254 results on '"Kaori Suzuki"'
Search Results
102. Simple quantification of lansoprazole and rabeprazole concentrations in human serum by liquid chromatography/tandem mass spectrometry
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Nariyasu Mano, Takanori Hishinuma, Tomoyuki Koike, Toru Shimosegawa, Hatsushi Yamagishi, Hiroaki Yamaguchi, Kaori Suzuki, Shuichi Ohara, and Junichi Goto
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Male ,Analyte ,Clinical Biochemistry ,Rabeprazole ,Lansoprazole ,Tandem mass spectrometry ,Sensitivity and Specificity ,Biochemistry ,2-Pyridinylmethylsulfinylbenzimidazoles ,Analytical Chemistry ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,medicine ,Ammonium formate ,Humans ,Chromatography ,medicine.diagnostic_test ,Cell Biology ,General Medicine ,chemistry ,Therapeutic drug monitoring ,Quantitative analysis (chemistry) ,Chromatography, Liquid ,medicine.drug - Abstract
A rapid, simple and highly sensitive method was developed for the quantitative determination of lansoprazole and rabeprazole concentrations in 20 microL of human serum using high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS). Analytes, along with an internal standard (lansoprazole deuterium derivatives), were separated using a mobile phase of acetonitrile/1mM ammonium formate (140/60, v/v) on a C18 analytical column and analyzed in the selected reaction-monitoring (SRM) mode. The lower limit of quantification was 0.25 ng/mL. A good linear response was observed for each analyte (from 0.25 ng to 2.5 microg/mL). This method was useful for therapeutic drug monitoring and pharmacokinetic studies.
- Published
- 2008
103. Relation between Preparation Conditions and Characteristics of OLED
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Katsuyoshi Shinyama, Jin Li, Shigetaka Fujita, Kaori Suzuki, Takanori Sasaki, and Yoshimine Tanabu
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Materials science ,Relation (database) ,business.industry ,OLED ,Optoelectronics ,business - Published
- 2008
104. A CASE OF PENETRATION OF THE SMALL INTESTINAL WALL BY A TOOTHPICK
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Kaori Suzuki, Yasuhiko Nagano, Toshio Imada, Ryutaro Mori, Hiroshi Shimada, and Chikara Kunisaki
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business.industry ,General Engineering ,General Earth and Planetary Sciences ,Small intestinal wall ,Medicine ,Penetration (firestop) ,Nuclear medicine ,business ,General Environmental Science ,Toothpick - Abstract
症例は59歳,男性.2004年10月 右季肋部痛を主訴に当院を受診した.同部位に著明な圧痛,反跳痛を認め,また,腹部CTでは回腸周囲のfat densityの上昇および右側腹直筋の肥厚を認め大腸憩室炎と診断された.入院後絶飲食,抗生剤投与を行い症状は一時改善したが,経口摂取開始後再び発熱と上腹部痛を認め開腹手術を施行した.圧痛部位の直下に手拳大の腫瘤を認め,空腸,横行結腸が巻き込まれていたため,腫瘤を含め小腸部分切除及び横行結腸部分切除術を施行した.腫瘤内部は膿瘍を形成しており,内部に小腸と交通する爪楊枝を認め,爪楊枝による消化管穿孔と診断した.爪楊枝による消化管穿孔は稀で,病歴から誤飲の有無を聞き出せないことも多く,診断に難渋する.本症例は,急性腹症の鑑別診断のひとつとして重要な症例と考え報告した.
- Published
- 2008
105. Simultaneous quantification of seven prostanoids using liquid chromatography/tandem mass spectrometry: The effects of arachidonic acid on prostanoid production in mouse bone marrow-derived mast cells
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Junichi Goto, Masayoshi Saito, Yoshihisa Tomioka, Izumi Kaneko, Naoto Suzuki, Masao Ono, Hiroaki Yamaguchi, Kaori Suzuki, and Takanori Hishinuma
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Male ,Thromboxane ,Clinical Biochemistry ,Prostaglandin ,Bone Marrow Cells ,Mass spectrometry ,Sensitivity and Specificity ,Mass Spectrometry ,Mice ,chemistry.chemical_compound ,Liquid chromatography–mass spectrometry ,medicine ,Animals ,Mast Cells ,Cells, Cultured ,Unsaturated fatty acid ,Arachidonic Acid ,Chemistry ,Prostanoid ,Cell Biology ,respiratory system ,musculoskeletal system ,Mast cell ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Biochemistry ,Prostaglandins ,cardiovascular system ,lipids (amino acids, peptides, and proteins) ,Arachidonic acid ,Chromatography, Liquid - Abstract
We have developed a method for the simultaneous estimation of the levels of the prostanoids 6-keto prostaglandin (PG) Flalpha, PGB2, PGD2, PGE2, PGF2(alpha), PGJ2, and thromboxane (TX) B2 in blood- or serum-containing medium using liquid chromatography-tandem mass spectrometry. These prostanoids and their deuterium derivatives, which were used as internal standards, were subjected to solid-phase extraction using Empore C18 HD disk cartridges and analyzed in the selected reaction-monitoring mode. A linear response curve starting at 10 pg of prostanoid/tube was observed for each prostanoid. The accuracy of the method was demonstrated with samples containing known amounts of the prostanoids. Furthermore, we used this method to analyze the prostanoids produced in mouse bone marrow-derived mast cells stimulated with arachidonic acid, which resulted in the production of PGD2, PGE2, PGF2alpha, and TXB2. The results suggest that this simultaneous quantification method is useful for the analysis of the production of biomedically important prostanoids.
- Published
- 2007
106. Tim2 is expressed in mouse fetal hepatocytes and regulates their differentiation
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Hitoshi Kikutani, Natsumi Watanabe, Atsushi Kumanogoh, Kaori Suzuki, Atsushi Miyajima, and Minoru Tanaka
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Signal peptide ,Hepatocyte differentiation ,Small interfering RNA ,Hepatology ,Cellular differentiation ,Down-Regulation ,Gene Expression Regulation, Developmental ,Membrane Proteins ,Cell Differentiation ,Protein Sorting Signals ,Biology ,Flow Cytometry ,Molecular biology ,Fusion protein ,Mice ,Liver ,Membrane protein ,Downregulation and upregulation ,Hepatocytes ,Extracellular ,Animals - Abstract
Liver development is regulated by various extracellular molecules such as cytokines and cell surface proteins. Although several such regulators have been identified, additional molecules are likely to be involved in liver development. To identify such molecules, we employed the signal sequence trap (SST) method to screen cDNAs encoding a secreted or membrane protein from fetal liver and obtained a number of clones. Among them, we found that T cell immunoglobulin and mucin domain 2 (Tim2) was expressed specifically on immature hepatocytes in the fetal liver. Tim2 has been shown to regulate immune responses, but its role in liver development had not been studied. We have examined the possible role of Tim2 in hepatocyte differentiation. At first, we prepared a soluble Tim2 fusion protein consisting of its extracellular domain and the Fc domain of human IgG (Tim2-hFc) and found that it bound to fetal and adult hepatocytes, suggesting that there are Tim2-binding molecules on hepatocytes. Second, Tim2-hFc inhibited the differentiation of hepatocytes in fetal liver primary culture, i.e., the expression of mature hepatic enzymes and accumulation of glycogen were severely reduced. Third, Tim2-hFc also inhibited proliferation of fetal hepatocytes. Fourth, down-regulation of Tim2 expression by small interfering RNA (siRNA) enhanced the expression of liver differentiation marker genes. Conclusion: It is strongly suggested that Tim2 is involved in the differentiation of fetal hepatocytes. (HEPATOLOGY 2007;45:1240–1249.)
- Published
- 2007
107. Fano 3-folds with divisible anticanonical class
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Gavin Brown and Kaori Suzuki
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Divisor ,General Mathematics ,Mathematical analysis ,Codimension ,Algebraic geometry ,Fano plane ,Rank (differential topology) ,Combinatorics ,symbols.namesake ,Number theory ,symbols ,Gravitational singularity ,Mathematics ,Hilbert–Poincaré series - Abstract
We show the nonvanishing of H0(X,−KX) for any a Fano 3-fold X for which −KX is a multiple of another Weil divisor in Cl(X). The main case we study is Fano 3-folds with Fano index 2: that is, 3-folds X with rank Pic(X)=1, \({\mathbb{Q}}\) -factorial terminal singularities and −KX = 2A for an ample Weil divisor A. We give a first classification of all possible Hilbert series of such polarised varieties (X,A) and deduce both the nonvanishing of H0(X,−KX) and the sharp bound (−KX)3≥ 8/165. We find the families that can be realised in codimension up to 4.
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- 2007
108. Impact of Obstructive Sleep Apnea on Clinical and Angiographic Outcomes Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome
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Yukio Tsurumi, Dai Yumino, Kaori Suzuki, Atsushi Takagi, and Hiroshi Kasanuki
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Male ,medicine.medical_specialty ,Acute coronary syndrome ,medicine.medical_treatment ,Myocardial Infarction ,Comorbidity ,Coronary Angiography ,Severity of Illness Index ,Disease-Free Survival ,Japan ,Risk Factors ,Internal medicine ,Prevalence ,medicine ,Humans ,Myocardial infarction ,Sleep study ,Angioplasty, Balloon, Coronary ,Aged ,Sleep Apnea, Obstructive ,business.industry ,Hazard ratio ,Percutaneous coronary intervention ,Middle Aged ,medicine.disease ,respiratory tract diseases ,Obstructive sleep apnea ,Apnea–hypopnea index ,Multivariate Analysis ,Conventional PCI ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
There has been growing evidence associating obstructive sleep apnea (OSA) with cardiovascular pathogenesis. We hypothesized that OSA may affect outcomes after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We performed a sleep study in 89 consecutive patients with ACS who were successfully treated with PCI. Patients with an apnea hypopnea indexor =10/hour were considered to have OSA. Co-morbidity of OSA with ACS was found in 51 patients (57%). There were no differences in baseline demographics between patients with and without OSA, except for significantly higher high-sensitivity C-reactive protein levels (0.59 +/- 0.75 vs 0.29 +/- 0.20 mg/dl, p = 0.019) in patients with OSA. Patients were followed for a mean period of 227 days. The incidence of major adverse cardiac events (cardiac death, reinfarction, and target vessel revascularization) was significantly higher in patients with OSA (23.5% vs 5.3%, p = 0.022). By multivariate analysis, the presence of OSA was an independent predictor for major adverse cardiac events (hazard ratio 11.61, 95% confidence interval 2.17 to 62.24, p = 0.004). In addition, quantitative coronary angiography at 6-month follow-up depicted significantly greater late loss (1.28 +/- 0.84 vs 0.69 +/- 0.81 mm, p = 0.003) and a higher binary restenosis rate (36.5% vs 15.4%, p = 0.026) in patients with OSA compared with those without OSA. In conclusion, the present study showed a high prevalence of OSA among patients with ACS. Moreover, OSA appeared to be an independent predictor for clinical and angiographic outcomes after PCI.
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- 2007
109. Dominant effects of first monolayer energetics at donor/acceptor interfaces on organic photovoltaics
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Kyohei Nakano, Kazuhito Hashimoto, Keisuke Tajima, Seiichiro Izawa, and Kaori Suzuki
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Materials science ,Organic solar cell ,Mechanics of Materials ,Cascade ,Mechanical Engineering ,Monolayer ,Energy landscape ,General Materials Science ,Heterojunction ,Charge (physics) ,Photochemistry ,Acceptor ,Recombination - Abstract
Energy levels of the first monolayer are manipulated at donor/acceptor interfaces in planar heterojunction organic photovoltaics by using molecular self-organization. A "cascade" energy landscape allows thermal-activation-free charge generation by photoirradiation, destabilizes the energy of the interfacial charge-transfer state, and suppresses bimolecular charge recombination, resulting in a higher open-circuit voltage and fill factor.
