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

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

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Cell-free synthesis of stable isotope-labeled internal standards for targeted quantitative proteomics

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Synthetic and Systems Biotechnology 2018年第2期3卷 97-104页

作者： Ryohei Narumi Keiko Masuda Takeshi Tomonaga Jun Adachi Hiroki RUeda yoshihiro Shimizu Laboratory of Proteome Research National Institutes of Biomedical InnovationHealth and Nutrition7-6-8Satio-AsagiIbarakiOsaka 567-0085Japan Laboratory for Single Cell Mass Spectrometry RIKEN Quantitative Biology Center(QBiC)6-2-3FuruedaiSuitaOsaka 565-0874Japan Department of Systems Pharmacology Graduate School of MedicineThe University of Tokyo7-3-1 HongoBunkyo-kuTokyo 113-0033Japan Laboratory for Synthetic Biology RIKEN Quantitative Biology Center(QBiC)6-2-3FuruedaiSuitaOsaka 565-0874Japan Laboratory for Cell-Free Protein Synthesis RIKEN Quantitative Biology Center(QBiC)6-2-3FuruedaiSuitaOsaka 565-0874Japan

High-sensitivity mass spectrometry approaches using selected reaction monitoring(SRM)or multiple reaction monitoring(MRM)methods are powerful tools for targeted quantitative proteomics-based investigation of dynamics in specific biological *** high-sensitivity detection of lowabundance proteins and their quantification using this technique employ stable isotope-labeled peptide internal ***,there are various ways for preparing standards,including chemical peptide synthesis,cellular protein expression,and cell-free protein or peptide ***-free protein synthesis(CFPS)or in vitro translation(IVT)systems in particular provide high-throughput and low-cost preparation methods,and various cell types and reconstituted forms are now commercially ***,we review the use of such systems for precise and reliable protein quantification.

关键词： Absolute quantification Mass spectrometry Cell-free protein synthesis system In vitro translation Targeted quantitative proteomics PURE system

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Neoadjuvant chemotherapy for locally advanced cervical cancer

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Chinese Journal of Cancer Research 2016年第2期28卷 235-240页

作者： Takashi Iwata Azumi Miyauchi Yukako Suga Hiroshi Nishio Masaru Nakamura Akiko Ohno Nobumaru hirao Tohru Morisada Kyoko Tanaka Hiroki Ueyama Hidemichi Watari Daisuke Aoki Department of Obstetrics and Gynecology Keio University School of Medicine Department of Obstetrics and Gynecology Hokkaido University Graduate School of Medicine

Neoadjuvant chemotherapy followed by surgery （NCS） has not been fully evaluated clinically. Currently, the main regimen of neoadjuvant chemotherapy （NAC） used in NCS includes cisplatin. The antitumor effects of NAC reduce lymph node metastasis and the tumor diameter in patients prior to surgery, and this can reduce the number of high risk patients who require postoperative radiation therapy. Many randomized controlled trials （RCTs） have examined the long-term prognosis of NCS compared to primary surgery, but the utility of NCS remains uncertain. The advent of concurrent chemoradiotherapy （CCRT） has markedly improved the outcome of radiotherapy （RT）, and CCRT is now used as a standard method in many cases of advanced bulky cervical cancer. NCS gives a better treatment outcome than radiation therapy alone, but it is important to verify that NCS gives a similar or better outcome compared to CCRT.

关键词： Neoadjuvant chemotherapy (NAC) cervical cancer

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Optimal treatment strategies for hepatic portal venous gas:A retrospective assessment

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World Journal of Gastroenterology 2020年第14期26卷 1628-1637页

作者： Masanori Gonda Tatsuya Osuga yoshihiro Ikura Kazunori Hasegawa Kentaro Kawasaki Takatoshi Nakashima Department of Gastroenterology Takatsuki General HospitalTakatsuki 5691192Japan Department of Pathology Takatsuki General HospitalTakatsuki 5691192Japan Department of Surgery Takatsuki General HospitalTakatsuki 5691192Japan

