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

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

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Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C: A randomized controlled trial

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World Journal of Gastroenterology 2005年第26期11卷 4013-4017页

作者： Yoshiharu Motoo Hisatsugu Mouri Koushiro Ohtsubo Yasushi Yamaguchi Hiroyuki Watanabe norio sawabu Department of Internal Medicine and Medical Oncology Cancer Research Institute Kanazawa University Kanazawa Japan

AIM:Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated. RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59±1.10 g/dL) was significantly (P= 0.026) smaller than that in the control group (3.71±0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Thl/Th2 balance between the two groups. There was no specific adverse effect in NYT administration. CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.

关键词： Chronic hepatitis C Ribavirin Interferon Herbal medicine Anemia

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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

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胰腺癌组织中基质金属蛋白酶-7(MMP7)的表达(英文)

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癌症 2000年第6期19卷 521-523页

作者：胡育新李平刘宝姝 Watanabe Hiroyuki sawabu norio 上海长海医院肿瘤科上海200433 日本金泽大学癌症研究所内科部

目的：有研究表明基质金属蛋白酶-７（ｍａｔｒｉｘ　ｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ　７，ＭＭＰ７）与部分人肿瘤的浸润和转移有一定关系。本研究旨在探讨胰腺癌组织中ＭＭＰ７的表达及其在本病发展过程中的作用。材料与方法：... 详细信息

目的：有研究表明基质金属蛋白酶-７（ｍａｔｒｉｘ　ｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ　７，ＭＭＰ７）与部分人肿瘤的浸润和转移有一定关系。本研究旨在探讨胰腺癌组织中ＭＭＰ７的表达及其在本病发展过程中的作用。材料与方法：用免疫组化染色方法检测了５１例胰腺癌石蜡包埋组织（其中２２例为早期病变，２９例为晚期病变）中ＭＭＰ７的表达。结果：５１例胰腺癌组织中３５例（６８.６％）显示有ＭＭＰ７表达。而且，晚期胰腺癌ＭＭＰ７表达的阳性率（７９.３％，２３／２９）比早期（５４.５％，１２／２２）高，两组比较差异显著（Ｐ＜０.０５）。结论：胰腺癌组织中ＭＭＰ７的表达与肿瘤进展有一定关系，可被视为一种反映胰腺癌生物侵袭性的有价值的标志物。

关键词：胰腺肿瘤基质金属蛋白酶-7 MMP7 免疫组织化学

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Consensus of primary care in acute pancreatitis in Japan

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World Journal of Gastroenterology 2006年第21期12卷 3314-3323页

The incidence of acute pancreatitis in Japan is increasing and ranges from 187 to 347 cases per million populations. Case fatality was 0.2% for mild to moderate, and 9.0% for severe acute pancreatitis in Japan in 2003. Experts in pancreatitis in Japan made this document focusing on the practical aspects in the early management of patients with acute pancreatitis. The correct diagnosis of acute pancreatitis and severity stratification should be made in all patients using the criteria for the diagnosis of acute pancreatitis and the multifactor scoring system proposed by the Research Committee of Intractable Diseases of the Pancreas as early as possible. All patients diagnosed with acute pancreatitis should be managed in the hospital. Monitoring of blood pressure, pulse and respiratory rate, body temperature, hourly urinary volume, and blood oxygen saturation level is essential in the management of such patients. Early vigorous intravenous hydration is of foremost importance to stabilize circulatory dynamics. Adequate pain relief with opiates is also important. In severe acute pancreatitis, prophylactic intravenous administration of antibiotics at an early stage is recommended. Administration of protease inhibitors should be initiated as soon as thediagnosis of acute pancreatitis is confirmed. A combination of enteral feeding with parenteral nutrition from early stage is recommended if there are no clear signs and symptoms of ileus and gastrointestinal bleeding. Patients with severe acute pancreatitis should be transferred to ICU as early as possible to perform special measures such as continuous regional arterial infusion of protease inhibitors and antibiotics, and continuous hemodiafiltration. The Japanese Government covers medical care expense for severe acute pancreatitis as one of the projects of Research on Measures for Intractable Diseases.

