本文選題：膠質(zhì)瘤　切入點(diǎn)：基因芯片　出處：《第二軍醫(yī)大學(xué)》2017年博士論文

【摘要】：腦膠質(zhì)瘤是中樞神經(jīng)系統(tǒng)最常見的惡性腫瘤,約占全部顱內(nèi)腫瘤的40%-65%,是顱內(nèi)腫瘤患者的主要死因之一。其中低級別膠質(zhì)瘤患者的預(yù)后往往較好,10年的總體生存率可以達(dá)到47%左右,而絕大多數(shù)高級別膠質(zhì)瘤患者預(yù)后較差,其中多形性膠質(zhì)母細(xì)胞瘤(glioblastoma multiforme,GBM)的惡性程度最高,其5年的存活率甚至小于3%,明確診斷后的平均生存時(shí)間只有12月左右。盡管醫(yī)學(xué)界對膠質(zhì)瘤患者的治療已經(jīng)做出了巨大的努力,但是對膠質(zhì)瘤患者的預(yù)后改善仍然較差。造成膠質(zhì)瘤治療效果欠佳的原因不僅包括腫瘤本身增長迅速,血管密集,血運(yùn)豐富,對放化療的的耐受性,也包括腫瘤細(xì)胞向周圍正常腦組織侵潤的特性。膠質(zhì)瘤的發(fā)生發(fā)展是一個(gè)非常復(fù)雜的生物學(xué)過程,其中涉及到了非常多的基因和細(xì)胞生物學(xué)行為的改變,為提高膠質(zhì)瘤的治療效果,新的治療手段如基因靶向治療開始興起并應(yīng)用于膠質(zhì)瘤的治療,然而目前臨床上應(yīng)用的藥物,如替莫唑胺、貝伐單抗等,在患者中的有效率仍然很低。因此,只有全面深入地了解膠質(zhì)瘤發(fā)生發(fā)展的分子機(jī)制,才能為臨床對膠質(zhì)瘤的診治提供效率更高的分子靶向藥物和更為精準(zhǔn)的輔助診斷標(biāo)志物。隨著基因測序、基因芯片和基因組學(xué)等研究技術(shù)的發(fā)展,越來越多的長鏈非編碼RNA(long non-coding RNA,lncRNA)被發(fā)現(xiàn)參與到了中樞神經(jīng)系統(tǒng)的病理生理過程中,在中樞神經(jīng)系統(tǒng)的發(fā)展及疾病的發(fā)生過程中起到了重要的作用。長鏈非編碼RNA的異常表達(dá)可能會(huì)導(dǎo)致一系列中樞系統(tǒng)疾病的發(fā)生,其對神經(jīng)元細(xì)胞的分化影響巨大。并且長鏈非編碼RNA在腦膠質(zhì)瘤病理生理過程中的重要作用也越來越被廣泛接受,其不僅可通過調(diào)控多種通路及與不同分子的相互作用來調(diào)控膠質(zhì)瘤的發(fā)生發(fā)展,且在膠質(zhì)瘤的轉(zhuǎn)移和復(fù)發(fā)、分型和預(yù)后,及維持膠質(zhì)瘤細(xì)胞干性上都發(fā)揮了重要的作用。因此本研究通過lncRNAs芯片,表達(dá)譜芯片等高通量篩選技術(shù),篩選出在膠質(zhì)瘤發(fā)生發(fā)展過程中可能發(fā)揮重要作用的長鏈非編碼RNA分子LINC01116,并結(jié)合生物信息學(xué)分析及一系列經(jīng)典分子生物學(xué)技術(shù)等,在膠質(zhì)瘤臨床樣本、體外膠質(zhì)瘤細(xì)胞系、體內(nèi)裸鼠荷瘤模型中對LINC01116分子在膠質(zhì)瘤臨床樣本中的表達(dá)情況,以及其在膠質(zhì)瘤發(fā)生發(fā)展過程中的所起到的具體的生物學(xué)功能及相關(guān)的分子機(jī)制進(jìn)行全面而深入的研究。通過本課題的研究,我們期待明確LINC01116在膠質(zhì)瘤發(fā)生發(fā)展過程中的功能與機(jī)制,并明確其在膠質(zhì)瘤臨床診斷和評估預(yù)后上的作用,為膠質(zhì)瘤的診斷和預(yù)后提供新的標(biāo)志物,并為其作為潛在藥物作用靶點(diǎn)提供有力的實(shí)驗(yàn)依據(jù)。第一部分正常腦組織和腦膠質(zhì)瘤腫瘤組織中長鏈非編碼rna與mrna的芯片檢測和分析研究目的:觀察在正常腦組織和膠質(zhì)瘤腫瘤組織中差異表達(dá)的長鏈非編碼rna分子和信使rna(messengerrna,mrna)分子的表達(dá)變化情況,挑選關(guān)鍵的長鏈非編碼rna分子作為進(jìn)行深入研究的對象。研究方法:收集2014年12月至2015年5月間在上海長征醫(yī)院神經(jīng)外科收治并手術(shù)切除的5例膠質(zhì)母細(xì)胞瘤臨床組織樣本和5例正常腦組織樣本,使用arraystar人類lncrna芯片v3.0芯片系統(tǒng)地檢測長鏈非編碼rna和信使rna的表達(dá),篩選差異倍數(shù)≥2的長鏈非編碼rna和信使rna,并應(yīng)用配對t檢驗(yàn)計(jì)算長鏈非編碼rna和信使rna在兩組間差異的顯著性,p≤0.05時(shí)差異具有統(tǒng)計(jì)學(xué)意義,最終取差異倍數(shù)≥2,且p≤0.05的長鏈非編碼rna和信使rna,并隨機(jī)挑選12個(gè)分子采用實(shí)時(shí)定量pcr(quantitativerealtimepolymerasechainreaction,qrt-pcr)在原5對正常腦組織和膠質(zhì)母細(xì)胞瘤樣本驗(yàn)證芯片數(shù)據(jù)的可靠性。利用生物信息學(xué)靶定與膠質(zhì)瘤發(fā)生發(fā)展密切相關(guān)的長鏈非編碼rna分子。結(jié)果:共有4502條lncrna和5492條mrna在兩組樣品間表達(dá)差異明顯。其中2601條lncrna和2693條mrna表達(dá)上調(diào),1901條lncrna和2799條mrna表達(dá)下調(diào)。qrt-pcr的結(jié)果提示挑選出的12個(gè)分子的表達(dá)與lncrna和mrna芯片結(jié)果的表達(dá)趨勢一致。其中長鏈非編碼linc01116在腫瘤組織中顯著上調(diào)表達(dá),提示它可能對膠質(zhì)瘤的發(fā)生發(fā)展具有重要作用。結(jié)論:(1)通過基因芯片檢測發(fā)現(xiàn),對比正常腦組織,在腦膠質(zhì)瘤組織中存在大量差異表達(dá)的長鏈非編碼rna和信使rna,這些差異表達(dá)的分子可能與膠質(zhì)瘤的發(fā)生發(fā)展和遷移侵襲過程密切相關(guān),為后續(xù)進(jìn)一步篩選與膠質(zhì)瘤發(fā)生發(fā)展相關(guān)的關(guān)鍵長鏈非編碼rna提供了基礎(chǔ)。(2)qrt-pcr驗(yàn)證了基因芯片的結(jié)果,證明lncrna和mrna芯片結(jié)果是可靠的。(3)生物信息學(xué)分析靶定了可能在膠質(zhì)瘤發(fā)生發(fā)展過程中發(fā)揮關(guān)鍵作用候選長鏈非編碼rna分子linc01116。第二部分長鏈非編碼rna-linc01116在人腦膠質(zhì)瘤臨床樣本中的表達(dá)情況及臨床意義研究目的:擴(kuò)大臨床樣本驗(yàn)證linc01116分子在不同級別膠質(zhì)瘤中的表達(dá)情況,分析其與膠質(zhì)瘤患者的臨床病理指標(biāo)及生存預(yù)后是否存在關(guān)聯(lián),并為其是否能作為膠質(zhì)瘤診斷和治療的靶點(diǎn)及評估膠質(zhì)瘤患者預(yù)后的指標(biāo)提供有力的實(shí)驗(yàn)依據(jù)。研究方法:收集2004年1月至2015年12月間上海長征醫(yī)院收治并手術(shù)的89例不同級別的腦膠質(zhì)瘤患者的臨床樣本與臨床資料及13例正常腦組織樣本,通過qrt-pcr檢測linc01116分子在個(gè)樣本中的表達(dá)。采用獨(dú)立樣本t檢驗(yàn)、單因素分析、多因素分析、卡方檢驗(yàn)、相關(guān)性分析及生存分析等統(tǒng)計(jì)學(xué)方法分析其與腦膠質(zhì)瘤患者臨床病理指標(biāo)及生存預(yù)后的相關(guān)性。