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Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis

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World Journal of Gastroenterology 2018年第15期24卷 1622-1631页

作者： Yusuke Ozawa Takafumi Tamura Yohei Owada yoshio shimizu Akira Kemmochi Katsuji Hisakura Takashi Matsuzaka Hitoshi Shimano hiroko Isoda Nobuhiro Ohkohchi Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of Medicine University of Tsukuba Department of Endocrinology and Metabolism Faculty of Medicine University of Tsukuba Faculty of Life and Environmental Sciences University of Tsukuba

AIM To investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis(NASH) model influences surgical *** For establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl_4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy(PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after *** In the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups(P < 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase(AST) levels and total bilirubin(T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups(AST: P < 0.05, T-Bil: P < 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group(P < 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group(P < 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and *** The function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.

关键词： Hepatectomy Liver regeneration Residual liver Liver proliferation Nonalcoholic steatohepatitis

Cortical transcriptome analysis after spinal cord injury reveals the regenerative mechanism of central nervous system in CRMP2 knock-in mice

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Neural Regeneration Research 2021年第7期16卷 1258-1265页

作者： Ayaka Sugeno Wenhui Piao Miki Yamazaki Kiyofumi Takahashi Koji Arikawa hiroko Matsunaga Masahito Hosokawa Daisuke Tominaga yoshio Goshima Haruko Takeyama Toshio Ohshima Laboratory for Molecular Brain Science Department of Life Science and Medical BioscienceGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Biomolecular Engineering Laboratory Department of Life Science and Medical BioscienceGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Computational Bio Big-Data Open Innovation Laboratory(CBBD-OIL) National Institute of Advanced Industrial Science and Technology(AIST)TokyoJapan Research Organization for Nano and Life Innovation Waseda UniversityTokyoJapan Institute for Advanced Research of Biosystem Dynamics Waseda Research Institute for Science and EngineeringGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology(AIST)TsukubaJapan Department of Molecular Pharmacology and Neurobiology Graduate School of MedicineYokohama City UniversityYokohamaJapan

Recent studies have shown that mutation at Ser522 causes inhibition of collapsin response mediator protein 2(CRMP2) phosphorylation and induces axon elongation and partial recovery of the lost sensorimotor function after spinal cord injury(SCI).We aimed to reveal the intracellular mechanism in axotomized neurons in the CRMP2 knock-in(CRMP2KI) mouse model by performing transcriptome analysis in mouse sensorimotor cortex using micro-dissection punching *** to that, we analyzed the structural pathophysiology in axotomized or neighboring neurons after SCI and found that somatic atrophy and dendritic spine reduction in sensorimotor cortex were suppressed in CRMP2KI *** analysis of the transcriptome has aided in the identification of four hemoglobin genes Hba-a1, Hba-a2, Hbb-bs, and Hbb-bt that are significantly upregulated in wild-type mice with concomitant upregulation of genes involved in the oxidative phosphorylation and ribosomal pathways after ***, we observed substantial upregulation in channel activity genes and downregulation of genes regulating vesicles, synaptic function, glial cell differentiation in CRMP2KI ***, the transcriptome profile of CRMP2KI mice has been discussed wherein energy metabolism and neuronal pathways were found to be differentially *** results showed that CRMP2KI mice displayed improved SCI pathophysiology not only via microtubule stabilization in neurons, but also possibly via the whole metabolic system in the central nervous system, response changes in glial cells, and *** together, we reveal new insights on SCI pathophysiology and the regenerative mechanism of central nervous system by the inhibition of CRMP2 phosphorylation at *** these experiments were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee at Waseda University, Japan(2017-A027 approved on March 21, 2017;2018-A003 approved on March 25, 2018;2019-A026 approved on March

关键词： CNS regeneration cortex CRMP2 hemoglobin metabolic pathway spinal cord injury spine transcriptome

A new index for non-invasive assessment of liver fibrosis

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World Journal of Gastroenterology 2010年第38期16卷 4809-4816页

作者： Naohiro Ichino Keisuke Osakabe Toru Nishikawa hiroko Sugiyama Miho Kato Shiho Kitahara Senju Hashimoto Naoto Kawabe Masao Harata Yoshifumi Nitta Michihito Murao Takuji Nakano Yuko Arima Hiroaki shimazaki Koji Suzuki Kentaro yoshioka Faculty of Medical Technology School of Health SciencesFujita Health UniversityToyoakeAichi 470-1192Japan Department of Clinical Laboratory Fujita Health University Hospital Department of Liver Biliary Tract and Pancreas DiseasesFujita Health University

AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4.

