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BCR–ABL-specific CD4^(+) T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells

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Cellular & Molecular Immunology 2018年第1期15卷 15-26页

作者： norihiro ueda Rong Zhang Minako Tatsumi Tian-YiLiu Shuichi Kitayama YutakaYasui Shiori Sugai Tatsuaki Iwama Satoru Senju Seiji Okada Tetsuya Nakatsura Kiyotaka Kuzushima Hitoshi Kiyoi Tomoki Naoe Shin Kaneko Yasushi Uemura Division of Immunology Aichi Cancer Center Research InstituteNagoya464-0021Japan Shin Kaneko Laboratory Department of Cell Growth and DifferentiationCenter for iPS cell Research and Application(CiRA)Kyoto UniversityKyoto606-8507Japan Department of Hematology and Oncology Nagoya University Graduate School of MedicineNagoya466-0065Japan Division of Cancer Immunotherapy Exploratory Oncology Research&Clinical Trial CenterNational Cancer CenterKashiwa277-8577ChibaJapan Key Laboratory of Cancer Center Chinese PLA General HospitalBeijing100853China Department of Immunogenetics Graduate School of Medical SciencesKumamoto UniversityKumamoto860-8556Japan Division of Hematopoiesis Center for AIDS ResearchKumamoto UniversityKumamoto860-0811Japan National Hospital Organization Nagoya Medical Center Nagoya460-0001Japan

The advent of tyrosine kinase inhibitor(TKI)therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia(CML).However,the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKIs are remaining challenges;therefore,an effective therapeutic has been *** BCR–ABL p210 fusion protein’s junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen-specific T-cell ***–ABL p210 fusion-region-specific CD4+T-helper(Th)cells possess antileukemic potential,but their function remains *** this study,we established a BCR–ABL p210 b3a2 fusion-region-specific CD4+Th-cell clone(b3a2-specific Th clone)and examined its dendritic cell(DC)-mediated antileukemic *** b3a2-specific Th clone recognized the b3a2 peptide in the context of HLA-DRB1*09:01 and exhibited a Th1 *** of this clone through T-cell antigen receptor stimulation triggered DC maturation,as indicated by upregulated production of CD86 and IL-12p70 by DCs,which depended on CD40 ligation by CD40L expressed on b3a2-specific Th ***,in the presence of HLA-A*24:02-restricted Wilms tumor 1(WT1)235–243 peptide,DCs conditioned by b3a2-specific Th cells efficiently stimulated the primary expansion of WTI-specific cytotoxic T lymphocytes(CTLs).The expanded CTLs were cytotoxic toward WT1235–243-peptide-loaded HLA-A*24:02-positive cell lines and exerted a potent antileukemic effect in ***,the b3a2-specific Th-clone-mediated antileukemic CTL responses were strongly inhibited by both TKIs and interferon-α.Our findings indicate a crucial role of b3a2-specific Th cells in leukemia antigen-specific CTL-mediated immunity and provide an experimental basis for establishing novel CML immunotherapies.

关键词： BCR-ABL cancer immunotherapy CML dendritic cell T helper cell

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Relationship between portal hypertension and liver stiffness measurements in the treatment of hepatocellular carcinoma from the surgeon’s point of view in the Baveno VII era

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 150-153页

作者： Nobuyuki Takemura norihiro Kokudo Hepato-Biliary Pancreatic Surgery Division Department of SurgeryNational Center for Global Health and MedicineShinjyuku-kuTokyoJapan

Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide(1).It often arises from the backgrounds of damaged liver due to viral hepatitis,alcoholic,or non-alcoholic liver *** the proportion of patients with HCC of non-hepatitis B and C origins has increased in recent years,hepatitis B and C viruses still cause more than half of all carcinogenesis in patients with HCC(2).Patients with HCC often develop portal hypertension(PHT)from cirrhosis due to the deterioration of the background liver,which proves to be the greatest obstacle to various types of treatments for HCC.

