本文關(guān)鍵詞：FKBP14對(duì)上皮性卵巢癌細(xì)胞增殖和遷移能力的影響　出處：《南京醫(yī)科大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： FKBP14 上皮性卵巢癌 FKBP14 干擾RNA 增殖 凋亡 侵襲 轉(zhuǎn)移

【摘要】：卵巢癌是最常見(jiàn)的婦科惡性腫瘤,具有極高的病死率。絕大多數(shù)的卵巢癌是上皮性來(lái)源(Epithelial Ovarian Cancer,EOC),常因其高侵襲性和化療耐藥性導(dǎo)致患者預(yù)后不良。近年來(lái),雖然手術(shù)技術(shù)不斷改進(jìn),化療藥物不斷更新,但總體上上皮性卵巢癌的5年生存率并未得到顯著提升,因此研究卵巢癌特別是上皮性卵巢癌的發(fā)生、發(fā)展及浸潤(rùn)轉(zhuǎn)移的相關(guān)分子機(jī)制,有助于尋找合理有效的治療靶點(diǎn),是提高卵巢癌生存率、延長(zhǎng)生存期的關(guān)鍵。FKBP14屬于FK506結(jié)合蛋白家族(FK506-binding proteins,FKBPs),其是免疫抑制劑FK506和雷帕霉素的細(xì)胞內(nèi)受體,具有PPIase(peptidyl-prolyl cis-trans isomerase肽脯氨酰順?lè)串悩?gòu)酶)活性。近年來(lái)的研究發(fā)現(xiàn)分布廣泛,含量豐富的FKBPs家族成員具有多樣的生物學(xué)作用,包括：抑制T細(xì)胞的活化、信號(hào)調(diào)節(jié)、細(xì)胞內(nèi)鈣離子的釋放、甾體激素受體復(fù)合物的形成以及細(xì)胞周期抑制等。例如FKBP12是調(diào)控細(xì)胞周期和維持細(xì)胞內(nèi)鈣穩(wěn)態(tài)的生理因子,而FKBP38是細(xì)胞凋亡的負(fù)向調(diào)控因子。一項(xiàng)近期研究發(fā)現(xiàn),FKBP14在果蠅發(fā)育中調(diào)節(jié)Presenilin蛋白水平和Notch信號(hào)通路。FKBP14基因突變?cè)谌祟悤?huì)導(dǎo)致一種特殊類型結(jié)締組織病Ehlers-Danlos syndrome(EDS),而受到廣泛關(guān)注。FKBP14基因突變患者皮膚成纖維細(xì)胞內(nèi)質(zhì)網(wǎng)池腫大,而在體外實(shí)驗(yàn)中,來(lái)自FKBP14缺失患者的成纖維細(xì)胞,體外培養(yǎng)發(fā)現(xiàn)多種細(xì)胞外基質(zhì)(ECM)成分的改變：膠原Ⅰ,Ⅲ,Ⅵ,細(xì)胞粘合素(tenascin, TN),纖連蛋白(fibronectin FN),β1整合素(integrins)以及血小板反應(yīng)蛋白(thrombospondin)明顯減少甚至缺失。在腫瘤研究中,FKBPs家族成員多樣化的生理作用為探討腫瘤細(xì)胞異常增殖、侵襲轉(zhuǎn)移途徑、以及血管形成機(jī)制等提供了新思路。目前國(guó)內(nèi)外已有較多FKBPs在腫瘤組織中表達(dá)的相關(guān)研究報(bào)道：FKBP11和FKBP52在肝細(xì)胞性肝癌中過(guò)表達(dá),FKBP5在前列腺癌、黑色素瘤、神經(jīng)膠質(zhì)細(xì)胞瘤中過(guò)表達(dá)。FKBP65在高級(jí)別卵巢漿液性癌中表達(dá)下降。Vougioukas VI等的研究發(fā)現(xiàn),FKBP14作為EGFR信號(hào)通路蛋白之一,參與調(diào)控惡性神經(jīng)膠質(zhì)細(xì)胞瘤(GBM)對(duì)抗腫瘤藥物Erlotinib的敏感性。雖然目前尚缺乏FKBP14在人類腫瘤細(xì)胞中表達(dá)的直接研究,但細(xì)胞外基質(zhì)(ECM)的合成、分布及降解與惡性腫瘤的增殖、侵襲密切相關(guān)已經(jīng)得到廣泛共識(shí)及驗(yàn)證,Notch信號(hào)通路的異常激活或結(jié)構(gòu)性活化也與多種組織惡性腫瘤的發(fā)病相關(guān),而先前研究發(fā)現(xiàn)的FKBP14對(duì)細(xì)胞外基質(zhì)(ECM)合成的影響、以及對(duì)Notch信號(hào)通路的調(diào)控作用,讓我們有理由推測(cè)FKBP14可能參與了腫瘤的發(fā)生發(fā)展過(guò)程。在本研究中,我們檢測(cè)了FKBP14在上皮性卵巢癌組織中的表達(dá)。同時(shí)觀察靶向沉默F(xiàn)KBP14表達(dá)后對(duì)卵巢癌細(xì)胞增殖、細(xì)胞周期和凋亡、遷移侵襲等生物學(xué)特征的影響,并探討其可能的作用機(jī)制。本研究提示在上皮性卵巢癌中FKBP14可能是一種癌基因,并可能成為潛在的治療靶點(diǎn)。第一部分FKBP14在上皮性卵巢癌組織中的表達(dá)及其意義研究目的：檢測(cè)卵巢癌組織及非癌組織中FKBP14的表達(dá),探討FKBP14與卵巢癌的相關(guān)性。研究方法：1.采用RT-PCR方法檢測(cè)40例卵巢癌組織和40例非癌組織中FKBP14 mRNA的表達(dá),分析其表達(dá)是否存在差異。2.采用免疫組化SP方法檢測(cè)60例不同病理類型上皮性卵巢癌組織中FKBP14蛋白的表達(dá)情況,以20例卵巢上皮性良性囊腫組織為對(duì)照,分析FKBP14與上皮性卵巢癌之間的相關(guān)性。結(jié)果：上皮性卵巢癌組織中FKBP14 mRNA及蛋白表達(dá)水平均比對(duì)照組顯著升高,這種表達(dá)差異提示FKBP14可能是上皮性卵巢癌的一個(gè)癌基因。結(jié)論：FKBP14可能參與了上皮性卵巢癌的發(fā)生發(fā)展過(guò)程。第二部分干擾抑制FKBP14的表達(dá)對(duì)卵巢癌細(xì)胞系增殖和遷移能力的影響研究目的：利用RNA干擾技術(shù)靶向抑制卵巢癌細(xì)胞系SKOV3和H08910中FKBP14的表達(dá),觀察基因沉默后對(duì)卵巢癌細(xì)胞系生物學(xué)行為：生長(zhǎng)增殖、凋亡和侵襲轉(zhuǎn)移等能力的影響,探討FKBP14在卵巢癌發(fā)病機(jī)制中的作用,為卵巢癌的分子靶向治療提供理論依據(jù)。研究方法：1.利用Real-time PCR和Western blot方法檢測(cè)五個(gè)卵巢癌細(xì)胞系：A2780,OVCAR3, SKOV3,3A0及H08910中FKBP14蛋白的表達(dá)情況,篩選出2個(gè)高表達(dá)FKBP14基因的上皮性卵巢癌細(xì)胞系(SKOV3和HO-8910)。