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Development And Application Of Tumor Metastasis-associated Gene CDNA Microarray

Posted on:2003-06-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q SunFull Text:PDF
GTID:1104360092965553Subject:Pathology
Abstract/Summary:PDF Full Text Request
The metastasis is the major character of cancer and is the main cause which affects the therapeutic efficacy and leads to the death of cancer patients. Working out the metastasis-associated factors and finding out the preventive and therapeutic methods become the most urgent.Metastasis is a multiple-step process that begins with cancer cells leaving the primary tumor site and ends with relocating in a remote organ. A tumor cell must detach from the primary tumor, migrate through the basement membrane and extracellular matrix, invade into vessels and travel in the circulation to the new site, before reattachment, extravasation, and develop a new focus and neovascularization. Metastatic cascade is controled by many specific genes. They are either up-regulated or down-regulated, interacted or interfered, and eventually influence the biological properties of cancer cells.There are hundreds of genes that were reported to involve in the metastatic process. They may stimulate cancer cell motility, participatein specific cell-cell and cell- extracellular matrix interactions, degrade the matrix and ease tumor cell migration and induce the angiogenesis. All of them are contributed to the metastasis.However, most of the detecting methods can only find one or several genes. It is difficult to know which are the specific genes that cause metastasis and their relationships to each other. But the cDNA microarray made it possible. It is a systematic, rapid, convenient, accurate and high throughput method that can detect the genes. By this way, we can simultaneously evaluate lots of genes that could be from the same tissues or different ones in a single experiment. We can also identify new genes and genetic changes, analyse complex disease and their associated genes, and find out the distribution as well as their quantity. All of those are unparalleled superiority.Up to now, there are no reports in regard to make metastasis related gene cDNA microarray. We have looked for the known metastasis-associated human genes, designed and developed a cDNA microarray that consists of most of the known metastasis related genes, and optimized its technical procedures. It showed analytic pots with uniform background and clear signal using ScanArrayTM 4000. The optimized method was highly sensitive and utility for detecting gene expression profile. Then we obtained the specific mRNA expression profiles of the colorectal cancer and the lung cancer. There are 30 genes showing consistently upregulated and downregulated in those cases. These genes include motility factors, adhesion molecules,extracellular matrix-degrading enzymes, oncogenes, tumor- suppressor genes, apoptosis and anti-apoptosis genes, tumor angiogenesis factors and signal transduction factors, etc. It is significant for screening the specific genes of cancer metastasis and understanding the molecular mechanism of the process.
Keywords/Search Tags:Metastasis related human genes, cDNA microarray, Development and Optimization, Colorectal cancer, Lung cancer, Gene expression profile
PDF Full Text Request
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