【摘要】：胃癌是危害人類健康的主要惡性腫瘤之一,全球胃癌的發(fā)病率和死亡率居高不下。據(jù)最新的統(tǒng)計(jì)數(shù)據(jù)表明,我國胃癌的發(fā)病率和死亡率在所有腫瘤中均居第二位,每年死于胃癌的人數(shù)高達(dá)50萬。因此,研究影響胃癌發(fā)生發(fā)展的因素具有重要意義。目前,世界范圍內(nèi)幽門螺桿菌(Helicobacter pylori,H.pylor)的感染率約50%,部分地區(qū)高達(dá)80%(Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report,2012)。在我國,H.pylori的感染率總體上也很高,成人中感染率達(dá)40-60%(第四次全國幽門螺桿菌感染處理共識報(bào)告,2012),WHO早在1994年就已將其列為胃癌的Ⅰ類致癌因子。雖然H.pylori在人群中的感染率很高,但只有部分感染者最終發(fā)展為胃癌,究其原因,H.pylori的致病性與其菌株的種類、宿主遺傳因素及環(huán)境因素等有關(guān)。H.pylori菌株類型的不同是導(dǎo)致不同臨床結(jié)局的重要原因。2012年歐洲馬斯特里赫特共識中提到,胃癌的發(fā)生發(fā)展受H.pylori毒力因子的影響,其循證醫(yī)學(xué)的證據(jù)等級為1a。細(xì)胞毒素相關(guān)基因A(cytotoxin-associated gene A,CagA)編碼的CagA蛋白作為重要的毒力因子之一,其陽性菌株感染后導(dǎo)致嚴(yán)重臨床后果的危險(xiǎn)性明顯大于陰性菌株,具有CagA基因的菌株是H.pylori中重要的致病菌株。CagA是由H.pylori的cag致病島(cag pathogenicity island,cag PAI)上CagA基因編碼的蛋白,通過cag PAI編碼Ⅳ型分泌系統(tǒng)將CagA“注入”宿主細(xì)胞,是H.pylori唯一能進(jìn)入宿主細(xì)胞而發(fā)揮生物學(xué)作用的蛋白。最新的循證醫(yī)學(xué)證據(jù)表明,CagA~+H.pylori菌株增加胃癌發(fā)生的風(fēng)險(xiǎn)。CagA轉(zhuǎn)基因小鼠的胃癌發(fā)生率明顯增加,證實(shí)CagA是促進(jìn)胃癌發(fā)生的關(guān)鍵分子。腫瘤干細(xì)胞(cancer stem cells,CSCs)學(xué)說認(rèn)為腫瘤組織中存在一小部分具有干細(xì)胞性質(zhì)的細(xì)胞群體,具有無限的自我更新和誘導(dǎo)腫瘤發(fā)生的能力,是腫瘤產(chǎn)生的種子細(xì)胞,由于其同時(shí)具有高轉(zhuǎn)移潛能、對放化療等治療抵抗等特性,而被認(rèn)為是惡性腫瘤復(fù)發(fā)轉(zhuǎn)移的關(guān)鍵。以往有關(guān)H.pylori的研究主要集中于其在促進(jìn)胃癌細(xì)胞增殖和抑制胃癌細(xì)胞凋亡中的作用。但最新的研究發(fā)現(xiàn),CagA~+H.pylori可以通過誘導(dǎo)胃癌細(xì)胞發(fā)生上皮-間葉轉(zhuǎn)化(epithelial mesenchymal transition,EMT),從而使胃癌細(xì)胞獲得胃癌干細(xì)胞特征。本課題進(jìn)一步確認(rèn)CagA~+h.pylori在促胃癌細(xì)胞干性特征增強(qiáng)中的作用,并闡明其機(jī)制。因此,本課題豐富了CagA~+h.pylori菌株感染的致病機(jī)理,有助于加深CagA~+h.pylori在胃癌發(fā)生發(fā)展中作用的認(rèn)識,為特異性根除CagA~+h.pylori提供新的理論依據(jù)�！狙芯磕康摹�1、構(gòu)建h.pylori感染胃癌細(xì)胞模型,評價(jià)CagA~+h.pylori對胃癌細(xì)胞干性特征的影響;2、探討CagA~+h.pylori促胃癌細(xì)胞干性特征增強(qiáng)的分子機(jī)制�！狙芯糠椒ā�1、評價(jià)CagA~+h.pylori對胃癌細(xì)胞干性特征的影響:(1)構(gòu)建h.pylori感染胃癌細(xì)胞的模型;(2)通過流式細(xì)胞技術(shù),分別檢測CagA~+h.pylori(h.pylori菌株nctc11637)感染組、caga-h.pylori(以h.pylori菌株nctc11637為背景的caga敲除株)感染組及未感染組中胃癌干細(xì)胞表面標(biāo)志物陽性的胃癌細(xì)胞比例;(3)通過pcr從mrna水平進(jìn)一步分析上述各組中胃癌干細(xì)胞表面標(biāo)志物的轉(zhuǎn)錄水平;(4)通過體外成球?qū)嶒?yàn)評價(jià)上述各組中胃癌細(xì)胞的體外成球能力;(5)通過免疫印記(westernblotting,wb)檢測上述各組中胃癌細(xì)胞干性轉(zhuǎn)錄因子的表達(dá)水平;(6)光鏡下觀察上述各組中胃癌細(xì)胞形態(tài)學(xué)的改變,wb檢測emt標(biāo)志物的表達(dá)變化。2、探討CagA~+h.pylori促胃癌細(xì)胞干性特征增強(qiáng)的分子機(jī)制:(1)通過免疫熒光實(shí)驗(yàn),在激光共聚焦下觀察β-catenin在上述各組胃癌細(xì)胞中的定位情況;(2)通過雙熒光素酶報(bào)告基因?qū)嶒?yàn)檢測上述各組胃癌細(xì)胞中wnt/β-catenin信號通路的活化水平;(3)通過wb檢測CagA~+h.pylori及caga-h.pylori感染胃癌細(xì)胞不同時(shí)相點(diǎn)β-catenin核轉(zhuǎn)位關(guān)鍵磷酸化位點(diǎn)ser675和ser552的表達(dá)水平;(4)使用c-met抑制劑su11274及pi3k/akt抑制劑gsk690693分別預(yù)處理胃癌細(xì)胞,通過wb進(jìn)一步檢測CagA~+h.pylori感染后胃癌細(xì)胞中β-catenin的ser675和ser552位點(diǎn)磷酸化水平;(5)使用wnt/β-catenin抑制劑xav預(yù)處理胃癌細(xì)胞,通過流式細(xì)胞技術(shù)、pcr以及成球?qū)嶒?yàn),分別檢測CagA~+h.pylori的感染對胃癌細(xì)胞中胃癌干細(xì)胞表面標(biāo)志物陽性的胃癌細(xì)胞比例、胃癌干細(xì)胞表面標(biāo)志物mrna水平以及胃癌細(xì)胞成球能力的影響;(6)使用wnt/β-catenin抑制劑xav預(yù)處理胃癌細(xì)胞,通過wb和pcr分別檢測CagA~+h.pylori的感染對胃癌細(xì)胞中干性轉(zhuǎn)錄因子nanog和oct4蛋白表達(dá)水平及mrna水平的影響;(7)構(gòu)建nanog和oct4啟動(dòng)子區(qū)域的雙熒光素酶報(bào)告質(zhì)粒,通過雙熒光素酶報(bào)告實(shí)驗(yàn)檢測CagA~+h.pylori介導(dǎo)的β-catenin核轉(zhuǎn)位對nanog和oct4啟動(dòng)子活性的影響;(8)生物信息學(xué)預(yù)測β-catenin在nanog和oct4啟動(dòng)子上的可能結(jié)合區(qū)域,通過染色質(zhì)免疫共沉淀(chromatinimmunoprecipitation,chip)實(shí)驗(yàn)檢測β-catenin作用于nanog和oct4啟動(dòng)子的區(qū)域;(9)通過c13尿素酶呼氣試驗(yàn)及檢測血清中caga抗體,將胃癌患者分為CagA~+h.pylori感染組及caga-h.pylori感染組,分別檢測兩組患者胃癌組織標(biāo)本中nanog和oct4蛋白表達(dá)水平及mrna水平�！