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Intervention on toll-like receptors in pancreatic cancer

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World Journal of Gastroenterology 2014年第19期20卷 5808-5817页

作者： Juan Vaz Roland Andersson Department of Surgery Clinical Sciences LundSkne University Hospital LundLund UniversitySE-221 85 LundSweden

Pancreatic ductal adenocarcinoma(PDA)is a devastating disease with pronounced morbidity and a high mortality rate.Currently available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success rate.Experimental stimulation of the immune system in murine PDA models has revealed some promising results.tolllike receptors(TLRs)are pillars of the immune system that have been linked to several forms of malignancy,including lung,breast and colon cancer.In humans,TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines,whereas they are not expressed in the normal pancreas.In the present review,we explore the current knowledge concerning the role of different TLRs associated to PDA.Even if almost all known TLRs are expressed in the pancreatic cancer microenvironment,there are only five TLRs suggested as possible therapeutic targets.Most data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as e.***.future adjuvant therapies.The elucidation of the role of TLR3 in PDA is only in its initial phase.The inhibition/blockage of TLR4-related pathways has shown some promising effects,but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic agents.Finally,TLR7 antagonists seem to be potential candidates for therapy.Independent of their potential in immunotherapies,all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.

关键词： Pancreatic cancer Pathophysiological mechanism tol

Helicobacter pylori and serum kynurenine-tryptophan ratio in patients with colorectal cancer

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World Journal of Gastroenterology 2015年第12期21卷 3636-3643页

作者： Ayse Basak Engin Bensu Karahalil Ali Esat Karakaya Atilla Engin Department of Toxicology Faculty of Pharmacy Gazi University Department of General Surgery Faculty of Medicine Gazi University

AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori Ig G seropositivity. Exposure to H. pylori was determined by Ig G seropositivity which was detected by enzyme linked immunoassay(ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased(controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased(controls vs patients; seronegative: 52.85± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls(P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patie

关键词： Colorectal cancer Kynurenine/tryptophan Immune tol

Markers of acute rejection and graft acceptance in liver transplantation

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World Journal of Gastroenterology 2015年第4期21卷 1061-1068页

作者： Giacomo Germani Kryssia Rodriguez-Castro Francesco Paolo Russo Marco Senzolo Alberto Zanetto Alberto Ferrarese Patrizia Burra Multivisceral Transplant Unit Department of SurgeryOncology and GastroenterologyPaduaUniversity Hospital35128 PaduaItaly

The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct posttransplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of theimmunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined.

关键词： Liver transplantation Acute cellular rejection tol

溶藻弧菌转运蛋白tolB的免疫原性与免疫保护性

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生物技术通报 2015年第7期31卷 143-149页

作者：庞欢瑛周泽军张燕飞李静邱明生丁燏简纪常吴灶和广东海洋大学水产学院湛江524088 广东省水产经济动物病原生物学及流行病学重点实验室广东省教育厅水产经济动物病害控制重点实验室湛江524088 仲恺农业工程学院广州510225

旨在研究溶藻弧菌(Vibrio alginolyticus)HY9901转运蛋白tol B作为疫苗候选抗原的可能性,根据已发表的全基因组序列,设计特异性引物PCR扩增tol B的基因全长序列。序列分析显示,该基因(Gen Bank登录号JQ846501)全长1 353 bp,共编码450个... 详细信息

旨在研究溶藻弧菌(Vibrio alginolyticus)HY9901转运蛋白tol B作为疫苗候选抗原的可能性,根据已发表的全基因组序列,设计特异性引物PCR扩增tol B的基因全长序列。序列分析显示,该基因(Gen Bank登录号JQ846501)全长1 353 bp,共编码450个氨基酸残基。BLAST分析发现,溶藻弧菌tol B基因与其他已知弧菌的tol B具有较高的同源性,序列保守,可作为共同抗原候选蛋白。用原核表达的tol B蛋白免疫SPF级小鼠,制备多克隆抗体,ELISA效价达1∶40 000。免疫印迹表明鼠抗tol B血清能与诱导后的重组蛋白发生特异反应。为进一步研究tol B对石斑鱼(Epinephelus awoara)的免疫保护性,用tol B蛋白两次免疫石斑鱼,ELISA检测发现,免疫石斑鱼血清的抗体效价在第4周达到峰值(1∶2 048)。攻毒实验结果表明tol B对石斑鱼的免疫保护率为76%。结果表明,溶藻弧菌转运蛋白tol B具有较好的免疫原性和免疫保护性,可作为弧菌亚单位疫苗的候选抗原。

关键词：溶藻弧菌 tol B基因免疫原性免疫保护

Optimization of clinical outcome of women with previous one lower segment cesarean section

