Showing papers by "Kumamoto University published in 2017"
Monash University1, Kyoto University2, Kindai University3, United States Department of Energy4, Kobe University5, National Institute of Genetics6, Austrian Academy of Sciences7, Nara Institute of Science and Technology8, University of Osnabrück9, Universidad Veracruzana10, University of Cambridge11, CINVESTAV12, University of Oxford13, University of Tennessee14, Plant & Food Research15, Uppsala University16, Institut de recherche pour le développement17, University of Zurich18, University of Tokyo19, Nagoya University20, Okayama University21, National Institutes of Natural Sciences, Japan22, Tohoku University23, Gregor Mendel Institute24, University of Kentucky25, Tokyo University of Agriculture26, National Taiwan University27, Cold Spring Harbor Laboratory28, Autonomous University of Madrid29, University of Arizona30, Max Planck Society31, Tokyo Metropolitan University32, University of Minnesota33, Kumamoto University34, University of Ulm35, Saitama University36
TL;DR: Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant.
774 citations
University of Toronto1, University of Düsseldorf2, German Cancer Research Center3, University of Pittsburgh4, Ontario Institute for Cancer Research5, Seoul National University6, University of Warsaw7, University of Lyon8, Mayo Clinic9, The Chinese University of Hong Kong10, Johns Hopkins University11, University of Alabama at Birmingham12, Fred Hutchinson Cancer Research Center13, University of Washington14, University of California, San Francisco15, McMaster University16, Hamilton Health Sciences17, Vanderbilt University18, University of Colorado Denver19, Semmelweis University20, Erasmus University Rotterdam21, University of Ulsan22, Kitasato University23, Mexican Social Security Institute24, Masaryk University25, Emory University26, University of Debrecen27, University of Naples Federico II28, Washington University in St. Louis29, McGill University30, Montreal Children's Hospital31, Virginia Commonwealth University32, Chonnam National University33, University of Queensland34, University of Calgary35, University of São Paulo36, University of Cincinnati37, University of Arkansas for Medical Sciences38, The Catholic University of America39, University of California, Los Angeles40, University of Sydney41, Kumamoto University42, Saint Louis University43, Case Western Reserve University44
TL;DR: Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes.
737 citations
ETH Zurich1, Buck Institute for Research on Aging2, University of Zurich3, Institute for Systems Biology4, Johns Hopkins University School of Medicine5, University of California, San Francisco6, Lunenfeld-Tanenbaum Research Institute7, University of Toronto8, Washington University in St. Louis9, Kumamoto University10, Macquarie University11
TL;DR: This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification.
Abstract: Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently detect and reproducibly quantify >4000 proteins from HEK293 cells. Using synthetic peptide dilution series, we show that the sensitivity, dynamic range and reproducibility established with SWATH-mass spectrometry are uniformly achieved. This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification. SWATH-mass spectrometry consists of a data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics on the scale of thousands of proteins. Here, using data generated by eleven groups worldwide, the authors show that SWATH-MS is capable of generating highly reproducible data across different laboratories.
372 citations
TL;DR: JPOSTrepo (https://repository.jpostdb.org/) as mentioned in this paper is a large-scale proteomics data repository with high-speed file uploading, flexible file management and easy-to-use interfaces.
Abstract: Major advancements have recently been made in mass spectrometry-based proteomics, yielding an increasing number of datasets from various proteomics projects worldwide. In order to facilitate the sharing and reuse of promising datasets, it is important to construct appropriate, high-quality public data repositories. jPOSTrepo (https://repository.jpostdb.org/) has successfully implemented several unique features, including high-speed file uploading, flexible file management and easy-to-use interfaces. This repository has been launched as a public repository containing various proteomic datasets and is available for researchers worldwide. In addition, our repository has joined the ProteomeXchange consortium, which includes the most popular public repositories such as PRIDE in Europe for MS/MS datasets and PASSEL for SRM datasets in the USA. Later MassIVE was introduced in the USA and accepted into the ProteomeXchange, as was our repository in July 2016, providing important datasets from Asia/Oceania. Accordingly, this repository thus contributes to a global alliance to share and store all datasets from a wide variety of proteomics experiments. Thus, the repository is expected to become a major repository, particularly for data collected in the Asia/Oceania region.