狙芯拷Y(jié)果】1、CagA~+h.pylori感染的胃癌細(xì)胞,與caga-h.pylori感染組及未感染組相比,更多的胃癌細(xì)胞表現(xiàn)出胃癌干細(xì)胞樣特征;2、CagA~+h.pylori活化wnt/β-catenin信號通路,包括促進(jìn)β-catenin的核轉(zhuǎn)位及增強(qiáng)β-catenin的轉(zhuǎn)錄活性;3、CagA~+h.pylori通過c-met和/或akt介導(dǎo)的通路促β-cateninc末端ser675和ser552位點(diǎn)的磷酸化,使β-catenin發(fā)生核轉(zhuǎn)位;4、wnt/β-catenin信號通路的活化是CagA~+h.pylori促胃癌細(xì)胞干性特征增強(qiáng)的重要環(huán)節(jié);5、wnt/β-catenin信號通路的活化參與CagA~+h.pylori上調(diào)干性轉(zhuǎn)錄因子nanog和oct4;6、CagA~+h.pylori感染的胃癌患者,與caga-h.pylori感染的胃癌患者相比,胃癌組織標(biāo)本中nanog和oct4的表達(dá)明顯增加�！窘Y(jié)論】CagA~+h.pylori通過活化wnt/β-catenin信號通路,上調(diào)nanog和oct4的表達(dá),促胃癌細(xì)胞干性特征增強(qiáng)�！狙芯恳饬x】目前,國內(nèi)外指南均推薦高風(fēng)險(xiǎn)人群(慢性萎縮性胃炎、潰瘍、腸上皮化生、異型增生及胃癌術(shù)后等)根除h.pylori的治療,但其分子機(jī)制并不清楚。本課題證實(shí)h.pylori中的高毒力致病菌株——CagA~+h.pylori可以促胃癌細(xì)胞干性特征增強(qiáng),這可能是胃粘膜上皮細(xì)胞從異常增生到最終發(fā)展為胃癌的重要原因,也可能是胃癌根除術(shù)后少數(shù)殘余胃癌細(xì)胞致胃癌復(fù)發(fā)轉(zhuǎn)移的重要原因。因此,本課題為深入理解和認(rèn)識H.pylori感染的致病機(jī)制提供了新的視角,有助于加深CagA~+H.pylori在胃癌發(fā)生發(fā)展中作用的認(rèn)識,為特異性根除CagA~+H.pylori提供新的理論依據(jù)。
[Abstract]:Gastric cancer is one of the main malignant tumors that harm human health. The incidence and mortality of global gastric cancer are high. According to the latest statistics, the incidence and mortality of gastric cancer in China are second in all tumors, and the number of people dying of gastric cancer is up to 500 thousand every year. At present, the infection rate of Helicobacter pylori (H.pylor) is about 50% in the world, and in some regions up to 80% (Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report, 2012). In China, the infection rate is also high, and the infection rate in adults is fourth times. The national consensus report on the treatment of Helicobacter pylori infection, 2012), WHO has been listed as a class I carcinogen of gastric cancer as early as 1994. Although the infection rate of H.pylori in the population is very high, only some of the infected people eventually develop into gastric cancer. The cause of the infection is the pathogenicity of H.pylori and the species of its strains, host genetic factors and environmental factors. The difference in the type of.H.pylori isolates is an important cause of different clinical outcomes. The European Maastricht consensus in.2012 is that the occurrence and development of gastric cancer are affected by H.pylori virulence factors, and the evidence level of evidence-based medicine is the CagA protein encoded by the 1a. cytotoxin related gene A (cytotoxin-associated gene A, CagA). One of the important virulence factors is that the positive strain is more dangerous than the negative strain after infection. The strain with CagA gene is an important pathogenic strain in H.pylori,.CagA is a protein encoded by the CagA gene on the CAG pathogenic island of H.pylori (cag pathogenicity island, CAG PAI). The CagA "injection" of the host cell is the only protein that H.pylori can enter the host cell. The latest evidence-based evidence suggests that the CagA~+H.pylori strain increases the risk of gastric cancer, and the incidence of gastric cancer is significantly increased in.CagA transgenic mice. CagA is the key molecule to promote the occurrence of gastric cancer. Cancer stem cells (CSCs) theory holds that there are a small group of cell groups with stem cell properties in the tumor tissue, with unlimited self renewal and the ability to induce tumorigenesis. It is the seed cell produced by the tumor. Because of its high metastatic potential and resistance to radiotherapy and