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Open Journal of Obstetrics and Gynecology 2012年第3期2卷 265-269页

作者： Mamdoh Eskandar Jameelah Aboud Majed Alshahrani Mervat Hassanein Azza Alyamani Department of Family and Community Medicine College of Medicine King Khalid University Abha KSA Department of Obstetrics and Gynecology and Reproductive Medicine College of Medicine King Khalid University Abha KSA Department of Obstetrics and Gynecology Abha General Hospital Abha KSA

Background and Objectives: To investigate the outcome in women with planned (VBAC) in comparison to Repeat Cesarean Section (RCS) and to those undergoing vaginal birth. Design and settings: Retrospective study, women with a history of one lower segment cesarean section (LSCS) admitted to Abha General Hospital for delivery from September, 2010 to February, 2011. Subjects and Methods: The demographic maternal and neonatal data and data concerning the course of delivery were reviewed in 418 women underwent trial of labor (tol) and subjected to statistical analysis to study the predictive factors and outcome. All cases were divided into 3 groups, VBAC group (212 women), RCS group (206 women) and the neonates of the VBAC group were compared to those of a control group consists of 287 neonates who delivered vaginally. Results: The success rate of VBAC was 50.72%, with no uterine rupture or wound dehiscence. Failure to progress was the most common (40.2%) indication of RCS followed by fetal distress (29.9%). Young maternal age (P tol, continuous fetal monitoring and, ultrasound evaluation of the previous scar are recommended. Emergency CS should be considered if duration of the tol is prolonged with non reassuring CTG.

关键词： VBAC tol RCS Pregnancy Outcome

复方血竭对结肠炎模型大鼠toll样受体4/核因子κB及树突状细胞表型的影响(英文)

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中国组织工程研究 2015年第5期19卷 752-758页

作者：李楠王雪明稽杨石玉玲王欣李娜苏丽沙丽娜解放军总参谋部总医院(309)消化科北京市100091 解放军总参谋部总医院(309)药剂科北京市100091 解放军总后勤部药品仪器检验所药理室北京市100071

背景:树突状细胞可调节肠道内环境的免疫反应,这一功能缺陷会导致炎症性肠病,toll样受体4/核因子κB通路与上述反应密切相关。目的:构建实验性结肠炎模型大鼠,观察复方血竭对其树突状细胞及toll样受体4/核因子κB表达的影响并探讨其作... 详细信息

背景:树突状细胞可调节肠道内环境的免疫反应,这一功能缺陷会导致炎症性肠病,toll样受体4/核因子κB通路与上述反应密切相关。目的:构建实验性结肠炎模型大鼠,观察复方血竭对其树突状细胞及toll样受体4/核因子κB表达的影响并探讨其作用机制。方法:将大鼠随机抽样法分为空白对照组、模型组、复方血竭组和5-氨基水杨酸治疗组。除空白对照组外,其他3组大鼠建立2,4,6-三硝基苯磺酸诱导的实验性结肠炎模型。造模成功后,复方血竭组和5-氨基水杨酸治疗组分别给予复方血竭[0.75 g/(kg·d)]和5-氨基水杨酸[(100 mg/(kg·d)]灌胃治疗10 d。结果与结论:复方血竭组较模型组大鼠的疾病活动指数评分、大体形态损伤评分、病理组织学评分均显著降低(Ptoll样受体4,核因子κB表达较其他3组均显著升高(Ptoll样受体4及核因子κB表达明显低于5-氨基水杨酸治疗组。结果证实,复方血竭可部分缓解实验性结肠炎模型大鼠的症状,有效抑制其肠系膜淋巴结中树突状细胞的活化。复方血竭可能通过抑制大鼠肠黏膜细胞toll样受体4和核因子κB的表达而缓解肠道的炎症反应。

关键词：实验动物消化系统损伤模型复方血竭 2,4,6-三硝基苯磺酸结肠炎树突状细胞 tol 样受体4 流式细胞仪大鼠免疫组织化学病理北京市自然科学基金

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STYLE NOTEBOOK

明日风尚 2009年第6期 107-109页

作者： Jacqueline Yiu Ron Lam Kiki Feng Nicola Lai

VIKTOR & ROLF版歌剧魅影>02被誉为美国最重要的先锋戏剧艺术家的Robert Wilson执导歌剧《Der Freisch(?)tz》,找来同样先锋的时装设计师组合Viktor&Rolf设计戏服。歌剧中充满着浓郁的超自然神秘色彩,Viktor & Rolf想像力大发,设计了一... 详细信息