結(jié)果:對比正常腦組織,qrt-pcr結(jié)果提示linc01116在腦膠質(zhì)瘤樣本中呈顯著上調(diào)表達(dá),其在高級別膠質(zhì)瘤中的表達(dá)明顯高于低級別(p0.001)。通過將linc01116在本組膠質(zhì)瘤臨床樣本中的表達(dá)與本組腦膠質(zhì)瘤患者的生存與預(yù)后進(jìn)行統(tǒng)計(jì)分析我們發(fā)現(xiàn):linc01116的表達(dá)與本組膠質(zhì)瘤患者的完全無進(jìn)展生存期(progressionfreesurvival,pfs)及總體生存期(overallsurvival,os)均存在顯著的統(tǒng)計(jì)學(xué)關(guān)系(p=0.043,p=0.008),linc01116表達(dá)量低的患者,其復(fù)發(fā)和總體生存情況均較好。結(jié)論:長鏈非編碼rna分子linc01116在腦膠質(zhì)瘤組織中呈顯著高表達(dá),且其與腦膠質(zhì)瘤患者的臨床病理級別及生存預(yù)后情況密切相關(guān),具備成為腦膠質(zhì)瘤輔助性診斷分子標(biāo)志物和評估腦膠質(zhì)瘤患者生存預(yù)后指標(biāo)的潛能。第三部分長鏈非編碼rna-linc01116在腦膠質(zhì)瘤發(fā)生發(fā)展過程中的生物學(xué)功能與分子機(jī)制研究研究目的:明確長鏈非編碼rna分子linc01116在膠質(zhì)瘤發(fā)生發(fā)展過程中的生物學(xué)功能;初步探索linc01116分子發(fā)揮生物學(xué)功能的分子機(jī)制及其下游可能的調(diào)控靶點(diǎn),以期為膠質(zhì)瘤的分子診斷和臨床治療提供新的藥物作用靶點(diǎn)和思路,并提供相應(yīng)的理論和有力的實(shí)驗(yàn)依據(jù)。研究方法:通過在膠質(zhì)瘤細(xì)胞系u251、u87mg、a172、u118mg中利用慢病毒載體構(gòu)建穩(wěn)定表達(dá)的干擾或過表達(dá)linc01116分子的膠質(zhì)瘤細(xì)胞系,并在體外細(xì)胞實(shí)驗(yàn)中利用流式細(xì)胞技術(shù)檢測細(xì)胞周期、cck8實(shí)驗(yàn)檢測細(xì)胞的增殖能力、transwell小室實(shí)驗(yàn)檢測細(xì)胞的遷移侵襲能力,及小管形成實(shí)驗(yàn)檢測linc01116分子對huvec細(xì)胞小管形成能力的影響,在u87mg細(xì)胞系中構(gòu)建干擾linc01116分子的穩(wěn)轉(zhuǎn)細(xì)胞系進(jìn)行裸鼠皮下荷瘤檢測linc01116分子在體內(nèi)實(shí)驗(yàn)中對腫瘤形成的影響。通過在干擾linc01116分子的u251穩(wěn)轉(zhuǎn)細(xì)胞系中構(gòu)建表達(dá)譜基因芯片,結(jié)合qrt-pcr、westernbolt、雙熒光素酶報(bào)告系統(tǒng)等實(shí)驗(yàn)技術(shù)靶定linc01116分子的下游靶基因及相關(guān)信號通路。結(jié)果:通過實(shí)驗(yàn)我們發(fā)現(xiàn)干擾linc01116的表達(dá)后,在體外細(xì)胞水平提示:膠質(zhì)瘤細(xì)胞生長周期阻滯在g1期,腫瘤細(xì)胞生長減慢,增殖能力下降,同時(shí)腫瘤細(xì)胞的遷移和侵襲能力顯著下降。在體內(nèi)裸鼠皮下荷瘤提示:干擾linc01116分子的表達(dá)后,裸鼠皮下成瘤能力顯著下降,對生成的腫瘤進(jìn)行血管內(nèi)皮生長因子(vascular endothelial growth fact A,VEGFA)、CD31等分子的免疫組化發(fā)現(xiàn),VEGFA、CD31的表達(dá)顯著下降,腫瘤內(nèi)部血管生成能力顯著下降。通過分析表達(dá)譜芯片結(jié)果并結(jié)合生物信息學(xué)分析,我們發(fā)現(xiàn)VEGFA為LINC01116分子的下游靶基因,且LINC01116分子與VEGFA分子的3’UTR區(qū)均存在miR-31-5p的結(jié)合位點(diǎn),雙熒光素酶報(bào)告實(shí)驗(yàn)提示LINC01116與VEGFA分子的3’UTR區(qū)均可吸附miR-31-5p分子。Western bolt提示干擾LINC01116后VEGFA的蛋白表達(dá)下降。結(jié)論:長鏈非編碼RNA-LINC01116可以通過調(diào)控膠質(zhì)瘤細(xì)胞的生長周期進(jìn)而調(diào)控膠質(zhì)瘤細(xì)胞的增殖能力,且其在維持膠質(zhì)瘤細(xì)胞的遷移和侵襲能力方面發(fā)揮著重要作用;LINC01116可通過競爭性吸附miR-31-5p在轉(zhuǎn)錄后水平調(diào)節(jié)VEGFA分子的表達(dá),從而影響膠質(zhì)瘤血管的生成,進(jìn)而影響腫瘤的生成。
[Abstract]:Glioma is the most common malignant tumors of the central nervous system, accounting for 40%-65% of all intracranial tumors, is one of the main causes of death in patients with intracranial tumors. The prognosis of patients with low grade gliomas often better overall 10 year survival rate can reach about 47%, and most of the high level of poor prognosis in patients with glioma. The glioblastoma multiforme (glioblastoma multiforme, GBM) of the highest degree of malignancy, the survival rate at 5 years or even less than 3%, clear the average survival time after diagnosis only around December. Although the treatment medicine for glioma patients has made great efforts, but to improve the prognosis of glioma patients is still poor. The cause of poor therapeutic effect on glioma includes not only the rapid growth of the tumor, vascular density, abundant blood supply, tolerance to chemotherapy, including tumor cells to surrounding it The characteristics of ordinary brain tissue invasion. The development of glioma is a complex biological process, which involves the genetic and cell biological behavior is very much changed, in order to improve the treatment of glioma, new therapeutic methods such as gene targeting therapy began to rise and application