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- 2015
110. Development of speech technologies to support hearing through mobile terminal users
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Takeshi Otani, Taro Togawa, Kaori Suzuki, and Tomohiko Taniguchi
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Voice activity detection ,Multimedia ,Computer science ,Speech recognition ,Signal Processing ,Speech technology ,Intelligibility (communication) ,computer.software_genre ,Speech rate ,computer ,Information Systems - Abstract
Mobile terminals have become the most familiar communication tool we use, and various types of people have come to use mobile terminals in various environments. Accordingly, situations in which we talk over the telephone in noisy environments or with someone who speaks fast have increased. However, it is sometimes difficult to hear a person's voice in these cases. To make the voice received through mobile terminals easy to hear, authors have developed two technologies. One is a voice enhancement technology that emphasizes a caller's voice according to the noise surrounding the recipient, and the other is a speech rate conversion technology that slows speech while maintaining voice quality. In this paper, we explain the trends and the features of these technologies and discuss ways to implement their algorithms on mobile terminals.
- Published
- 2015
111. Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation ofGADD153 gene
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Masami Suganuma, Miki Kurusu, Kaori Suzuki, Emi Tasaki, and Hirota Fujiki
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Cancer Research ,medicine.medical_specialty ,Programmed cell death ,Lung Neoplasms ,p38 mitogen-activated protein kinases ,Blotting, Western ,Biology ,Polymerase Chain Reaction ,Catechin ,Phenols ,Downregulation and upregulation ,Cell Line, Tumor ,Internal medicine ,medicine ,Anticarcinogenic Agents ,Humans ,Cyclooxygenase Inhibitors ,heterocyclic compounds ,RNA, Messenger ,Flavonoids ,Mitogen-Activated Protein Kinase Kinases ,Sulfonamides ,Tea ,Plant Extracts ,Reverse Transcriptase Polymerase Chain Reaction ,Kinase ,Gadd45 ,MEK inhibitor ,Polyphenols ,food and beverages ,Cancer ,Drug Synergism ,Flow Cytometry ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Endocrinology ,Oncology ,Celecoxib ,Apoptosis ,Cancer research ,Pyrazoles ,Transcription Factor CHOP - Abstract
To more clearly understand the molecular mechanisms involved in synergistic enhancement of cancer preventive activity with the green tea polyphenol (−)-epigallocatechin gallate (EGCG), we examined the effects of cotreatment with EGCG plus celecoxib, a cyclooxygenase-2 selective inhibitor. We specifically looked for induction of apoptosis and expression of apoptosis related genes, with emphasis on growth arrest and DNA damage-inducible 153 (GADD153) gene, in human lung cancer cell line PC-9: Cotreatment with EGCG plus celecoxib strongly induced the expression of both GADD153 mRNA level and protein in PC-9 cells, while neither EGCG nor celecoxib alone did. However, cotreatment did not induce expression of other apoptosis related genes, p21WAF1 and GADD45. Judging by upregulation of GADD153, only cotreatment with EGCG plus celecoxib synergistically induced apoptosis of PC-9 cells. Synergistic effects with the combination were also observed in 2 other lung cancer cell lines, A549 and ChaGo K-1. Furthermore, EGCG did not enhance GADD153 gene expression or apoptosis induction in PC-9 cells in combination with N-(4-hydroxyphenyl)retinamide or with aspirin. Thus, upregulation of GADD153 is closely correlated with synergistic enhancement of apoptosis with EGCG. Cotreatment also activated the mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38 MAPK: Preteatment with PD98059 (ERK1/2 inhibitor) and UO126 (selective MEK inhibitor) abrogated both upregulation of GADD153 and synergistic induction of apoptosis of PC-9 cells, while SB203580 (p38 MAPK inhibitor) did not do so, indicating that GADD153 expression was mediated through the ERK signaling pathway. These findings indicate that high upregulation of GADD153 is a key requirement for cancer prevention in combination with EGCG. © 2006 Wiley-Liss, Inc.
- Published
- 2006
112. Single‐Step Multisyntheses of Glycosyl Acceptors: Benzylation of n‐1 Hydroxyl Groups of Phenylthio Glycosides of Xylose, Mannose, Glucose, Galactose, 2‐Azido‐2‐deoxy‐glucose, and 2‐Azido‐2‐deoxy‐galactose
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Isao Ohtsuka, Takuro Ako, Kaori Suzuki, Takuya Kanemitsu, and Osamu Kanie
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chemistry.chemical_classification ,Stereochemistry ,Organic Chemistry ,Glycoside ,Mannose ,Oligosaccharide ,Xylose ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Galactose ,Monosaccharide ,Organic chemistry ,Triol ,Glycosyl - Abstract
An array of synthons is required to access an oligosaccharide library; however, multistep and thus time‐consuming synthesis is inevitable. To rapidly access such synthetic units, multiple benzylation reactions of monosaccharides under phase‐transfer conditions were examined. Multiple benzyl groups were successfully incorporated in one step, especially in the cases of reactions with triol systems.
- Published
- 2005
113. Mode of transgene expression after fusion to early or late viral genes of a conditionally replicating adenovirus via an optimized internal ribosome entry site in vitro and in vivo
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David T. Curiel, Victor Krasnykh, Minghui Wang, Taco Gilles Uil, Kaori Suzuki, Dirk M. Nettelbeck, and Angel A. Rivera
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Time Factors ,Genes, Viral ,viruses ,Transgene ,Genetic Vectors ,Mice, Nude ,Biology ,Adenoviridae ,Viral vector ,Mice ,Gene therapy ,IRES ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Virology ,Conditionally replicative adenovirus ,Animals ,Humans ,Luciferase ,RNA, Messenger ,Transgenes ,Virotherapy ,Luciferases ,Viral oncolysis ,Timing of transgene expression ,Armed oncolytic adenovirus ,Proto-Oncogene Proteins c-ets ,Genetic Therapy ,Neoplasms, Experimental ,Adenovirus E2 Proteins ,Artificial Gene Fusion ,Oncolytic virus ,Internal ribosome entry site ,Gene Expression Regulation ,Viral replication ,Early and late transgene expression ,Female ,Adenovirus E1A Proteins ,Ribosomes ,Oncovirus - Abstract
The expression of therapeutic genes by oncolytic viruses is a promising strategy to improve viral oncolysis, to augment gene transfer compared with a nonreplicating adenoviral vector, or to combine virotherapy and gene therapy. Both the mode of transgene expression and the locale of transgene insertion into the virus genome critically determine the efficacy of this approach. We report here on the properties of oncolytic adenoviruses which contain the luciferase cDNA fused via an optimized internal ribosome entry site (IRES) to the immediate early adenoviral gene E1A (AdDeltaE1AIL), the early gene E2B (AdDeltaE2BIL), or the late fiber gene (AdDeltafiberIL). These viruses showed distinct kinetics of transgene expression and luciferase activity. Early after infection, luciferase activities were lower for these viruses, especially for AdDeltaE2BIL, compared with nonreplicating AdTL, which contained the luciferase gene expressed from the strong CMV promoter. However, 6 days after infection, luciferase activities were approximately four (AdDeltaE1AIL) to six (AdDeltafiberIL) orders of magnitude higher than for AdTL, reflecting virus replication and efficient transgene expression. Similar results were obtained in vivo after intratumoral injection of AdDeltaE2BIL, AdDeltafiberIL, and AdTL. AdDeltafiberIL and the parental virus, Ad5-Delta24, resulted in similar cytotoxicity, but AdDeltaE2BIL and AdDeltaE1AIL were slightly attenuated. Disruption of the expression of neighboring viral genes by insertion of the transgene was minimal for AdDeltaE2BIL and AdDeltafiberIL, but substantial for AdDeltaE1AIL. Our observations suggest that insertion of IRES-transgene cassettes into viral transcription units is an attractive strategy for the development of armed oncolytic adenoviruses with defined kinetics and strength of transgene expression.
- Published
- 2004
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114. Inter-patient variation in efficacy of five oncolytic adenovirus candidates for ovarian cancer therapy
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Akseli Hemminki, Masato Yamamoto, Koichi Takayama, Gerd J. Bauerschmitz, Kaori Suzuki, David T. Curiel, Anna Kanerva, Minghui Wang, Bin Liu, Snehal M. Bhoola, John T. Lam, Ronald D. Alvarez, Gene P. Siegal, and Mack N. Barnes
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Vascular Endothelial Growth Factor A ,Oncolytic adenovirus ,Genetic enhancement ,Genetic Vectors ,Cell ,Adenocarcinoma ,Biology ,Virus Replication ,Polymerase Chain Reaction ,Adenoviridae ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Spheroids, Cellular ,Drug Discovery ,Tumor Cells, Cultured ,Genetics ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Promoter Regions, Genetic ,Solid tumor ,Molecular Biology ,Genetics (clinical) ,030304 developmental biology ,Ovarian Neoplasms ,0303 health sciences ,Cell Death ,Genetic Therapy ,Neoplasms, Experimental ,medicine.disease ,Virology ,3. Good health ,Oncolytic virus ,Cancer treatment ,Treatment Outcome ,Real-time polymerase chain reaction ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,DNA, Viral ,Cancer research ,Molecular Medicine ,Female ,Ovarian cancer - Abstract
Gene therapy offers a new strategy for cancer treatment. Adenoviruses represent the most widely used gene therapy vector and feature an excellent safety record. Conditionally replicative adenoviruses (CRAds) effect solid tumor penetration and tumor selective oncolysis and consequently offer potential efficacy for metastatic disease treatment. We evaluated five CRAds as candidate clinical agents for ovarian cancer therapy: RGDCRADcox-2R, Ad5VEGFE1, Ad5/3VEGFE1, Ad5-Delta24RGD, and Ad5/3-Delta24.DNA replication by these five CRAds, wild-type adenovirus, and an E1-deleted control was measured in purified primary ovarian cancer cell spheroids by quantitative PCR. CRAd-mediated oncolysis was quantified in ovarian cancer cell monolayers and three-dimensional spheroids by cellular viability assays. The therapeutic efficacy of each CRAd was tested by intraperitoneal administration in mice with peritoneally disseminated human ovarian cancer.An increase in viral DNA was noted in primary tumor cell spheroids for all replicative viruses tested. Variation was noted in viral DNA replication between patient samples. All five CRAds induced remarkable oncolysis. They also prolonged survival in vivo compared with the wild-type control group.All five CRAds tested showed robust DNA replication, oncolysis, and in vivo therapeutic efficacy. Each virus has potential for clinical testing, and such further testing will ultimately determine its safety and relative usefulness. Variation of CRAd DNA replication between different patient samples suggests that target tissue features, such as surface receptors and endogenous transcription factors, may affect CRAd infectivity and replicativity. Evaluation of such factors may become important to optimize cancer therapy for individual patients.
