| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Research Abstract |
Over the last decade, a number of molecular targets and biomarkers for cancer therapy have been reported. However, suppression of some of the target molecules can provide survival benefits to a small subset of the patients, and only a limited number of practical biomarkers are presently available for selection of treatment modalities. In order to identify molecules involved in pulmonary and esophageal carcinogenesis and those which could be useful as therapeutic biomarkers for lung and esophageal cancer, we have established an effective screening system. The strategy was as follows ; i) To identify up-regulated genes in lung cancers by genome-wide screening using the cDNA microarray representing 32,256 genes and pure populations of tumor cells taken from 120 lung and esophageal cancer tissues by laser microdissection, ii) To verify the candidate genes for their very low level of expression in normal tissues by cDNA microarray and northern-blot analyses, iii) To validate the clinicopathological significance of its over-expression by means of tissue microarray containing hundreds of archived lung-cancer samples, iv) To verify whether the target gene is essential for the cell growth or motility of cancer cells by RNAi and cell growth/invasion assays, v) To evaluate its function and relevant molecular pathways by use of the gene-targeting technology for somatic cells. Through this systematic approach, we identified a set of molecules that appear to fall into the category of cancer-testis antigens and whose up-regulation is a frequent and important feature of the malignant nature of cancer. We provided evidence to indicate that the molecules identified can be regarded as potential targets for the development of highly sensitive and specific biomarkers as well as being useful in the development of small-molecular compounds, antibodies, and cancer vaccines that could have a more specific and efficient anti-cancer effect with minimal risk of adverse effects.
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