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大腸癌早診篩查隨訪策略及脫氧膽酸促進(jìn)腸癌發(fā)生的機(jī)制研究

發(fā)布時(shí)間:2018-06-13 18:30

  本文選題:大腸癌 + 篩查策略; 參考:《昆明醫(yī)科大學(xué)》2016年博士論文


【摘要】:背景:大腸癌嚴(yán)重危害人類健康,脫氧膽酸在大腸癌發(fā)生發(fā)展中具有一定作用。但可通過篩查和致病因素的研究達(dá)到預(yù)防、早期診斷和早期治療,從而明顯改善預(yù)后之目的。因此值得深入研究適合我國當(dāng)前國情的大腸癌篩查隨訪策略和探索脫氧膽酸的致大腸癌作用及其機(jī)制。目的:1、研究社區(qū)人群和醫(yī)院門診人群患大腸腫瘤發(fā)病風(fēng)險(xiǎn),探索大腸癌篩查模式及結(jié)腸鏡監(jiān)測隨訪最佳間隔時(shí)間。2、研究脫氧膽酸促大腸癌發(fā)生的作用及機(jī)制。方法:1、2011-2013年隨機(jī)選取昆明安寧社區(qū)連然和金方兩個(gè)街道辦事處轄區(qū)內(nèi)18-90(包括18歲和90歲在內(nèi))常住漢族人口3338人和昆明醫(yī)科大學(xué)第一附屬醫(yī)院門診就診者2000人,通過問卷調(diào)查獲取患者一般情況,經(jīng)過結(jié)腸鏡檢查確診是否患大腸腫瘤。分析患大腸腫瘤的危險(xiǎn)因素,期望探索出大腸腫瘤高危問卷調(diào)查初篩出高危人群再進(jìn)行結(jié)腸鏡精篩的篩查模式。2、選擇昆明醫(yī)科大學(xué)第一附屬醫(yī)院消化內(nèi)鏡室2000年-2013年所有接受過兩次以上電子結(jié)腸鏡檢查(如有息肉,所有檢出息肉都經(jīng)內(nèi)鏡完整切除)且保存資料完好的患者為研究對象,分析結(jié)腸鏡初檢正常、非腺瘤性息肉、非進(jìn)展期腺瘤和進(jìn)展期腺瘤患者結(jié)腸鏡監(jiān)測腺瘤檢出/復(fù)發(fā)的危險(xiǎn)因素和最佳隨訪時(shí)間間隔。3、用人正常結(jié)腸上皮細(xì)胞CCD 841 CoN和Min小鼠作為模型,觀察脫氧膽酸和細(xì)胞共培養(yǎng)或喂養(yǎng)小鼠后腸粘膜細(xì)胞增殖、凋亡、Wnt信號通路蛋白(β-catenin蛋白)變化以及Min小鼠成瘤和腺瘤癌變情況。結(jié)果與結(jié)論:1、高危因素問卷調(diào)查可作為社區(qū)和門診大腸癌篩查的初篩工具;2、大腸癌及其癌前病變的高危因素有性別、年齡、本人癌癥史或腸息肉病史、慢性腹瀉、慢性便秘、粘液血便、高血壓、吸煙、經(jīng)常吃煙熏油炸食物等。3、慢性膽囊炎和膽石癥患者對大腸癌影響可能是作用于腺瘤形成之后或通過“腺瘤-癌”之外的途徑;4、結(jié)腸鏡監(jiān)測隨訪檢出腺瘤或腺瘤復(fù)發(fā)的危險(xiǎn)因素有性別、年齡、息肉分布部位、腺瘤大小及位置;5、結(jié)腸鏡隨訪監(jiān)測最佳時(shí)間間隔是:初診正常者4.76(95% CI,4.32-5.22)年,初診為非腺瘤性息肉者3.32(95%CI,2.79-3.87)年,初診為非進(jìn)展期腺瘤者2.85(95%CI,2.53-3.17)年,初診為進(jìn)展期腺瘤者2.06(95%CI,1.71-2.45)年;6、脫氧膽酸通過β-catenin轉(zhuǎn)位,活化Wnt/β-catenin信號通路,增加S期細(xì)胞、促進(jìn)結(jié)腸上皮細(xì)胞增殖而起促大腸癌形成作用的。
[Abstract]:Background: colorectal cancer is a serious hazard to human health, deoxycholic acid has a certain role in the occurrence and development of colorectal cancer. However, prevention, early diagnosis and early treatment can be achieved through screening and the study of pathogenic factors, thus significantly improving the prognosis. Therefore, it is worth studying the follow-up strategy of colorectal cancer screening and exploring the mechanism of deoxycholic acid in colorectal cancer. Objective: to study the risk of colorectal cancer in community and outpatient population, to explore the screening mode of colorectal cancer and the optimal interval time of colonoscopy monitoring, and to study the role and mechanism of deoxycholic acid in promoting colorectal cancer. Methods from 2011 to 2013, 3338 residents of Han nationality (including 18 and 90 years old) and 2000 outpatients of the first affiliated Hospital of Kunming Medical University were randomly selected from Lianran and Jinfang subdistrict offices in the Anning District, Kunming, China. The general condition of the patients was obtained by questionnaire, and the colonoscopy confirmed whether the patients had colorectal tumors. To analyze the risk factors of colorectal cancer, It is expected to explore the screening model of high risk population for colonoscopy screening. 