关键词： Fluid resuscitation Protease inhibitor treatment Antibiotic treatment Continuous regional arterial infusion Contrast-enhanced computed tomography

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血浆k-ras基因突变检测对胆道系统癌的诊断意义

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临床肝胆病杂志 2000年第3期16卷 164-166页

作者：刘海林渡边弘之泽武纪雄上海第二医科大学附属第九人民医院消化内科上海200011 日本金泽大学癌研究所附属医院内科

探讨胆道系统癌患者外周血中是否存在ｋ－ｒａｓ基因突变及其诊断价值。方法提取血浆DNA，通过ｍｕｔａｎｔ　ａｌｌｅｌｅ　ｓｐｅｃｉｆｉｃ　ａｍｐｌｉｆｉｃａｔｉｏｎ（ＭＡＳＡ）方法检测ｋ－ｒａｓ基因codon　１２突变。结果 ... 详细信息

探讨胆道系统癌患者外周血中是否存在ｋ－ｒａｓ基因突变及其诊断价值。方法提取血浆DNA，通过ｍｕｔａｎｔ　ａｌｌｅｌｅ　ｓｐｅｃｉｆｉｃ　ａｍｐｌｉｆｉｃａｔｉｏｎ（ＭＡＳＡ）方法检测ｋ－ｒａｓ基因codon　１２突变。结果 7例胆囊癌中5例ｋ－ｒａｓ基因突变阳性（１７．４％），６例肝内胆管细胞癌和3例总胆管癌中分别有2例（３３．３％）及1例（３３．３％)ｋ－ｒａｓ基因突变检测阳性。ｋ－ｒａｓ基因突变检测阳性而血清CA１９－９、CEA水平均正常者胆囊癌、肝内胆管细胞癌与总胆管癌各1例。结论胆道系统癌外周血中存在肿瘤DNA，特别是胆囊癌检测血浆ｋ－ｒａｓ基因突变具有较高的诊断意义。

关键词： MASA法胆囊癌 K-ras基因基因突变诊断

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胆道系统癌与血浆k-ras基因突变检测

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上海交通大学学报（医学版） 2000年第S1期24卷 42-43,74页

作者：刘海林渡边弘之泽武纪雄上海第二医科大学第九人民医院消化内科上海200011 日本金泽大学癌研究所附属病院内科

目的探讨胆道系统癌患者外周血中是否存在k -ras基因突变及其诊断价值。　方法提取血浆DNA ,通过突变等位基因特异性扩增 (MASA)方法检测k -ras基因codon1 2突变。　结果 7例胆囊癌中 5例k -ras基因突变阳性 (71 .4% ) ,6例肝内胆管细... 详细信息

目的探讨胆道系统癌患者外周血中是否存在k -ras基因突变及其诊断价值。　方法提取血浆DNA ,通过突变等位基因特异性扩增 (MASA)方法检测k -ras基因codon1 2突变。　结果 7例胆囊癌中 5例k -ras基因突变阳性 (71 .4% ) ,6例肝内胆管细胞癌和 3例总胆管癌中分别有 2例 (33.3% )及 1例 (33.3% )k -ras基因突变检测阳性。k -ras基因突变检测阳性而血清CA19-9、CEA水平均正常的胆囊癌、肝内胆管细胞癌与总胆管癌各 1例。　结论胆道系统癌外周血中存在肿瘤DNA ,特别是胆囊癌检测血浆k -ras基因突变具有较高的诊断意义。

关键词：癌基因基因ras 等位基因特异性扩增

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Study on the flow structure around discontinued vertically layered vegetation in an open channel

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Journal of Hydrodynamics 2020年第3期32卷 454-467页

作者： Naveed Anjum norio Tanakia Graduate School of Science and Engineering Saitama UniversitySaitama-shiJapan International Institute for Resilient Society Saitama UniversitySaitama-shiJapan

