發(fā)布時(shí)間：2018-09-10 10:27

【摘要】：第一部分膠質(zhì)瘤細(xì)胞在低氧條件下侵襲性的表現(xiàn) 目的：探討正常條件和低氧條件下U251膠質(zhì)瘤細(xì)胞侵襲性的表現(xiàn)。 方法：低氧條件下培養(yǎng)U251膠質(zhì)瘤細(xì)胞,Western Blotting檢測(cè)低氧條件下細(xì)胞中HIF-1α表達(dá),明確細(xì)胞的低氧環(huán)境是否成功建立；在正常條件和低氧條件下培養(yǎng)U251膠質(zhì)瘤細(xì)胞,Transwell實(shí)驗(yàn)檢測(cè)正常條件和低氧條件下U251膠質(zhì)瘤細(xì)胞的侵襲能力；明膠酶譜法檢測(cè)正常條件和低氧條件下U251膠質(zhì)瘤細(xì)胞分泌到培養(yǎng)液中活性MMP-2的量。采用統(tǒng)計(jì)學(xué)軟件SPSS19.0進(jìn)行數(shù)據(jù)統(tǒng)計(jì)學(xué)分析。結(jié)果：在低氧條件下U251膠質(zhì)瘤細(xì)胞中HIF-1α的表達(dá)隨著培養(yǎng)時(shí)間的延長(zhǎng)而增加；在低氧條件下U251膠質(zhì)瘤細(xì)胞的侵襲能力明顯高于正常條件下U251膠質(zhì)瘤細(xì)胞的侵襲能力(p0.05)；在低氧條件下U251膠質(zhì)瘤細(xì)胞分泌到培養(yǎng)液中的活性MMP-2明顯高于正常條件下U251膠質(zhì)瘤細(xì)胞分泌到培養(yǎng)液中MMP-2的活性(p0.01)。 結(jié)論：低氧條件能夠增加U251膠質(zhì)瘤細(xì)胞的侵襲能力,而且這種侵襲能力的增加是通過U251膠質(zhì)瘤細(xì)胞向周圍分泌活性MMP-2實(shí)現(xiàn)的。 第二部分：低氧條件下c-Jun NH2末端酶在U251膠質(zhì)瘤細(xì)胞侵襲中的作用 目的：探討在低氧條件下c-Jun NH2末端酶在U251膠質(zhì)瘤細(xì)胞侵襲中的作用； 方法：低氧條件下培養(yǎng)U251膠質(zhì)瘤細(xì)胞,Western Blotting檢測(cè)低氧條件下細(xì)胞中磷酸化c-Jun和磷酸化JNK的表達(dá)；Western Blotting檢測(cè)低氧條件下利用JNK抑制劑處理U251膠質(zhì)瘤細(xì)胞24小時(shí)p-c-Jun和p-JNK的表達(dá)；Transwell實(shí)驗(yàn)檢測(cè)低氧條件下利用JNK抑制劑處理U251膠質(zhì)瘤細(xì)胞24小時(shí)細(xì)胞侵襲性的變化；明膠酶譜法檢測(cè)低氧條件下利用JNK抑制劑處理U251膠質(zhì)瘤細(xì)胞24小時(shí)分泌到培養(yǎng)液中活性MMP-2的量。采用統(tǒng)計(jì)學(xué)軟件SPSS19.0進(jìn)行數(shù)據(jù)統(tǒng)計(jì)學(xué)分析。 結(jié)果：在低氧條件下U251膠質(zhì)瘤細(xì)胞中p-c-Jvn和p-JNK的表達(dá)隨培養(yǎng)時(shí)間的延長(zhǎng)而增加；在低氧條件下JNK抑制劑抑制p-c-Jun和p-JNK的表達(dá)；在低氧條件下JNK抑制劑抑制U251膠質(zhì)瘤細(xì)胞的侵襲能力；在低氧條件下JNK抑制劑抑制細(xì)胞向周圍分泌活性MMP-2。 結(jié)論：低氧條件下JNK-c-Jun途徑參與了低氧條件誘導(dǎo)的U251膠質(zhì)瘤細(xì)胞侵襲能力增加的機(jī)制。通過抑制JNK-c-Jun途徑可以抑制低氧誘導(dǎo)的U251膠質(zhì)瘤細(xì)胞侵襲能力的增加。 第三部分：低氧條件下RhoA對(duì)JNK-c-Jun途徑和U251膠質(zhì)瘤細(xì)胞侵襲性的影響 目的：探討在低氧條件下RhoA對(duì)JNK-c-Jun途徑和U251膠質(zhì)瘤細(xì)胞侵襲性的調(diào)控機(jī)制； 方法：低氧條件下培養(yǎng)U251膠質(zhì)瘤細(xì)胞,Western Blotting檢測(cè)低氧條件下細(xì)胞中活性RhoA的表達(dá)；Western Blotting檢測(cè)低氧條件下利用RhoA-siRNA和GGTase抑制劑處理U251膠質(zhì)瘤細(xì)胞24小時(shí)活性RhoA、p-c-Jun和p-JNK的表達(dá)；Transwell實(shí)驗(yàn)檢測(cè)低氧條件下利用RhoA-siRNA和GGTase抑制劑處理U251膠質(zhì)瘤細(xì)胞24小時(shí)細(xì)胞侵襲性的變化；明膠酶譜法檢測(cè)低氧條件下利用RhoA-siRNA和GGTase抑制劑處理U251膠質(zhì)瘤細(xì)胞24小時(shí)分泌到培養(yǎng)液中活性MMP-2的量。采用統(tǒng)計(jì)學(xué)軟件SPSS19.0進(jìn)行數(shù)據(jù)統(tǒng)計(jì)學(xué)分析。 結(jié)果：在低氧條件下U251膠質(zhì)瘤細(xì)胞中活性RhoA的表達(dá)隨培養(yǎng)時(shí)間的延長(zhǎng)而增加；在低氧條件下RhoA-siRNA和GGTase抑制劑抑制活性RhoA、p-c-Jun和p-JNK的表達(dá)；在低氧條件下RhoA-siRNA和GGTase抑制劑抑制U251膠質(zhì)瘤細(xì)胞的侵襲能力；在低氧條件下RhoA-siRNA和GGTase抑制劑抑制細(xì)胞向周圍分泌活性MMP-2。 結(jié)論：低氧條件下RhoA通過JNK-c-Jun途徑參與了低氧條件誘導(dǎo)的U251膠質(zhì)瘤細(xì)胞侵襲能力增加的機(jī)制。通過抑制RhoA可以抑制低氧誘導(dǎo)的U251膠質(zhì)瘤細(xì)胞侵襲能力的增加。 目的： 越來越多的證據(jù)表明糖尿病可能與多種腫瘤的發(fā)病相關(guān)。然而,糖尿病與腦腫瘤的發(fā)病風(fēng)險(xiǎn)目前還不清楚。 方法： 我們通過PubMed和EMBASASE數(shù)據(jù)庫(kù)檢索了到2012年5月24日以前的相關(guān)文獻(xiàn),并通過相關(guān)文獻(xiàn)的引文擴(kuò)大檢索范圍。所有數(shù)據(jù)由兩名人員獨(dú)立按照數(shù)據(jù)提取標(biāo)準(zhǔn)進(jìn)行提取。運(yùn)用隨機(jī)模型計(jì)算了總的相對(duì)危險(xiǎn)(SRR)和95%置信區(qū)間(95%CI)。研究間的異質(zhì)性通過Cochran's Q和12進(jìn)行統(tǒng)計(jì)評(píng)估。在本篇薈萃分析中共有13個(gè)研究被納入,包括了整個(gè)丹麥的人口和來自其它地區(qū)和國(guó)家的5107506個(gè)參與者,共有2206腦腫瘤病例。 