| Summary: | 博士 === 臺北醫學大學 === 醫學科學研究所 === 101 === Gastric cancer is one of the leading causes of cancer death and its malignancy, resulted from the disseminated cancer cells of diffuse type, is clinically manifested as metastases to the liver and peritoneum. The present study is to investigate the efficacy of intravenously administered paclitaxel treatment and identify putative tumor metastasis-associated genes in human gastric cancer cells of diffuse type. MKN45 cell line constitutively expressing green fluorescent proteins (MKN45-GFP) was established and selected using orthotopically animal and Transwell® system for invasive sublines MKN45-GFP-ip4, MKN45-GFP-4, MKN45-GFP-10 and MKN45-GFP-12. MKN45-GFP-ip4 and MKN45-GFP-12 are highly invasive compared to the others. The effects of intravenously administered paclitaxel against the growing peritoneally disseminated and metastasized tumors in nude mice were monitored by MKN45-GFP-ip4 subline. The intravenous paclitaxel is active against the metastases of human gastric cancer of peritoneal diffuse type, which encourages further investigations on optimizing the perioperative paclitaxel therapeutic regimens for gastric cancer in patients. On the other hand, the mRNA levels of whole genes were measured with cDNA microarray and correlated with their invasion abilities in MKN45-GFP, MKN45-GFP-4, MKN45-GFP-10 and MKN45-GFP-12 sublines. The putative gastric tumor metastasis-associated genes, including novel genes, were identified. These genes and their protein products are to be further explored for functional roles associated with tumor metastasis. The molecular profiles of these identified genes, gene transcripts, and proteins in the patient specimens are likely to be useful biomarkers for diagnostic, therapeutic, and/or prognostics. Most importantly, they may be used as molecular targets for discovery of anti-tumor metastasis drugs against human gastric cancer.
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