in the treatment of glioma. However, the current clinical application of drugs, such as temozolomide, bevacizumab, in patients with efficiency is still low. Therefore, only a thorough understanding of the molecular mechanism of the occurrence and development of glioma, for clinical diagnosis and treatment of glioma molecular target to provide higher efficiency and more auxiliary drug the precise diagnosis markers. With the development of gene sequencing, gene chip technology and genomics, more and more non long chain encoding RNA (long non-coding RNA, lncRNA) were found in the central nervous system disease Physical and physiological process, in the process of development and diseases of the central nervous system plays an important role. The abnormal expression of long chain non encoding of RNA may lead to a series of central nervous system diseases and its influence on the differentiation of neurons is huge. And long chain non important role in the pathophysiological process of RNA encoding glioma is more and more widely accepted, it can not only regulate the development of glioma by regulating various pathways and interactions with different molecules, and the metastasis and recurrence of glioma, typing and prognosis of glioma cells, and maintain the dry have played an important role. Therefore this study through the lncRNAs chip, such as microarray high-throughput screening technology, selection of long chain may play an important role in the development of glioma in the non encoding RNA molecule LINC01116, and Bioinformatics Analysis and a series of classic molecular biology technology, in clinical samples of glioma, glioma cell lines in vitro, tumor bearing nude mice model of LINC01116 molecule expression in glioma clinical samples, and its occurrence in the development of gliomas by up to specific biological functions and related molecules the mechanism of comprehensive and in-depth study. Through this study, we look forward to developing LINC01116 function and mechanism in the development of glioma, and clearly in the glioma clinical diagnosis and prognosis assessment on the role, to provide new markers for diagnosis and prognosis of glioma, and to provide experimental evidence the potential drug targets for the long chain non RNA encoding and mRNA chip detection and analysis to the first part of normal brain tissue and glioma tumor tissues were observed in the normal brain: The long chain of differentially expressed RNA molecules and non encoding messenger RNA tissues and glioma tumor tissues (messengerrna, mRNA) expression of long chain molecules, select key non encoding RNA molecules as the object of in-depth study. Research methods: from December 2014 to May 2015 in 5 cases of glioblastoma clinical tissue samples the Department of Neurosurgery of Shanghai Changzheng Hospital were resected and 5 cases of normal brain tissue samples, using arraystar human lncrna chip V3.0 system to detect expression of long chain non encoding RNA and RNA Messenger, more than 2 fold difference screening of long chain non encoding RNA and RNA Messenger, and the application of significant paired t test calculation of long chain non encoding RNA and the messenger RNA in the difference between the two groups, statistically significant difference when p is less than or equal to 0.05, then more than 2 fold difference, and the long chain P is less than or equal to 0.05 of non encoding RNA and RNA Messenger, and