結(jié)果： 通過對(duì)這13個(gè)研究分析,我們發(fā)現(xiàn)與非糖尿病個(gè)體相比糖尿病患者可能存在腦腫瘤發(fā)病風(fēng)險(xiǎn)(SRR,1.12;95%CI,0.89-1.42)。各研究間存在明顯的異質(zhì)性(P0.001；I2,93.5%)。亞組分析發(fā)現(xiàn)女性糖尿病患者腦腫瘤的發(fā)病風(fēng)險(xiǎn)增加了24.2%(SRR,1.242;95%CI,1.026-1.502),但未在男性糖尿病患者發(fā)現(xiàn)明顯的發(fā)病風(fēng)險(xiǎn)。本研究中未見明顯的發(fā)表偏依。 結(jié)論： 本薈萃分析發(fā)現(xiàn)糖尿病患者較非糖尿病人存在可能的發(fā)病風(fēng)險(xiǎn)。雖然我們發(fā)現(xiàn)在女性中發(fā)現(xiàn)糖尿病與腦腫瘤的發(fā)病風(fēng)險(xiǎn)成正相關(guān),但是在男性中我們并未發(fā)現(xiàn)。
[Abstract]:The first part is the aggressive expression of glioma cells under hypoxic condition.
Objective: To investigate the invasiveness of U251 glioma cells under normal and hypoxic conditions.
Methods: U251 glioma cells were cultured under hypoxic conditions. The expression of HIF-1a in U251 glioma cells under hypoxic conditions was detected by Western Blotting to determine whether the hypoxic environment of U251 glioma cells was successfully established. Results: The expression of HIF-1a in U251 glioma cells increased with the prolongation of culture time under hypoxia condition. The invasiveness of glioma cells was significantly higher than that of U251 glioma cells under normal conditions (p0.05), and the activity of MMP-2 secreted by U251 glioma cells in culture medium under hypoxia was significantly higher than that secreted by U251 glioma cells under normal conditions (p0.01).
CONCLUSION: Hypoxia can increase the invasive ability of U251 glioma cells, and this increase is achieved by secreting MMP-2 from U251 glioma cells.
The second part: the role of c-Jun NH2 terminal enzyme in the invasion of U251 glioma cells under hypoxia.
Objective: To investigate the role of c-Jun NH2 terminal enzyme in the invasion of U251 glioma cells under hypoxia.
Methods: U251 glioma cells were cultured under hypoxia, and the expression of phosphorylated c-Jun and phosphorylated JNK were detected by Western Blotting, the expression of p-c-Jun and p-JNK were detected by JNK inhibitor under hypoxia, and the expression of JNK was detected by Transwell assay under hypoxia. U251 glioma cells were treated with inhibitors for 24 hours. The amount of active MMP-2 secreted by U251 glioma cells treated with JNK inhibitors for 24 hours in culture medium was detected by gelatin zymography under hypoxic conditions.
Results: The expression of p-c-Jvn and p-JNK in U251 glioma cells increased with the prolongation of culture time under hypoxic conditions; JNK inhibitors inhibited the expression of p-c-Jun and p-JNK under hypoxic conditions; JNK inhibitors inhibited the invasive ability of U251 glioma cells under hypoxic conditions; JNK inhibitors inhibited the peripheral components of U251 glioma cells under hypoxic conditions; and JNK inhibitors Secretory activity MMP-2.
CONCLUSION: The JNK-c-Jun pathway is involved in the mechanism of hypoxia-induced invasion of U251 glioma cells. Inhibition of JNK-c-Jun pathway can inhibit the increase of hypoxia-induced invasion of U251 glioma cells.
