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Reactive oxygen species (ROS) activate uncoupler protein 1 (UCP1) in brown adipose tissue (BAT) under physiological cold exposure and noradrenaline (NA) stimulation to increase thermogenesis. However, the endogenous regulator of ROS in activated BAT and its role in pathological conditions remain unclear. We show that serum levels of selenoprotein P (SeP; encoded by SELENOP) negatively correlate with BAT activity in humans. Physiological cold exposure downregulates Selenop in BAT. Selenop knockout mice show higher rectal temperatures and UCP1 sulfenylation during cold exposure. SeP treatment to brown adipocytes eliminated the NA-induced mitochondrial ROS by upregulating glutathione peroxidase 4 and impaired cellular thermogenesis. A high-fat/high-sucrose diet elevates serum SeP levels and diminishes the elevated NA-induced thermogenesis in BAT- Selenop KO mice. Therefore, SeP is the intrinsic factor inducing reductive stress that impairs thermogenesis in BAT and may be a potential therapeutic target for obesity and diabetes. [Display omitted] • High-serum SeP is associated with low BAT activity in humans • Selenop KO mice show higher UCP1 activation and thermogenesis in BAT • SeP impairs UCP1 activation by eliminating the mitochondrial ROS via GPX4 • Elevated serum SeP in diabetes impairs BAT thermogenesis in mice ROS-mediated sulfenylation is essential for the activation of UCP1 in brown adipose tissue (BAT). Selenoprotein P (SeP) is the diabetes-associated hepatokine. Oo et al. reveal that local and circulating SeP impairs UCP1 sulfenylation and thermogenesis via reductive stress in BAT and may be a therapeutic target against obesity and diabetes. [ABSTRACT FROM AUTHOR]

NBS1 is the causative gene product of Nijmegen breakage syndrome (NBS), a recessive genetic disorder resulting in chromosomal instability and immunodeficiency. We isolated DNMT1 cDNA by two-hybrid screening by using NBS1 as bait to study its function in DNA replication and damage checkpoint. DNMT1 encodes DNA methyltransferase 1, which maintains the genomic methylation pattern and also regulates the checkpoint pathway via interactions with various factors, such as CHK1, p53, Rb and ATM. The interaction between NBS1 and DNMT1 was observed under conditions of hydroxyl urea treatment, resulting in replication stall and mitomycin C treatment resulting in DNA damage. Additionally, we mapped their binding regions to the N-terminus of NBS1 (including the forkhead-associated domain) and amino acids 1401–1503 in the target recognition domain in the C-terminus of DNMT1. Under DNA replication stall conditions, DNMT1 was recruited to the survivin promoter by p53, and it repressed survivin expression via hetrochromatin formation; this regulation was dependent on the NBS1 genotype. These results suggest that DNMT1 function in the regulatory response is controlled by NBS1. [ABSTRACT FROM PUBLISHER]

Abstract: We investigate the properties of NiO thin films prepared by sol–gel solution and the photovoltaic performance of bulk-heterojunction (BHJ) solar cells based on NiO thin films as anode buffer layers with various film thickness and amorphous–crystalline phase. Optoelectronic properties and surface morphology of NiO films strongly depend on the thickness and phase of the NiO. The performance of solar cells based on nanocrystaline (nc-) NiO exhibits better photovoltaic characteristics in comparison to those employing an amorphous (a-) NiO. The obtained power conversion efficiency (PCE, η) of a solar cell with a 20-nm-thick nc-NiO is 2.24%, with a short-circuit density (J SC) of 7.77mA/cm2, open-circuit voltage (V OC) of 0.57V, and fill factor (FF) of 0.50. [Copyright &y& Elsevier]

One-quarter of a century ago, identification of the human retinoblastoma gene ( RB) loci proved Knudson's 'two-hit theory' that tumor suppressor genes exist. Since then, numerous works delineated crucial roles for the RB protein (pRB)-E2F transcription factor complex in G1-S phase transition. In addition, discovering the relationship between pRB and tissue-specific transcription factors enabled a better understanding of how cell cycle exit and terminal differentiation are coupled. Recent works provoked many exciting twists in views on pRB functions during cancer initiation and progression beyond its previously well-appreciated roles. Various mitogenic and cytostatic cellular signals appeared to modulate pRB functions and thus affect a wide variety of effector molecules. In addition, genetic studies in mice as well as other creatures incessantly force us to revise our views on pRB functions. This review will focus particularly on the roles of pRB in regulating intracellular signaling, cell metabolism, chromatin function, stem cells and cancer stem cells. ( Cancer Sci 2012; 103: 1182-1188) [ABSTRACT FROM AUTHOR]

