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Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 581-589页

作者： Yuichi Hori Tsukasa Ikeura takashi Yamaguchi Katsunori yoshida Koichi Matsuzaki Mitsuaki Ishida Sohei Satoi Kazuichi Okazaki Department of Gastroenterology and Hepatology Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan Department of Pathology Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan Department of Surgery Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan

Background:Malignant intraductal papillary mucinous neoplasm(IPMN)has poor prognosis.The carcinogenesis of IPMN is not clear.The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods:By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013.We also examined the expression of Ki-67,c-Myc and p-JNK.Results:The median immunostaining index of pSmad3C was 79.2%in low-grade dysplasia,74.9%in highgrade dysplasia,and 42.0%in invasive carcinoma(P<0.01),whereas that of pSmad3L was 3.4%,4.3%,and 42.4%,respectively(P<0.01).There was a negative relationship between the expression of pSmad3C and c-Myc(P<0.001,r=-0.615)and a positive relationship between the expression of pSmad3L and c-Myc(P<0.001,r=0.696).Negative relationship between the expression of pSmad3C and Ki-67(P<0.01,r=-0.610)and positive relationship between the expression of pSmad3L and Ki-67(P<0.01,r=0.731)were confirmed.p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells.The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58(range,0.05–0.93),3.83(range,0.85–5.96),respectively(P=0.02).The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91(range,0–36.9)and 82.1(range,46.2–97.1),respectively(P=0.02).The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9(range 5.7–30.8)and 90.9(range 52.9–98.5),respectively(P=0.02).Conclusions:pSmad3L was upregulated in malignant IPMN.pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

关键词： Intraductal papillary mucinous neoplasms of the pancreas Immunohistochemistry Phosphorylated Smad Carcinogenesis Prognosis

New methods for the management of esophageal varices

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World Journal of Gastroenterology 2007年第11期13卷 1641-1645页

作者： Hiroshi yoshida Yasuhiro Mamada Nobuhiko Taniai takashi Tajiri Department of Surgery Nippon Medical School Tokyo 1138603 Japan

Bleeding from esophageal varices (EVs) is a catastrophic complication of chronic liver disease. Many years ago, surgical procedures such as esophageal transection or distal splenorenal shunting were the only treatments for EVs. In the 1970s, interventional radiology procedures such as transportal obliteration, left gastric artery embolization, and partial splenic artery embolization were introduced, improving the survival of patients with bleeding EVs. In the 1980s, endoscopic treatment, endoscopic injection sclerotherapy (EIS), and endoscopic variceal ligation (EVL), further contributed to improved survival. We combined IVR with endoscopic treatment or EIS with EVL. Most patients with EVs treated endoscopically required follow- up treatment for recurrent varices. Proper management of recurrent EVs can significantly improve patients’ quality of life. Recently, we have performed EVL at 2-mo (bimonthly) intervals for the management of EVs. Longer intervals between treatment sessions resulted in a higher rate of total eradication and lower rates of recurrence and additional treatment.

关键词：食管静脉曲张内镜治疗干预放射学管理方法栓塞

Numerical Simulation of Flow over an Open Cavity with Self-Sustained Oscillation Mode Switching

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Open Journal of Fluid Dynamics 2016年第4期6卷 361-370页

作者： Takashi yoshida takashi Watanabe Department of Mechanical Systems Engineering Shinshu University Nagano Japan Graduate School of Information and Science Nagoya University Nagoya Japan

Numerical simulations are used to investigate the self-sustained oscillating flows past an open cavity. The two-dimensional incompressible Navier-Stokes equations are solved directly by using the finite difference method for cavities with an upstream laminar boundary layer. A series of simulations are performed for a variety of cavity length-to-depth ratio. The results show the switching among some flow modes including non-oscillation mode, shear layer mode and wake mode. The variation of the Strouhal number is in favorable agreement with available experimental data. The results of flow fields in the cavity reveal the relationship between the cavity shear layer oscillation modes and recirculating vortices in the cavity.

关键词： Open Cavity Flow Self-Sustained Oscillations Incompressible Flow Numerical Simulation

New methods for the management of gastric varices

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World Journal of Gastroenterology 2006年第37期12卷 5926-5931页

作者： Hiroshi yoshida Yasuhiro Mamada Nobuhiko Taniai takashi Tajiri Department of Surgery Nippon Medical SchoolTokyo 113-8603 Japan

Bleeding from gastric varices has been successfully treated by endoscopic modalities. Once the bleeding from the gastric varices is stabilized, endoscopic treatment and/or interventional radiology should be performed to eradicate varices completely. Partial splenic artery embolization is a supplemental treatment to prolong the obliteration of the veins feeding and/or draining the varices. The overall incidence of bleeding from gastric varices is lower than that from esophageal varices. No studies to date have defi nitively characterized the causal factors behind bleeding from gastric varices. The initial episodes of bleeding from esophageal varices or gastric varices without prior treatment may be at least partly triggered by a violation of the mucosal barrier overlying varices. This is especially likely in the case of varices of the fundus. In view of the high rate of hemostasis achieved among bleeding gastric varices, treatment should be administered in selective cases. Among untreated cases, steps to prevent gastric mucosal injury confer very important protection against gastric variceal bleeding.

关键词：治疗胃疾病静脉曲张病理机制

Diagnosis and initial management of cholangiocarcinoma with obstructive jaundice

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World Journal of Gastroenterology 2008年第19期14卷 3000-3005页

作者： takashi Tajiri Hiroshi yoshida Yasuhiro Mamada NobuhikoTaniai Shigeki Yokomuro Yoshiaki Mizuguchi Departmentof Surgery Nippon Medical School1-1-5 SendagiBunkyo-ku

Cholangiocarcinoma is the second most common primary hepatic cancer. Despite advances in diagnostic techniques during the past decade, cholangiocarcinoma is usually encountered at an advanced stage. In this review, we... 详细信息

关键词：胆管癌梗阻性黄疸诊断治疗方法

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第41期20卷 15018-15027页

作者： Miki Murata Katsunori yoshida takashi Yamaguchi Koichi Matsuzaki Department of Gastroenterology and Hepatology Kansai Medical University

Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma(HCC).HCC develops over several decades and is associated with fibrosis.This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis.The transforming growth factor-β(TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases.The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors,which phosphorylate Smad proteins.TGF-β typeⅠreceptor activates Smad3 to create COOH-terminally phosphorylated Smad3(pSmad3C),while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3(pSmad3L).During chronic liver disease progression,virus components,together with pro-inflammatory cytokines and somatic mutations,convert the Smad3 signal from tumor-suppressive pS-mad3C to fibro-carcinogenic pSmad3 L pathways,accelerating liver fibrosis and increasing the risk of HCC.The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.

关键词： Chronic viral hepatitis Transforming growth factor

Relationship between office workers’staying and workstation attributes in a non-territorial office using ultra wide band sensor network

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Frontiers of Structural and Civil Engineering 2010年第4期4卷 438-449页

作者： Xinnan ZHANG takashi IZATO Junzo MUNENOTO Daisuke MATSUSHITA Tetsu yoshida Department of Architecture Kyoto UniversityKyoto 615-8540Japan Architecture&Engineering Division TAISEI CorporationTokyo 163-0606Japan Department of Architecture Okayama University of ScienceOkayama 700-0005Japan Department of Architecture Faculty of EngineeringKyoto UniversityKyoto 615-8540Japan

This paper investigates the staying and moving characteristics of office workers in a non-territorial office using an ultra wide band(UWB)impulse radio sensor network.The differences between office workers’staying and moving are clarified according to the individual workstation type that they select.The study determines the characteristics of each type of workstation.By clarifying office workers’preference for staying and moving with regard to individual workstation types and office worker post,the reasons why office workers in different posts tended to select different types of workstations were revealed.Specifically,leaders tended to select workstations at the“inner meeting corner side”most frequently,as they had a greater need to stay in other areas.In contrast,ordinary staff needed to visit office workers in other areas less often,and as such,they tended to select individual workstations at the“middle meeting corner side.”Barring this,they tended to select individual workstations at the“middle corridor side”or“outer-meeting corner side.”Temporary staff members had little need to visit or stay at other places so they tended to select individual workstations at the“window side,”which is seldom visited or stayed at by other office workers and they could be disturbed less often from their solo work.

关键词： workplace non-territorial office staying behavior ultra wide band(UWB) sensor network

The inner solar system cratering record and the evolution of impactor populations

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Research in Astronomy and Astrophysics 2015年第3期15卷 407-434页

作者： Robert G.Strom Renu Malhotra Zhi-Yong Xiao takashi Ito Fumi yoshida Lillian R Ostrach Lunar and Planetary Laboratory The University of Arizona Planetary Science Institute China University of Geosciences(Wuhan) National Astronomical Observatory NASA Goddard Space Flight Center

We review previously published and newly obtained crater size-frequency distributions in the inner solar system. These data indicate that the Moon and the ter- restrial planets have been bombarded by two populations of objects. Population 1, dominating at early times, had nearly the same size distribution as the present-day asteroid belt, and produced heavily cratered surfaces with a complex, multi-sloped crater size-frequency distribution. Population 2, dominating since about 3.8-3.7 Gyr, had the same size distribution as near-Earth objects （NEOs） and a much lower im- pact flux, and produced a crater size distribution characterized by a differential -3 single-slope power law in the crater diameter range 0.02 km to 100 km. Taken to- gether with the results from a large body of work on age-dating of lunar and meteorite samples and theoretical work in solar system dynamics, a plausible interpretation of these data is as follows. The NEO population is the source of Population 2 and it has been in near-steady state over the past ～ 3.7-3.8 Gyr; these objects are derived from the main asteroid belt by size-dependent non-gravitational effects that favor the ejection of smaller asteroids. However, Population 1 was composed of main belt as- teroids ejected from their source region in a size-independent manner, possibly by means of gravitational resonance sweeping during orbit migration of giant planets; this caused the so-called Late Heavy Bombardment （LHB）. The LHB began some time before ～3.9 Gyr, peaked and declined rapidly over the next ～ 100 to 300 Myr, and possibly more slowly from about 3.8-3.7 Gyr to ～2 Gyr. A third crater population （Population S） consisted of secondary impact craters that can dominate the cratering record at small diameters.

关键词： solar system： formation -- minor planets asteroids -- Earth -- Moon