- Published
- 2004
115. Expression of hyaluronan synthase in intraocular proliferative diseases: regulation of expression in human vascular endothelial cells by transforming growth factor-β
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Kiyoka Suzuki, Paraskevi Heldin, Teiko Yamamoto, Hidetoshi Yamashita, Kaori Suzuki, and Tomohiko Usui
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medicine.medical_specialty ,Proliferative vitreoretinopathy ,Eye Diseases ,Becaplermin ,Xenopus Proteins ,Transforming Growth Factor beta1 ,Western blot ,Transferases ,Transforming Growth Factor beta ,Internal medicine ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Glucuronosyltransferase ,Cells, Cultured ,HAS1 ,Platelet-Derived Growth Factor ,Messenger RNA ,Membranes ,medicine.diagnostic_test ,biology ,Glycosyltransferases ,Membrane Proteins ,Proto-Oncogene Proteins c-sis ,General Medicine ,medicine.disease ,Immunohistochemistry ,Recombinant Proteins ,Cell biology ,Reverse transcription polymerase chain reaction ,Ophthalmology ,Hyaluronan synthase ,Endocrinology ,biology.protein ,Endothelium, Vascular ,Hyaluronan Synthases ,Transforming growth factor - Abstract
Purpose To investigate the role of hyaluronan (HA) and elucidate the mechanisms that regulate the expression of hyaluronan-synthesizing enzymes in vascular endothelial cells (VECs) in intraocular proliferative diseases. Methods Cultured VECs were used. Hyaluronan synthase (HAS) expression was determined on the mRNA products obtained by reverse transcription polymerase chain reaction (RT-PCR). The effect of transforming growth factor-β 1 (TGF-β 1 ) and/or platelet-derived growth factor-BB (PDGF-BB) on HAS expression was examined by quantitative RT-PCR and Western blot analysis. HAS expression in intraocular proliferative membranes was observed by immunohistochemistry. Results Cultured VECs expressed the three HAS isoforms. Stimulation of VECs with TGF-β 1 induced a marked increase in the expression level of HAS2 mRNA and protein. The stimulatory effect of PDGF-BB was less potent. A synergistic or additive effect between TGF-β 1 and PDGF-BB-induced HA synthesis was not observed. Furthermore, HAS1 and HAS2 exhibited differential expression in VECs and non-VECs populating intraocular proliferative membranes. Conclusions The expression of each HAS isoform is regulated differently by growth factors and cytokines in VECs. Importantly, HA-synthesizing enzymes were expressed in cells populating proliferative membranes obtained from eyes of patients with proliferative vitreoretinal diseases, and thus may be key molecules in the events that control progression of the proliferative diseases.
- Published
- 2003
116. Enhanced therapeutic efficacy for ovarian cancer with a serotype 3 receptor-targeted oncolytic adenovirus
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Gerd J. Bauerschmitz, Minghui Wang, Bin Liu, Tanja Hakkarainen, Tandra R. Chaudhuri, Anna Kanerva, Zhihong Cao, David T. Curiel, Akseli Hemminki, Kaori Suzuki, Kurt R. Zinn, John T. Lam, Ronald D. Alvarez, and Taco Gilles Uil
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Oncolytic adenovirus ,Time Factors ,viruses ,Genetic enhancement ,Receptors, Cell Surface ,Mice, SCID ,Biology ,medicine.disease_cause ,Adenoviridae ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,Genetics ,medicine ,Animals ,Bioluminescence imaging ,Virotherapy ,Molecular Biology ,030304 developmental biology ,Ovarian Neoplasms ,Pharmacology ,0303 health sciences ,medicine.disease ,Virology ,3. Good health ,Oncolytic virus ,030220 oncology & carcinogenesis ,Luminescent Measurements ,Cancer cell ,Cancer research ,Molecular Medicine ,Female ,Ovarian cancer - Abstract
Oncolytic viruses that are replication competent in tumor but not in normal cells represent a novel approach for treating neoplastic diseases. However, the oncolytic potency of replicating agents is determined directly by their capability of infecting target cells. Most adenoviruses used for gene therapy or virotherapy have been based on serotype 5 (Ad5). Unfortunately, expression of the primary receptor for Ad5 (the coxsackie-adenovirus receptor, or CAR) is highly variable on ovarian and other cancer cells. By performing genetic fiber pseudotyping, we created Ad5/3-Delta24, a conditionally replicating adenovirus that does not bind CAR but facilitates entry into and killing of ovarian cancer cells. We show replication of Ad5/3-Delta24 and subsequent oncolysis of ovarian adenocarcinoma lines. Replication was also analyzed with quantitative PCR on three-dimensional primary tumor cell spheroids purified from patient samples. Moreover, in a therapeutic orthotopic model of peritoneal carcinomatosis, dramatically enhanced survival was noted. Finally, Ad5/3-Delta24 achieved a significant antitumor effect as assessed by noninvasive, in vivo bioluminescence imaging. Therefore, the preclinical therapeutic efficacy of Ad5/3-Delta24 is improved over the respective CAR- and integrin-binding controls. Taken together with promising biodistribution and toxicity data, this approach could translate into successful clinical interventions for ovarian cancer patients.
- Published
- 2003
117. Preclinical Characterization of the Antiglioma Activity of a Tropism-Enhanced Adenovirus Targeted to the Retinoblastoma Pathway
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Frederick F. Lang, Candelaria Gomez-Manzano, Ta Jen Liu, Michael G. Lemoine, W. K. Alfred Yung, Gregory N. Fuller, Charles A. Conrad, Ramon Alemany, Raymond Sawaya, David T. Curiel, Asadullah Khan, Hong Jiang, Kaori Suzuki, and Juan Fueyo
- Subjects
Integrins ,Cancer Research ,Lipoproteins ,Transplantation, Heterologous ,Integrin ,Mice, Nude ,Nerve Tissue Proteins ,Injections, Intralesional ,Biology ,Adenoviridae ,Flow cytometry ,Mice ,Antigens, Neoplasm ,Glioma ,Hippocalcin ,Biomarkers, Tumor ,Recoverin ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Coloring Agents ,Eye Proteins ,Tropism ,Fluorescent Dyes ,medicine.diagnostic_test ,Brain Neoplasms ,Retinoblastoma ,Calcium-Binding Proteins ,Trypan Blue ,Flow Cytometry ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Oncolytic virus ,Gene Expression Regulation, Neoplastic ,Oncology ,Viral replication ,Cell culture ,Astrocytes ,biology.protein - Abstract
Background: Oncolytic adenoviruses are promising therapies for the treatment of gliomas. However, untargeted viral replication and the paucity of coxsackie-adenovirus receptors (CARs) on tumor cells are major stumbling blocks for adenovirus-based treatment. We studied the antiglioma activity of the tumor-selective Delta-24 adenovirus, which encompasses an early 1 A adenoviral (E1A) deletion in the retinoblastoma (Rb) protein-binding region, and of the Delta-24-RGD adenovirus. Delta-24-RGD has an RGD-4C peptide motif inserted into the adenoviral fiber, which allows the adenovirus to anchor directly to integrins. Methods: CAR and integrin expression were examined by flow cytometry in six glioma cell lines and in normal human astrocytes (NHAs). Adenoviral vectors containing green fluorescent protein (GFP) (AdGFP and AdGFP-RGD) were used to infect glioma cell lines with high or low CAR expression. Viability of glioma cells infected with different adenoviruses was assessed by trypan blue staining. Adenovirus replication was quantified with the infection-dose replication assay. Athymic mice carrying glioma xenografts received intratumoral injections of Delta-24-RGD or Delta-24 and were followed for survival, which was analyzed by the Kaplan-Meier method and the log-rank test. All statistical tests were two-sided. Results: Half the glioma cell lines expressed low levels of CAR (defined as
- Published
- 2003
118. Fiber shaft extension in combination with HI loop ligands augments infectivity for CAR-negative tumor targets but does not enhance hepatotropism in vivo
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Marianne G Rots, Igor Dmitriev, Taco Gilles Uil, Toshiro Seki, Kaori Suzuki, Elena Kashentseva, Hongju Wu, Minghui Wang, Koichi Takayama, and David T. Curiel
- Subjects
Coxsackie and Adenovirus Receptor-Like Membrane Protein ,Genetic Vectors ,Biology ,Coxsackievirus ,Ligands ,medicine.disease_cause ,Mice ,Capsid ,In vivo ,Neoplasms ,Tumor Cells, Cultured ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Tropism ,Infectivity ,Reporter gene ,Adenoviruses, Human ,Genetic transfer ,Gene Transfer Techniques ,Genetic Therapy ,biology.organism_classification ,Virology ,Molecular biology ,Adenoviridae ,Liver ,Cell culture ,Gene Targeting ,Receptors, Virus ,Molecular Medicine ,Neoplasm Transplantation - Abstract
Recent studies demonstrate that the fiber shaft length, which ranges from six beta-repeats to 23 beta-repeats in human adenoviruses (Ads), influences viral tropism. We have previously shown that artificial extension of the shaft length inhibits infectivity in CAR (coxsackievirus and Ad receptor)-positive cell lines, but does not affect infectivity in a CAR-independent, integrin-dependent cell entry pathway. On the basis of these findings, we hypothesized that Ad vectors with shaft extension might display lower infectivity in liver, which expresses high levels of CAR. We also postulated that infectivity of Ad vectors with shaft extension in CAR-negative tumors could be increased by exploiting a CAR-independent cell entry by incorporation of an RGD4C motif into the fiber knob HI-loop. We thus compared gene transfer efficiencies of our Ad serotype 5 (Ad5) capsid-based 'longer-shafted' Ad vector with or without an RGD4C motif in the HI-loop of the fiber knob (Ad5long and Ad5RGDlong, 32 beta-repeats) to wild-type Ad vector (Ad5, 22 beta-repeats) in vitro and in vivo. In this study, Ad5long showed similar infectivity in CAR-negative tumors (69.7%, P = 0.098), but significantly reduced infectivity in CAR-positive tumors (19.1%, P = 0.000038) and in liver (12.5%, P = 0.0047) compared with Ad5. On the other hand, Ad5RGDlong demonstrated similar infectivity in CAR-positive tumors (70.5%, P = 0.012) and in liver (83.4%, P = 0.51), but significantly increased infectivity in CAR-negative tumors (327%, P = 0.0000042) compared with Ad5. Importantly, Ad5RGDlong demonstrated an augmented gene transfer capacity for CAR negative tumors, but no enhanced hepatotropism in vivo. We suggest that Ad vectors with artificial fiber shaft extension in combination with HI loop ligands may be useful for gene therapy applications.