2.構(gòu)建FKBP14基因重組慢病毒干擾載體：采用全基因化學(xué)法合成小干擾siRNA FKBP14靶向序列(GACCACTTTCACTGATTAT)及非沉默序列(CCTAAGGTTAAGTCGCCCTCG),折疊成shRNA后,克隆至PLKO.1逆轉(zhuǎn)錄病毒載體上,并通過(guò)脂質(zhì)體Lipofectamine 2000轉(zhuǎn)染HEK293細(xì)胞。培養(yǎng)48小時(shí)后,收集逆轉(zhuǎn)病毒穩(wěn)轉(zhuǎn)靶細(xì)胞,以親本細(xì)胞和空載體轉(zhuǎn)染細(xì)胞作為對(duì)照。3.應(yīng)用CCK8實(shí)驗(yàn)檢測(cè)干擾組(RNAi)、空白對(duì)照組(WT)、非干擾序列組(NC)卵巢癌細(xì)胞系的增殖能力變化。4. Annexin V-FITC/PI雙染法流式細(xì)胞儀檢測(cè)干擾組(RNAi)、空白對(duì)照組(WT)、非干擾序列組(NC)卵巢癌細(xì)胞系的細(xì)胞周期及凋亡變化。5.應(yīng)用Transwell小室技術(shù),檢測(cè)干擾組(RNAi)、空白對(duì)照組(WT)、非干擾序列組(NC)卵巢癌細(xì)胞系遷移和侵襲能力的變化。6.通過(guò)Real-time PCR和Western blot技術(shù)檢測(cè)干擾組(RNAi)、空白對(duì)照組(WT)、非干擾序列組(NC)卵巢癌細(xì)胞系相關(guān)通路蛋白的表達(dá)：E-cadherin, Twistl,MMP2, BCL-2, BAX, capspase3, PCNA等。7. SPSS 13.0軟件進(jìn)行數(shù)據(jù)分析,計(jì)量資料用平均值±標(biāo)準(zhǔn)差表示,組間差異用獨(dú)立樣本t檢驗(yàn)分析。結(jié)果：1.干擾組(RNAi)卵巢癌細(xì)胞中FKBP14蛋白表達(dá)與空白對(duì)照組(WT)和非干擾序列組(NC)相比下降了90%,而WT組和NC組間FKBP14表達(dá)水平?jīng)]有差異。2.NC組和WT組間細(xì)胞增殖差異沒(méi)有統(tǒng)計(jì)意義,提示干擾shRNA'慢病毒轉(zhuǎn)染系統(tǒng)對(duì)卵巢癌細(xì)胞沒(méi)有細(xì)胞毒作用。FKBP14干擾組細(xì)胞SKOV3和H08910在轉(zhuǎn)染后48小時(shí),72小時(shí)都表現(xiàn)出明顯增殖抑制。3.FKBP14 shRNA轉(zhuǎn)染后,對(duì)比WT組和NC組,RNAi組表現(xiàn)出G0/G1期比例增加,S期比例減少。RNAi組細(xì)胞凋亡率比NC組升高9倍。而細(xì)胞周期和凋亡情況在NC組和WT組間無(wú)差異。4.對(duì)比WT組和NC組,RNAi組中細(xì)胞增殖相關(guān)蛋白PCNA、抗凋亡蛋白Bcl-2表達(dá)顯著下降,凋亡標(biāo)志蛋白Caspase3和促凋亡蛋白Bax表達(dá)上升。在FKBP14表達(dá)抑制后,Bax/Bcl-2比率顯著上升。5.細(xì)胞侵襲遷移實(shí)驗(yàn)中,RNAi組細(xì)胞侵襲、遷移率均低于WT組和NC組細(xì)胞。6.RNAi組基質(zhì)金屬蛋白酶MMP2和EMT誘導(dǎo)因子Twist表達(dá)均低于WT組和NC組,而上皮性標(biāo)志物E-cadherin表達(dá)高于WT組和NC組。結(jié)論：1.FKBP14參與了卵巢癌細(xì)胞的增殖、凋亡、遷移和侵襲的過(guò)程,沉默其表達(dá)能顯著降低細(xì)胞增殖、促進(jìn)細(xì)胞凋亡以及減弱其侵襲遷移能力。提示FKBP14可能是卵巢癌發(fā)生發(fā)展中的一個(gè)癌基因,暗示我們FKBP14有可能成為卵巢癌基因治療的潛在靶點(diǎn)。2. FKBP14 shRNA通過(guò)GO/G1細(xì)胞周期捕獲抑制細(xì)胞增殖,FKBP14通過(guò)調(diào)控Bax/Bcl-2比率抑制細(xì)胞凋亡。3. FKBP14促進(jìn)卵巢癌細(xì)胞侵襲和轉(zhuǎn)移的機(jī)制可能與調(diào)控上皮細(xì)胞間質(zhì)化(EMT)過(guò)程以及影響細(xì)胞外基質(zhì)(ECM)成分有關(guān)。
[Abstract]:Ovarian cancer is the most common gynecologic malignant tumor, the mortality rate is high. The majority of ovarian cancer is epithelial origin (Epithelial Ovarian Cancer, EOC), often because of its high invasiveness and resistance to chemotherapy leads to poor prognosis. In recent years, although the surgical technique of continuous improvement, chemotherapy drugs constantly updated, but overall on the epithelial ovarian cancer 5 years survival rate has not improved significantly, so the study of ovarian cancer is epithelial ovarian cancer occurrence, development and metastasis related molecular mechanism, can help to find reasonable and effective therapeutic targets, is to improve the survival rate of ovarian cancer, the key to prolong the survival of.FKBP14 belongs to the FK506 binding protein family (FK506-binding proteins, FKBPs), which is immune inhibitor FK506 and rapamycin intracellular receptors, with PPIase (peptidyl-prolyl cis-trans isomerase peptide prolyl