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Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

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Cancer Communications 2023年第4期43卷 415-434页

作者： Hiroyuki Suzuki Hideki Iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko Imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono Yu Noda Naoki Kamachi Miwa Sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu hirohisa yano Yihai Cao Hironori Koga Takuji Torimura Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume CityFukuokaJapan Liver Cancer Research Division Research Center for Innovative Cancer TherapyKurume UniversityKurume CityFukuokaJapan Iwamoto Internal Medicine Clinic Kitakyushu CityFukuokaJapan Department of Microbiology Tumor and Cell biologyKarolinska InstitutetStockholmSweden Department of Surgery and Science Graduate School of Medical ScienceKyushu UniversityFukuoka CityFukuokaJapan Department of Pathology Kurume University School of MedicineKurume CityFukuokaJapan

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not *** aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in ***:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC *** evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC *** on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were ***,in vivo genetic and pharmacological gain-and loss-of-function experiments were ***:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall ***,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor ***-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase ***,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib ***:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic *** TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 *** data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

关键词： hepatocellular carcinoma hypoxia IGFBP-1 lenvatinib molecular targeting resistance tyrosine kinase inhibitors

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Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

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World Journal of Gastroenterology 2012年第28期18卷 3673-3680页

作者： Yoshiki Naito Hironori Kusano Osamu Nakashima Eiji Sadashima Satoshi Hattori Tomoki Taira Akihiko Kawahara Yoshinobu Okabe Kazuhide Shimamatsu Jun Taguchi Seiya Momosaki Koji Irie Rin Yamaguchi Hiroshi Yokomizo Michiko Nagamine Seiji Fukuda Shinichi Sugiyama Naoyo Nishida Koichi Higaki Munehiro Yoshitomi Masafumi Yasunaga Koji Okuda Hisafumi Kinoshita Masayoshi Kage Masamichi Nakayama Makiko Yasumoto Jun Akiba hirohisa yano Departments of Pathology Kurume University School of Medicine Kurume 830-0011 Japan Biostatistics Center Kurume University Kurume 830-0011 Japan Department of Diagnostic Pathology Kurume University Hospital Kurume 830-0011 Japan Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume 830-0011 Japan Department of Pathology Omuta City General Hospital Omuta 836-8567 Japan Department of Pathology Asakura Medical Association Hospital Fukuoka 838-0069 Japan Department of Pathology National Hospital Organization Kyushu Medical Center Fukuoka 810-8563 Japan Department of Pathology Shin-Koga Hospital Tenjinkai 120 Tenjincho Kurume 830-0033 Japan Department of Pathology Kurume University Medical Center 155-1 Kokubumachi Kurume 839-0863 Japan Department of Surgery Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Department of Pathology Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Division of Surgery Saiseikai Kumamoto Hospital Kumamoto 861-4193 Japan Department of Pathology St Mary's Hospital Kurume 830-8543 Japan Department of Surgery Kurume University School of Medicine Kurume 830-0011 Japan

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

关键词： Intraductal biliary neoplasm Intraductal papillary neoplasm of the bile duct Intraductal tubular neoplasm of the bile duct Intraductal tubulopapillary neoplasm of the bile duct Mucin expression

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Crowd evacuation of pairs of pedestrians

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Communications in Theoretical Physics 2022年第4期74卷 97-112页

作者： Ryosuke yano Tokio Marine d R Co.ltd. 1-5-1OtemachiChiyoda-kuTokyo100-0004Japan

The crowd evacuation of pairs of pedestrians(*** consisting of a parent and a child)is numerically ***,it is assumed that all pedestrians have their own partners,and move randomly inside the bounded domain of the right-hand room as an initial *** pedestrians start their evacuations after they contact their *** evacuations are completed by the transfer of all the pairs from the right-hand room to the left-hand room through an exit.A frozen swarm tends to appear in the right-hand room as the total number of pedestrians *** frozen swarm moves without changing its form,unless it is dissolved by a strong collision with a pair of pedestrians that comes back from the left-hand room by ***,the evacuation speed also depends on the area of the Escape Zone,whereas an obstacle placed in front of an exit also changes the speed of the evacuation in accordance with the type of motion of the children.

