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Relationship between outcomes and relative dose intensity of lenvatinib treatment in patients with advanced hepatocellular carcinoma

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Liver Research 2020年第4期4卷 199-205页

作者： Takamasa Ohki Koki Sato Mayuko Kondo Eriko Goto Takahisa Sato Yuji Kondo Masatoshi Akamatsu Shinpei Sato Hideo Yoshida yukihiro koike Shuntaro Obi Department of Gastroenterology Mitsui Memorial HospitalTokyoJapan Department of Gastroenterology Kanto Central HospitalTokyoJapan Department of Gastroenterology Teikyo University Medical CenterChiba PrefectureJapan Department of Gastroenterology and Hepatology Kyoundo HospitalTokyoJapan Department of Gastroenterology JR Tokyo General HospitalTokyoJapan Department of Gastroenterology Japanese Red Cross Medical CenterTokyoJapan

Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in *** retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS).Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December *** patients were divided into two groups:RDI≥70%(RDI 70 group,N=70)or RDI<70%(control group,N=53)in the first 30 *** following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and *** and OS were analyzed using the Kaplan-Meier method,followed by the log-rank *** identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were<0.10 in univariate ***:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3%vs.28.3%,P<0.01).Dose interruption due to adverse events was significantly more common in the control *** response rate was significantly higher in the RDI 70 group than that in the control group(35.7%vs.11.3%,P<0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P<0.01).Multivariate analysis showed that RDI≥70%(hazard ratio(HR)=0.55,P=0.025),hypertension grade≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved *** OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P<0.01)were independently associated with improved ***≥70%was not statistically significant in multivariate ***:Our study revealed the importance of achieving

关键词： Advanced hepatocellular carcinoma Lenvatinib(LEN) Relative dose intensity(RDI) Chemotherapy Tyrosine kinase inhibitor

Blastomas of the digestive system in adults:A review

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1030-1042页

作者： Yu Liu Tony El Jabbour Jonathan Somma yukihiro Nakanishi Saverio Ligato Hwajeong Lee Zhi-Yan Fu Department of Pathology LSU Health Sciences Center School of MedicineNew OrleansLA 70112United States Department of Pathology Hartford HealthCareHartfordCT 06102United States Department of Pathology Moffitt Cancer CenterTampaFL 33612United States Department of Pathology and Laboratory Medicine Albany Medical CenterAlbanyNY 12208United States

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast *** review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and *** is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to *** addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been *** is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic ***,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially *** approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular *** treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some *** vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of *** review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

关键词： Adult blastomas Gastroblastoma Hepatoblastoma Pancreatoblastoma Digestive system

T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

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World Journal of Gastroenterology 2012年第20期18卷 2443-2451页

作者： yukihiro Shimizu Gastroenterology Unit Takaoka City Hospital 4-1 Takara-machi Takaoka city Toyama 933-8550 Japan

Hepatitis B is caused by the host immune response and T cells play a major role in the immunopathogenesis. More importantly,T cells not only destroy hepatocytes infected by hepatitis B virus(HBV),but also control HBV replication or eradicate HBV in a noncytolytic ***,analysis of T cell immune response during acute and chronic HBV infection is important to develop a strategy for successful viral control,which could lead to immunotherapy for terminating persistent HBV *** have been many attempts at immunotherapy for chronic HBV infection,and some have shown promising *** viral load has been shown to suppress antiviral immune responses and immunoinhibitory signals have been recently elucidated, therefore,viral suppression by nucleos(t)ide analogs, stimulation of antiviral immune response,and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.

关键词： T cells Immunopathogenesis Immunotherapy Hepatitis B virus infection

Astrocytic Kir4.1 potassium channels as a novel therapeutic target for epilepsy and mood disorders

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Neural Regeneration Research 2018年第4期13卷 651-652页

作者： yukihiro Ohno Laboratory of Pharmacology Osaka University of Pharmaceutical Sciences

Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,mainte... 详细信息

关键词： Astrocytic Kir4.1 potassium channels as a novel therapeutic target for epilepsy and mood disorders Figure

Liver in systemic disease

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World Journal of Gastroenterology 2008年第26期14卷 4111-4119页

作者： yukihiro Shimizu Division of Internal Medicine Center for Gastroenterology and HepatologyKyoto Katsura Hospital17 Yamada-HiraoNishikyoKyoto 615-8256Japan

Potential causes of abnormal liver function tests include viral hepatitis,alcohol intake,nonalcoholic fatty liver disease,autoimmune liver diseases,hereditary diseases,hepatobiliary malignancies or infection,gallstones and drug-induced liver ***,the liver may be involved in systemic diseases that mainly affect other ***,in patients without etiology of liver injury by screening serology and diagnostic imaging,but who have systemic diseases,the abnormal liver function test results might be caused by the systemic *** most of these patients,the systemic disease should be treated ***,some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

