective target point for preventing and curing colorectal cancers and FAP. ChapterⅡClinical study on familial adenomatous polyposis treated by high frequency electric cutting under endoscope in the BALB/c mice modelsObjective:The goal of this study is to prepare the BALB/c mice models with FAP and investigate the therapeutic effects of high frequency electric cutting to FAP.Methods:The BALB/c mice models with FAP were prepared by intragastric administration of N-Nitroso-diethylamine.1 month,3 months, 6 months,9 months and 12 months after being treated by high frequency electric cutting,the expression levels of APC,Lgr5,Musashi-1 and PTEN in the colon tissues of the FAPmin mice have been detected by immunohistochemical assay and semi-quantitive RT-PCR analysis. Additionally,In situ terminal transferase labeling technique has been used to detect the apoptosis index of adenoma cells in different groups.Results:1 month,3 months,6 months,9 months and 12 months after being treated by high frequency electric cutting,the expression levels of APC,Lgr5,Musashi-1 in model group have been increased, while that decreased in treatment group.The differences between these two groups have statistic significance(p<0.01).Moreover,the apoptosis index of adenoma cells in treatment group also increased from (20.08±1.21)%to(32.79±3.62)%,while in model group decreased from (8.29±0.98)%to(7.76±1.34)%.The differences between these two groups have statistic significance(p<0.01)Conclusion:These results indicate that the intragastric administration of N-Nitroso- diethylamine can prepare the BALB/c mice models with FAP successfully.The treatment of high frequency electric cutting on FAP is effective in the reduction of numbers and atypia degree of adenomas,which is the experimental basis of clinical application in the future. ChapterⅢClinical study on familial adenomatous polyposis treated by high frequency electric cutting under endoscope combined with sulindacObjective:To investigate the therapeutic effects of sulindac combined with endoscopy on familial adenomatous polyposis.Methods:20 patients diagnosed as familial adenomatous polyposis were randomly divided into two groups.The sulindac+endoscopy group took 400 mg of sulindac daily after endoscopy treatment;the sulindac group took 400 mg of sulindac daily only.In both group,the changes of number,histopathological subtype and degree of atypia of adenomas and apoptotic index(AI) in adenomas cells were compared before and after treatment.Results:In the sulindac+ endoscopy group,the elimination rates in the adenomas after the treatment in 4,8,12 months were 90.96%,95.66 and 98.81%;in the sulindac group were 80.08%,85.35%and 89.78%, respectively,the difference was statistically significant(p＜0.05).In the sulindac+ endoscopy group,the percentages of the degreeⅢof atypia of adenomas after the treatment decreased dramatically.AI in adenomas cells in the sulindac+ endoscopy group after treatment in 4,8,12 months were(20.08±1.21)%,(25.67±2.07)%and(32.79±3.62)%;in the sulindac group,they are(13.29±0.98)%,(19.83±1.56)%and(25.18±2.31)%, respectively,the difference was statistically significant(p＜0.05).Conclusion:The treatment of sulindac combined with endoscopy on familial adenomatous polyposis is effective in the reduction of numbers and atypia degree of adenomas in patients.