isomerase activity). The study found that in recent years are widely distributed, rich members of the FKBPs family with a variety of biological functions, including: activation, inhibition of T cell signaling, intracellular calcium release, the formation of steroid hormone receptor complexes and cell cycle inhibition. For example, FKBP12 is the control of cell cycle and maintain intracellular physiological factor calcium homeostasis, cell apoptosis and FKBP38 is a negative regulatory factor. A recent study found that FKBP14 in Drosophila development in regulating the protein level of Presenilin and Notch signaling pathway in human.FKBP14 gene mutation leads to a special type of connective tissue disease Ehlers-Danlos syndrome (EDS), has received widespread attention in patients with.FKBP14 mutation into the skin fiber cell endoplasmic reticulum enlargement, in vitro, fibroblasts from FKBP14 deficient patients, found a variety of extracellular matrix in vitro (ECM) The changes of the composition of collagen I, III, VI, cell adhesion factor (tenascin, TN), fibronectin (fibronectin FN), integrin beta 1 (integrins) and thrombospondin (thrombospondin) significantly reduced or absent. In cancer research, the physiological role of FKBPs family members in order to explore the variety of abnormal proliferation tumor cell invasion and metastasis, pathway, provides a new idea and mechanism of angiogenesis. Relevant research reports at home and abroad are more FKBPs in the tumor tissues: FKBP11 and FKBP52 expression in hepatocellular carcinoma, FKBP5 in prostate cancer, melanoma, glioma in overexpression decreased the expression of.Vougioukas VI.FKBP65 in high grade ovarian serous carcinoma, FKBP14 as one of the EGFR signaling protein involved in the regulation of malignant glioma (GBM) antitumor drug sensitive Erlotinib . although there is a lack of direct research on the expression of FKBP14 in human tumor cells, but the extracellular matrix (ECM) synthesis, distribution and degradation and proliferation of malignant tumor, is closely related to the invasion has been a broad consensus and verify the pathogenesis of abnormal activation of Notch pathway activation and structure or tumors the previous studies found that FKBP14 on extracellular matrix (ECM) synthesis, and the Notch signaling pathway regulation, so we have reason to speculate that FKBP14 may be involved in the process of tumor development. In this study, we examined the expression of FKBP14 in epithelial ovarian cancer tissues also observed at the same time. Targeted expression of FKBP14 silencing on ovarian cancer cell proliferation, cell cycle and apoptosis, migration and invasion effect and other biological characteristics, and to explore its possible mechanism. This study suggests that in epithelial eggs FKBP14 ovarian cancer may be a cancer gene, and may become a potential target for treatment. Objective to study