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Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma

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Cancer Innovation 2024年第2期3卷 80-95页

作者： Satoru Sasagawa Jun Kumai toru Wakamatsu Yoshihiro Yui Molecular Biology Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Sarcoma Treatment Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Department of Musculoskeletal Oncology Service Osaka International Cancer InstituteOsakaJapan

Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the *** deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi *** provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture ***:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective ***38 was concomitantly used as an ameliorant drug with romidepsin ***,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug *** addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on ***:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell *** the apoptotic inducible cells,co-treatment with SN38 enhanced cell *** nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction *** a novel efficacy of SN38,we revealed TWIST1 suppression in SS *** the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive *** demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the ***:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and

关键词： HDAC inhibitor MICA/B SN38 spheroid synovial sarcoma TWIST1

Low-molecular-weight dextran for optical coherence tomography may not be protective against kidney injury in patients with renal insufficiency

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World Journal of Nephrology 2021年第2期10卷 8-20页

作者： toru misawa Tomoyo Sugiyama Yoshihisa Kanaji Masahiro Hoshino Masao Yamaguchi Masahiro Hada Tatsuhiro Nagamine Kai Nogami Yumi Yasui Eisuke Usui Tetsumin Lee Taishi Yonetsu Tetsuo Sasano Tsunekazu Kakuta Department of Cardiovascular Medicine Tsuchiura Kyodo General HospitalIbaraki 300-0028Japan Department of Interventional Cardiology Tokyo Medical and Dental UniversityTokyo 113-8519Japan Department of Cardiovascular Medicine Tokyo Medical and Dental UniversityTokyo 113-8519Japan

BACKGROUND Low-molecular-weight dextran(LMWD)is considered a safe alternative to contrast media for blood displacement during optical coherence tomography(OCT)*** To investigate whether the use of LMWD for OCT is protective against kidney injury in patients with advanced renal *** In this retrospective cohort study,we identified 421 patients with advanced renal insufficiency(estimated glomerular filtration rate<45 mL/min/1.73 m2)who underwent coronary angiography or percutaneous coronary intervention;79 patients who used additional LMWD for OCT imaging(LMWD group)and 342 patients who used contrast medium exclusively(control group).We evaluated the differences between these two groups and performed a propensity score-matched subgroup *** The median total volume of contrast medium was 133.0 mL in the control group vs 140.0 mL in the LMWD *** baseline renal function was not statistically different between these two groups,the LMWD group demonstrated a strong trend toward the progression of renal insufficiency as indicated by the greater change in serum creatinine level during the 1-year follow-up compared with the control *** in the LMWD group experienced worsening renal function more frequently than patients in the control *** score matching adjusted for total contrast media volume consistently indicated a trend toward worsening renal function in the LMWD group at the 1-year *** serum creatinine at 1-year follow-up was significantly greater in the LMWD group than that in the control group[0.06(-0.06,0.29)vs-0.04(-0.23,0.08)mg/dL,P=0.001],despite using similar contrast *** OCT using LMWD may not be protective against worsening renal function in patients with advanced renal insufficiency.

关键词： Coronary artery disease Kidney injury Contrast media Dextran Optical coherence tomography Renal insufficiency

Superconducting joints using reacted multifilament MgB_(2)wires:A technology toward cryogen-free MRI magnets

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Journal of Magnesium and Alloys 2024年第1期12卷 159-170页

作者： Dipak Patel Akiyoshi Matsumoto Hiroaki Kumakura Yuka Hara toru Hara Minoru Maeda Hao Liang Yusuke Yamauchi Seyong Choi Jung Ho Kim Md Shahriar A.Hossain School of Mechanical and Mining Engineering The University of QueenslandSt LuciaQueensland 4072Australia National Institute for Materials Science(NIMS) 1-2-1 SengenTsukubaIbaraki 305-0047Japan Department of Electrical Engineering and Kangwon High Magnetic Field Center Institute of Quantum Convergence TechnologyKangwon National UniversityGangwon 24341Republic of Korea Australian Institute for Bioengineering and Nanotechnology(AIBN) The University of QueenslandSt LuciaQueensland 4072Australia Department of Materials Process Engineering Graduate School of EngineeringNagoya UniversityNagoyaAichi 464-8603Japan Institute for Superconducting and Electronic Materials Australian Institute for Innovative MaterialsUniversity of WollongongNorth WollongongNew South Wales 2500Australia

