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Pharmacology & Pharmacy 2013年第8期4卷 578-583页

作者： hiroyuki takabe Moriyuki Ohkuma Yasunori Iwao Shuji Noguchi Shigeru Itai Department of Pharmaceutical Engineering Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan. Drug Formulation Department Central Research Laboratories Kaken Pharmaceutical Co. Ltd. Shizuoka Japan Drug Formulation Department Central Research Laboratories Kaken Pharmaceutical Co. Ltd. Shizuoka Japan Department of Pharmaceutical Engineering Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan.

An initial burst is often observed during the release of active pharmaceutical ingredients (APIs) from poly-lactic-coglycolic-acid (PLGA) microparticles (MPs) which have been prepared by the emulsion-solvent evaporation method. Herein, we describe the development of a simple one-step coating method that suppresses the initial burst release process. This new method involves coating the PLGA-MPs with PLGA, with the coating process being performed through the phase separation of PLGA on the surface of PLGA-MPs using the emulsion-solvent evaporation method. Bovine serum albumin (BSA) was encapsulated in the PLGA-MPs as a model API. The coated MPs were spherical in shape with no pores on their smooth surface, whereas the non-coated PLGA-MPs had porous surfaces. An in vitro release study showed that the residual levels of BSA in the coated and non-coated PLGA-MPs after 1 h were about 99% and 16% of the original loads, respectively. The one-step coating method therefore represents a useful method for preparing PLGA-MPs that do not give an initial burst release of proteinaceous APIs.

关键词： Poly-Lactic-Co-Glycolic-Acid Microparticle Suppression of Initial Burst Release Coating Bovine Serum Albumin

Chemokines,chemokine receptors and the gastrointestinal system

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World Journal of Gastroenterology 2013年第19期19卷 2847-2863页

作者： Hiroshi Miyazaki Kazuaki takabe W Andrew Yeudall Department of Biochemistry and Molecular Biology Virginia Commonwealth UniversityRichmondVA 23298United States Philips Institute of Oral and Craniofacial Molecular Biology Virginia Commonwealth UniversityRichmondVA 23298United States Massey Cancer Center Virginia Commonwealth UniversityRichmondVA 23298United States Department of Biochemistry and Molecular Biology Virginia Commonwealth UniversityRichmondVA 23298United State Department of Surgery Virginia Commonwealth UniversityRichmondVA 23298United Statess

The biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors,which include epidermal growth factor receptor agonists and members of the transforming growth factor β ***,the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small,immunomodulatory proteins also play key roles in carcinogenesis and may,therefore,be potential targets for novel therapeutic *** this review,we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

关键词： Chemokine Receptor Signal transduction Tumor progression Targeted therapeutics Digestive system Cancer

Advances in the management of peritoneal mesothelioma

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World Journal of Gastroenterology 2014年第33期20卷 11700-11712页

作者： Ali Raza Wei-Ching Huang Kazuaki takabe Division of Surgical Oncology Department of Surgery Virginia Commonwealth University School of Medicine and Massey Cancer Center Richmond VA 23298-0011 United States

Malignant peritoneal mesothelioma(PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction(CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Ac-cordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1(SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease.

关键词： Peritoneal mesothelioma Mesothelioma Hyperthermic intraperitoneal chemotherapy Cytore-duction Sphingosine kinase Sphingosine-1-phosphate FTY720

Mechanisms of Salt Tolerance in Transgenic Arabidopsis thaliana Carrying a Peroxisomal Ascorbate Peroxidase Gene from Barley

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Pedosphere 2008年第4期18卷 486-495页

作者： XU Wei-Feng SHI Wei-Ming A. UEDA T. takabe State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil Science Chinese Academy of Sciences Nanjing 210008 （China）. Graduate School of the Chinese Academy of Sciences Beijing 100049 （China） Graduate School of Bioagricultural Sciences Nagoya University Nagoya 464-8601 （Japan

