RNF43 interacts with NEDL1 and regulates p53-mediated transcription

The ubiquitin-proteasomal system plays a crucial role in oncogenesis in colorectal tissues. Recent studies have shown that stability of β-catenin, which functions as an oncogene for colorectal cancer, is regulated by ubiquitin-mediated degradation. It has been reported that a putative E3 ubiquitin ligase, RNF43, is highly expressed in human colorectal carcinoma and that RNF43 promotes cell growth. However, the involvement of RNF43 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (NEDL1), which enhances pro-apoptotic activity by p53. In addition, we found that RNF43 also interacts with p53 and that RNF43 suppresses transcriptional activity of p53 in H1299 cells and attenuates apoptosis induced by ultraviolet irradiation. These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis

Effects of Natural Reduced Water on Cognitive Function, Body Composition, and Psychological Function in Older Adults: Study Protocol for a Randomized Controlled Trial

Natural reduced water is natural water that contains active hydrogen and reduces oxidation. It is rare in the world, and in Japan, it is produced in the Hita area of Oita Prefecture (Hita Tenryosui water). Previous studies in humans have examined the effects of natural reduced water on diabetes, which is one of the known risks for dementia. Animal studies of natural reduced water have revealed anti-obesity and anti-anxiety effects. However, the effects of natural reduced water on cognitive function, body composition, and psychological function in humans are unknown. Therefore, we investigated the relationship between these items in elderly people who continuously consume natural reduced water. In this study, we recruited participants aged between 65 and 74 years. The participants were randomly and blindly assigned to a natural reduced water (Hita Tenryosui water) group or a control (tap water) group and drank 1 L of water daily for 6 months. Cognitive function, body composition, and psychological function were measured before and after the 6-month intervention period

Effects of Natural Reduced Water on Cognitive Function, Body Composition, and Psychological Function in Older Adults: Study Protocol for a Randomized Controlled Trial

Natural reduced water is natural water that contains active hydrogen and reduces oxidation. It is rare in the world, and in Japan, it is produced in the Hita area of Oita Prefecture (Hita Tenryosui water). Previous studies in humans have examined the effects of natural reduced water on diabetes, which is one of the known risks for dementia. Animal studies of natural reduced water have revealed anti-obesity and anti-anxiety effects. However, the effects of natural reduced water on cognitive function, body composition, and psychological function in humans are unknown. Therefore, we investigated the relationship between these items in elderly people who continuously consume natural reduced water. In this study, we recruited participants aged between 65 and 74 years. The participants were randomly and blindly assigned to a natural reduced water (Hita Tenryosui water) group or a control (tap water) group and drank 1 L of water daily for 6 months. Cognitive function, body composition, and psychological function were measured before and after the 6-month intervention period

IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater's ampulla and the bile duct.

Autoimmune pancreatitis is commonly associated with immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC). The discrimination between IgG4-SC and pancreatobiliary malignancies or primary sclerosing cholangitis (PSC) is now an important issue. The present study was carried out to examine the usefulness of endoscopic biopsies from Vater's ampulla and the bile duct to diagnose IgG4-SC

Pancreatic metastasis from renal cell carcinoma with intraportal tumor thrombus.

A 68-year-old woman with a history of renal cell carcinoma (RCC) resected curatively 12 years previously was admitted to our department for scrutiny of pancreatic tumors. Various imaging studies demonstrated heterogeneously well-enhanced masses in the head and tail of the pancreas. The well-enhanced mass in the head of the pancreas was connected with the tumor thrombus in the portal vein. To differentially diagnose the multiple pancreatic lesions, we performed endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB). Histopathologic findings of the EUS-FNAB specimens were similar to those of the renal clear cell carcinoma previously resected. The patient underwent a surgical operation with segmental resection of the portal vein with the preoperative diagnosis of RCC metastasis to the pancreas with intraportal growth. Histopathological examination of the resected specimen revealed that the masses in the pancreas were multiple pancreatic metastases with intraportal tumor thrombus of RCC. The pancreas is a rare target for metastasis. This is a rare case of pancreatic metastasis from RCC with intraportal extension, and is the first preoperatively definitely diagnosed case using EUS-FNAB

