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小鼠皮下人乳腺癌移植瘤模型的建立及應(yīng)用

發(fā)布時(shí)間:2018-03-09 10:50

  本文選題:人乳腺癌 切入點(diǎn):異種移植腫瘤動(dòng)物模型 出處:《吉林大學(xué)》2009年碩士論文 論文類型:學(xué)位論文


【摘要】: 人類腫瘤動(dòng)物模型是抗腫瘤藥物藥效學(xué)研究的重要手段。盡管裸鼠和SCID鼠是異種移植性動(dòng)物模型中最常用的實(shí)驗(yàn)動(dòng)物,可用于抗腫瘤藥物的篩選與開發(fā),但不適合腫瘤疫苗的研究。腫瘤疫苗主要通過增強(qiáng)機(jī)體的主動(dòng)免疫達(dá)到治療腫瘤目的。因此,對(duì)于腫瘤疫苗研究,必須建立免疫功能正常的腫瘤模型。MUC1是粘蛋白家族成員,是腫瘤疫苗研究的理想靶分子。MUC1-MBP是本研究組通過基因工程技術(shù)制備的融合蛋白,能特異性誘導(dǎo)小鼠細(xì)胞免疫應(yīng)答和體液免疫應(yīng)答,抑制小鼠Lewis肺癌的生長,但其對(duì)人乳腺癌的作用還不清楚。本研究利用ICR小鼠建立人類乳腺癌皮下移植瘤模型,利用該模型初步探討MUC1-MBP抗人乳腺癌作用。 研究采用ICR小鼠,先經(jīng)X射線和免疫抑制劑處理后使其暫時(shí)處于免疫抑制狀態(tài),然后皮下注入人類乳腺癌細(xì)胞;通過解剖觀察、HE染色和免疫組織化學(xué)染色對(duì)人乳腺癌組織進(jìn)行鑒定;篩選5 Gy X射線照射,每只ICR鼠皮下注射乳腺癌MCF-7細(xì)胞3 X 10~6,FTY-720灌胃4-6天為最佳實(shí)驗(yàn)條件,成功建立小鼠皮下人乳腺癌移植瘤動(dòng)物模型。采用Amylose Resin親和層析獲得純化的MUC1-MBP及MBP蛋白。利用已經(jīng)建立的乳腺癌動(dòng)物模型,觀察MUC1-MBP和MBP抗乳腺癌作用。結(jié)果顯示MUC1-MBP和MBP蛋白免疫對(duì)人乳腺癌的預(yù)防和治療均具有明顯的作用,MUC1-MBP比MBP抗腫瘤作用顯著。 本研究建立的腫瘤模型方法簡(jiǎn)便,成瘤率高,死亡率低,可用于觀察腫瘤疫苗的抗腫瘤活性,為腫瘤免疫治療研究提供新的研究工具。
[Abstract]:Animal models of human tumor is an important means to study efficacy of antitumor drugs. Although nude mice and SCID mice are the most commonly used experimental animal xenograft animal model, can be used for screening and development of anti-tumor drugs, but not suitable for the study of tumor vaccine. The tumor vaccine mainly through enhanced active immune to cancer therapy objective. Therefore, for the study of tumor vaccine, must establish the tumor model.MUC1 normal immune function is a member of the mucin family, is the ideal target molecule.MUC1-MBP of tumor vaccine is the study of fusion protein by genetic engineering technology to prepare the mice cellular immune response and humoral immune responses induced by the specific inhibition of Lewis lung cancer in mice the growth of human breast cancer, but its role is still unclear. This study used ICR mice model of human breast cancer xenograft model, using the model at the beginning The effect of MUC1-MBP on human breast cancer is discussed step by step.
Study on the ICR mice by X ray and immunosuppressive treatment make it temporarily areimmunosuppressed, then subcutaneous injection of human breast cancer cells; through anatomical observation, HE staining and immunohistochemical staining were used to identify breast cancer screening; 5 Gy X rays, each ICR rat subcutaneous injection of breast cancer MCF-7 3 X 10~6 FTY-720 cells, by gavage for 4-6 days for the best experimental conditions, successfully established animal model of mice breast cancer. Using Amylose Resin MUC1-MBP and MBP protein was purified by affinity chromatography. The animal model of breast cancer has been established, MUC1-MBP and MBP to observe the effect of anti breast cancer. The results showed that the prevention and treatment of MUC1-MBP and MBP protein in human breast cancer have obvious effect, MUC1-MBP than the antitumor effect of MBP is significant.
The tumor model established in this study is simple, with high tumorigenicity and low mortality. It can be used to observe the anti-tumor activity of tumor vaccine and provide a new research tool for the research of tumor immunotherapy.

【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2009
【分類號(hào)】:R-332;R737.9

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