random selection of 12 A molecule by quantitative real-time PCR (quantitativerealtimepolymerasechainreaction, qRT-PCR) on the reliability of the original 5 of normal brain tissues and glioblastoma samples verify the microarray data. Long chain using bioinformatics and targeting glioma is closely related to the development of non encoding RNA molecules. Results: a total of 4502 lncrna and 5492 mRNA expression. In two groups of samples. Among which 2601 lncrna and 2693 mRNA expression, consistent expression trend of 12 molecules down regulated the expression of.Qrt-pcr results of the 1901 lncrna and 2799 mRNA were selected and the expression of lncrna and mRNA chip. The results of long chain non encoding linc01116 expression was significantly up-regulated in tumor tissues. Suggesting that it may play an important role in the development of glioma. Conclusion: (1) by gene chip detection showed that compared with normal brain tissue in glioma tissues are large The amount of long chain expression differences of RNA and non encoding messenger RNA molecules may differentially expressed with glioma is closely related to the occurrence and development of migration and invasion, non encoding RNA provides the basis for further screening and glioma occurrence and development of long chain related key. (2) qRT-PCR to verify the microarray results. Lncrna and mRNA chip results are reliable. (3) the bioinformatics analysis of the target in the development of glioma may play a key role in the process of long chain non candidate RNA molecules encoding the second part linc01116. of long chain non objective to study the expression of rna-linc01116 encoding in clinical samples of human glioma and its clinical significance in expanding the expression: the clinical sample validation of linc01116 molecules in different grade gliomas, and to analyze the clinicopathological parameters and prognosis of glioma patients is related, and it is It can be used as indicators of prognosis of patients with glioma target for diagnosis and treatment of glioma and evaluation provide powerful experimental basis. Methods: clinical samples and clinical data and 13 cases of normal brain tissue samples collected from January 2004 to December 2015 in Shanghai Changzheng Hospital were analyzed and surgery in 89 cases with different levels of brain glioma patients, through the detection of expression linc01116 molecule qRT-PCR in the samples. The independent sample t test, single factor analysis, multi factor analysis, chi square test, correlation analysis and survival analysis were used to analyze its correlation with glioma patients with clinicopathological parameters and prognosis. Results: compared with normal brain tissue, the results of qRT-PCR showed that linc01116 was significantly increase in glioma samples in the expression, the expression in high grade gliomas was significantly higher than that of low level (p0.001). The linc01116 in this group of glue The survival and prognosis of the expression of stromal tumor in clinical samples and the group of brain glioma patients for statistical analysis we found that the expression of linc01116 and the group of glioma patients was progression free survival (progressionfreesurvival, PFS) and overall survival (overallsurvival, OS) were statistically significant relationship (p=0.043, p=0.008) the expression of linc01116, patients with low volume, recurrence and overall survival were