家族性腺瘤性息肉病腺瘤干细胞的研究以及高频电切对家族性腺瘤性息肉病的治疗作用
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摘要
研究背景
关于肿瘤的发生、发展、侵袭、转移和治疗一直是医学研究的热点。传统观点认为,肿瘤由成熟细胞突变而来,是由均一的肿瘤细胞共同增殖构成的,所有肿瘤细胞都有无限增殖能力。因此临床上常以肿瘤体积是否缩小或消失作为衡量肿瘤疗效的一个标准.但临床上许多肿瘤患者,在手术切除肿瘤或经过其他治疗,病情已获稳定一段时间后,却又出现肿瘤的复发或转移,不能获得彻底治愈。
新近研究发现:肿瘤组织中存在极少量干细胞样亚群,它具有无限增殖的潜能,在启动肿瘤形成和生长中起着决定性的作用,而其余的大多数细胞,经过短暂的分化,最终死亡。肿瘤生长是肿瘤组织中极少量具有特殊表面标志的肿瘤干细胞增殖的结果。这提示肿瘤治疗应针对在肿瘤发生、发展中起决定性作用的肿瘤干细胞,而不是大部分无增殖、分化能力的肿瘤实体细胞。这可能促进肿瘤治疗学发生革命性改变。
家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)是常见的遗传性大肠肿瘤之一,约占总大肠肿瘤的1%,可分为经典型家族性腺瘤性息肉病(Classical FAP,CFAP),衰减型家族性腺瘤性息肉病(Attenuated FAP,AFAP)和MYH相关性息肉病(MYH associatedFAP,MAP)三种,其临床表现为青春发育期发生结直肠腺瘤,后逐渐增多,甚至满布所有结直肠粘膜,如不及时干预治疗,将发生癌变。
肿瘤干细胞理论提示FAP可能也来源于腺瘤干细胞(Adenomastem cells)。分离、培养、鉴定腺瘤干细胞并研究其性质具有重要意义。肿瘤干细胞研究的难点在于确定其特异性表面标志或表面标志的组合方案。应用有针对性的抗原去检测细胞亚群的表面标志将节省大量的时间和研究经费,并有望形成高效的分选方案。
我们通过一种新的干细胞标记物微管相关蛋白DCAMKL-1来鉴定FAP腺瘤干细胞,并通过研究干细胞中某些蛋白的表达,研究腺瘤发生发展及转归的机制。
第一章家族性腺瘤性息肉病腺瘤干细胞的鉴定、分离、培养以及相关蛋白的研究
目的:通过一种新的胃肠干细胞标志物DCAMKL-1对FAP患者腺瘤干细胞进行鉴定,并建立腺瘤细胞分离和培养的办法。研究PCNA、β-catenin、COX-2等蛋白在腺瘤细胞中的表达及这些蛋白与腺瘤发生发展的关系。
方法:采用免疫组化的方法,对正常结肠粘膜,FAP腺瘤上皮及癌变的腺瘤上皮进行DCAMKL-1染色,观察DCAMKL-1阳性表达细胞的位置。对比MSI-1阳性表达细胞的位置,对腺瘤细胞进行Hoechst染色。观察PCNA、β-catenin、COX-2等蛋白在腺瘤细胞的表达,并探讨β-catenin、COX-2在正常结肠粘膜,FAP腺瘤上皮及癌变的腺瘤上皮中表达的相关性。
结果:在正常结肠粘膜,FAP腺瘤上皮及癌变的腺瘤上皮中,DCAMKL-1阳性表达细胞主要位于结肠隐窝的底部,与用于标记肠干细胞的MSI—1阳性表达位置一致,且随着病变的发展,在腺瘤中逐渐呈现表达增多的现象。DCAMKL-1阳性表达细胞细胞核不能为Hoechst33342染色。PCNA、β-catenin、COX-2的表达均与腺瘤病变的发展相关。
结论:DCAMKL-1是一种新奇的胃肠干细胞的标记物,其阳性表达的细胞可能为家族性腺瘤性息肉病及正常结肠粘膜的干细胞。对腺瘤的治疗关键在于切除腺瘤干细胞,以及抑制与腺瘤病情发展呈正相关的COX-2蛋白等。
第二章高频电切腺瘤性息肉对家族性腺瘤性息肉病裸鼠病程的影响及转归
目的:建立FAPmin裸鼠模型并考察高频电切治疗对FAPmin裸鼠结肠腺瘤发生、发展及转归的影响。
方法:采用N-二乙基亚硝胺灌胃诱变的方法建立了FAPmin裸鼠模型;与高频电切治疗后1、3、6、9、12个月,通过免疫组织化学染色技术检测APC、Lgr5、Musashi-1及PTEN蛋白阳性表达率的变化;半定量RT-PCR技术检测APC、Lgr5、Musashi-1及PTEN mRNA表达水平的变化;原位末端转移酶标记技术检测腺瘤细胞凋亡指数的变化。
结果:高频电切治疗后1、3、6、9、12个月,模型组裸鼠结肠组织中APC、Lgr5、Musashi-1蛋白及基因表达水平显著升高,而电切组裸鼠上述分子的表达水平则显著下降,两组的变化存在差异,具有统计学意义(p＜0.01);两组腺瘤细胞凋亡指数的变化存在差异,模型组腺瘤细胞凋亡指数从1月到12月的变化范围为(8.29±0.98)%～(7.76±1.34)%,对照组的变化范围为(20.08±1.21)%～(32.79±3.62)%,两组间及组内在各个时间点上存在的差异具有统计学意义(p＜0.01)。
结论:采用N-二乙基亚硝胺灌胃诱变的方法能够建立FAPmin裸鼠模型;经高频电切治疗FAP,裸鼠的病情得到了控制,并且随着治疗后时间的延长,FAPmin裸鼠能够逐渐恢复健康。
第三章舒林酸联合内镜下高频电切治疗家族性腺瘤性息肉病的临床研究
目的:探讨舒林酸联合内镜下高频电切治疗家族性腺瘤性息肉病的新方法及临床疗效。
方法:20例经结肠镜检查和组织病理学检查确诊的家族性腺瘤性息肉病患者,随机分为两组,每组10例:舒林酸联合内镜组、舒林酸组。舒林酸联合内镜组患者,行内镜下高频电凝、电切及热活检钳治疗结束后即口服舒林酸400 mg/d,疗程为12个月;舒林酸组患者,仅口服舒林酸400 mg/d,疗程为12个月。两组患者均为每4个月结肠镜复查一次,观察腺瘤的数目、类型、异型增生程度以及治疗后腺瘤细胞凋亡指数变化。
结果:舒林酸联合内镜组于治疗后4、8、12个月腺瘤消退率分别为90.96%、95.66%和98.81%,而舒林酸组分别为80.08%、85.35%和89.78%,两组比较差异有统计学意义(p＜0.05)。舒林酸联合内镜组患者,经治疗后腺瘤Ⅲ级异型增生程度明显降低。舒林酸联合内镜组于治疗后4、8、12个月腺瘤细胞凋亡指数分别为(20.08±1.21)%、(25.67±2.07)%、(32.79±3.62)%,舒林酸组分别为(13.29±0.98)%、(19.83±1.56)%、(25.18±2.31)%,两组比较差异有统计学意义(p＜0.05)。
结论:通过对以上两种方法的疗效比较可知,舒林酸联合内镜下高频电切治疗家族性腺瘤性息肉病是有效的,且优于单纯服用舒林酸的传统治疗方法。
BACKGROUD
It 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-L
Objective: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 models
Objective: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 sulindac
Objective: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.
