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Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer

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Description:This dissertation, "Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer" by Ching, Eunice, Chan, 陳清, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer Submitted by Chan Ching, Eunice For the Degree of Doctor of Philosophy at the University of Hong Kong in May 2007 Lung cancer is the leading cause of cancer death in the United States and worldwide. Despite the improvement of diagnostic techniques and the understanding of molecular biology of lung cancers in recent years, the 5-year survival rate has remained poor. Epigenetic silencing of gene expression by promoter CpG islands is a common phenomenon in cancers. The detection of aberrant promoter methylation using methylation-specific PCR (MSP) of tumor suppressor genes has been proposed to be a potential screening approach for the early detection of lung cancers. The patterns of aberrant gene methylation of the genes CDKN2A, RARβ, DAP kinase and MGMT in non-small cell lung cancer (NSCLC) of 75 (44 adenocarcinomas and 31 squamous cell carcinomas, SCC) Chinese patients and its iuse in detecting cancer cells in 68 BAL samples of patients with suspected lung cancer were studied. Significantly more females had adenocarcinomas than SCC. Aberrant methylation in at least one gene was found in 63 of 75 (84%) NSCLCs. Females with NSCLC showed more frequent CDKN2A methylation (92%) than males and this frequency was one of the highest known. The frequency of RARβ methylation was 71%, which was considerably higher than that in Western patients; whereas DAP kinase and MGMT were methylated at frequencies of 35% and 15% respectively. From the cytology negative and MSP positive results in the BAL samples, 35 out of 41 were eventually shown to have malignant lung lesions, suggesting that MSP of a panel of genes might be a useful biomarker for the detection of lung cancer. Polymorphisms of genes involved in detoxification of carcinogens and modulating or repairing DNA damage after carcinogen exposure have been linked to the risks of lung cancer. The effect of polymorphism of GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes on lung cancer risk was examined. In male patients, GSTM1 null genotype, the MPO wildtype G allele and the XRCC1 26304 C→T allele were found to be associated with an apparent reduced risk of lung cancer. The -463 G allele of MPO wildtype was significantly associated with an increased risk of iiCDKN2A methylation. The XRCC1 26304 C→T was significantly associated with CDKN2A and RARβ methylation. In female patients, GSTP1 2627 A→G polymorphism was significantly associated with lung cancer and the AG/GG genotype of GSTP1 2627 was significantly associated with CDKN2A and RARβ aberrant methylation. These results showed that functional deficiencies in metabolic pathways that protect cells from carcinogen induced DNA damage might be linked to aberrant promoter methylation of the CDKN2A and RARβ genes during lung carcinogenesis. Aberrant activation of the Wnt signalling is associated with carcinogenesis and other degenerative diseases. Both sFRP1 and WIF-1 are Wnt antagonists and high frequencies (82-94%) of aberrant promoter methylated were reported in both genes in lung cancers. sFRP1 and WIF-1 genes were aberrantly methylated in lung cancer cell lines, corresponding to suppressed gene expression. De-methylation and re-expression of sFRP1 and WIF-1 was achieved by treatment with 5-azacytidine. iii DOI: 10.5353/th_b3955781 Subjects: Lungs - CancerWe have made it easy for you to find a PDF Ebooks without any digging. And by having access to our ebooks online or by storing it on your computer, you have convenient answers with Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer. To get started finding Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer, you are right to find our website which has a comprehensive collection of manuals listed.
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Description: This dissertation, "Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer" by Ching, Eunice, Chan, 陳清, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer Submitted by Chan Ching, Eunice For the Degree of Doctor of Philosophy at the University of Hong Kong in May 2007 Lung cancer is the leading cause of cancer death in the United States and worldwide. Despite the improvement of diagnostic techniques and the understanding of molecular biology of lung cancers in recent years, the 5-year survival rate has remained poor. Epigenetic silencing of gene expression by promoter CpG islands is a common phenomenon in cancers. The detection of aberrant promoter methylation using methylation-specific PCR (MSP) of tumor suppressor genes has been proposed to be a potential screening approach for the early detection of lung cancers. The patterns of aberrant gene methylation of the genes CDKN2A, RARβ, DAP kinase and MGMT in non-small cell lung cancer (NSCLC) of 75 (44 adenocarcinomas and 31 squamous cell carcinomas, SCC) Chinese patients and its iuse in detecting cancer cells in 68 BAL samples of patients with suspected lung cancer were studied. Significantly more females had adenocarcinomas than SCC. Aberrant methylation in at least one gene was found in 63 of 75 (84%) NSCLCs. Females with NSCLC showed more frequent CDKN2A methylation (92%) than males and this frequency was one of the highest known. The frequency of RARβ methylation was 71%, which was considerably higher than that in Western patients; whereas DAP kinase and MGMT were methylated at frequencies of 35% and 15% respectively. From the cytology negative and MSP positive results in the BAL samples, 35 out of 41 were eventually shown to have malignant lung lesions, suggesting that MSP of a panel of genes might be a useful biomarker for the detection of lung cancer. Polymorphisms of genes involved in detoxification of carcinogens and modulating or repairing DNA damage after carcinogen exposure have been linked to the risks of lung cancer. The effect of polymorphism of GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes on lung cancer risk was examined. In male patients, GSTM1 null genotype, the MPO wildtype G allele and the XRCC1 26304 C→T allele were found to be associated with an apparent reduced risk of lung cancer. The -463 G allele of MPO wildtype was significantly associated with an increased risk of iiCDKN2A methylation. The XRCC1 26304 C→T was significantly associated with CDKN2A and RARβ methylation. In female patients, GSTP1 2627 A→G polymorphism was significantly associated with lung cancer and the AG/GG genotype of GSTP1 2627 was significantly associated with CDKN2A and RARβ aberrant methylation. These results showed that functional deficiencies in metabolic pathways that protect cells from carcinogen induced DNA damage might be linked to aberrant promoter methylation of the CDKN2A and RARβ genes during lung carcinogenesis. Aberrant activation of the Wnt signalling is associated with carcinogenesis and other degenerative diseases. Both sFRP1 and WIF-1 are Wnt antagonists and high frequencies (82-94%) of aberrant promoter methylated were reported in both genes in lung cancers. sFRP1 and WIF-1 genes were aberrantly methylated in lung cancer cell lines, corresponding to suppressed gene expression. De-methylation and re-expression of sFRP1 and WIF-1 was achieved by treatment with 5-azacytidine. iii DOI: 10.5353/th_b3955781 Subjects: Lungs - CancerWe have made it easy for you to find a PDF Ebooks without any digging. And by having access to our ebooks online or by storing it on your computer, you have convenient answers with Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer. To get started finding Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer, you are right to find our website which has a comprehensive collection of manuals listed.
Our library is the biggest of these that have literally hundreds of thousands of different products represented.

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Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer

Pathogenetic Role of Aberrant Promoter Methylation in Lung Cancer

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