Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been...Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been reported to be complicated by malignant tumors. Based on the criteria of the International Cowden Consortium, this disease is mainly diagnosed as trichilemmoma of the face and oral mucosal papillomatosis. However, Cowden's disease patients themselves often do not recognize trichilemmoma of the face and oral mucosal papillomatosis. We report a case of Cowden's disease in a 33-year-old female patient who was diagnosed based on the characteristic findings at gastrointestinal endoscopy. Clinically, the patient was aware of having bloody stools. Multiple polyps found endoscopically in the esophagus, stomach, ileum, colon and rectum showed histopathologically hamartomatous changes and epithelial hyperplasia. Physical examination revealed oral papillomatosis and facial trichilemmomas. A germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was found in this case. It was a point mutation of C to T at codon 1003 (CGA→TGA, arginine→stop codon). The characteristic findings on gastrointestinal endoscopy led us to a diagnosis of Cowden's disease. It has been reported that gastrointestinal polyposis with esophageal polyposis is found in about 85.7% of Japanese patients with Cowden's disease. The characteristic findings on gastrointestinal endoscopy can be a useful diagnostic clue to Cowden's disease.展开更多
Wolfram syndrome, an autosomal recessive disorder associated with diabetes and optic atrophy, is caused by mutations in the WFS1 gene encoding wolframin, an endoplasmic reticulum membrane protein. Recent development o...Wolfram syndrome, an autosomal recessive disorder associated with diabetes and optic atrophy, is caused by mutations in the WFS1 gene encoding wolframin, an endoplasmic reticulum membrane protein. Recent development of incretin-based drugs demonstrates promising outcomes for treatment of diabetes mellitus. The aim of this study is to evaluate whether dipeptidyl peptidase-4 inhibition is effective for treating endoplasmic reticulum stress-mediated β-dell failure and impaired glucose tolerance in WFS1-deficient mice (Wfs1-/-). Wfs1-/- mice were orally administrated with vildagliptin (50 mg/kg), a dipeptidyl peptidase-4 inhibitor, twice a day for 4 weeks. The pancreases of these mice were subjected to morphological and biochemical analyses and their glucose tolerance was studied. Electron microscopic studies revealed that vildagliptin reduced number of β-cell containing swollen endoplasmic reticulum in Wfs1-/-?mice. Vildagliptin treatment increased pancreatic insulin content by 30% in Wfs1-/- mice. Oral and intraperitoneal glucose tolerance tests showed improved glucose tolerance in vildagliptin-treated Wfs1-/- mice with increased glucose responsiveness of insulin secretion as compared with vehicle-treated mutant mice. These effects by dipeptidyl peptidase-4 inhibition were partly prevented by glucagon-like peptide-1 receptor blockade. These findings provide evidence that activation of the incretin system by dipeptidyl peptidase-4 inhibition plays a protective role against β-cell failure in wolframin-deficiency. Our data suggest that diabetes in patients affected with Wolfram syndrome could be treated by incretin-based drugs. Furthermore, since WFS1 dysfunction could be involved in common forms of type 2 diabetes mellitus, our results strengthen the mechanistic rational of using this drug for the disease.展开更多
文摘Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been reported to be complicated by malignant tumors. Based on the criteria of the International Cowden Consortium, this disease is mainly diagnosed as trichilemmoma of the face and oral mucosal papillomatosis. However, Cowden's disease patients themselves often do not recognize trichilemmoma of the face and oral mucosal papillomatosis. We report a case of Cowden's disease in a 33-year-old female patient who was diagnosed based on the characteristic findings at gastrointestinal endoscopy. Clinically, the patient was aware of having bloody stools. Multiple polyps found endoscopically in the esophagus, stomach, ileum, colon and rectum showed histopathologically hamartomatous changes and epithelial hyperplasia. Physical examination revealed oral papillomatosis and facial trichilemmomas. A germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was found in this case. It was a point mutation of C to T at codon 1003 (CGA→TGA, arginine→stop codon). The characteristic findings on gastrointestinal endoscopy led us to a diagnosis of Cowden's disease. It has been reported that gastrointestinal polyposis with esophageal polyposis is found in about 85.7% of Japanese patients with Cowden's disease. The characteristic findings on gastrointestinal endoscopy can be a useful diagnostic clue to Cowden's disease.
文摘Wolfram syndrome, an autosomal recessive disorder associated with diabetes and optic atrophy, is caused by mutations in the WFS1 gene encoding wolframin, an endoplasmic reticulum membrane protein. Recent development of incretin-based drugs demonstrates promising outcomes for treatment of diabetes mellitus. The aim of this study is to evaluate whether dipeptidyl peptidase-4 inhibition is effective for treating endoplasmic reticulum stress-mediated β-dell failure and impaired glucose tolerance in WFS1-deficient mice (Wfs1-/-). Wfs1-/- mice were orally administrated with vildagliptin (50 mg/kg), a dipeptidyl peptidase-4 inhibitor, twice a day for 4 weeks. The pancreases of these mice were subjected to morphological and biochemical analyses and their glucose tolerance was studied. Electron microscopic studies revealed that vildagliptin reduced number of β-cell containing swollen endoplasmic reticulum in Wfs1-/-?mice. Vildagliptin treatment increased pancreatic insulin content by 30% in Wfs1-/- mice. Oral and intraperitoneal glucose tolerance tests showed improved glucose tolerance in vildagliptin-treated Wfs1-/- mice with increased glucose responsiveness of insulin secretion as compared with vehicle-treated mutant mice. These effects by dipeptidyl peptidase-4 inhibition were partly prevented by glucagon-like peptide-1 receptor blockade. These findings provide evidence that activation of the incretin system by dipeptidyl peptidase-4 inhibition plays a protective role against β-cell failure in wolframin-deficiency. Our data suggest that diabetes in patients affected with Wolfram syndrome could be treated by incretin-based drugs. Furthermore, since WFS1 dysfunction could be involved in common forms of type 2 diabetes mellitus, our results strengthen the mechanistic rational of using this drug for the disease.