- Published
- 2002
119. Telomerase activity and expression of human telomerase catalytic subunit gene in esophageal tissues
- Author
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Tatsuro Tominaga, Masayuki Itabashi, Hiromasa Kashimura, Akira Nakahara, Kaori Suzuki, Naomi Tanaka, Jun Ohkawa, and Masayuki Noguchi
- Subjects
Adult ,Male ,Telomerase ,Esophageal Neoplasms ,cells ,Biology ,Esophageal Diseases ,medicine.disease_cause ,Telomerase RNA component ,Esophagus ,medicine ,Humans ,Telomerase reverse transcriptase ,RNA, Messenger ,Esophagitis, Peptic ,neoplasms ,Aged ,Ribonucleoprotein ,Aged, 80 and over ,Messenger RNA ,Gastroenterology ,RNA ,Middle Aged ,Molecular biology ,Reverse transcriptase ,DNA-Binding Proteins ,enzymes and coenzymes (carbohydrates) ,embryonic structures ,Cancer research ,Female ,biological phenomena, cell phenomena, and immunity ,Carcinogenesis ,Biomarkers - Abstract
Telomerase, the ribonucleoprotein enzyme that synthesizes telomeric DNA, is thought to be necessary for cellular immortality and carcinogenesis. Telomerase activity is associated with the majority of malignant human cancers. The mRNA that encodes the telomerase catalytic subunit (human telomerase repeat transcriptase; hTERT) has recently been identified, and the expression of the hTERT gene is thought to regulate the activation of telomerase. However, the expression of hTERT mRNA in esophageal tissues has not been reported. We investigated hTERT gene expression in cancerous and noncancerous esophageal tissues, and determined the relationship between hTERT mRNA expression and telomerase activity.Tissues from esophageal carcinomas in 14 patients, reflux esophagitis in 12 patients, esophageal acanthosis in 2 patients, esophageal papilloma in 1 patient, radiation esophagitis in 1 patient, and normal esophageal epithelium in 11 patients (including 3 specimens of normal epithelium from patients with esophageal carcinoma) were examined. All specimens were taken endoscopically. hTERT gene expression was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Quantitative analysis of telomerase activity was analyzed by fluorescence telomeric repeat amplification protocol (F-TRAP) assay.Thirteen of the 14 (93%) esophageal carcinoma specimens expressed hTERT mRNA and revealed detectable telomerase activity. Noncancerous esophageal lesions had not only hTERT mRNA expression with a high frequency (14 of 16 cases; 88%) but also detectable telomerase activity (12 of 13 cases; 92%). Normal esophageal epithelium also highly expressed hTERT mRNA (10 of 11 cases; 91%) and revealed detectable telomerase activity (all 9 cases; 100%). In 32 of the 35 specimens analyzed for both hTERT mRNA and telomerase activity (91%), the expression of hTERT mRNA was consistent with detectable telomerase activity.The expression of hTERT mRNA was detected not only in cancerous but also in noncancerous esophageal tissues at a high frequency. This result was different from that reported for other gastrointestinal epithelium. Moreover, telomerase activity in esophageal carcinoma was significantly stronger than that in reflux esophagitis and normal epithelium. In addition, there was a strong relation ship between the detection of telomerase activity and the expression of hTERT mRNA in cancerous and noncancerous esophageal tissues. Thus, the qualitative analysis of hTERT mRNA expression may not be useful as a biomarker of carcinoma in esophageal tissues. Nevertheless, the quantitative analysis of telomerase activity may be somewhat useful.
- Published
- 2002
120. Artificial Extension of the Adenovirus Fiber Shaft Inhibits Infectivity in Coxsackievirus and Adenovirus Receptor-Positive Cell Lines
- Author
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Toshiro Seki, Elena Kashentseva, David T. Curiel, Kaori Suzuki, Marianne G Rots, Igor Dmitriev, and Koichi Takayama
- Subjects
Coxsackie and Adenovirus Receptor-Like Membrane Protein ,Recombinant Fusion Proteins ,viruses ,Genetic Vectors ,Immunology ,Integrin ,Gene delivery ,Biology ,Microbiology ,Capsid ,Virology ,Humans ,Structural motif ,Receptor ,Tropism ,Cell Line, Transformed ,Enterovirus ,Infectivity ,integumentary system ,Adenoviruses, Human ,Molecular biology ,Virus-Cell Interactions ,Cell biology ,body regions ,Insect Science ,Tissue tropism ,biology.protein ,Receptors, Virus ,Capsid Proteins ,Genetic Engineering ,HeLa Cells - Abstract
The utility of adenovirus (Ad) for the delivery and expression genes both in vitro and in vivo is based on the widespread host range and the remarkable efficiency of cellular entry processes allowing high-level gene expression, together with their relative ease of preparation and purification (28). To achieve effective infection, two virus-cellular receptor interactions are required. The adsorption of Ad to target cell receptors, which have been identified as coxsackievirus and Ad receptor (CAR), histocompatibility class I molecule, or sialoglycoproteins, is initiated via the knob portion of the fiber (13, 20, 28). Subsequently, the interaction of the penton base with αV integrins facilitates the entry of Ad via clathrin-mediated endocytosis (1, 11, 22, 28). Ad can infect a wide range of cell types because the primary cellular receptors for Ad are expressed on most cells (28). However, specific gene delivery to a target cell is precluded due to the ubiquitous expression of CAR. On the other hand, Ad gene transfer is poor to some cell types due to a low level of Ad receptors on these cells (23, 28). It is thus apparent that receptor recognition is one of the key factors involved in viral tropism. To develop effective and specific gene delivery to target cells (resulting in increased safety in gene therapy applications), a number of recombinant Ad vectors have been constructed. Major attention has been given to modification of virus-cellular receptor interactions, including bispecific conjugates (6, 10, 28, 36), genetic modification of the fiber knob (5, 17, 28, 35, 37), modification of the hexon (3) or penton (34), ablation of the binding site on the knob (25, 28), and construction of chimeric vectors (9, 18, 28). However, it has become clear that virus-cellular receptor interactions (knob-CAR and penton base-αV integrins) are not the sole determinants of viral tropism. In this regard, Roelvink et al. reported that Ad type 2 (Ad2) and Ad9 utilize the same cellular fiber receptor but that the shorter fiber of Ad9 permitted fiber-independent binding of Ad9 penton base to αV integrins (24). Moreover, they showed that Ads belonging to subgroups A, C, D, E, and F all bind to the same cellular fiber receptor CAR and suggested that differences in subgroup tropism is significantly influenced by the length of the fiber shaft (26). Additional data regarding the importance of shaft length were obtained by Ad5 capsid-based vectors with chimeric fibers (15, 30). These observations led to a more systematic analysis of the role of fiber shaft length in Ad infectivity. Shayakhmetov et al. generated viruses with chimeric fibers containing short shafts (Ad9 or Ad35) or long shafts (Ad5) in combination with CAR (Ad5 and Ad9)- or non-CAR (Ad35)-recognizing knob domains (29). For Ad5 or Ad9 knob-possessing vectors, long shafts were critical for efficient infection compared with the weak attachment of the engineered short-shafted vectors. In contrast, for the Ad35 knob-possessing vectors, which infected cells by a CAR-independent pathway, fiber shaft length had no significant influence on infection. This study clearly demonstrated that the length of the fiber shaft influenced CAR- and αV integrin-mediated infections. Taken together, these reports have established shaft length as a key parameter whose modulation might allow tropism alternations. In this regard, the long-shafted Ad uses its fiber interaction (higher affinity than penton base-αV integrin interaction) exclusively for attachment to cell surface proteins and for charge-dependent repulsion (24, 26, 29), followed by internalization by the αV integrins. In contrast, for short-shafted Ad, including artificial fiberless Ad (19, 33), direct binding to the αV integrins (lower affinity than knob-CAR interaction) becomes dominant. In this instance, infectivity is decreased. Indeed, when the short-shafted fiber of Ad9 was engineered into the Ad5 capsid, a significant decrease in infectivity was observed compared to wild-type Ad5 (29). However, there is no significant difference in infection between wild-type Ad2 and wild-type Ad9, which expresses its short-shafted fiber but also the natural Ad9 capsid proteins, including the penton base (24). It is expected that Ad9 capsid does not require long-shafted fibers for efficient infection. On this basis, we hypothesized that the shaft length provides optimal spatial proportion between knob-CAR interaction and penton base-αV integrin interaction, especially when Ad uses CAR-integrin pathway for infection. Therefore, the length of shaft is limited from 6 β-repeats to 23 β-repeats in the process of evolution. Paradoxically, these observations provided us with the basis to explore whether artificial extension of the shaft alters the infectivity profile of Ad. We focused on rescuing recombinant Ad vectors, which express artificial longer shaft over 23 β-repeats. The primary sequence of the fiber shaft consists of 15-residue pseudorepeats. The length of the shaft is determined by the number of β-repeats, which ranges from 6 (Ad3, Ad11, and Ad35) β-repeats to 23 (Ad12) β-repeats in human Ads (2). Green et al. predicted that these repeats contained two β-strands and two turns (the cross-β model) (12). Stouten et al. subsequently proposed a triple β-helical model, taking into account length measurements from electron microscopy and fiber diffraction patterns (31). Recently, van Raaij et al. revealed a novel structural motif for the shaft as a triple β-spiral model based on the crystallographic data (32). According to this model, we attempted to make Ad5 capsid-based longer-shafted Ad vectors by incorporating Ad2 shaft fragments of different lengths into Ad5 shaft and investigated whether extension of the shaft over 23 β-repeats altered the infectivity profiles of human Ads.
- Published
- 2002
121. Quercetin inhibits human vascular smooth muscle cell proliferation and migration
- Author
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David Whitley, Jesus F. Salazar-Gonzalez, Marty T. Sellers, Kirby I. Bland, William D. Jordan, Francisco Alcocer, Chastity MacRae, Kaori Suzuki, and Devin E. Eckhoff
- Subjects
medicine.medical_specialty ,Vascular smooth muscle ,Flavonoid ,Cell ,Biology ,Pharmacology ,p38 Mitogen-Activated Protein Kinases ,Antioxidants ,Muscle, Smooth, Vascular ,chemistry.chemical_compound ,Cell Movement ,Internal medicine ,medicine ,Humans ,heterocyclic compounds ,Aorta, Abdominal ,Phosphorylation ,Protein kinase A ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Cell growth ,Cell Cycle ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Cell culture ,Quercetin ,Surgery ,Mitogen-Activated Protein Kinases ,Signal transduction ,Cell Division - Abstract
Background. The French paradox has been associated with regular intake of red wine, which is enriched with flavonoids. Quercetin, a flavonoid present in the human diet, exerts cardiovascular protection through its antioxidant properties. We hypothesized that the beneficial effect of quercetin also could be related to the inhibition of vascular smooth muscle cell proliferation and migration. Methods. Human aortic smooth muscle cells (AoSMC) were grown in culture in the presence of serum. Quercetin inhibited the serum-induced proliferation of AoSMC. This inhibition was dose-dependent and not attributed to toxicity. Cell cycle analysis revealed that quercetin arrested AoSMC in the G 0 /G 1 phase. The effect of quercetin on AoSMC migration was examined using explant migration and Transwell migration assays. Quercetin significantly decreased migration in both assays in a consistent manner. Finally, Western blot analysis of AoSMC exposed to quercetin demonstrated a significant reduction in the activation of mitogen-activated protein kinase, a signaling pathway associated with the migration of vascular smooth muscle cells. Conclusions. Quercetin inhibits the proliferation and migration of AoSMC, concomitant with inhibition of mitogen-activated protein kinase phosphorylation. These findings provide new insights and a rationale for the potential use of quercetin in the prophylaxis of cardiovascular diseases. (Surgery 2002;131:198-204.)
- Published
- 2002
122. Exploring the influence of the gut microbiota and probiotics on health: a symposium report
- Author
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Linda V. Thomas, T. Ockhuizen, and Kaori Suzuki
- Subjects
Intestinal microbiota ,Population ,Medicine (miscellaneous) ,Faecalibacterium prausnitzii ,Context (language use) ,Disease ,Gut flora ,medicine.disease_cause ,digestive system ,Intestinal mucosa ,Metabolic Diseases ,medicine ,Animals ,Humans ,Intestinal Mucosa ,education ,Immunity, Mucosal ,Inflammation ,education.field_of_study ,Nutrition and Dietetics ,biology ,Microbiota ,Probiotics ,Pathogenic bacteria ,Congresses as Topic ,Full Papers ,biology.organism_classification ,Nutrition Disorders ,Intestinal Diseases ,Metabolism ,Immune System ,Immunology ,Metagenomics ,Akkermansia muciniphila - Abstract
The present report describes the presentations delivered at the 7th International Yakult Symposium, ‘The Intestinal Microbiota and Probiotics: Exploiting Their Influence on Health’, in London on 22–23 April 2013. The following two themes associated with health risks were covered: (1) the impact of age and diet on the gut microbiota and (2) the gut microbiota's interaction with the host. The strong influence of the maternal gut microbiota on neonatal colonisation was reported, as well as rapid changes in the gut microbiome of older people who move from community living to residential care. The effects of dietary changes on gut metabolism were described and the potential influence of inter-individual microbiota differences was noted, in particular the presence/absence of keystone species involved in butyrate metabolism. Several speakers highlighted the association between certain metabolic disorders and imbalanced or less diverse microbiota. Data from metagenomic analyses and novel techniques (including anex vivohuman mucosa model) provided new insights into the microbiota's influence on coeliac, obesity-related and inflammatory diseases, as well as the potential of probiotics.Akkermansia muciniphilaandFaecalibacterium prausnitziiwere suggested as targets for intervention. Host–microbiota interactions were explored in the context of gut barrier function, pathogenic bacteria recognition, and the ability of the immune system to induce either tolerogenic or inflammatory responses. There was speculation that the gut microbiota should be considered a separate organ, and whether analysis of an individual's microbiota could be useful in identifying their disease risk and/or therapy; however, more research is needed into specific diseases, different population groups and microbial interventions including probiotics.
