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The aim of this study was to examine the effects of hypoxia on radiosensitivity and to analyze the mechanisms responsible for radiation resistance in gastric and esophageal cancer.A gastric cancer cell line, OCUM-12, and an esophageal cancer cell line, TE-6, were used. The effects of hypoxia with irradiation on the growth-activity, cell cycle distribution, and gene expression were examined.Both acute and chronic hypoxia decreased radiosensitivity of cancer cells. The radiosensitivity of chronic hypoxic cells was significantly enhanced by reoxygenation. Acute and chronic all hypoxia reduced the percentage of cells in the G(2)/M and S phases, respectively. In acute hypoxia, the mRNA expression of BRCA1 and BRCA2 was reduced in cancer cells. Reoxygenation increased the expression of BRCA1 and BRCA2.Hypoxia is associated with radiation resistance. Therefore, reoxygenation may enhance the radiosensitivity of hypoxic cells. BRCA1 and BRCA2 may be associated with factors for radiation resistance by regulation of cell cycle progression.

The aim of this study was to establish drug-resistant cell lines and to elucidate mechanisms leading to multi-drug resistance in gastric cancer.Five cancer cell lines resistant to 5-fluorouracil, paclitaxel, oxaliplatin, irinotecan, or gemcitabine, were respectively established from a parent gastric cancer cell line, OCUM-2M, by stepwise exposure to each chemotherapeutical agent.Cell death by apoptosis induced by anti-cancer drugs was low in 5 chemo-resistant cell lines. Percentage of cells in S and G(0)/G(1) phase was low in cell lines resistant to oxaliplatin or irinotecan. Cell lines resistant to paclitaxel, oxaliplatin, and gemcitabine showed multi-drug resistance. Alterations in MRP, DAPK1, or DAPK2 expression were found in multi-drug resistant cell lines.The cell-cycle distribution and alterations of MRP, DAPK1, and DAPK2 genes may be integral part of mechanisms responsible for chemo-resistance. These cell lines might be useful to study molecular mechanisms leading to multi-drug resistance.

Embryonic stem cell expressed Ras (ERas) oncogene is associated with the tumorigenicity of embryonic stem cells. The aim of this study was to clarify the significance of ERas expression in clinical samples of gastric carcinomas.Three hundred and few tissues from gastric cancer patients were analyzed by immunohistochemical techniques using an anti-ERas antibody. ERas mRNA expression in 77 gastric carcinomas was examined by reverse-transcription polymerase chain reaction.ERas expression was positive in 135 (44%) of 304 gastric carcinomas. ERas-positive expression had a significant relationship with invasion depth (p0.01), histological type (p0.01), clinical stage (p=0.013) and curability (p=0.001). Prognosis of ERas-negative patients was significantly (p=0.029) poorer than that of ERas-positive patients, while ERas was not an independent prognostic factor. Expression of ERas mRNA was found in 35 (45%) out of 77 gastric cancer tissues.ERas oncogene is associated with the tumorigenic process of human gastric carcinomas.