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大腸癌肝轉(zhuǎn)移動(dòng)物模型建立方法的改進(jìn)及評(píng)價(jià)

發(fā)布時(shí)間:2019-03-31 01:15
【摘要】:背景和目的:結(jié)直腸癌(CRC)是一種常見的嚴(yán)重威脅人類生命健康的惡性腫瘤。遠(yuǎn)處轉(zhuǎn)移和浸潤性生長是人類結(jié)直腸癌致死的主要原因,Cady等通過對(duì)罹患結(jié)腸癌死亡的患者進(jìn)行尸檢證實(shí),其中約60%~70%的患者存在肝臟轉(zhuǎn)移。因此,建立一種易于觀察、生物學(xué)行為更為接近于臨床表現(xiàn)的結(jié)直腸癌肝轉(zhuǎn)移動(dòng)物模型,對(duì)于了解結(jié)直腸癌生長、演進(jìn)、轉(zhuǎn)移的過程及正確評(píng)價(jià)各種治療方案的療效等都具有重要意義。目前現(xiàn)有的大腸癌肝轉(zhuǎn)移模型建模周期較長,成功率較低,模型不穩(wěn)定。我們針對(duì)這一缺點(diǎn)進(jìn)行模型改良,從而建立高轉(zhuǎn)移、高浸潤、穩(wěn)定的模型。方法:以近交系BALB/c小鼠為研究對(duì)象,隨機(jī)分為兩組,第一組選取鼠大腸癌細(xì)胞株CT26經(jīng)皮下傳3代后制成細(xì)胞懸液,將此懸液接種到小鼠脾臟被膜下,5min后切去脾臟。另一組將CT26細(xì)胞懸液直接接種于BALB/c小鼠脾臟內(nèi),5min后切除脾臟。觀察兩組小鼠成瘤情況、肝臟轉(zhuǎn)移率、淋巴轉(zhuǎn)移率、肺轉(zhuǎn)移率及生存期,并對(duì)2種模型進(jìn)行初步比較。留肝臟標(biāo)本做病理檢查。結(jié)果用spss17.0做統(tǒng)計(jì)學(xué)分析。結(jié)果:術(shù)后第12d實(shí)驗(yàn)組肝臟轉(zhuǎn)移率(75%)高于對(duì)照組(28.6%)(P0.05);術(shù)后第15d及21d后實(shí)驗(yàn)組肝臟轉(zhuǎn)移率(93.7%、100%)也明顯高于對(duì)照組(50%、66.7%)(P0.05),但肺臟轉(zhuǎn)移率及淋巴轉(zhuǎn)移率(12.5%、25%;26.7%、53.3%)與對(duì)照組(0、6.25%;0%、16.7%)相比無明顯差異(PPP0.05)。平均生存期實(shí)驗(yàn)組為(23.56±3.17)d,對(duì)照組為(28.14土4.19)d。兩組無明顯統(tǒng)計(jì)學(xué)差別。病理結(jié)果證實(shí)肝轉(zhuǎn)移腫瘤符合典型的低分化腺癌特征。結(jié)論:CT26細(xì)胞經(jīng)小鼠皮下傳代后建模比傳統(tǒng)建模方法成瘤時(shí)間更短,轉(zhuǎn)移率更高。
[Abstract]:Background and objective: colorectal cancer (CRC) is a common malignant tumor which is a serious threat to human life and health. Distant metastasis and invasive growth are the main causes of death in human colorectal cancer. Cady et al confirmed liver metastasis in about 60% of the patients who died of colon cancer by autopsy. Therefore, in order to understand the growth and progression of colorectal cancer, an animal model of liver metastasis of colorectal cancer is established, which is easy to observe and the biological behavior is more similar to the clinical manifestation. The process of metastasis and the correct evaluation of therapeutic effects are of great significance. At present, the current models of liver metastasis from colorectal cancer have a long period of modeling, a low success rate and unstable models. We improve the model to build a model with high metastasis, high infiltration and stability. Methods: inbred BALB/c mice were randomly divided into two groups. In the first group, a mouse colorectal cancer cell line CT26 was subcutaneously propagated for 3 generations to make a cell suspension. The suspension was inoculated under the membrane of the spleen of mice, and the spleen was cut off after 5min. In the other group, the CT26 cell suspension was inoculated directly into the spleen of BALB/c mice, and the spleen was resected after 5min. The tumorigenesis, liver metastasis rate, lymph node metastasis rate, lung metastasis rate and survival time of the two groups were observed. Liver specimens were left for pathological examination. Results spss17.0 was used for statistical analysis. Results: the liver metastasis rate in the experimental group (75%) was higher than that in the control group (28.6%) on the 12th day after operation (P0.05). The liver metastasis rate in the experimental group (93.7%, 100%) was significantly higher than that in the control group (50%, 66.7%) (P0.05), but the lung metastasis rate and lymph node metastasis rate (12.5%, 25%) were significantly higher than those in the control group (P0.05). There was no significant difference (PPP0.05) between 26.7%, 53.3% and the control group (0,6.25%, 16.7%). The mean survival time was (23.56 鹵3.17) days in the experimental group and (28.14 鹵4.19) d in the control group. There was no statistical difference between the two groups. The pathological results showed that the metastatic liver tumors were in accordance with the typical features of poorly differentiated adenocarcinoma. Conclusion: the time of tumorigenesis and metastasis rate of CT26 cells after subcutaneously passage is shorter and higher than that of traditional modeling methods.
【學(xué)位授予單位】:新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2011
【分類號(hào)】:R-332

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