The development of superconducting joining technology for reacted magnesium diboride(MgB_(2))conductors remains a critical challenge for the advancement of cryogen-free MgB_(2)-based magnets for magnetic resonance imaging(MRI).Herein,the fabrication of superconducting joints using reacted carbon-doped multifilament MgB_(2)wires for MRI magnets is *** achieve successful superconducting joints,the powder-in-mold method was employed,which involved tuning the filament protection mechanism,the powder compaction pressure,and the heat treatment *** fabricated joints demonstrated clear superconducting-to-normal transitions in self-field,with effective magnetic field screening up to 0.5 T at 20 *** evaluate the interface between one of the MgB_(2)filaments and the MgB_(2)bulk within the joint,serial sectioning was conducted for the first time in this type of superconducting *** serial sectioning revealed space formation at the interface,potentially caused by the volume shrinkage associated with the MgB_(2)formation or the combined effect of the volume shrinkage and the different thermal expansion coefficients of the MgB_(2)bulk,the filament,the mold,and the sealing *** findings are expected to be pivotal in developing MgB_(2)superconducting joining technology for MRI magnet applications through interface engineering.

关键词： Mg B2 superconducting joint MgB_(2)conductor MRI applications Cryogen-free magnet Persistent-mode operation

Functional Confirmation Using a Medical X-Ray System of a Semiconductor Survey Meter

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Open Journal of Radiology 2024年第1期14卷 1-13页

作者： Katsunao Suzuki toru Negishi Yoh Kato Yasuhisa Kono Michiharu Sekimoto Department of Radiological Technology Kariya Toyota General Hospital Kariya Japan Department of Radiological Sciences Graduate School of Human Health Science Tokyo Metropolitan University Tokyo Japan Department of Radiological Technology Faculty of Medical Technology Niigata University of Health and Welfare Niigata Japan

In recent years, semiconductor survey meters have been developed and are in increasing demand worldwide. This study determined if it is possible to use the X-ray system installed in each medical facility to calculate the time constant of a semiconductor survey meter and confirm the meter’s function. An additional filter was attached to the medical X-ray system to satisfy the standards of N-60 to N-120, more copper plates were added as needed, and the first and second half-value layers were calculated to enable comparisons of the facility’s X-ray system quality with the N-60 to N-120 quality values. Next, we used a medical X-ray system to measure the leakage dose and calculate the time constant of the survey meter. The functionality of the meter was then checked and compared with the energy characteristics of the meter. The experimental results showed that it was possible to use a medical X-ray system to reproduce the N-60 to N-120 radiation quality values and to calculate the time constant from the measured results, assuming actual leakage dosimetry for that radiation quality. We also found that the calibration factor was equivalent to that of the energy characteristics of the survey meter.

关键词： Semiconductor Survey Meter Functional Confirmation Medical X-Ray System Calibration Factor Time Constant

Inverse relationship between platelet Akt activity and hippocampal atrophy:A pilot case-control study in patients with diabetes mellitus

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World Journal of Clinical Cases 2024年第2期12卷 302-313页

作者： Haruhiko Tokuda Takamitsu Hori Daisuke Mizutani Tomoyuki Hioki Kumi Kojima Takashi Onuma Yukiko Enomoto Tomoaki Doi Rie Matsushima-Nishiwaki Shinji Ogura Hiroki Iida toru Iwama Takashi Sakurai Osamu Kozawa Department of Metabolic Research Research InstituteNational Center for Geriatrics and GerontologyObu 474-8511Japan Department of Clinical Laboratory National Center for Geriatrics and GerontologyObu 474-8511Japan Department of Pharmacology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Neurosurgery Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Dermatology Central Japan International Medical CenterMinokamo 505-8510Japan Department of Anesthesiology and Pain Medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Emergency Medicine Faculty of MedicineUniversity of ToyamaToyama 930-0194Japan Department of Emergency and Disaster Medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Research Institute National Center for Geriatrics and GerontologyObu 474-8511Japan

BACKGROUND Akt plays diverse roles in *** is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin *** also plays a vital role in human platelet ***,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without *** To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM *** Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched *** pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric *** volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal *** The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were ***,this relationship was not observed in the control *** These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM *** findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

关键词： Akt Platelet Hippocampal atrophy Magnetic resonance imaging Diabetes mellitus

Population-based X-ray gastric cancer screening in Hiroshima prefecture, Japan

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World Journal of Clinical Oncology 2024年第2期15卷 271-281页

