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New genes emerging for colorectal cancer predisposition

World Journal of Gastroenterology 2014年第8期20卷 1961-1971页

作者： Clara Esteban-Jurado Pilar Garre Maria Vila Juan José Lozano Anna Pristoupilova Sergi Beltrán Anna Abulí Jenifer Muoz Francesc Balaguer Teresa Ocaa an.on. castells Josep M Piqué Angel Carracedo Clara Ruiz-Ponte Xavier Bessa Montserrat Andreu Luis Bujanda Trinidad Caldés Sergi Castellví-Bel Department of Gastroenterology Hospital ClínicCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBEREHD)Institut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)University of Barcelona08036 BarcelonaCataloniaSpain Molecular Oncology Laboratory Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain Bioinformatics platform Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)08036 BarcelonaSpain Centre Nacional d’Anàlisi Genòmica (CNAG) Parc Científic de Barcelona08028 BarcelonaSpain Department of Gastroenterology Hospital del Mar-IMIM (Hospital del Mar Medical Research Centre)Pompeu Fabra University08003 BarcelonaSpain Galician Public Foundation of Genomic Medicine (FPGMX) Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)Genomics Medicine GroupHospital ClínicoSantiago de CompostelaUniversity of Santiago de Compostela15706 GaliciaSpain Center of Excellence in Genomic Medicine Research King Abdulaziz University21589 JeddahKingdom of Saudi Arabia Gastroenterology Department Hospital DonostiaNetworked Biomedical Research Centre for Hepatic and Digestive Diseases (CIBEREHD)Basque Country University20080 San SebastiánSpain

Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed *** cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic *** syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common *** hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic *** can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate *** far,30 common,low-penetrance susceptibility variants have been identified for ***,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease *** using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.

关键词： Colorectal neoplasm, genetic predisposition to disease Next generation sequencing Genotype-phenotype correlation Genetic variant Single nucleotide polymorphism

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不同来源粗饲料对荷斯坦犊牛生长性能及采食行为的影响

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中国畜牧兽医 2013年第2期40卷 150-150页

作者： castells 孙鹏

选用179头荷斯坦公犊牛(体重44.7kg、日龄8.3d)参与3个试验,用以评价不同来源粗饲料对其生长性能、表观消化率和采食行为的影响。在每个试验中,犊牛均被分为3组,对照组(CON)犊牛饲喂开食料,不添加任何粗饲料,其他2个处理组饲喂相同的开... 详细信息

选用179头荷斯坦公犊牛(体重44.7kg、日龄8.3d)参与3个试验,用以评价不同来源粗饲料对其生长性能、表观消化率和采食行为的影响。在每个试验中,犊牛均被分为3组,对照组(CON)犊牛饲喂开食料,不添加任何粗饲料,其他2个处理组饲喂相同的开食料并各添加1种粗饲料:第1个试验中添加切碎的苜蓿(AH)或黑麦干草(RH);第2个试验中添加燕麦干草(OH)或大麦秸秆(BS);第3个试验中添加玉米青贮(CS)或小黑麦青贮(TS)。所有犊牛通过奶瓶饲喂2L代乳料,含量占干物质含量的12.5%,每日饲喂2次,直到日龄第50天。断奶前1周内同样饲喂2L代乳料,含量占干物质含量的12.5%(57d前)。试验在犊牛日龄达到71d时结束,每日记录开食料、代乳料和粗饲料采食量,每周测定犊牛体重。犊牛单圈饲养,且牛床上铺有刨花。结果表明,与对照组相比,添加OH、TS和BS组犊牛开食料采食量升高(0.88vs.1.14、1.17、1.06kg/d),且日增重显著提高(0.72vs.0.93、0.88、0.88kg/d)。饲喂RH、BS、CS和TS组犊牛粗饲料采食量(51g/d)低于AH(120g/d)和OH组(101g/d)。各处理组有机物、干物质和中性洗涤纤维的表观消化率无显著差异(分别为81.5%、81.1%、54.4%)。RH、CS和AH组粗蛋白质的表观消化率高于对照组(80.5%vs.76.4%)。与对照组相比,AH组犊牛开食料采食量下降,躺卧的时间较短,AH和RH组犊牛反刍时间延长,优势比(OR)分别为5.24和5.40,且AH和RH组犊牛进行非营养性口腔行为所耗费的时间较少(OR分别为0.38和0.34)。TS组犊牛在饲喂代乳料和固体饲料后1h内进行非营养性口腔行为的时间有缩短的趋势(OR:0.21)。总之,以自由选择的方式给犊牛供应不同来源的粗饲料可以提高采食量和生长性能,且不影响干物质、有机物、粗蛋白质和中性洗涤纤维的表观消化率;同时,不同来源的粗饲料还可以减少非营养性口腔行为并刺激反刍。