better. Conclusion: long chain non encoding RNA molecule expression of linc01116 was significantly higher in glioma tissues, and the patients with glioma clinical pathological grade and prognosis are closely related, and have become the evaluation of brain glioma the survival prognostic indicators of potential markers of brain glioma assisted molecular diagnosis. The third part of long chain non encoding rna-linc01116 biological function and molecular mechanism in the development of brain glioma Objective: To study the biological function of long chain non explicit encoding RNA molecule linc01116 in the process of the occurrence and development of glioma; preliminary exploration of linc01116 molecules play a biological function of molecular mechanism and its possible downstream targets, in order to provide drug targets and new ideas for clinical treatment and molecular diagnosis of glioma, and to provide the corresponding theory and powerful experimental basis. Research methods: through U251, in U87MG glioma cell line, A172, interference vector construction and stable expression or overexpression of linc01116 glioma cell line by lentiviral u118mg molecules, and the use of flow cytometry to detect the cell cycle in vitro, CCK8 assay cell proliferation and migration of Transwell cell invasion assay, and tube formation experimental detection of linc01116 molecules forming ability of HUVEC tubules. Sound construction effect of interfering linc01116 molecules of stabletransfection cell lines for detection of linc01116 molecules in nude mice subcutaneous tumor formation in vivo of tumor in U87MG cell lines. The interference in the linc01116 molecule of U251 stable cell lines to construct the gene chip, combined with qRT-PCR, westernbolt and downstream target gene target experiment technology luciferase reporter system such as linc01116 molecules and signaling pathways. Results: through the experiment we found that interfering the expression of linc01116, suggesting that in vitro cellular level: glioma cell cycle arrest in G1 phase, the growth of tumor cell proliferation decreased at the same time, slow down, migration and invasion of tumor cells in vivo suggest that decreased significantly. Subcutaneous tumor: interfering expression of linc01116 molecules after subcutaneous tumor formation ability decreased significantly, the generation of tumor vascular endothelial growth factor (vascular endothelial growth fact sub A, VEGFA), group of immune CD31 molecules found that VEGFA, CD31 expression significantly decreased tumor angiogenesis capacity decreased significantly. The microarray and bioinformatics analysis by analyzing the expression, we found VEGFA LINC01116 downstream target gene, miR-31-5p binding sites there are 3 UTR region and the LINC01116 and VEGFA molecules, dual luciferase reporter experiments showed that LINC01116 molecules of VEGFA and VEGFA protein expression was decreased 3 UTR region can be adsorbed miR-31-5p.Western bolt interference LINC01116. Conclusion: after a long chain of non encoding RNA-LINC01116 can regulate cell proliferation through growth cycle glioma cells, and in the maintenance of glioma cell migration and invasion ability plays an important role in LINC01116 by competitive; The adsorption of miR-31-5p at the post transcriptional level regulates the expression of VEGFA molecules, which affects the angiogenesis of glioma, and then affects the formation of the tumor.