370 citations
TL;DR: Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARS have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo.
Abstract: Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins in Escherichia coli and mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substrate L-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.
314 citations
TL;DR: In this article, kidney organoids were assembled from mouse and human pluripotent stem cells (PSCs) and reassembled to reconstruct the structure of the human ureteric organs.
308 citations
TL;DR: It is shown that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram-positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment, and the importance of the gut-liver axis in obesity-associated HCC is shown.
Abstract: Obesity increases the risk of cancers, including hepatocellular carcinomas (HCC). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram-positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment. LTA enhances the senescence-associated secretory phenotype (SASP) of hepatic stellate cells (HSC) collaboratively with an obesity-induced gut microbial metabolite, deoxycholic acid, to upregulate the expression of SASP factors and COX2 through Toll-like receptor 2. Interestingly, COX2-mediated prostaglandin E2 (PGE2) production suppresses the antitumor immunity through a PTGER4 receptor, thereby contributing to HCC progression. Moreover, COX2 overexpression and excess PGE2 production were detected in HSCs in human HCCs with noncirrhotic, nonalcoholic steatohepatitis (NASH), indicating that a similar mechanism could function in humans.Significance: We showed the importance of the gut-liver axis in obesity-associated HCC. The gut microbiota-driven COX2 pathway produced the lipid mediator PGE2 in senescent HSCs in the tumor microenvironment, which plays a pivotal role in suppressing antitumor immunity, suggesting that PGE2 and its receptor may be novel therapeutic targets for noncirrhotic NASH-associated HCC. Cancer Discov; 7(5); 522-38. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 443.
290 citations
TL;DR: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important and postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died.
Abstract: Objective: To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. Methods: We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. Results: There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti–acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients9 daily living activity. Conclusions: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.
274 citations
TL;DR: The favorable physiological degradation behavior of pure zinc stents makes zinc a promising candidate for future stent applications.
235 citations
TL;DR: It is shown that in vivo lipopolysaccharide (LPS) application induces proliferation of dormant HSCs directly via TLR4 and that sustained LPS exposure impairs HSC self-renewal and competitive repopulation activity.
196 citations
TL;DR: A dilute solution system with the highest circularly polarized luminescence intensity achieved to date and a dissymmetry factor of over 0.1 was identified.
Abstract: A new strategy is described for generating strong circularly polarized luminescence with highly tunable emission bands through chiral induction in nonchiral, totally organic, low-molecular-weight fluorescent dyes by chiral nanotemplate systems. Our approach allows the first systematic investigation to clarify the correlation between the circular dichroism and circularly polarized luminescence intensities. As a result, a dilute solution system with the highest circularly polarized luminescence intensity achieved to date and a dissymmetry factor of over 0.1 was identified.
Kyoto University1, University of Tokushima2, National Presto Industries3, Jichi Medical University4, University of Tsukuba5, University of Edinburgh6, University College London7, Kōchi University8, Kumamoto University9, Gunma University10, University of Tokyo11, University of Miyazaki12, Laval University13, Institute of Medical Science14, Kansai Medical University15, Wakayama Medical University16
TL;DR: Analysis of ALS patient iPSC-derived motor neurons indicates that Src/c-Abl inhibitors may have potential for treating ALS, and a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout shows that inhibitors of Src or c-ABL kinases promoted autophagy and rescued ALS motor neurons from degeneration.
Abstract: Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1) Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro Knockdown of Src or c-Abl with small interfering RNAs (siRNAs) also rescued ALS motor neuron degeneration One of the hits, bosutinib, boosted autophagy, reduced the amount of misfolded mutant SOD1 protein, and attenuated altered expression of mitochondrial genes Bosutinib also increased survival in vitro of ALS iPSC-derived motor neurons from patients with sporadic ALS or other forms of familial ALS caused by mutations in TAR DNA binding protein (TDP-43) or repeat expansions in C9orf72 Furthermore, bosutinib treatment modestly extended survival of a mouse model of ALS with an SOD1 mutation, suggesting that Src/c-Abl may be a potentially useful target for developing new drugs to treat ALS
TL;DR: It is suggested that based on the available data, differences in clinical trial outcomes between nivolumab and pembrolizumab are more likely drug-independent than drug-dependent.