关键词：犊牛粗饲料生长性能

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不同来源粗饲料对荷斯坦犊牛生长性能和摄食行为的影响

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中国畜牧兽医 2012年第9期39卷 194-194页

作者： castells 孙鹏

179头荷斯坦公犊牛(体重44.7kg,日龄8.3d)参与3个试验,用以评价不同来源粗饲料对其生长性能、表观消化率和摄食行为的影响。在每项研究中犊牛均被分为3个不同日粮处理组:对照组(CON)犊牛饲喂开食料,不添加任何粗饲料(这一处理组在3个试... 详细信息

179头荷斯坦公犊牛(体重44.7kg,日龄8.3d)参与3个试验,用以评价不同来源粗饲料对其生长性能、表观消化率和摄食行为的影响。在每项研究中犊牛均被分为3个不同日粮处理组:对照组(CON)犊牛饲喂开食料,不添加任何粗饲料(这一处理组在3个试验中重复使用),其他2个处理组饲喂相同的开食料各添加一种粗饲料:第1个试验中添加切碎的苜蓿(AH)或黑麦干草(RH);第2个试验中添加燕麦干草(OH)或大麦秸秆(BS);第3个试验中添加玉米青贮(CS)或小黑麦青贮(TS)。所有犊牛通过奶瓶饲喂2L代乳料,相当于干物质含量的12.5%,每日饲喂2次,直到50日龄。断奶前1周内同样饲喂2L代乳料,含量占干物质含量的12.5%(57d前)。试验在犊牛日龄达到71d时结束。每日记录开食料、代乳料和粗饲料采食量,每周测定犊牛体重。犊牛单圈饲养,牛床上铺有刨花。与对照组相比,添加OH、TS和BS组犊牛开食料采食量升高(0.88对1.14、1.17、1.06kg/d),且日增重显著提高(0.72对0.93、0.88、0.88kg/d)。饲喂RH、BS、CS和TS组犊牛粗饲料采食量(51g/d)低于AH(120g/d)和OH组(101g/d)。各处理组有机物、干物质和中性洗涤纤维的表观消化率无差异(分别为81.5%、81.1%、54.4%)。RH、CS和AH组粗蛋白的表观消化率高于对照组(80.5%对76.4%)。与对照组相比,AH组犊牛开食料采食量下降,躺卧的时间较短,AH和RH组犊牛反刍时间延长,优势比(OR)分别为5.24和5.40。且AH和RH组犊牛进行非营养性口腔行为所耗费的时间较少(OR分别为0.38、0.34)。TS组犊牛在饲喂代乳料和固体饲料后1h内进行非营养性口腔行为的时间有缩短的趋势(OR:0.21)。总之,以自由选择的方式给犊牛供应不同来源的粗饲料可以提高采食量和生长性能,且不影响干物质、有机物、粗蛋白和中性洗涤纤维的表观消化率。同时,不同来源的粗饲料还可以减少非营养性口腔行为并刺激反刍。

关键词：犊牛粗饲料生长性能

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Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado an.on. castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes Medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

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对遗传性胃肠道息肉综合征患者行小肠部位无线胶囊内镜和钡剂造影检查的一项前瞻性研究

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世界核心医学期刊文摘（胃肠病学分册） 2005年第9期1卷 33-34页

作者： Mata A. Llach J. castells A. 徐瑞 Digestive Endoscopy Unit Gastroenterology Department Hospital Clnic Villarroel 170 08036-Barcelona Catalonia Spain Dr.

