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Circulating tumor DNA dynamics analysis in a xenograft mouse model with esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2021年第41期27卷 7134-7143页

作者： Hiroyuki Terasawa Hideaki Kinugasa Kazuhiro Nouso Shumpei Yamamoto Mami Hirai Takehiro Tanaka akinobu takaki Hiroyuki Okada Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan Department of Pathology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan

BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always *** use liquid biopsies clinically,it will be very important to address these *** To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA *** Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell *** of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA *** of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)*** Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week *** hTERT was detected at week 4,but it was detected at week ***,in four-site xenograft mice,hTERT was detected both at week 4 and week *** experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of *** resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after *** We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important *** also found that when the tumor was completely resected,ctDNA was absent after one or more days.

关键词： Liquid biopsy Circulating tumor DNA Xenograft Esophageal squamous cell carcinoma Dynamics of circulating tumor DNA

Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

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World Journal of Gastroenterology 2012年第44期18卷 6427-6436页

作者： Masaya Iwamuro Hiroyuki Okada Katsuyoshi Takata Katsuji Shinagawa Shigeatsu Fujiki Junji Shiode Atsushi Imagawa Masashi Araki Toshiaki Morito Mamoru Nishimura Motowo Mizuno Tomoki Inaba Seiyu Suzuki Yoshinari Kawai Tadashi Yoshino Yoshiro Kawahara akinobu takaki Kazuhide Yamamoto Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan Department of Endoscopy Okayama University HospitalOkayama 700-8558Japan Department of Pathology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan Department of Hematology and Oncology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan Department of Internal Medicine Tsuyama Central HospitalTsuyama 708-0841Japan Department of Internal Medicine Okayama Saiseikai General HospitalOkayama 700-8511Japan Department of Gastroenterology Mitoyo General HospitalKanonji 769-1695Japan Department of Internal Medicine Kagawa Rosai HospitalMarugame 763-8502Japan Department of Anatomic Pathology Kagawa Rosai HospitalMarugame 763-8502Japan Department of Internal Medicine Okayama Citizens' HospitalOkayama 700-8557Japan Department of Internal Medicine Hiroshima City HospitalHiroshima 730-8518Japan Department of Gastroenterology Kagawa Prefectural Central HospitalTakamatsu 760-8557Japan Department of Internal Medicine Sumitomo Besshi HospitalNiihama 792-8543Japan Department of Gastroenterology Onomichi Municipal HospitalOnomichi 722-8503Japan

AIM:To investigate the capacity for 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography(PET) to evaluate patients with gastrointestinal lesions of follicular ***:This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October *** for endoscopic,radiological,and biological examinations performed were retrospectively reviewed from clinical records.A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value(SUVmax).Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed,patients were subdivided into two *** identify potential predictive factors for 18F-FDG positivity,these two groups were compared with respect to gender,age at diagnosis of lymphoma,histopathological grade,pattern of follicular dendritic cells,mitotic rate,clinical stage,soluble interleukin-2 receptor levels detected by 18F-FDG-PET,lactate dehydrogenase(LDH) levels,hemoglobin levels,bone marrow involvement,detectability of gastrointestinal lesions by computed tomography(CT) scanning,and follicular lymphoma international prognostic index(FLIPI) ***:Involvement of follicular lymphoma in the stomach,duodenum,jejunum,ileum,cecum,colon,and rectum was identified in 1,34,6,3,2,3,and 6 patients,*** patient had esophageal *** total,19/41(46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal *** contrast,false-negative 18F-FDG uptake was detected in 24 patients(58.5%),while false-positive 18F-FDG uptake was detected in 5 patients(12.2%).In the former case,2/19 patients had both 18F-FDG-positive lesions and 18F-FDGnegative lesions in the gastrointestinal *** patients with 18F-FDG avidity,the SUVmax value of the involved gast

关键词： Follicular lymphoma Gastrointestinal endoscopy F-fluorodeoxyglucose positron emission tomography Gastrointestinal lymphoma Duodenal neoplasm

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

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development

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World Journal of Hepatology 2015年第19期7卷 2220-2228页

作者： Yasuto Takeuchi Fusao Ikeda Toshiya Osawa Yasuyuki Araki Kouichi Takaguchi Youichi Morimoto Noriaki Hashimoto Kousaku Sakaguchi Tatsuro Sakata Masaharu Ando Yasuhiro Makino Shuji Matsumura Hiroki Takayama Hiroyuki Seki Shintarou Nanba Yuki Moritou Tetsuya Yasunaka Hideki Ohnishi akinobu takaki Kazuhiro Nouso Yoshiaki Iwasaki Kazuhide Yamamoto Department of Gastroenterology and Hepatology Okayama University Graduate School of Medicine Dentistry and Pharma- ceutical Sciences Department of Molecular Hepatology Okayama University Graduate School of Medicine Dentistry and Pharma- ceutical Sciences Department of Internal Medicine Okayama Saiseikai General Hospital Department of Internal Medicine Hiroshima City Hospital Department of Internal Medicine Kagawa Prefectural Central Hospital Department of Internal Medicine Kurashiki Central Hospital Department of Internal Medicine Mihara Red Cross hospital Department of Internal Medicine Fukuyama City Hospital Department of Internal Medicine National Hospital Organization Fukuyama Clinical Center Department of Internal Medicine Mitoyo General Hospital Department of Gastroenterology National Hospital Organization Iwakuni Clinical Center Department of Internal Medicine Sumitomo Besshi Hospital Department of Gastroenterology Tsuyama Central Hospital Health Service Center Okayama University

AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m ***: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

关键词： Hepatitis C virus Interferon Hepatocellular carcin

Contribution of adult-born neurons to memory consolidation during rapid eye movement sleep

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Neural Regeneration Research 2022年第2期17卷 307-308页

作者： akinobu Ohba Masanori Sakaguchi International Institute for Integrative Sleep Medicine(WPI-IIIS) University of TsukubaTsukubaIbarakiJapan

Introduction: Memory consolidation stabilizes newly acquired memories by integrating them into pre-existing memory networks, which is thought to occurvia changes in synaptic strength. Sleep may influence memory consol... 详细信息

关键词： strength. sleep integrating

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

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)

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