發(fā)布時間：2018-08-29 14:59

【摘要】：腎細(xì)胞癌(renal cell carcinoma,RCC)是起源于腎小管上皮的惡性腫瘤,占腎臟惡性腫瘤的80%-90%,是成人泌尿系統(tǒng)常見的惡性腫瘤之一[1]。腎細(xì)胞癌的生物學(xué)行為及其特征較為復(fù)雜,其發(fā)生發(fā)展的機(jī)制尚未完全明確。目前,外科手術(shù)是根治腎細(xì)胞癌的主要方法,約有1/3的腎細(xì)胞癌患者初次就診時就已發(fā)現(xiàn)有轉(zhuǎn)移,無法接受根治性手術(shù)治療[2],約有1/3的局限性腎癌患者行根治性手術(shù)后仍會出現(xiàn)遠(yuǎn)處轉(zhuǎn)移[3],對于局限性腎癌患者,行根治性腎切除術(shù)或保留腎單位手術(shù)后,約90%以上患者能獲得五年無病生存。同時,轉(zhuǎn)移性腎癌(metastatic renal cell carcinoma,mRCC)對傳統(tǒng)放化療均不敏感,其5年生存率小于10%[4]。因此,探索腎細(xì)胞癌發(fā)生、發(fā)展的分子機(jī)制,尋找有效的生物學(xué)標(biāo)記物,已成為腎細(xì)胞癌研究的熱點,以便為腎細(xì)胞癌的生物治療提供新的靶點和新思路。近年來分子靶向藥物治療成為腫瘤治療的熱點,并已在多種腫瘤的治療中獲得了重大進(jìn)展,已成為抗腫瘤治療的重要組成部分[5]。分子靶向治療是以腫瘤細(xì)胞中過度表達(dá)的某些標(biāo)志性大分子物質(zhì)作為靶點,利用藥物阻斷這些大分子物質(zhì)相關(guān)的信號轉(zhuǎn)導(dǎo)路徑,從而得到控制腫瘤的生長、進(jìn)展及轉(zhuǎn)移等作用。研究發(fā)現(xiàn)缺氧誘導(dǎo)因子(hypoxia-inducible factor, HIF)、血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)、血小板衍生生長因子(platelet-derived growth factor, PDGF)、表皮生長因子(epidermal growth factor, EGF)及其受體(EGFR)、哺乳動物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)等均為分子靶向治療的重要靶向分子。這些分子的異常表達(dá)與腎癌特別是腎透明細(xì)胞癌的預(yù)后有著密切關(guān)系,使之成為腎細(xì)胞癌分子靶向治療的基礎(chǔ)和作用靶點。RCC分子靶向治療中最為重要的分子信號通路主要包括VEGF通路和mTOR通路。VEGF是腫瘤誘導(dǎo)產(chǎn)生新生血管的關(guān)鍵細(xì)胞因子,研究發(fā)現(xiàn)在腎細(xì)胞癌組織中VEGF、VEGFR-1、VEGFR-2mRNA異常高度表達(dá),同時腫瘤組織中的微血管密度顯著大于正常腎組織[6,7]。VEGF與其受體結(jié)合后可激活細(xì)胞內(nèi)信號傳導(dǎo)通路,包括PI3K/Akt/mTOR和Ras/Raf/絲裂原激活蛋白激酶的激酶(mitogen activated protein kinase kinase,MAPKK)/細(xì)胞外信號調(diào)節(jié)激酶(extracellular signal regulated kinase, ERK)等信號通路,促進(jìn)內(nèi)皮細(xì)胞的增生和分化,進(jìn)而廣泛參與腎癌的生長、增殖、分化等過程。SARM(Sterile-alpha and HEAT/Armadillo motif containing protein)是 TLR(Toll-like receptor)信號通路中含有 TIR (Toll/interleukin-l receptor)結(jié)構(gòu)域的五個接頭蛋白之一,其在進(jìn)化上非常保守,從線蟲、果蠅、文昌魚到哺乳動物都有類似結(jié)構(gòu)的分子[8]。目前對SARM的功能研究發(fā)現(xiàn),SARM是TLR信號通路中依賴 TRIF (TIR domain-containing adaptor inducing IFN- β , TRIF)的負(fù)性調(diào)控蛋白,在天然免疫應(yīng)答和炎癥發(fā)應(yīng)中發(fā)揮重要作用[9-11];同時,有研究發(fā)現(xiàn),SARM在壓力條件下能促進(jìn)小鼠神經(jīng)元細(xì)胞凋亡[12]。但是目前尚無關(guān)于SARM在腫瘤發(fā)生、發(fā)展作用的研究報道,對SARM在腎細(xì)胞癌中的表達(dá)水平、是否參與調(diào)控腎細(xì)胞癌的發(fā)生、發(fā)展及其分子機(jī)制目前仍尚不清楚。因此對SARM在腎癌細(xì)胞中的功能及其分子機(jī)制的研究將是非常有意義的工作,其研究結(jié)果將為腎癌的分子靶向治療提供新的靶點。研究目的本研究將通過體外體內(nèi)實驗,以腎癌細(xì)胞株、BALB/C-nu裸鼠移植瘤和腎癌臨床組織標(biāo)本為研究模型,檢驗SARM在腎癌組織和腎癌細(xì)胞株與癌旁正常腎組織和腎小管上皮細(xì)胞的表達(dá)水平有無差異,探討SARM在腎癌細(xì)胞的生長的作用功能、誘導(dǎo)細(xì)胞自噬發(fā)生的作用,同時觀察分子靶向藥物舒尼替尼與SARM的相互作用,并從分子水平初步探討SARM調(diào)控腎癌細(xì)胞生長的可能機(jī)制。以期明確SARM對腎癌細(xì)胞的生長的調(diào)控作用及其可能分子機(jī)制,為腎癌的分子靶向治療藥物的研究提供新的靶點和新的思路。研究方法一、臨床標(biāo)本和細(xì)胞株研究:提取腎透明細(xì)胞癌組織和癌旁正常腎組織、正常腎小管上皮細(xì)胞(HK-2)和腎癌細(xì)胞株(786-O、OS-RC-2)的蛋白和RNA,利用免疫印跡法和半定量PCR技術(shù)觀察SARM在正常腎組織和細(xì)胞與腎透明細(xì)胞癌組織和細(xì)胞中的蛋白水平和RNA表達(dá)水平的差異。