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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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构成单材料裂纹和双材料界面裂纹有限应力集中的一般解析函数

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应用数学和力学 2018年第12期39卷 1364-1376页

作者：段树金藤井康寿中川建治石家庄铁道大学土木工程学院石家庄050043 东海学院大学人间关系学部岐阜国立大学工学部

对构成裂纹尖端附近有限应力集中解析函数的方法进行了综述.含裂纹平面问题的应力函数可以用无理函数和指数函数两种型式表示.对单材料裂纹,将裂纹长度作为参数,对无理函数型解析函数采用直接加权积分可以消除裂纹尖端应力的奇异性,构... 详细信息

对构成裂纹尖端附近有限应力集中解析函数的方法进行了综述.含裂纹平面问题的应力函数可以用无理函数和指数函数两种型式表示.对单材料裂纹,将裂纹长度作为参数,对无理函数型解析函数采用直接加权积分可以消除裂纹尖端应力的奇异性,构造有限连续的应力函数和尖劈型的张开位移函数.对指数函数型解析函数的间接积分适用于界面裂纹问题,但会使积分区间的应力分布出现正负反转和不合理的张开位移形状;结合选择不同权函数的叠加可以得到满足精度要求的有限应力集中解析函数.给出了中心裂纹和对称边裂纹在面内拉伸、剪切和弯曲等6种受力状态下的基本解.阐述了作为解析函数何以回避裂纹尖端应力奇异性的理由.

关键词：裂纹界面裂纹内聚裂纹区有限应力集中解析函数加权积分

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Experiment and simulation of turbulent flow in local scour around a spur dyke

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International Journal of Sediment Research 2009年第1期24卷 33-45页

作者： Hajime nakagawa kenji KAWAIKE Yasuyuki BABA Disaster Prevention Research Institute Kyoto University

The turbulent flow in the local scour hole around a single non-submerged spur dyke is investigated with both experimental and numerical methods. The experiments are conducted under clear-water scour regime with an impermeable spur dyke. The scour geometry and flow velocities are measured in details with a high-resolution laser displacement meter,electro-magnetic velocimetries and PIV(Particle image velocimetry). A 3D non-linear k-ε model is developed to simulate the complex local flow field around the scour area. The numerical model is formulated using FVM(Finite volume method) on a collocated unstructured mesh,capable of resolving complex geometries and boundaries. It is found that the simulation results are reasonably consistent with those of the experimental measurements. Based on the study results,the nature of the flow structure around a spur dyke with local scour hole is analyzed.

关键词： Spur dyke Local scour 3D flow Non-linear k-ε model Unstructured mesh

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Effects of hydraulic structures on river morphological processes

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International Journal of Sediment Research 2011年第3期26卷 283-303页

作者： Hiroshi TERAGUCHI Hajime nakagawa kenji KAWAIKE Yasuyuki BABA Disaster Prevention Research Institute Kyoto UniversityJapan

Study of hydraulic structures such as groins and bandal-like structures can provide valuable information on their influences on morphological processes in natural rivers.These structures usually used for bank protection and formation of deep navigation channel can locally create complex flow patterns,reduce flow velocities and also increase the flood levels.Most of the previous studies are focused on structures like groins under non-submerged flow condition.However,the recent demand of nature friendly low cost and sustainable methods for river bank protection and channel formation leads to the necessity of study different type of structures like bandal-like structures.In this context, this study investigates the flow characteristics and sediment transport process influenced by bandal-like structures through laboratory experiments.The experiments were carried out under live-bed scour condition with sediment supplied from the inlet for two submergence(non-submerged and submerged)conditions.The experimental measurements contribute to better understand the mechanism of deposition/erosion process around different type of hydraulic structures.The performance of bandal-like structures considering the erosion around the structures,the deposition near the bank and the formation of deep main channel show promising results compared with conventional structures such as groins(impermeable and permeable ones).