2. Select the digestive endoscopy room of the first affiliated hospital of Kunming Medical University from 2000 to 2013. Colonoscopy (if there are polyps, All patients whose polyps were completely removed by endoscope) and whose data were well preserved were analyzed for normal and nonadenomatous polyps. The risk factors for detection / recurrence of adenomas were monitored by colonoscopy in patients with non-advanced and advanced adenomas and the optimal interval of follow-up time was .3. the normal colonic epithelial cells were used as the model of CCD841 CoN and Min mice. The proliferation of intestinal mucosal cells, the changes of 尾 -catenin protein and the carcinogenesis of tumor and adenoma in Min mice were observed after co-culture or feeding of deoxycholic acid and cells. Results and conclusion 1. The questionnaire of high risk factors can be used as a screening tool for the screening of colorectal cancer in community and outpatient clinics. The high risk factors for colorectal cancer and its precancerous lesions are sex, age, history of cancer or polyp, chronic diarrhea. Chronic constipation, mucus stool, hypertension, smoking, often smoked fried food, etc., chronic cholecystitis and cholelithiasis patients may affect colorectal cancer after the formation of adenoma or through the "adenomator-cancer" pathway; 4. The risk factors of adenoma or adenoma recurrence were sex, age, distribution of polyps, size and location of adenoma. The best interval of colonoscopy was 4.7695% CI4.32-5.22). The first diagnosis of nonadenomatous polyps was 3.3295 CI2. 79-3.87), the first diagnosed non-advanced adenoma was 2. 85 / 95 CI2.53-3.17) and the first diagnosed as advanced adenoma was 2. 06 / 95CI1. 71-2.45) years. Deoxycholic acid translocated through 尾-catenin, activated Wnt/ 尾-catenin signaling pathway and increased S phase cells. Promote the proliferation of colon epithelial cells and promote the formation of colorectal cancer.
【學(xué)位授予單位】:昆明醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2016
【分類號】:R735.34

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Guh Jung Seo;Dae Kyung Sohn;Kyung Su Han;Chang Won Hong;Byung Chang Kim;Ji Won Park;Hyo Seong Choi;Hee Jin Chang;Jae Hwan Oh;;Recurrence after endoscopic piecemeal mucosal resection for large sessile colorectal polyps[J];World Journal of Gastroenterology;2010年22期



本文編號:2014995

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