Upregulation of matrix metalloproteinase triggers transdifferentiation of retinal pigmented epithelial cells in Xenopus laevis: A Link between inflammatory response and regeneration.

In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, it was examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid. A potent MMP inhibitor, 1,10-PNTL, suppressed RPE cell migration, proliferation, and formation of an epithelial structure in vitro. The mechanism involved in upregulation of Mmps was further investigated. After retinal removal, inflammatory cytokine genes, IL-1ß and TNF-α, were upregulated both in vivo and in vitro. When the inflammation inhibitors dexamethasone or Withaferin A were applied in vitro, RPE cell migration was severely affected, suppressing transdifferentiation. These results demonstrate that Mmps play a pivotal role in retinal regeneration, and suggest that inflammatory cytokines trigger Mmp upregulation, indicating a direct link between the inflammatory reaction and retinal regeneration. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1086-1100, 2017.

[A case of advanced mullerian cancer successfully treated with S-1 chemotherapy].

A 79-year-old woman was referred to our hospital with complaints of dyspnea. She was diagnosed with massive pleural effusion and cytology demonstrated the presence of adenocarcinoma, but no solid tumors were found in the systemic examination. Her serum CYFRA and CA125 level were increased. She was diagnosed with an effusion type of lung cancer or a cancer of unknown origin. S-1/CDDP was the chemotherapy of choice. After 2 courses of the treatment, her serum CYFRA level and CA125 level were normalized, and a chest CT detected no pleural effusion. Two years and 3 months after the first treatment, her CA125 level was increased. We found an FDG accumulation in her pelvic lesion by PET examination. To identify the FDG accumulated lesion in her pelvis, an operation was performed. Histopathological examination of the right ovary demonstrated the presence of an adenocarcinoma. Postoperatively, we administered 2 courses of paclitaxel/carboplatin combination treatment, considering the right ovarian tumor was the primary lesion. The patient remained alive and in good condition without any signs of recurrence 2 years after second treatment. This case suggests that S-1 therapy may be effective for patients with mullerian cancer.