【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R739.41

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 周志華;易良;卞修武;;膠質(zhì)瘤干細(xì)胞研究進(jìn)展[J];中華病理學(xué)雜志;2007年03期

2 徐俊杰;于洪泉;國巍;趙偉;金宏;溫娜;齊玲;;西蘭花多肽對大鼠C6膠質(zhì)瘤細(xì)胞生長的影響[J];中風(fēng)與神經(jīng)疾病雜志;2012年11期

3 徐俊杰;于洪泉;趙偉;金宏;溫娜;齊玲;劉興吉;;西蘭花多肽對C6膠質(zhì)瘤細(xì)胞的誘導(dǎo)凋亡作用[J];吉林大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2013年01期

4 仝海波,江澄川,唐鎮(zhèn)生,金一尊;膠質(zhì)瘤細(xì)胞化學(xué)增敏作用實(shí)驗(yàn)研究[J];山西臨床醫(yī)藥;2000年07期

5 李嗍,王楓,繆珊,駱文靜;過量鋅對鼠膠質(zhì)瘤細(xì)胞體外生長的影響[J];解放軍預(yù)防醫(yī)學(xué)雜志;2001年04期

6 梁一鳴,郭國慶,鄭少俊,沈偉哉;膠質(zhì)瘤血管內(nèi)皮生長因子表達(dá)的調(diào)節(jié)[J];臨床與實(shí)驗(yàn)病理學(xué)雜志;2001年02期

7 曲元明,韓韜,李桂林,王成偉;血管內(nèi)皮細(xì)胞生長因子抗體對膠質(zhì)瘤生長的影響[J];山東醫(yī)科大學(xué)學(xué)報(bào);2001年02期

