本文選題：宮頸癌 + 神經(jīng)營養(yǎng)因子�。� 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：神經(jīng)營養(yǎng)因子(neurotrophin,NT)最早發(fā)現(xiàn)于神經(jīng)系統(tǒng),參與神經(jīng)細(xì)胞的生長和分化,NT由神經(jīng)生長因子(nerve growth factor,NGF)、腦源性神經(jīng)營養(yǎng)因子(brain-derived neurotrophic factor,BDNF)和NT-3、NT-4/5以及源自哺乳動物的NT-6和NT-7組成,目前發(fā)現(xiàn)的NT受體有兩類,即低親和力受體P75受體及高親和力受體酪氨酸激酶受體(Tyrosine kinase receptor,Trk),Trk可分為3種類型,即TrkA、TrkB和TrkC,它們選擇性地與不同的NT特異性結(jié)合,兩類受體常在同一神經(jīng)元同時表達(dá),共同調(diào)節(jié)神經(jīng)元對NT的反應(yīng)。近年來,越來越多的研究表明神經(jīng)營養(yǎng)因子及其受體與腫瘤的生長相關(guān),包括促進(jìn)腫瘤細(xì)胞增值,腫瘤細(xì)胞生存和浸潤,對乳腺癌、卵巢癌、前列腺癌、大腸癌等的研究均證實(shí)了上述觀點(diǎn),而有關(guān)神經(jīng)營養(yǎng)因子及其受體在宮頸癌中的研究甚少,已有的研究尚不全面,納入的病例數(shù)有限,因此本研究主要對神經(jīng)營養(yǎng)因子及其受體在宮頸鱗癌癌灶中的表達(dá)進(jìn)行定性定量研究,并分析不同觀察指標(biāo)之間的關(guān)系,并進(jìn)一步推斷其在宮頸鱗癌的發(fā)生發(fā)展中的作用,為后續(xù)對宮頸癌發(fā)生機(jī)制的研究提供方向。第一章神經(jīng)營養(yǎng)因子及其受體在宮頸鱗癌及正常宮頸中的表達(dá)第一節(jié)神經(jīng)營養(yǎng)因子及其受體在正常宮頸中的表達(dá)[目的]探討神經(jīng)營養(yǎng)因子及其受體在正常宮頸組織中表達(dá)的定性定量情況[方法]免疫組化,生物體視學(xué)[結(jié)果](1)NGF僅表達(dá)于正常宮頸上皮的基底層細(xì)胞,為核表達(dá),呈線狀分布,表達(dá)量平均光密度值為0.0347±0.0567;BDNF表達(dá)均勻分布于正常宮頸上皮全層,為細(xì)胞膜及胞漿的共表達(dá),表達(dá)量平均光密度值為0.2560±0.0992;P75在宮頸上皮的分布呈由基底細(xì)胞層至角化層依次遞減趨勢,為單純細(xì)胞膜表達(dá),表達(dá)量平均光密度值為0.0482±0.0239;TrkA及TrkB均勻分布于正常宮頸上皮細(xì)胞全層,呈細(xì)胞核及胞漿的共表達(dá),表達(dá)量平均光密度值分別為0.0506±0.0390、0.1199±0.0390;(2)宮頸基質(zhì)中未見神經(jīng)營養(yǎng)因子及受體表達(dá)陽性的相關(guān)結(jié)構(gòu);[結(jié)論]神經(jīng)營養(yǎng)因子及其受體參與了正常宮頸上皮細(xì)胞的生長,第二節(jié)神經(jīng)營養(yǎng)因子及其受體在ⅠB1-ⅡB期宮頸鱗癌中的表達(dá)[目的]探討神經(jīng)營養(yǎng)因子及其受體在ⅠB1-ⅡB期宮頸鱗癌組織中表達(dá)的定性定量情況[方法]免疫組化,免疫熒光,生物體視學(xué)[結(jié)果](1)NGF主要定位于癌細(xì)胞的細(xì)胞核,陽性率為92.4%,表達(dá)量與正常宮頸上皮細(xì)胞中的表達(dá)量之間差異無統(tǒng)計學(xué)意義(0.0321±0.0254:0.0347±0.0567,t=-0.260,P0.05);BDNF及P75均主要定位于細(xì)胞膜,陽性率均為100%,相比于正常宮頸上皮細(xì)胞,前者表達(dá)量低(0.1409±0.0550:0.2560±0.0992,t=-4.421,P0.05),后者表達(dá)量高(0.1072±0.0694:0.0482±0.0239,t=6.797,P0.05);TrkA主要定位于胞漿,陽性表達(dá)率為96.8%,TrkB主要為膜漿共表達(dá),陽性表達(dá)率為94.4%,相比于正常宮頸上皮細(xì)胞,前者表達(dá)量高(0.0844±0.0658:0.0506±0.0390,t=6.797,P0.05),后者表達(dá)量低(0.0421±0.0334:0.1199±0.0390,t=-4.421,P0.05);(2)神經(jīng)營養(yǎng)因子及其特異性受體在宮頸鱗癌細(xì)胞中存在共表達(dá)的關(guān)系;(3)在宮頸鱗癌癌灶中,可見P75陽性神經(jīng)纖維,陽性率為50.8%(63/124),TrkA及TrkB可見表達(dá)于癌灶內(nèi)的彈性動脈管壁或脈管的內(nèi)皮細(xì)胞,未見BDNF及NGF在癌灶間質(zhì)的表達(dá);(4)宮頸鱗癌中BDNF與TrkB、P75與TrkA、TrkA與TrkB表達(dá)量呈正相關(guān)關(guān)系(r=0.294,P0.05)、(r=0.452,P0.05)、(r=0.452,P0.05),其余各神經(jīng)營養(yǎng)因子及受體表達(dá)量之間無相關(guān)關(guān)系。[結(jié)論](1)神經(jīng)營養(yǎng)因子及其受體的表達(dá)量變化與宮頸鱗癌的發(fā)生有關(guān),且各因子表達(dá)量之間存在相互調(diào)節(jié)的關(guān)系,共同表達(dá)于腫瘤細(xì)胞內(nèi),促進(jìn)腫瘤細(xì)胞的生長(2)癌灶間質(zhì)可見神經(jīng)營養(yǎng)因子受體表達(dá)陽性的相關(guān)組織結(jié)構(gòu),表明神經(jīng)營養(yǎng)因子受體可能影響腫瘤生長微環(huán)境。第二章宮頸鱗癌癌灶中各神經(jīng)營養(yǎng)因子表達(dá)量及表達(dá)位置與腫瘤分期的關(guān)系[目的]研究神經(jīng)營養(yǎng)因子及其受體的定性定量表達(dá)與分期的關(guān)系[方法]采用spearman秩相關(guān)、兩個獨(dú)立樣本比較的Wilcoxon秩和檢驗(yàn)、及單因素方差分析對納入的臨床病理指標(biāo)與實(shí)驗(yàn)結(jié)果進(jìn)行分析比較[結(jié)果](1)表達(dá)位置與分期:BDNF及P75膜漿共表達(dá)組分期均高于單純膜表達(dá)組(X~2=22.841,P0.05)、(X~2=23.442,P0.05),其余因子及受體表達(dá)位置在各分期之間無差異;(2)表達(dá)量與分期:NGF表達(dá)量在ⅠB1-ⅡB期之間存在差異(F=5.303,P0.05),ⅡA2 期宮頸鱗癌表達(dá)量最高(0.0571 ±0.0281),且ⅠB1-ⅡA2期表達(dá)量與分期呈上升趨勢,其余因子及受體表達(dá)量在各分期之間無差異;(3)P75受體與TrkA受體的表達(dá)量之比與分期呈負(fù)相關(guān)關(guān)系(r=-0.257,P0.05)。[結(jié)論]NGF的表達(dá)量、P75與TrkA受體的表達(dá)量之比、BDNF及P75的表達(dá)位置與宮頸鱗癌的進(jìn)展相關(guān)
