Author Correction: Nrf2 contributes to the weight gain of mice during space travel.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nrf2 contributes to the weight gain of mice during space travel.

Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS).

Number of positive lymph nodes and lymphatic invasion are significant prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma.

Early recurrence of distal cholangiocarcinoma (DCC) may result in a poorer prognosis. This study aimed to evaluate the clinicopathological factors that predict survival and recurrence in patients with DCC. Fifty-five patients with DCC who underwent pancreaticoduodenectomy between 2005 and 2015 were studied retrospectively.

Concomitant Nrf2- and ATF4-activation by Carnosic Acid Cooperatively Induces Expression of Cytoprotective Genes.

Carnosic acid (CA) is a phytochemical found in some dietary herbs, such as L., and possesses antioxidative and anti-microbial properties. We previously demonstrated that CA functions as an activator of nuclear factor, erythroid 2 (NF-E2)-related factor 2 (Nrf2), an oxidative stress-responsive transcription factor in human and rodent cells.

GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice.

The transcription factor GATA2 regulates normal hematopoiesis, particularly in- stem cell maintenance and myeloid differentiation. Various heteroallelic GATA2 gene mutations are associated with a variety of hematological neoplasms, including myelodysplastic syndromes and leukemias. Here, we report that impaired GATA2 expression induces myelodysplastic and myeloproliferative neoplasm development in elderly animals, and this neoplasm resembles chronic myelomonocytic leukemia in humans.

Prognostic Factors Associated with Preoperative Clinicophysiological Outcomes of Distal Cholangiocarcinoma.

Background/aims: Although biliary tract cancer is generally associated with a high mortality rate, patients with distal cholangiocarcinoma have better prognoses, compared to those with periampullary cancer. This study aimed to determine the preoperative clinicophysiological factors predictive of survival and recurrence in patients with distal cholangiocarcinoma.

Methods: Forty-five patients (34 men) with distal cholangiocarcinoma who underwent pancreaticoduodenectomy between 2005 and 2013 were examined retrospectively at our center and associated hospitals.

Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer.

The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1-14.

Efficacy of non-stented pancreaticojejunostomy demonstrated in the hard pancreas.

Background/aims: The aim of this study was to compare hard and soft pancreas for short-term complications of pancreaticoduodenectomy performed with a duct-to-mucosa anastomosis of pancreaticojejunostomy without a stenting tube.

Methodology: We investigated 156 patients with pancreaticojejunostomy who were classified into two groups of hard pancreas (group A: 79) and soft pancreas (group B: 77). Outcomes, including complications and operative procedures, are reported.

Adjuvant chemotherapy using gemcitabine for resected distal bile duct and ampullary cancers.

Background/aims: This retrospective study aimed to evaluate adjuvant chemotherapy using gemcitabine for resected distal bile duct and ampullary cancers.

Methodology: Thirty-seven patients who had curative surgery for distal bile duct and ampullary cancers were classified into two groups: A, 19, surgery alone, and B, 18, surgery plus gemcitabine adjuvant chemotherapy between 2004 and 2010. Outcomes, including backgrounds, overall survival (OS), disease free survival (DFS), and adverse events are reported.

Nrf2 activation is associated with Z-DNA formation in the human HO-1 promoter.

Using a luciferase reporter assay, we previously demonstrated that a Z-DNA-forming sequence of alternating thymine-guanine repeats in the human heme oxygenase-1 gene (HO-1) promoter is involved in nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2)-mediated HO-1 promoter activation. However, the actual Z-DNA formation in this native genomic locus has not been experimentally demonstrated. To detect Z-DNA formation in vivo, we generated a construct containing the Z-DNA-binding domain of human adenosine deaminase acting on double-stranded RNA 1 fused with enhanced green fluorescence protein, designated as the Z-probe.

Retrospective study of gemcitabine plus S-1 versus gemcitabine alone in cases with unresectable advanced pancreatic cancer.

Background/aims: The aim of this study was to compare gemcitabine plus S-1 (GS) combination chemotherapy to gemcitabine (GEM) monotherapy in cases with unresectable advanced pancreatic cancer.

Methods: We retrospectively reviewed 107 consecutive patients with unresectable advanced pancreatic cancer who received GEM monotherapy or GS combination chemotherapy between 2004 and 2010. In 73 patients, GEM (1000 mg/m2) was administered intravenously on days 1, 8 and 15, repeated every four weeks.

Pancreaticoduodenectomy can be safely performed in the elderly.

Background: Although pancreaticoduodenectomy has been recognized in the past for its severe complications, improvements in operative methods and perioperative management have made it a safe procedure. Therefore, pancreaticoduodenectomy can be performed in elderly patients, and our experience and outcomes are described in this report.

Methods: We retrospectively investigated 142 patients in whom pancreaticoduodenectomy was performed without stenting tubes during pancreaticojejunostomy.

Nrf2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation.

Atherosclerosis is the major etiology underlying myocardial infarction and stroke, and strategies for preventing atherosclerosis are urgently needed. In the context of atherosclerosis, the deletion of the Nrf2 gene, which encodes a master regulator of the oxidative stress response in mammals, reportedly attenuates atherosclerosis formation. However, the precise mechanisms of protection against atherosclerosis are largely unknown.

Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis.

Background: The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is a key regulator for induction of hepatic antioxidative stress systems. We aimed to investigate whether activation of Nrf2 protects against steatohepatitis.

Method: Wild-type mice (WT), Nrf2 gene-null mice (Nrf2-null) and Keap1 gene-knockdown mice (Keap1-kd), which represent the sustained activation of Nrf2, were fed a methionine- and choline-deficient diet (MCDD) for 13 weeks and analyzed.

[A case of bile duct cancer with positive surgical margin obtaining long-term survival after S-1 monotherapy].

