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Monitoring Gene Expression Profile Changes In Human Pancreatic Cancer Using CDNA Microarray

Posted on:2003-08-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:G JinFull Text:PDF
GTID:1104360092965027Subject:General Surgery
Abstract/Summary:PDF Full Text Request
Pancreatic cancer is the twelveth most common cause of cancer death in China , which is one of the most aggressive human tumors and is virtually incurable. Its incidence and mortality rates are almost identical even though receive the surgical resection and ;radiotherapy and chemical therapy . The 5-year survival rate is approximately 1%, and the median survival time after surgical treatment is 14 months. The etiology of pancreatic cancer is still unknown. There is clearly a need for novel more effective diagnostic and therapeutic methods.Oncogenesis and development of neoplasm is a comlpex multiphase process, which involves overexpression of oncogenes or inactivation of tumor suppresor genes, mutation or depletion of normal genes, pleiotropic effects and immunology function. Nowadays, we believe there are three types of gene anomalies related to pancreatic cancer: ①overexpression or activation of oncogenes, ②inactivation of anti-oncogenes, ③abnormality of mismatch repair genes. The Human Genome Project(HGP) is the most important biology project that has ever been undertaken, it aims to translate the puzzle of life. Today we have finished the sequencing of the human genome. Now we known it is a giant challenge to identify all the estimated 70,000-100,000 genes and their functions. After implementation of HGP, we have understand the genes involving in vital process of life, such as gene expression accommodation, immunology or cell differentiation, which are arrangenment in some "cluster", in which all the members are controled in unity. In the process of oncogenesis, there may exist some different cluster of tumor related genes. It is important to find such unique gene clusters involving in carcinogenesis , invasion and metastasis processing. current focus of molecular profiling is the large-scale analysis of geneexpression using new DNA array technology. This powerful technology is being used to study many biological processes. The experimental or clinical goals range from insights into pathogenesis, cancer diagnosis and prediction of clinical outcome to identification of therapeutic targets. In this way, DNA array analysis is providing the first glimpse of a substantial improvement in our understanding of cancer biology and diagnosis.Identifying and sequencing a set of full-length cDNAs that represent all human genes would help in both gene discovery and functional analysis. Constructing a high-quality cDNA library with good representation of full-length cDNAs is very important for full-length cDNA cloning. Nine patients were screened for expression of 4,096 human genes. The hybridizations for each individual were repeated twice. According the results of hybridization to the microarray, 184 genes , whose ratios of Cy5/Cy3 were higher than 2.0 or lower than 0.5, were screened out after Nine couples of hybridizations. In the cancerous tissue 87 of them showed higher expression and 97 lower. There include 11 novel human gene. These differentially expressed genes are always involved in the physiological processes such as signal transduction, apoptosis and cell cycle, etc. The overexpressed genes in pancreatic cancers include: ①Oncogenes; ②cell-cycle-related gene; ③signal-transduction-related genes;④extracellular matrix and skeleton related genes; ⑤transcription factors . The downexpressed genes in pancreatic cancer include: ①tumor suppression gene; ②DNA damage and repair related genes; ③apoptosis-related genes; ④cell-cycle-related genes; ⑤signal-transduction-related genes ; ⑥aladherent-molecule-related gene;and DNA transcription related genes. The study shows that pancreatic cancer are much more active than normal cells in many steps of multiple pathways of signal transduction. The stable state of normal somatic cells depends on the dynamic equilibrium of apoptosis and proliferation. apoptosis-related gene was down-expressed in cancer . In pancreatic cancer tissue, many metastasis related genes, such as ECM and cell skeleton related gene showed high expression level. T...
Keywords/Search Tags:pancreatic neoplasms, Gene, cDNA microarray
PDF Full Text Request
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