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Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells

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World Journal of Gastroenterology 2006年第10期12卷 1597-1602页

作者： Pei-Hong Jiang yoshiharu Motoo Norio Sawabu Toshinari Minamoto Department of Internal Medicine and Medical Oncology Cancer Research Institute Kanazawa University Kanazawa Japan Department of Medical Oncology Kanazawa Medical University Uchinada Ishikawa Japan Division of Diagnostic Molecular Oncology Cancer Research InstituteKanazawa University Kanazawa Japan

AIM： TO investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in human pancreatic cancer cells. METHODS： A human pancreatic cancer cell line, PANC-1, was cultured. 1 × 10^4 PANG-1 cells were plated in 96-well microtiter plates. After being incubated for 24 h, gemcitabine was added to the medium at concentrations ranging 2.5 -1 000 mg/L. The AlamarBlue dye method was used for cell growth analysis. DNA fragmentation was quantitatively assayed using a DNA fragmentation enzyme-linked immunosorbent assay （ELISA） kit. PAP and TP53INP1 mRNA expression was determined using the reverse transcription-polymerase chain reaction with semi-quantitative analysis. The expression of GSK-3β and phospho-GSK-3β proteins was examined with Western blot analysis. RESULTS： The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L. The growth of PANC-1 cells was inhibited by gemcitabine in a concentration-dependent manner （P〈 0.0001） and the cell growth was also inhibited throughout the time course （P〈0.0001）. The DNA fragmentation rate in the gemcitabine-treated group at 48 h was 44.7 %, whereas it was 25.3 % in the untreated group. The PAP mRNA expression was decreased after being treal^l with gemcitabine, whereas the TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis showed that phospho- GSK-3βZ^ser9 was induced by the gemcitabine treatment. CONCLUSION： Gemcitabine suppresses PANC-1 cell proliferation and induces apoptosis. Apoptosis is considered to be associated with the inhibition of PAPand GSK-3β, and the activation of TP53INP1 and pospho- GSK-3β^ser9 .

关键词： Gemcitabine Pancreatitis-associated protein TPS3INP1 GSK-3β PANC-1

Pancreatitis-associated protein:From a lectin to an anti-inflammatory cytokine

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World Journal of Gastroenterology 2007年第2期13卷 170-174页

作者： Daniel Closa yoshiharu Motoo Juan L Iovanna Department of Experimental Pathology IIBB- CSIC IDIBAPS Barcelona Spain Department of Medical Oncology Kanazawa Medical University Ishikawa Japan INSERM U.624 Stress Cellulaire Marseille France

Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti- inflammatory cytokine.

关键词： Pancreatitis-associated protein Pancreatitis .1anus kinases STAT3 SOCS3 Anti-inflammatory Lectin

Traditional Japanese Medicine,Kampo:Its History and Current Status

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Chinese Journal of Integrative Medicine 2011年第3期17卷 85-87页

作者： yoshiharu Motoo Takashi Seki Kiichiro Tsutani The Japan Society for Oriental Medicine Tokyo105-0022 Japan Department of Medical Oncology Kanazawa Medical UniversityUchinadaIshikawa920-0293Japan Department of Traditional Asian Medicine Tohoku University Graduate School of MedicineSendai980-8575Japan Department of Drug Policy and Management Graduate School of Pharmaceutical SciencesThe University of TokyoTokyo113-0033Japan

Traditional Japanese medicine,Kampo,is used by over 80%of medical doctors in *** to its high quality and safety,Kampo has been integrated into modern medicine,and there are 345 randomized controlled trials using Kampo in Japan as of *** there are a number of articles in top journals about basic science research,we can find only small numbers of high-quality clinical *** undergraduate education on Kampo has been established,integrative approach with the balanced combination of modern medicine and Kampo is expected to generate good clinical evidence in the near future.

关键词： Kampo traditional medicine evidence randomized controlled trial integrative medicine

Standards of Reporting Kampo Products (STORK) in research articles

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Journal of Integrative Medicine 2017年第3期15卷 182-185页

作者： yoshiharu Motoo Takashi Hakamatsuka Nobuo Kawahara Ichiro Arai Kiichiro Tsutani Committee for Evidence-based Medicine Japan Society for Oriental Medicine Tokyo Japan Department of Medical Oncology Kanazawa Medical University Ishikawa 920-0293 Japan Division of Pharmacognosy phytochemistry and Narcotics National Institute of Health Sciences Tokyo 158- 8501 Japan Research Center for Medicinal Plant Resources National Institutes of Biomedical Innovation Health and Nutrition Ibaraki 305-1843 Japan Department of Kampo Medicine Nihon Pharmaceutical University Saitama 362-0806 Japan Faculty of Health Sciences Tokyo Ariake University of Medical and Health Sciences Tokyo 135-0063 Japan

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials （CONSORT） checklist, we hereby propose the use of the Standards of Reporting Kampo Products （STORK） website, http：//***/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

关键词： medicine, Kampo Evidence Reports on Kampo Treatment randomized controlled trial Consolidated Standards of Reporting Trials (CONSORT) Standards of Reporting Kampo Products (STORK)

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负离子源及其应用

微细加工技术 1993年第2期 82-88页

作者： yoshiharu Mori Junzo ishikawa 罗应明

本文简要介绍了近年研制出的几种主要类型负离子源及其工作原理,重点是等离子溅射型重金属负离子源。概述了这些负离子源在材料科学中的应用前景,如离子注入和薄膜淀积等。

关键词：离子束等离子体溅射负离子源

Acupuncture improved lipid metabolism by regulating intestinal absorption in mice