二、體外實驗研究:本研究采用細(xì)胞轉(zhuǎn)染和慢病毒包裝感染方法構(gòu)建了786-O和OS-RC-2穩(wěn)定表達(dá)SARM的腎癌細(xì)胞株,通過細(xì)胞計數(shù)法、平板克隆形成實驗檢測了穩(wěn)定表達(dá)SARM對腎癌細(xì)胞生長和增殖的影響;采用PI染色和Annexin V-PE/7AAD雙染色、利用流式細(xì)胞儀觀察穩(wěn)定表達(dá)SARM對腎癌細(xì)胞周期進(jìn)行和細(xì)胞凋亡的影響;應(yīng)用分子靶向藥物舒尼替尼處理腎癌細(xì)胞,觀察分子靶向藥物與SARM的相互作用;采用無血清饑餓方法誘導(dǎo)穩(wěn)定表達(dá)SARM腎癌細(xì)胞發(fā)生自噬,探討SARM與自噬的關(guān)系。三、體內(nèi)試驗研究:通過OS-RC-2穩(wěn)定表達(dá)SARM腎癌細(xì)胞構(gòu)建腎癌BALB/C-nu裸鼠移植瘤模型,檢測穩(wěn)定表達(dá)SARM后對腎癌裸鼠移植瘤生長曲線及荷瘤體積有無影響。四、分子機(jī)制的初步探討:利用免疫印跡法研究穩(wěn)定表達(dá)SARM對PI3K/Akt/mTOR信號通路及ERK/MAPK信號通路影響,探討穩(wěn)定表達(dá)SARM對腎癌細(xì)胞生長、增殖、周期進(jìn)行、凋亡的調(diào)控及誘導(dǎo)腎癌細(xì)胞自噬發(fā)生的可能分子機(jī)制。五、統(tǒng)計學(xué)方法:每組實驗均重復(fù)三次,用平均數(shù)土標(biāo)準(zhǔn)差進(jìn)行統(tǒng)計學(xué)描述,根據(jù)實驗設(shè)計分別采用兩獨立樣本t檢驗(Independent sample t test)、重復(fù)測量數(shù)據(jù)的方差分析、析因設(shè)計資料的方差分析進(jìn)行組間差異比較。實驗數(shù)據(jù)采用IBM SPSS19.0軟件進(jìn)行上述統(tǒng)計學(xué)分析,P 0.05則表示為具有統(tǒng)計學(xué)意義。研究結(jié)果一、SARM在腎透明細(xì)胞癌組織蛋白表達(dá)水平降低腎透明細(xì)胞癌組織和腎癌細(xì)胞株中SARM的RNA水、平較癌旁正常腎組織和腎小管上皮細(xì)胞顯著升高,但是在蛋白表達(dá)水平上較癌旁正常腎組織和細(xì)胞株顯著減少,采用蛋白酶體抑制劑MG132抑制泛素發(fā)生后,SARM的蛋白水平明顯升高,說明SARM在從RNA翻譯到蛋白合成可能由于發(fā)生泛素化修飾,導(dǎo)致其在蛋白水平表達(dá)低下。二、成功構(gòu)建穩(wěn)定表達(dá)SARM細(xì)胞株通過X-tremeGENE HP DNA Transfection Reagen轉(zhuǎn)染和慢病毒包裝感染方法、流式細(xì)胞儀分選單克隆細(xì)胞成功構(gòu)建了穩(wěn)定表達(dá)SARM的786-0和OS-RC-2的細(xì)胞株,免疫印跡法對GFP-SARM蛋白表達(dá)水平進(jìn)行驗證。三、穩(wěn)定表達(dá)SARM抑制了腎癌細(xì)胞的生長和增殖細(xì)胞計數(shù)法結(jié)果顯示,與GFP對照組相比,穩(wěn)定表達(dá)SARM后顯著抑制了腎癌細(xì)胞的生長(P0.05),同時平板克隆形成實驗結(jié)果發(fā)現(xiàn)穩(wěn)定表達(dá)SARM對腎癌細(xì)胞的增殖有顯著抑制作用(P0.05)。四、穩(wěn)定表達(dá)SARM阻滯細(xì)胞周期進(jìn)行和促進(jìn)細(xì)胞死亡流式細(xì)胞儀檢測發(fā)現(xiàn),與GFP對照組相比,穩(wěn)定表達(dá)SARM能夠阻滯腎癌細(xì)胞從G1期進(jìn)入S期,同時穩(wěn)定表達(dá)SARM的腎癌細(xì)胞凋亡增多,說明SARM能阻滯細(xì)胞周期的進(jìn)行、促進(jìn)腎癌細(xì)胞死亡(P0.05)。五、SARM可促進(jìn)舒尼替尼誘導(dǎo)腎癌細(xì)胞發(fā)生自噬免疫印跡法檢測發(fā)現(xiàn)舒尼替尼可以增強(qiáng)SARM在腎癌細(xì)胞株的表達(dá)水平和誘導(dǎo)腎癌細(xì)胞自噬發(fā)生。穩(wěn)定表達(dá)SARM可以促進(jìn)腎癌細(xì)胞發(fā)生自噬,抑制SARM后可減弱舒尼替尼誘導(dǎo)腎癌細(xì)胞自噬發(fā)生,說明SARM在調(diào)控舒尼替尼誘導(dǎo)腎癌細(xì)胞自噬的發(fā)生中發(fā)揮重要作用。六、穩(wěn)定表達(dá)SARM可抑制腎癌裸鼠移植瘤的生長將穩(wěn)定表達(dá)SARM的OS-RC-2細(xì)胞株接種于4周齡的雌性BALB/C-nu裸鼠皮下,觀察裸鼠移植瘤生長曲線,荷瘤生長21天后處死裸鼠收獲荷瘤,發(fā)現(xiàn)穩(wěn)定表達(dá)SARM抑制了裸鼠移植瘤的生長,其瘤塊體積較GFP對照組顯著減小(P0.05)。七、穩(wěn)定表達(dá)SARM誘導(dǎo)腎癌細(xì)胞發(fā)生自噬通過無血清饑餓法誘導(dǎo)穩(wěn)定表達(dá)SARM細(xì)胞株發(fā)生自噬,免疫印跡法檢測LC-3和p62蛋白表達(dá)水平。與對照組相比,穩(wěn)定表達(dá)SARM后LC-3蛋白表達(dá)水平顯著升高,p62蛋白表達(dá)顯著降低。相反,干擾SARM后,LC-3蛋白水平顯著降低。說明SARM能誘導(dǎo)腎癌細(xì)胞發(fā)生自噬。八、穩(wěn)定表達(dá)SARM抑制腎癌細(xì)胞PI3K/Akt/mTOR信號通路免疫印跡法檢測發(fā)現(xiàn),穩(wěn)定表達(dá)SARM后,Akt、mTOR和p70S6K的磷酸化水平降低,說明穩(wěn)定表達(dá)SARM能抑制PI3K/Akt/mTOR信號通路。