关于肿瘤的发生、发展、侵袭、转移和治疗一直是医学研究的热点。传统观点认为,肿瘤由成熟细胞突变而来,是由均一的肿瘤细胞共同增殖构成的,所有肿瘤细胞都有无限增殖能力。因此临床上常以肿瘤体积是否缩小或消失作为衡量肿瘤疗效的一个标准.但临床上许多肿瘤患者,在手术切除肿瘤或经过其他治疗,病情已获稳定一段时间后,却又出现肿瘤的复发或转移,不能获得彻底治愈。
新近研究发现:肿瘤组织中存在极少量干细胞样亚群,它具有无限增殖的潜能,在启动肿瘤形成和生长中起着决定性的作用,而其余的大多数细胞,经过短暂的分化,最终死亡。肿瘤生长是肿瘤组织中极少量具有特殊表面标志的肿瘤干细胞增殖的结果。这提示肿瘤治疗应针对在肿瘤发生、发展中起决定性作用的肿瘤干细胞,而不是大部分无增殖、分化能力的肿瘤实体细胞。这可能促进肿瘤治疗学发生革命性改变。
家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)是常见的遗传性大肠肿瘤之一,约占总大肠肿瘤的1%,可分为经典型家族性腺瘤性息肉病(Classical FAP,CFAP),衰减型家族性腺瘤性息肉病(Attenuated FAP,AFAP)和MYH相关性息肉病(MYH associatedFAP,MAP)三种,其临床表现为青春发育期发生结直肠腺瘤,后逐渐增多,甚至满布所有结直肠粘膜,如不及时干预治疗,将发生癌变。
肿瘤干细胞理论提示FAP可能也来源于腺瘤干细胞(Adenomastem cells)。分离、培养、鉴定腺瘤干细胞并研究其性质具有重要意义。肿瘤干细胞研究的难点在于确定其特异性表面标志或表面标志的组合方案。应用有针对性的抗原去检测细胞亚群的表面标志将节省大量的时间和研究经费,并有望形成高效的分选方案。
我们通过一种新的干细胞标记物微管相关蛋白DCAMKL-1来鉴定FAP腺瘤干细胞,并通过研究干细胞中某些蛋白的表达,研究腺瘤发生发展及转归的机制。
第一章家族性腺瘤性息肉病腺瘤干细胞的鉴定、分离、培养以及相关蛋白的研究
目的:通过一种新的胃肠干细胞标志物DCAMKL-1对FAP患者腺瘤干细胞进行鉴定,并建立腺瘤细胞分离和培养的办法。研究PCNA、β-catenin、COX-2等蛋白在腺瘤细胞中的表达及这些蛋白与腺瘤发生发展的关系。
方法:采用免疫组化的方法,对正常结肠粘膜,FAP腺瘤上皮及癌变的腺瘤上皮进行DCAMKL-1染色,观察DCAMKL-1阳性表达细胞的位置。对比MSI-1阳性表达细胞的位置,对腺瘤细胞进行Hoechst染色。观察PCNA、β-catenin、COX-2等蛋白在腺瘤细胞的表达,并探讨β-catenin、COX-2在正常结肠粘膜,FAP腺瘤上皮及癌变的腺瘤上皮中表达的相关性。
结果:在正常结肠粘膜,FAP腺瘤上皮及癌变的腺瘤上皮中,DCAMKL-1阳性表达细胞主要位于结肠隐窝的底部,与用于标记肠干细胞的MSI—1阳性表达位置一致,且随着病变的发展,在腺瘤中逐渐呈现表达增多的现象。DCAMKL-1阳性表达细胞细胞核不能为Hoechst33342染色。PCNA、β-catenin、COX-2的表达均与腺瘤病变的发展相关。
结论:DCAMKL-1是一种新奇的胃肠干细胞的标记物,其阳性表达的细胞可能为家族性腺瘤性息肉病及正常结肠粘膜的干细胞。对腺瘤的治疗关键在于切除腺瘤干细胞,以及抑制与腺瘤病情发展呈正相关的COX-2蛋白等。
第二章高频电切腺瘤性息肉对家族性腺瘤性息肉病裸鼠病程的影响及转归
目的:建立FAPmin裸鼠模型并考察高频电切治疗对FAPmin裸鼠结肠腺瘤发生、发展及转归的影响。
方法:采用N-二乙基亚硝胺灌胃诱变的方法建立了FAPmin裸鼠模型;与高频电切治疗后1、3、6、9、12个月,通过免疫组织化学染色技术检测APC、Lgr5、Musashi-1及PTEN蛋白阳性表达率的变化;半定量RT-PCR技术检测APC、Lgr5、Musashi-1及PTEN mRNA表达水平的变化;原位末端转移酶标记技术检测腺瘤细胞凋亡指数的变化。
结果:高频电切治疗后1、3、6、9、12个月,模型组裸鼠结肠组织中APC、Lgr5、Musashi-1蛋白及基因表达水平显著升高,而电切组裸鼠上述分子的表达水平则显著下降,两组的变化存在差异,具有统计学意义(p＜0.01);两组腺瘤细胞凋亡指数的变化存在差异,模型组腺瘤细胞凋亡指数从1月到12月的变化范围为(8.29±0.98)%～(7.76±1.34)%,对照组的变化范围为(20.08±1.21)%～(32.79±3.62)%,两组间及组内在各个时间点上存在的差异具有统计学意义(p＜0.01)。
结论:采用N-二乙基亚硝胺灌胃诱变的方法能够建立FAPmin裸鼠模型;经高频电切治疗FAP,裸鼠的病情得到了控制,并且随着治疗后时间的延长,FAPmin裸鼠能够逐渐恢复健康。
第三章舒林酸联合内镜下高频电切治疗家族性腺瘤性息肉病的临床研究
目的:探讨舒林酸联合内镜下高频电切治疗家族性腺瘤性息肉病的新方法及临床疗效。
方法:20例经结肠镜检查和组织病理学检查确诊的家族性腺瘤性息肉病患者,随机分为两组,每组10例:舒林酸联合内镜组、舒林酸组。舒林酸联合内镜组患者,行内镜下高频电凝、电切及热活检钳治疗结束后即口服舒林酸400 mg/d,疗程为12个月;舒林酸组患者,仅口服舒林酸400 mg/d,疗程为12个月。两组患者均为每4个月结肠镜复查一次,观察腺瘤的数目、类型、异型增生程度以及治疗后腺瘤细胞凋亡指数变化。
结果:舒林酸联合内镜组于治疗后4、8、12个月腺瘤消退率分别为90.96%、95.66%和98.81%,而舒林酸组分别为80.08%、85.35%和89.78%,两组比较差异有统计学意义(p＜0.05)。舒林酸联合内镜组患者,经治疗后腺瘤Ⅲ级异型增生程度明显降低。舒林酸联合内镜组于治疗后4、8、12个月腺瘤细胞凋亡指数分别为(20.08±1.21)%、(25.67±2.07)%、(32.79±3.62)%,舒林酸组分别为(13.29±0.98)%、(19.83±1.56)%、(25.18±2.31)%,两组比较差异有统计学意义(p＜0.05)。
结论:通过对以上两种方法的疗效比较可知,舒林酸联合内镜下高频电切治疗家族性腺瘤性息肉病是有效的,且优于单纯服用舒林酸的传统治疗方法。
BACKGROUD
It 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-L
Objective: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 models
Objective: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 sulindac
Objective: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.
引文
[1]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells[J].Nature,2001,414:105-111.
[2]Al-Hajj M,Wicha MS.Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells[J].Proc Natl Acad Sic USA,2003,100:3983-3988.
[3]Singh SK,Clarke ID,Teraski M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Res,2003,63:5821-5828.
[4]Dontu D,Al-Hajj M,Abdallah WM,et al.Stem cells in normal breast development and breast cancer[J].Cell Prolif,2003,36:59-72.
[5]Webb T.Work on breast cancer stem cells raises questions about treatment strategies[J].J Cancer Ins,2003,95:774-775.
[6]Ross S,spencer SD.Holcomb I,et al.Prostate stem cell antigen as therapy target:tissue expression and in vivo efficacy of an immunoconjugate[J].Cancer Res,2002,62:2546-2553.
[7]Kummermehr JC.Tulnor stem cells-the evidence and the ambiguity[J].Acta Oncol,2001,40:981-988.
[8]Wallace NH,Phillips RK.Upper gastrointestinal disease in patients with familial adenomatous polpsis[J].Br J Surg,1998,85(6):742-750.
[9]Glaser EM.Inherited predisposition to colon cancer[J].Cancer Nursing,1998,21(6):377-383.
[10]Potten CS,Boot HC.Tudor GL,et al.Identification of a putative intestinal stem cell and early lineage marker musashi-1[J].Differentiation,2003,71(1):28-41.
[11]Imai T.Tokunaga A,Yoshida T,et al.The neural RNA-binding protein musashi-1translationally regulates mammalian numb gene expression by interacting with its mRNA[J].Molecular Cell Biology,2001,21(12):3888-3900.
[12]Kinzler kW,Vogelstein B.Lessons from hereditary colorectal cancer[J].Cell,1996,87:159-170.
[13]Wallis YL.Macdonald F,Hulten M,et al.Genotype-phenotype correlation between position of constitutional APC gene mutation and CHRPE expression in familial adenomatous polyposis[J].Hum Genet 1994,94:543-548.
[14]Scott RJ,Froggart NJ,Trembath RC,et al.Familial infiltrative fibromatosis (desmoid tumours)(MIM135290) caused by a recurrent 3-prime APC gene mutation[J].Hum Molec Genet 1996,5:1921-1924.
[15]Luongo C,Moser AR,Gledhill S,et al.Loss of Apc+ in intestinal adenomas from Min mice[J].Cancer Res,1994,54:5947-5952.
[16]Shoemaker AR,Luongo C,Moser AR.et al.Dove WF Somatic mutational mechanisms involved in intestinal tumor formation in Min mice[J].Cancer Res,1997,57:1999-2006.