chemotherapy, it is considered to be malignant. The study of H.pylori has focused on its role in promoting the proliferation of gastric cancer cells and inhibiting the apoptosis of gastric cancer cells. However, the latest research has found that CagA~+H.pylori can induce the epithelial mesenchymal transition (epithelial mesenchymal transition, EMT) in gastric cancer cells to make gastric cancer cells This subject further confirms the role of CagA~+h.pylori in promoting the enhancement of the dry character of gastric cancer cells and clarifies its mechanism. Therefore, this topic enriches the pathogenesis of CagA~+h.pylori infection, and helps to deepen the understanding of the role of CagA~+h.pylori in the development of gastric cancer and to eradicate CagA~+h.pyl specifically. Ori provides new theoretical basis. [Objective] 1 to construct a H.pylori infected gastric cancer cell model, evaluate the effect of CagA~+h.pylori on the dry characteristics of gastric cancer cells; 2, to explore the molecular mechanism of the enhancement of the dry character of gastric cancer cells by CagA~+h.pylori. [method] 1, to evaluate the effect of CagA ~+h.pylori on the dry character of gastric cancer cells: (1) A model of H.pylori infection of gastric cancer cells was built; (2) through flow cytometry, the proportion of CagA~+h.pylori (H.pylori strain NCTC11637) infection group, caga-h.pylori (H.pylori strain NCTC11637 as the background CagA knockout) and the gastric cancer stem cell surface markers positive in the uninfected group were measured, and (3) from PCR from mRNA. The transcriptional level of the surface markers of gastric cancer stem cells in the above groups was further analyzed. (4) the in vitro ability of gastric cancer cells in the above groups was evaluated by the in vitro test. (5) the expression level of the dry transcription factors of gastric carcinoma in all the groups was detected by westernblotting (WB); (6) the above observation was observed under the light microscope. The morphological changes of gastric cancer cells in the group and the change of the expression of EMT markers by WB,.2, to explore the molecular mechanism of enhancing the dry character of gastric cancer cells by CagA~+h.pylori: (1) the localization of beta -catenin in the above gastric cancer cells was observed by the immunofluorescence test, and (2) the double luciferase reporter gene experiment was carried out. The activation level of wnt/ beta -catenin signaling pathway in all the gastric cancer cells was detected. (3) the expression level of ser675 and ser552 of CagA~+h.pylori and caga-h.pylori infected gastric cancer cells at different phase point beta -catenin nuclear transposition sites was detected by WB; (4) su11274 and pi3k/akt inhibitor gsk690693 were pre placed respectively. In gastric cancer cells, the phosphorylation level of ser675 and ser552 loci of beta -catenin in gastric cancer cells after CagA~+h.pylori infection was further detected by WB. (5) gastric cancer cells were pretreated with wnt/ beta -catenin inhibitor xav, and the gastric cancer stem cells in gastric cancer cells were detected by flow cytometry, PCR and ball formation test. The proportion of gastric cancer cells with positive surface markers, the surface marker mRNA level of gastric cancer stem cells and the ability of gastric cancer cells to form the ball; (6) the gastric cancer cells were pretreated with the wnt/ beta -catenin inhibitor xav, and the expression