Molecular Role of RNF43 in Canonical and Noncanonical Wnt Signaling

Wnt signaling pathways are tightly regulated by ubiquitination, and dysregulation of these pathways promotes tumorigenesis. It has been reported that the ubiquitin ligase RNF43 plays an important role in frizzled-dependent regulation of the Wnt/beta-catenin pathway. Here, we show that RNF43 suppresses both Wnt/beta-catenin signaling and noncanonical Wnt signaling by distinct mechanisms. The suppression of Wnt/beta-catenin signaling requires interaction between the extracellular protease-associated (PA) domain and the cysteine-rich domain (CRD) of frizzled and the intracellular RING finger domain of RNF43. In contrast, these N-terminal domains of RNF43 are not required for inhibition of noncanonical Wnt signaling, but interaction between the C-terminal cytoplasmic region of RNF43 and the PDZ domain of dishevelled is essential for this suppression. We further show the mechanism by which missense mutations in the extracellular portion of RNF43 identified in patients with tumors activate Wnt/beta-catenin signaling. Missense mutations of RNF43 change their localization from the endosome to the endoplasmic reticulum (ER), resulting in the failure of frizzled-dependent suppression of Wnt/beta-catenin signaling. However, these mutants retain the ability to suppress noncanonical Wnt signaling, probably due to interaction with dishevelled. RNF43 is also one of the potential target genes of Wnt/beta-catenin signaling. Our results reveal the molecular role of RNF43 and provide an insight into tumorigenesis

Autoimmune pancreatitis associated with hemorrhagic pseudocysts: a case report and literature review.

Autoimmune pancreatitis (AIP) is a new category of pancreatic diseases. AIP associated with pseudocysts is rare; only 8 cases have been reported in the literature. A 63-year-old man was admitted to our department because of upper left abdominal pain and back pain. Various imaging studies demonstrated swelling of the tail of the pancreas with hemorrhagic pseudocysts. The patient underwent a surgical operation. A pancreatogram of the specimen revealed total occlusion of the main pancreatic duct in the tail of the pancreas. Histopathological examination revealed that it was AIP with hemorrhagic pseudocysts

Endoscopic retrograde cholangiography versus peroral cholangioscopy to evaluate intraepithelial tumor spread in biliary cancer

Background and study aims: Localized-type bile duct carcinoma (LBDC) is often accompanied by extensive intraepithelial tumor spread (ITS) ≥2 cm which makes radical resection more difficult. This retrospective case review compared the diagnostic accuracy of endoscopic retrograde cholangiography (ERC) and peroral cholangioscopy (POCS) to detect ITS beyond the visible LBDCs. Patients and methods: Forty-four consecutive LBDC patients diagnosed between April 2004 to October 2008 who underwent radical resection with histopathological analysis were included in this study. Extensive ITS was found histopathologically in one-third of the cases (32%). The outcome parameters were the presence or absence of extensive ITS and the extent of extensive ITS proximal and distal to the main tumor. Results: It was not possible to pass the cholangioscopic through the tumor sites in 6 cases. ERC correctly identified the presence of extensive ITS in 11/14 cases and did not yield any false-positive results. The three ERC-negative cases were all correctly identified by POCS plus biopsy since the cholangioscope could be passed in all three cases. The extent of extensive ITS was correctly diagnosed by ERC alone, ERC with POCS, and ERC with POCS plus mapping biopsy in 22%, 77%, and 100% of cases, respectively. Conclusions: The presence of extensive ITS could be correctly detected in 80% of cases by ERC alone. POCS with mapping biopsy provided perfect diagnostic accuracy of not only the presence/absence but also the extent of extensive ITS. However, POCS has the limitation that the cholangioscope cannot be passed through the tumor sites in approximately 15% of cases