The flow structure and geomorphology of rivers are significantly affected by vegetation patterns. In the present study, the effect of vegetation in the form of discontinuous and vertically double layered patches particularly on the resulting flow turbulence was examined computationally in an open channel. A k-ɛ model was implemented in this research work which was developed using 3-D numerical code FLUENT (ANSYS). After the validation process of numerical model, the impact of discontinuous layered vegetation patches on the flow turbulence was investigated against varying vegetation density and patch length. The mean stream-wise velocities at specified positions showed larger spatial fluctuations directly upstream and downstream of vegetation elements, whereas sharp inflections in the profiles were witnessed at the top of smaller submerged elements i.e. z/hs= 1 (where z is the flow depth and hs is the smaller vegetation height). The reduction in flow velocity due to tall vegetation structure was more as compared with that of short vegetation. The mean velocity in the patch regions was visibly higher than that in the gap regions. The profiles of turbulent flow properties showed more rise and fall within the patches with a high vegetation density i.e. Ss/d= 4;and St/d= 8 (where Ss/d and St/d are the smaller and taller vegetation spacing, while d is the vegetation diameter) as compared with low vegetation density i.e. Ss/d= 8;and St/d= 16. The turbulent flow structure in the large patch and gap regions was found to be more stable than that in the small patches and gaps;whereas, due to the variation in distribution form of the patch, turbulence is relatively unaffected, and the flow structure variation is low. Turbulence was observed to be large, followed by a saw-tooth distribution within the patches;whereas, low turbulence is observed in the non-vegetation regions. The turbulent intensity acquired maximum of 13% turbulence for dense vegetation arrangement as compared t

关键词： Discontinuous and layered vegetation patches open channel flow numerical simulation mean flow velocity turbulence modeling flow characteristics

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Adaptive Process for SMART Community Governance under Persistent Disruptive Risks

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International Journal of Disaster Risk Science 2018年第4期9卷 454-463页

作者： norio Okada Institute of Disaster Area Revitalization Regrowth and Governance Kwansei Gakuin University

This article addresses the increasing need for participatory approaches to disaster reduction at the community level. Based on the author's 30-year engagement in the mountainous community Chizu Town, Tottori Prefecture, Japan, a unique participatory approach called ‘‘Zeroto-One Movement'' has been strategically studied. The study areas are found to have adaptively increased their coping capacity. Their unique participatory process is shown to be an adaptive process for SMART community governance under persistent disruptive risks—‘‘S'' represents small-sized and survivability-minded, ‘‘M'' modestscale and multiple-stakeholder involved, ‘‘A'' anticipatory and adaptive, ‘‘R'' risk-concerned and responsive, and ‘‘T''is transformative. Finally, the Case Station-Field Campus scheme is proposed to serve as a platform for studying the adaptive processes over a long period of time.

关键词： Case Station-Field Campus scheme Japan Persistent disruptive risks SMART governance Zero-to-One movement

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Numerical investigation of velocity distribution of turbulent flow through vertically double-layered vegetation

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Water Science and Engineering 2019年第4期12卷 319-329页

作者： Naveed Anjum norio Tanaka Graduate School of Science and Engineering Saitama UniversitySaitama 338-8570Japan International Institute for Resilient Society Saitama UniversitySaitama 338-8570Japan

The velocity structures of flow through vertically double-layered vegetation(VDLV)as well as single-layered rigid vegetation(SLV)were investigated computationally with a three-dimensional(3D)Reynolds stress turbulence model,using the computational fluid dynamics(CFD)code *** detailed velocity distribution was explored with a varying initial Froude number(Fr),with consideration of the steady subcritical flow conditions of an inland *** VDLV flows,the numerical model successfully captured the inflection point in the profiles of mean streamwise velocities in the mixing-layer region around the top of short submerged *** upward and downward movement of flow occurred at the positions located just behind the tall and short vegetation,***,higher streamwise velocities were observed in the upper vegetation layer due to high porosity,with Pr=98%(sparse vegetation,where Pr is the porosity),as compared to those in the lower vegetation layer,which had comparatively low porosity,with Pr=91%(dense vegetation).A rising trend of velocities was found as the flow passed through the vegetation region,followed by a clear sawtooth distribution,as compared to the regions just upstream and downstream of vegetation where the flow was almost *** VDLV flows,a rising trend in the flow resistance was observed with the increase in the initial Froude number,i.e.,Fr?0.67,0.70,and ***,the flow resistance in the case of SLV was relatively very *** numerical results also show the flow structures within the vicinity of short and tall vegetation,which are difficult to attain through experimental measurements.

关键词： Vertically double-layered vegetation Single-layered rigid vegetation Numerical modeling FLUENT Velocity distribution Turbulent flow

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