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World Journal of Gastroenterology 2020年第34期26卷 5118-5129页

作者： Jia Han Xin Guo Xiang-Jin Meng Jing Zhang Reimon Yamaguchi yoshiharu Motoo Sohsuke Yamada Department of Pathology and Laboratory Medicine Kanazawa Medical UniversityIshikawa 920-0293Japan Department of Oncology Kanazawa Medical UniversityIshikawa 920-0293Japan Department of Pathology Kanazawa Medical University HospitalIshikawa 920-0293Japan Department of Dermatology Kanazawa Medical UniversityIshikawa 920-0293Japan

BACKGROUND Non-alcoholic fatty liver disease(NAFLD),in which abnormal lipid metabolism plays an important role in disease progression,has become a *** lipid metabolism,for example an increased fat intake,has been thought to be an initial factor leading to *** small intestine is the main site of dietary lipid absorption.A number of clinical trials have shown that acupuncture has positive effects in the regulation of lipid metabolism,which is closely associated with the progression of *** therefore hypothesized that,acupuncture can improve the conditions of NAFLD by regulating intestinal absorption of *** To study the role of acupuncture treatment in the improvement of metabolic syndrome secondary to NAFLD by mouse *** 8-wk-old male C57BL/6J mice were fed a methionine-and choline-deficient diet for 3 ***,all mice were separated randomly into acupoints group(AG)or non-acupoints group(NG)with high fat diet *** treatment was performed at Zu san li,Guan yuan and Yong quan acupoints as acupuncture treatment to AG mice while non-acupoints place to NG ***,mice were anesthetized with an injection of ketamine-medetomidine and euthanized by *** An apparent improvement of obesity was found in AG mice after acupuncture *** AG mice,the body weight was much lower(22.6±1.2 g vs 28.1±1.0 g,P<0.005)in comparison to NG *** length of small intestine in AG mice was significantly shorter(26.7±2.3 cm vs 32.7±2.7 cm,P<0.005).A large amount of chyme was observed in the lumen of the AG small *** expression of microsomal triglyceride transfer protein,apolipoprotein B and apolipoprotein C2 was ***(TGs),total cholesterol and nonesterified fatty acid(NEFA)levels of the small intestinal tissue were significantly higher in AG mice,but the serum TGs and NEFA levels were reduced in AG *** These results indicate that acupuncture at Zu san li,Guan yuan and

关键词： Acupuncture Non-alcoholic fatty liver disease Small intestine Lipid metabolism Apolipoproteins

Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

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World Journal of Gastroenterology 2006年第5期12卷 691-696页

作者： Pei-Hong Jiang yoshiharu Motoo Stéphane Garcia Juan Lucio Iovanna Marie-Josèphe Pébusque Norio Sawabu Department of Internal Medicine and Medical Oncology Cancer Research InstituteKanazawa University Kanazawa Japan Department of Medical Oncology Kanazawa Medical University Ishikawa Japan INSERM U624 Marseille France

AIM： Overexpression of tumor protein p53-induced nudear protein 1 （TP53INP1） induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer, METHODS： TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed. RESULTS： TP53INP1 was expressed in 98% （139/142 cases） of non-cancerous gastric tissues and was downexpressed in 64% （91/142 cases） of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased （43.9%） in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma （81.6%）. Cancers invading the submucosa or deeper showed lower positively （59.1%） compared with mucosal cancers （85.2%）. Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion （54.3% vs 82.0% without lymphatic invasion） and node-positive patients （31.3% vs 68.3% in node-negative patients）. P53 was expressed in 68 （47.9%） patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells： the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP41-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis （P= 0.0006）.CONCLUSION： TPS3INP1-positive rate decreases with the progression of gastric cancer. TPS3INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TPS3INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TPS3INP

关键词： Tumor protein 53-induced nuclear protein 1 p53 Gastric cancer

In-situ evaluation for activated concrete in accelerator facility with scintillation-type gamma-ray spectrometer

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辐射防护 2020年第6期40卷 545-549页

作者： Go Yoshida Hiroshi Matsumura Koichi Nishikawa Akihiro Toyoda yoshiharu Miyazaki Kazuyoshi Masumoto Hajime Nakamura Taichi Miura High Energy Accelerator Research Organization(KEK) 1-1 OhoTsukubaIbaraki 305-0801Japan The Medical and Pharmacological Research Center Foundation Wo-32Inoyama-machiHakuiIshikawa 925-0613Japan

The assessment of activated concrete is particularly difficult during the decommissioning of an accelerator *** analysis by core boring is the only method of investigating the activity of concrete *** address this problem,an in-situ and nondestructive analysis method was developed to determineγ-ray-emitting nuclides and their specific activities in the concrete walls and floor by using a portable germanium semiconductor *** this work,we examined a substitute for Ge detector to establish a simpler and more convenient *** candidates,we focused on some scintillation type spectrometers,and the possibility of a substitute for a Ge detector was examined by both simulation and *** detection limits were roughly estimated through Monte Carlo simulation for various scintillation crystals,and it was found that 1.5-inch LaBr3,CeBr3,and SrI2 could distinguish the clearance *** was confirmed that the 1.5-inch LaBr3 could reproduce the calibration curve of the Ge detector in the *** required thickness and length of the radiation shield for suppressing the background radiation during the measurement was also determined for the convenience of an actual decommissioning work.

关键词： activation accelerator concrete scintillation detector PHITS code