[17]Clarke AR,Cummings MC,Harrison DJ.Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy[J].Oncogene,1995,11:1913-1920.
[18]Umanoff H,Edelmann W,Pellicer A,et al.The routine N-ras gene is not essential for growth and development[J].Proc Natl Acad Sci USA.1995,92:1709-1713.
[19]Laken SJ,Petersen GM,Gruber SB,et al.Familial colorectal cancer in ashkenazim due to a hypermutable tract in APC[J].Nature Genet,1997,17:79-83.
[20]Sakanaka C,Weiss JB,Williams LT,et al.Bridging of catenin and glycogen synthase kinase-3 by axin and inhibition of catenin-mediated transcription[J].Proc natl Acad Sci USA,1998,95:3020-3023.
[21]Beroud C,Soussi T.APC gene:database of germline and somatic mutations in human tumors and cell lines[J].Nucleic Acids Res,1996,24:121-124.
[22]Moser AR,Mattes EM,Dove WF,et al.Apc(Min),a mutation in the murine apc gene,predisposes to mammary carcinomas and focal alveolar hyperplasias[J].proc Nat Acad Sci,1993,90:8977-8981.
[23]Herrmann C,Block C,Geisen C.et al.Sulindac sulfide inhibits ras signaling[J].Oncogene,1998,17:1769-1776.
[24]Panj AA.A novel method for the establishment of a purepopulation of nontransfonned human intestinal primary epithelial cell(HIPEC) lines in long-term culture[J].Laboratorial Investigation,2000,80:1473-1475.
[25]Mckaig BC,Makh SS,Hawkey CS,et al.Normal human colonic subepithelial migratin via TGFβ3[J].AmJ physiol,1999,276:G1087-G1093.
[26]Booth D,Haley JD.Arthur MB.et al.Transforming growth factorβ3 protects murine small intestinal crypt stem cells and animal survival after irradiation possibly by reducing stem cell cycling[J].Ent J Cancer,2000.86:53-59.
[27]Bach SP,Renehan AG,potton CS.Stem cells:the intestinal stem cell as a paradigm[J].Carcinogenesis,2000,21(3):469-467.
[28]Booth C,Potton CS.Gut instincts:thoughts on epithelial stem cells[J].J Clin Invest,2000,105(8):1493-1499.
[29]Merritt AJ.Allen TD,Potton CS,et al.Apoptsis in the small intestinal epithelium from 53 null mice:evidence for a delayed.P53 independent G2/M associated cell death after gamma irradiation[J].Oncogene,1997.14(23):2759-2766.
[30]内镜下高频电切治疗家族性腺瘤性息肉病的临床研究[J],中国现代医学杂志,2006,16(4):568-570.
[31]Nick Barker,John H,Van Es,et al.Indentification of stem cells in small intestine and colon by marker gene Lgr5[J].Nature,2007,449(25):1003-08.
[32]司徒镇强.吴军.细胞培养[M].西安:世界图书出版公司,1994:114-117.
[33]Lucia Ricci-Vitian,Dario G.Lombard,Emanuela Pilozzi,et al.Identification and expansion of human colon-cancer-initiating cells[J].Nature,doi:10.1038/05384:1-5.
[34]Catherine A.O'Brien,Aaron Pollett,Steven Gallinger,et al.A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J].Nature,doi:10.1038/05372:1-5.
[35]Gregorieff,A&Clevers,H.Wnt signaling in the intestinal epithelium:from endoderm to cancer[J].Genes Dev,2005,19:877-890.
[36]Randal May,Terrence E.Riehl,Clayton Hunt,et al.Identification of a noval putative gastrointestinal stem cell and adenoma stem cell marker,Doublecortin and CaM Kinase-Like-1,following Radiation Injury and in Adenomatous polyposis coli/multiple intestinal neoplasia mice[J].Stem cell,2008,26:630-637.
[37]Kawai N,Tsujii M,Tsuji S.Cyclooxygenases and colon cancer[J]Prostaglandins Ot her Lipid Mediat,2002,68269:187-196.
[38]Williams CS,Luongo C,Radhika A,et al.Elevated cyclooxygenase-2 levels in Min mouse adenomas[J].Gast roenterology,1996,111:1134-1140.
[39]Takeda H,Sonoshita M,Oshima H,et al.Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis[J].Cancer Res,2003,63:4872-4877.
[40]J acoby RF,Seibert K,Cole CE,et al.The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis[J].Cancer Res,2000,60:5040-.5044.
[41]Eberhart CE,Cofey RJ,Radhika A,et al.Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenomas and adenocarcinoma.Gastroenterology, 1994;107(4):1183-1188.
[42]Derrick J.Rossi,Anti Ylikorkala,Nina Korsisaari,et al.Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis.Proc Natl Acad Sci USA,2002;99(19):12327-12332.
[43]Barnes CJ,Lee M.Chemo-prevention of spontaneous intestinal adenomas and the adenomatous polyposis coli in Min model with aspirinGastroenterology,1998;114:873-877.
[44]Giovanncci E.The prevention of colorectal cancer by aspirin use.Biomed Pharmacother,1999;53:303-308
[45]Cruz-Correa M,Giardiello F.Familial adenomatous polyposis.Gastrointestinal Endoscopy,2003,58(6):885-894
[46]Morpurgo E,Vitale GC,Galandiuk S,et al.Clinical characteristics of familial adenomatouspolyposis andmanagement of duodenal adenomas.Journal of Gastrointestinal Surgery,2004,8(5):559-564
[47]廖国庆,晏仲舒.家族性腺瘤性息肉病.中国普通外科杂志.2004.13(4):295-297
[48]郑芝田,主编.胃肠病学.北京:人民卫生出版社,2000,3:852-855.
[49]Jarvinena HJ,Peltomakib P.The complex genotype-phenotype relationship in familial adenomatous polyposis.European Journal of Gastroenterology &Hepatology,2004,16(1):528
[50]Ishikawa H.Chemoprevention of carcinogenesis in familial tumors.Int J Clin Oncol,2004,9(4):299-303
[51]RANDAL MAY,TERRENCE E.RIEHL,CLAYTON HUNT,SRIPATHI M.SUREBAN,SHRIKANT ANANT,COURTNEY W.HOUCHEN.Identification of a Novel Putative Gastrointestinal Stem Cell and Adenoma Stem Cell Marker,Doublecortin and CaM Kinase-Like-1,Following Radiation Injury and in Adenomatous Polyposis Coli/Multiple Intestinal Neoplasia Mice.Stem cells.2008;26;630-637
[52]Milo Frattini,Ileana Carnevali,Stefano Signoroni,Debora Balestra,Maria Luisa Moiraghi,Paolo Radice,Liliana Varesco,Viviana Gismondi,Giovanni Ballardini,Paola Sala,Marco A.Pierotti,Silvana Pilotti,Lucio Bertario. Cyclooxygenase-2 Expression in FAP Patients Carrying Germ Line MYH Mutations.Cancer Epidemiol Biomarkers Prev 2005;14(8):2049-2053.
[53]Imad Shureiqi,Yuanqing Wu,Dongning Chen,Xiu L.Yang,Baoxiang Guan,Jeffrey S.Morris,Peiying Yang,Robert A.Newman,Russell Broaddus,Stanley R.Hamilton,Patrick Lynch,Bernard Levin,Susan M.Fischer,Scott M.Lippman.The Critical Role of 15-Lipoxygenase-1 in Colorectal Epithelial Cell Terminal Differentiation and Tumorigenesis.Cancer Res 2005;65(24):11486-11493
[54]Witek,M.E.et al.The putative tumor suppressor Cdx2 is overexpressed by human colorectal adenocarcinomas.Clin.Cancer Res.11,8549-8556.(2005).
[55]Wang,J.C.& Dick,J.E.Cancer stem cells:lessons from leukemia.Trends Cell Biol.15,494-501(2005).
[56]Clevers,H.Stem cells,asymmetric division and cancer.Nature Genet.37,1027-1028(2005).
[57]Cruz-Correa M,Giardiello F.Familial adenomatous polyposis.Gastrointestinal Endoscopy,2003,58(6):885-894
[58]Morpurgo E,Vitale GC,Galandiuk S,et al.Clinical characteristics of familial adenomatouspolyposis andmanagement of duodenal adenomas.Journal of Gastrointestinal Surgery,2004,8(5):559-564
[59]廖国庆,晏仲舒.家族性腺瘤性息肉病.中国普通外科杂志.2004.13(4):295-297
[60]李军,吕愈敏,顾芳,安燕芳,钱跃清.舒林酸长期治疗家族性腺瘤性息肉病的临床研究.中华消化杂志.2005.25(3):153-156
[61]Cruz-Correa M,Hylind LM,Romans KE,et al.Long-term treatment with sulindac in familial adenomatous polyposis:a prospective cohort study.Gast roenterology,2002,122:641-645.
