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Identification of a dihydroorotate dehydrogenase inhibitor thatinhibits cancer cell growth by proteomic profiling

肿瘤学研究(英文) 2023年第6期31卷 833-844页

作者： makoto KAWATANI HARUMI AONO SAYOKO HIRANUMA TAKESHI SHIMIZU makoto MUROI TOSHIHIKO NOGAWA TOMOKAZU OHISHI SHUN-ICHI OHBA MANABU KAWADA KANAMI YAMAZAKI SHINGO DAN NAOSHI DOHMAE HIROYUKI OSADA Biomolecular Characterization Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Chemical Resource Development Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Chemical Biology Research Group RIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Molecular Structure Characterization Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Institute of Microbial Chemistry(BIKAKEN) NumazuMicrobial Chemistry Research FoundationShizuoka410-0301Japan Division of Molecular Pharmacology Cancer Chemotherapy CenterJapan Foundation for Cancer ResearchTokyo135-8550Japan Department of Pharmaceutical Sciences University of ShizuokaShizuoka422-8526Japan

Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune *** study presents the identification of a potent DHODH inhibitor by proteomic ***-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer *** profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic ***,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic *** results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell ***,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.

关键词： Anticancer agents Differentiating agents Drug target identification

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Accuracy of shoulder joint injections with ultrasound guidance:Confirmed by magnetic resonance arthrography

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World Journal of Orthopedics 2022年第3期13卷 259-266页

作者： Kosuke Kuratani makoto Tanaka Hiroto Hanai Kenji Hayashida Department of Orthopedic Surgery Japan Community Healthcare Organization Osaka HospitalOsaka 553-0003Japan Center for Sports Medicine Daini Osaka Police HospitalOsaka 543-8922Japan Department of Orthopaedic Surgery Osaka University Graduate School of MedicineSuita 565-0871Japan Department of Orthopaedic Surgery Daini Osaka Police HospitalOsaka 543-8922Japan

BACKGROUND Intra-articular glenohumeral joint injections are essential procedures for treating various shoulder disorders. Fluoroscopy-guided injections have been extensively used;however, they pose a risk of radiation exposure and are expensive and timeconsuming. Recently, it has been suggested that ultrasound-guided injections are accurate and cost effective *** To evaluate the accuracy of ultrasound-guided glenohumeral injections using a posterior approach that is confirmed using magnetic resonance arthrography(MRA).METHODS The study included 179 shoulders of patients with recurrent anterior instability(150 patients;103 and 76 right and left shoulders, respectively;160 males and 19 females;average age = 20.5 years;age range: 14-63 years) who underwent MRA for preoperative diagnosis. They were injected with 12 m L lidocaine(1%) using the ultrasound-guided posterior approach and then underwent magnetic resonance imaging. Two shoulder surgeons, except for the injector, evaluated the transverse relaxation(T2)-weighted images of axial planes and classified the intraarticular condition of injected contrast into three groups based on one of the three following scenarios: no leakage, injection into the glenohumeral joint without leakage;minor leakage, practical intra-articular injection with some leakage outside the posterior rotator cuffs;and major leakage, inaccurate injection with mass leakage without any contrast into the joint. The inter-rater reliability between two assessors was also evaluated by calculating Cohen’s kappa coefficient. The learning curve was assessed regarding the inaccurate injection rate by analyzing Spearman’s rank correlation *** Of the 179 injections, 163 shoulders(91.0%) had no leakage, 10 shoulders(5.6%) had minor leakage, and six shoulders(3.4%) had major leakage. In total, 173 shoulders(96.6%) were intraarticularly injected;thus, we could detect anterior labrum and capsular pathologies. Regarding the inter-rater

关键词： Shoulder injections Glenohumeral injections Ultrasound guidance Magnetic resonance arthrography

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Yield of OH radicals in water under heavy ion *** on mass,specific energy,and elapsed time

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Nuclear Science and Techniques 2007年第1期18卷 35-38页