九、穩(wěn)定表達(dá)SARM抑制ERK信號通路免疫印跡法檢測發(fā)現(xiàn)穩(wěn)定表達(dá)SARM后,與對照組相比,磷酸化ERK1/2的表達(dá)水平顯著降低,表明穩(wěn)定表達(dá)SARM能抑制ERK信號通路。結(jié)論本研究首次研究SARM在腫瘤組織和細(xì)胞中的表達(dá)水平,首次研究并發(fā)現(xiàn)SARM對腎癌細(xì)胞生長的抑制作用及SARM可誘導(dǎo)腎癌細(xì)胞發(fā)生自噬,并初步探討了 SARM調(diào)控腎癌生長和誘導(dǎo)腎癌細(xì)胞發(fā)生自噬的初步分子機(jī)制:SARM可能通過抑制P13K/Akt/mTOR信號通路和抑制ERK信號通路參與調(diào)控腎細(xì)胞癌的生長,SARM誘導(dǎo)的腎細(xì)胞癌細(xì)胞的自噬可能通過PI3K/Akt/mTOR信號通路。同時發(fā)現(xiàn)SARM可能是多靶點酪氨酸激酶抑制劑舒尼替尼的作用靶點,SARM參與調(diào)控舒尼替尼誘導(dǎo)腎癌細(xì)胞的自噬。SARM可作為腎癌分子靶向治療的一個新的靶點,為腎癌分子靶向治療研究提供了一個新的靶點和新的思路。
[Abstract]:Renal cell carcinoma (RCC) is a malignant tumor originating from renal tubular epithelium, accounting for 80% - 90% of renal malignancies. It is one of the common malignant tumors in adult urinary system. About 1/3 of the patients with RCC had metastasis at the time of their first visit and were unable to undergo radical surgery. About 1/3 of the patients with localized RCC still had distant metastasis after radical surgery. For localized RCC patients, radical nephrectomy or nephron-sparing surgery was performed, and about 90% of them had distant metastasis. At the same time, metastatic renal cell carcinoma (mRCC) is insensitive to conventional radiotherapy and chemotherapy, and its 5-year survival rate is less than 10%[4]. In recent years, molecular targeted drug therapy has become a hotspot in tumor therapy, and has made great progress in the treatment of many kinds of tumors. It has become an important part of anti-tumor therapy [5]. Hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF) and platelet-derived growth factor (p) have been found in the study. Latlet-derived growth factor (PDGF), epidermal growth factor (EGF) and its receptor (EGFR), mammalian target of rapamycin (mTOR) are all important target molecules for molecular targeted therapy. Abnormal expression of these molecules and the prognosis of renal cell carcinoma, especially clear cell renal cell carcinoma (RCC) are important. The most important molecular signaling pathways in RCC molecular targeted therapy include VEGF pathway and mTOR pathway. Vascular density in tumor tissues was significantly higher than that in normal kidney tissues [6,7]. Vascular growth factor binding to its receptor activates intracellular signal transduction pathways, including PI3K/Akt/mTOR and Ras/Raf/mitogen-activated protein kinase (MAPKK)/extracellular signal-regulated kinase (extrace). Llular signal regulated kinase (ERK) and other signaling pathways promote the proliferation and differentiation of endothelial cells, and thus participate in the growth, proliferation and differentiation of renal cell