- Published
- 2014
123. On Morrison's Cone Conjecture for Klt Surfaces with Kx≡0
- Author
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Kaori, Suzuki
- Published
- 2001
124. Excitotoxicity induces changes in rat brain gangliosides
- Author
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Kaori Suzuki, Yoshikazu Morita, Tania Valdes-Gonzalez, and Tatsuo Ido
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Excitotoxicity ,AMPA receptor ,Biology ,medicine.disease_cause ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Functional Laterality ,chemistry.chemical_compound ,Reference Values ,Gangliosides ,Internal medicine ,Excitatory Amino Acid Agonists ,medicine ,Animals ,Hippocampus (mythology) ,Receptors, AMPA ,Rats, Wistar ,Ibotenic Acid ,Ganglioside ,General Neuroscience ,Glutamate receptor ,Amino Acids, Diamino ,Brain ,General Medicine ,Olfactory Bulb ,Rats ,Olfactory bulb ,Endocrinology ,nervous system ,Biochemistry ,chemistry ,beta-Alanine ,NMDA receptor ,lipids (amino acids, peptides, and proteins) ,Ibotenic acid - Abstract
The patterns of major gangliosides in the rat hippocampi and olfactory bulbs was examined in vivo after microinjections of Ibotenic acid and l -BOAA (NMDA and AMPA receptor agonists, respectively) which were given under free-movement conditions. The excitotoxicity induced by injections of Ibotenic acid promoted transient ganglioside changes in olfactory bulbs and permanent changes in hippocampus. Four days after injections, the amount of gangliosides in the hippocampus increased significantly for GQ1b, GT1b and GD1b and decreased in the olfactory bulb for GQ1b, GT1b, GD1b, GD1a and GM1 compared to normal ganglioside levels. The alterations of gangliosides were minimal 1 day after injections. After 5 weeks, the amounts of GQ1b, GT1b and GD1b dramatically decreased in the hippocampus while in the olfactory bulbs gangliosides recovered to normal levels. The results obtained with l -BOAA 4 days after injections strengthen the results observed in the experiments using Ibotenic acid and corroborate our suggestion that gangliosides have an active role in the compensatory mechanism to maintain the number of glutamate receptors during the excitotoxicity.
- Published
- 2001
125. Blood clearance rates of adenovirus type 5 in mice
- Author
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David T. Curiel, Kaori Suzuki, and Ramon Alemany
- Subjects
Latex beads ,Infectivity ,viruses ,Genetic enhancement ,Genetic Vectors ,Genetic Therapy ,Biology ,Virus Replication ,Virology ,Molecular biology ,Virus ,Mastadenovirus ,Mice ,Blood ,Viral replication ,PEG ratio ,PEGylation ,Animals ,Clearance rate - Abstract
Persistence of adenovirus type 5 in blood has implications for the pathogenicity of the virus infection and for the use of this virus in oncolysis and gene therapy. In this study, the kinetics of adenovirus clearance from blood in mice has been evaluated. After a single inoculation of concentrated virus into the vena cava, virus half-life was less than 2 min. Depletion of Kupffer cells (KC) resulted in increased viraemia. After tail-vein injection, virus and latex beads co-localized within KC. An important factor in clearance by KC is the negative charge of particles. Deletion of the hexon hypervariable region 1 acidic stretch decreased the negative charge of the virion but it did not increase blood persistence. Coating with PEG (‘PEGylation’) reduced the clearance rate but also reduced infectivity.
- Published
- 2000
126. Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions
- Author
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Naomi Tanaka, Hiromasa Kashimura, Akira Nakahara, Masayuki Itabashi, Teruo Watanabe, Hiroshi Muto, Kaori Suzuki, Tatuo Sawahata, and Jun Ohkawa
- Subjects
Adult ,Male ,Telomerase ,Pathology ,medicine.medical_specialty ,cells ,Chronic gastritis ,Biology ,medicine.disease_cause ,Helicobacter Infections ,Stomach Neoplasms ,Catalytic Domain ,Gastric mucosa ,medicine ,Humans ,Telomerase reverse transcriptase ,RNA, Messenger ,neoplasms ,Aged ,Aged, 80 and over ,Helicobacter pylori ,Hepatology ,Gastroenterology ,Intestinal metaplasia ,Middle Aged ,medicine.disease ,biology.organism_classification ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,enzymes and coenzymes (carbohydrates) ,medicine.anatomical_structure ,embryonic structures ,Cancer research ,RNA ,Female ,biological phenomena, cell phenomena, and immunity ,Gastritis ,medicine.symptom ,Carcinogenesis ,Precancerous Conditions - Abstract
Background and Aims: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia. Methods: Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol. Results: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P = 0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA. Conclusions: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.
- Published
- 2000
127. Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection
- Author
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Hiroshi Mutoh, T. Sawahata, A Nakahara, Kaori Suzuki, Naoki Tanaka, Toshio Watanabe, Kazuto Ikezawa, H. Kashimura, and M. Hassan
- Subjects
medicine.medical_specialty ,Intention-to-treat analysis ,Hepatology ,biology ,business.industry ,Gastroenterology ,Lansoprazole ,Rapid urease test ,Polaprezinc ,Helicobacter pylori ,biology.organism_classification ,Surgery ,Regimen ,Internal medicine ,Clarithromycin ,medicine ,Pharmacology (medical) ,business ,medicine.drug ,Antibacterial agent - Abstract
Aim : To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori. Methods : Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment. Results : Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72–100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P
- Published
- 1999
128. A metastatic melanoma of the small intestine diagnosed by single-balloon enteroscopy
- Author
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Michio Tanaka, Takashi Nonaka, Keiko Akimoto, Shin Maeda, Shigeru Koyama, Yusuke Sekino, Akisa Tsunemi, Masahiko Inamori, Atsushi Nakajima, Nobutaka Fujisawa, Kaori Suzuki, Eiji Gotoh, and Hiroshi Iida
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,Metastatic melanoma ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,Single-Balloon Enteroscopy ,business ,Small intestine - Published
- 2015
129. Pancreaticoduodenal artery aneurysms associated with celiac axis stenosis due to compression by median arcuate ligament and celiac plexus
- Author
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Naomi Tanaka, Akira Nakahara, Hiroshi Muto, Katashi Fukao, Mahmudul Hassan, Hikaru Yokota, Kenji Yuzawa, Kaori Suzuki, Mikio Sato, and Hiromasa Kashimura
- Subjects
Adult ,Male ,medicine.medical_specialty ,Diaphragm ,Celiac plexus ,Context (language use) ,Celiac Plexus ,Constriction, Pathologic ,Aneurysm ,Humans ,Medicine ,cardiovascular diseases ,Ultrasonography, Doppler, Color ,Pancreas ,Ligaments ,business.industry ,Median arcuate ligament ,Gastroenterology ,Pancreatic Diseases ,nutritional and metabolic diseases ,medicine.disease ,Uncus ,digestive system diseases ,Diaphragm (structural system) ,Surgery ,Stenosis ,medicine.anatomical_structure ,cardiovascular system ,Female ,Radiology ,business ,Artery - Abstract
Celiac axis stenosis is frequently associated with pancreaticoduodenal artery aneurysms. Although the cause of stenosis was not clear in most of the reported cases, compression of the median arcuate ligament of the diaphragm was found to be responsible for the stenosis in 7 of 42 reported cases of this type of aneurysm. We report a case of aneurysm caused by compression of the median arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old Japanese man was admitted with a low echoic lesion in the uncus of pancreas. Computed tomographic scan and angiogram revealed stenosis of the celiac axis and two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac plexus and median arcuate ligament were divided surgically and normal flow was reestablished in the celiac axis. One of the aneurysms was resected and the afferent artery of the other aneurysm was ligated. In the setting of pancreaticoduodenal artery aneurysm associated with celiac axis stenosis, management of stenosis should be considered in addition to local treatment of the aneurysm. In this context, division of median arcuate ligament and celiac plexus or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade and could be effective in preventing aneurysm reformation.
- Published
- 1998
130. A Study on the Use of Public Library in Aichi Prefecture by Senior Citizens
- Author
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Michiko, TANIMOTO and Kaori, SUZUKI
- Published
- 1998
131. ERC-55, a Binding Protein for the Papilloma Virus E6 Oncoprotein, Specifically Interacts with Vitamin D Receptor among Nuclear Receptors
- Author
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Kaori Suzuki, Tukasa Shimojima, Hiroshi Handa, Yasuhisa Nogi, Takuya Kitamoto, Yoshikazu Masuhiro, Takamichi Hashimoto, Koichiro Matsuda, Shouichi Masushige, Atsuko Sugita, Shigeaki Kato, Masami Muramatsu, Hiroki Matsumoto, and Takeshi Imai
- Subjects
DNA, Complementary ,Recombinant Fusion Proteins ,Two-hybrid screening ,Molecular Sequence Data ,Biophysics ,Saccharomyces cerevisiae ,In Vitro Techniques ,Biology ,Retinoid X receptor ,Biochemistry ,Calcitriol receptor ,Mice ,Gene expression ,Animals ,Humans ,Amino Acid Sequence ,Papillomaviridae ,Molecular Biology ,Base Sequence ,Sequence Homology, Amino Acid ,Binding protein ,Calcium-Binding Proteins ,Promoter ,Oncogene Proteins, Viral ,Cell Biology ,Molecular biology ,Nuclear receptor ,Receptors, Calcitriol ,lipids (amino acids, peptides, and proteins) ,Function (biology) - Abstract
VDR regulates gene expression in a ligand-dependent way by binding to cognate enhancer elements of target gene promoters. The ligand-dependent activation function, AF-2, of VDR is thought to require transcriptional co-activators/co-repressors together with basal transcriptional machinery. Using a yeast two hybrid system with VDR, we have isolated a mouse Ca2+-binding protein(designated as VAF1) specifically interacting in vivo and in vitro with VDR among nuclear receptors like RAR, RXR, ER and GR. VAF1 is a mouse homologue to human ERC-55, which has recently been shown to interact with human papillomavirus oncogenic protein, E6[1]. Unlike those of many previously identified co-activators, the VDR-VAF1 interaction was ligand-independent. Thus, VAF1 seems a putative VDR-specific cofactor modulating its function.