the expression and significance of the first part of FKBP14 in epithelial ovarian carcinoma: to detect the expression of FKBP14 in ovarian cancer tissues and non cancer tissues, to explore the relationship between FKBP14 and ovarian cancer. Methods: 1. by RT-PCR method to detect the expression of 40 cases of ovarian cancer and 40 cases of non cancerous tissues in FKBP14 mRNA, the expression of.2. was used to detect whether there are differences in FKBP14 protein of SP was detected in 60 cases of different pathological types of epithelial ovarian carcinoma. The expression of the situation, in 20 cases of ovarian benign cyst tissues correlation analysis between FKBP14 and epithelial ovarian cancer. Results: epithelial ovarian carcinoma tissues, the expression level of FKBP14 protein and mRNA were significantly higher than that of control group, the difference of expression suggests that FKBP14 may be epithelial A cancer gene of ovarian cancer. Conclusion: FKBP14 may be involved in the process of occurrence and development of epithelial ovarian carcinoma. The second part of the interference suppression of FKBP14 expression on the proliferation and migration of ovarian cancer cells objective to investigate the influence of using RNA interference targeting inhibition of FKBP14 expression in ovarian cancer cell lines SKOV3 and H08910. Observation of gene silencing on the biological behavior of ovarian cancer cells: proliferation, apoptosis and invasion ability, the role of FKBP14 in the pathogenesis of ovarian cancer, as the molecular target for ovarian cancer treatment to provide the theory basis. Methods: 1. using Real-time PCR and Western blot for the detection of five ovarian cancer cell lines: A2780, OVCAR3, FKBP14 protein expression of SKOV3,3A0 and H08910, selected 2 high expression in epithelial ovarian cancer cell lines FKBP14 gene (SKOV3 and HO-8910).2. construction FK Lentiviral vector recombinant BP14 gene by gene chemical synthesis of small interfering siRNA targeting FKBP14 sequence (GACCACTTTCACTGATTAT) and non silencing sequence (CCTAAGGTTAAGTCGCCCTCG), folded into shRNA, cloned into PLKO.1 retroviral vector, and through Lipofectamine 2000 transfection HEK293 cells. After cultured for 48 hours, collect the virus reverse stability turn the target cell to the parental cells and empty vector transfected cells as compared to.3. using CCK8 assay interference group (RNAi), control group (WT group), non interference sequence (NC) proliferation of ovarian cancer cell line.4. Annexin V-FITC/PI double staining flow cytometry to detect interference group (RNAi). The blank control group (WT group), non interference sequence (NC) of ovarian cancer cell line apoptosis and cell cycle changes of.5. by Transwell assay technology, detection of interference group (RNAi), control group (WT), non interference sequence Group.6. (NC) changes in migration and invasion of ovarian cancer