Ascorbate peroxidases （APX）, localized in the cytosol, peroxisome, mitochondria, and chloroplasts of plant cells, catalyze the reduction of H2O2 to water by using ascorbic acid as the specific electron donor. To determine the role of peroxisomal type ascorbate peroxidase （pAPX）, an antioxidant enzyme, in protection against salt-induced oxidative stress, transgenic Arabidopsis thaliana plant carrying a pAPX gene （HvAPX1） from barley （Hordeum vulgate L.） was analyzed. The transgenic line pAPX3 was found to be more tolerant to salt stress than the wild type. Irrespective of salt stress, there were no significant differences in Na^＋, K^＋, Ca^2＋, and Mg^2＋ contents and the ratio of K^＋ to Na^＋ between pAPX3 and the wild type. Clearly, the salt tolerance in pAPX3 was not due to the maintenance and reestablishment of cellular ion homeostasis. However, the degree of H2O2 and lipid peroxidation （measured as the levels of malondialdehyde） accumulation under salt stress was higher in the wild type than in pAPX3. The mechanism of salt tolerance in transgenic pAPX3 can thus be explained by reduction of oxidative stress injury. Under all conditions tested, activities of superoxide, glutathione reductase, and catalase were not significantly different between pAPX3 and the wild type. In contrast, the activity of APX was significantly higher in the transgenic plant than in wild type under salt stress. These results suggested that in higher plants, HvAPX1 played an important role in salt tolerance and was a candidate gene for developing salttolerant crop plants.

关键词： ascorbate peroxidase oxidative stress peroxisome soil salinity transgenic Arabidopsis thaliana

Current treatment options for colon cancer peritoneal carcinomatosis

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World Journal of Gastroenterology 2014年第35期20卷 12493-12500页

作者： Tomoyoshi Aoyagi Krista P Terracina Ali Raza Kazuaki takabe Division of Surgical Oncology Department of SurgeryVirginia Commonwealth University School of Medicine Division of Surgical Oncology Department of SurgeryVirginia Commonwealth University School of MedicineRichmond

Peritoneal carcinomatosis(PC),the dissemination of cancer cells throughout the lining of the abdominal cavity,is the second most common presentation of colon cancer distant *** remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years,it has been repeatedly shown that these therapies remain ineffective for colon cancer ***,there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC) prolongs the life of colon cancer PC ***,we will review the clinical presentation,the mechanisms of disease progression,and current treatment options for colon cancer PC,with a focus on the benefits and limitations of CRSHIPEC.

关键词： Cancer Colorectal Carcinomatosis Peritoneal Hyperthermic intraperitoneal chemotherapy Intraperitoneal chemotherapy Cytoreductive surgery Mechanism

Recent progress of laboratory astrophysics with intense lasers

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High Power Laser Science and Engineering 2021年第4期9卷 7-40页

作者： Hideaki takabe Yasuhiro Kuramitsu School of Engineering Osaka UniversitySuitaOsaka 565-0871Japan Institute of Laser Engineering Osaka UniversitySuitaOsaka 565-0871Japan Institute of Radiation Physics Helmholtz Zentrum Dresden Rossendorf01328 DresdenGermany

Thanks to a rapid progress of high-power lasers since the birth of laser by *** in 1960,intense lasers have been developed mainly for studying the scientific feasibility of laser *** confinement fusion with an intense laser has attracted attention as a new future energy source after two oil crises in the 1970s and *** the beginning,the most challenging physics is known to be the hydrodynamic instability to realize the spherical implosion to achieve more than 1000 times the solid *** studies have been performed theoretically and experimentally on the hydrodynamic instability and resultant turbulent mixing of compressible *** such activities in the laboratory,the explosion of supernova SN1987A was observed in the sky on 23 February *** X-ray satellites have revealed that the hydrodynamic instability is a key issue to understand the physics of supernova *** collaboration between laser plasma researchers and astrophysicists,the laboratory astrophysics with intense lasers was proposed and promoted around the end of the *** original subject was mainly related to hydrodynamic ***,after two decades of laboratory astrophysics research,we can now find a diversity of research *** has been demonstrated theoretically and experimentally that a variety of nonlinear physics of collisionless plasmas can be studied in laser ablation plasmas in the last *** the present paper,we shed light on the recent 10 topics studied intensively in laboratory experiments.A brief review is given by citing recent ***,modeling cosmic-ray acceleration with lasers is reviewed in a following session as a special topic to be the future main topic in laboratory astrophysics research.