- Published
- 1997
132. The contribution of endogenous mono-ADP-ribosylation to kindling-induced epileptogenesis
- Author
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Hiroto Iwasa, Shuichi Kikuchi, Naoko Morinaga, Kaori Suzuki, Toshio Sato, Masami Miyake, and Masatoshi Noda
- Subjects
Male ,Nitroprusside ,Sodium ,Molecular Sequence Data ,chemistry.chemical_element ,Nerve Tissue Proteins ,Endogeny ,Pharmacology ,Hippocampus ,Epileptogenesis ,Nitric oxide ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Kindling, Neurologic ,medicine ,Animals ,Amino Acid Sequence ,Molecular Biology ,Adenosine Diphosphate Ribose ,Epilepsy ,Membranes ,Kindling ,General Neuroscience ,Glyceraldehyde-3-Phosphate Dehydrogenases ,Carbamazepine ,Rats ,chemistry ,Anticonvulsants ,Electrophoresis, Polyacrylamide Gel ,Phenobarbital ,Neurology (clinical) ,Sodium nitroprusside ,Developmental Biology ,medicine.drug - Abstract
We examined the alteration of endogenous mono ADP-ribosylation in the hippocampus of amygdaloid kindled rats to clarify the neurochemical basis of epilepsy. A significant increase of the ADP-ribosylation on the 38 kDa protein was observed in the hippocampal membrane of the kindled rat. Several antiepileptics (phenytoin, phenobarbital, carbamazepine, sodium valproate) significantly decreased the ADP-ribosylation on the 38 kDa protein and effaced the increase in the kindled group. The ADP-ribosylation was largely increased by sodium nitroprusside, a nitric oxide generating compound, in both the kindled and control groups. Carbamazepine could not affect the ADP-ribosylation in the presence of sodium nitroprusside. Twenty amino acids from the N-terminus of the ADP-ribosylated 38 kDa protein were determined by sequential analysis. The sequence was completely identical to that of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that the endogenous mono-ADP-ribosylation which increased in the kindled group and decreased by the antiepileptics might be a specific reaction associated with the mechanisms of epileptogenesis.
- Published
- 1997
133. Estimation of Face Orientation from Shading Images
- Author
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Hideo Saito, Kaori Suzuki, and Shinji Ozawa
- Subjects
Estimation ,Computer science ,business.industry ,Computer vision ,Artificial intelligence ,Shading ,Face orientation ,Electrical and Electronic Engineering ,business - Published
- 1997
134. Mechanism-based inhibition of cancer metastasis with (-)-epigallocatechin gallate
- Author
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Zhenghao Li, Kaori Suzuki, Anupom Mondal, Tatsuro Watanabe, Masami Suganuma, Takashi Yamazaki, Hirota Fujiki, Atsushi Takahashi, and Miki Kurusu-Kanno
- Subjects
Epithelial-Mesenchymal Transition ,Biophysics ,Motility ,Vimentin ,Antineoplastic Agents ,Epigallocatechin gallate ,Biology ,Microscopy, Atomic Force ,Biochemistry ,Catechin ,Cell membrane ,chemistry.chemical_compound ,Mice ,Cell Movement ,Cell Line, Tumor ,Elastic Modulus ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Molecular Biology ,Cell Membrane ,beta-Cyclodextrins ,food and beverages ,Cell migration ,Cell Biology ,In vitro ,medicine.anatomical_structure ,Cholesterol ,chemistry ,Cell culture ,Cancer cell ,Immunology ,Cancer research ,biology.protein ,sense organs ,Snail Family Transcription Factors ,Transcription Factors - Abstract
Cell motility and cell stiffness are closely related to metastatic activity of cancer cells. (-)-Epigallocatechin gallate (EGCG) has been shown to inhibit spontaneous metastasis of melanoma cell line into the lungs of mice, so we studied the effects of EGCG on cell motility, cell stiffness, and expression of vimentin and Slug, which are molecular phenotypes of epithelial-mesenchymal transition (EMT). Treatments of human non-small cell lung cancer cell lines H1299 and Lu99 with 50 and 100 μM EGCG reduced cell motility to 67.5% and 43.7% in H1299, and 71.7% and 31.5% in Lu99, respectively in in vitro wound healing assay. Studies on cell stiffness using atomic force microscope (AFM) revealed that treatment with 50 μM EGCG increased Young's modulus of H1299 from 1.24 to 2.25 kPa and that of Lu99 from 1.29 to 2.28 kPa, showing a 2-fold increase in cell stiffness, i.e. rigid elasticity of cell membrane. Furthermore, treatment with 50 μM EGCG inhibited high expression of vimentin and Slug in the cells at a leading edge of scratch. Methyl-β-cyclodextrin, a reagent to deplete cholesterol in plasma membrane, showed inhibition of EMT phenotypes similar that by EGCG, suggesting that EGCG induces inhibition of EMT phenotypes by alteration of membrane organization.
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- 2013
135. Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori
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Tatsuro, Watanabe, Atsushi, Takahashi, Kaori, Suzuki, Miki, Kurusu-Kanno, Kensei, Yamaguchi, Hirota, Fujiki, and Masami, Suganuma
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Epithelial-Mesenchymal Transition ,Dose-Response Relationship, Drug ,Helicobacter pylori ,Tumor Necrosis Factor-alpha ,Blotting, Western ,MAP Kinase Kinase 1 ,RNA-Binding Proteins ,Microscopy, Atomic Force ,Phosphoproteins ,Recombinant Proteins ,Bacterial Proteins ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,Humans ,RNA Interference ,Pseudopodia ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Cell Shape - Abstract
Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large amounts of Tipα, which are incorporated into gastric cancer cells by directly binding to nucleolin on the cell surface, which is a receptor of Tipα. The binding complex induces expression of TNF-α and chemokine genes, and activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). To understand the mechanisms of Tipα in tumor progression, we looked at numerous effects of Tipα on human gastric cancer cell lines. Induction of cell migration and elongation was found to be mediated through the binding to surface nucleolin, which was inhibited by the nucleolin-targeted siRNAs. Tipα induced formation of filopodia in MKN-1 cells, suggesting invasive morphological changes. Tipα enhanced the phosphorylation of 11 cancer-related proteins in serine, threonine and tyrosine, indicating activation of MEK-ERK signal cascade. Although the downregulation of E-cadherin was not shown in MKN-1 cells, Tipα induced the expression of vimentin, a significant marker of the epithelial-mesenchymal transition (EMT). It is of great importance to note that Tipα reduced the Young's modulus of MKN-1 cells determined by atomic force microscopy: This shows lower cell stiffness and increased cell motility. The morphological changes induced in human gastric cancer cells by Tipα are significant phenotypes of EMT. This is the first report that Tipα is a new inducer of EMT, probably associated with tumor progression in human gastric carcinogenesis.
- Published
- 2013
136. Inhibitory effects and specificity of synthetic sialyldendrimers toward recombinant human cytosolic sialidase 2 (NEU2)
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Mustafizur Rahman, Kaori Suzuki, Kohji Itoh, Daisuke Tsuji, Fumiko Matsuzawa, Koji Matsuoka, Seiichi Aikawa, Jun-Ichi Sakamoto, and Satoshi Kitao
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Dendrimers ,Stereochemistry ,Molecular Sequence Data ,Mutation, Missense ,Neuraminidase ,Sialidase ,Biochemistry ,law.invention ,Substrate Specificity ,NEU2 ,chemistry.chemical_compound ,Residue (chemistry) ,law ,Trisaccharide ,Amino Acid Sequence ,Enzyme Inhibitors ,chemistry.chemical_classification ,Binding Sites ,Galactose ,Hydrogen Bonding ,In vitro ,N-Acetylneuraminic Acid ,Recombinant Proteins ,Molecular Docking Simulation ,Glucose ,chemistry ,Carbohydrate Sequence ,Docking (molecular) ,Recombinant DNA ,Trisaccharides - Abstract
Human sialidase 2 (NEU2) is a cytoplasmic sialidase that degrades sialylglycoconjugates, including glycoproteins and gangliosides, via hydrolysis of terminal sialic acids to produce asialo-type molecules. Here, we first report the inhibitory effects of a series of synthetic sialyldendrimers comprising three types [Dumbbell(1)6-S-Neu5Ac(6), Fan(0)3-S-Neu5Ac(3) and Ball(0)4-S-NeuAc(4)] toward recombinant human NEU2 in vitro. Among them, Dumbbell(1)6-S-Neu5Ac(6) exhibited the most potent inhibitory activity (concentration causing 50% inhibition (IC(50)), 0.4 ∼ 0.5 mM). In addition, NeuSLac and NeuSCel carrying thiosialyltrisaccharide moieties exhibited more potent inhibitory effects than NeuSGal and NeuSGlc carrying thiosialyldisaccharides. Docking models composed of NEU2 and the thiosialyloligosaccharide suggested that the active pocket of NEU2 prefers the second galactose-β (Galβ) to the glucose-β (Glcβ) residue in the trisaccharide structure, there being a hydrogen bond between the 4-hydroxy group of the second Galβ and the side chain of the D46 residue of NEU2. The third Glcβ residues of NeuSLac and NeuSCel were also predicted to be stabilized by hydrogen bonds with the side chains of the R21, R304, D358 and Y359 residues of NEU2. NEU2 mutants (D358A and Y359A) exhibited reduced affinity for NeuSLac carrying thiosialyltrisaccharide moieties, suggesting the significant roles of D358 and Y359 residues in recognition of thiosialyltrisaccharide moieties of NeuSLac bound in the active pocket of NEU2. Thus, the present sialyldendrimers could be utilized not only as a new class of NEU2 inhibitors but also as molecular probes for evaluating the biological functions of NEU2, including the catalytic activity and mechanism as to natural substrates carrying sialyloligosaccharides.
- Published
- 2013
137. Reduction of field through read element using shorter read shield.
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Masafumi Mochizuki, Kaori Suzuki, Chiaki Ishikawa, Kimitoshi Etoh, Hiroyuki Katada, Yasutaka Nishida, and Tomohiro Okada
- Abstract
Values for field through the read element (Hread) in longitudinal and perpendicular magnetic recording are compared with the aid of three-dimensional (3d) finite element models. We show that the Hread of the single-pole-type head used in perpendicular magnetic recording (PMR) was larger than that of the inductive ring head used in longitudinal magnetic recording (LMR). This is because that the medium for a PMR system includes a soft under layer (SUL). The Hread of PMR is affected by the permeability and thickness of SUL. The characteristic length of the upper and lower shield layers at which the Hread starts to decrease is found to be roughly equal to the length of the return pole. Decreasing the length of the upper and lower shield is shown to be the most practicable and effective way to realize the reduction of Hread. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
138. Monoclonal antibody against lymphocyte function-associated antigen 1 inhibits the formation of primary biliary cirrhosis-like lesions induced by murine graft-versus-host reaction
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Kaori Suzuki, T. Osuga, Michio Fujiwara, Takeshi Kimura, S. Inada, A. Hayashi, Yumi Matsuzaki, M Isobe, and N. Tanaka
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Pathology ,medicine.medical_specialty ,Hepatology ,medicine.drug_class ,Cell adhesion molecule ,Lymphocyte ,Spleen ,Biology ,medicine.disease ,Monoclonal antibody ,Primary biliary cirrhosis ,medicine.anatomical_structure ,Antigen ,Cancer research ,medicine ,biology.protein ,Lymphocyte function-associated antigen 1 ,Antibody - Abstract
Interaction between intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) might be involved in the pathogenesis of liver diseases. We investigated whether monoclonal antibodies (mAbs) against these two adhesion molecules could inhibit the formation of primary biliary cirrhosis (PBC)-like lesions in an animal model using graft-versus-host reaction (GVHR) with major histocompatibility complex class II disparity. PBC-like hepatic lesions such as cellular infiltration of portal area and nonsupprative destructive cholangitis (NSDC) were generated by injecting spleen T cells of C57BL/6 (B6) mice into (B6. C-H-2bm12 X B6) F1 mice. In the liver of these mice, increased number of LFA-1-positive cells and enhanced expression of ICAM-1 on sinusoidal endothelial cells and bile duct epithelial cells were observed immunohistochemically, when compared with F1 mice without GVHR. Hepatic lesions of these mAb-treated mice were almost completely inhibited in these mice compared with GVHR mice. Furthermore, we studied to determine which anti-LFA-1 mAb or anti-ICAM-1 mAb was essential to inhibit the hepatic lesions. Mice solely treated with anti-LFA-1 mAb showed significant inhibition of hepatic lesions, whereas treatment with anti-ICAM-1 mAb could not inhibit the lesions. Despite the inhibition of hepatic lesions, induction of GVHR and production of antimitochondrial antibodies were not impaired in mAb-treated mice. We conclude that LFA-1 mediates cell infiltration into the liver in this murine model of GVHR and suggest a possible therapeutic role of mAbs to this adhesion molecule in selective autoimmune liver diseases.