关键词： Evacuation of paired pedestrians force chain network escape from crowd

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Ongoing Applicative Studies of Plant Thioredoxins

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Molecular Plant 2014年第1期7卷 4-13页

作者： Hiroyuki yano National Food Research Institute National Agriculture and Food Research Organization Kannondai 2-1-12 Tsukuba Ibaraki 305-8642 Japan

Studies triggered by the discovery of the function of thioredoxin （Trx） in photosynthesis have revealed its role throughout biology. Parallel biochemical and proteomic analyses have led to the identification of its numerous puta- tive targets. Recently, to verify the biological significance of these targets, in vivo studies using transformants in which Trx is overexpressed or suppressed are in progress, and the transformants themselves that are being used in such studies show their potential applicative values. Moreover, Trx＇s mitigation of allergenicity for some proteins offers promising prospects in the food industry. Practical studies based on redox regulation, once only on the horizon, are now achieving new dimensions. This short review focuses on the industrial applications of Trx studies, the current situation, and future perspectives. The putative targets obtained by the proteomics approach in comparison with in vivo observations of the transformants are also examined. Applicative studies of glutathione, a counterpart of Trx, are also discussed briefly.

关键词： allergen food redox regulation target thioredoxin.

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INTELLIGENT METATAL COMPLEXES CONTAINING N-GLYCOSIDES FORMED FROM TRIS (2-AMINOETHYL) AMINE AND ALDOSES, HAVING MOLECULAR RECOGNITION ABILITY

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Chinese Journal of Polymer Science 1998年第3期16卷 193-206页

作者： yano Shigenobu Department of Chemistry Nara Women's University Kitauoyanishimachi Nara 630-8263 Japan

Assembly of carbohydrates on nickel (Ⅱ) center by utilizing N-glycosidicbond formation with a branched amine: tris(2-aminoethyl)amine (tren), an unprecedentedchiral inversion around the metal center (Co or Mn) induced by an interaction betweensugars and sulfate anions, peroxo-bridged dinuclear cobalt (Ⅲ) complex containing N-glycoside ligands from tren and D-glucose and its reversible dioxygen binding property,and novel trimanganese complexes with a linear Mn_3 (Ⅱ, Ⅲ, Ⅱ) assemblage bridged bycarbohydrates are described.

关键词： Intelligent sugar complex Molecular recognition N-glycoside complex

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A new algorithm based on metaheuristics for data clustering

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2010年第12期11卷 921-926页

作者： Tsutomu SHOHDOHJI Fumihiko yano Yoshiaki TOYODA Department of Computer and Information Engineering Faculty of EngineeringNippon Institute of Technology Division of Integrated Sciences J.F.Oberlin University Aoyama Gakuin University

This paper presents a new algorithm for clustering a large amount of *** improved the ant colony clustering algorithm that uses an ant’s swarm intelligence,and tried to overcome the weakness of the classical cluster analysis *** our proposed algorithm,improvements in the efficiency of an agent operation were achieved,and a new function "cluster condensation" was *** proposed algorithm is a processing method by which a cluster size is reduced by uniting similar objects and incorporating them into the cluster *** with classical cluster analysis methods,the number of steps required to complete the clustering can be suppressed to 1% or less by performing this procedure,and the dispersion of the result can also be ***,our clustering algorithm has the advantage of being possible even in a small-field cluster *** addition,the number of objects that exist in the field decreases because the cluster condenses;therefore,it becomes possible to add an object to a space that has become *** other words,first,the majority of data is put on *** are then clustered,gradually adding parts of the standby data to the clustering *** method can be adopted for a large amount of *** experiments confirmed that our proposed algorithm can theoretically applied to an unrestricted volume of data.

关键词： Metaheuristics Ant colony clustering Data clustering Swarm intelligence

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Short-and long-term outcome of interferon therapy for chronic hepatitis B infection

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World Journal of Gastroenterology 2014年第37期20卷 13284-13292页

作者： Yasushi Seo Yoshihiko yano Division of Gastroenterology Department of Internal MedicineKobe University Graduate School of Medicine Internal Medicine and Ophthalmology Clinic

Hepatitis B virus (HBV) infection is a serious clinical problem worldwide. Conventional interferon (IFN)-α has been approved for the treatment of chronic hepatitis B (CHB). Short-term studies have demonstrated that IFN-based therapy is moderately effective in inducing the loss of hepatitis e antigen (HBeAg) or seroconversion (30%-40%) in HBeAg-positive patients and also produces sustained HBV DNA suppression (20%-30%) in HBeAg-negative patients. Many studies have reported a correlation between the HBV genotype and response to IFN treatment. The highest response rate to IFN treatment was found in patients infected with HBV genotype A, followed by HBV genotypes B, C, and D. The long-term effect of IFN-α on CHB has not yet been elucidated. The ability of IFN-α treatment to prevent new cirrhosis, complications associated with cirrhosis, and development of hepatocellular carcinoma (HCC) is controversial. The beneficial effect of IFN-α treatment in reducing the development of HCC has mainly been observed in treatment responders who already have cirrhosis. These inconsistent findings may be attributed to the inevitable limitations of comparisons across studies, including differences in the baseline characteristics of the study and the moderate suppression of HBV replication by IFN-α relative to nucleoside/nucleos(t)ide analogs.