[62]郑芝田,主编.胃肠病学.北京:人民卫生出版社,2000,3:852-855.
[63]Jarvinena HJ,Peltomakib P.The complex genotype-phenotype relationship in familial adenomatous polyposis.European Journal of Gastroenterology &Hepatology,2004,16(1):528
[64]Ishikawa H.Chemoprevention of carcinogenesis in familial tumors.Int J Clin Oncol,2004,9(4):299-303
[65]钱跃清,吕愈敏,叶嗣懋,等.舒林酸治疗散发性结直肠腺瘤的临床研究.中 华消化杂志,2001,21(12):710-712.
[66]BabbarN,Ignatenko NA,Casero RA J r,et al.Cyclooxygenase 2 independent induction of apop tosis by sulindac sulfone is mediated by polyamines in colon cancer[J].J Biol Chem,2003,278:47762-47775.
[67]Thun MJ,Henley SJ,Patrono C.Nonsteroidal anti-inflammatory drugs as anticancer agents:mechanistic,pharmacologic,and clinical issues[J].J Natl Cancer Inst,2002,94:252-266.
[68]Shaheen NJ,Straus WL,Sandler RS.Chemop revention of gastrointestinal malignancies with nonsteroidal anti-inflammatory drugs[J].Cancer,2002,94:950-963.
[69]安燕芳,吕愈敏,叶嗣懋.舒林酸对家族性腺瘤性息肉病的疗效及作用机制的探讨[J].中华消化杂志,2000,20:243-245.
[70]李军,吕愈敏,顾芳,等.舒林酸长期治疗家族性腺瘤性息肉病的临床研究[J].中华消化杂志,2005,25:153-156.
[71]李军,吕愈敏,金珠,等.舒林酸对家族性腺瘤性息肉病结直肠残存腺瘤组织病理学表现的影响[J].北京大学学报(医学版),2005,37:371-373.
[72]钱跃清,吕愈敏,叶嗣懋,等.舒林酸治疗散发性结直肠腺瘤的临床研究[J].中华消化杂志,2001,21:710-712.
[73]BrownWA,Skinner SA,Maclontenti2Wilson C,et al.Non-steroidal antiinflammatory drugs with different cyclooxygenase inhibitory p rofiles that p revent aberrant cryptfoci formation but vary in acute gastrotoxicity in a rat model [J].J Gastroenterol Hepatol,2000,15:1386-1392.
[74]Houseknecht KL,ColebM,Steele PJ.Peroxisome proliferators activated receptor gamma and review[J].Domest Anim Endocrinol,2002,22:1-23.
[75]Sarraf P,Mueller E,JonesD,et al.Differentiation and reversal of malignant changes in colon cancer through PPAR γ[J].Nature Med,1998:1046-1052.
[76]Strakova N,Ehrmann J,Dzubak P,et al.The synthetic ligand of peroxisome p roliferator activated receptor-gamma ciglitazone affects human glioblastoma cell lines[J].J Pharmacol Exp Ther,2004,309:1239-1247.
[77]WachterA,Loitsch SM,Stein J.PPAR gamma is selectively upregulated in Caco-cells by butyrate[J].Biochem Biophys Res Commu,2000,272:380-385.
[78]NagamineM,Okumura T,Tanno S,et al.PPAR gamma ligand induced apoptosis through a p53 dependent mechanism in human gastric cancer cells[ J ]. Cancer Sci, 2003, 94:338 - 343.
[79] Piazza GA, Rahm AL, Krutzsch M, et al. Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res, 1995, 55( 14): 3110-3116.
[1]OLSschwang S,Laurent-Puin P,Melot T,et al.High resolution genetic map of the adenomatous polyposis coli gene(APC)region[J].AmJ Med Genet,1995,56(4):413-419.
[2]梁君林,高枫,唐宗江.APC基因与结肠直肠肿瘤[J].大肠肛门病外科杂志.2001,7(2):56-60.
[3]杨翔,高志刚,谢德红,等.家族性腺瘤性息肉病[J].中华普通外科杂志,1997,12(5)299-301.
[4]李增烈,廖宁逊.家族性结肠息肉病[J].中国实用内科杂志,2000,20(2):73-74.
[5]Herrera L,Kakati S,Gibas L,el al.Gardner syndrome in a man with an interstitial deletion of 5q[J].Am J med Genel,1986,25(3):473-476.
[6]Bodimer WF,Bailey C,Bodmer J.et al.Localization of the gene for familial adenomatous polyposis on chromosome 5.Nature,1987,328:614.
[7]Thliveris A.Long-range physicalmap and deletion characterization of the 1100-kb Not I restriction fragment harboring the APC gene[J].Genomics,1996,34:268-270.
[8]Kinzler KW,Vogelstein B.Lessons from hereditary colorectal cancer[J].Cell.1996,87:159-170.
[9]Su LK,Johan KA,Smith KJ,et al.Assoiation between wild type andmutant APC gene products[J].Cancer Res,1993,53:2728-2731.
[10]Gryfe R,Swallow C,Bapat B,et al.Molecular biology of colorectal cancer.Curr Probl Cancer[J].1997,9:238-299.
[11]Mimori-Kiyosue Y,Shiina N,Tsukita S.A denomatous polyposis coli(APC)protein moves along microtubules and concentrates at their growing ends in epithelial cells[J].J Cell Biol,2000,148:505-518.
[12]Barth AM,Pollack AL,Altschuler Y,et al.NH-terminal deletion of β-catenin results in stable colocalization of mutantβ-catenin with APC protein and altered MDCK cell adhesion[J].J Cell Biol,1997,136:693-706.
[13]Heinen CD.Goss KH,Cornelius JR,et al.The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway[J].Gostroenterology.2002,123(3):935-939.
[14]Trzepacz C,Lowy AM,Kordich JJ,et al.Phosphory lation of the tumor suppressor adenomatous polyposis coli(APC) by the cyclin-dependent kinase p34cdc2[J].J Biol Chem,1997,272:21681-21684.
[15]Goss KH,Groden J.Biology of the adenomatous polyposis coli tumor suppressor[J].J.Clin.Oncol,2000,18:1967-1979.
[16]Homfray TF,Cottrell SE,Ilyas M,et al.Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumours[J].HumMutat,1998,11(2):114-120.
[17]萧树东.江绍基胃肠病学[M].上海:上海科学技术出版社,2001.
[18]Nicola SF,Michael P,Walier F.The ABC of APC[J].Human Molecular Genetics,2001,10(7):721-733.
[19]Takaku K,Oshima M,Miyoshi H.Intestinal tumorigenesis in compound mutant mice of both DPC4(Smad4) and APC genes[J].Cell,1998,92(5):645-647.
[20]Schwarte I,Klein S,Blass Kampmann S,et al.DPC4/SMAD4 mediated tumor suppression of colon carcinoma cells is associated with reduced urokinase expression[J].Oncogene,1999,18(20):3152-3154.
[21]Liam O,David CS,Lorraine AO,et al.Apoptosis and cell division[J].Currt Opin Cell Biol,2000,12(2):257-263.
[22]Comelia SS,Rachel AF,Kaede H,et al.NF-κB determines location and features of cell death in epidemis[J].J Clin Inves,2000,105(3):253-260.
[23]Tomozawa S,Tsuno NH,Sunami E,et al.Cyclooxygenase-2 overexpression correlates with tumour recurrence,especially haematogenous metastasis,of colorectal cancer[J].Br J Cancer,2000,83(3):324.
[24]Dixon DA,Kaplan CD,Mclntyre TM,et al.Post-transcriptional control of cyclooxygenase-2 gene expression.The role of the 3'-untranslated region[J].J Biol Chem,2000,275(16):11750.
[25]Ohno R,Yoshinaga K,Fujita T,et al.Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma[J].Cancer,2001,91(10):1876.
[26]Uefuji K,Ichikura T,Mochizuki H.Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer[J].Clin Cancer Res,2000,6(1):135.
[27]Ottino P,Bazan HE.Corneal stimulation of MMP-1,-9 and uPA by platelet-activating factor is mediated by cyclooxygenase-2 metabolites[J].Curr Eye Res,2001,23(2):77.
[28]Noda M,Tatsumi Y,Tomizawa M,et al.Effects of etodolac,a selective cyclooxygenase-2 inhibitor,on the expression of β-cadherin-catenin complexes in gastrointestinal cell lines[J].J Gastroenterol,2002,37(11):896.
[29]Wallace NH,Phillips RK.Upper gastrointestinal disease in patients With familial adenomatous polpsis[J].Br J Surg,1998,85(6):742-750.
[30]Glaser EM.Inherited predisposition to colon cancer[J]Cancer Nursing,1998,21(6):377-383.