作者： Mitsumasa TAGUCHI Takuji kojima Organic Pollutant Removal Technology Group Japan Atomic Energy Agency1233 WatanukiTakasakiGunma370-1292 Japan

Dependence of yields of OH (hydroxyl) radicals on the mass and specific energy of heavy ions and elapsed time after irradiation was investigated,to understand chemical reactions of aqueous *** yields of irradiation products of phenol,super-linearly increased with the incident energy of He,C,and Ne ions ranging from 2 to 18 MeV/*** yields of the OH radicals were estimated by analyzing the yields of the irradiation products of phenol. The yields of the OH radicals increased with the specific energy for each ion,but decreased both with the mass of each ion at the same specific energy and elapsed time after irradiation.

关键词：重离子辐射水辐射分解羟自由基产率质量耗用时间

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Innovative nanocrystal-based technologies for ceramic devices with novel electronic functions

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Journal of Advanced Ceramics 2012年第2期1卷 79-88页

作者： makoto KUWABARA 4-36-501 Shimoshirouzu-kita KasugaFukuoka 816-0854Japan

There has been a great progress in the synthesis of a variety of inorganic colloidal nanocrystals(NCs)with highly controlled size and shape in the last *** achievement has promoted comprehensive researches on the fabrication and engineering of NC devices with novel structure and function with the aim of utilizing them in a wide area of applications,including electronics and optoelectronics,by using various NC assembling and patterning ***,colloidal NCs having been extensively investigated so far are mostly metals,semiconductors and magnetic materials,and only limited investigations on oxide NCs from a point of view of NC ceramic engineering have been ***,innovative nanocrystal-based technologies necessary for the fabrication of NC ceramic devices with novel and gigantic electronic functions,limiting the materials to perovskite oxides,and a new perspective on the future ceramic technology are discussed.

关键词： nanocrystals electronic functions Perovskite bottom-up process

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Modulation of Pain and Itch by Spinal Glia

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Neuroscience Bulletin 2018年第1期34卷 178-185页

作者： makoto Tsuda Department of Life Innovation Graduate School of Pharmaceutical Sciences Kyushu University Department of Molecular and System Pharmacology Graduate School of Pharmaceutical Sciences Kyushu University

Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.

关键词： Neuropathic pain Chronic itch Microglia Astrocytes Spinal dorsal horn

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Hepatocellular carcinoma effective stereotactic body radiotherapy using Gold Anchor and the Synchrony system:Two case reports and review of literature

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World Journal of Clinical Cases 2022年第8期10卷 2591-2603页

作者： Sakue Masuda Toshitaka Tsukiyama Yumiko Minagawa Kazuya Koizumi makoto Kako Takeshi Kinbara Uojima Haruki Department of Gastroenterology Shonankamakura General HospitalKanagawa 247-8533Japan Department of Interventional Radiology Center Shonan Kamakura General HospitalKanagawa 247-8533Japan Department of Radiation Oncology Shonan Kamakura General HospitalKanagawa 247-8533Japan

BACKGROUND Radiotherapy for hepatocellular carcinoma(HCC)is considered to have limited efficacy because of treatment intensity considering that the irradiated area includes the liver,which is highly *** this report,we present two cases in which tumor control by surgical resection,radiofrequency ablation,transcatheter arterial chemoembolization(TACE),and lenvatinib administration was difficult,but stereotactic body radiotherapy(SBRT)using the Synchrony system by Radixact?and Gold Anchor?(GA)was *** SUMMARY A 60-year-old man had a single 10-cm HCC in the right *** lesions remained after TACE,and levels of alpha-fetoprotein and protein induced by vitamin K antagonists II(PIVKA-II)decreased and quickly *** performed SBRT with *** weeks after implantation,localized radiotherapy(SBRT;40 Gy/5 fractions)was performed using the Synchrony system by Radixact?.Four weeks later,the viable lesion had disappeared,and the PIVKA-II levels decreased.A 77-year-old man had a single 12-cm HCC in the right *** patient experienced recurrence after *** recurrence occurred after TACE,and we performed SBRT with *** of the proximity of the HCC to the gastrointestinal tract,localized radiotherapy(SBRT;39 Gy/13 fractions)to the HCC was performed 3 wk after implantation using the Synchrony system by Radixact?.Four weeks later,the viable lesion had disappeared on computed tomography,and the PIVKA-Ⅱlevels *** SBRT using the Synchrony system and GA can deliver a large dose accurately and safely,and could have a high therapeutic effect.