关键词： Chronic hepatitis B Hepatitis B virus Interferon α Long-term outcome Hepatocellular carcinoma

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Fabrication of Mie-resonant silicon nanoparticles using laser annealing for surface-enhanced fluorescence spectroscopy

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Microsystems & Nanoengineering 2024年第2期10卷 133-141页

作者： Tatsuya Fukuta Ryo Kato Takuo Tanaka Taka-aki yano Institute of Post-LED Photonics Tokushima University2-1 Minami-JosanjimaTokushima770-8506Japan Innovative Photon Manipulation Research Team RIKEN Center for Advanced PhotonicsWakoSaitama351-0198Japan Metamaterials Laboratory RIKEN Cluster for Pioneering ResearchWakoSaitama351-0109Japan

Silicon nanostructures with unique Mie resonances have garnered considerable attention in the field of ***,we present a simple and efficient method for the fabrication of silicon(Si)nanoparticle substrates using continuous-wave(CW)laser *** resulting silicon nanoparticles exhibit Mie resonances in the visible region,and their resonant wavelengths can be precisely ***,laser-annealed silicon nanoparticle substrates show a 60-fold enhancement in *** tunable and fluorescence-enhancing silicon nanoparticle platform has tremendous potential for highly sensitive fluorescence sensing and biomedical imaging applications.

关键词： nanoparticles annealing resonant

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Arsenic speciation for the phytoremediation by the Chinese brake fern,Pteris vittata

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Journal of Environmental Sciences 2008年第12期20卷 1463-1468页

作者： R.Shoji R.Yajima Y.yano Department of Chemical Science and Engineering Tokyo National College of Technology1220-2 KunugidaHachioji

Arsenic(As)speciation for the phytoremediation by the Chinese brake fern was *** particular,the mechanism of how plants induce compounds containing thiol(SH)and proteins by As exposure in terms of the relationship between As and phosphate uptaken into plant cells was *** vittata callus could effciently reduce As(V)to As(III)by the rapid introduction of reductase and synthesize thiols leading to phytochelatins ***,Pteris vittata could control phosphate concentration in t...

关键词： arsenic hyper accumulator phosphorus thiol phytochelatin

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Current hepatitis B virus infection situation in Indonesia and its genetic diversity

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World Journal of Gastroenterology 2016年第32期22卷 7264-7274页

作者： Maria Inge Lusida Juniastuti Yoshihiko yano Institute of Tropical Disease Airlangga Health Science Institute Airlangga University Department of Microbiology Faculty of Medicine Airlangga University Center for Infectious Diseases Kobe University Graduate School of Medicine

Indonesia has a moderate to high endemicity of hepatitis B virus(HBV) infection. The risk for chronic HBV infection is highest among those infected during infancy. Since 1997, hepatitis B(Hep B) vaccination of newborns has been fully integrated into the National Immunization Program. Al though HBV infection has been reduced by the universal newborn Hep B immunization program, it continues to occur in Indonesia. The low birth dose coverage and the presence of vaccine escape mutants might contribute to this endemicity among children. Although limited information is available for an analysis of occult HBV infection(OBI), several variations and substitutions in the pre-S/S region have been detected in Indonesian HBV strains. Additionally, persistent infection and disease progression of chronic hepatitis B are related to not only viral factors but also the host genome. Indonesia is one of the most ethnically heterogeneous nations, with Javanese and Sundanese as the two highest ethnic groups. This multi-ethnicity makes genomic research in Indonesia difficult. In this article, we focused on and reviewed the following aspects: the current hepatitis B immunization program and its efficacy, OBI, HBV infection among high-risk patients, such as hemodialysis patients, and research regarding the host genome in Indonesia.

关键词： Hepatitis B virus Immunization Occult infection Hemodialysis Indonesia

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