关键词： Bandal-like structures Groins Sediment transport Submerged condition

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Estimation of debris flow discharge coefficient considering sediment concentration

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International Journal of Sediment Research 2019年第1期34卷 1-7页

作者： Namgyun Kim Hajime nakagawa kenji Kawaike Hao Zhang Department of Civil and Earth Resource Engineering Kyoto University 2. Disaster Prevention Research CenterKyoto University Disaster Prevention Section Science Research CenterKochi University

A sabo dam has a purpose to block the path of debris flow. However, when overflow occurs, a sabo dam works as a weir, a vertical obstruction, where the fluid must flow over. Many empirical formulas and discharge coefficients for weirs relating flow depth to discharge have been proposed to calculate overflow discharges. However, only a few studies about overflow discharge coefficients are available in the case of debris flow. In this paper, experiments and numerical simulations were done to estimate debris flow discharge coefficients by considering the sediment concentration. In the numerical simulation, a complete overflow equation and a free overfall equation were implemented to calculate debris overflow discharges at a sabo dam. To determine the discharge coefficients for each equation, single factor regression analysis was used. Laboratory experiments were done to calibrate and to compare with the simulation. Study results showed that the discharge coefficients increase as the sediment concentration increases. This finding suggests debris flow discharge coefficients are derived to calculate the debris overflow discharges at a sabo dam.

关键词： Numerical simulation Debris flow Sabo dam Discharge coefficient

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Study on hydraulic characteristics of sabo dam with a flap structure for debris flow

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International Journal of Sediment Research 2017年第3期32卷 452-464页

作者： Yeonjoong Kim Hajime nakagawa kenji Kawaike Hao Zhang Department of Civil and Earth Resources Engineering Disaster Prevention Research InstituteKyoto University Department of Civil and Earth Resources Engineering Director of Ujigawa Hydraulics Laboratory

The front part of the flow is very important and complex in the case of debris flow where there is an accumulation of large boulders. It is important to control or dampen the energy of the frontal part of a debris flow for the safety of the downstream area because the impact pressure of debris flow is much greater than that of clear fluid. The main objective of this study is to analyze the hydraulic characteristics of the proposed dam(i.e. closed-type dam with flap). The vertical pressure distribution of this type is compared with conventional dam types. In the experiments, the total pressure associated with major debris flows was recorded in real time by a system consisting of four dynamic pressure sensors installed on different types of dam. The results from experimental data clearly show that the dam with the flap has advantages of capturing the debris flow with large boulders and controls the total pressure by flow circulation due to presence of the flap structure compared to a closed-type dam without flap. Furthermore, the empirical coefficients of hydrodynamic and solid collision models were proposed and compared with available coefficients.

关键词： Debris flow Flap structure Empirical coefficient Total pressure

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A Study on Cyclone Aila Recovery in Koyra, Bangladesh:Evaluating the Inclusiveness of Recovery with Respect to Predisaster Vulnerability Reduction

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International Journal of Disaster Risk Science 2018年第1期9卷 28-43页

作者： Md.Shibly Sadik Hajime nakagawa Rezaur Rahman Rajib Shaw kenji Kawaike Kumiko Fujita Department of Civil and Earth Resources Engineering Kyoto University Center for Environmental and Geographic Information Services (CEGIS) Disaster Prevention Research Institute (DPRI) Kyoto University Institute of Water and Flood Management Bangladesh University of Engineering and Technology Graduate School of Media and Governance Shonan Fujisawa Campus (SFC) Keio University