关键词： Fiducial marker Hepatocellular carcinoma Gold Anchor■ Radixact■ Stereotactic body radiotherapy Case report

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Micelle-crosslinked hydrogels with stretchable,self-healing,and selectively adhesive properties:Random copolymers work as dynamic yet self-sorting domains

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聚集体(英文) 2023年第3期4卷 71-83页

作者： Hiroaki Asai Motoki Shibata Mikihito Takenaka Shinichi Takata Kosuke Hiroi makoto Ouchi Takaya Terashima Department of Polymer Chemistry Graduate School of EngineeringKyoto UniversityKatsuraKyotoJapan Office of Society-Academia Collaboration for Innovation Kyoto UniversityYoshida-honmachiKyotoJapan Institute for Chemical Research Kyoto UniversityUjiKyotoJapan RIKEN SPring-8 Center Sayo-choSayo-gunHyogoJapan J-PARC Center Japan Atomic Energy AgencyTokaiIbarakiJapan

The design of crosslinking domains is a vital factor to create functional hydrogels with controlled physical,mechanical,and adhesive *** paper demonstrates versatile synthetic systems of micelle-crosslinked hydrogels with highly stretchable,self-healing,and selectively adhesive *** this,methacrylate-bearing random copolymer micelles are designed as physical and covalent crosslink domains via the self-assembly of amphiphilic random copolymers carrying hydrophilic poly(ethylene glycol)(PEG),hydrophobic butyl or dodecyl groups,and methacrylate-terminal PEG in *** size,aggregation number,and pendant methacrylate number of the micelles are controlled by the composition and degree of *** are efficiently obtained from the free radical polymerization of hydrophilic monomers such as PEG acrylate and acrylamide in the presence of the micelle crosslinkers in *** to the dynamic yet selective chain exchange properties of the micelle domains,the hydrogels are highly stretchable up to over 1000%and show self-healing and selectively adhesive *** self-healing of hydrogels is promoted upon heating due to the fast chain exchange of the micelle domains,whereas hydrogels consisting of micelles with different alkyl groups are never adhesive because of their self-sorting properties.

关键词： adhesion hydrogel random copolymer micelle self-assembly self-healing self-sorting

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An Analysis of the Women Commuters’ Satisfaction in the Public Bus Service in Bangladesh: A Survey on Local Buses in Major Cities

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Journal of Transportation Technologies 2022年第4期12卷 559-577页

作者： Ayesha Umme kojima Aya Kubota Hisashi Graduate School of Science and Engineering Saitama University Saitama Japan

Bangladesh is one of the most populated developing countries where public bus service plays a vital role as a public transport mode since it is easily available and cost-effective. In the social, commercial, educational, and administrative spheres, women’s participation in the labor force in economic enterprises is steadily expanding in the country. Very little research considers only women commuters to analyze the service quality of public buses and they selected only Dhaka city as a study area. However, a large number of trips were generated by women commuters in the industrial and commercial zones such as Gazipur, Narayanganj, and Dhaka. This paper ascertains the public bus service attributes that affect women commuters’ satisfaction as well as finds out the major problems of women commuters while traveling on public buses and the possible solutions to them. This survey included 766 women commuters from Dhaka, Narayanganj, and Gazipur who were interviewed face to face. Structural Equation Model (SEM) was used as the instrument for identifying the service quality (SQ) attributes that influenced the women commuters’ satisfaction. A series of models were developed based on the trial-and-error method and the model M3 is selected as the best fit according to SEM fit indices values. The study’s main goal was to compile a list of service quality attributes that influence women commuters’ satisfaction. Major issues with the current public bus service in terms of safety and security, as well as remedies, were identified through discussions with experienced female commuters. These findings reveal that women commuters’ satisfaction is primarily influenced by safety and security, as well as the degree of comfort provided by bus service because they frequently encounter major safety and security issues on public buses and want an immediate remedy. This paper offers some potential strategies for addressing the issues, which may prompt policymakers to pay more attent

