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Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand

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World Journal of Gastrointestinal Pathophysiology 2023年第2期14卷 21-33页

作者： Gyokukou You Lu Zeng Hideaki tanaka Emi Ohta Takahiro Fujii Kazuhiko Ohshima masakazu tanaka Nobuyuki Hamajima Chutiwan Viwatthanasittiphong Mantana Muangphot Dhiraphol Chenvidhya Adisorn Jedpiyawongse Banchob Sripa Masanao Miwa Satoshi Honjo Department of Bioscience Nagahama Institute of Bio-Science and TechnologyNagahama 526-0829ShigaJapan Division of Neuroimmunology Joint Research Center for Human Retrovirus InfectionKagoshima UniversityKagoshima 890-8544KagoshimaJapan Department of Healthcare Administration Nagoya University Graduate School of MedicineNagoya 466-8550AichiJapan Department of Diagnostic and Interventional Radiology Ubon Cancer CentreUbon Ratchathani 34000Thailand Department of Pathology Ubon Cancer CentreUbon Ratchathani 34000Thailand Department of Surgery Ubon Cancer CentreUbon Ratchathani 34000Thailand Research Division National Cancer InstituteBangkok 10400Thailand Department of Pathology Khon Kaen UniversityKhon Kaen 40002Thailand Department of Paediatirics National Hospital OrganizationFukuoka National HospitalFukuoka 811-1394FukuokaJapan

BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest *** with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA ***,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in ***,in humans,other environmental and genetic factors may also be *** To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related *** This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and *** examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and *** of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also *** Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild *** presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic *** In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.

关键词： Opisthorchis Glutathione transferase Cytochrome P-450 CYP2E1 Case-control study

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Exploiting fly models to investigate rare human neurological disorders

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Neural Regeneration Research 2025年第1期20卷 21-28页

作者： Tomomi tanaka Hyung-Lok Chung Department of Neurology Houston Methodist Research InstituteHoustonTXUSA Department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 Drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

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Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand

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World Journal of Gastrointestinal Pathophysiology 2014年第4期5卷 570-578页

作者： Masanao Miwa Satoshi Honjo Gyokukou You masakazu tanaka Kazuhiko Uchida Petcharin Srivatanakul Thiravud Khuhaprema Watcharin Loilome Anchalee Techasen Chaisiri Wongkham Temduang Limpaiboon Puangrat Yongvanit Sopit Wongkham Nagahama Institute of BioScience and Technology Nagahama Shiga 526-0829 Japan Department of Biochemistry and Molecular Oncology Institute of Basic Medical Sciences University of Tsukuba Tsukuba Ibaraki 305-8575 Japan Department of Pediatrics National Hospital Organization Fukuoka National Hospital Fukuoka 811-1394 Japan Department of Microbiology Faculty of Medicine Kansai Medical University Hirakata City Osaka 573-1010 Japan Cancer Control Unit National Cancer Institute Department of Biochemistry and Liver Fluke and Cholangiocarcinoma Research Center Faculty of Medicine Khon Kaen University Faculty of Associated Medical Sciences Khon Kaen University

Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients' lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.

关键词： Alcohol drinking Cholangiocarcinoma DNA polymorphism Glutathione S transferase 8-oxoguanine glycosylase 1 Liver fluke Opisthorchis viverrini Thailand

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Triple Crossing Numbers of Graphs

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Communications in Mathematical Research 2016年第1期32卷 1-38页

作者： tanaka HIROYUKI TERAGAITO masakazu Graduate School of Education Hiroshima University 1-1-1 Kagamiyama Higashi-hiroshima 739-8524 Japan Department of Mathematics Education Hiroshima University 1-1-1 Kagamiyama Higashi-hiroshima 739-8524 Japan

We introduce the triple crossing number, a variation of the crossing number, of a graph, which is the minimal number of crossing points in all drawings of the graph with only triple crossings. It is defined to be zero for planar graphs, and to be infinite for non-planar graphs which do not admit a drawing with only triple crossings. In this paper, we determine the triple crossing numbers for all complete multipartite graphs which include all complete graphs.

关键词： crossing number triple crossing number complete multipartite graph2010 MR subject classification: 05C10

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Molecular vulnerabilities and therapeutic resistance in hormone receptor positive and HER2 dependent breast cancer tumours

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Cancer Drug Resistance 2022年第2期5卷 487-497页

作者： Ravi Velaga Sunao tanaka masakazu Toi Breast Surgery Graduate School of MedicineKyoto University HospitalKyoto University54 Shogoin-KawarachoSakyo-kuKyoto 606-8507Japan

Over the past two decades,high sensitivity to HER2-amplified primary breast cancers has been achieved with HER2-targeted ***4/6 inhibitors have long been identified as a potential treatment option for advanced breast cancer ***,acquired HER2 heterogeneity leading to resistance during the treatment has been identified as a *** review focuses on the recent resistance mechanisms identified and potential therapeutic targets for conventional and combination endocrine therapies with CDK4/6 inhibitors by various breast cancer clinical trials and research groups in HER amplified and/or mutated breast cancer *** HER2 alterations,JNK pathway,hyperactivated TORC1,co-mutations in HER2 and HER3,phenotypic changes of HER2,and few other advanced findings are identified as potential therapeutic targets in treating current HER2 endocrine therapy-resistant *** with the HER2-focused resistance mechanisms,we also describe how the microbiome may play a role in breast cancer therapy and its potential for new therapeutic strategies to overcome drug resistance in breast cancers.

