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Colorectal cancer prognosis twenty years later

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World Journal of Gastroenterology 2010年第7期16卷 862-867页

作者： Luis Bujanda Cristina Sarasqueta Elisabeth Hijona Lander Hijona Angel Cosme Ines Gil Jose Luis Elorza Jose I Asensio Santiago Larburu José m Enríquez-Navascués Rodrigo Jover Francesc Balaguer Xavier Llor Xavier Bessa montserrat Andreu Artemio Paya Antoni castells Gastrointestinal Oncology Group of the Spanish Gastroenterological Association Department of Gastroenterology Donostia HospitalUniversity of Basque CountryCentro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas(CIBEREHD)20014 San SebastiánSpain Department of Epidemiology Donostia HospitalCIBERESP20014 San SebastiánSpain Department of Surgery Donostia Hospital20014 San SebastiánSpain Department of Gastroenterology General Hospital Department of Gastroenterology Clinic HospitalCIBEREHDIDIBAPS08036 BarcelonaSpain Digestive Diseases and Nutrition Secion University of IllinoisChicagoIL 60607United States Department of Gastroenterology Del Mar Hospital08003 BarcelonaSpain Department of Gastroenterology General Hospital 03010 AlicanteSpain

AIm:To evaluate changes in colorectal cancer(CRC) survival over the last 20 ***:We compared two groups of consecutive CRC patients that were prospectively recruited:Group Ⅰincluded 1990 patients diagnosed between 1980 and ***Ⅱincluded 871 patients diagnosed in ***:The average follow up time was 21 mo(1-229)for GroupⅠand 50 mo(1-73.4)for GroupⅡ.Overall median survival was significantly longer in Group Ⅱthan in GroupⅠ(73 mo vs 25 mo,Pmor *** surgical mortality was 8% for GroupⅠand 2% for Group Ⅱ(Pmotherapy compared with 50% of GroupⅡpatients(Pms to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality.

关键词： Colon cancer Prognosis Survival Chemotherapy Surgery

New genes emerging for colorectal cancer predisposition

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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 Antoni 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

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 Antoni 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

少数2型糖尿病和肥胖青少年的纤溶酶原激活剂抑制因子-1和组织纤溶酶原激活剂

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世界核心医学期刊文摘（儿科学分册） 2006年第2期2卷 58-59页

作者： Umpaichitra V. Hussain m.m. castells S. 王一飞 Pediatric Endocrinology Department of Pediatrics Brookdale University Hospital and Medical Center One Brookdale Plaza Brooklyn NY 11212 United States Dr.

Increased plasminogen activator inhibitor-1 (PAI-1) and decreased tissue-plasminogen activator (t-PA) activities lead to impaired fibrinolysis, which is critical for cardiovascular disease. We studied these hemostatic factors at fasting state and after an oral fat load in 12 type 2 diabetic and 17 nondiabetic obese adolescents, matched for age, sex, body mass index, and sexual maturation. Plasma PAI-1, t-PA, and glucose as well as serum C-peptide, insulin, total cholesterol, triglyceride, and HDL and LDL cholesterol levels were measured at 0, 2, 4, and 6 h after the fat load. metabolic responses were expressed as the area under the curve (AUC). PAI-1 activities were signifi-cantly greater in patients than in control subjects fasting, 23.4 ± 2.6 versus 12.9 ± 2.0 U/mL (p mL-1 (p mL; p meter that was significantly different in the patients than in the control subjects fasting, 1.5 ± 0.2 versus 0.9 ± 0.1 mm (p mmol· h-1· L-1 (p mated by the homeostasis model assessment was greater in the patients than in the control subjects (14.4 ± 2.8 versus 4.6 ± 0.7; p minished t-PA activities, suggestive of suppressed fibrinolysis, are present in our adolescents with type 2 diabetes; adding another risk factor for cardiovascular disease and acute high fat load does not further negatively affect this suppressed fibrinolysis.