The need to consider disaster risk reduction at the time of recovery is well-recognized. Viable disaster risk reduction measures should resolve the root causes of predisaster vulnerabilities. Accordingly, we investigated the recovery from the impact of Cyclone Aila in Koyra Upazila, Bangladesh, which was severely damaged by this2009 cyclone. Our research focused on understanding preAila vulnerabilities to cyclone impact and examined the degree of inclusion of vulnerability reduction measures within the recovery process. A composite methodology that included an institutional survey, key informant interviews,collection of the judgment of experts, focus group discussions, and a score-based quantification technique was adopted. Through a process of understanding pre-Aila vulnerabilities, recognition of the root causes of these inherent weaknesses, and identification of appropriate measures for pre-Aila vulnerability reduction, a set of 23 indicators were selected to represent the most desirable vulnerability reduction measures to implement duringrecovery. A score-based technique was applied to measure the degree of inclusion of vulnerability reduction within the recovery with respect to the indicators. The scoring result shows that the degree of inclusion of vulnerability reduction within the recovery was poor. The result specifies that among the 23 indicators of potential vulnerability reduction measures, 10 are completely missing and the rest are only partially included. The overall findings imply that the Koyra community continues to live with a vulnerability similar to that of the pre-Aila period.

关键词： Bangladesh Cyclone Aila Diagnostic analysis Disaster risk reduction Post-disaster reconstruction

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Familial occurrence of congenital bile duct dilatation

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World Journal of Gastroenterology 2008年第6期14卷 941-943页

作者： Junji Iwasaki Yoshifumi Ogura Shunichi nakagawa kenji Kato Akinobu Kondo Katsuya Shiraki Department of Surgery Matsusaka City Hospital 1550 Tono-machi Matsusaka Mie 515-8544 Japan First Department of Internal Medicine Mie University School of Medicine 2-174 Edobashi Tsu Mie 514-8507 Japan

Congenital bile duct dilatation (CBD) that developed in a parent and son is presented. Familial occurrence of CBD is rare, with only a few male cases having been reported. Since the initial report of CBD occurring in siblings in 1981, a total of 20 cases (10 pairs) have been published as of 2007. Clinical and genetic features of CBD are discussed.

关键词：家族疾病遗传因素胆汁胆管疾病

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Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus

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World Journal of Gastroenterology 2013年第4期19卷 536-541页

作者： kenji Makita Riko Kitazawa Shuho Semba Koto Fujiishi Miku nakagawa Ryuma Haraguchi Sohei Kitazawa Division of Molecular Pathology Ehime University Graduate School of MedicineToon 791-0295Japan Division of Pathology Kobe University Graduate School of MedicineKobe 650-0017Japan

AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.Isolated clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.RESULTS:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.The definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.Methylation of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and IMC.Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.CONCLUSION:Cdx2 expression is restored irrespective of the methylation status of its promoter.Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.

关键词： Barrett ’s esophagus Caudal type homebox transcription factor 2 Intestinal metaplasia Promoter hypermethylation

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Remain Aggressive Behavior in Children with Temporal Lobe Epilepsy after Surgery

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Journal of Behavioral and Brain Science 2015年第3期5卷 81-87页

作者： Sayuri Sukigara Eiji nakagawa Masanori Ishikawa kenji Sugai Masayuki Sasaki Takanobu Kaido Akio Takahashi Taisuke Otsuki Department of Child Neurology National Center Hospital National Center of Neurology and Psychiatry (NCNP) Tokyo Japan Department of Psychiatry NCNP Tokyo Japan Department of Neurosurgery NCNP Tokyo Japan

Behavioral problems have a high rate in patients with temporal lobe epilepsy but there have been few detailed reports about pediatric patients. We report two children with temporal lobe epilepsy who manifest behavior abnormality remaining after surgery. One child developed complex partial seizures at 10 years and 3 months of age caused by a left temporal ganglioglioma and manifested behavioral problems of lability, aggression, impulsivity and disinhibition. Seizures were relieved after temporal lobe resection at 10 years and 8 months of age but behavioral symptoms had been remained. The second child developed epilepsy at 3 years of age. He manifested similar behavioral problems at 7 years old. Seizures were relieved after temporal lobe resection at 13 years old but behavioral symptoms had been remained. Their courses suggested that aggressive behavior might be associated with not only temporal lesion but also other lesions such as frontal lobe or neural circuitry between both lobes. It is important to inform families of patients that behavioral disorders may not improve after epileptic surgery.

关键词： Temporal Lobe Epilepsy Behavioral Disorder Aggression Epileptic Surgery

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