level of Nanog and Oct4 protein of the dry transcription factors in gastric cancer cells and m were detected by WB and PCR respectively. The effect of RNA level; (7) to construct a double luciferase reporter plasmid of Nanog and Oct4 promoter region, and to detect the effect of CagA~+h.pylori mediated beta -catenin nuclear transposition on the activity of Nanog and Oct4 promoter through double luciferase reporter assay; (8) bioinformatics predicts the possible binding area of beta -catenin on Nanog and Oct4 promoters by staining. The chromatinimmunoprecipitation (chip) test was used to detect the effect of beta -catenin on the promoter of Nanog and Oct4. (9) through the C13 exhalation test and the detection of CagA antibody in the serum, the gastric cancer patients were divided into CagA~+h.pylori infection group and caga-h.pylori infection group, and the nano of the two groups of gastric cancer tissue specimens were detected respectively. G and Oct4 protein expression level and mRNA level. [results] 1, CagA~+h.pylori infected gastric cancer cells, compared with the caga-h.pylori infection group and the uninfected group, more gastric cancer cells showed the gastric cancer stem cell like characteristics; 2, CagA~+h.pylori activated wnt/ beta -catenin signaling pathway, including the promotion of beta -catenin nuclear translocation and enhanced beta -cateni. The transcriptional activity of N; 3, CagA~+h.pylori through c-met and / or Akt mediated pathway to promote the phosphorylation of ser675 and ser552 loci at the end of beta -cateninc, and the nuclear transposition of the beta -catenin; 4, the activation of the wnt/ beta -catenin signaling pathway is a critical link in the enhancement of the dry character of gastric cancer cells; 5, activation of the wnt/ beta signaling pathway is involved in the activation of the pathway. AgA~+h.pylori up-regulated the dry transcription factors Nanog and Oct4; 6, CagA~+h.pylori infected gastric cancer patients, compared with caga-h.pylori infected gastric cancer patients, the expression of Nanog and Oct4 in gastric cancer tissues increased significantly. [Conclusion] CagA~+h.pylori promotes the expression of Nanog and Oct4, and promotes gastric cancer cell stem by activating the wnt/ beta -catenin signaling pathway. At present, both domestic and foreign guidelines recommend the treatment of high risk people (chronic atrophic gastritis, ulcers, intestinal metaplasia, dysplasia and gastric cancer) to eradicate H.pylori, but its molecular mechanism is not clear. This topic confirms that the high virulent strain in H.pylori, CagA~+h.pylori, can promote gastric cancer. The enhancement of cell dry characteristics may be an important cause of gastric mucosal epithelial cells from abnormal proliferation to final development of gastric cancer. It may also be an important reason for the recurrence and metastasis of gastric cancer cells after gastric cancer eradication. Therefore, this topic provides a new perspective for understanding and understanding the pathogenesis of H.pylori infection. It is helpful to deepen the understanding of the role of CagA~+H.pylori in the occurrence and development of gastric cancer and provide a new theoretical basis for the specific eradication of CagA~+H.pylori.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R735.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 于成功,李敏,莫?jiǎng)χ?蕭樹東;胃癌細(xì)胞垂體腺苷環(huán)化酶激活肽相關(guān)受體分析[J];胃腸病學(xué);2000年02期

