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超分子免疫磁珠定量PCR技術的建立及大腸癌轉移相關標志物的探討

發(fā)布時間:2018-07-28 07:41
【摘要】:大腸癌是一種常見惡性腫瘤,發(fā)病率呈逐年上升的趨勢,目前在我國惡性腫瘤中列第五位、在歐美發(fā)達國家列第三位。盡管近些年臨床對大腸癌的診治水平有明顯提高,但大腸癌的病死率仍居高不下,其主要原因是大腸癌較難被早期發(fā)現(xiàn),大部分患者到中晚期才被發(fā)現(xiàn),錯過了手術的最佳時機,復發(fā)和轉移仍是患者死亡的主要原因。因此,闡明大腸癌發(fā)生和轉移機制、發(fā)現(xiàn)新的大腸癌特異性標志物、研究新的標志物檢測技術以及對標志物的作用機制的研究成為目前該領域研究的熱點課題。 大腸癌是在環(huán)境和遺傳因素共同作用下,經(jīng)歷多基因,多步驟、多階段復雜的生物學過程演變而來。大腸癌發(fā)生發(fā)展的經(jīng)典模式是:結直腸上皮細胞增生—腺瘤—非典型增生—癌—轉移癌。在大腸癌發(fā)病過程的不同階段,,腫瘤細胞由于基因組改變產(chǎn)生一些腫瘤相關和/或腫瘤特異的小分子蛋白質/肽,分泌某些細胞因子或相關抗體,這些物質可釋放到血液中,形成大腸癌血清腫瘤標志物。目前已證實有許多癌基因和抑癌基因如環(huán)氧化酶2基因、P53基因等在大腸癌發(fā)病過程中發(fā)生顯著的變化,這些基因產(chǎn)物分泌到血液中,便可成為某些特異大腸癌血清標志物。但由于血清是一種十分復雜和多樣化的液態(tài)基質,盡管大腸癌發(fā)生后可導致血清蛋白在結構和數(shù)量上發(fā)生某些特征性的變化,但由于目前我們對血清蛋白的了解有限,只有很少一部分血清蛋白如癌胚抗原(CEA)、乳糖蛋白系列(CA125,CA199)用于常規(guī)的臨床診斷,而其它大腸癌相關基因產(chǎn)物如環(huán)氧化酶
[Abstract]:Colorectal cancer is a common malignant tumor, the incidence of which is increasing year by year. At present, colorectal cancer ranks fifth among malignant tumors in China and third in developed countries in Europe and America. Although the clinical diagnosis and treatment of colorectal cancer has improved significantly in recent years, the fatality rate of colorectal cancer is still high. The main reason is that colorectal cancer is difficult to be detected early, and most patients are not discovered until the middle and late stages. Missed the optimal time for surgery, recurrence and metastasis is still the main cause of death. Therefore, to clarify the mechanism of colorectal cancer occurrence and metastasis, to find new specific markers of colorectal cancer, to study new marker detection techniques and the mechanism of action of markers has become a hot topic in this field. Colorectal cancer is a complex biological process with multiple genes, steps and stages under the combined action of environment and genetic factors. The classic pattern of colorectal carcinogenesis and progression is colorectal epithelial cell proliferation-adenoma-atypical hyperplasia-carcinoma-metastasis. At different stages of the development of colorectal cancer, tumor cells produce small tumor-related and / or tumor-specific proteins / peptides that secrete cytokines or antibodies that can be released into the blood as a result of genomic changes. The serum tumor markers of colorectal cancer were formed. It has been proved that many oncogenes and tumor suppressor genes such as cyclooxygenase-2 gene and p53 gene have changed significantly in the pathogenesis of colorectal cancer. These gene products secreted into the blood can become some specific colorectal cancer serum markers. However, because the serum is a very complex and diverse liquid matrix, although the occurrence of colorectal cancer can lead to some characteristic changes in the structure and quantity of serum protein, due to the current limited understanding of serum protein, Only a few serum proteins, such as carcinoembryonic antigen (CEA), lactoglycoprotein series (CA125, CA199), are used for routine clinical diagnosis, while other colorectal cancer related gene products such as cyclooxygenase
【學位授予單位】:第一軍醫(yī)大學
【學位級別】:博士
【學位授予年份】:2006
【分類號】:R735.34;R392

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