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Multiplexed bioluminescence imaging of cancer cell response to hypoxia and inflammation in the caudal-artery injection model of bone metastasis during zoledronic acid treatment

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 69-80页

作者： Misa Minegishi Takahiro Kuchimaru Kenji Nakagawa Tatsuhiro Isozaki Satoshi Fujimori tetsuya kadonosono Shinae Kizaka-Kondoh School of Life Science and Technology Tokyo Institute of TechnologyKanagawa 226-8501Japan Center for Molecular Medicine Jichi Medical UniversityTochigi 329-0498Japan.

Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis.However,therapeutic agents including zoledronic acid(ZA)are insufficient to regress established bone metastasis.Therefore,new treatment strategies are desired,and unraveling the status of cancer cells during bone metastatic progression will help develop therapeutic strategies.Methods:We developed a unique multiplexed reporter system for bioluminescent imaging(MRS-BLI)using three luciferase reporter genes.This system allows for the noninvasive and quantitative monitoring of tumor growth and activities of nuclear factor-kappa B(NF-κB)and hypoxia-inducible factor(HIF),which are the key transcriptional factors in response to inflammation and hypoxia,respectively.PC-3/MRS-BLI,a human prostate cancer cell line that stably retains the MRS-BLI reporter genes,was applied to the caudal-artery injection model of bone metastasis to observe the status of cancer cells during bone metastasis development and ZA treatment(<1 month).Results:MRS-BLI reveals key events during the bone metastasis development:NF-κB and HIF are activated in cancer cells after migration to the bone marrow and are transiently reduced,followed by rapid activation before proliferation begins.ZA treatment suppresses the growth of metastasized cancer cells by suppressing NF-κB and HIF activities that may be indirectly induced by osteoclast activation.Conclusion:By visualizing the NF-κB and HIF activities of PC-3/MRS-BLI in bone,MRS-BLI has enabled new discoveries regarding the regulation of bone metastases.Further analysis of the progression of bone metastases using MRS-BLI may provide important information for developing new therapeutic strategies.

关键词： Bone metastasis multiplexed bioluminescence imaging zoledronic acid nuclear factor-kappa B hypoxia inducible factor

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ROR2 regulates the survival of murine osteosarcoma cells in lung capillaries

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 611-621页

作者： Diem Thi Phuong Tran Takahiro Kuchimaru Mongkol Pongsuchart Kha The Nguyen John Clyde Co Soriano tetsuya kadonosono Shinae Kizaka-Kondoh School of Life Science and Technology Tokyo Institute of TechnologyYokohama 226-8501Japan Center for Molecular Medicine Jichi Medical UniversityTochigi 329-0498Japan

Aim:Lung metastasis is a leading cause of death in patients with osteosarcoma(OS).No effective therapy exists that improves the five-year overall survival rate of OS patients with metastasis.Therefore,finding novel therapeutic targets will help develop new treatment strategies for OS patients with lung metastasis.Methods:Based on analysis of gene expression profiles between sublines of the Dunn OS LM8 cell line with high(LM8-H)and low(LM8-L)metastatic ability,we have identified Wnt signal-related genes that play an important role in lung metastasis of OS.Function of the genes was investigated by establishing sublines of gene knockout and assessing their metastatic ability using a mouse lung metastasis model.The molecular mechanism underlying the function of the genes was further investigated by in vitro experiments.Results:We have identified that receptor tyrosine kinase-like orphan receptor 2(ROR2),a receptor of the non-canonical Wnt signaling pathway,was involved in OS cell survival in lung capillaries during metastasis.LM8-H knocked out of Ror2(H/Ror2-KO)significantly reduced lung metastasis by decreasing the viability in lung capillaries 48 h after intravenous injection.In vitro study revealed that ROR2 increased anoikis resistance through AKT activation.Reconstitution of ROR2 expression in H/Ror2-KO cells restored their metastatic ability and viability in lung capillaries.Conclusion:The results demonstrate a novel ROR2 function in OS lung metastasis and may inform new treatment strategies for OS patients.