2 薛英威,耿敬姝,劉曉民,劉立人,高小敏,陳國林,張豈凡,趙家宏;胃癌細(xì)胞的流式分析及臨床意義[J];腫瘤防治研究;2000年03期

3 陳堅(jiān),林庚金,錢立平,程建,施冬云,張亞東,劉珊林;內(nèi)源性活性氧水平及錳型超氧化物歧化酶的表達(dá)與胃癌細(xì)胞分化、增殖相關(guān)[J];生物物理學(xué)報(bào);2003年02期

4 李瑩,藥立波,韓炯,王立峰,韓月恒,劉新平,林樹新,俞強(qiáng);胃癌細(xì)胞抗脫落凋亡的分子機(jī)制[J];醫(yī)學(xué)分子生物學(xué)雜志;2004年02期

5 羅和生,王維,包鵬輝,張翼;核因子-κB活性增強(qiáng)參與胃癌細(xì)胞長春新堿耐藥[J];中華消化雜志;2004年08期

6 劉冀紅,曹偉新,紀(jì)玉寶,張軼,劉炳亞,朱正綱,燕敏,林言箴;右旋甲硫氨酸對胃癌細(xì)胞作用初探[J];腸外與腸內(nèi)營養(yǎng);2005年01期

7 齊元玲;于皆平;劉啟勝;鄧全軍;曹俊;于紅剛;;抑癌基因PTEN在胃癌細(xì)胞中的表達(dá)及意義[J];廣東醫(yī)學(xué);2006年03期

8 何必立;呂賓;徐毅;苗青;范一宏;;溫郁金對胃癌細(xì)胞的抑制作用及其對血管內(nèi)皮生長因子表達(dá)的影響[J];中醫(yī)藥學(xué)刊;2006年09期

9 郭強(qiáng);李榮;李慶芳;夏紹友;杜曉輝;王立生;;高表達(dá)鞘氨醇激酶對胃癌細(xì)胞生物學(xué)特性的影響[J];解放軍醫(yī)學(xué)雜志;2006年12期

10 陳先來;肖曉旦;楊榮;劉建平;;基于誤差反向傳播神經(jīng)網(wǎng)絡(luò)的胃癌細(xì)胞識別研究[J];中國循證醫(yī)學(xué)雜志;2007年09期