[31]唐宗江,高枫.家族性腺瘤性息肉病的外科治疗[J].中国普通外科杂志1999,7(6):344-346.
[32]郑芝田,黄莛庭.胃肠病学,第2版[M],北京:人民卫生出版社,1995,706-709.
[33]Helm JF,Sandler RS.Colorectal cancer screening[M].Med Clin North Am,1999:1403.
[34]Spirio L,Olschwang S,Groden J,et al.Alleles of the APC gene:An attenuated form of familial polyposis[J].Cell,1993,75:951.
[35]Hamilton SR,Liu B,Parsons RE,et al.The molecular basis of"Turcot syndrome"[J].N Engl J Med,1995,332:839.
[36]唐贵林,张阳德,吕海宝.大肠组织自全变光光谱的判别诊断研究.中国现代医学杂志[J].2001,11(12):21-23.
[37]胡念平,晏仲舒,吕新生.截短蛋白检测用于家族性腺瘤性息肉病的基因诊断[J].中国普通外科杂志,2000,9(3):240-242.
[38]Celisken O,Yocel A,Coler K,et al.Ocular findings in familial adenomatous polyposis[J].Int Ophthalmol,1998,21:205-208.
[39]Steinbach G,Lynch PM,Phillips RK,et al.The effect of celecoxib,a cyclooxygenase-2 inhibitor,in familial adenomatous polyposis[J].N Engl J Med,2000,342(26):1946.
[40]Altorki NK,Keresztes RS,Port JL,et al.Celecoxib,a selective Cyclooxygenase-2inhibitor,enhances the response to preoperative paclitaxel and carboplatin in early stage non-small cell lung Cancer[J].Clin Oncol,2003,21(14):2645.
[41]郜恒俊,萧树东.NSAIDS化学预防直肠癌研究的新进展[J].国外医学.消化系疾病分册.2001,21(5):86-89.
[42]Willianson SLH,Kartheuser A,Coaler J,et al.Intestinal tumorgenesis in the Apc1638 N mouse treated with asprin and resistant starch for up to 5months[J].Carcinogenesis,1999,20(5):805-810.
[43]安燕东,吕愈敏,叶嗣懋.舒林酸对家族性腺瘤性息肉病的疗效及作用机制[J].中华消化杂志,2000,20(4):243-245.
[44]Mahamoud NN,Dannenberg AJ,Mestre J,et al.Asprin prevents tumors in a murine model of familial adenomatous polyposis[J].Surgery,1998,124(2):225-231.
[45]Ichikawa D,Takahashi T,Adachi T,et al.Postoperative management of the preserved rectal segment in patients with familial polyposis:the use of 5-fluorouracil suppositories and green tea extract to inhibit tumor growth[J].Nippon Geka Gakkai Zushi,1998,99(6):391-395.
[46]Beveridge IG,Swain DJ,Groves CJ,et al.Large villous adenomas arising in ileal pouches in familial adenomatous polyposis:report of two cases[J].Dis colon rectum,2004,47(1):123-126.
[47]胡友主,王存川,陈 鏊.腹腔镜手术治疗结直肠良恶性病变103例分析[J].中国内镜杂志,2003,9(7):31-33.
[48]池畔,林惠铭.腹腔镜辅助全大肠切除治疗家族性腺瘤性息肉病4例报告[J].中国实用外科杂志,2004,24(8):507.
[49]郑明华.论腹腔镜结肠直肠手术[J].外科理论与实践,2004,9(6):453.
[50]Inoue Y,Noro H,Komoda H,et al.Completely laparoscopic total colectomy for chronic constipation:report of a case[J].Surg Today,2002,32(6):551-554.
[1]刘海峰,大肠息肉679例临床特征及内镜、病理学特点分析[J]武警医学,2008,19(2):133-134.
[2]Gupta SK,Fitzgerald JF,Croffie JM,et al.Experience with juvenile polyps in North American children:the need for pancolonoseopy.Am J Gastroenterol,2001,96(6):1695-1697.
[3]Woodford-Richens K,Williamson J,Bevan Set al.Allelicloss at SMAD4 in polyps from juvenile polyposis patients and use of fluorescence in sire hybridization to demonstrate clonalorigin of the epithelium.Cancer Res,2000,60(9):2 477
[4]Repici A,Tricerri R.Endoscopic polypectomy:techniques,complications and follow- up.Tech Coloproctol,2004,8(Suppl 2):s283
[5]陈春华,邱立华.大肠息肉1884例患者的临床观察及恶变特征分析.肿瘤防治杂志,2005,12(24):1 888
[6]吴子刚,吴子光,全华斌.大肠良恶性息肉的临床特征及内镜、病理形态学特点[J].中华消化内镜杂志,1999,16(3):141-143.
[7]郑芝田.胃肠病学[M].北京:人民卫生出版社,2002.702-706.
[8]Winawer S,Fletcher R.Colorectal cancer screening and surveillance[J].Gastroenterology,2003,124(2):553-554
[9]宇野良治,韩英,栋方昭博,等.实用大肠镜诊断及治疗学[J].北京:科学出版社,2001.
[10]Peter Cotton,Christopher Williams.1996 Practical Gastrointestinal Endoscopy [J].4th Editionll Science.Clements RH,Jordan LM,Webb WA.Critical decisionsin the management of endoscopic perforations of the colon[J].Ame Surg,2000,66:91-92.
[11]Kozarek RA,Eurnest DL,Silverstein ME,et al.Airpressure-induced colon injury during diagnostic colonoscopy[J].Gastroenterol,1980,78:7-14.
[12]Gedebou TM,Wong RA,Rappaport wd.Clinical presentation and management of iatrogenic colon perforation[J].Am J Surg,1996,172:454-458.
[13]Mattei P,Alonso M,Justinich C.Laparoscopic repair of colonoscopy in children:report of 2 cases and review of the literature[J].J Pediatric Sur,g2005,40:1651-1653.
[14]Raju GS,Ahmed I,Brining D,et al.Endoluminal closure of large perforation of colon with clios in a porcine[J].Gastrointestinal Endoscopy,2006,64:640-646.
[15]Zeno BR,Sahn SA.Colonoscopy-associated pneumothorax..A case of tension pneumothorax and review of the literature[J].Am J Med sci,2006,323:153-155.
[16]Lovisetto F,Zonta S,Rota E,et al.Left pneumothorax secondary to colonoscopic perforation of the sigmoid colon:a case report[J].Surg Lapar Endos&Percul Techni,q2007,17:62-64.
[17]Fu KI,Sano Y,Kato S,et al.Pneumoscrotum:a rare manifestation of perforation associated with therapeutic colonoscopy[J].World J Gastroentero,12005,11:5061-5063.
[18]Chorost MI,Wu JT,Webb H,et al.Vertebral venous air embolism:An unusual complication following colonoscopy[J].Dis Colon Rectu,m2003,46:1138-1140.
[19]Rosen L,Bub D,Reed J,et al.Hemorrhage following colonoscopic polypectomy[J].Dis Colon Rectu,m1993,36:1126-1131.
[20]Rathgaber S,Wick TM.Colonoscopy completion and complication rates in a community gastroenterology practice[J].Gastrointestinal Endosc,2006,64:556-562.
[21]Watabe H,Yamaji Y,Okamoto M,et al.Risk assessment for delayed hemorrhagic complication of colonic polypectom:ypolyp-related factors and patient-related factors[J].Gastrointest Endos,c2006,64:73-78.
[22]Singaram C,Torbey CF,Jacoby RF.Delayed postpolypectomy bleeding[J].Am J Gastroentero,11995,90:146-147.
[2]Al-Hajj M,Wicha MS.Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells[J].Proc Natl Acad Sic USA,2003,100:3983-3988.
[3]Singh SK,Clarke ID,Teraski M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Res,2003,63:5821-5828.
[4]Dontu D,Al-Hajj M,Abdallah WM,et al.Stem cells in normal breast development and breast cancer[J].Cell Prolif,2003,36:59-72.
[5]Webb T.Work on breast cancer stem cells raises questions about treatment strategies[J].J Cancer Ins,2003,95:774-775.
[6]Ross S,spencer SD.Holcomb I,et al.Prostate stem cell antigen as therapy target:tissue expression and in vivo efficacy of an immunoconjugate[J].Cancer Res,2002,62:2546-2553.
[7]Kummermehr JC.Tulnor stem cells-the evidence and the ambiguity[J].Acta Oncol,2001,40:981-988.
[8]Wallace NH,Phillips RK.Upper gastrointestinal disease in patients with familial adenomatous polpsis[J].Br J Surg,1998,85(6):742-750.
[9]Glaser EM.Inherited predisposition to colon cancer[J].Cancer Nursing,1998,21(6):377-383.
[10]Potten CS,Boot HC.Tudor GL,et al.Identification of a putative intestinal stem cell and early lineage marker musashi-1[J].Differentiation,2003,71(1):28-41.