关键词： Non-invasive fi brosis index Fibro-Stiffness index Chronic hepatitis C Liver stiffness Liver fi brosis

Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine:Case report

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World Journal of Gastroenterology 2010年第30期16卷 3853-3856页

作者： Shoichi Nakazuru Toshiyuki yoshio Shigeki Suemura Mari Itoh Manabu Araki Chiaki yoshioka Makiyo Ohta Yuka Sueyoshi Takashi Ohta hiroko Hasegawa Kaori Morita Takashi Toyama Noriyoshi Kuzushita Yoshinori Kodama Masayuki Mano Eiji Mita Department of Gastroenterology and Hepatology National Hos- pital OrganizationOsaka National Hospital2-1-14 HouenzakaChuo-kuOsaka CityOsaka 540-0006Japan Department of Pathology National Hospital OrganizationOsaka National Hospital2-1-14 HouenzakaChuo-kuOsaka CityOsaka 540-0006Japan

Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as thirdline chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partialtumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.

关键词： Poorly differentiated endocrine carcinoma Pancreatic endocrine tumor Gemcitabine Chemotherapy

Changes of shear-wave velocity by interferon-based therapy in chronic hepatitis C

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World Journal of Gastroenterology 2015年第35期21卷 10215-10223页

作者： Keisuke Osakabe Naohiro Ichino Toru Nishikawa hiroko Sugiyama Miho Kato Ai Shibata Wakana Asada Naoto Kawabe Senju Hashimoto Michihito Murao Takuji Nakano Hiroaki shimazaki Toshiki Kan Kazunori Nakaoka Yuka Takagawa Masashi Ohki Takamitsu Kurashita Tomoki Takamura Kentaro yoshioka Faculty of Medical Technology School of Health SciencesFujita Health University Center of Ultrasound Diagnosis Fujita Health University Hospital Department of Liver Biliary Tract and Pancreas DiseasesFujita Health University

AIM: To evaluate the changes of shear-wave velocity(Vs) by acoustic radiation force impulse after treatment in chronic hepatitis ***: Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon(IFN) plus ribavirin(RBV). Vs value(m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment(EOT), 1 year after EOT, and 2 years after ***: In patients with a sustained virological response(SVR)(n = 41), Vs significantly decreased at EOT [1.19(1.07-1.37), P = 0.0004], 1 year after EOT [1.10(1.00-1.22), P = 0.0001], and 2 years after EOT [1.05(0.95-1.16), P < 0.0001] compared with baseline [1.27(1.11-1.49)]. In patients with a relapse(n = 26), Vs did not significantly decrease at EOT [1.23(1.12-1.55)], 1 year after EOT [1.20(1.12-1.80)], and 2 years after EOT [1.41(1.08-2.01)] compared with baseline [1.39(1.15-1.57)]. In patients with a nonvirological response(n = 20), Vs did not significantly decrease at EOT [1.64(1.43-2.06)], 1 year after EOT [1.66(1.30-1.95)], and 2 years after EOT [1.61(1.36-2.37)] compared with baseline [1.80(1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28(1.04-1.40)] than in non-SVR patients [1.56(1.20-1.83)](P = 0.0142).CONCLUSION: Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.

关键词： Hepatitis C virus Fibrosis Interferon and ribaviri

Human IgG1 antibodies suppress angiogenesis in a target-independent manner

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Signal Transduction and Targeted Therapy 2016年第1期1卷 158-171页

作者： Sasha Bogdanovich Younghee Kim Takeshi Mizutani Reo Yasuma Laura Tudisco Valeria Cicatiello Ana Bastos-Carvalho Nagaraj Kerur yoshio Hirano Judit Z Baffi Valeria Tarallo Shengjian Li Tetsuhiro Yasuma Parthasarathy Arpitha Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Menotti Ruvo Annamaria Sandomenico Miho Nozaki Ryo Ijima Hiroki Kaneko Yuichiro Ogura hiroko Terasaki Balamurali K Ambati Jeanette HW Leusen Wallace Y Langdon Michael R Clark Kathryn L Armour Pierre Bruhns J Sjef Verbeek Bradley D Gelfand Sandro De Falco Jayakrishna Ambati Department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA Department of Ophthalmology and Visual Science Nagoya City University Graduate School of Medical SciencesNagoyaJapan Department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly Department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CEINGE—Biotecnologie Avanzate s.c.a.r.l.NaplesItaly Istituto di Biostrutture e Bioimmagini CNRNaplesItaly Department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA Department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands School of Pathology and Laboratory Medicine University of Western AustraliaCrawleyWAAustralia Division of Immunology Department of PathologyUniversity of CambridgeCambridgeUK Department of Immunology Unit of Antibodies in Therapy and PathologyInstitut PasteurParisFrance Institut National de la Santéet de la Recherche Médicale(INSERM)U1222 ParisFrance Department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands Department of Biomedical Engineering University of KentuckyLexingtonKYUSA Department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly Department of Physiology University of KentuckyLexingtonKYUSA.

Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s *** most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human *** bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in *** we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage *** approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized *** anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated ***,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA ***,mice deficient in FcγRI exhibited increased developmental and pathological *** findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.

关键词： CD64 angiogenesis antibodies