cell line Real-time by detecting PCR and Western blot (RNAi), interference group, blank control group (WT group), non interference sequence (NC) expression in ovarian cancer cell line related pathway proteins: E-cadherin, Twistl, MMP2, BCL-2, BAX, capspase3 PCNA,.7. SPSS 13 software was used for data analysis, measurement data with the average standard deviation analysis, independent sample t test for differences between groups. Results: 1. interference group (RNAi) and blank control group the expression of FKBP14 protein in ovarian cancer cells (WT) and non interference group (NC) compared to a decrease of 90%, WT group and NC group had no difference between the expression level of FKBP14 in.2.NC group and WT group have no statistically significant differences between cell proliferation, suggesting that shRNA'interference lentiviral transfection system no cytotoxic effect of.FKBP14 SKOV3 and H08910 stem cells in the rejection group after transfection for 48 of ovarian cancer cells Hours, 72 hours are shown to inhibit.3.FKBP14 shRNA proliferation after transfection significantly, compared with the WT group and NC group, RNAi group showed the percentage of G0/G1 phase increased, the proportion of S phase decreases the apoptosis rate of.RNAi group increased 9 times than in NC group. Cell cycle and apoptosis in NC group and WT group had no difference compared to.4. WT group and NC group, RNAi group, cell proliferation related protein PCNA, anti apoptotic protein Bcl-2 expression decreased significantly, the apoptosis marker protein Caspase3 and pro apoptotic protein Bax expression increased. In the suppression of FKBP14 expression, the ratio of Bax/Bcl-2 significantly increased the migration and invasion of.5. cells in experimental group RNAi cells, invasion, migration rates were lower than WT group and the cells of NC group.6.RNAi group of matrix metalloproteinase MMP2 and EMT inducing factor Twist expression was lower than WT group and NC group, while the epithelial marker E-cadherin was higher than that of WT group and NC group. Conclusion: 1.FKBP14 is involved in the ovarian cancer cell proliferation, apoptosis, migration Shift and invasion process, its silencing can significantly reduce cell proliferation, promote cell apoptosis and decrease the invasion and migration. It suggested that FKBP14 may be a cancer gene in the occurrence and development of ovarian cancer, we suggest FKBP14 may become a potential target for the.2. FKBP14 shRNA gene therapy for ovarian cancer GO/G1 cells through inhibition of cell cycle arrest the proliferation of FKBP14 can promote the invasion and metastasis of ovarian cancer cells by regulating the ratio of Bax/Bcl-2.3. FKBP14 inhibits apoptosis and possible mechanism of regulating epithelial mesenchymal transition (EMT) process and the effect of extracellular matrix (ECM) components.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R737.31