Background: In 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU) for postoperative loco-regional recurrent esophageal cancer. Methods: Between 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days). The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity. Results: A total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy. Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence) and number of recurrent lesions (worse for patients with multiple recurrent lesions) were statistically significant prognostic factors for overall survival. Conclusions: Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The Emergency Coma Scale (ECS) was developed in Japan in 2003. We planned a multicenter study to evaluate the utility of the ECS by comparison of the ECS and the Glasgow Coma Scale (GCS). Methods: Ten medical facilities, including 4 university hospitals in Japan, participated in this study. We evaluated and recorded the level of consciousness, using the ECS and GCS, of all patients transported to these medical facilities by ambulance. We then performed a statistical analysis of the level of rater agreement of each scale using the average weighted κ coefficient according to the types of diagnosis at time of discharge and the occupations of the raters. We then evaluated the relationship between outcome of patients and their scores on the ECS and GCS by logistic regression analysis. Results: The ECS showed the greater agreement among raters in patient scoring (0.802). In patients with traumatic brain injury and cerebrovascular disease, the ECS also yielded the higher agreement (0.846 and 0.779, respectively). The ECS score appears to be more strongly related than the GCS to patient outcome as measured by the Glasgow Outcome Scale (GOS). Conclusions: Our results showed that the ECS is a simple and readily understandable coma scale for a wide range of professionals in the field of neurologic emergencies. Furthermore, ECS appears to be suitable for evaluating patients in neurologic emergency settings. [Copyright &y& Elsevier]

We describe a case of an intracranial solitary fibrous tumor that recurred three times consecutively in an 11-year period. A 72-year-old man presented with a headache and gait disturbance. Magnetic resonance imaging (MRI) revealed a dumbbell tumor at the left tentorium. The tumor was removed but recurred. The first diagnosis was hemangiopericytoma, but all specimens showed a “patternless pattern” and few reticulin fibers, which features were not compatible with hemangiopericytoma. All tumors showed immunoreactivity for CD34 and bcl-2. These results point to a solitary fibrous tumor (SFT) and not to hemangiopericytoma. We present here a hypercellular spindle-cell tumor that was very similar to hemangiopericytoma but is better diagnosed as SFT. [ABSTRACT FROM AUTHOR]

Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1+/− animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1+/− mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1+/−Nras+/− animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression. [ABSTRACT FROM AUTHOR]

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase inhibitor, and experimental studies have shown that RECK can suppress tumor progression through angiogenesis inhibition. We have already revealed that enhanced RECK expression is significantly correlated with a favorable prognosis in non–small-cell lung cancer (NSCLC). In this study, further analyses focused on pN2 disease were conducted to assess the clinical significance of RECK expression. A total of 118 patients with completely resected pathologic stage IIIA N2 NSCLC were retrospectively examined. RECK expression in the primary tumor, along with involved N2 nodes, was examined immunohistochemically. RECK expression in the primary tumor was strong in 53 patients (44.9%) and was weak in the other 65 patients. The 5-year survival rate of patients with RECK-strong tumor (42.9%) was significantly higher than that of patients with RECK-weak tumor (23.1%; P = .017). Reduced RECK expression significantly correlated with a poor prognosis for patients with a single N2 node involved ( P = .019), but not for patients with multiple N2 nodes involved ( P = .440). A multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis ( P = .031). RECK expression in involved N2 nodes was significantly higher than in primary tumors ( P < .001). RECK status was a novel prognostic factor in pathologic stage IIIA N2 NSCLC. [ABSTRACT FROM AUTHOR]

The membrane-anchored MMP-regulator RECK is down regulated in many solid tumors; the extent of RECK down regulation correlates with poor prognosis. Forced expression of RECK in tumor cells results in suppression of angiogenesis, invasion, and metastasis. Studies on the roles and the mechanisms of regulation of the RECK gene during normal development may therefore yield important insights into how the malignant behaviors of tumor cells arise and how they can be controlled. Our previous studies indicate that mice lacking RECK die around E10.5 with reduced tissue integrity. In the present study, we have found that in later stage wild-type embryos, RECK is abundantly expressed in skeletal muscles, especially in the areas where the myoblast differentiation factor MRF4 is expressed. Consistent with this finding, the RECK-promoter is activated by MRF4 in cultured cells. In contrast, a myoblast determination factor MyoD suppresses the RECK-promoter. Myoblastic cells lacking RECK expression give rise to myotubes at higher efficiency than the cells expressing RECK, indicating that RECK suppresses myotube formation. These findings suggest that MyoD down regulates RECK to facilitate myotube formation, whereas MRF4 up regulates RECK to promote other aspects of myogenesis that require extracellular matrix integrity.Oncogene (2005) 24, 5850–5857. doi:10.1038/sj.onc.1208733; published online 4 July 2005 [ABSTRACT FROM AUTHOR]

Background. We constructed a remote radiotherapy planning system, and we examined the usefulness of and faults in our system in this study. Methods. Two identical radiotherapy planning systems, one installed at our institution and the other installed at an affiliated hospital, were used for radiotherapy planning. The two systems were connected by a wide area network (WAN), using a leased line. Beam data for the linear accelerator at the affiliated hospital were installed in the two systems. During the period from December 2001 to December 2002, 43 remote radiotherapy plans were made using this system. Results. Data were transmitted using a file transfer protocol (FTP) software program. The 43 radiotherapy plans examined in this study consisted of 13 ordinary radiotherapy plans, 28 radiotherapy plans sent to provide assistance for medical residents, and 2 radiotherapy plans for emergency cases. There were ten minor planning changes made in radiotherapy plans sent to provide assistance for medical residents. Conclusion. Our remote radiotherapy planning system based on WAN using a leased line is useful for remote radiotherapy, with advantages for both radiation oncologists and medical residents. [ABSTRACT FROM AUTHOR]