Background: Capsule endoscopy has demonstrated its clinical utility in the evaluation of the small bowel, and, accordingly, it has been suggested that it could be useful for the identification of small-intestinal polyps in patients with polyposis syndromes. The objective was to establish the effectiveness of wireless capsule endoscopy for detecting small-bowel polyps in patients with hereditary GI polyposis syndromes in comparison with barium contrast series. Methods: Consecutive patients with GI polyposis syndromes were included. Small-bowel follow-through series and capsule endoscopy were performed within 1 week, in a blind fashion. The number and the location of polyps were analyzed. Results: Twenty-four patients with familial adenomatous polyposis (n = 20) or Peutz-Jeghers syndrome (n = 4) were included. Capsule endoscopy detected small-bowel polyps in 7 of 24 patients (29%), whereas a barium contrast study identified small-intestinal polyps in only 3 of these 7 patients. In the 4 remaining patients, all of them with familial adenomatous polyposis, polyps detected by the capsule but missed in radiographic series were located at either ileum (2 patients), jejunum (1), or duodenum (1). No procedure-related complication was observed in any patient. Conclusions: Wireless capsule endoscopy is a highly accurate technique for the detection of small-bowel polyps in patients with hereditary GI polyposis syndromes, and it represents a valuable alternative to barium contrast series in the surveillance of patients with Peutz-Jeghers syndrome.

关键词：钡剂造影胶囊内镜单盲法性腺瘤队列研究放射影像替代方法临床实用性

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重新思考信息时代:网络社会中的传播

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全球传媒学刊 2022年第5期9卷 3-7页

作者：曼纽尔·卡斯特美国南加利福尼亚大学安纳伯格传播学院美国南加利福尼亚大学传播技术与社会研究中心西班牙巴塞罗那加泰罗尼亚开放大学

本文系国际知名学者曼纽尔·卡斯特(Manuel castells)在IAMCR北京2022年会所发表的主旨演讲的编译。卡斯特重点关注了网络社会中传播的变革及其产生的影响,结合实例从技术变革、组织和制度变革两个层面深入阐述,认为技术变革推动大众传... 详细信息

本文系国际知名学者曼纽尔·卡斯特(Manuel castells)在IAMCR北京2022年会所发表的主旨演讲的编译。卡斯特重点关注了网络社会中传播的变革及其产生的影响,结合实例从技术变革、组织和制度变革两个层面深入阐述,认为技术变革推动大众传播向大众自传播转变,研究者需要适应新的技术现实并采用全局性的视角来展开研究。在理解信息时代的媒体组织和媒体集团时,应当从网络视角来分析他们的商业化、分众化等趋势。

关键词：信息时代网络社会社会变革新型社会结构

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Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

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World Journal of Gastroenterology 2014年第42期20卷 15820-15829页

作者： Xabier García-Albéniz Rosa Gallego Ralf Dieter Hofheinz Gloria Fernández-Esparrach Juan Ramón Ayuso-Colella Josep an.on. Bombí Carles Conill Miriam Cuatrecasas Salvadora Delgado Angels Ginés Rosa Miquel Mario Pagés Estela Pineda Verónica Pereira Aarón Sosa Oscar Reig Iván Victoria Luis Feliz an.on.o María de Lacy an.on. castells Iris Burkholder Andreas Hochhaus Joan Maurel Department of Epidemiology Harvard School of Public Health Department of Medical Oncology Hospital Clínic ICMHO IDIBAPS CIBEREHD University of Barcelona Interdisciplinary Tumor Center Mannheim and Ⅲ Medical Clinic University Hospital Mannheim University of Heidelberg Department of Gastroenterology Endoscopy Unit Hospital Clínic ICMDiM IDIBAPS CIBEREHD University of Barcelona Department of Radiology Hospital Clínic CDI IDIBAPS University of Barcelona Department of Pathology Hospital Clínic IDIBAPS University of Barcelona Department of Radiation Oncology Hospital Clínic ICMHO University of Barcelona Department of Gastrointestinal Surgery Hospital Clínic ICMDiM IDIBAPS CIBEREHD University of Barcelona Department of Gastroenterology Hospital Clínic ICMDiM IDIBAPS CIBEREHD University of Barcelona Department of Nursing and Health University of Applied Sciences of the Saarland Department for Hematology and Oncology Clinic for Internal Medicine Ⅱ Jena University Hospital

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.

关键词： Exercise Follow-up Gastrointestinal diseases Irritable bowel syndrome Physical activity

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空间调味品

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现代装饰（家居） 2015年第6期 58-65页

作者： Pavel Vetro Dmitry Kozinenko Nissa Kinialina Matteo Agati Valenca castells Legchatov Ilya 李薇范嘉苑

如果食物缺少了佐料的辅助,耶将很难成为美食,而这对于＂美食控＂的人来说是一件痛苦的事儿,诸如陈醋、方糖、料酒、辣椒酱这样家庭必备的调味品丰富了食物的味道,给我们带来多种多样的美食休验。而我们居住的空间,它就像一份未加工过... 详细信息

