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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan division of Molecular pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration research 2024年第1期19卷 29-34页

作者： Marta Zagrebelsky Martin Korte division of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz Centre for Infection research AG NINDBraunschweigGermany

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological *** has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the *** to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological *** r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic ***,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side *** re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational *** the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist *** this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological ***,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist *** benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal ***,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin recepto

关键词： Alzheimer's disease brain-derived neurotrophic factor depression Parkinson's disease tropomyosin receptor kinase B receptor

Investigating epithelial-neuronal signaling contribution in visceral pain through colon organoid-dorsal root ganglion neuron co-cultures

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Neural Regeneration research 2024年第6期19卷 1199-1200页

作者： Francesco Margiotta Lorenzo Di Cesare Mannelli Antonino Morabito Carla Ghelardini Elena Lucarini Department of Neuroscience PsychologyDrug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology SectionUniversity of FlorenceFlorenceItaly Department of Neuroscience PsychologyDrug Research and Child Health-NEUROFARBAUniversity of FlorenceFlorenceItaly Meyer Children’s Hospital IRCCS FlorenceItaly

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs),affecting about 20%of the global population(Grundy et al.,2019).Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects,hence the need to identify novel molecular and cellular targets for drug development.

关键词： pain visceral colon

Practical operating flexibility of a bifunctional freestanding membrane for efficient anion exchange membrane water electrolysis across all current ranges

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Carbon Energy 2024年第9期6卷 306-324页

作者： Hong-Jin Son Jeemin Hwang Min Young Choi Seung Hee Park Jae Hyuk Jang Byungchan Han Sung Hoon Ahn Department of Bio-Chemical Engineering Chosun UniversityGwangjuRepublic of Korea Fuel Cell research and Demonstration Center Hydrogen Energy Research DivisionKorea Institute of Energy Research(KIER)Buan-gunJeollabuk-doRepublic of Korea Department of Chemical and Biomolecular Engineering Yonsei UniversitySeoulRepublic of Korea Center for research Equipment Korea Basic Science InstituteDaejeonRepublic of Korea

This study explores a symmetric configuration approach in anion exchange membrane(AEM)water electrolysis,focusing on overcoming adaptability challenges in dynamic ***,a rapid and mild synthesis technique for fabricating fibrous membrane-type catalyst electrodes is *** method leverages the contrasting oxidation states between the sulfur-doped NiFe(OH)2 shell and the metallic Ni core,as revealed by electron energy loss *** evaluations confirm that the S–NiFe(OH)_(2) active sites optimize free energy for alkaline water electrolysis *** technique bypasses traditional energy-intensive processes,achieving superior bifunctional activity beyond current *** symmetric AEM water electrolyzer demonstrates a current density of 2 A cm^(-2) at 1.78 V at 60℃ in 1 M KOH electrolyte and also sustains ampere-scale water electrolysis below 2.0 V for 140 h even in ambient *** results highlight the system's operational flexibility and structural stability,marking a significant advance-ment in AEM water electrolysis technology.

关键词： AEM water electrolysis fibrous membrane iR correction free operational stability symmetric configuration

Influences of Co-Flow and Counter-Flow Modes of Reactant Flow Arrangement on a PEMFC at Start-Up

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1337-1356页

作者： Qianqian Shao Min Wang Nuo Xu School of Petroleum Engineering Guangdong University of Petrochemical TechnologyMaoming525000China Mechanics division Beijing Computational Science Research CenterBeijing100193China