BACKGROUND Hepatic portal venous gas(HPVG)generally indicates poor prognoses in patients with serious intestinal *** surgical removal of the damaged portion is effective,some patients can recover with conservative *** To establish an optimal treatment strategy for HPVG,we attempted to generate computed tomography(CT)-based criteria for determining surgical indication,and explored reliable prognostic factors in non-surgical *** Thirty-four cases of HPVG(patients aged 34-99 years)were *** for surgery had been determined mainly by CT findings(***-air,embolism,lack of contrast enhancement of the intestinal wall,and intestinal pneumatosis).The clinical data,including treatment outcomes,were analyzed separately for the surgical cases and non-surgical *** Laparotomy was performed in eight cases(surgical cases).Seven patients(87.5%)survived but one(12.5%)*** each case,severe intestinal damage was confirmed during surgery,and the necrotic portion,if present,was ***-occlusive mesenteric ischemia was the most common cause(n=4).Twentysix cases were treated conservatively(non-surgical cases).Surgical treatments had been required for twelve but were abandoned because of the patients’poor general ***,however,three(25%)of the twelve inoperable patients *** remaining 14 of the 26 cases were diagnosed originally as being sufficiently cured by conservative treatments,and only one patient(7%)*** analyses of the fatal(n=10)and recovery(n=16)cases revealed that ascites,peritoneal irritation signs,and shock were significantly more frequent in the fatal *** mortality was 90%if two or all of these three clinical findings were *** HPVG related to intestinal necrosis requires surgery,and our CT-based criteria are probably useful to determine the surgical *** non-surgical cases,ascites,peritoneal irritation signs and shock were closely associated

关键词： Hepatic portal venous gas Surgical treatment Conservative treatment Computed tomography Intestinal necrosis Prognostic factor

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Steering performance of an inverted pendulum vehicle with pedals as a personal mobility vehicle

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Theoretical & Applied Mechanics Letters 2013年第1期3卷 71-76页

作者： Chihiro Nakagawa Kimihiko Nakano yoshihiro Suda Yuki Hirayama Mechanical Engineering Osaka Prefecture University Interdisciplinary Information Studies University of Tokyo Institute of Industrial Science University of Tokyo

From the viewpoints of environmental protection, support for the aged and ensuring the right to mobility, there is a need to develop a new type of mobility vehicle that provides more effective transportation. The authors propose an inverted pendulum vehicle with pedals as one of the forms of personal mobility vehicles （PMVs）. In this paper, the steering performance of the inverted pendulum vehicle with pedals is discussed based on experiments on a prototype. From the experimental results, it was confirmed that the errors from the five subjects for the target trajectory and the five-grade evaluation of the maneuverability were similar. Finally, we created an inverted pendulum vehicle with pedals to which was added a reaction actuator for the steering system. From the experimental results, it was found that setting appropriate feedback gains for the handle steering angle and its rate of rotation, which control the right and left wheel driving torques, resulted in greatly improved maneuverability. C 2013 The Chinese Society of Theoretical and Applied Mechanics. [doi：10.1063/2.1301309]

关键词： steering control stability inverted pendulum vehicle

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The rpoS deficiency suppresses acetate accumulation in glucose-enriched culture of Escherichia coli under an aerobic condition

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Frontiers of Chemical Science and Engineering 2012年第2期6卷 152-157页

作者： Prayoga SURYADARMA yoshihiro OJIMA Yuto FUKUDA Naohiro AKAMATSU Masahito TAYA Division of Chemical Engineering Graduate School of Engineering Science Osaka University Osaka 560-8531 Japan

The role ofEscherichia coli rpoS on the central carbon metabolism was investigated through analyzing the deficiency of this regulon gene under aerobic and glucose- enriched culture conditions. The experimental results showed that while the wild type cells exhibited an overflow metabolism effect, the rpoS-deleting mutation alleviated this effect with the significant suppression of acetate accumulation under a high glucose condition. This gene deletion also induced the twofold upregulation ofgltA and one-tenth downregulation of poxB, respectively. The overflow metabolism effect was confirmed to be recovered by re-introducing rpoS gene into the mutant. These results demonstrated rpoS changed the central carbon metabolism toward acetate overflow through dehydrogenation of pyruvate and reduction of TCA cycle activity.

关键词： Escherichia coli rpoS aerobic and glucoseenriched culture overflow metabolism

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Analysis of stress fractures in athletes based on our clinical experience

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World Journal of Orthopedics 2011年第1期2卷 7-12页

作者： Jun Iwamoto yoshihiro Sato Tsuyoshi Takeda Hideo Matsumoto Institute for Integrated Sports Medicine Keio University School of MedicineTokyo 160-8582Japan Department of Neurology Mitate HospitalFukuoka 826-0041Japan