carcinoma. SARM (Sterile-alpha and HEAT/Armadillo motif containing protein) is a TLR (Toll-like receptor) signaling pathway containing TIR (Toll/interleukin-l receptor) structure. One of the five adaptor proteins of the TLR domain, which is evolutionarily conserved, has similar structure molecules from nematodes, fruit flies, amphioxus to mammals [8]. Answer and inflammatory response play an important role [9-11]; at the same time, some studies have found that SARM can promote the apoptosis of neurons in mice under pressure [12]. However, there are no reports about the role of SARM in tumorigenesis and development. The molecular mechanism of SARM in renal cell carcinoma is still unclear. Therefore, it is very meaningful to study the function and molecular mechanism of SARM in renal cell carcinoma. The results will provide a new target for molecular targeted therapy of renal cell carcinoma. To study the expression of SARM in renal cell carcinoma tissue and renal cell line, normal renal tissue and renal tubular epithelial cells adjacent to cancer, and to explore the role of SARM in the growth of renal cell carcinoma cells and the role of inducing autophagy, and to observe the interaction of molecular targeted drug sunitinib with SARM. In order to clarify the regulation of SARM on the growth of renal cell carcinoma and its possible molecular mechanism, and to provide new targets and new ideas for the research of molecular targeted therapy drugs for renal cell carcinoma. Protein and RNA expression in normal renal tissues and adjacent normal renal tissues, normal renal tubular epithelial cells (HK-2) and renal carcinoma cell lines (786-O, OS-RC-2) were detected by immunoblotting and semi-quantitative PCR. 2. In vitro Experimental study: In this study, 786-O and OS-RC-2 renal cell lines stably expressing SARM were constructed by cell transfection and lentiviral package infection. The effects of stably expressing SARM on the growth and proliferation of renal cell carcinoma cells were detected by cell counting and plate cloning assay. PI staining and Annexin V-PE/7AAD double staining were used, and flow cytometry was used. The effects of stable expression of SARM on cell cycle progression and apoptosis of renal cell carcinoma cells were observed. Molecular targeting drug sunitinib was used to treat renal cell carcinoma cells and the interaction between molecular targeting drugs and SARM was observed. Serum-free starvation was used to induce autophagy of renal cell carcinoma cells stably expressing SARM, and the relationship between SARM and autophagy was discussed. Study: The BALB/C-nu