We report a case of bile duct cancer with a positive surgical margin obtaining long-term survival after S-1 monotherapy. A 79-year-old male with fever and liver dysfunction was admitted to our hospital. After a series of examinations he was diagnosed as hilar cholangiocarcinoma, which was treated with bile duct resection and biliary reconstruction for adhesion and pulmonary dysfunction of tuberculosis.

Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes.

Nerve growth factor (NGF) is a neurotrophic factor that plays an important role in neuronal cell development and survival. Carnosic acid (CA), a hydrophobic constituent of the herb rosemary, induces NGF production in human T98G glioblastoma cells, but the mechanism through which it works remains unknown. In the present study, we found a redox-sensitive transcription factor, Nrf2, which coordinates the expression of cytoprotective phase 2 genes, also participates in CA-inducible NGF expression.

The novel Nrf2-interacting factor KAP1 regulates susceptibility to oxidative stress by promoting the Nrf2-mediated cytoprotective response.

The transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2) co-ordinately regulates ARE (antioxidant-response element)-mediated induction of cytoprotective genes in response to electrophiles and oxidative stress; however, the molecular mechanism controlling Nrf2-dependent gene expression is not fully understood. To identify factors that regulate Nrf2-dependent transcription, we searched for proteins that interact with the Nrf2-NT (N-terminal Nrf2 transactivation domain) by affinity purification from HeLa nuclear extracts. In the present study, we identified KAP1 [KRAB (Krüppel-associated box)-associated protein 1] as a novel Nrf2-NT-interacting protein.

[Effectiveness of adjuvant chemotherapy using gemcitabine for resected pancreatic cancer].

Background: The aim was to evaluate the adjuvant chemotherapy using gemcitabine (GEM) for resected pancreatic cancer.

Methods: We investigated 69 patients who had undergone curative operations for pancreatic cancer. They were classified into two groups of patients using GEM (group A: 37) and patients with surgery alone (group B: 32) between 2009 and 1998.

Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages.

Iron is an essential element of hemoglobin, and efficient iron recycling from senescent erythrocytes by splenic macrophages is required for erythrocyte hemoglobin synthesis during erythropoiesis. Ferroportin 1 (Fpn1) is the sole iron exporter in mammals, and it also regulates iron reutilization. In this study, we demonstrated genetically that a redox-sensitive transcription factor, Nrf2, regulates Fpn1 mRNA expression in macrophages.

[Risk associated with severe hematological toxicity in patients with advanced or recurrent colonic cancer receiving combination chemotherapy of S-1 and irinotecan hydrochloride].

The aim of this study was to analyze the risk factors for grade 3 to 4 hematological toxicity after primary chemotherapy (Tegafur, gimeracil, oteracil potassium (S-1)/irinotecan hydrochloride (CPT-11)) in 87 (56 male, 31 female; median age 66.1 years) patients with unresectable or recurrent colonic cancer between April 2005 and May 2009, and to prepare a risk classes (low-risk, intermediate-risk or high-risk groups). The rate of grade 3 to 4 hematological toxicity was 16.

Pancreaticoduodenectomies with a duct-to-mucosa pancreaticojejunostomy anastomosis with and without a stenting tube showed no differences in long-term follow-up.

Background/purpose: The aim of this study was to evaluate the long-term complications of pancreaticoduodenectomy with a duct-to-mucosa pancreaticojejunostomy anastomosis without a stenting tube.

Methods: Patients were followed for at least 3 years after pancreaticoduodenectomy. They were classified into two groups: duct-to-mucosa pancreaticojejunostomy anastomosis with a stenting tube (group A: 24) and without a stenting tube (group B: 21).

Pancreatic schwannoma: a case report and literature review with special reference to imaging features.

Context: We report the imaging features of pancreatic schwannomas, a rare benign type of pancreatic tumor.

Case Report: A 66-year-old woman was admitted to our hospital with a pancreatic tumor indicated in medical examinations. Computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) revealed a solid and cystic tumor, 3 cm in diameter, within the body of the pancreas.

Appraisal of the Imaizumi modification of the Beger procedure: the TWMU experience.

Background/purpose: We developed the Imaizumi modification of the Beger procedure, a duodenum-preserving pancreatic head resection. The Imaizumi modification allows for removal of more of the subtotal pancreatic head than in the conventional Beger procedure, including the intrapancreatic bile duct, for chronic pancreatitis with common bile duct stenosis. A retrospective study was performed to evaluate the efficacy of the Imaizumi modification compared to a pylorus-preserving pancreaticoduodenectomy (PPPD), based on the early and late postoperative results.

[A case of pathologic complete response of primary esophageal carcinoma treated with 5-FU/CDDP as neoadjuvant chemotherapy].

A 77-year-old man with advanced esophageal carcinoma and lymph node swelling of abdomen and mediastinum, underwent neoadjuvant chemotherapy (NAC) with 5-FU/CDDP. Adverse reactions were general fatigue and nausea of grade 3 and stomatitis of grade 2. Primary tumor and lymph node swelling revealed remarkable effectiveness after 1 course of NAC, so 2 courses of NAC were given.

[Risk associated with severe hematological toxicity in patients with advanced or recurrent gastric cancer receiving primary combination chemotherapy of cisplatin and S-1 or cisplatin and irinotecan hydrochloride].

The purpose of this study was to analyze the risk factor for grade 3 to 4 hematological toxicity after primary chemotherapy(cisplatin(CDDP)/tegafur, gimeracil, oteracil potassium(S1)or CDDP/irinotecan hydrochloride(CPT-11)) in 75 patients with unresectable or recurrent gastric cancer between April 2005 and May 2008. The rate of grade 3 to 4 hematological toxicity was 17.3%(13 patients).