The third part: the effect of RhoA on JNK-c-Jun pathway and invasion of U251 glioma cells under hypoxia.
Objective: To investigate the regulatory mechanism of RhoA on JNK-c-Jun pathway and U251 glioma cell invasion under hypoxia.
Methods: U251 glioma cells were cultured under hypoxic conditions, and the expression of RhoA, p-c-Jun and p-JNK was detected by Western Blotting, and the expression of RhoA-siRNA and GGTase inhibitor in U251 glioma cells was detected by Western Blotting. The invasiveness of U251 glioma cells was treated with RhoA-siRNA and GGTase inhibitors for 24 hours. The amount of active MMP-2 secreted by U251 glioma cells in 24 hours was detected by gelatin zymography under hypoxia. The data were analyzed by statistical software SPSS19.0.
Results: The expression of active RhoA in U251 glioma cells increased with the prolongation of culture time under hypoxic conditions; RhoA-siRNA and GGTase inhibitors inhibited the expression of active RhoA, p-c-Jun and p-JNK under hypoxic conditions; RhoA-siRNA and GGTase inhibitors inhibited the invasion of U251 glioma cells under hypoxic conditions; Inhibitors of RhoA-siRNA and GGTase inhibit the secretion of active MMP-2. from surrounding cells.
CONCLUSION: RhoA participates in the mechanism of hypoxia-induced U251 glioma cell invasion through JNK-c-Jun pathway under hypoxia, and inhibits hypoxia-induced U251 glioma cell invasion by inhibiting RhoA.
Objective:
Increasing evidence suggests that diabetes may be associated with a variety of tumors. However, the risk of diabetes and brain tumors remains unclear.
Method:
We retrieved the relevant literature up to May 24, 2012 from PubMed and EMBASASE databases and expanded the search scope by citing relevant literature. All data were extracted independently by two people according to the data extraction criteria. The total relative risk (SRR) and 95% confidence interval (95% CI) were calculated using a stochastic model. Qualitative assessments were conducted using Cochran's Q and 12. In this meta-analysis, 13 studies were included, including the Danish population as a whole and 510,7506 participants from other regions and countries, with a total of 2206 brain tumors.
Result:
Based on these 13 studies, we found that diabetic patients may have a risk of brain tumors compared with non-diabetic individuals (SRR, 1.12; 95% CI, 0.89-1.42). There was significant heterogeneity between studies (P 0.001; I 2, 93.5%). Subgroup analysis found that the risk of brain tumors in female diabetic patients increased by 24.2% (SRR, 1.242; 95% CI, 1.026). - 1.502), but no significant risk was found in male diabetic patients.
Conclusion:
This meta-analysis found that diabetes was associated with a higher risk of developing brain tumors than non-diabetes. Although we found a positive correlation between diabetes and the risk of brain tumors in women, we did not find it in men.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.41