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7 Hopkins L.;Fung Kee Fung M.;王穎;;上皮性卵巢癌進(jìn)展期輔助和補(bǔ)救化療過(guò)程中患者生活質(zhì)量評(píng)估[J];世界核心醫(yī)學(xué)期刊文摘(婦產(chǎn)科學(xué)分冊(cè));2005年11期

8 王鑫;呂杰強(qiáng);朱雪瓊;;胰島素樣生長(zhǎng)因子系統(tǒng)在上皮性卵巢癌中的研究進(jìn)展[J];國(guó)外醫(yī)學(xué).婦產(chǎn)科學(xué)分冊(cè);2006年04期

9 李海玲;任慕蘭;錢(qián)惠勤;;上皮性卵巢癌血管內(nèi)皮生長(zhǎng)因子表達(dá)及微血管密度[J];江蘇醫(yī)藥;2007年01期

10 賀國(guó)麗;;鉑類敏感的復(fù)發(fā)上皮性卵巢癌二次腫瘤細(xì)胞減滅術(shù)的指南和選擇標(biāo)準(zhǔn)[J];國(guó)外醫(yī)學(xué)(婦產(chǎn)科學(xué)分冊(cè));2007年02期

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2 許紅;;Ⅲ期上皮性卵巢癌的治療與預(yù)后分析[A];中國(guó)抗癌協(xié)會(huì)婦科腫瘤專業(yè)委員會(huì)第六次全國(guó)學(xué)術(shù)會(huì)議論文匯編[C];2001年

3 周慧梅;黃惠芳;潘凌亞;沈鏗;吳鳴;楊佳欣;;血清CA125值的變化對(duì)判斷上皮性卵巢癌預(yù)后的臨床價(jià)值[A];中華醫(yī)學(xué)會(huì)第九次全國(guó)婦科腫瘤學(xué)術(shù)會(huì)議論文匯編[C];2006年

4 葉海燕;陳建國(guó);徐嘉文;陳志紅;;has-miRNA let-7a在上皮性卵巢癌中的表達(dá)及其臨床意義[A];中華醫(yī)學(xué)會(huì)第十次全國(guó)婦產(chǎn)科學(xué)術(shù)會(huì)議婦科腫瘤會(huì)場(chǎng)（婦科腫瘤學(xué)組、婦科病理學(xué)組）論文匯編[C];2012年

5 謝敏;李藝;崔恒;;復(fù)發(fā)性上皮性卵巢癌的手術(shù)治療[A];中華醫(yī)學(xué)會(huì)第十次全國(guó)婦產(chǎn)科學(xué)術(shù)會(huì)議婦科腫瘤會(huì)場(chǎng)（婦科腫瘤學(xué)組、婦科病理學(xué)組）論文匯編[C];2012年

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7 郄明蓉;楊小蕓;張崇淑;;28例Ⅳ期及復(fù)發(fā)上皮性卵巢癌的治療選擇與預(yù)后分析[A];中國(guó)抗癌協(xié)會(huì)婦科腫瘤專業(yè)委員會(huì)第七次全國(guó)學(xué)術(shù)會(huì)議論文匯編[C];2003年

8 郄明蓉;鄭艾;楊小蕓;張崇淑;;28例Ⅳ期及復(fù)發(fā)上皮性卵巢癌的治療選擇與預(yù)后分析[A];第八次全國(guó)婦產(chǎn)科學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2004年

9 郄明蓉;張崇淑;鄭艾;楊小蕓;;28例Ⅳ期及復(fù)發(fā)上皮性卵巢癌的治療選擇與預(yù)后分析[A];第八次全國(guó)婦產(chǎn)科學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2004年

10 彭素蓉;王金華;陳小祥;;上皮性卵巢癌系統(tǒng)性腹膜后淋巴結(jié)切除術(shù)及臨床意義——附102例報(bào)告[A];江蘇省抗癌協(xié)會(huì)婦科腫瘤專業(yè)委員會(huì)第四次腫瘤學(xué)術(shù)研討會(huì)暨無(wú)錫市婦產(chǎn)科年會(huì)論文匯編[C];2005年

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2 金佟;CA125/T ELISA法用于CA125升高的良惡性鑒別及其臨床應(yīng)用[D];復(fù)旦大學(xué);2014年

3 嚴(yán)春曉;水通道蛋白亞型AQP5及AQP9在上皮性卵巢癌細(xì)胞增殖與遷移中的功能研究[D];浙江大學(xué);2015年

4 黃宇婷;基于定量多色熒光原位雜交技術(shù)的卵巢癌多基因拷貝數(shù)異常的研究[D];天津醫(yī)科大學(xué);2015年

5 冷若冰;Rac1在上皮性卵巢癌上皮間質(zhì)轉(zhuǎn)化中的作用及機(jī)制的初步研究[D];重慶醫(yī)科大學(xué);2015年

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8 陸萌;FKBP14對(duì)上皮性卵巢癌細(xì)胞增殖和遷移能力的影響[D];南京醫(yī)科大學(xué);2016年

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