本文選題：孤兒核受體　切入點(diǎn)：Nurr1　出處：《復(fù)旦大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：胃癌、結(jié)腸癌均為臨床上最常見的惡性腫瘤之一。在全球范圍內(nèi),胃癌、結(jié)腸癌的發(fā)病率和死亡率均較高。近年來,隨著人民生活水平的不斷提高,飲食習(xí)慣和飲食結(jié)構(gòu)的改變,特別是冰箱的廣泛應(yīng)用,胃癌的發(fā)病率有所下降,而結(jié)腸癌的發(fā)病率卻在我國呈逐年上升趨勢(shì)。胃癌、結(jié)腸癌還可以引起梗阻、穿孔等嚴(yán)重的并發(fā)癥,即使經(jīng)過常規(guī)放化療、手術(shù)等治療,但腫瘤病人,尤其是晚期病人的生存率仍不夠理想。因此,加大對(duì)胃癌、結(jié)腸癌的基礎(chǔ)研究,深入探討其發(fā)生、發(fā)展及浸潤轉(zhuǎn)移的機(jī)理,顯得尤為迫切重要。孤兒核受體家族為即早基因,屬于類固醇類激素、甲狀腺激素核受體超家族,主要表達(dá)在中樞神經(jīng)系統(tǒng)內(nèi),可被環(huán)境中的刺激信號(hào)快速誘導(dǎo),作為非配體依賴的轉(zhuǎn)錄因子和早期反應(yīng)基因行使功能,與胚胎發(fā)育早期神經(jīng)系統(tǒng)的發(fā)育和分化密切相關(guān)。近年來,對(duì)孤兒核受體家族及其成員的研究,是分子生物學(xué)、臨床醫(yī)學(xué)以及藥理學(xué)等眾多相關(guān)領(lǐng)域的研究熱點(diǎn)。目前已經(jīng)發(fā)現(xiàn)的孤兒核受體家族成員包括Nurr1、Nur77和NOR-1三種基因。他們除了共同參與調(diào)節(jié)基因表達(dá)及神經(jīng)細(xì)胞的生存、發(fā)展、分化以外,在各自的分布器官／組織中亦發(fā)揮著重要作用。近幾年的研究表明,孤兒核受體家族成員不僅在正常機(jī)體組織中有所表達(dá),而且在腫瘤的發(fā)生、發(fā)展過程中有著重要作用。例如,Nur77在細(xì)胞核內(nèi)有促進(jìn)胃癌細(xì)胞生長的作用。當(dāng)受到某種機(jī)制的調(diào)控時(shí),其靶點(diǎn)會(huì)轉(zhuǎn)移至線粒體,這會(huì)改變Nur77的促生長表型,最終觸發(fā)細(xì)胞色素C的釋放,導(dǎo)致細(xì)胞凋亡；NOR-1可使BP17基因表達(dá)上調(diào),纖維細(xì)胞生長因子結(jié)合蛋白分泌增多而促進(jìn)肝癌血管生成。而Nurr1在胃癌、結(jié)腸癌中的作用尚未有明確的定論。我們利用免疫組織化學(xué)方法,對(duì)孤兒核受體家族成員Nurr1在胃癌、結(jié)腸癌中的表達(dá)情況及其與腫瘤生物學(xué)行為和患者預(yù)后之間的關(guān)系、作用機(jī)制進(jìn)行研究,為胃癌結(jié)腸癌治療藥物和轉(zhuǎn)移復(fù)發(fā)機(jī)制的研究提供可能的靶點(diǎn)。材料與方法：對(duì)本院2008年進(jìn)行根治性手術(shù)切除的胃癌、結(jié)腸癌病人進(jìn)行隨訪,從中選取具有完整臨床及隨訪資料的病例,其中胃癌病人78例,結(jié)腸癌病人76例。我們使用免疫組織化學(xué)(SABC)方法對(duì)所選病人的石蠟切片進(jìn)行染色,然后對(duì)染色結(jié)果統(tǒng)計(jì)分析。具體而言,選取4例正常胃組織中的染色情況,以此作為基準(zhǔn)進(jìn)而觀察Nurr1在胃癌及癌周正常組織中的表達(dá)強(qiáng)度。選取3例結(jié)腸正常組織中的染色情況,以此為對(duì)照觀察結(jié)腸癌、癌周組織中Nurr1的表達(dá)情況。然后從腫瘤分化程度、TNM分期等方面對(duì)各組病例進(jìn)行分類,統(tǒng)計(jì)Nurr1免疫組化結(jié)果與胃癌、結(jié)腸癌的分化程度、TNM分期等的關(guān)系,并進(jìn)一步分析Nurr1的表達(dá)強(qiáng)度與患者生存率之間有無相關(guān)性。結(jié)果：Nurr1在正常胃粘膜細(xì)胞及癌周組織中表達(dá)較弱；在胃癌細(xì)胞中有且表達(dá)較強(qiáng),其表達(dá)與腫瘤的分期呈正相關(guān)；Nurr1在伴有淋巴結(jié)或遠(yuǎn)處轉(zhuǎn)移、TNM晚期的腫瘤中表達(dá)較強(qiáng)；Nurr1表達(dá)越強(qiáng)的胃癌患者預(yù)后越差。Nurr1在正常結(jié)腸細(xì)胞及癌周組織中表達(dá)較弱；在結(jié)腸癌細(xì)胞中有且表達(dá)較強(qiáng),其表達(dá)與腫瘤的分期呈正相關(guān)；Nurr1在伴有淋巴結(jié)或遠(yuǎn)處轉(zhuǎn)移、TNM晚期的腫瘤中表達(dá)較強(qiáng)；Nurr1表達(dá)越強(qiáng)的結(jié)腸癌患者預(yù)后越差。結(jié)論：Nurr1在胃癌、結(jié)腸癌中表達(dá)較高,其表達(dá)強(qiáng)度與腫瘤的淋巴結(jié)轉(zhuǎn)移情況,分期等生物學(xué)行為之間存在顯著正相關(guān),Nurr1在胃癌、結(jié)腸癌中的表達(dá)與患者的預(yù)后有關(guān),表達(dá)越高,其預(yù)后越差。
[Abstract]:Objective: gastric cancer, colon cancer is one of the most common malignant tumors. Clinical gastric cancer worldwide, colorectal cancer incidence and mortality are high. In recent years, with the improvement of people's life, eating habits and diet changes, especially the wide application of the refrigerator, the incidence of gastric cancer decreased, and the incidence of colon cancer in China has increased year by year. Gastric cancer, colon cancer can also cause obstruction, perforation and other serious complications, even after conventional chemotherapy, surgery and other treatment, but the survival rate of cancer patients, especially the patients in advanced stage is still not ideal. Therefore, increase on gastric cancer. Basic research of colorectal cancer, to explore its occurrence, development and mechanism of invasion and metastasis, is particularly important. For early gene orphan nuclear receptor family, which belongs to the steroid hormone, thyroid hormone nuclear receptor superfamily, Lord To express in the central nervous system, can be rapidly induced stimuli in the environment, as a ligand dependent transcription factor genes and early response function, and is closely related to early embryonic development and differentiation of the nervous system. In recent years, the research on the