The roles of ASK family proteins in stress responses and diseases

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase family, which activates c-Jun N-terminal kinase and p38 in response to a diverse array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. In the past decade, various regulatory mechanisms of ASK1 have been elucidated, including its oxidative stress-dependent activation. Recently, it has emerged that ASK family proteins play key roles in cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the recent findings on ASK family proteins and their implications in various diseases

卓球におけるドライブ打法の重要性とその練習に関する提言

Acquisition of "Basic Posture" must be the initial practise in table tennis. Basic posture means the posture before and after one hits the ball. All action should start from the basic posture before hitting and should end with the basic posture after hitting the ball. The fundamental theory must be explained to giue better understanding to this "Driue technique". When this technique is employed, everyone would notice that the player swing his racket up from lower position then the center of his body and swing up diagonally to the upper front of the body. This technique can be analized into two major motions. Driue motion (the stroke made for giving the ball a forward spin by hitting the ball until the ball receives enough friction to spin. Speed motion hitting the ball from back to front in order to give the ball, "forward moving power". There are the reasons why "Driue" and "Speed". are necessary. First "drive motion" can give the ball a "forward spinning motion". and this motion helps the ball drop the moment the spinning ball faces the air receiving the air-resistance. Thus, higher percentage of success in the other side of the table will be expected. This is, therefore, "Driue technique" is all about. I belieue that tennis world of Japan should with no exception employ this technique. Aboue are why I would like to discuss this subject and I would be honored to re ceivie your comments and opinions

Relative stereochemical determination of the C61–C83 fragment of symbiodinolide using a stereodivergent synthetic approach

Structural determination is required in the use of marine natural products to create novel drugs and drug leads in medicinal chemistry. Symbiodinolide, which is a polyol marine natural product with a molecular weight of 2860, increases the intracellular Ca2+ concentration and exhibits inhibitory activity against cyclooxygenase-1. Seventy percent of the structure of symbiodinolide has been stereochemically clarified. Herein, we report the elucidation of the relative configuration of the C61–C83 fragment, which is among the remaining thirty percent, using a stereodivergent synthetic strategy. We first assigned the relative configuration of the C61–C74 fragment. Two candidate diastereomers of the C61–C74 fragment were synthesized, and their NMR data were compared with those of the natural product, revealing the relative stereochemistry of this component. We then narrowed down the candidate compounds for the C69–C83 fragment from 16 possible diastereomers by analyzing the NMR data of the natural product, and we thus selected eight candidate diastereomers. Stereodivergent synthesis of the candidates for this fragment and comparison of the NMR data of the natural product and the eight synthetic products resulted in the relative stereostructural clarification of the C69–C83 fragment. These individually determined relative stereochemistries of the C61–C74 and C69–C83 fragments were connected via the common C69–C73 tetrahydropyran moiety of the fragments. Finally, the relative configuration of the C61–C83 fragment of symbiodinolide was determined. The stereodivergent synthetic approach used in this study can be extended to the stereochemical determination of other fragments of symbiodinolide

本学部のスポーツ傷害に関する調査報告

Sport injury that occurred in sport activity or during training has become a serious problem in resent years. Here we know a fact that is in all the developed countries, people have more leisure time and need more sport activities as a part of their daily life. It\u27s simply a matter of fact that is the more the people participated in sport activities the more the chance of injury increased. So there is a question, how could people lose their valuable life or became handicap through whole of his life simple by way of sport? We still know the most important thing for sport is to promot ones\u27 physical condition toword soundly body status. Today the students in sport clubs, they believe the suprume goal of sport is to win. In this paper we try to arouse the student and their instructors to pay more attention to the facts, what coused sport injury and how to prevent it occur, especially for these kinds of sport as aquatics, skiing, maintain claim, combatives and ball games. Here we summarized the students of this college as insurant for sport injury in 1978. We wish some findings may be of benifet to the works of prevention and improvement of the sport injury as follow ; 1. Above 50% of the case is occupied by the students of freshment, and the persentage decreased with the grade from freshment to senior. 2. There is nearly 80% of the whole cases that advented from the students in the club of Rugby. 3. Above 90% of the injury is occurred from the students in doing their club activities. 4. The most advented injury occurred in the body is the lower extrimities, it occupied half of the whole case. 5. May, March and October in a year are the months caused more injury, August, September are the months less injury occurred. 6. No significant relationship could be seen between sports and the kinds of injury in this study

Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma

Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2-STAT3-OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2-STAT3-OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness

A pilot study of the multiherb Kampo medicine bakumondoto for cough in patients with chronic obstructive pulmonary disease

Objectives: To evaluate the effect of bakumondoto. Kampo medicine, on cough in patients with chronic obstructive pulmonary disease (COPD). Design: A 16-week, randomized, open-labeled, cross-over design. Setting: Outpatient clinics at one university hospital and two general hospitals in Japan from May 2007 to March 2009. Participants: Twenty-four elderly patients (14 men and 9 women aged over 65) with COPD. Intervention: Treatment with or without bakumondoto for 8 weeks in a cross-over design. Measurements: The primary outcome measurements were the frequency and intensity of cough assessed by a visual analogue scale (VAS) and a daily cough diary. Secondary outcome measurements were quality of life (QOL) assessed using St. George's Respiratory Questionnaire (SGRQ) and lung functions measured using spirometry. Results: Treatment with bakumondoto significantly improved cough severity during the first treatment period (week 0 vs. week 8, p = 0.004) and showed a trend to decrease during the second treatment period (week 8 vs. week16, p=0.129) assessed by the VAS. Neither QOL nor lung function was affected by the treatment with bakumondoto. Conclusion: Bakumondoto may be effective in suppressing cough in elderly patients with COPD. To further confirm the efficacy, a larger and placebo-controlled study with objective cough assessment is necessary

Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration

Glioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells

Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC

Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits. Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing. Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004). Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers