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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 *** 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 *** 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 *** 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 *** quantity and quality of these samples will be compatible with omics *** 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

Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

Deformation mechanism of bimodal microstructure in Ti-6Al-4V alloy:The effects of intercritical annealing temperature and constituent hardness

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Journal of Materials Science & Technology 2021年第12期71卷 138-151页

作者： Yan Chong Tilak Bhattacharjee Yanzhong Tian akinobu Shibata Nobuhiro Tsuji Department of Materials Science and Engineering Kyoto UniversityKyotoJapan Department of Materials Science and Engineering University of CaliforniaBerkeleyCAUSA Elements Strategy Initiative for Structural Materials(ESISM) Kyoto UniversityKyotoJapan Key Laboratory for Anisotropy and Texture of Materials School of Materials Science and EngineeringNortheastern UniversityShenyang 110819China Research Center for Metallic Wires Northeastern UniversityShenyang 110819China

The so-called bimodal microstructure of Ti-6 Al-4 V alloy,composed of primaryαgrains(α_(p))and transformed β areas(β_(trans)),can be regarded as a"dual-phase"structure to some extent,the mechanical properties of which are closely related to the sizes,volume fractions,distributions as well as nanohardness of the two *** this study,the volume fractions of primaryαgrains(vol.%(α_(p)))were systematically modified in three series of bimodal microstructures with fixed primaryαgrain sizes(0.8μm,2.4μm and 5.0μm),by changing the intercritical annealing temperature(T_(int)).By evaluating the tensile properties at room temperature,it was found that with increasing T_(int)(decreasing vol.%(α_(p))),the yield strength of bimodal microstructures monotonically increased,while the uniform elongation firstly increased with T_(int)until 910°C and then drastically decreased afterwards,thereby dividing the T_(int)into two regions,namely region I(830-910°C)and region II(910-970℃).The detailed deformation behaviors within the two regions were studied and compared,from the perspectives of strain distribution analysis,slip system analysis as well as dislocation *** bimodal microstructures in region I,due to the much lower nano-hardness ofβ_(trans)thanα_(p),there was a clear strain partitioning between the two constituents as well as a strain gradient from theα_(p)/β_(trans)interface to the grain interior ofα_(p).This activated a large number of geometrically necessary dislocations(GNDs)near the interface,mostly with components,which contributed greatly to the extraordinary work-hardening abilities of bimodal microstructures in region *** increasing T_(int),theα_(p)/β_(trans)interface length density gradually increased and so was the density of GNDs with components,which explained the continuous increase of uniform elongation with T_(int)in this *** bimodal microstructures in region II,where the nano-hardness ofβ_(trans)andα_(p)were comparable,neither a clear s

关键词： Ti-6Al-4V Bimodal microstructure Intercritical annealing temperature Strain distribution dislocation

Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

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World Journal of Hepatology 2015年第7期7卷 968-979页

作者： akinobu Takaki Kazuhide Yamamoto Department of Gastroenterology and Hepatology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences

Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease(CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.

关键词： Liver cancer Liver cirrhosis Hepatitis B Viral protein C Non-alcoholic steatohepatitis Reactiveoxygen species

Monoclonal antibody pharmacogenomics in cancer treatment

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Journal of Cancer Metastasis and Treatment 2019年第11期4卷 23-35页

作者： Shigehiro Yagishita akinobu Hamada Division of Molecular Pharmacology National Cancer Center Research InstituteChuo-kuTokyo 104-0045Japan

Conventionally, in the pharmacokinetic/pharmacodynamic analysis of small molecule compounds such as cytotoxic anticancer drugs, polymorphism analysis of genes related to absorption, distribution, metabolism, and excretion has been performed in addition to the analyses of blood concentrations of drugs. Such pharmacogenetic factors play an important role in predicting therapeutic effects and adverse events and in the proper use of drugs. With the recent launch of immune checkpoint inhibitors (ICIs) and the rapid development of antibody-drug conjugates (ADCs) currently underway, there is no doubt that antibody drugs, which are large molecule compounds, will become key drugs in anticancer drug treatment. However, the pharmacokinetic and pharmacodynamic analysis of antibody drugs is still not sufficient, and further elucidation of factors and mechanisms affecting their dynamics in the human body is necessary. Moreover, the pharmacogenomic factors of antibody drugs have not yet been fully studied. There are many factors that should be clarified, such as factors that regulate the host immune response in ICI therapy and the effects of ATP-binding cassette transporter and cytochrome P450 on the payload of ADCs. This review provides an outline of antibody drugs in cancer treatment and summarizes the pharmacogenomic factors of antibody drugs known to date.

关键词： Pharmacogenomics antibody drug antibody-dependent cellular cytotoxicity immune checkpoint inhibitor antibody-drug conjugate

Strain-dependence of deformation microstructures in ultra-low-C IF steel deformed to high strains by torsion at elevated temperatures

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Nano Materials Science 2020年第1期2卷 83-95页

作者： Reza Gholizadeh Daisuke Terada akinobu Shibata Nobuhiro Tsuji Department of Materials Science and Engineering Kyoto UniversityYoshida HonmachiSakyo-kuKyoto606-8501Japan ESISM(Elements Strategy Initiative for Structural Materials) Kyoto UniversityYoshida HonmachiSakyo-kuKyoto606-8501Japan Department of Advanced Materials Science and Engineering Chiba Institute of TechnologyTsudanumaNarashino275-0016Japan

Single-phase bcc-ferrite in an interstitial free(IF)steel was deformed to different strains in a wide range from low to high strains(ε=1–7)by torsion under different Zener-Hollomon(Z)*** specimens were rapidly quenched after the torsion to preserve microstructures formed under different deformation *** results showed that during high-Z(low-temperature)deformation,grains were subdivided by geometrically necessary boundaries(GNBs)via the grain subdivision *** to high strains(ε>5)led to the ultrafine lamellar structures(with grain sizes1μm)were realized with decreasing *** significance of the grain subdivision and the thermally activated phenomena on the formation of various microstructures under different deformation conditions is discussed.

关键词： Severe plastic deformation Grain subdivision Ultrafine grains Zener-Hollomon parameter Boundary migration Electron backscattering diffraction(EBSD)

Transition of Groundwater and Subsurface Thermal Environment in the Tokyo Metropolitan Area,Japan

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地学前缘 2009年第S1期16卷 15-16页

作者： akinobu Miyakoshi Takeshi Hayashi Institute for Geo-Resources and Environment National Institute of Advanced Industrial Science and Technology Faculty of Education and Human Studies Akita University

Information on three-dimensional subsurface temperature distribution and its change were examined by measuring of temperature-depth profiles at observation wells in 2001-2002 and 2005-2006,to evaluate the subsurface t... 详细信息

关键词： groundwater flow subsurface temperature urban subsurface environment urbanization Tokyo

Familial occurrence of congenital bile duct dilatation

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World Journal of Gastroenterology 2008年第6期14卷 941-943页

作者： Junji Iwasaki Yoshifumi Ogura Shunichi Nakagawa Kenji Kato akinobu Kondo Katsuya Shiraki Department of Surgery Matsusaka City Hospital 1550 Tono-machi Matsusaka Mie 515-8544 Japan First Department of Internal Medicine Mie University School of Medicine 2-174 Edobashi Tsu Mie 514-8507 Japan

Congenital bile duct dilatation (CBD) that developed in a parent and son is presented. Familial occurrence of CBD is rare, with only a few male cases having been reported. Since the initial report of CBD occurring in siblings in 1981, a total of 20 cases (10 pairs) have been published as of 2007. Clinical and genetic features of CBD are discussed.

关键词： Congenital bile duct dilatation Familial occurrence Choledochal cyst Choledochocele Anomalous pancreaticobiliary duct junction

High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 454-463页

作者： Shingo Shimada Toshiya Kamiyama Tatsuya Orimo Akihisa Nagatsu Hirofumi Kamachi akinobu Taketomi Department of Gastroenterological Surgery I Hokkaido University Graduate School of MedicineSapporoJapan

Background:Currently,the population with type 2 diabetes mellitus(DM)is increasing ***,the influence of DM or hyperglycemia on the outcome of resected hepatocellular carcinoma(HCC)is ***:We analyzed 756 patients with HCC who underwent *** patients were assigned to an HbA1c≥7.0%(H-A1c;n=100)or HbA1c<7.0%(L-A1c;n=656)group depending on their HbA1c level at *** investigated prognoses,clinicopathological characteristics and surgical outcomes including morbidities of HCC patients with high HbA1c,prognoses according to the treatment for DM were also ***:Among all patients and those with hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,overall survival(OS)and relapse-free survival(RFS)did not differ significantly between the H-A1c and L-A1c *** contrast,the 5-year OS rate of the H-A1c group was 55%and that of the L-A1c group 71%among patients without HBV and HCV(NBNC patients)(P=0.03).Among NBNC patients,the median RFS of the H-A1c group was 13 months,and that of the L-A1c group was 26 months(P=0.02).In addition,metformin use was an independent favorable factor for both OS and *** H-A1c group had significantly higher rates of hyperbilirubinemia,wound infection,and ***:HCC patients with high HbA1c might have poor prognoses for both survival and recurrence in *** HbA1c may also be a risk factor for morbidities after *** use may constitute a good option for NBNC patients with HCC.

关键词： Hepatocellular carcinoma(HCC) HbA1c diabetes mellitus(DM) hepatectomy metformin