【共引文獻(xiàn)】

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3 別黎;跨平臺(tái)整合微陣列數(shù)據(jù)篩選與膠質(zhì)瘤級(jí)別相關(guān)基因的實(shí)驗(yàn)研究[D];吉林大學(xué);2011年

4 王春琳;MDM4在人腦膠質(zhì)母細(xì)胞瘤中的表達(dá)與功能研究[D];第二軍醫(yī)大學(xué);2011年

5 陶幫寶;Stathmin在膠質(zhì)細(xì)胞瘤表達(dá)及其化療藥物敏感性研究[D];第二軍醫(yī)大學(xué);2011年

6 李維卿;Med19在星形細(xì)胞瘤中的表達(dá)及對(duì)其惡性生物學(xué)行為調(diào)控的實(shí)驗(yàn)研究[D];第二軍醫(yī)大學(xué);2011年

7 屈永濤;低氧微環(huán)境對(duì)體外培養(yǎng)hep-2頭頸鱗癌細(xì)胞系CSC增殖與分化的影響[D];河北醫(yī)科大學(xué);2011年

8 趙世斗;OCT4假基因在膠質(zhì)瘤和乳腺癌中的表達(dá)及其意義的研究[D];山東大學(xué);2011年

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1 顏偉;人膠質(zhì)瘤中骨橋蛋白功能的初步研究[D];南京醫(yī)科大學(xué);2010年

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9 王佳寧;顱內(nèi)腫瘤影像與病理對(duì)照研究[D];河北醫(yī)科大學(xué);2011年

10 王書杰;EGF+61 G/A與腦膠質(zhì)瘤易感性分析[D];復(fù)旦大學(xué);2011年

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