[Abstract]:Neurotrophin (NT) was first found in the nervous system and involved in the growth and differentiation of nerve cells. NT was composed of nerve growth factor (NGF), brain-derived neurotrophic factor, BDNF) and NT-3, and derived from mammals. There are two types, the low affinity receptor P75 receptor and the high affinity receptor tyrosine kinase receptor (Tyrosine kinase receptor, Trk), and Trk can be divided into 3 types, namely TrkA, TrkB and TrkC, which selectively bind to different NT specifically. The two types of receptors are often expressed at the same time in the same neuron and jointly regulate the reaction of neurons to NT. In recent years, the more The more studies have shown that neurotrophic factors and their receptors are associated with tumor growth, including the promotion of tumor cell proliferation, tumor cell survival and infiltration, and studies on breast, ovarian, prostate and colorectal cancer, which have been confirmed, and there are few studies on neurotrophic factors and their receptors in cervical cancer. The study is not comprehensive and the number of cases included is limited. Therefore, this study mainly studies the expression of neurotrophic factor and its receptor in cervical squamous cell carcinoma, and analyzes the relationship between different observation indexes, and further infer its role in the development of cervical squamous cell carcinoma, in order to follow up the mechanism of cervical cancer. The expression of neurotrophic factor and its receptor in cervical squamous cell carcinoma and normal cervix; the expression of the first neurotrophic factor and its receptor in the normal cervix [Objective] to investigate the qualitative and quantitative analysis of neurotrophic factors and their receptors in normal cervical tissues. Results: (1) the expression of NGF was only expressed in the basal layer cells of normal cervical epithelium, which was nuclear expression and linear distribution, and the average density of the expression was 0.0347 + 0.0567. The expression of BDNF was evenly distributed in the whole layer of normal cervical epithelium and co expressed in the cell membrane and cytoplasm. The average density of the expression was 0.2560 + 0.0992, and the distribution of P75 in the cervical epithelium was presented. The basal cell layer to keratinized layer descended in turn, which was a simple cell membrane expression, and the average density of the expression was 0.0482 + 0.0239. TrkA and TrkB were evenly distributed in the whole layer of normal cervical epithelial cells, presenting the co expression of the nucleus and cytoplasm, and the mean optical density of the expression was 0.0506 + 0.0390,0.1199 + 0.0390, respectively. (2) the cervical matrix was not found. Neurotrophic factor and receptor expression related structure; [Conclusion] neurotrophic factor and its receptor are involved in the growth of normal cervical epithelial cells. The expression of second ganglion neurotrophic factor and its receptor in stage I B1- II B cervical squamous cell carcinoma (objective) to investigate the expression of neurotrophic factor and its receptor in stage I B1- II B cervical squamous cell carcinoma The qualitative and quantitative situation [method], immunofluorescence, immunofluorescence, and biological vision (1) NGF were mainly located in the nucleus of cancer cells, the positive rate was 92.4%. There was no significant difference between the expression and the expression of normal cervical epithelial cells (0.0321 + 0.0254: 0.0347 + 0.0567, t=-0.260, P0.05); BDNF and P75 were mainly