OBJECTIVEDocosahexaenoic acid (DHA) is known as a chemopreventive substance for cancers. Previously we reported that DHA induces apoptosis in HL-60 cells. The aim of this study was to clarify the role of phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling during DHA-induced apoptosis in HL-60 cells.

METHODSThe inhibitory effects of dibutyryl cAMP (db-cAMP) or LY294002 (a specific inhibitor of the PI3-kinase/Akt pathway) on DHA-induced apoptosis in HL-60 cells were evaluated by the appearance of apoptosis, and from the activities of caspases (3 and 8), the phospholylation of Akt, and cleavage of Bid using DNA indexes, emzymatic measurement of fragmented substrates, and Western blotting, respectively.

RESULTSThe pre-incubation of db-cAMP reduced the activation of caspasses (3 and 8) during the occurrence of DHA-induced apoptosis in HL-60. However, the inhibition of PI3-kinase/Akt signaling by LY294002 resulted in recovery of the caspases' activities, appearance of apoptotic cells, and cleavage of the Bid molecule when LY294002 was co-treated with db-cAMP before the occurrence of DHA-induced apoptosis in HL-60. It was also confirmed that LY294002 strongly inhibited phospholylation of Akt during db-cAMP induced-reduction of DHA-induced apoptosis in HL-60.

CONCLUSIONWe demonstrated that DHA-induced apoptosis was sensitive to the modulation of PI3-kinase activity by treatment with db-cAMP or LY294002. These results may provide new insights into the mechanisms of the anti-cancer activity of DHA.

It is common knowledge that exposure to asbestos causes asbestos-related diseases, such as asbestosis, lung cancer and malignant mesothelioma, not only in people who have had long-term contact with asbestos in their work environment but also in residents living near factories that handle asbestos. Since the summer of 2005, these revelations turned into a large medical problem and caused and social unrest. We have focused on the immunological effects of both asbestos and silica on the human immune system. In this brief review, we introduce immunological alterations found in patients with malignant mesothelioma and describe the experimental background in which these were found. Analyzing the immunological effects of asbestos may improve our understanding of the biological effects of asbestos.

Silica and silicates may disturb immune functions such as autoimmunity and tumor immunity, because people who are exposed to the materials sometimes develop autoimmune and malignant diseases, respectively. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer in 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate the nation wide anxiety about these malignancies.

Purpose: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Materials and Methods: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Results: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLIbright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Conclusions Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.