TL;DR: A new growth strategy employing chemical vapor deposition is developed to grow monolayer 2D alloys of Re-doped MoSe2 with show composition tunable structural phase variations which provide opportunities to study novel phenomena such as magnetism which broadens the range of their applications.
Abstract: Alloying in 2D results in the development of new, diverse, and versatile systems with prospects in bandgap engineering, catalysis, and energy storage. Tailoring structural phase transitions using alloying is a novel idea with implications in designing all 2D device architecture as the structural phases in 2D materials such as transition metal dichalcogenides are correlated with electronic phases. Here, this study develops a new growth strategy employing chemical vapor deposition to grow monolayer 2D alloys of Re-doped MoSe2 with show composition tunable structural phase variations. The compositions where the phase transition is observed agree well with the theoretical predictions for these 2D systems. It is also shown that in addition to the predicted new electronic phases, these systems also provide opportunities to study novel phenomena such as magnetism which broadens the range of their applications.
TL;DR: In this article, the authors analyzed several combinations of explosively welded alloys and concluded that the heating rate at the interfaces was of the order of 10 9 K/s, while the cooling rate achieved 10 7 K/S. The formation of different types of metastable phases is discussed with respect to the compositions of the welded materials.
TL;DR: In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE coupled with single-molecule sequencing to represent the consequence of transcriptional regulation in each analyzed state of mammalian cells.
Abstract: In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
University of Tasmania1, Norwegian University of Science and Technology2, Auckland University of Technology3, Royal Hobart Hospital4, St Thomas' Hospital5, Taipei Veterans General Hospital6, Imperial College London7, University College London8, National Institute for Health Research9, Aarhus University Hospital10, Shanghai Jiao Tong University11, Abbott Northwestern Hospital12, Flinders University13, Nagoya City University14, Chiba University15, University of Erlangen-Nuremberg16, Polytechnic Institute of Coimbra17, University of Perugia18, Kumamoto University19, Guy's and St Thomas' NHS Foundation Trust20, State University of New York Upstate Medical University21, Monash University22, University of Auckland23, University of North Carolina at Chapel Hill24, Tokyo Medical University25, VU University Medical Center26, University of Duisburg-Essen27, University of Tokushima28
TL;DR: Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification, indicating that stronger accuracy standards for BP devices may improve cardiovascular risk management.
TL;DR: It is demonstrated that the vascular network could administer biological substances to the interior of the spheroid, and the perfusable vasculature model opens up new possibilities for a long-term tissue culture in vitro.
Abstract: Creating vascular networks in tissues is crucial for tissue engineering Although recent studies have demonstrated the formation of vessel-like structures in a tissue model, long-term culture is still challenging due to the lack of active perfusion in vascular networks Here, we present a method to create a three-dimensional cellular spheroid with a perfusable vascular network in a microfluidic device By the definition of the cellular interaction between human lung fibroblasts (hLFs) in a spheroid and human umbilical vein endothelial cells (HUVECs) in microchannels, angiogenic sprouts were induced from microchannels toward the spheroid; the sprouts reached the vessel-like structures in a spheroid to form a continuous lumen We demonstrated that the vascular network could administer biological substances to the interior of the spheroid As cell density in the spheroid is similar to that of a tissue, the perfusable vasculature model opens up new possibilities for a long-term tissue culture in vitro
TL;DR: Many of the genes with increased expression in CAFs compared with NFs were associated with transforming growth factor beta 1 (TGFB1) activity, and RHBDF2 appeared to regulate oncogenic and non-canonical TGFB 1 signaling.