[11]Imai T.Tokunaga A,Yoshida T,et al.The neural RNA-binding protein musashi-1translationally regulates mammalian numb gene expression by interacting with its mRNA[J].Molecular Cell Biology,2001,21(12):3888-3900.
[12]Kinzler kW,Vogelstein B.Lessons from hereditary colorectal cancer[J].Cell,1996,87:159-170.
[13]Wallis YL.Macdonald F,Hulten M,et al.Genotype-phenotype correlation between position of constitutional APC gene mutation and CHRPE expression in familial adenomatous polyposis[J].Hum Genet 1994,94:543-548.
[14]Scott RJ,Froggart NJ,Trembath RC,et al.Familial infiltrative fibromatosis (desmoid tumours)(MIM135290) caused by a recurrent 3-prime APC gene mutation[J].Hum Molec Genet 1996,5:1921-1924.
[15]Luongo C,Moser AR,Gledhill S,et al.Loss of Apc+ in intestinal adenomas from Min mice[J].Cancer Res,1994,54:5947-5952.
[16]Shoemaker AR,Luongo C,Moser AR.et al.Dove WF Somatic mutational mechanisms involved in intestinal tumor formation in Min mice[J].Cancer Res,1997,57:1999-2006.
[17]Clarke AR,Cummings MC,Harrison DJ.Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy[J].Oncogene,1995,11:1913-1920.
[18]Umanoff H,Edelmann W,Pellicer A,et al.The routine N-ras gene is not essential for growth and development[J].Proc Natl Acad Sci USA.1995,92:1709-1713.
[19]Laken SJ,Petersen GM,Gruber SB,et al.Familial colorectal cancer in ashkenazim due to a hypermutable tract in APC[J].Nature Genet,1997,17:79-83.
[20]Sakanaka C,Weiss JB,Williams LT,et al.Bridging of catenin and glycogen synthase kinase-3 by axin and inhibition of catenin-mediated transcription[J].Proc natl Acad Sci USA,1998,95:3020-3023.
[21]Beroud C,Soussi T.APC gene:database of germline and somatic mutations in human tumors and cell lines[J].Nucleic Acids Res,1996,24:121-124.
[22]Moser AR,Mattes EM,Dove WF,et al.Apc(Min),a mutation in the murine apc gene,predisposes to mammary carcinomas and focal alveolar hyperplasias[J].proc Nat Acad Sci,1993,90:8977-8981.
[23]Herrmann C,Block C,Geisen C.et al.Sulindac sulfide inhibits ras signaling[J].Oncogene,1998,17:1769-1776.
[24]Panj AA.A novel method for the establishment of a purepopulation of nontransfonned human intestinal primary epithelial cell(HIPEC) lines in long-term culture[J].Laboratorial Investigation,2000,80:1473-1475.
[25]Mckaig BC,Makh SS,Hawkey CS,et al.Normal human colonic subepithelial migratin via TGFβ3[J].AmJ physiol,1999,276:G1087-G1093.
[26]Booth D,Haley JD.Arthur MB.et al.Transforming growth factorβ3 protects murine small intestinal crypt stem cells and animal survival after irradiation possibly by reducing stem cell cycling[J].Ent J Cancer,2000.86:53-59.
[27]Bach SP,Renehan AG,potton CS.Stem cells:the intestinal stem cell as a paradigm[J].Carcinogenesis,2000,21(3):469-467.
[28]Booth C,Potton CS.Gut instincts:thoughts on epithelial stem cells[J].J Clin Invest,2000,105(8):1493-1499.
[29]Merritt AJ.Allen TD,Potton CS,et al.Apoptsis in the small intestinal epithelium from 53 null mice:evidence for a delayed.P53 independent G2/M associated cell death after gamma irradiation[J].Oncogene,1997.14(23):2759-2766.
[30]内镜下高频电切治疗家族性腺瘤性息肉病的临床研究[J],中国现代医学杂志,2006,16(4):568-570.
[31]Nick Barker,John H,Van Es,et al.Indentification of stem cells in small intestine and colon by marker gene Lgr5[J].Nature,2007,449(25):1003-08.
[32]司徒镇强.吴军.细胞培养[M].西安:世界图书出版公司,1994:114-117.
[33]Lucia Ricci-Vitian,Dario G.Lombard,Emanuela Pilozzi,et al.Identification and expansion of human colon-cancer-initiating cells[J].Nature,doi:10.1038/05384:1-5.
[34]Catherine A.O'Brien,Aaron Pollett,Steven Gallinger,et al.A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J].Nature,doi:10.1038/05372:1-5.
[35]Gregorieff,A&Clevers,H.Wnt signaling in the intestinal epithelium:from endoderm to cancer[J].Genes Dev,2005,19:877-890.
[36]Randal May,Terrence E.Riehl,Clayton Hunt,et al.Identification of a noval putative gastrointestinal stem cell and adenoma stem cell marker,Doublecortin and CaM Kinase-Like-1,following Radiation Injury and in Adenomatous polyposis coli/multiple intestinal neoplasia mice[J].Stem cell,2008,26:630-637.
[37]Kawai N,Tsujii M,Tsuji S.Cyclooxygenases and colon cancer[J]Prostaglandins Ot her Lipid Mediat,2002,68269:187-196.
[38]Williams CS,Luongo C,Radhika A,et al.Elevated cyclooxygenase-2 levels in Min mouse adenomas[J].Gast roenterology,1996,111:1134-1140.
[39]Takeda H,Sonoshita M,Oshima H,et al.Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis[J].Cancer Res,2003,63:4872-4877.
[40]J acoby RF,Seibert K,Cole CE,et al.The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis[J].Cancer Res,2000,60:5040-.5044.
[41]Eberhart CE,Cofey RJ,Radhika A,et al.Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenomas and adenocarcinoma.Gastroenterology, 1994;107(4):1183-1188.
[42]Derrick J.Rossi,Anti Ylikorkala,Nina Korsisaari,et al.Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis.Proc Natl Acad Sci USA,2002;99(19):12327-12332.
[43]Barnes CJ,Lee M.Chemo-prevention of spontaneous intestinal adenomas and the adenomatous polyposis coli in Min model with aspirinGastroenterology,1998;114:873-877.
[44]Giovanncci E.The prevention of colorectal cancer by aspirin use.Biomed Pharmacother,1999;53:303-308
[45]Cruz-Correa M,Giardiello F.Familial adenomatous polyposis.Gastrointestinal Endoscopy,2003,58(6):885-894
[46]Morpurgo E,Vitale GC,Galandiuk S,et al.Clinical characteristics of familial adenomatouspolyposis andmanagement of duodenal adenomas.Journal of Gastrointestinal Surgery,2004,8(5):559-564
[47]廖国庆,晏仲舒.家族性腺瘤性息肉病.中国普通外科杂志.2004.13(4):295-297
[48]郑芝田,主编.胃肠病学.北京:人民卫生出版社,2000,3:852-855.
[49]Jarvinena HJ,Peltomakib P.The complex genotype-phenotype relationship in familial adenomatous polyposis.European Journal of Gastroenterology &Hepatology,2004,16(1):528
[50]Ishikawa H.Chemoprevention of carcinogenesis in familial tumors.Int J Clin Oncol,2004,9(4):299-303
[51]RANDAL MAY,TERRENCE E.RIEHL,CLAYTON HUNT,SRIPATHI M.SUREBAN,SHRIKANT ANANT,COURTNEY W.HOUCHEN.Identification of a Novel Putative Gastrointestinal Stem Cell and Adenoma Stem Cell Marker,Doublecortin and CaM Kinase-Like-1,Following Radiation Injury and in Adenomatous Polyposis Coli/Multiple Intestinal Neoplasia Mice.Stem cells.2008;26;630-637
[52]Milo Frattini,Ileana Carnevali,Stefano Signoroni,Debora Balestra,Maria Luisa Moiraghi,Paolo Radice,Liliana Varesco,Viviana Gismondi,Giovanni Ballardini,Paola Sala,Marco A.Pierotti,Silvana Pilotti,Lucio Bertario. Cyclooxygenase-2 Expression in FAP Patients Carrying Germ Line MYH Mutations.Cancer Epidemiol Biomarkers Prev 2005;14(8):2049-2053.
[53]Imad Shureiqi,Yuanqing Wu,Dongning Chen,Xiu L.Yang,Baoxiang Guan,Jeffrey S.Morris,Peiying Yang,Robert A.Newman,Russell Broaddus,Stanley R.Hamilton,Patrick Lynch,Bernard Levin,Susan M.Fischer,Scott M.Lippman.The Critical Role of 15-Lipoxygenase-1 in Colorectal Epithelial Cell Terminal Differentiation and Tumorigenesis.Cancer Res 2005;65(24):11486-11493
[54]Witek,M.E.et al.The putative tumor suppressor Cdx2 is overexpressed by human colorectal adenocarcinomas.Clin.Cancer Res.11,8549-8556.(2005).