nude mice model of renal cell carcinoma was established by OS-RC-2 stably expressing SARM cells. The effects of stable expression of SARM on the growth curve and tumor-bearing volume of transplanted renal cell carcinoma in nude mice were detected. Fourthly, the preliminary study of molecular mechanism: The PI3K/Akt/mTOR signaling pathway and ERK/MAPK signaling were studied by Western blot. To explore the possible molecular mechanism of stably expressing SARM on the growth, proliferation, cycle progression, apoptosis regulation and autophagy of renal cell carcinoma. 5. Statistical methods: Each group of experiments were repeated three times, and were statistically described by mean soil standard deviation. According to the experimental design, two independent sample t test was used (In The experimental data were analyzed by IBM SPSS 19.0 software, and P 0.05 was statistically significant. Results 1. The expression of SARM protein in clear cell carcinoma of kidney decreased renal dialysis. The level of SARM protein in clear cell carcinoma and renal cell lines was significantly higher than that in normal renal tissues and renal tubular epithelial cells, but the level of protein expression was significantly lower than that in normal renal tissues and renal tubular epithelial cells. NA translation to protein synthesis may be due to ubiquitination modification, resulting in its low expression at protein level. 2. A stable expression of SARM cell line was successfully constructed by X-tremeGENE HP DNA Transfection Reagen transfection and lentiviral packaging infection. Flow cytometry sorted monoclonal cells successfully constructed 786-0 and OS-RC stably expressing SARM. The expression level of GFP-SARM protein was verified by Western blot. 3. The stable expression of SARM inhibited the growth and proliferation of renal cell carcinoma cells. Compared with the GFP control group, the stable expression of SARM significantly inhibited the growth of renal cell carcinoma cells (P 0.05). At the same time, the results of plate cloning showed stable expression of S. ARM significantly inhibited the proliferation of renal cell carcinoma cells (P 0.05). 4. Steady expression of SARM inhibited cell cycle and promoted cell death. Compared with GFP control group, stable expression of SARM inhibited the progression of renal cell carcinoma cells from G1 phase to S phase, and increased apoptosis of renal cell carcinoma cells stably expressing SARM, suggesting that SARM could block the apoptosis of renal cell carcinoma cells. Cell cycle progression, promote renal cell death (P 0.05). Fifthly, SARM can promote sunitinib-induced renal cell autophagy Western blot assay found that sunitinib can enhance the expression of SARM in renal cell lines and induce renal cell autophagy. Stable expression of SARM can promote renal cell autophagy, inhibit SARM. SARM plays an important role in the regulation of Sunitinib-induced autophagy. 