AIM:To analyze stress fractures in athletes based on experience from our sports medicine ***:We investigated the association between stress fractures and age,sex,sports level,sports activity,and skeletal site in athletes seen at our sports medicine clinic between September 1991 and April *** fractures of the pars interarticularis were excluded from this ***:During this period(18 years and 8 mo),14276 patients(9215 males and 5061 females)consulted our clinic because of sports-related injuries,and 263 patients(1.8%)[171 males(1.9%)and 92 females(1.8%)]sustained stress *** average age of the patients with stress fractures was 20.2 years(range 10-46 years);112 patients(42.6%)were 15-19 years of age and 90(34.2%)were 20-24 years of ***,90 patients(34.2%)were active at a high recreational level and 173(65.8%)at a competitive *** highest proportion of stress fractures was seen in basketball athletes(21.3%),followed by baseball(13.7%),track and field(11.4%),rowing(9.5%),soccer(8.4%),aerobics(5.3%),and classical ballet(4.9%).The most common sites of stress fractures in these patients were the tibia(44.1%),followed by the rib(14.1%),metatarsal bone(12.9%),ulnar olecranon(8.7%)and pelvis(8.4%).The sites of the stress fractures varied from sport to *** ulnar olecranon was the most common stress fracture site in baseball players,and the rib was the most common in *** and classical ballet athletes predominantly sustained stress fractures of the tibia and metatarsal *** and field and soccer athletes predominantly sustained stress fractures of the tibia and pubic *** athletes predominantly sustained stress fractures of the *** and long distance female runners who sustained multiple stress fractures had the female athlete ***:The results of this analysis showed that stress fractures were seen in high-level young athletes,with similar proportions for males and females

关键词： Athletes Bone mineral density Female athlete triad Stress fracture Vitamin D insufficiency

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Carcinosarcoma of the liver with mesenchymal differentiation

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World Journal of Gastroenterology 2007年第5期13卷 809-812页

作者： Shinichi Sumiyoshi Masataka Kikuyama Yuji Matsubayashi Fujito Kageyama yoshihiro Ide Yoshimasa Kobayashi Hirotoshi Nakamura Department of Gastroenterology Hamamatsu Rosai Hospital Hamamatsu Japan Department of Pathology Hamamatsu Rosai Hos-pital Hamamatsu Japan Second Division Department of Internal Medicine Hamamatsu University School of Medicine Hamamatsu Japan

We report an extremely rare case where a mesenchymal differentiation, especially embryonal sarcoma, was demonstrated in cholangiocarcinoma. At autopsy, a yellowish-white tumor （15 cm× 12 cm） was found in the right hepatic lobe, and there were several daughter nodules in both hepatic lobes. Histologically, most of the main tumor and all of the daughter nodules examined showed sarcomatous changes （spindle cells, pleomorphic ceils and hyalization）. Histologic examination of a part of the main tumor disclosed a focus of adenocarcinoma within the tumor. The frequent transitions between the adenocarcinomatous areas and the sarcomatous areas suggested that sarcomatous transformation occurred in the cholangiocarcinoma and then spread rapidly. Immunohistochemically, the adenocarcinomatous elements were positive for cytokeratin, carcinoembryonic antigen （CEA） and epithelial membrane antigen, and negative in the sarcomatous cells. Vimentin was positive only in the sarcomatous elements. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop sarcomatous elements via metaplasia of the epithelial element.

关键词： Cholangiocarcinoma Carcinosarcoma Mesenchymal differentiation

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Character of Frontier Orbitals of Antiviral Drugs: Candidate Drugs against Covid-19

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Open Journal of Physical Chemistry 2020年第3期10卷 158-165页

作者： yoshihiro Mizukami Faculty of Education Shiga University Otsu Japan

We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and lowest unoccupied molecular orbital) at optimized structure of each molecule were obtained. T-705RTP (active triphosphate metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes of frontier orbitals. We also obtained similar shapes of frontier orbitals among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical viewpoint, we suggest T-705RTP is a CTP analogue and dihydroxy GS-441524 triphosphate is an ATP analogue.

关键词： Covid-19 Antiviral Drugs Frontier Orbitals Ribonucleotides

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Nash Equilibrium of a Fixed-Sum Two-Player Game

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American Journal of Computational Mathematics 2024年第3期14卷 346-357页

作者： yoshihiro Tanaka Faculty of Economics Hokkaido University Sapporo Japan

It is well established that Nash equilibrium exists within the framework of mixed strategies in strategic-form non-cooperative games. However, finding the Nash equilibrium generally belongs to the class of problems known as PPAD (Polynomial Parity Argument on Directed graphs), for which no polynomial-time solution methods are known, even for two-player games. This paper demonstrates that in fixed-sum two-player games (including zero-sum games), the Nash equilibrium forms a convex set, and has a unique expected payoff. Furthermore, these equilibria are Pareto optimal. Additionally, it is shown that the Nash equilibrium of fixed-sum two-player games can theoretically be found in polynomial time using the principal-dual interior point method, a solution method of linear programming.

关键词： Nash Equilibrium Fixed-Sum Two-Player Game Principal-Dual Interior Point Method

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