关键词： Hepatocellular carcinoma(HCC) portal hypertension(PHT) Baveno VII hepatectomy clinically significant portal hypertension(CSPH)

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Near-Field Birefringence Response of Liquid Crystal Molecules in Thickness Direction of Liquid Crystal Thin Film Orientated by Shear Force

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Chinese Physics Letters 2007年第10期24卷 2906-2909页

作者： Jing QIN norihiro UMEDA Faculty of Engineering Tokyo University of Agriculture and Technology 2-24-16 Naka-cho Koganei Tokyo 184-8588 3apan

Information of molecular orientation in nematic liquid crystal （LC） is attractive and important for applications in the field of display devices. We demonstrate a novel method using a birefringence scanning near-field optical microscope （Bi-SNOM） with a probe which is inserted into the LC thin film to detect the molecular orientation from its birefringence responses in the thickness direction of the LC thin film. The probe is laterally vibrated when going forward into the LC thin film, and the retardation and azimuth angle are recorded as the probe going down. Firstly, the thickness of the LC thin film is measured by the shear force detection. Since the shear force acts as a stimulation to reorientate the LC molecules above the substrate surface, we can detect the molecular orientation caused by a polyimide alignment substrate and the effect to molecular orientation caused by vibration of fibre probe. As a result, the orientation profiling of the LC film in depth direction is obtained in both the cases that the direction of probe vibrating is vertical/parallel to the rubbing direction of the alignment film. Furthermore, the thickness of completely orientated layers just above the substrate surface can also be obtained by either vibrating probe or no-vibrating probe. Ultimately, the LC thin film can be modelled in thickness direction from all the results using this method.

关键词： coated conductor buffer layer self-epitaxy CeO2

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Clinical practice guidelines for hepatocellular carcinoma:the first evidence based guidelines from Japan

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World Journal of Gastroenterology 2006年第5期12卷 828-829页

作者： Masatoshi Makuuchi norihiro Kokudo Department of Surgery Hepato-Biliary-Pancreatic Surgery DivisionUniversity of TokyoTokyoJapan

Hepatocellular carcinoma （HCC） is one of the leading causes of cancer death in Japan, ranked 3^rd in males and 5^th in females. Thanks to recent progress, there are several definitive treatment modalities available for HCC, including surgery （liver resection and transplantation）, ablation therapy, and transarterial chemoembolization （TACE）. It is fortunate for both patients and doctors to have multiple treatment options, however, there have been very few evidence-based guidelines for decision-making. Sup- ported by the Japanese Ministry of Health, Labour and Welfare, we have compiled the ＂Clinical practice guidelines for hepatocellular carcinoma＂. This set of guidelines covers 6 fields for HCC, including prevention, diagnosis and surveillance, surgery, chemotherapy, TACE, and ablation therapy. We have surveyed 7192 publications on HCC extracted mainly from MEDLINE （1966-2002）, and selected 334 articles to form 58 pairs of research questions and recommendations. For convenience in practical use, we have also created algorithms for the surveillance and treatment of HCC.

关键词： Hepatocellular carcinoma Surgery

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Design and Synthesis of 6α-Corticosteroid Haptens and Their Bovine Serum Albumin (BSA) Conjugates

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Chinese Chemical Letters 2003年第3期14卷 259-262页

作者： Pi SUN norihiro KOBAYASHI Junichi GOTO Graduate School of Pharmaceurical Sciences Tohoku UniversityAobayamaAoba-kuSendai 980-8578Japan

The site of attachment of protein carrier to corticosteroids has great influence on the specificity of produced antibody. In order to obtain highly specific and accurate antibodies for bioimmunoassay determination of cortisol, different tether lengths of 6-corticosteroid haptens and their BSA conjugates were designed and synthesized.

关键词： Cortisol hapten monocolonal antibody bioimmunoassay.

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Lensless Vanderlugt optical correlator using two phase-only spatial light modulators(Invited Paper)

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Chinese Optics Letters 2009年第12期7卷 1131-1133页

作者： norihiro Fukuchi Takashi Inoue Haruyoshi Toyoda Tsutomu Hara Central Research Laboratory Hamamatsu Photonics K.K.Hamamatsu 434-8601 Japan

A lensless Vanderlugt optical correlator using two phase-only spatial light modulators （SLMs） is proposed. The SLMs are used for displaying input and filter patterns respectively. The SLMs are also used as programmable lenses in order to realize the lensless construction. This lensless system is simple and its alignment adjustment is easy. The performance of the SLMs as programmable lenses is also described.