关键词： collisionless shock compressible hydrodynamics cosmic rays equation of state high-energy-density plasmas intense laser magnetic turbulence opacity experiment particle accelerations relativistic plasmas turbulent mixing wakefield acceleration Weibel instability

Cancer cachexia,mechanism and treatment

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World Journal of Gastrointestinal Oncology 2015年第4期7卷 17-29页

作者： Tomoyoshi Aoyagi Krista P Terracina Ali Raza Hisahiro Matsubara Kazuaki takabe Division of Surgical Oncology Department of SurgeryVirginia Commonwealth University School of Medicine and the Massey Cancer Center Department of Frontier Surgery Graduate School of Medicine Chiba University

It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responsesto chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.

关键词： Physical exercise Pharmacological treatment Cancer cachexia

Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

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World Journal of Clinical Cases 2016年第7期4卷 155-164页

作者： Kazuki Moro Masayuki Nagahashi Rajesh Ramanathan Kazuaki takabe Toshifumi Wakai Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Division of Surgical Oncology Department of Surgery Virginia Commonwealth University School of Medicine and the Massey Cancer Center

Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids(ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins astargets in inflammatory diseases and cancers.

关键词： Anti-inflammatory lipid mediators Resolvin Omega three polyunsaturated fatty acids Inflammatory diseases Cancer

Bile acids as global regulators of hepatic nutrient metabolism

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Liver Research 2017年第1期1卷 10-16页

作者： Phillip B.Hylemon Kazuaki takabe Mikhail Dozmorov Masayuki Nagahashi Huiping Zhou Department of Microbiology and Immunology Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA McGuire VA Medical Center RichmondVAUSA Department of Surgery Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA Department of Biostatistics Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA Department of Surgery Niigata UniversityJapan

Bile acids(BA)are synthesized from cholesterol in the *** are essential for promotion of the absorption of lipids,cholesterol,and lipid-soluble vitamins from the *** are hormones that regulate nutrient metabolism by activating nuclear receptors(farnesoid X receptor(FXR),pregnane X receptor,vitamin D)and G protein-coupled receptors(e.g.,TGR5,sphingosine-1-phosphate receptor 2(S1PR2))in the liver and *** the liver,S1PR2 activation by conjugated BAs activates the extracellular signal-regulated kinase 1/2 and AKT signaling pathways,and nuclear sphingosine kinase *** latter produces sphingosine-1-phosphate(S1P),an inhibitor of histone deacetylases 1/2,which allows for the differential up-regulation of expression of genes involved in the metabolism of sterols and *** discuss here the emerging concepts of the interactions of BAs,FXR,insulin,S1P signaling and nutrient metabolism.

关键词： Sphingosine-1-phosphate Sphingosine kinase 2 Sphingosine-1-phosphate receptor 2 Fatty liver Epigenetics

Maximizing magnetic field generation in high power laser-solid interactions

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High Power Laser Science and Engineering 2019年第2期7卷 11-21页

作者： L.G.Huang H.takabe T.E.Cowan Helmholtz-Zentrum Dresden-Rossendorf(HZDR) 01328 DresdenGermany Institute of Laser Engineering Osaka University565-0871 SuitaOsakaJapan Technische Universitat Dresden 01062 Dresd enGermany

In order to understand the transport of fast electrons within solid density targets driven by an optical high power laser,we have numerically investigated the dynamics and structure of strong self-generated magnetic fields in such *** we present a systematic study of the bulk magnetic field generation due to the ponderomotive current,Weibel-like instability and resistivity gradient between two solid *** particle-in-cell simulations,we observe the effect of varying the laser and target parameters,including laser intensity,focal size,incident angle,preplasma scale length,target thickness and material and experimental *** simulation results suggest that the strongest magnetic field is generated with laser incident angles and preplasma scale lengths that maximize laser absorption *** recent commissioning of experimental platforms equipped with both optical high power laser and X-ray free electron laser(XFEL),such as European XFEL-HED,LCLS-MEC and SACLA beamlines,provides unprecedented opportunities to probe the self-generated bulk magnetic field by X-ray polarimetry via Faraday rotation with simultaneous high spatial and temporal *** expect that this systematic numerical investigation will pave the way to design and optimize near future experimental setups to probe the magnetic fields in such experimental platforms.

关键词： laser-plasmas interaction high energy density physics X-ray free electron laser probing