关键词： Abnormal liver function tests Jaundice Systemic disease

Gut microbiota in common elderly diseases affecting activities of daily living

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World Journal of Gastroenterology 2018年第42期24卷 4750-4758页

作者： yukihiro Shimizu Gastroenterology center Nanto Municipal Hospital

Gut microbiota are involved in the development or prevention of various diseases such as type 2 diabetes,fatty liver, and malignancy such as colorectal cancer,breast cancer and hepatocellular carcinoma. Alzheimer'sdisease, osteoporosis, sarcopenia, atherosclerotic stroke and cardiovascular disease are major diseases associated with decreased activities of daily living(ADL), especially in elderly people. Recent analyses have revealed the importance of gut microbiota in the control of these diseases. The composition or diversity of these microbiota is different between patients with these conditions and healthy controls, and administration of probiotics or prebiotics has been shown effective in the treatment of these diseases. Gut microbiota may affect distant organs through mechanisms that include regulating the absorption of nutrients and/or the production of microbial metabolites, regulating and interacting with the systemic immune system, and translocating bacteria/bacterial products through disrupted mucosal ***, the gut microbiota may be important regulators in the development of diseases that affect ADL. Although adequate exercise and proper diet are important for preventing these diseases, their combination with interventions that manipulate the composition and/or diversity of gut microbiota could be a promising strategy for maintaining health condition and preserving ADL. This review thus summarizes current understanding of the role of gut microbiota in the development or prevention of diseases closely associated with the maintenance of ADL.

关键词： Probiotics Prebiotics Alzheimer’s disease Osteoporosis Sarcopenia Gut microbiota Cardiovascular disease Cerebrovascular disease

Direct measurement of the three-dimensional distribution of leaf area density and light conditions in a mature oak stand by the cube method

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林业研究:英文版 2023年第6期34卷 1817-1827页

作者： Chiharu Migita yukihiro Chiba Tanaka Kenzo Forestry and Forest Products Research Institute TsukubaIbaraki 305-8687Japan Japan International Research Centre for Agricultural Sciences TsukubaIbaraki 305-8686Japan

Although the distributions of foliage and light play major roles in various forest functions,accurate,nondestructive measurement of these distributions is difficult due to the complexity of the canopy *** evaluate the foliage and light distributions directly and nondestructively in a mature oak stand,we used the cube method by dividing the forest canopy into small cubes(50 cm per side)and directly measured leaf area density(LAD,the total one-sided leaf area per unit volume,i.e.,cube)and relative irradiance(RI)within each *** distribution of LAD and of RI was highly heterogeneous,even at the same canopy *** heterogeneity reflected the presence of foliage clusters associated with multiple forking *** relationship between cumulative LAD at the canopy surface and average RI followed the Beer-Lambert *** mean light extinction coefficient(K)was ***,K was overestimated by more than double(0.80)when calculated based on the classical method using RI at the forest *** overestimation was caused by the lower RI due to light absorption by nonleaf plant parts below the *** findings on the complex foliage and light distributions in canopy layers should help improve the accuracy of RI and K measurements and thus more accurate predictions of environmental responses and forest functions.

关键词： Beer-Lambert law Canopy structure Foliage cluster Leaf area density Leaf area index Relative light intensity

Study on multimers and their structures in molecular association mixture

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Science China Chemistry 2007年第1期50卷 23-31页

作者： YAMAGUCHI Yoshinori OZAKI yukihiro Consolidated Research Institute for Advanced Science and Medical Care Waseda UniversityJapan Department of Chemistry School of Science and TechnologyKwansei-Gakuin UniversitySandaHyogo 669-1337Japan

Self-association system of(R)-1,3-butanediol in dilute carbon tetrachloride(CCl4)solution is studied as a model of molecular association *** methods including FSMWEFA(fixed-size moving window evolving factor analysis)combined with PCA(principal component analysis),SIMPLISMA (simple-to-use interactive self-modeling mixture analysis),and ITTFA(iterative target transformation factor analysis)are adopted to resolve infrared spectra of(R)-1,3-butanediol *** number and equilibrium constant are computed.(R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium *** investigation of trimer structures is carried out with DFT(density functional theory),and structural factors are analyzed.

关键词： (R)-1 3-butanediol multimer chemometrics density functional theory

Practical guidelines for diagnosis and early management of drug-induced liver injury

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World Journal of Gastroenterology 2008年第44期14卷 6774-6785页

作者： Kazuto Tajiri yukihiro Shimizu Department of Gastroenterology and Hematology Graduate School of Medical and Pharmaceutical SciencesUniversity of ToyamaSugitani 2630ToyamaJapan Center for Gastroenterology and Hepatology Kyoto Katsura Hospital17 Yamada-HiraoNishikyoKyoto 615-8256Japan

The spectrum of drug-induced liver injury （DILI） is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method （CIOMS/RUCAM） scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, and total bilirubin （T-Bil）. However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.

关键词： Diagnosis Drug-induced liver injury Guidelines Management