[55]Wang,J.C.& Dick,J.E.Cancer stem cells:lessons from leukemia.Trends Cell Biol.15,494-501(2005).
[56]Clevers,H.Stem cells,asymmetric division and cancer.Nature Genet.37,1027-1028(2005).
[57]Cruz-Correa M,Giardiello F.Familial adenomatous polyposis.Gastrointestinal Endoscopy,2003,58(6):885-894
[58]Morpurgo E,Vitale GC,Galandiuk S,et al.Clinical characteristics of familial adenomatouspolyposis andmanagement of duodenal adenomas.Journal of Gastrointestinal Surgery,2004,8(5):559-564
[59]廖国庆,晏仲舒.家族性腺瘤性息肉病.中国普通外科杂志.2004.13(4):295-297
[60]李军,吕愈敏,顾芳,安燕芳,钱跃清.舒林酸长期治疗家族性腺瘤性息肉病的临床研究.中华消化杂志.2005.25(3):153-156
[61]Cruz-Correa M,Hylind LM,Romans KE,et al.Long-term treatment with sulindac in familial adenomatous polyposis:a prospective cohort study.Gast roenterology,2002,122:641-645.
[62]郑芝田,主编.胃肠病学.北京:人民卫生出版社,2000,3:852-855.
[63]Jarvinena HJ,Peltomakib P.The complex genotype-phenotype relationship in familial adenomatous polyposis.European Journal of Gastroenterology &Hepatology,2004,16(1):528
[64]Ishikawa H.Chemoprevention of carcinogenesis in familial tumors.Int J Clin Oncol,2004,9(4):299-303
[65]钱跃清,吕愈敏,叶嗣懋,等.舒林酸治疗散发性结直肠腺瘤的临床研究.中 华消化杂志,2001,21(12):710-712.
[66]BabbarN,Ignatenko NA,Casero RA J r,et al.Cyclooxygenase 2 independent induction of apop tosis by sulindac sulfone is mediated by polyamines in colon cancer[J].J Biol Chem,2003,278:47762-47775.
[67]Thun MJ,Henley SJ,Patrono C.Nonsteroidal anti-inflammatory drugs as anticancer agents:mechanistic,pharmacologic,and clinical issues[J].J Natl Cancer Inst,2002,94:252-266.
[68]Shaheen NJ,Straus WL,Sandler RS.Chemop revention of gastrointestinal malignancies with nonsteroidal anti-inflammatory drugs[J].Cancer,2002,94:950-963.
[69]安燕芳,吕愈敏,叶嗣懋.舒林酸对家族性腺瘤性息肉病的疗效及作用机制的探讨[J].中华消化杂志,2000,20:243-245.
[70]李军,吕愈敏,顾芳,等.舒林酸长期治疗家族性腺瘤性息肉病的临床研究[J].中华消化杂志,2005,25:153-156.
[71]李军,吕愈敏,金珠,等.舒林酸对家族性腺瘤性息肉病结直肠残存腺瘤组织病理学表现的影响[J].北京大学学报(医学版),2005,37:371-373.
[72]钱跃清,吕愈敏,叶嗣懋,等.舒林酸治疗散发性结直肠腺瘤的临床研究[J].中华消化杂志,2001,21:710-712.
[73]BrownWA,Skinner SA,Maclontenti2Wilson C,et al.Non-steroidal antiinflammatory drugs with different cyclooxygenase inhibitory p rofiles that p revent aberrant cryptfoci formation but vary in acute gastrotoxicity in a rat model [J].J Gastroenterol Hepatol,2000,15:1386-1392.
[74]Houseknecht KL,ColebM,Steele PJ.Peroxisome proliferators activated receptor gamma and review[J].Domest Anim Endocrinol,2002,22:1-23.
[75]Sarraf P,Mueller E,JonesD,et al.Differentiation and reversal of malignant changes in colon cancer through PPAR γ[J].Nature Med,1998:1046-1052.
[76]Strakova N,Ehrmann J,Dzubak P,et al.The synthetic ligand of peroxisome p roliferator activated receptor-gamma ciglitazone affects human glioblastoma cell lines[J].J Pharmacol Exp Ther,2004,309:1239-1247.
[77]WachterA,Loitsch SM,Stein J.PPAR gamma is selectively upregulated in Caco-cells by butyrate[J].Biochem Biophys Res Commu,2000,272:380-385.
[78]NagamineM,Okumura T,Tanno S,et al.PPAR gamma ligand induced apoptosis through a p53 dependent mechanism in human gastric cancer cells[ J ]. Cancer Sci, 2003, 94:338 - 343.
[79] Piazza GA, Rahm AL, Krutzsch M, et al. Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res, 1995, 55( 14): 3110-3116.
[1]OLSschwang S,Laurent-Puin P,Melot T,et al.High resolution genetic map of the adenomatous polyposis coli gene(APC)region[J].AmJ Med Genet,1995,56(4):413-419.
[2]梁君林,高枫,唐宗江.APC基因与结肠直肠肿瘤[J].大肠肛门病外科杂志.2001,7(2):56-60.
[3]杨翔,高志刚,谢德红,等.家族性腺瘤性息肉病[J].中华普通外科杂志,1997,12(5)299-301.
[4]李增烈,廖宁逊.家族性结肠息肉病[J].中国实用内科杂志,2000,20(2):73-74.
[5]Herrera L,Kakati S,Gibas L,el al.Gardner syndrome in a man with an interstitial deletion of 5q[J].Am J med Genel,1986,25(3):473-476.
[6]Bodimer WF,Bailey C,Bodmer J.et al.Localization of the gene for familial adenomatous polyposis on chromosome 5.Nature,1987,328:614.
[7]Thliveris A.Long-range physicalmap and deletion characterization of the 1100-kb Not I restriction fragment harboring the APC gene[J].Genomics,1996,34:268-270.
[8]Kinzler KW,Vogelstein B.Lessons from hereditary colorectal cancer[J].Cell.1996,87:159-170.
[9]Su LK,Johan KA,Smith KJ,et al.Assoiation between wild type andmutant APC gene products[J].Cancer Res,1993,53:2728-2731.
[10]Gryfe R,Swallow C,Bapat B,et al.Molecular biology of colorectal cancer.Curr Probl Cancer[J].1997,9:238-299.
[11]Mimori-Kiyosue Y,Shiina N,Tsukita S.A denomatous polyposis coli(APC)protein moves along microtubules and concentrates at their growing ends in epithelial cells[J].J Cell Biol,2000,148:505-518.
[12]Barth AM,Pollack AL,Altschuler Y,et al.NH-terminal deletion of β-catenin results in stable colocalization of mutantβ-catenin with APC protein and altered MDCK cell adhesion[J].J Cell Biol,1997,136:693-706.
[13]Heinen CD.Goss KH,Cornelius JR,et al.The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway[J].Gostroenterology.2002,123(3):935-939.
[14]Trzepacz C,Lowy AM,Kordich JJ,et al.Phosphory lation of the tumor suppressor adenomatous polyposis coli(APC) by the cyclin-dependent kinase p34cdc2[J].J Biol Chem,1997,272:21681-21684.
[15]Goss KH,Groden J.Biology of the adenomatous polyposis coli tumor suppressor[J].J.Clin.Oncol,2000,18:1967-1979.
[16]Homfray TF,Cottrell SE,Ilyas M,et al.Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumours[J].HumMutat,1998,11(2):114-120.
[17]萧树东.江绍基胃肠病学[M].上海:上海科学技术出版社,2001.
[18]Nicola SF,Michael P,Walier F.The ABC of APC[J].Human Molecular Genetics,2001,10(7):721-733.
[19]Takaku K,Oshima M,Miyoshi H.Intestinal tumorigenesis in compound mutant mice of both DPC4(Smad4) and APC genes[J].Cell,1998,92(5):645-647.
[20]Schwarte I,Klein S,Blass Kampmann S,et al.DPC4/SMAD4 mediated tumor suppression of colon carcinoma cells is associated with reduced urokinase expression[J].Oncogene,1999,18(20):3152-3154.
[21]Liam O,David CS,Lorraine AO,et al.Apoptosis and cell division[J].Currt Opin Cell Biol,2000,12(2):257-263.
[22]Comelia SS,Rachel AF,Kaede H,et al.NF-κB determines location and features of cell death in epidemis[J].J Clin Inves,2000,105(3):253-260.
[23]Tomozawa S,Tsuno NH,Sunami E,et al.Cyclooxygenase-2 overexpression correlates with tumour recurrence,especially haematogenous metastasis,of colorectal cancer[J].Br J Cancer,2000,83(3):324.