6. Stable expression of SARM can inhibit the growth of renal cell carcinoma xenografts in nude mice. OS-RC-2 cell line stably expressing SARM was inoculated subcutaneously in 4-week-old female BALB/C-nu mice to observe the effect of SARM on the autophagy. The growth curve of transplanted tumor was observed. The stable expression of SARM inhibited the growth of transplanted tumor in nude mice, and the tumor volume was significantly smaller than that of GFP control group (P 0.05). 7. The stable expression of SARM induced autophagy of renal cancer cells. The stable expression of SARM induced autophagy of renal cancer cells by serum-free starvation induced stable expression of SARM cell lines. The expression of LC-3 and p62 protein was detected by Western blot. Compared with the control group, the expression of LC-3 protein was significantly increased and that of p62 protein was significantly decreased after stably expressing SARM. On the contrary, the expression of LC-3 protein was significantly decreased after interfering with SARM. The phosphorylation levels of Akt, mTOR and p70S6K decreased after stably expressing SARM, indicating that stably expressing SARM could inhibit PI3K/Akt/mTOR signaling pathway. Ninth, stably expressing SARM inhibiting ERK signaling pathway was detected by immunoblotting. After stably expressing SARM, the phosphorylated ERK1/2 expression level was significantly lower than that of the control group. Conclusion This study is the first to study the expression level of SARM in tumor tissues and cells. It is the first to find that SARM can inhibit the growth of renal cell carcinoma cells and induce autophagy of renal cell carcinoma cells. Initial Molecular Mechanisms: SARM may be involved in regulating the growth of renal cell carcinoma by inhibiting P13K/Akt/mTOR signaling pathway and ERK signaling pathway. SARM-induced autophagy of renal cell carcinoma cells may be mediated by PI3K/Akt/mTOR signaling pathway. SARM may be the target of Sunitinib, a multi-target tyrosine kinase inhibitor. SARM can be used as a new target for molecular targeted therapy of renal cell carcinoma, which provides a new target and a new idea for molecular targeted therapy of renal cell carcinoma.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R737.11