关键词： Osteosarcoma lung metastasis cell survival lung capillary ROR2

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Anti-aquaporin-4 antibody(AQP4-IgG)and anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)in the cerebrospinal fluid

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Neural Regeneration Research 2024年第5期19卷 949-950页

作者： tetsuya Akaishi Tatsuro Misu Department of Neurology Tohoku UniversitySendaiJapan

In the last decade,a new neurological disease concept known as anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)-associated disease(MOGAD)has emerged and is currently one of the most focused research areas in the field of neuroimmunology.MOG is a membrane protein mainly expressed on the surface of oligodendrocytes(Zhou et al.,2006).The exact pathogenic role of MOG-IgG in patients with MOGAD remains unclear;however,MOG-IgG has been suggested to cause tissue alterations and damage MOG-expressing cells(Zhou et al.,2006).The pathogenicity of MOG-IgG is further supported by the observation that only a few patients with acquired central nervous system(CNS)demyelinating syndromes exhibit both anti-aquaporin-4 antibody(AQP4-IgG)and MOG-IgG simultaneously,particularly with clear positivity levels of these antibodies as indicated by a cell-based assay result with a titer≥1:100(Sechi et al.,2021;Banwell et al.,2023).

关键词： AQP4 myelin

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Statistical evaluation of cluster formation of relapse in neuromyelitis optica spectrum disorder

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Neural Regeneration Research 2024年第9期19卷 1888-1889页

作者： tetsuya Akaishi Ichiro Nakashima Department of Neurology Tohoku UniversitySendaiJapan Department of Neurology Tohoku Medical and Pharmaceutical UniversitySendaiJapan

Evaluating the cluster formation of clinical attacks in chronic relapsing diseases is an important statistical issue because the presence of attack clusters may influence therapeutic strategies for relapse prevention.We recently reported the occurrence of unevenly clustered attacks in patients with anti-aquaporin-4(AQP4)antibody-positive neuromyelitis optica spectrum disorder(NMOSD)(Akaishi et al.,2020a).

关键词： AQP4 relapse

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Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 545-550页

作者： tetsuya Muto Shigeki Machida Shinichiro Imaizumi Department of Ophthalmology Dokkyo Medical University Saitama Medical CenterKoshigaya 343-8555Japan Imaizumi Eye Hospital Koriyama 963-8877Japan Fukushima Medical University Fukushima 960-1295Japan

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

关键词： aflibercept intraocular pressure vitreous reflux intravitreal injection

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Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

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World Journal of Gastroenterology 2024年第13期30卷 1871-1886页

作者： Kentaro Kojima Kenji Watanabe Mikio Kawai Soichi Yagi Koji Kaku Maiko Ikenouchi Toshiyuki Sato Koji Kamikozuru Yoko Yokoyama tetsuya Takagawa Masahito Shimizu Shinichiro Shinzaki Department of Gastroenterology Hyogo Medical UniversityNishinomiya 663-8501Japan Department of Gastroenterology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Internal Medicine for Inflammatory Bowel Disease The University of ToyamaToyama 930-0194Japan Center for Clinical Research and Education Hyogo Medical UniversityNishinomiya 663-8501Japan

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

关键词： Ulcerative colitis Tofacitinib Janus kinase inhibitor Real-world Biologics

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The Development of the “Monitoring Application for Inappropriate Expressions in Nursing Records”for PsyNACS^©

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Journal of Computer and Communications 2024年第5期12卷 42-52页

作者： Hirokazu Ito Yuko Yasuhara tetsuya Tanioka Department of Nursing Institute of Biomedical Sciences Tokushima University Graduate School Tokushima Japan

Lengthening periods of hospitalization, increasing numbers of patients with age-related complications, and a shortage of nursing staff have been of great concern in medical psychiatry in Japan. Under these circumstances, countries such as Japan that face a super-aging society and a decline in the working-age population, have been recommended for use of advanced information and communications technology (ICT) to improve the efficiency of medical treatment and care. This study aims to develop the “Monitoring Application for Inappropriate Expressions in Nursing Records” for using PsyNACS©, which will enable psychiatric nursing plans to harness the advantages of ICT. The functions considered necessary are as follows: 1) identification of users who enter information;2) a necessary database for lists of inappropriate expressions;3) development of a matching function to recommend proper writing input and a warning function;and 4) a management function for an inappropriate expression list database. A demonstration experiment for developing the application in this study was conducted at a specialized psychiatric hospital. To introduce them to the application, nurses and nurse managers were informed about the system developed in this study, and a survey regarding their opinions on the functions of the application was conducted with ten nurse managers. The results were evaluated in terms of usefulness for nursing care, documentation, and the education of nurses from an ethical perspective. This study suggests that matching their input with an inappropriate expression database will allow nurses to record more appropriate expressions. From an ethical perspective, the ability to use appropriate expressions makes records more likely to withstand disclosure requests from patients and their families.