关键词：组织纤溶酶原激活剂 2型糖尿病患者抑制因子-1 尿病肥胖青少年纤溶酶原激活剂抑制因子 PAI-1活性空腹状态血浆C肽心血管疾病

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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钼靶X线假阳性女性患乳腺癌的风险

国际医学放射学杂志 2016年第5期 569-570页

作者： X.castells I.Torá-Rocamora m.Posso m.Román ***-Tomas A.Rodríguez-Arana 栗敏 Departments of Epidemiology and Evaluation IMIM (Hospital del Mar Medical Research Institute)

摘要目的根据钼靶X线假阳性结果的放射学分类评估女性患乳腺癌的风险。材料与方法研究获得伦理委员会批准并免除知情同意书。此项回顾性队列研究共包含了自1994年—2010年部分经西班牙乳腺癌筛查项目并随访至2012年的521 200名女性,年... 详细信息

摘要目的根据钼靶X线假阳性结果的放射学分类评估女性患乳腺癌的风险。材料与方法研究获得伦理委员会批准并免除知情同意书。此项回顾性队列研究共包含了自1994年—2010年部分经西班牙乳腺癌筛查项目并随访至2012年的521 200名女性,年龄50～69岁。采用Cox比例风

关键词：钼靶乳腺癌乳腺肿瘤假阳性女性

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治疗用单克隆抗体的超敏反应:表型和内型

中华临床免疫和变态反应杂志 2018年第5期12卷 583-596页

作者： Ghislaine Annie C.Isabwe marlene Garcia Neuer Leticia de las Vecillas Sanchez Donna-marie Lynch FNP-BC,Kathleen marquis mariana castells 顾建青(翻译) 王良录(审校) 不详中国医学科学院、北京协和医学院、北京协和医院变态(过敏)反应科

背景单克隆抗体的广泛的应用导致了超敏反应(HSRs)发生率的增加,这阻碍了单克隆抗体作为一线治疗方法在临床上的应用。HRSs的症状、诊断方法及定向治疗方法均尚未标准化。目的我们基于临床表型、潜在的内型和生物标志物进行脱敏的治疗... 详细信息

背景单克隆抗体的广泛的应用导致了超敏反应(HSRs)发生率的增加,这阻碍了单克隆抗体作为一线治疗方法在临床上的应用。HRSs的症状、诊断方法及定向治疗方法均尚未标准化。目的我们基于临床表型、潜在的内型和生物标志物进行脱敏的治疗方法提出一种新的基于循证医学的m Ab HSR分类方法。方法描述了104例患者对16种m Abs HSR的表型、内型和生物标志物,并与526次皮下及静脉脱敏治疗结果进行比较。结果初始反应呈现4种模式:Ⅰ型样反应占63%,细胞因子释放反应占13%,混合反应占21%,Ⅳ型迟发反应占3%。与之形成鲜明对比的是,在脱敏治疗期间突发的HSRs为23%,其中52%为细胞因子释放反应,32%为Ⅰ型反应,12%为混合型反应,4%为Ⅰ型伴Ⅳ型迟发超敏反应。58例患者对10种m Abs进行皮肤试验,41%的患者出现阳性。在脱敏治疗期间,1例患者血清类胰蛋白酶水平升高,8例患者IL-6水平升高,均为细胞因子释放表型。结论 m Abs引起的HSRs可界定为Ⅰ型、细胞因子释放型、混合(Ⅰ型/细胞因子释放型)型和Ⅳ型反应,可通过生物标志物如皮肤试验、类胰蛋白酶和IL-6进行鉴别分型。当确诊为m Abs HSR时,这些表型有助于患者接受个性化和精准医学治疗,并为脱敏治疗的实施提供依据。脱敏治疗是一种安全有效的治疗手段,可使出现过变态反应的m Abs仍能作为一线治疗方法。

关键词：单克隆抗体超敏反应表型内型生物标志物类胰蛋白酶白细胞介素-6 皮肤试验脱敏疗法精准医学

不同来源饲草对荷斯坦犊牛生产性能和饲养行为的影响

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饲料博览 2012年第3期22卷 36-36页

作者： castells L L Bach A Araujo G montoro C Terré m 张树金不详

采用公荷斯坦犊牛(44.7 kg、8.3 d)179头进行3个系列试验,旨在评估不同饲草来源对犊牛生产性能、表观消化率和饲养行为的影响。在每个试验中,犊牛随机分配给3个不同的日粮处理:对照组(CON组)犊牛饲喂开食料,不提供饲草(3个试验对照组相... 详细信息