关键词： HER2 CDK4/6 MONALESSA-2 trial JNK pathway HER2 and HER3 co-mutations microbiome hot and cold tumour drug resistance

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Autoimmune hepatitis triggered by acute hepatitis A

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World Journal of Gastroenterology 2005年第38期11卷 6069-6071页

作者： Hiroto tanaka Hiroto Tujioka Hiroki Ueda Hiroko Hamagami Youhei Kida masakazu Ichinose 3rd Department of Internal Medicine

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on： aspartate aminotransferase （AST）, 1 076 IU/L; alanine aminotransferase （ALT）, 1 400 IU/L; total bilirubin （TB）, 20.9 mg/dL; and prothrombin time rate （PT%）, 46.9%. Acute hepatitis A （HA） was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin （Ig） M HA antibody, but elevation of anti-nuclear antigen （×320） and IgG （3 112 mg/dL） led to suspicion of autoimmune hepatitis （AIH）. Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALl began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

关键词： Acute hepatitis A Autoimmune hepatitis International criteria for AIH HLA

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Hepatic encephalopathy with status epileptics: A case report

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World Journal of Gastroenterology 2006年第11期12卷 1793-1794页

作者： Hiroto tanaka Hiroki Ueda Yohei Kida Hiroko Hamagami Tomikimi Tsuji masakazu Ichinose The Third Department of Internal Medicine Wakayama Medical University 811-1 KimiideraWakayama City641-0015Japan the Department of Neuropsychology Wakayama Medical University 811-1 KimiideraWakayama City641-0015Japan

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epileptic us. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy （phenytoin sodium） and treatment for hepatic encephalopathy （Branched chain amino acids）. The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

关键词： Status epilepticus Hepatic encephalopathy Decompensated liver cirrhosis Electroencephalogram

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Stability analysis of a noise control system in a duct by using delay differential equation

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Acta Mechanica Sinica 2009年第1期25卷 131-137页

作者： masakazu Haraguchi MOE Key Laboratory of Structure Mechanics and Control for Aircraft Nanjing University of Aeronautics and Astronautics

The paper deals with the criteria for the closed- loop stability of a noise control system in a duct. To study the stability of the system, the model of delay differential equation is derived from the propagation of acoustic wave governed by a partial differential equation of hyperbolic type. Then, a simple feedback controller is designed, and its closed- loop stability is analyzed on the basis of the derived model of delay differential equation. The obtained criteria reveal the influence of the controller gain and the positions of a sensor and an actuator on the closed-loop stability. Finally, numerical simulations are presented to support the theoretical results.

关键词： Stability analysis Delay differential equation Closed-loop stability Noise control Acoustic system

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A new reduction-based LQ control for dynamic systems with a slowly time-varying delay

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Acta Mechanica Sinica 2009年第4期25卷 529-537页

作者： masakazu Haraguchi MOE Key Lab of Structure Mechanics and Control for Aircraft Nanjing University of Aeronautics and Astronautics

Time delays in the feedback control often dete- riorate the control performance or even cause the instability of a dynamic system. This paper presents a control strategy for the dynamic system with a constant or a slowly time-varying input delay based on a transformation, which sire-plifies the time-delay system the relation is discussed for into a delay-free one. Firstly, two existing reduction-based linear quadratic controls. One is continuous and the other is discrete. By extending the relation, a new reduction-based control is then developed with a numerical algorithm presented for practical control implementation. The controller suggested by the proposed method has such a promising property that it can be used for the cases of different values of an input time delay without redesign of controller. This property provides the potential for stabilizing the dynamic system with a time-varying input delay. Consequently, the application of the proposed method to the dynamic system with a slowly time-varying delay is discussed. Finally, numerical simulations are given to show the efficacy and the applicability of the method.

关键词： Time delay Time-varying delay State transformation System reduction Linear quadratic control

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Estimating effects from trapped magnetic fluxes in superconducting magnetic levitation measurement

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仪器仪表学报 2008年第3期29卷 449-452页

作者： masakazu Nakanishi Metrology Institute of Japan National Institute of Advanced Industrial Science and Technology 1-1-1 Umezono Tsukuba-shi Ibaraki 305-8563 Japan

Superconducting magnetic levitation measurement is one of the most promising approaches to define mass standard based on the fundamental physical constants. However, the present system has unknown factors causing error larger than 50 ppm. We examined the effects of magnetic fluxes trapped in the superconducting coil and the superconducting floating body. When fluxes were trapped in either coil or floating body, their effects were able to be cancelled by reversing polarities of current and magnetic field, as had been believed. However, fluxes trapped in both coil and body induced an attractive force between them and caused error. In order to reduce the fluxes, the coil and the floating body should be cooled in low magnetic field in magnetic and electromagnetic shields.

关键词：截留磁通量超导电磁飘浮测量基本物理常量

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