Chiba University1, Yokohama City University2, Kyushu University3, Japanese Foundation for Cancer Research4, Kyoto University5, Kansai Medical University6, Kagoshima University7, Kindai University8, Kumamoto University9, Tokai University10, Tohoku University11, Nagoya City University12, Fukushima Medical University13, University of Occupational and Environmental Health Japan14, Kyorin University15
TL;DR: Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G2, and both showed distinct clinicopathologic characteristics.
Abstract: Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival. Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed. Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625–32. ©2017 AACR.
TL;DR: It is shown that cell–cell interaction between these two cell types induced recruitment and activation of each other, and that the combined activities of these cells were involved in neuroblastoma progression.
Abstract: Many non-tumour host cells such as inflammatory cells, fibroblasts, and endothelial cells are present in the tumour microenvironment and affect the malignant potential and chemo-resistance of the tumour cells Macrophages and fibroblasts are the main components of infiltrating stromal cells and are referred to as tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively TAMs and CAFs are reported to be involved in tumour progression, although their functions change to those of an anti-tumour phenotype under specific conditions Notably, recent work published in The Journal of Pathology by Hashimoto and colleagues provided critical evidence indicating the significance of collaboration between TAMs and CAFs for tumour progression They showed that cell-cell interaction between these two cell types induced recruitment and activation of each other, and that the combined activities of these cells were involved in neuroblastoma progression Although many research groups are now interested in the significance of stromal cells such as CAFs and TAMs for tumour progression, only a few studies have been published describing the cell-cell interactions of these cells Cell-cell interactions of stromal cells potentially play important roles in tumour progression and should be a focus for further oncology research Copyright © 2016 Pathological Society of Great Britain and Ireland Published by John Wiley & Sons, Ltd
01 Jan 2017
TL;DR: The findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.
Abstract: Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8+ T cell responses in skin-draining LNs. Our findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.
TL;DR: In this article, zinc hydroxychloride nanosheets (ZHCNs) were deposited on 3D graphene-nickel foam (NiF-G) by employing a simple hydrothermal synthesis method to form NiFG-G/ZHCN composite electrode materials.
TL;DR: PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker, and the combination with TIL status enabled further classification patients according to clinical outcome.
Abstract: Objectives:To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer.Summary Background Data:PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based t
TL;DR: Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety and significantly decreased alanine aminotransferase and gamma-glutamyltransferase levels, whereas fen ofibrate increased both of them.
TL;DR: The importance of this pathophysiological event of EPR effect can be applied to macromolecular drug-delivery, or tumor selective delivery, which takes hours to achieve in the primary as well as metastatic tumors, not to mention of the inflamed tissues.
Abstract: History of the EPR (enhanced permeability and retention) effect is discussed, which goes back to the analyses of molecular pathology in bacterial infection and edema (extravasation) formation. The first mediator we found for extravasation was bradykinin. Later on, were found nitric oxide and superoxide, then formation of peroxynitrite, that activates procollagenase. In this inflammatory setting many other vascular mediators are involved that are also common to cancer vasculature. Obviously cancer vasculature is defective architechtally, and this makes macromolecular drugs more permeable through the vascular wall. The importance of this pathophysiological event of EPR effect can be applied to macromolecular drug-delivery, or tumor selective delivery, which takes hours to achieve in the primary as well as metastatic tumors, not to mention of the inflamed tissues. The retention of the EPR means that such drugs will be retained in tumor tissues more than days to weeks. This was demonstrated initially, and most dramatically, using SMANCS, a protein-polymer conjugated-drug dissolved in lipid contrast medium (Lipiodol) by administering intraarterially. For disseminating the EPR concept globally, or in the scientific community, Professor Ruth Duncan played a key role at the early stage, as she worked extensively on polymer- therapeutics, and knew its importance.
TL;DR: Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis and clinicopathologic factors retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology were retrieved.
Abstract: Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy.
TL;DR: It is demonstrated that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A, and links sequence specific target recognition by the MAX/MGA complex to PRC 1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.
Abstract: The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.
TL;DR: Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting.
Abstract: Background:The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. Methods:The JPAD t...