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The Contributional Effect Of The Inflammationary Microenviroment On The Laryngeal Squamous Cell Cancer

Posted on:2009-09-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:L LiFull Text:PDF
GTID:1114360245463465Subject:Otolaryngology
Abstract/Summary:PDF Full Text Request
Background: There are a lot of inflammatory cells in the tumor tissue, so Virchow first predicted that cancer might be originated from the lesion of inflammation. And recent evidence indicates a new hypothesis that the network among the inflammatory cell and the proinflammatory factors may also involve in the tumor development. In the advanced tumor, the inflammatory environment protects the tumor cell from the attack of the host immune system.There are many similar characters between the inflammation and tumor in the tisse and molecular level, including the inflammatory cells and inflammatory mediator, and even some pathological process. The inflammatory environment is composed by varieties of TAM (tumor associated macrophage) and DC (dentictic cell) and inflammation-related cytokines e.g. interlein, interferon and chemtants. But the mechanisms of the tumor inflammatory environment under the tumor development are not classified yet, especially the its role as whole.To investigate the expression profile of 128 inflammation related genes in laryngeal squamous cell tumor by functional gene chip technology and to probe into the role of correlative genes in relationship between tumor and inflammation and also the immune pathogenesis of laryngeal squamous cell cancer. And next we investigate mRNA and protein expression of MCP-3 (monocyte chemotactic protein-3) in the laryngeal squamous cell cancer tissue, so as to classify its function in the tumor development.Methods: The total RNAs were respectively extracted from two pair samples of laryngeal tumor and the normal tissue around the tumor, and then were reversely transcribed to cDNAs, then synthesized to cRNAs. The cRNAs labeled with the hybridization probes. The probes were then hybridized with four pieces of inflammation related genes associated gene chip. It was chemiluminescent detected and the images were scanned by laser scanner and the acquired image was analyzed by software. Immunohistochemical staining and RT-PCR, and western blot were performed on the sample from the laryngeal tumor suffered, including both tumor and the normal tissue nearby.Results: 40 genes were differently expressed in inflammation related gene profile of laryngeal tumor, among which 22 genes were upregulated and 18 genes were down regulated. 13 genes were shown differential expression in both chips with 10 upregulated genes and 3 downregulated genes. The differentially expressed genes mostly involved in chemokines and their receptors, interleukine and their receptors and TNF. RT-PCR: all the tumor tissue were founded to be higher expression of MCP-3 according to the clinic stage(t=1.875 , p=0.047) compared with the normal tissue(t=2.671 , p=0.014). Western Blot: all the tumor tissue were founded to be higher expression of MCP-3 according to the clinic stage (t=1.654, p=0.013) compares with the normal tissue (t=2.943, p=0.004). Immunohistochemical staining: positive staining of MCP-3 was yellow and mainly detected in the tumor cell cytoplasm and also in some glandular epitheliums.Conclusion: The differently expressed genes in inflammation related gene chips will provide clues and theoretical foundation for the investigation of the relationship between tumor and inflammation, and also the immune pathogenesis of laryngeal tumor. Furthermore CCL-7 may have an important role in the occurrence of laryngeal tumor, and the role of immunity of the pathogenesis of laryngeal tumor needs further researches. MCP-3 might be involved in the mechanism of the tumor development, its function of chemotaxis and activation of the tumor-associated macrophages would be highlighted, so that the inflammatory microenvironment might play an important role in the development of tumor.
Keywords/Search Tags:laryngeal cancer, gene chip, gene expression, inflammation, immunity, monocyte chemoctacic protein-3, neoplasm, larynx
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