VIKTOR & ROLF版歌剧魅影>02被誉为美国最重要的先锋戏剧艺术家的Robert Wilson执导歌剧《Der Freisch(?)tz》,找来同样先锋的时装设计师组合Viktor&Rolf设计戏服。歌剧中充满着浓郁的超自然神秘色彩,Viktor & Rolf想像力大发,设计了一系列色彩斑斓、夸张美妙的戏服。整个设计系列看起来就像是一出连环漫画。

关键词：时装设计师 STYLE NOTEBOOK 就职典礼舞台气氛鞋履 Melissa 剧中人物 tol

toll样受体2、3、4、9在胎盘组织中的表达及其与自发性早产的关系

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浙江医学 2014年第7期36卷 553-556页

作者：黄坚王珏林珍云商宏恺马林卓广超冯国芳张治芬杭州市第一人民医院妇产科 310006 杭州市第一人民医院检验科 310006

目的：探讨tol 样受体（TLRs）2、3、4、9在不同孕期胎盘组织中的表达及其与自发性早产的关系。方法选择自发性早产患者的胎盘样本38份作为早产组（其中孕28-34周和孕35~36周各19份）。选择同期正常妊娠自然分娩产妇的胎盘样本38份（孕3... 详细信息

目的：探讨tol 样受体（TLRs）2、3、4、9在不同孕期胎盘组织中的表达及其与自发性早产的关系。方法选择自发性早产患者的胎盘样本38份作为早产组（其中孕28-34周和孕35~36周各19份）。选择同期正常妊娠自然分娩产妇的胎盘样本38份（孕37-40周）作为对照组。采用real- time PCR法检测两组胎盘中TLR 2、3、4、9 mRNA的表达，并用Western blot法检测胎盘中TLRs 2、3、4、9蛋白的表达，对结果进行统计学分析。结果（1）两组孕产妇胎盘组织中均可检测到TLRs 2、3、4、9的表达。（2）早产组胎盘组织TLR 2、3、9 mRNA的表达均高于对照组，两者间差异有统计学意义（均P＜0.05）；TLR4 mRNA的表达两组间无统计学差异（P＞0.05）。（3）早产组TLR 2、3、4、9的蛋白表达均高于对照组，两者差异均有统计学意义（均P＜0.05）。（4）早产组中，28~34孕周组和35~36孕周组胎盘中TLRs mRNA表达量均无统计学差异（均P＞0.05）。结论早产患者胎盘组织中TLRs过度表达，提示TLRs介导的母胎界面的免疫反应可能是启动自发性早产的重要因素。

关键词： tol 样受体早产免疫反应胎盘

右美托咪啶对老年患者全麻术后炎症因子水平及单核细胞TLR2和TLR4表达的影响

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浙江医学 2016年第15期38卷 1250-1252,1298页

作者：王文伟叶克平王丽姝叶琦刚符新春王华庆台州市第一人民医院麻醉科 318020

目的观察右美托咪啶对老年腹部手术患者围术期炎症因子水平及单核细胞TLR2和TLR4表达的影响。方法选择老年全麻患者91例,采用随机数字表法将患者分为:右美托咪啶组(D组)46例和对照组(C组)45例。两组均常规咪达唑仑、顺苯磺酸阿曲库铵、... 详细信息

目的观察右美托咪啶对老年腹部手术患者围术期炎症因子水平及单核细胞TLR2和TLR4表达的影响。方法选择老年全麻患者91例,采用随机数字表法将患者分为:右美托咪啶组(D组)46例和对照组(C组)45例。两组均常规咪达唑仑、顺苯磺酸阿曲库铵、舒芬太尼、依托咪酯行麻醉诱导,诱导前10min,D组静脉输注右美托咪啶针,负荷量0.5μg/kg,再分别恒速静脉输注右美托咪啶针0.5μg/(kg·h)至术毕前30min;C组采用同样方法静脉输注等容量0.9%氯化钠溶液。记录舒芬太尼、瑞芬太尼和异丙酚用量。于麻醉前(T_0)、手术开始1h(T_1)、手术结束后12h(T_2)及24h(T_3)时各采集右颈内静脉血5ml,采用ELISA测定HMGBl、TNF-α、IL-6水平,并采用流式细胞仪检测单核细胞TLR2和TLR4的表达水平。结果与C组比较,D组瑞芬太尼针和丙泊酚针用量明显减少(P0.05)。与C组比较,D组TNF-α、IL-6和HMGB1水平在T_1、T_2、T_33个时点均明显降低(P<0.05);D组单核细胞TLR2和TLR4的表达水平在T_1、T_2、T_33个时点均明显降低(均P<0.05)。结论右美托咪啶可以降低老年腹部手术患者围术期炎症因子水平及抑制单核细胞TLR2和TLR4表达。

关键词：右美托咪啶老年患者炎症因子 tol 样受体