- Published
- 1996
139. Primary diaphragmatic schwannoma with a typical target appearance: Correlation of CT and MR imagings and histologic findings
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Tsunehiko Maruyama, Masahiro Araki, Shohei Koyama, Masaaki Otsuka, Kaori Suzuki, Katashi Fukao, Hisayuki Fukutomi, and Yumi Mun
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Adult ,Neurilemoma ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Diaphragm ,Gastroenterology ,Diaphragmatic breathing ,Magnetic resonance imaging ,Schwannoma ,medicine.disease ,Magnetic Resonance Imaging ,Respiratory Tract Neoplasms ,Diaphragm (structural system) ,Humans ,Medicine ,Female ,Tomography ,Tomography, X-Ray Computed ,business ,Neurilemmoma ,Calcification ,Geographic difference - Abstract
A rare case of benign diaphragmatic schwannoma in a 38-year-old female is reported. Precontrast computed tomography (CT) showed an encapsulated well-defined round homogeneous tumor with central calcification, measuring approximately 5 cm in diameter, arising from the left diaphragm. Contrast-enhanced CT and gadolinium-enhanced T1-weighted magnetic resonance (MR) imaging showed focal enhancement in the central portion of the tumor. The tumor showed a typical target appearance of increased peripheral signal intensity and decreased central signal intensity on unenhanced T2-weighted images. Pathological examination of resected specimens of the tumor showed two zonal histological components: a hypercellular portion of spindle cells with nuclear palisading (Antoni A tissue) and a hypocellular portion of cells with cystic degeneration, together with focal calcification and hemangeomatous vascular changes (Antoni B tissue). We consider the radiological characteristics of diaphragmatic schwannoma on CT and MR imagings to represent the geographic difference between the histologic zones of the tumor.
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- 1996
140. Transient elastography for monitoring the fibrosis of non-alcoholic fatty liver disease for 4 years
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Kaori, Suzuki, Masato, Yoneda, Kento, Imajo, Hiroyuki, Kirikoshi, Atsushi, Nakajima, Shin, Maeda, and Satoru, Saito
- Abstract
There have been some reports on the use of paired biopsies for monitoring disease progression in non-alcoholic fatty liver disease (NAFLD) patients. Recently, transient elastography has been developed as a non-invasive method for predicting the severity of liver fibrosis. We investigated 4-year disease progression in NAFLD patients by evaluating liver stiffness measurements (LSM) obtained using transient elastography.Of 97 biopsy-proven NAFLD patients whose LSM were obtained 4 years prior, we revaluated 36 who were available for follow up and compared their current stage of fibrosis with that at initial assessment. Fibrosis stage was diagnosed according to the cut-off values previously reported by our institution. We also investigated correlations between changes in LSM and changes in non-invasive fibrosis markers obtained by performing biochemical tests and clinical data.A total of nine (25%) patients had fibrosis progression, 17 (47.2%) had static disease and 10 (27.8%) had fibrosis remission. Among patients with stage 0 fibrosis as per initial LSM (n = 16), 11 had static disease and five had fibrosis progression according to LSM obtained 4 years later. Changes in LSM correlated with changes in the FIB4 index (R = 0.519, P = 0.0011) and aspartate aminotransferase-to-platelet ratio index (R = 0.346, P = 0.0412), but not with changes in other non-invasive markers.Transient elastography is non-invasive and easy to use; therefore, it can be a useful tool for monitoring the severity of hepatic fibrosis in NAFLD patients.
- Published
- 2012
141. Glioma-Initiating Cell Elimination by Metformin Activation of FOXO3 via AMPK
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Yoshitaka Narita, Soichiro Shibui, Atsushi Sato, Chifumi Kitanaka, Kaori Suzuki, Masashi Okada, Shizuka Seino, Jun Sunayama, Takamasa Kayama, Eriko Watanabe, and Keita Shibuya
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medicine.medical_specialty ,endocrine system diseases ,Cell ,Population ,Transplantation, Heterologous ,Mice, Nude ,Biology ,AMP-Activated Protein Kinases ,Mice ,Internal medicine ,Glioma ,Cancer Stem Cells ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Protein kinase A ,education ,neoplasms ,education.field_of_study ,Mice, Inbred BALB C ,Brain Neoplasms ,Forkhead Box Protein O3 ,AMPK ,Cell Differentiation ,Forkhead Transcription Factors ,Cell Biology ,General Medicine ,medicine.disease ,Metformin ,nervous system diseases ,medicine.anatomical_structure ,Endocrinology ,Glucose ,Blood-Brain Barrier ,Cancer research ,FOXO3 ,Systemic administration ,Neoplastic Stem Cells ,Glioblastoma ,Developmental Biology ,medicine.drug - Abstract
Control of the cancer stem/initiating cell population is considered key to realizing the long-term survival of glioblastoma patients. Recently, we demonstrated that FOXO3 activation is sufficient to induce differentiation of glioma-initiating cells having stem-like properties and inhibit their tumor-initiating potential. Here we identified metformin, an antidiabetic agent, as a therapeutic activator of FOXO3. Metformin activated FOXO3 and promoted differentiation of such stem-like glioma-initiating cells into nontumorigenic cells. Furthermore, metformin promoted FOXO3 activation and differentiation via AMP-activated protein kinase (AMPK) activation, which was sensitive to extracellular glucose availability. Importantly, transient, systemic administration of metformin depleted the self-renewing and tumor-initiating cell population within established tumors, inhibited tumor formation by stem-like glioma-initiating cells in the brain, and provided a substantial survival benefit. Our findings demonstrate that targeting glioma-initiating cells via the AMPK-FOXO3 axis is a viable therapeutic strategy against glioblastoma, with metformin being the most clinically relevant drug ever reported for targeting of glioma-initiating cells. Our results also establish a novel, direct link between glucose metabolism and cancer stem/initiating cells.
- Published
- 2012
142. Temperature-Insensitive Second-Harmonic Generation at 0.5321 µm in YCa4O(BO3)3
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Kiyoshi Kato, Yusuke Mori, Masashi Yoshimura, Takatomo Sasaki, Kaori Suzuki, Nobuhiro Umemura, Eiko Takaoka, and Miwako Ando
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Temperature sensitivity ,Materials science ,Physics and Astronomy (miscellaneous) ,Plane (geometry) ,business.industry ,General Engineering ,Zero (complex analysis) ,General Physics and Astronomy ,Second-harmonic generation ,Molecular physics ,Frequency conversion ,Optics ,Nd:YAG laser ,Dispersion (optics) ,business - Abstract
YCa4O(BO3)3 has been found to have the phase-matching points where the temperature variation of the phase-matching angle (dθobs/dT) becomes zero for type-1 second-harmonic generation at 0.5321 µm at θ=30.8° and =180°. We also found that the temperature sensitivity of the phase-matching angle in the zx plane differs between the =0° and =180° propagation directions in this material. In addition, the thermo-optic dispersion formula of YCa4O(BO3)3 is presented.
- Published
- 2003
143. Evaluation of the Liver Fibrosis Index calculated by using real-time tissue elastography for the non-invasive assessment of liver fibrosis in chronic liver diseases
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Wataru, Tomeno, Masato, Yoneda, Kento, Imajo, Kaori, Suzuki, Yuji, Ogawa, Yoshiyasu, Shinohara, Hironori, Mawatari, Koji, Fujita, Wataru, Shibata, Hiroyuki, Kirikoshi, Shin, Maeda, Atsushi, Nakajima, and Satoru, Saito
- Abstract
A rapid and non-invasive method of detecting fibrosis in patients with chronic liver diseases is of major clinical interest. The purpose of this study was to comparatively investigate the effectiveness of the Liver Fibrosis Index (LF Index) calculated using real-time tissue elastography (RTE) in patients with non-alcoholic fatty liver disease (NAFLD) and patients with chronic hepatitis C (CHC).Twenty-seven patients with biopsy-proven NAFLD and 93 patients with biopsy-proven CHC were included. They underwent transient elastography (TE), serum liver fibrosis marker testing and RTE to calculate the LF Index.The LF Index showed a stepwise increase with increasing histological severity of fibrosis in CHC patients (P = 0.0102), whereas no significant correlation of the LF Index with the histological severity of liver fibrosis in NAFLD patients (P = 0.852). There was a significant correlation between the LF Index and liver stiffness measured by TE in CHC patients (r = 0.319, P = 0.0009). On the other hand, no such correlation was observed in NAFLD patients. While in CHC patients, the LF Index was correlated with the FIB-4 index, no such correlation was observed in NAFLD patients.The LF Index calculated by RTE is effective for assessment of liver fibrosis in patients with CHC. On the other hand, it is not useful in patients with NAFLD. This is the first study to compare the clinical usefulness of RTE as non-invasive assessment of liver fibrosis between CHC and NAFLD. Further investigations are required to refine statistical assessment of RTE.
- Published
- 2012
144. Targeting JNK for therapeutic depletion of stem-like glioblastoma cells
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Atsushi Sato, Kenichiro Matsuda, Yoshitaka Narita, Kaori Suzuki, Eriko Watanabe, Keita Shibuya, Chifumi Kitanaka, Takamasa Kayama, Shizuka Seino, Soichiro Shibui, and Masashi Okada
- Subjects
Male ,MAP Kinase Signaling System ,Population ,Cell ,Mice, Nude ,Antineoplastic Agents ,Biology ,Article ,Mice ,Cancer stem cell ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Phosphorylation ,education ,Adverse effect ,Protein Kinase Inhibitors ,education.field_of_study ,Multidisciplinary ,Brain Neoplasms ,JNK Mitogen-Activated Protein Kinases ,Cancer ,Cell Differentiation ,medicine.disease ,Xenograft Model Antitumor Assays ,Tumor Burden ,medicine.anatomical_structure ,Cell culture ,Immunology ,Neoplastic Stem Cells ,Systemic administration ,Cancer research ,Glioblastoma - Abstract
Control of the stem-like tumour cell population is considered key to realizing the long-term survival of patients with glioblastoma, one of the most devastating human malignancies. To date, possible therapeutic targets and targeting methods have been described, but none has yet proven to target stem-like glioblastoma cells in the brain to the extent necessary to provide a survival benefit. Here we show that targeting JNK in vivo, the activity of which is required for the maintenance of stem-like glioblastoma cells, via transient, systemic administration of a small-molecule JNK inhibitor depletes the self-renewing and tumour-initiating populations within established tumours, inhibits tumour formation by stem-like glioblastoma cells in the brain, and provide substantial survival benefit without evidence of adverse events. Our findings not only implicate JNK in the maintenance of stem-like glioblastoma cells but also demonstrate that JNK is a viable, clinically relevant therapeutic target in the control of stem-like glioblastoma cells.