To investigate the influences of co-flowand counter-flowmodes of reactant flowarrangement on a proton exchange membrane fuel cell(PEMFC)during start-up,unsteady physical and mathematical models fully coupling the flow,heat,and electrochemical reactions in a PEMFC are *** continuity equation and momentum equation are solved by handling pressure-velocity coupling using the SIMPLE *** electrochemical reaction rates in the catalyst layers(CLs)of the cathode and anode are calculated using the Butler-Volmer *** multiphase mixture model describes the multiphase transport process of gas mixtures and liquid water in the fuel *** validation,the influences of co-flow and counter-flow modes on the PEMFC performance are investigated,including the evolution of the current density,flow field,temperature field,and reactant concentration field during start-up,as well as the steady distribution of the current density,reactant concentration,andmembrane water content when the start-up ***-flow and counter-flow modes influence the current density distribution and temperature *** the one hand,the co-flow mode accelerates the start-up process of the PEMFC and leads to a more evenly distributed current density than the counter-flow *** the other hand,the temperature difference between the inlet and outlet sections of the cell is up to 10.1℃ under the co-flow mode,much larger than the 5.0℃ observed in the counter-flow ***,the counter-flowmode results in a more evenly distributed temperature and a lower maximum temperature than the co-flow ***,in the flow field design of a PEMFC,the reactant flow arrangements can be considered to weigh between better heat management and higher current density distribution of the cell.

关键词： PEMFC full coupling model Butler-Volmer equation multiphase mixture model co-flow mode counter-flow mode

Targeting KRAS in pancreatic cancer

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Oncology research 2024年第5期32卷 799-805页

作者： SANDRA STICKLER BARBARA RATH GERHARD HAMILTON Institute of pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient *** Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for ***,the most common KRAS mutations in PDAC are G12D(44%),G12V(34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung *** G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of ***,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in *** other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(GEF)Son of Sevenless 1 that drives *** agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

Surface activation of viscose textiles via air,argon,and oxygen dielectric barrier discharge plasma:influence of peak voltage

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Plasma Science and Technology 2024年第7期26卷 134-147页

作者： Shrouk ELASHRY Usama M.RASHED Mostafa A.WAHBA Hend M.AHMED Nabil M.ELSIRAGY Plasma Laboratory Physics DepartmentFaculty of scienceTanta UniversityTanta 31527Egypt Physics Department Faculty of Science(Male)Al-Azhar UniversityCairo 11651Egypt Textile research Industrial division National Research CentreDokkiGiza 12622Egypt

This paper discusses the use of atmospheric pressure dielectric barrier discharge(DBD)plasma treatment to enhance the surface qualities of viscose *** study explores the effects of different plasma gases,discharge voltages,and exposure times on the treated *** findings emphasize the importance of optimizing the plasma's peak voltage to achieve the desired surface treatment *** document also presents data on colour strength,wettability,colour fastness,and tensile strength of the treated fabrics,as well as scanning electron microscopy(SEM)analysis of surface morphology and chemical analysis using fouriertransition infrared spectroscopy(FTIR)and energy dispersive X-ray(EDX).The results show that treatment at a peak voltage of 11.83 k V is more efficient,except for the tensile strength which is enhanced at a peak voltage of 8.92 k *** oxygen plasma treatment significantly improves the colour strength,which exhibits an increase from 11 to *** intensified colour was attributed to the significant influence of electrostatic interactions between the charged hydroxyl groups of the oxygen plasma treated viscose textiles and the dye molecules,which enhance the *** oxygen DBD plasma exhibits a higher ability to enhance the properties of textiles when compared to air and argon *** study presents a sustainable,economical,secure,and ecologically friendly approach to explore new fabrics for specific uses.

关键词： Lissajous diagrams printability wettability tensile strength SEM EDX FTIR

CRABP1-mediated non-canonical retinoic acid signaling in motor neurons and neural stem cells

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Neural Regeneration research 2024年第6期19卷 1169-1170页

作者： Li-Na Wei Department of pharmacology University of Minnesota Medical SchoolMinneapolisMNUSA

Retinoic acid(RA),the active metabolite of vitamin A(the retinoids),elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems(Corcoran et al.,2002).The effects of RA are mediated by two very distinct pathways;the first is manifested in the nucleus by binding to a large family of nuclear RA receptors(RARs)to regulate proper expression of RAtargeted genes.

关键词： canonical spectrum critical