如果食物缺少了佐料的辅助,耶将很难成为美食,而这对于＂美食控＂的人来说是一件痛苦的事儿,诸如陈醋、方糖、料酒、辣椒酱这样家庭必备的调味品丰富了食物的味道,给我们带来多种多样的美食休验。而我们居住的空间,它就像一份未加工过的食物原料,给它添加什么佐料,做成什么样的味道,我们可以根据自己的喜好来设定。灯与墙面的设计在居住空间中可以起到很重要的装饰与调味作用。一盏与众不同的灯具可以让居住空间看起来更有亮点;一个出其不意的墙面设计也可以在美化空间的同时又巧妙地利用空间,成为摆放书籍和小物品的地方。

关键词：居住空间调味品食物原料调味作用利用空间美食辣椒酱佐料

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卡铂超敏反应:一项6h12步35疗程的脱敏方案对妇科恶性肿瘤患者的有效性及肥大细胞/IgE介导过敏反应的机制

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世界核心医学期刊文摘（妇产科学分册） 2005年第3期1卷 48-49页

作者： Lee C.- W. Matulonis U.A. castells M.C. 郭慧方

The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12- step desensitization protocol and to characterizethe immune mechanism of carboplatin HR. We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom continued treatment with carboplatin was considered advantageous. The patients were treated with carboplatin using a 6- h, 12- step desensitization protocol with a 30- min premedication regimen. Skin tests were performed on five patients. Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization. The 6- h, 12- step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen specific mast cell desensitization.

关键词： IgE 妇科恶性肿瘤超敏反应肥大细胞脱敏治疗脱敏作用抗原特异性皮试阳性方案应用

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Rare germline copy number variants in colorectal cancer predisposition characterized by exome sequencing analysis

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Journal of Genetics and Genomics 2018年第1期45卷 41-45页

作者： Sebastia Franch-Exposito Clara Esteban-Jurado Pilar Garre Isabel Quintanilla Saray Duran-Sanchon Marcos Diaz-Gay Laia Bonjoch Miriam Cuatrecasas Esther Samper Jenifer Munoz Teresa Ocana Sabela Carballal Maria Lopez-Ceron an.on. castells Maria Vila-Casadesus Sophia Derdak Steven Laurie Sergi Beltran Jaime carvajal Luis Bujanda Clara Ruiz-Ponte Jordi Camps Meritxell Gironella Juan Jose Lozano Francesc Balaguer Joaquin Cubiella Trinidad Caldes Sergi Castellvi-Bel Gastroenterology Department Hospital Clinic de Barcelona August Pi i Sunyer Biomedical Research Institute CIBER of Hepatic and Digestive Diseases University of Barcelona Barcelona 08036 Spain Molecular Oncology Laboratory Hospital Clinico San Carlos Health Research Institute of the Hospital Clinico San Carlos Madrid 28040 Spain Department of Pathology Hospital Clinic de Barcelona Barcelona 08036 Spain EPICOLON consortium Bioinformatics Platform CIBER of Hepatic and Digestive Diseases Barcelona 08036 Spain National Center of Genomic Analysis Science Park of Barcelona Barcelona 08028 Spain Andalusian Developmental Biology Institute CSIC-Pablo de Olavide University-Andalusian Regional Government SeviUa 41013 Spain Gastroenterology Department Hospital Donostia-Biodonostia Institute CIBER of Hepatic and Digestive Diseases University of the Basque Country (UPV/EHU) San Sebastian 20080 Spain Galician Public Foundation of Genomic Medicine (FPGMX) CIBER of Rare Diseases Genomics Medicine Group Hospital Clinico Universitario University of Santiago de Compostela Santiago de Cornpostela 15706 Spain Castroenterology Department Complexo Hospitalario Universitario de Ourense Ourense Biomedical Research Institute Ourense 32005 Spain

Colorectal cancer （CRC） is one of the most common neoplasms and an important cause of mortality worldwide （http：//globocan. ***]）. Approximately 35% of the variation in CRC susceptibility is likely due to heritable factors （Lichtenstein et al., 2000}. Genetic variations in the human genome include single nucleotide variants （SNVs）, short insertions and deletions, and larger structural variants resulting in gain or loss of genomic DNA larger than 1 kb, such as copy number variants （CNVs）. Leaving aside the importance of CNVs in sporadic tumor development, these variants can also be present in the germline DNA of healthy individuals from the general population and be considered polymorphic.

关键词： WHOLE-EXOME GENE

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