采用公荷斯坦犊牛(44.7 kg、8.3 d)179头进行3个系列试验,旨在评估不同饲草来源对犊牛生产性能、表观消化率和饲养行为的影响。在每个试验中,犊牛随机分配给3个不同的日粮处理:对照组(CON组)犊牛饲喂开食料,不提供饲草(3个试验对照组相同),其他两个处理由同样的开食料和饲草组成:第1个试验,铡碎苜蓿(AH组)和黑麦草干草(RH组);第2个试验,铡碎燕麦草(OH组)和铡碎大麦秸(BS);第3个试验,玉米青贮(CS组)和黑小麦(TS组)。所有犊牛通过饲喂12.5%干物质代乳品2 L直到50日龄;断奶前(57日龄)1周,饲喂12.5%干物质代乳品2 L。试验至犊牛71日龄。每天记录开食料、代乳品和饲草采食量,每周测定犊牛的体重。犊牛单独关养,用木屑作垫料。结果表明,与对照组相比,获得OH、TS和BS的犊牛采食较多的开食料(分别为0.88,1.14、1.17、1.06 kg.d-1)和较高的平均日增重(分别为0.72,0.93、0.88、0.88 kg.d-1)。RH、BS、CS和TS组犊牛比AH组犊牛(120 g.d-1)和OH组犊牛(101 g.d-1)采食较少的饲草(51 g.d-1)。处理之间的有机物、干物质和中性洗涤纤维表观消化率无显著差异(分别为81.5、81.1和54.4%)。RH组、CS组和AH组的粗蛋白表观消化率比CON组大(分别为80.5、76.4%)。饲喂代乳品和固体饲料1 h后,与CON组犊牛相比,AH组犊牛采食开食料和躺卧时间较少,AH组和RH组犊牛反刍时间较长,比值分别为5.24和5.40。AH组和RH组犊牛作出非营养性口唇行为的时间较少(OR分别为0.38和0.34),TS组犊牛作出非营养性行为的时间趋于较少(OR为0.21)。结果表明,犊牛自由选择饲草来源可改善其采食量和生产性能,而不会影响干物质、有机物、粗蛋白质、中性洗涤纤维的消化率,并且依据饲草来源,减少非营养性口唇行为,促进反刍。

关键词：犊牛饲草生产性能

紫杉醇和多西紫杉醇超敏反应的快速脱敏疗法:一种成功应用于77例患者的新标准方案

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世界核心医学期刊文摘（妇产科学分册） 2005年第7期1卷 44-44页

作者： Feldweg A.m. Lee C.- W. matulonis U.A. castells m. 刘秀娟 Department of medicine Brigham and Women' s Hospital Harvard Medical School 1 Jimmy Fund Way Boston MA 02115 United States

Objective. Administration of paclitaxel is associated with hypersensitivity reactions (HSRs) in up to 9% of patients despite premedication. The purpose of this study was to evaluate the effectiveness of a standardized desensitization protocol in patients with HSRs to taxanes, based on our experience with carboplatin desensitization. methods. We analyzed seventeen consecutive patients with documented HSRs to taxanes who required continued treatment with a taxane agent. The patients were treated with either paclitaxel or docetaxel using the 6- to 7- h standard desensitization protocol. Results. Seventeen patients who previously had severe taxane HSRs successfully completed 77 planned cycles of desensitization to paclitaxel or docetaxel, 72 of which were without reactions. Four patients developed HSRs during the desensitization protocol that were much less severe than their original HSRs and tolerated the re- administration of infusions without further reactions. Of these four patients, the first had palmar erythema 8 h after her 1st desensitization. The second patient had mild abdominal pain during her 1st cycle, and the third patient developed mild chest burning during her 2nd and 4th cycles. These three patients also completed subsequent desensitization cycles without reactions. The fourth patient developed a delayed urticaria reaction and gastrointestinal symptoms 6 h after completing her 1st desensitization. She elected to be treated with an alternative chemotherapy and did not receive additional courses of desensitization. Conclusion. The rapid standard desensitization protocol provides a safe and effective strategy for the re- administration of paclitaxel or docetaxel even after severe HSRs.

关键词：快速脱敏超敏反应药物过敏过敏患者脱敏治疗紫杉烷类化学疗法掌红斑肠道症状应用标准