关键词： PsyNACS© Monitoring Application Inappropriate Expressions Nursing Records

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From bench to bedside:Opportunities and challenges for iLABMED

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iLABMED 2024年第1期2卷 1-5页

作者： tetsuya Asakawa Yi‐Wei Tang Hongzhou Lu Institute of Neurology National Clinical Research Center for Infectious Diseasesthe Third People's Hospital of ShenzhenShenzhenGuangdongChina Medical Affairs Danaher Corporation/CepheidNew YorkNew YorkUSA Department of Infectious Disease National Clinical Research Center for Infectious Diseasesthe Third People's Hospital of ShenzhenShenzhenGuangdongChina

Since the new iLABMED was founded in June 2023,it has published three issues with 21 articles(till Dec 2023).As a journal majored in laboratory medicine,iLABMED also has to face many opportunities and challenges of laboratory medicine.This editorial summarized the main opportunities and challenges faced by iLABMED.The future prospects of laboratory medicine,which must be highlighted by iLABMED were also discussed based on a brief review of the current advances in laboratory medicine.iLABMED will continue to provide a useful platform for general‐interested,insightful,and informative articles with high quality.

关键词： journal summarized challenges

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Distortion-free PCA on sample space for highly variable gene detection from single-cell RNA-seq data

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Frontiers of Computer Science 2023年第1期17卷 133-142页

作者： Momo MATSUDA Yasunori FUTAMURA Xiucai YE tetsuya SAKURAI Department of Computer Science University of TsukubaTsukuba 305-8573Japan

Single-cell RNA-seq (scRNA-seq) allows the analysis of gene expression in each cell, which enables the detection of highly variable genes (HVG) that contribute to cell-to-cell variation within a homogeneous cell population. HVG detection is necessary for clustering analysis to improve the clustering result. scRNA-seq includes some genes that are expressed with a certain probability in all cells which make the cells indistinguishable. These genes are referred to as background noise. To remove the background noise and select the informative genes for clustering analysis, in this paper, we propose an effective HVG detection method based on principal component analysis (PCA). The proposed method utilizes PCA to evaluate the genes (features) on the sample space. The distortion-free principal components are selected to calculate the distance from the origin to gene as the weight of each gene. The genes that have the greatest distances to the origin are selected for clustering analysis. Experimental results on both synthetic and gene expression datasets show that the proposed method not only removes the background noise to select the informative genes for clustering analysis, but also outperforms the existing HVG detection methods.

关键词： single-cell RNA-sequencing feature selection principal component analysis highly variable gene detection background noise clustering analysis

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Prediction of exchangeable potassium in soil through mid-infrared spectroscopy and deep learning:From prediction to explainability

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Artificial Intelligence in Agriculture 2022年第1期6卷 230-241页

作者： Franck Albinet Yi Peng tetsuya Eguchi Erik Smolders Gerd Dercon Independent Researcher&Consultant GuétharyFrance Soil and Water Management&Crop Nutrition Laboratory Joint FAO/IAEA Centre of Nuclear Techniques in Food and AgricultureSeibersdorfAustria Global Soil Partnership Food and Agriculture Organization of the United NationsViale delle Terme di Caracalla00153 RomeItaly Agricultural Radiation Research Center Tohoku Agricultural Research CenterNational Agriculture and Food Research OrganizationFukushimaJapan Soil and Water Management Unit KU LeuvenBelgium

The ability to characterize rapidly and repeatedly exchangeable potassium(Kex)content in the soil is essential for optimizing remediation of radiocaesium contamination in agriculture.In this paper,we show how this can be now achieved using a Convolutional Neural Network(CNN)model trained on a large Mid-Infrared(MIR)soil spectral library(40,000 samples with Kex determined with 1 M NH4OAc,pH 7),compiled by the National Soil Survey Center of the United States Department of Agriculture.Using Partial Least Squares Regression as a base-line,we found that our implemented CNN leads to a significantly higher prediction performance of Kex when a large amount of data is available(10000),increasing the coefficient of determination from 0.64 to 0.79,and reducing the Mean Absolute Percentage Error from 135%to 31%.Furthermore,in order to provide end-users with required interpretive keys,we implemented the GradientShap algorithm to identify the spectral regions considered important by the model for predicting Kex.Used in the context of the implemented CNN on various Soil Taxonomy Orders,it allowed(i)to relate the important spectral features to domain knowledge and(ii)to demonstrate that including all Soil Taxonomy Orders in CNN-based modeling is beneficial as spectral features learned can be reused across different,sometimes underrepresented orders.

关键词： High-throughput soil characterization Machine learning Convolutional neural network Agriculture Nuclear emergency response Remediation Interpretability

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