关键词： SLM Invited Paper FLPs Lensless Vanderlugt optical correlator using two phase-only spatial light modulators

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Added value of indocyanine green fluorescence imaging in liver surgery

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 310-317页

作者： Nobuyuki Takemura Kyoji Ito Fuyuki Inagaki Fuminori Mihara norihiro Kokudo Department of Surgery Hepato-Biliary Pancreatic Surgery DivisionNational Center for Global Health and Medicine1-21-1 ToyamaShinjyuku-kuTokyo162-8655Japan

Recently,indocyanine green(ICG)fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery,to detect hepatic tumors,for accurate anatomical hepatectomy,and to increase the safety and accuracy of minimally invasive(laparoscopic and robotic)*** clinical relevance of this method has been increasing gradually,as new procedures develop in this *** important roles and the latest added value of ICG fluorescence imaging in liver surgery are discussed in this report.

关键词： Florescence imaging Indocyanine green Hepatocellular carcinoma Colorectal metastasis Hepatectomy Minimally invasive surgery

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Classification of hepatic venous tumor thrombus in hepatocellular carcinoma: should it describe tumor status or predict patient survival?

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 534-536页

作者： norihiro Kokudo Wei Tang Takashi Kokudo Department of HPB Surgery National Center for Global Health and MedicineTokyoJapan

Tumor thrombus in the hepatic veins or inferior vena cava(HVTT/IVCTT)is the second most common of the three types of vascular invasion by hepatocellular carcinoma(HCC).According to the most recent nationwide survey in Japan,vascular invasion of the portal vein(PVTT)is present 13.2%of newly diagnosed HCCs,followed by HVTT/IVCTT(6.2%)and bile duct tumor thrombus(BDTT,3.4%)based on imaging findings(1).

关键词： thrombus invasion hepatic

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Observation of mitochondrial activity based on temporal and spatial pH variations measured by near-field fluorescent ratiometry

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Science China(Physics,Mechanics & Astronomy) 2011年第12期54卷 2225-2229页

作者： LI YongBo SHIONHARA Ryosuke IWAMI Kentaro OHTA Yoshihiro UMEDA norihiro Department of Mechanical Systems Engineering Tokyo University of Agriculture and Technology Tokyo 184-8588 Japan Department of Biotechnology and Life Science Tokyo University of Agriculture and Technology Tokyo 184-8588 Japan

A novel method combining dual wavelength fluorescent ratiometry with scanning near-field optical microscopy (SNOM) is proposed and developed to measure the concentration and distribution of protons in the vicinity of biological samples. This method involves immersing mitochondria in a pH-sensitive fluorescent dye solution instead of injecting the dye into the surface of the mitochondrial membrane. It uses a dual emission pH-sensitive dye and SNOM with a thermally pulled and metal-coated optical fiber probe to improve the spatial resolution. The time dependence of the fluorescence intensity ratio (FIR) under acid addition and the response of mitochondria to nutritional supplementation were studied by using this method. Activation of mitochondria and a distance-dependent delay in the FIR response were observed. The results confirmed that mitochondrial activity could be observed by using this method.

关键词： local pH pH measurement SNOM proton concentration mitochondrial membrane ATP synthesis

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New ‘multi-omics' approach and its contribution to hepatocellular carcinoma in China

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Chinese Journal of Cancer Research 2014年第6期26卷 639-640页

作者： Yoshinori Inagaki Peipei Song norihiro Kokudo Wei Tang Hepato-Biliary-Pancreatic Surgery Division Department of Surgery Graduate School of Medicine the University of Tokyo Hongo 7-3-1 Bunkyo-ku Tokyo 113-8655 Japan

Hepatocellular carcinoma（HCC）is one of the most common liver neoplasms worldwide,and 70-80%cases are accounted in Asian countries（1）.Etiological background of HCC patients is different in each country or *** China,infection of hepatitis B virus （HBV） is a main etiological factor of increased incidence of HCC. In fact, 93 million HBV carriers are Chinese, accounting for 2/3 of such patients worldwide, and about 20 million of these people have chronic HBV infection （2）. Chronic HBV infection is a high risk factor for development of HCC. Therefore, the follow-up of those chronic viral hepatitis type B patients and the early-detection of HCC in those patients are pressing tasks to reduce the incidence of HCC in China （3）.

关键词： neoplasms accounted recurrence fetoprotein New multi-omics multifocal physiological incidence metastatic

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