located in the cells. The positive rate of cell membrane was 100%. Compared to normal cervical epithelial cells, the expression of the former was low (0.1409 + 0.0550:0.2560 + 0.0992, t=-4.421, P0.05), the latter was high (0.1072 + 0.0694:0.0482 + 0.0239, t=6.797, P0.05); TrkA was mainly located in the cytoplasm, the positive expression rate was 96.8%, TrkB was mainly expressed in membrane plasma, and the positive expression rate was 94.4%. Compared to normal cervical epithelial cells, the expression of the former was high (0.0844 + 0.0658:0.0506 + 0.0390, t=6.797, P0.05), the latter was low (0.0421 + 0.0334:0.1199 + 0.0390, t=-4.421, P0.05), and (2) the relationship between neurotrophic factor and its specific receptor in cervical squamous cell carcinoma cells; (3) in the squamous carcinoma of cervix, the P75 positive God was found. The positive rate was 50.8% (63/124), TrkA and TrkB were found in the endothelial cells of the elastic artery wall or pulse tube in the cancer, and no expression of BDNF and NGF in the cancer range; (4) BDNF and TrkB, P75 and TrkA, TrkA and TrkB expression in cervical squamous cell carcinoma were positively correlated (r=0.294,), and the rest of the gods. There is no correlation between the operating factor and the expression of the receptor. [Conclusion] (1) the expression of neurotrophic factor and its receptor is related to the occurrence of squamous cell carcinoma of the cervix, and there is a relationship between the expression of each factor and the expression of each factor in the tumor cells to promote the growth of cancer cells (2) the neurotrophic factor of the cancer range is visible. The related tissue structure of receptor positive expression indicates that neurotrophic factor receptor may affect the microenvironment of tumor growth. Second the relationship between the expression of neurotrophic factors and the expression position of neurotrophic factors in the squamous cell carcinoma of the cervix and the relationship between the tumor staging and the relationship [Objective] to study the relationship between the quantitative expression of neurotrophic factor and its receptor and its staging The Spearman rank correlation, the Wilcoxon rank sum test of two independent samples, and the single factor analysis of variance analysis were used to analyze the included clinicopathological indexes and experimental results. [results] (1) the expression position and staging of BDNF and P75 membrane plasma co expression group were higher than that of the simple membrane surface (X~2=22.841, P0.05), (X~2=23.442, P0.05), and the other factors. There was no difference in the expression position between the substages and the substages. (2) the expression amount and the stage of the expression of NGF were different (F=5.303, P0.05), and the expression of cervical squamous cell carcinoma in stage II A2 was the highest (0.0571 + 0.0281), and the expression of I B1- II A2 stage was on the rise and the expression of the other factors and receptors had no difference between the stages. (3) the ratio of P75 receptor to TrkA receptor is negatively correlated with staging (r=-0.257, P0.05). [conclusion the expression of]NGF, the ratio of P75 to TrkA receptor, the expression of BDNF and P75, is related to the progression of squamous cell carcinoma of the cervix.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.33

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