相關(guān)會(huì)議論文 前10條

1 韓霜;雷婷;韓者藝;劉杰;郭雪艷;丁睿;吳開春;丁杰;樊代明;;分化抑制因子1對胃癌細(xì)胞惡性生物學(xué)行為的影響[A];中華醫(yī)學(xué)會(huì)第七次全國消化病學(xué)術(shù)會(huì)議論文匯編（下冊）[C];2007年

2 陳韶華;吳靈嬌;吳鴻儒;吳雅春;厲有名;;低濃度酒精對胃癌細(xì)胞活性及周期抑制[A];中華醫(yī)學(xué)會(huì)第12次全國內(nèi)科學(xué)術(shù)會(huì)議論文匯編[C];2009年

3 陳韶華;吳靈嬌;吳鴻儒;吳雅春;厲有名;;低濃度酒精對胃癌細(xì)胞活性及周期抑制[A];第二屆浙江省消化病學(xué)術(shù)大會(huì)論文匯編[C];2009年

4 李娜;郭瑞芳;李文梅;邵建敏;汪浩;趙康;李書婷;王敬強(qiáng);王融;徐寧志;劉斯奇;呂有勇;;大蒜素處理在胃癌細(xì)胞中引發(fā)的蛋白質(zhì)表達(dá)響應(yīng)[A];中國蛋白質(zhì)組學(xué)第二屆學(xué)術(shù)大會(huì)論文摘要論文集[C];2004年

5 ;多西紫杉醇對胃癌細(xì)胞作用及其機(jī)制的研究[A];第四屆中國腫瘤大會(huì)中國藥理學(xué)會(huì)腫瘤藥理專業(yè)委員會(huì)分會(huì)場學(xué)術(shù)會(huì)議論文摘要[C];2006年

6 樓儷泓;;15-羥基前列腺素脫氫酶對胃癌細(xì)胞周期影響的試驗(yàn)研究[A];中華醫(yī)學(xué)會(huì)第七次全國消化病學(xué)術(shù)會(huì)議論文匯編（下冊）[C];2007年

7 朗瑋;;中藥方劑1號對胃癌細(xì)胞體外生長及細(xì)胞粘附分子的影響[A];浙江省中西醫(yī)結(jié)合學(xué)會(huì)消化專業(yè)第八次學(xué)術(shù)年會(huì)暨省中西醫(yī)結(jié)合消化系疾病新進(jìn)展學(xué)習(xí)班論文匯編[C];2007年

8 鞏龍靜;馬君;周涵婧;鄭榮兒;;胃癌細(xì)胞的表面增強(qiáng)拉曼光譜研究[A];中國光學(xué)學(xué)會(huì)2011年學(xué)術(shù)大會(huì)摘要集[C];2011年

9 謝少茹;沈洪;趙崧;張國新;郝波;劉增巍;施瑞華;;黃芪多糖對胃癌細(xì)胞的抑制作用及其機(jī)制[A];中華中醫(yī)藥學(xué)會(huì)脾胃病分會(huì)第十九次全國脾胃病學(xué)術(shù)交流會(huì)論文匯編[C];2007年

10 劉文超;任軍;張學(xué)庸;劉智廣;張曉楠;;防御素對胃癌細(xì)胞殺傷的體外實(shí)驗(yàn)研究[A];2000全國腫瘤學(xué)術(shù)大會(huì)論文集[C];2000年

