In vitro pharmacogenomic database and chemosensitivity predictive genes in gastric cancer

Abstract

Gastric cancer is one of the most common cancers worldwide, and there are clinical caveats in predicting tumor response to chemotherapy. This study describes the construction of an in vitro pharmacogenomic database, and the selection of genes associated with chemosensitivity in gastric cancer cell lines. Gene expression and chemosensitivity databases were integrated using the Pearson correlation coefficient to give the GC-matrix. The 85 genes were selected that were commonly associated with chemosensitivity of the major anticancer drugs. We then focused on the genes that were highly correlated with each specific drug. Classification of cell lines based on the set of genes associated with each drug was consistent with the division into resistant or sensitive groups according to the chemosensitivity results. The GC-matrix of the gastric cancer cell line database was used to identify different sets of chemosensitivity-related genes for specific drugs or multiple drugs.

Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells

“…Oligonucleotide microarray and significance analysis of microarray Oligonucleotide microarray analysis was performed with the Cancer Metastasis Research Center microarray (Jung et al 2009). In brief, the test samples (RNA isolated from each gastric cancer cell line) were labeled with Cy5 and individually co-hybridized to the Cy3-labeled reference RNA, and then incubated with a human oligo chip containing 22,740 oligonucleotide probes, which were 70 base pairs long.…”

“…Recently, spotted oligonucleotide microarrays, which use 70-base pair probes, have been applied to genome screening instead of cDNA microarrays. This technology has several advantages; it provides high quality results, avoids clone validation, tracking, and maintenance, and minimizes cross-hybridization (Jung et al 2009).…”

Docetaxel versus Paclitaxel Combined with 5-FU and Leucovorin in Advanced Gastric Cancer: Combined Analysis of Two Phase II Trials

“…There are almost no studies that have compared the efficacy of taxane in patients with stomach cancer. In a situation where there are a series of the pre-clinical evidences that there is a discrepancy in the pharmacodynamic characteristics between the two drugs contradictory to what has been predicted, the current study might be of significance in that it would provide the baseline data for the conduct of interventional studies and clinical ones that predict the efficacy/safety of drugs in patients with progressive stomach cancer (6). Actually, we're currently conducting the clinical trials to confirm the cross-reactivity of taxanes in patients with stomach cancer and a series of interventional studies to examine single nucleotide polymporphism (SNP) of binding sites for β -tubulin or the difference in the sensitivity of inactivation enzymes.…”

“…Through V325 study, a Phase III trial, a combination treatment of cisplatin +5-FU (CF) with docetaxel (DCF) showed that the survival period and quality of life were significantly improved. The occurrence of the toxicity of Grade 3�4 in severity proposed that the treatment dose and schedule should be re-considered to accept DCF as a standard treatment modality for cases of stomach cancer (5,6). For instance, Thus-Patience et al proposed that a single use of DF except for cisplatin had an equivalent profile of the efficacy to epirubicin + cisplatin +5-FU (ECF) or DCF (2).…”

“…It has been proposed, however, that there are significant differences in the binding sites for tubulin, the degree of affinity, toxicity and the expression of cross-reactivity between the two drugs. In recent years, genomic studies have also shown that there is a difference between the two drugs based on the reports that the gene groups are different in association with the sensitivity of two drugs (6). However, clinical trials have been attempted to directly compare the efficacy and safety of twp drugs in a very limited scope.…”