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王林輝,孫穎浩,錢松溪,彌靜,鞠佃文,曹雪濤,閔志廉;p~(16)基因轉(zhuǎn)染腎癌細(xì)胞體外生物學(xué)特性的研究[J];中華泌尿外科雜志;2000年05期

2 席志軍,俞莉章,郭應(yīng)祿,張凱,姜學(xué)軍,張志文;白細(xì)胞介素-6與腎癌細(xì)胞生長關(guān)系的實驗研究[J];中華醫(yī)學(xué)雜志;2000年04期

3 葉雄俊,張志文,林桂亭,金桂花,陳培拉,韓亮,黃世思,艾軍魁,辛殿祺,郭應(yīng)祿,常智杰;激活轉(zhuǎn)錄因子5在腎癌細(xì)胞系中的表達(dá)及意義[J];中華泌尿外科雜志;2003年04期

4 宋東奎,潘周輝,楊太森;人反義血管內(nèi)皮生長因子基因表達(dá)對腎癌細(xì)胞的影響[J];中華泌尿外科雜志;2003年08期

5 楊風(fēng)光;葉烈夫;林樂;李濤;何延瑜;張志文;郭應(yīng)祿;;過氧化物酶體增殖激活物受體γ配體對腎癌細(xì)胞血管生成的影響[J];福建醫(yī)藥雜志;2009年06期

6 龔明軍;;一種腎癌細(xì)胞基因復(fù)制表達(dá)順序研究的新方法[J];中國醫(yī)學(xué)創(chuàng)新;2012年26期

7 潘李珍，，張漪;人體腎癌細(xì)胞培養(yǎng)1例報告[J];首都醫(yī)科大學(xué)學(xué)報;1996年01期

8 吳偉成,巖村正嗣,小柴健;甲狀旁腺素相關(guān)蛋白在腎癌細(xì)胞中的表達(dá)及調(diào)節(jié)作用[J];中華泌尿外科雜志;1997年07期

9 許寧,石愛平,趙忠文,王乃義;腎癌細(xì)胞的凋亡與調(diào)控因子的表達(dá)[J];中華外科雜志;1998年07期

10 王威,劉梁,董雪,徐香蘭,沈彬,寇慧珠,劉濤,吳明明,虞頌庭;鈣粘蛋白E在腎癌細(xì)胞中的表達(dá)[J];中國腫瘤臨床;2000年04期

相關(guān)會議論文 前9條

1 王威;劉;董雪;徐香蘭;沈彬;寇慧珠;劉濤;吳明明;虞頌庭;;鈣粘蛋白E在腎癌細(xì)胞中的表達(dá)[A];2000全國腫瘤學(xué)術(shù)大會論文集[C];2000年

2 王志華;胡志全;葉章群;莊乾元;楊為民;陳志強(qiáng);劉繼紅;;樹突狀細(xì)胞的體外擴(kuò)增及培養(yǎng)上清液對腎癌細(xì)胞的作用[A];第十五屆全國泌尿外科學(xué)術(shù)會議論文集[C];2008年

3 申文江;孫凌飛;孫新臣;朱麗紅;邵彥;黃淵;;安替可對腎癌細(xì)胞的放射敏感性影響[A];第八屆全國中西醫(yī)結(jié)合腫瘤學(xué)術(shù)會議論文集[C];2000年

4 章小平;錢曉輝;李炎生;曾四平;肖亞軍;趙軍;曾甫清;肖傳國;;VHL表達(dá)逆轉(zhuǎn)腎癌細(xì)胞的TRAIL耐受性[A];第十五屆全國泌尿外科學(xué)術(shù)會議論文集[C];2008年

5 楊清滔;谷江;張永春;楊永安;王楠;朱致暉;祝慶亮;;高表達(dá)HIF-1α對腎癌細(xì)胞增殖及細(xì)胞內(nèi)STC-1、Ca2+水平影響的研究[A];2013年貴州省泌尿外科學(xué)術(shù)會議論文匯編[C];2013年

6 丁曉飛;沈茂;嚴(yán)巧娣;陳光;;pVHL調(diào)控NEK-8維持腎癌細(xì)胞原纖毛結(jié)構(gòu)穩(wěn)定的機(jī)制研究[A];2013醫(yī)學(xué)前沿論壇暨第十三屆全國腫瘤藥理與化療學(xué)術(shù)會議論文集[C];2013年

7 李金鋒;王國民;戎瑞明;朱同玉;;SiRNA對腎癌細(xì)胞系COX-2基因的抑制作用及其質(zhì)粒載體的構(gòu)建[A];第十五屆全國泌尿外科學(xué)術(shù)會議論文集[C];2008年

8 朱致暉;谷江;肖海濤;張永春;羅明俊;楊永安;王楠;楊清滔;;人類斯鈣素蛋白1對腎癌細(xì)胞中STC-1、HIF-1α及Ca2+影響的研究[A];2013年貴州省泌尿外科學(xué)術(shù)會議論文匯編[C];2013年

9 申文江;孫凌飛;孫新臣;朱麗紅;邵彥;黃淵;;安替可對腎癌細(xì)胞FasR、FasL和Bel-2基因表達(dá)的影響及意義[A];第八屆全國中西醫(yī)結(jié)合腫瘤學(xué)術(shù)會議論文集[C];2000年