[24]Dixon DA,Kaplan CD,Mclntyre TM,et al.Post-transcriptional control of cyclooxygenase-2 gene expression.The role of the 3'-untranslated region[J].J Biol Chem,2000,275(16):11750.
[25]Ohno R,Yoshinaga K,Fujita T,et al.Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma[J].Cancer,2001,91(10):1876.
[26]Uefuji K,Ichikura T,Mochizuki H.Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer[J].Clin Cancer Res,2000,6(1):135.
[27]Ottino P,Bazan HE.Corneal stimulation of MMP-1,-9 and uPA by platelet-activating factor is mediated by cyclooxygenase-2 metabolites[J].Curr Eye Res,2001,23(2):77.
[28]Noda M,Tatsumi Y,Tomizawa M,et al.Effects of etodolac,a selective cyclooxygenase-2 inhibitor,on the expression of β-cadherin-catenin complexes in gastrointestinal cell lines[J].J Gastroenterol,2002,37(11):896.
[29]Wallace NH,Phillips RK.Upper gastrointestinal disease in patients With familial adenomatous polpsis[J].Br J Surg,1998,85(6):742-750.
[30]Glaser EM.Inherited predisposition to colon cancer[J]Cancer Nursing,1998,21(6):377-383.
[31]唐宗江,高枫.家族性腺瘤性息肉病的外科治疗[J].中国普通外科杂志1999,7(6):344-346.
[32]郑芝田,黄莛庭.胃肠病学,第2版[M],北京:人民卫生出版社,1995,706-709.
[33]Helm JF,Sandler RS.Colorectal cancer screening[M].Med Clin North Am,1999:1403.
[34]Spirio L,Olschwang S,Groden J,et al.Alleles of the APC gene:An attenuated form of familial polyposis[J].Cell,1993,75:951.
[35]Hamilton SR,Liu B,Parsons RE,et al.The molecular basis of"Turcot syndrome"[J].N Engl J Med,1995,332:839.
[36]唐贵林,张阳德,吕海宝.大肠组织自全变光光谱的判别诊断研究.中国现代医学杂志[J].2001,11(12):21-23.
[37]胡念平,晏仲舒,吕新生.截短蛋白检测用于家族性腺瘤性息肉病的基因诊断[J].中国普通外科杂志,2000,9(3):240-242.
[38]Celisken O,Yocel A,Coler K,et al.Ocular findings in familial adenomatous polyposis[J].Int Ophthalmol,1998,21:205-208.
[39]Steinbach G,Lynch PM,Phillips RK,et al.The effect of celecoxib,a cyclooxygenase-2 inhibitor,in familial adenomatous polyposis[J].N Engl J Med,2000,342(26):1946.
[40]Altorki NK,Keresztes RS,Port JL,et al.Celecoxib,a selective Cyclooxygenase-2inhibitor,enhances the response to preoperative paclitaxel and carboplatin in early stage non-small cell lung Cancer[J].Clin Oncol,2003,21(14):2645.
[41]郜恒俊,萧树东.NSAIDS化学预防直肠癌研究的新进展[J].国外医学.消化系疾病分册.2001,21(5):86-89.
[42]Willianson SLH,Kartheuser A,Coaler J,et al.Intestinal tumorgenesis in the Apc1638 N mouse treated with asprin and resistant starch for up to 5months[J].Carcinogenesis,1999,20(5):805-810.
[43]安燕东,吕愈敏,叶嗣懋.舒林酸对家族性腺瘤性息肉病的疗效及作用机制[J].中华消化杂志,2000,20(4):243-245.
[44]Mahamoud NN,Dannenberg AJ,Mestre J,et al.Asprin prevents tumors in a murine model of familial adenomatous polyposis[J].Surgery,1998,124(2):225-231.
[45]Ichikawa D,Takahashi T,Adachi T,et al.Postoperative management of the preserved rectal segment in patients with familial polyposis:the use of 5-fluorouracil suppositories and green tea extract to inhibit tumor growth[J].Nippon Geka Gakkai Zushi,1998,99(6):391-395.
[46]Beveridge IG,Swain DJ,Groves CJ,et al.Large villous adenomas arising in ileal pouches in familial adenomatous polyposis:report of two cases[J].Dis colon rectum,2004,47(1):123-126.
[47]胡友主,王存川,陈 鏊.腹腔镜手术治疗结直肠良恶性病变103例分析[J].中国内镜杂志,2003,9(7):31-33.
[48]池畔,林惠铭.腹腔镜辅助全大肠切除治疗家族性腺瘤性息肉病4例报告[J].中国实用外科杂志,2004,24(8):507.
[49]郑明华.论腹腔镜结肠直肠手术[J].外科理论与实践,2004,9(6):453.
[50]Inoue Y,Noro H,Komoda H,et al.Completely laparoscopic total colectomy for chronic constipation:report of a case[J].Surg Today,2002,32(6):551-554.
[1]刘海峰,大肠息肉679例临床特征及内镜、病理学特点分析[J]武警医学,2008,19(2):133-134.
[2]Gupta SK,Fitzgerald JF,Croffie JM,et al.Experience with juvenile polyps in North American children:the need for pancolonoseopy.Am J Gastroenterol,2001,96(6):1695-1697.
[3]Woodford-Richens K,Williamson J,Bevan Set al.Allelicloss at SMAD4 in polyps from juvenile polyposis patients and use of fluorescence in sire hybridization to demonstrate clonalorigin of the epithelium.Cancer Res,2000,60(9):2 477
[4]Repici A,Tricerri R.Endoscopic polypectomy:techniques,complications and follow- up.Tech Coloproctol,2004,8(Suppl 2):s283
[5]陈春华,邱立华.大肠息肉1884例患者的临床观察及恶变特征分析.肿瘤防治杂志,2005,12(24):1 888
[6]吴子刚,吴子光,全华斌.大肠良恶性息肉的临床特征及内镜、病理形态学特点[J].中华消化内镜杂志,1999,16(3):141-143.
[7]郑芝田.胃肠病学[M].北京:人民卫生出版社,2002.702-706.
[8]Winawer S,Fletcher R.Colorectal cancer screening and surveillance[J].Gastroenterology,2003,124(2):553-554
[9]宇野良治,韩英,栋方昭博,等.实用大肠镜诊断及治疗学[J].北京:科学出版社,2001.
[10]Peter Cotton,Christopher Williams.1996 Practical Gastrointestinal Endoscopy [J].4th Editionll Science.Clements RH,Jordan LM,Webb WA.Critical decisionsin the management of endoscopic perforations of the colon[J].Ame Surg,2000,66:91-92.
[11]Kozarek RA,Eurnest DL,Silverstein ME,et al.Airpressure-induced colon injury during diagnostic colonoscopy[J].Gastroenterol,1980,78:7-14.
[12]Gedebou TM,Wong RA,Rappaport wd.Clinical presentation and management of iatrogenic colon perforation[J].Am J Surg,1996,172:454-458.
[13]Mattei P,Alonso M,Justinich C.Laparoscopic repair of colonoscopy in children:report of 2 cases and review of the literature[J].J Pediatric Sur,g2005,40:1651-1653.
[14]Raju GS,Ahmed I,Brining D,et al.Endoluminal closure of large perforation of colon with clios in a porcine[J].Gastrointestinal Endoscopy,2006,64:640-646.
[15]Zeno BR,Sahn SA.Colonoscopy-associated pneumothorax..A case of tension pneumothorax and review of the literature[J].Am J Med sci,2006,323:153-155.
[16]Lovisetto F,Zonta S,Rota E,et al.Left pneumothorax secondary to colonoscopic perforation of the sigmoid colon:a case report[J].Surg Lapar Endos&Percul Techni,q2007,17:62-64.
[17]Fu KI,Sano Y,Kato S,et al.Pneumoscrotum:a rare manifestation of perforation associated with therapeutic colonoscopy[J].World J Gastroentero,12005,11:5061-5063.
[18]Chorost MI,Wu JT,Webb H,et al.Vertebral venous air embolism:An unusual complication following colonoscopy[J].Dis Colon Rectu,m2003,46:1138-1140.
[19]Rosen L,Bub D,Reed J,et al.Hemorrhage following colonoscopic polypectomy[J].Dis Colon Rectu,m1993,36:1126-1131.
[20]Rathgaber S,Wick TM.Colonoscopy completion and complication rates in a community gastroenterology practice[J].Gastrointestinal Endosc,2006,64:556-562.
[21]Watabe H,Yamaji Y,Okamoto M,et al.Risk assessment for delayed hemorrhagic complication of colonic polypectom:ypolyp-related factors and patient-related factors[J].Gastrointest Endos,c2006,64:73-78.
[22]Singaram C,Torbey CF,Jacoby RF.Delayed postpolypectomy bleeding[J].Am J Gastroentero,11995,90:146-147.