作者： Nhu Thi Hanh Vu Yuji Urabe Duc Trong Quach Shiro Oka toru Hiyama Department of Internal Medicine University of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh 700000Viet Nam Department of Endoscopy Hiroshima University HospitalHiroshima 734-8551Japan Department of Gastrointestinal Endoscopy and Medicine Hiroshima University HospitalHiroshima 734-8551Japan Department of Gastroenterology Hiroshima University HospitalHiroshima 734-8551Japan Health Service Center Hiroshima UniversityHigashihiroshima 739-8514Japan

BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease ***-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of the method over 39 years have not been *** This was a population-based retrospective *** data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization,including the number and rate of participants and those requiring esophagogastroduodenoscopies(EGDs),the number and rate of participants diagnosed as having GC,and the positive predictive value of the abnormal findings detected by X-ray and confirmed by *** number and rate of esophageal cancers were also ***,the cost of detecting one GC was *** The number of participants has decreased during the last four decades,from 39925 in 1983 to 12923 in *** rate of those requiring EGDs decreased significantly in recent years(P<0.001).The number of participants diagnosed as having GC has also declined,from 76 to 10 ***,the rate of cases diagnosed as GC among the participants remained around 0.1%.The positive predictive value increased significantly in recent years except during *** number and rate of accidentally detected esophageal cancers have risen recently,from 0%in 2008 to 0.02%in 2021,one-fifth of the diagnosis rate of *** GC diagnosis costs approximately 4200000 Japanese Yen(30000 United States Dollars)for the X-ray screenings and *** X-ray GC screening in Hiroshima has been efficient,but one challenge is the *** cancers may also need to be considered because they have gradually increased in recent years.

关键词： Population Retrospective studies X-ray Gastric cancer Screening

Sahara’s surface transformation forced an abrupt hydroclimate decline and Neolithic culture transition in northern China

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The Innovation 2024年第1期5卷 70-79页

作者： Yandong Hou Hao Long Sumiko Tsukamoto Zhengyao Lu Jie Chen Daniel EIbarra toru Tamura Qiong Zhang Weiyi Sun Jingran Zhang Lei Gao Manfred Frechen Ji Shen State Key Laboratory of Lake Science and Environment Nanjing Institute of Geography and LimnologyChinese Academy of Sciences(NIGLAS)Nanjing 210008China Leibniz Institute for Applied Geophysics(LIAG) Department of Geochronology30655 HannoverGermany Department of Physical Geography and Ecosystem Science Lund University22100 LundSweden Key Laboratory of Western China’s Environmental Systems(Ministry of Education) College of Earth and Environmental SciencesLanzhou UniversityLanzhou 730000China College of Atmospheric Sciences Lanzhou UniversityLanzhou 730000China Institute at Brown for Environment and Society and Department of Earth Environmentaland Planetary SciencesBrown UniversityProvidenceRI 02912USA Geological Survey of Japan National Institute of Advanced Industrial Science and TechnologyTsukubaIbaraki 305-8567Japan Graduate School of Frontier Sciences University of TokyoKashiwaChiba 277-8561Japan Department of Physical Geography and Bolin Centre for Climate Research Stockholm University10691 StockholmSweden School of Geography Nanjing Normal UniversityJiangsu Centre for Collaborative Innovation in Geographical Information Resource Development and ApplicationKey Laboratory of Virtual Geographic EnvironmentMinistry of Education of ChinaNanjing 210023China School of Geography and Ocean Science Nanjing UniversityNanjing 210023China

The remote forcing from land surface changes in the Sahara is hypothesized to play a pivotal role in modulating the intensity of the East Asian summer monsoon(EASM)through ocean-atmospheric *** modulation has far-reaching consequences,particularly in facilitating societal shifts documented in northern ***,we present a well-dated lake-level record from the Daihai Lake Basin in northern China,providing quantitative assessments of Holocene monsoonal precipitation and the consequent migrations of the northern boundary of the *** reconstruction,informed by a water-and-energy balance model,indicates that annual precipitation reached700 mm during 8–5 ka,followed by a rapid decline to tween 5 and 4 *** shift coherently aligns with a signi550 mm be-ficant300 km northwestward movement of the EASM northern boundary during the Middle Holocene(MH),in contrast to its current *** findings underscore that these changes cannot be entirely attributed to orbital forcing,as corroborated by simulation *** model simulations deployed in our study suggest that the presence of the Green Sahara during the MH significantly strengthened the EASM and led to a northward shift of the monsoon rainfall ***,the Sahara’s reversion to a desert landscape in the late Holocene was accompanied by a corresponding southward retraction of monsoon *** dramatic hydroclimate changes during5–4 ka likely triggered or at least contributed to a shift in Neolithic cultures and societal transformation in northern *** decreasing agricultural productivity,communities transitioned from millet farming to a mixed rainfed agriculture and animal husbandry ***,our findings elucidate not only the variability of the EASM but also the profound implications of a remote forcing,such as surface transformations of the Sahara,on climatic changes and cultural evolution in northern China.