orphan nuclear receptor family and its members, molecular biology, research hotspot clinical medicine and pharmacology and many other related fields. It was found that the orphan nuclear receptor family members including Nurr1, Nur77 and NOR-1 three genes. In addition to their outside might participate in the regulation of gene expression and neuronal survival, development, differentiation, also plays an important role in the distribution of organ / tissue in their recent research. Years indicated that the orphan nuclear receptor family members not only in normal body tissues, and in tumor occurrence, development process plays an important role. For example, Nur7 7 in the nucleus has a function of promoting the growth of gastric cancer cells. When regulated by a mechanism, the target will be transferred to the mitochondria, which will change the growth phenotype of Nur77, eventually trigger the release of cytochrome C, leading to apoptosis; NOR-1 BP17 gene expression of fibroblast growth factor binding protein secretion increased angiogenesis and Nurr1 in gastric cancer, colon cancer has not been clarified. We use immunohistochemical method, the orphan nuclear receptor family member Nurr1 in gastric cancer, the relationship between the expression of colorectal carcinoma and its biological behavior and prognosis of tumors, study mechanism, provide a possible target for cancer therapeutics research and metastasis mechanism of node in gastric cancer. Materials and methods: in our hospital in 2008 for radical resection of gastric cancer and colon cancer patients. Were selected with complete clinical and follow-up data from cases, including 78 cases of patients with gastric cancer, 76 cases of colon cancer patients. We use immunohistochemistry (SABC) method of paraffin sections of selected patients were stained, and then statistical analysis. The staining results and specific staining, we selected 4 cases of normal stomach in the organization, as a benchmark and then observe the expression intensity of Nurr1 in gastric cancer and adjacent normal tissues were selected. 3 cases of normal colon tissues, as observed in colon cancer, the expression of Nurr1 in paracancerous tissues. Then the degree of tumor differentiation, TNM staging and classification of patients in each group Nurr1, the statistical results of immunohistochemistry and differentiation of gastric cancer, colon cancer, TNM staging, and further analysis there is no correlation between the expression intensity and the survival rate of Nurr1. Results: Nurr1 in normal The weak expression of gastric mucosal cells and cancerous peripheral tissue; and strong expression in gastric cancer cells, its expression stage was positively associated with tumor metastasis; Nurr1 in lymph node or distant, the strong expression of TNM in advanced tumor; the expression of Nurr1 in patients with gastric cancer prognosis is worse.Nurr1 weaker expression in normal colon cells and carcinoma; and strong expression in colon cancer cells, its expression stage was positively associated with tumor metastasis; Nurr1 in lymph node or distant, the strong expression of TNM advanced tumors; the more expression of Nurr1 in colon cancer patients with worse prognosis. Conclusion: high expression of Nurr1 in gastric cancer, colon cancer in its expression and lymph node metastasis, there was significant positive correlation between the stage of the biological behavior of Nurr1 in gastric cancer, colon cancer and expression in the prognosis of the patients, the higher the expression, its prognosis is Poor.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R735.2;R735.35

【共引文獻(xiàn)】

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