- Published
- 2012
145. Plasma free choline is a novel non-invasive biomarker for early-stage non-alcoholic steatohepatitis: A multi-center validation study
- Author
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Kento, Imajo, Koji, Fujita, Masato, Yoneda, Yoshiyasu, Shinohara, Kaori, Suzuki, Hironori, Mawatari, Junichiro, Takahashi, Yuichi, Nozaki, Yoshio, Sumida, Hiroyuki, Kirikoshi, Satoru, Saito, Makoto, Nakamuta, Nobuyuki, Matsuhashi, Koichiro, Wada, and Atsushi, Nakajima
- Abstract
Choline is a dietary component that is crucial for normal cellular function. Choline is predominantly absorbed from the small intestine and completely metabolized in the liver. We recently demonstrated that free choline (fCh) levels in blood reflect the level of phosphatidylcholine synthesis in the liver and is correlated with the onset of non-alcoholic steatohepatitis (NASH). Our aim here was to validate the utility of this biomarker for NASH diagnosis. Our cohort consisted of 110 patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) from four centers across Japan and 25 age-matched healthy controls. Plasma fCh levels were measured using high-performance liquid chromatography. Patients with diagnosed or borderline NASH had significantly increased plasma fCh levels when compared with control subjects, or patients not diagnosed with NASH. Interestingly, an association between plasma fCh levels and expression of microsomal triglyceride transfer protein, which catalyzes the transfer of triglyceride, was reflected in the markedly negative correlation between these two variables in patients with NAFLD. Moreover, the grade of liver steatosis and fibrosis stage increased with increasing plasma fCh levels (P 0.05). The area under the receiver-operating characteristic (ROC) curves for NASH, including borderline diagnosis, was 0.811. Additionally, the areas under the ROC for fibrosis stage were 0.816 forstage 1, 0.805 forstage 2, 0.809 forstage 3 and 0.818 forstage 4. Plasma fCh levels are closely related to the grade of liver steatosis and fibrosis, and predict NASH severity. Plasma fCh levels are therefore a potential diagnostic marker for early-stage NASH in clinical practice.
- Published
- 2012
146. Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?
- Author
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Atsushi Nakajima, Satoru Saito, Kensuke Kubota, Hironori Mawatari, Shingo Kato, Hiroyuki Kirikoshi, Noritoshi Kobayashi, Koji Fujita, Kaori Suzuki, Kento Imajo, Masato Yoneda, and Shin Maeda
- Subjects
Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Brief Article ,Group A ,Gastroenterology ,Group B ,Hepatic Artery ,Internal medicine ,medicine ,Humans ,Infusions, Intra-Arterial ,Chemoembolization, Therapeutic ,Survival rate ,Aged ,Cisplatin ,business.industry ,Liver Neoplasms ,Retrospective cohort study ,General Medicine ,Hepatology ,Middle Aged ,medicine.disease ,digestive system diseases ,Surgery ,Survival Rate ,Fluorouracil ,Hepatocellular carcinoma ,Multivariate Analysis ,Female ,business ,medicine.drug - Abstract
AIM: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE). METHODS: This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital. 5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir. Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU. The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A, n = 23), and another group who fulfilled the criteria for TACE resistance (group B, n = 19). We compared the outcomes in terms of the response and survival rates between the two groups. RESULTS: Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate: 48% vs 16%, P = 0.028, tumor suppression rate: 87% vs 53%, P = 0.014). Furthermore, both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-, 6-, 12-, and 24-mo = 83%, 70%, 29% and 20% vs 63%, 42%, 16% and 0%, respectively, P = 0.040, and 9.8 mo vs 6.2 mo, P = 0.040). A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P = 0.007). CONCLUSION: HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE. Other tools for treatment, i.e., molecular-targeting agents may be considered for these cases.
- Published
- 2012
147. MTR-16MISMATCH REPAIR DEFECTS PREDICT CLINICAL OUTCOME OF PRIMARY AND RECURRENT MALIGNANT GLIOMAS
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Yoshiaki Shiokawa, Satoshi Kume, Keiichi Kobayashi, Saki Shimizu, Nobuyoshi Sasaki, Kuniaki Saito, Motoo Nagane, and Kaori Suzuki
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Pathology ,medicine.medical_specialty ,Methyltransferase ,Temozolomide ,Biology ,medicine.disease ,MLH1 ,digestive system diseases ,nervous system diseases ,MSH6 ,Oncology ,MSH2 ,Glioma ,medicine ,Cancer research ,PMS2 ,DNA mismatch repair ,Neurology (clinical) ,Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology ,neoplasms ,medicine.drug - Abstract
INTRODUCTION: Temozolomide (TMZ), a standard drug for glioblastoma (GBM), induces inactivation of the DNA mismatch repair (MMR) system and hence causes hypermutator phenotype in the glioma especially with methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. MMR defects are also found in primary gliomas and are associated with resistance to TMZ and malignant progression to secondary GBM. However, the association between alteration of MMR system and clinical outcome of both primary and recurrent GBMs was yet to be elucidated. METHODS: We analyzed protein expression of MLH1, MSH2, MSH6, and PMS2 as well as MGMT methylation in a set of 117 primary GBMs and 34 paired sample of initial and recurrent gliomas. Protein expression was analyzed by Western blotting and/or immunohistochemistry. MGMT methylation was determined by methylation-specific PCR. Progression-free and overall survival times according to each molecular status were reviewed. RESULTS: Loss of MMR protein expression (MLH1, MSH2, MSH6, and PMS2) was observed in 12%, 10%, 50%, and 16% of the primary samples, respectively. Inactivation of MSH6 during the recurrence was associated with MGMT methylation at recurrence (p = 0.02), while MGMT methylation of the initial samples did not predict the changes of any MMR protein. Malignant progression from lower grade glioma was associated with inactivation of MSH6 (p = 0.035). Loss of MMR protein expression, as well as unmethylated MGMT promoter, was associated with shorter overall survival in patients with primary GBMs. In contrast, MMR inactivation was associated with longer survival in patients with recurrent GBMs, while MGMT methylation was not. CONCLUSION: Inactivation of MMR protein was associated with resistance to TMZ for primary GBMs, malignant progression of lower grade gliomas, and was predictive factor for survival of the patients with recurrent GBMs. Further investigation to define optimal treatment for glioma according to MGMT and MMR status is warranted.
- Published
- 2015
148. Modulation of Endogenous ADP-Ribosylation in the Kindling Model of Epilepsy
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Shuji Hasegawa, Shuichi Kikuchi, Toshio Sato, Masatoshi Noda, Naoko Morinaga, Kaori Suzuki, and Hiroto Iwasa
- Subjects
Male ,G protein ,Endogeny ,Pharmacology ,Nitric Oxide ,Synaptic Transmission ,Epileptogenesis ,Nitric oxide ,Rats, Sprague-Dawley ,Epilepsy ,chemistry.chemical_compound ,Kindling, Neurologic ,medicine ,Animals ,Cerebral Cortex ,Adenosine Diphosphate Ribose ,Chemistry ,Kindling ,General Neuroscience ,Membrane Proteins ,General Medicine ,Amygdala ,medicine.disease ,Rats ,Psychiatry and Mental health ,Neurology ,ADP-ribosylation ,Autoradiography ,Guanosine Triphosphate ,Neurology (clinical) ,Kindling model - Published
- 1994
149. Influence of longitudinal bias field on magnetization distribution in magnetoresistive head with shield films
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Chiaki Ishikawa, Yoshinobu Nakatani, Nobuo Hayashi, Yutaka Sugita, Kiminari Shinagawa, Kazuetsu Yoshida, and Kaori Suzuki
- Subjects
Materials science ,Field (physics) ,Condensed matter physics ,Magnetoresistance ,Demagnetizing field ,General Physics and Astronomy ,Shields ,Magnetic field ,Condensed Matter::Materials Science ,symbols.namesake ,Magnetization ,Maxwell's equations ,Remanence ,Condensed Matter::Superconductivity ,symbols - Abstract
The magnetization distribution in the magnetoresistive (MR) film has been calculated by self‐consistently solving the three‐dimensional field of the MR head. The magnetization distribution was calculated based on the Landau–Lifshitz–Gilbert equation and the head field was obtained by the Maxwell equation. The longitudinal bias field for the domain control was generated by exchange‐coupled antiferromagnetic or permanent magnetic films which were formed outside the sensing region of the MR film. The resistance change of the MR film was calculated from the magnetization distribution with shield films and without shield films. It was found that the resistance change with the antiferromagnetic film without the shields was about two times larger than that with the permanent magnetic film with the remanence Br of 0.7 T. The difference between them was reduced when the shields were formed because the stray field from the permanent magnetic film which is applied to the MR film was decreased by the shields. Further...
- Published
- 1994
150. FoxO3a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity
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Kenichiro Matsuda, Ken Tachibana, Jun Sunayama, Chifumi Kitanaka, Shizuka Seino, Takamasa Kayama, Yoshitaka Narita, Arata Tomiyama, Atsushi Sato, Kaori Suzuki, Eriko Watanabe, Kaori Sakurada, and Soichiro Shibui
- Subjects
MAPK/ERK pathway ,Male ,MAP Kinase Signaling System ,Mice, Nude ,Biology ,Mice ,Phosphatidylinositol 3-Kinases ,Downregulation and upregulation ,Tumor Cells, Cultured ,Animals ,Humans ,Protein kinase B ,Transcription factor ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,Mice, Inbred BALB C ,Kinase ,Brain Neoplasms ,TOR Serine-Threonine Kinases ,Forkhead Box Protein O3 ,Cell Differentiation ,Forkhead Transcription Factors ,Cell Biology ,Cell biology ,Up-Regulation ,Neoplastic Stem Cells ,Molecular Medicine ,Phosphorylation ,Female ,Signal transduction ,Mitogen-Activated Protein Kinases ,Glioblastoma ,Proto-Oncogene Proteins c-akt ,Developmental Biology ,Signal Transduction - Abstract
Glioblastoma is one of the most aggressive types of human cancer, with invariable and fatal recurrence even after multimodal intervention, for which cancer stem-like cells (CSLCs) are now being held responsible. Our recent findings indicated that combinational inhibition of phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (mTOR) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways effectively promotes the commitment of glioblastoma CSLCs to differentiation and thereby suppresses their tumorigenicity. However, the mechanism by which these two signaling pathways are coordinated to regulate differentiation and tumorigenicity remains unknown. Here, we identified FoxO3a, a common phosphorylation target for Akt and ERK, as a key transcription factor that integrates the signals from these pathways. Combinational blockade of both the pathways caused nuclear accumulation and activation of FoxO3a more efficiently than blockade of either alone, and promoted differentiation of glioblastoma CSLCs in a FoxO3a expression-dependent manner. Furthermore, the expression of a constitutively active FoxO3a mutant lacking phosphorylation sites for both Akt and ERK was sufficient to induce differentiation and reduce tumorigenicity of glioblastoma CSLCs. These findings suggest that FoxO3a may play a pivotal role in the control of differentiation and tumorigenicity of glioblastoma CSLCs by the PI3K/Akt/mTOR and MEK/ERK signaling pathways, and also imply that developing methods targeting effective FoxO3a activation could be a potential approach to the treatment of glioblastoma.
- Published
- 2011
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