关键词： Holocene monsoon abrupt

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二战前宪法学中的双重法律概念与法治行政

法治现代化研究 2024年第4期8卷 192-200页

作者： [日]毛利透王丹红(译) 日本京都大学法学部西北政法大学行政法学院

法律的概念、依法律行政原理是立宪主义国家的基石。日本虽然继受了德国的立宪主义学说,但关于该基础性概念和原理的内容却未形成通说。为探究其原因,本文梳理了二战前后德国和日本宪法学界六位代表性学者对形式性与实质性法律概念的各... 详细信息

法律的概念、依法律行政原理是立宪主义国家的基石。日本虽然继受了德国的立宪主义学说,但关于该基础性概念和原理的内容却未形成通说。为探究其原因,本文梳理了二战前后德国和日本宪法学界六位代表性学者对形式性与实质性法律概念的各自解读,以及它们对解释依法律行政、法律保留原则的内容、功能产生的不同影响,从而提示了对法律概念、法律保留原则新的理解思路,并以此说明任何理论都是历史的产物,服务于不同时期的宪政体制与不同学者的立宪主张。而不断发展变化的社会现实需要才是推动制度建构与理论发展的内在动力。

关键词：双重法律概念法规法律保留一般性规范

Effects of Kampo medicine hangebyakujutsutemmato on persistent postural-perceptual dizziness:A retrospective pilot study

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World Journal of Clinical Cases 2022年第20期10卷 6811-6824页

作者： toru Miwa Shin-ichi Kanemaru Department of Otolaryngology-Head and Neck Surgery Osaka Metropolitan UniversityOsaka 5458585Japan Department of Otolaryngology-Head and Neck Surgery Tazuke Kofukai Medical Research InstituteKitano HospitalOsaka 5308480Japan Department of Otolaryngology-Head and Neck Surgery Kyoto UniversityKyoto 7507501Japan

BACKGROUND Persistent postural-perceptual dizziness(PPPD)is a functional disorder,typically preceded by acute vestibular *** is characterized by a shift in processing spatial orientation information,to favor visual over vestibular and somatosensory inputs,and a failure of higher cortical *** date,no therapies for PPPD have been *** medicine hangebyakujutsutemmato(HBT)has been reported to alleviate disturbances of *** hypothesized that HBT would be a beneficial treatment for *** To examine the efficacy of HBT for the treatment of *** Patients with PPPD were enrolled and divided into two groups:The HBT group(n=24)and the non-HBT group(n=14).The participants completed questionnaire surveys[Niigata PPPD questionnaire(NPQ),dizziness handicap inventory,hospital anxiety and depression scale(HADS),orthostatic dysregulation questionnaire,pittsburg sleep quality index(PSQI),and motion sickness scores]before and after HBT ***,to identify HBT responders,multivariate regression analysis was performed using the results of the ques-tionnaire surveys and equilibrium tests;including stabilometry,and caloric,vestibular evoked myogenic response,and head-up tilt *** Thirty-eight outpatients were included in this study,of which 14 patients(3 men,11 women;mean age,63.5±15.9 years)received treatment without HBT,and 24(1 man,23 women;mean age,58.2±18.7 years)received combination treatment with *** HBT treatment,NPQ scores decreased significantly(baseline 40.1±10.0 vs 2 mo 24.6±17.7,P<0.001).No statistically significant changes were observed in the NPQ scores in the non-HBT group(baseline 38.6±12.2 vs 2 mo 39.4±14.4,P=0.92).Multivariable regression analysis revealed that the results of stabilometry(P=0.02)and the caloric(P=0.03),and head-up tilt tests(P<0.001),HADS(P=0.003),and PSQI(P=0.01)were associated with HBT responsiveness in PPPD *** HBT may be an effective adjunct therapy fo

关键词： Hangebyakujutsutemmato Kampo medicine Persistent postural-perceptual dizziness Niigata persistent postural-perceptual dizziness questionnaire score Sensory reweighting Treatment responder