| Theme | Re-thinking Chromoendoscopy | |
|---|---|---|
| Title | Gastric Cancer Specific Fluorescence after ALA Treatment | |
| Publish Date | 2009/09 | |
| Author | Hirofumi Matsui | Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba |
| Author | Tsuyoshi Kaneko | Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba |
| Author | Akira Nakahara | Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba |
| Author | Ichinosuke Hyodo | Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba |
| [ Summary ] | The application of δ-aminolevulinic acid (ALA) results in the endogenous accumulation of protoporphyrin IX and is a useful approach for photodynamic therapy (PDT) for cancer. We pose the following question in terms of clarifying mechanisms, "Why does ALA cause cancer specific fluorescence?". With this technology the most suitable patient selection is possible for PDT treatment. We conducted examinations in order to investigate the role of nitric oxide (NO) in the specific accumulation of protoporphyrin and ALA-induced PDT of cancerous cells. When the NOS2-expressing cells were treated with ALA and then exposed to visible light, they became more sensitive to light, exhibiting accumulating porphyrins, as compared to the ALA-treated control cells. An increase in the generation of NO in transfected cells led to the accumulation of protoporphyrin with a concomitant decrease of ferrochelatase, the final enzyme associated with heme biosynthesis. The treatment of cells with the NOS inhibitor, NGmonomethyl-L-arginine acetate, resulted in the inhibition of protoporphyrin accumulation and cell death. The levels of mitochondrial ferrochelatase in the NOS2-induced cells decreased. These results indicate that the generation of NO augments the ALA-induced accumulation of protoporphyrin IX and subsequent photo-damage in cancerous cells by decreasing the levels of mitochondrial iron-containing enzymes. Based on the fact that the production of NO in cancerous cells is elevated, NO in the cells is responsible for susceptibility with ALA-induced PDT. | |