相關(guān)重要報紙文章 前1條

1 記者 王丹;維生素C可讓腎癌細(xì)胞因“饑餓”死亡[N];健康報;2014年

相關(guān)博士學(xué)位論文 前10條

1 汪幫琦;SARM在腎癌細(xì)胞中的功能及其分子機(jī)制的初步研究[D];南方醫(yī)科大學(xué);2014年

2 馮陳陳;自噬聯(lián)合mTOR通路或磷酸戊糖途徑雙重抑制對腎細(xì)胞癌治療的研究[D];復(fù)旦大學(xué);2014年

3 陳鵬亮;miR-199靶向調(diào)控ROCK1影響腎癌細(xì)胞增殖、侵襲及凋亡的機(jī)制研究[D];南方醫(yī)科大學(xué);2015年

4 王志峰;索拉非尼對腎癌細(xì)胞系786-0干性相關(guān)表達(dá)影響[D];南方醫(yī)科大學(xué);2015年

5 洪正東;Rock2通過β-catenin/TCF4信號通路調(diào)控SCARA5表達(dá)影響腎癌細(xì)胞增殖的研究[D];南昌大學(xué);2016年

6 朱小軍;5-氮雜-2’-脫氧胞苷和順鉑通過去甲基化作用及增強(qiáng)凋亡酶激活因子1的活性協(xié)同誘導(dǎo)腎癌細(xì)胞凋亡的實驗研究[D];南方醫(yī)科大學(xué);2016年

7 張洪俠;miR-137在腎細(xì)胞癌中生物學(xué)功能及相關(guān)機(jī)制研究[D];吉林大學(xué);2016年

8 盧東源;p38IP在腎癌細(xì)胞中的功能[D];第二軍醫(yī)大學(xué);2015年

9 杜賢進(jìn);藍(lán)舌病毒湖北株選擇性誘導(dǎo)腎癌細(xì)胞死亡及其機(jī)制的研究[D];武漢大學(xué);2010年

10 楊林;腎癌細(xì)胞來源exosomes的提取鑒定及對腎癌惡性演進(jìn)的影響和機(jī)制研究[D];重慶醫(yī)科大學(xué);2013年

相關(guān)碩士學(xué)位論文 前10條

1 徐榮;腎癌細(xì)胞中內(nèi)源性Wnt以自分泌的方式刺激Fzd7的胞吞作用[D];蘇州大學(xué);2015年

2 吳本鶴;白介素-2聯(lián)合不同劑量索拉菲尼對腎癌細(xì)胞的體內(nèi)外殺傷效應(yīng)的初步研究[D];安徽醫(yī)科大學(xué);2015年

3 李麗;NFATs-ET1通路在腎癌細(xì)胞786O增殖和遷移中的作用及其機(jī)制[D];南昌大學(xué)醫(yī)學(xué)院;2015年

4 韓慶杰;siRNA沉默DAD1基因表達(dá)對腎癌細(xì)胞A498增殖與侵襲能力的影響[D];南華大學(xué);2015年

5 熊虎;沉默ACTN1基因表達(dá)能抑制腎癌細(xì)胞的生長且誘導(dǎo)細(xì)胞凋亡[D];蘭州大學(xué);2016年

6 史培X;Keap1在腎細(xì)胞癌中的表達(dá)及其作用的研究[D];山東大學(xué);2016年

7 黃巧麗;來氟米特對腎癌細(xì)胞增殖和凋亡的影響[D];浙江師范大學(xué);2016年

8 張瓊;白藜蘆醇對腎癌細(xì)胞的影響及機(jī)制研究[D];天津醫(yī)科大學(xué);2016年

9 付鈺;FBXW7在腎癌細(xì)胞凋亡機(jī)制中的初步研究[D];南華大學(xué);2016年

10 吳登爽;ATF2基因促進(jìn)腎癌細(xì)胞的增殖和轉(zhuǎn)移與臨床患者預(yù)后相關(guān)性的研究[D];第二軍醫(yī)大學(xué);2016年

本文編號：2211560