相關(guān)重要報(bào)紙文章 前8條

1 記者 陸葉清;發(fā)現(xiàn)抑制胃癌細(xì)胞的重要基因[N];上�？萍紙�(bào);2010年

2 衣曉峰　喬蕤琳 記者 趙宇清;抑制胃癌細(xì)胞生長研究有新發(fā)現(xiàn)[N];黑龍江日報(bào);2010年

3 記者 衣曉峰　通訊員 喬蕤琳;維生素E衍生物能抑制胃癌細(xì)胞生長[N];健康報(bào);2010年

4 王振嶺;我國抑制胃癌細(xì)胞生長研究有重要發(fā)現(xiàn)[N];中國醫(yī)藥報(bào);2002年

5 王振嶺;抗癌藥抑制胃癌細(xì)胞生長研究獲重要發(fā)現(xiàn)[N];中國中醫(yī)藥報(bào);2002年

6 王振嶺;7種抗癌藥體外抑制胃癌細(xì)胞的研究有新發(fā)現(xiàn)[N];醫(yī)藥經(jīng)濟(jì)報(bào);2002年

7 張中橋;胃癌細(xì)胞MDR機(jī)制研究取得新進(jìn)展[N];中國醫(yī)藥報(bào);2007年

8 吳一福 蘇玉軍;白藜蘆醇可誘導(dǎo)胃癌細(xì)胞脫落凋亡[N];中國醫(yī)藥報(bào);2005年

相關(guān)博士學(xué)位論文 前10條

1 李雙玲;IGF-1通過抑制Fox01核保留促進(jìn)胃癌細(xì)胞生長機(jī)制的研究[D];山東大學(xué);2015年

2 胡偉國;腫瘤相關(guān)成纖維細(xì)胞中Thy-1激活誘導(dǎo)上皮間質(zhì)轉(zhuǎn)化促進(jìn)胃癌細(xì)胞侵襲轉(zhuǎn)移的研究[D];上海交通大學(xué);2014年

3 周韻斕;應(yīng)激條件下胃癌細(xì)胞高表達(dá)線粒體活性氧和前梯度蛋白2促進(jìn)腫瘤進(jìn)展的研究[D];上海交通大學(xué);2014年

4 徐同鵬;SP1誘導(dǎo)的長非編碼RNA TINCR通過調(diào)控KLF2 mRNA穩(wěn)定性影響胃癌細(xì)胞的增殖與凋亡[D];南京醫(yī)科大學(xué);2015年

5 王暢;miR-34a通過miR-34a-c-myc/Bmi-1負(fù)反饋通路負(fù)調(diào)控胃癌干細(xì)胞樣特性[D];復(fù)旦大學(xué);2014年

6 羅貫虹;MGr1-Ag/37LRP參與PrP~C介導(dǎo)的胃癌細(xì)胞多藥耐藥[D];第四軍醫(yī)大學(xué);2014年

7 默董亮;人類解旋酶RecQL4調(diào)控胃癌細(xì)胞耐藥性分子機(jī)制研究[D];中國科學(xué)院北京基因組研究所;2016年

8 劉皎婧;PI3K/Akt/GSK3β/p190ARhoGAP/RhoA信號通路在Wnt5a誘導(dǎo)胃癌細(xì)胞遷移中作用的研究[D];南京醫(yī)科大學(xué);2014年

9 Muhammad Kamran（卡姆拉）;[D];大連醫(yī)科大學(xué);2015年

10 王瑛;PKGⅡ?qū)PA誘導(dǎo)的胃癌細(xì)胞徖移及RhoA和Rac1激活的影響[D];江蘇大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

1 林光錟;CyclinA/CDK2介導(dǎo)BAG3 Ser291位點(diǎn)的磷酸化并影響胃癌細(xì)胞的增殖和凋亡[D];福建醫(yī)科大學(xué);2015年

2 蔡洙哲;p12-LOX對胃癌細(xì)胞MKN-28的增殖和遷移的影響[D];延邊大學(xué);2015年

3 李龍;Her-2高表達(dá)對胃癌細(xì)胞侵襲、遷移的影響[D];長江大學(xué);2015年

4 趙婷婷;GPIbα對胃癌細(xì)胞粘附、遷移和侵襲能力的影響及其機(jī)制的初步探討[D];蘭州大學(xué);2015年

5 謝瑞霞;盤狀結(jié)構(gòu)域受體1調(diào)控上皮—間質(zhì)轉(zhuǎn)化影響胃癌侵襲轉(zhuǎn)移分子機(jī)制的研究[D];蘭州大學(xué);2015年

6 王東倉;NM23-H2通過抑制Wnt/β-catenin信號通路抑制胃癌細(xì)胞的侵襲遷移[D];蘭州大學(xué);2015年

7 朱瑞雪;NDRG2基因?qū)ξ赴┘?xì)胞惡性表型的影響[D];鄭州大學(xué);2015年

8 董凱楠;內(nèi)質(zhì)網(wǎng)應(yīng)激對胃癌細(xì)胞侵襲遷移能力的影響[D];鄭州大學(xué);2015年

9 單爭爭;二甲雙胍在IL-6誘導(dǎo)胃癌細(xì)胞EMT中的作用[D];鄭州大學(xué);2015年

10 田莉;NM23-H2通過誘導(dǎo)自噬抑制胃癌細(xì)胞EMT的發(fā)生[D];蘭州大學(xué);2015年

，

本文編號：2156442