8 黃強(qiáng),董軍;膠質(zhì)瘤的分子外科治療[J];中國微侵襲神經(jīng)外科雜志;2001年04期

9 葉明,周岱,周幽心,王瑋,傅建新,黃煜倫;血管內(nèi)皮生長因子在膠質(zhì)瘤中的表達(dá)[J];腫瘤;2002年06期

10 顧宇翔,陳銜城,王宇倩;膠質(zhì)瘤對親細(xì)胞非均質(zhì)分子脂質(zhì)和幾種藥物敏感性的比較[J];復(fù)旦學(xué)報(bào)(醫(yī)學(xué)版);2003年02期

相關(guān)會(huì)議論文 前10條

1 李飛;李梅;盧佳友;朱剛;林江凱;孟輝;吳南;陳志;馮華;;脂質(zhì)微區(qū)干擾劑甲基-β-環(huán)糊精影響C6膠質(zhì)瘤細(xì)胞侵襲和遷移的體外實(shí)驗(yàn)研究[A];中國醫(yī)師協(xié)會(huì)神經(jīng)外科醫(yī)師分會(huì)第四屆全國代表大會(huì)論文匯編[C];2009年

2 吳安華;王運(yùn)杰;Ohlfest JR;Wei Chen;Low WC;;膠質(zhì)瘤的生物治療-從實(shí)驗(yàn)室到臨床[A];中華醫(yī)學(xué)會(huì)神經(jīng)外科學(xué)分會(huì)第九次學(xué)術(shù)會(huì)議論文匯編[C];2010年

3 徐宏;韓楊云;孫中書;李新軍;;與膠質(zhì)瘤代謝通路相關(guān)的候選基因篩選[A];中華醫(yī)學(xué)會(huì)神經(jīng)外科學(xué)分會(huì)第九次學(xué)術(shù)會(huì)議論文匯編[C];2010年

4 潘冬生;;多基因修飾膠質(zhì)瘤細(xì)胞疫苗的抗腫瘤免疫反應(yīng)[A];中國醫(yī)師協(xié)會(huì)神經(jīng)外科醫(yī)師分會(huì)第六屆全國代表大會(huì)論文匯編[C];2011年

5 俞文華;車志豪;張祖勇;許培源;陸鏞民;傅林;朱強(qiáng);陳鋒;杜權(quán);;骨橋蛋白在膠質(zhì)瘤細(xì)胞中的表達(dá)及其信號傳導(dǎo)途徑[A];2005年浙江省神經(jīng)外科學(xué)術(shù)會(huì)議論文匯編[C];2005年

6 張震;徐克;;低強(qiáng)度超聲誘導(dǎo)C6膠質(zhì)瘤細(xì)胞凋亡的體外實(shí)驗(yàn)研究[A];中華醫(yī)學(xué)會(huì)第十三次全國超聲醫(yī)學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2013年

7 蔣偉峰;高方友;尹浩;;白細(xì)胞介素-17及其受體在膠質(zhì)瘤中的表達(dá)及臨床意義[A];2013年貴州省神經(jīng)外科年會(huì)論文集[C];2013年

8 徐慶生;張小兵;周永慶;;膠質(zhì)瘤干細(xì)胞及其放療敏感性[A];2011年浙江省神經(jīng)外科學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2011年

9 楊孔賓;趙世光;劉炳學(xué);陳曉豐;戴欽舜;;K~+通道阻斷劑四乙胺對大鼠膠質(zhì)瘤細(xì)胞的增殖和凋亡影響[A];中國醫(yī)師協(xié)會(huì)神經(jīng)外科醫(yī)師分會(huì)第四屆全國代表大會(huì)論文匯編[C];2009年

10 黃強(qiáng);;膠質(zhì)瘤生成細(xì)胞研究[A];第三屆中國腫瘤學(xué)術(shù)大會(huì)教育論文集[C];2004年

相關(guān)重要報(bào)紙文章 前5條

1 衣曉峰　馮宇曦;中藥三氧化二砷有望成為治療膠質(zhì)瘤新藥[N];中國醫(yī)藥報(bào);2011年

2 記者 匡遠(yuǎn)深;讓膠質(zhì)瘤干細(xì)胞不再“繁殖”[N];健康報(bào);2011年

3 張獻(xiàn)懷　張文;瘤區(qū)埋雷 持續(xù)殺傷[N];健康報(bào);2007年

4 白毅;人腦膠質(zhì)瘤基礎(chǔ)與應(yīng)用研究喜結(jié)“九大碩果”[N];中國醫(yī)藥報(bào);2006年

5 王德江；劉藏；王貴懷；曹勇；王新生；肖新如;交流最新進(jìn)展 提高診治水平[N];中國醫(yī)藥報(bào);2005年

相關(guān)博士學(xué)位論文 前10條

1 董軍;CUL4B在神經(jīng)膠質(zhì)細(xì)胞瘤中的作用研究[D];山東大學(xué);2015年

2 張睿;循環(huán)miR-221/222在膠質(zhì)瘤診斷與預(yù)后中的價(jià)值與基于CED的中樞神經(jīng)系統(tǒng)給藥新方法的研究[D];山東大學(xué);2015年