关键词： Public Bus Service Quality Women Commuters’ Satisfaction SEM

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Gap Analysis between Women Passengers’ Perception and Expectations about Bus Service: A Case Study on Bangladesh

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Journal of Transportation Technologies 2022年第2期12卷 258-285页

作者： Ayesha Umme kojima Aya Kubota Hisashi Graduate School of Science and Engineering Saitama University Saitama Japan

Since public bus service is frequently available and reasonably priced in major cities of Bangladesh including Dhaka, the capital city, a significant number of economically active women regularly commute to work utilizing public buses. Since female commuters experience unique challenges compared to their male counterparts, a gap analysis on the perception of men and women, as well as the difference between the female commuters’ perceptions and expectations, could help to pinpoint the issues. The aim of this paper is to determine the gap between female commuters’ perceptions and expectations of bus service quality in Bangladesh, as well as the current perception of both male and female passengers. In this paper, the data obtained is studied to determine the service quality needs which should be improved by analyzing the perception and expectation gaps for female passengers. SERVQUAL models were used to examine the disparities between perceptions and aspirations in Bangladesh’s major cities. Tangibility, reliability, responsiveness, assurance, and empathy are the five dimensions of SERVQUAL. The data for this study was collected from 1500 commuters in Bangladesh’s largest cities, including Dhaka, Gazipur, and Narayanganj. Primary data was gathered using a purpose-built questionnaire survey. The Gap values are negative in all dimensions, according to the findings of the study. In the data analysis, a negative gap value indicates that the expectation exceeds the perception. According to the gap analysis, the quality of bus service for passengers is insufficient. Bus service quality is seen and expected to be quite varied. It is vital to improve bus service to meet the needs of women. The findings could be valuable in planning future transportation policies that take female commuters’ needs into account.

关键词： Public Bus Public Transport Women Commuters Service Quality SERVQUAL Bangladesh Perceptions Expectations

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Exploring the Commuters’ Willingness-to-Pay and Its Influencing Factors for an Improved Public Bus Service in Dhaka City

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Journal of Transportation Technologies 2023年第2期13卷 139-157页

作者： Ayesha Umme kojima Aya Kubota Hisashi Graduate School of Science and Engineering Saitama University Saitama Japan

Improved transportation services are a crucial component of urban growth, particularly in emerging cities like Dhaka. Ensuring an improved public bus service quality is a challenge for the city’s transport planners and policy makers. Nevertheless, this challenge can’t be met without the support of the residents of this city. This study intends to evaluate the commuters’ willingness to pay (WTP) for an improved and better public bus service quality in Dhaka city. It also attempts to explore the factors affecting the commuters’ WTP amounts. In order to accomplish the study’s goals, a stated preference survey was designed to enquire into the whys and wherefores of female passengers’ harassment on public buses and also to prefer some influential service quality features. WTP values of respondents were calibrated using binary and ordinal logistic models, and these models were developed using SPSS version 26. The results indicate that the majority of respondents were willing to pay more for better service facilities, and they point to security as the most important factor in determining how much extra fare commuters are willing to pay. The results also demonstrate that commuters’ WTP amounts are highly influenced by the respondents’ monthly income. Results from this study have important policy implications, such as protecting women’s safety on public transportation and taking commuters’ socio-demographic characteristics into account before enacting any legislation or increasing fares.

关键词： WTP Public Bus Harassment Improved Service Quality Security Socio-Demographic Features

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