3 許森林;ALDH1A1在膠質(zhì)瘤侵襲和結(jié)直腸癌轉(zhuǎn)移中的作用和機(jī)制[D];第三軍醫(yī)大學(xué);2015年

4 王嘯;靶向嵌段共聚物膠束在膠質(zhì)瘤磁共振成像、藥物輸送及治療的應(yīng)用[D];安徽醫(yī)科大學(xué);2015年

5 廖紅展;鋅指轉(zhuǎn)錄因子SNAI2在miR-203的影響下通過上皮間質(zhì)轉(zhuǎn)化參與膠質(zhì)瘤耐藥機(jī)制的調(diào)節(jié)[D];南方醫(yī)科大學(xué);2015年

6 潘俊;IRG1促進(jìn)膠質(zhì)瘤增殖的作用機(jī)制及臨床意義[D];南方醫(yī)科大學(xué);2015年

7 鄭傳宜;膠質(zhì)瘤中GLUT3基因異常表達(dá)的意義及其相關(guān)調(diào)控機(jī)制[D];南方醫(yī)科大學(xué);2015年

8 徐紅超;氬氦冷凍消融聯(lián)合GM-CSF治療膠質(zhì)瘤小鼠的療效及其對小鼠脾臟樹突狀細(xì)胞免疫功能影響[D];南方醫(yī)科大學(xué);2015年

9 黃素寧;TNFRSF6B在膠質(zhì)瘤中的表達(dá)及對膠質(zhì)瘤細(xì)胞增殖及凋亡的作用研究[D];南方醫(yī)科大學(xué);2015年

10 熊偉;GBE1在人腦膠質(zhì)細(xì)胞瘤中的表達(dá)及干預(yù)實(shí)驗(yàn)研究[D];第四軍醫(yī)大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

1 張大慶;單核細(xì)胞趨化蛋白-1在骨髓間充質(zhì)干細(xì)胞向膠質(zhì)瘤細(xì)胞趨化中的作用研究[D];大連醫(yī)科大學(xué);2012年

2 黃俊龍;ADC值與膠質(zhì)瘤Ki-67、MGMT的相關(guān)性研究[D];福建醫(yī)科大學(xué);2015年

3 李明聰;下調(diào)Pygo2對U251及U251起源的膠質(zhì)瘤干細(xì)胞生物學(xué)特性的影響[D];福建醫(yī)科大學(xué);2015年

4 徐云峰;膠質(zhì)瘤干細(xì)胞的3D培養(yǎng)及其核酸適體篩選的探索[D];福建醫(yī)科大學(xué);2015年

5 張靜文;T細(xì)胞過繼免疫治療小鼠腦膠質(zhì)瘤原位模型的研究[D];河北醫(yī)科大學(xué);2015年

6 洪宇;膠質(zhì)瘤瘤周水腫、病理級別、Ki-67表達(dá)三者相關(guān)性研究[D];石河子大學(xué);2015年

7 姬云翔;磷酸化Cx43蛋白在人膠質(zhì)瘤細(xì)胞中表達(dá)及其與腫瘤細(xì)胞增殖相關(guān)性研究[D];石河子大學(xué);2015年

8 朱峰;OPN的異常表達(dá)與膠質(zhì)瘤的相關(guān)性研究[D];河北醫(yī)科大學(xué);2015年

9 劉兵;SENP1表達(dá)水平對人腦膠質(zhì)瘤發(fā)生發(fā)展的作用機(jī)制及其相關(guān)性[D];河北醫(yī)科大學(xué);2015年

10 李文華;Slit2/Robo1在人腦膠質(zhì)瘤中的表達(dá)及臨床意義[D];河北醫(yī)科大學(xué);2015年

，

本文編號：1699032