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Role of cetuximab in first-line treatment of metastatic colorectal cancer

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World Journal of Gastroenterology 2014年第15期20卷 4208-4219页

作者： Miguel Jhonatan Sotelo Beatriz García-Paredes carlos aguado Javier Sastre Eduardo Díaz-Rubio Center affiliate to the "Red Temática de Investigación Cooperativa (RD12/0036/006)" Instituto Carlos ⅢSpanish Ministry of Economy and Competitivity. Oncology DepartmentHospital Clínico San Carlos28040 MadridSpain Department of Medicine School of MedicineUniversidad Complutense de Madrid28040 MadridSpain

The treatment of metastatic colorectal cancer(mCRC)has evolved considerably in the last decade,currently allowing most mCRC patients to live more than two *** antibodies targeting the epidermal growth factor receptor(EGFR)and vascular endothelial growth factor play an important role in the current treatment of these ***,only antibodies directed against EGFR have a predictive marker of response,which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS).Cetuximab has been shown to be effective in patients with KRAS wild-type *** CRYSTAL study showed that adding cetuximab to FOLFIRI(regimen of irinotecan,infusional fluorouracil and leucovorin)significantly improved results in the first-line treatment of KRAS wildtype ***,results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are *** the other hand,recent advances in the management of colorectal liver metastases have improved survival in these *** cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of *** this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.

关键词： Cetuximab First-line Metastatic colorectal cancer Colorectal liver metastases Elderly patients

Neoadjuvant immunotherapy in non-small-cell lung cancer:Times are changing—and fast

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World Journal of Clinical Oncology 2022年第9期13卷 758-761页

作者： carlos aguado Unai Jiménez Maestre Xabier Mielgo-Rubio Department of Medical Oncology Hospital Universitario Clínico San CarlosMadrid 28040Spain Department of Thoracic Surgery Hospital Universitario CrucesBarakaldo 48903BizkaiaSpain Department of Medical Oncology Hospital Universitario Fundación AlcorcónAlcorcón 28922MadridSpain

Recent data from a phase 3 trial have shown that the addition of immunotherapy to neoadjuvant chemotherapy improves event-free survival in patients with nonsmall-cell lung cancer(NSCLC).This is the first positive phase 3 trial in this setting,although several phase 3 trials are currently investigating the efficacy of neoadjuvant and adjuvant immunotherapy in resectable NSCLC.

关键词： Neoadjuvant Immunotherapy NSCLC Perioperative Checkmate-816 nivolumab Chemo-immunotherapy

Neoadjuvant treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

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World Journal of Clinical Oncology 2022年第5期13卷 314-322页

作者： carlos aguado Luis Chara Mónica Antonanzas Jose Maria Matilla Gonzalez Unai Jiménez Raul Hernanz Xabier Mielgo-Rubio Juan carlos Trujillo-Reyes Felipe Counago Department of Medical Oncology Hospital Clínico Universitario San CarlosMadrid 28040Spain Department of Medical Oncology Hospital Universitario de GuadalajaraGuadalajara 19002Spain Department of Thoracic Surgery Hospital Clínico Universitario de ValladolidValladolid 47005Spain Department of Thoracic Surgery Hospital Universitario CrucesBarakaldoBizkaia 48903Basque CountrySpain Department of Radiation Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Medical Oncology Hospital Universitario Fundación AlcorcónAlcorcón 28922MadridSpain Department of Thoracic Surgery Hospital de la Santa Creu I Sant PauBarcelona 08029CataloniaSpain Department of Surgery Universitat Autonoma de BarcelonaBarcelona 08029CataloniaSpain Department of Radiation Oncology Hospital Universitario Quirónsalud MadridPozuelo de Alarcón 28223MadridSpain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Medicine Department School of Biomedical SciencesUniversidad Europea de MadridVillaviciosa de Odón 28670MadridSpain

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical *** chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable *** with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional *** immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term ***,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative ***,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival *** we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

关键词： Non-small cell lung cancer Neoadjuvant Immune checkpoint inhibitors Immunotherapy Anti-PD1 Anti-PD-L1 Complete pathological response

Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

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Cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce Rosa Alvarez Maria Eugenia Olmedo Sandra Falagan Xabier Mielgo Fatima Navarro Patricia Cruz Luis Cabezon-Gutierrez carlos aguado Gonzalo Colmenarejo Marta Munoz-Fernandez de Leglaria Ana Belen Enguita Maria Cebollero Amparo Benito Isabel Alemany Carolina del Castillo Ricardo Ramos Ana Ramirez de Molina Enrique Casado Maria Sereno Ana Ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y Cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain Clinico San carlos University Hospital Madrid 28040Spain Parque Cientifico de Madrid Foundation Madrid 28049Spain

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with *** are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the *** this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular ***:In the first step,we conducted a clinical-pathological characterization of the ***,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the ***:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of *** obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)***,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

Deep diving in the PACIFIC:Practical issues in stage III non-small cell lung cancer to avoid shipwreck

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World Journal of Clinical Oncology 2020年第11期11卷 898-917,I0003页

作者： Xabier Mielgo-Rubio Federico Rojo Laura Mezquita-Pérez Francesc Casas Amadeo Wals Manel Juan carlos aguado Javier Garde-Noguera David Vicente Felipe Couñago Department of Medical Oncology Hospital Universitario Fundación AlcorcónMadrid 28922Spain Department of Pathology IIS-Jiménez Díaz-CIBERONC FoundationMadrid 28040Spain Department of Medical Oncology Hospital ClinicLaboratory of Translational Genomics and Targeted Therapeutics in Solid TumorsIDIBAPSBarcelona 08036Spain Department of Radiation Oncology Hospital ClinicBarcelona 08036Spain Department of Radiation Oncology Hospital Universitario Virgen MacarenaSevilla 41009Spain Department of Immunology Service Hospital ClínicUniversitat de BarcelonaBarcelona 08036Spain Department of Medical Oncology Hospital Universitario Clínico San CarlosMadrid 28040Spain Department of Medical Oncology Hospital Universitario Virgen MacarenaSevilla 49001Spain Department of Radiation Oncology Hospital Universitario Quirónsalud MadridHospital La LuzUniversidad Europea de MadridMadrid 28028Spain

After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III *** is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of *** integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work *** aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC *** evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 *** addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical ***,we discuss unresolved questions and future *** short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

关键词： Durvalumab Non-small cell lung cancer PACIFIC Immunotherapy Immune checkpoint inhibitors Anti-programmed cell death ligand 1 Consolidation therapy Unresectable stage III lung cancer

Species and Plant Community Reorganization in the Trans-Mexican Volcanic Belt under Climate Change Conditions

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Journal of Mountain Science 2013年第6期10卷 923-931页

作者： VILLERS-RUIZ Lourdes CASTAEDA-aguado Diana Center of Atmospheric Sciences National Autonomous University of Mexico (UNAM) School of Science Biology Department National Autonomous University of Mexico (UNAM)

This study analyzes six vegetation communities in relation to current climatic parameters and eight climate change scenarios along an elevation gradient extending from 2,710 m to 4,210 m in the Trans-Mexican Volcanic Belt. The projected movements of 25 plant species with the current restricted or wide altitudinal distributions were also modeled. To relate climatic parameters to the species and communities, a Precipitation/Temperature （P/T） index was used both for the current and the different climate-change scenarios. The temperatures are expected to increase by 1.1℃ to 1.7℃ by 2020 and by 2℃ to 3℃ by 2o5o. A decrease of 4% to 13% in the annual precipitation is expected for the 2020 horizon, and a reduction between 3% and 20% is expected for 2050. The reductions in water availability were projected for all altitude levels and plant communities. The most marked reduction was under the HADLEY- A2 scenario, in which the lower limit of the altitudinal range increased from 2,71o to 3,31o m （2050 horizon） with reductions in the P/T index between 36% and 39% compared to the current climate. Most plant species tended to shift their distribution from 20o to 300 m upward in the 2020 temporal horizon scenarios. The Pinus hartwegii, Alnus jorullensis and Pinus montezumae communities would have a shorter altitudinal range as they move upward and merge with the remaining species at the higher altitudinal range. For the 2o5o temporal horizon, 3o% of the species, primarily those from the higher altitudinal range, would disappear because their P/Tindex values would be above the limit of plant survival （〉4,210 m）.

关键词： Forest communities Climate change Upward movement Natural protected areas

Alpha7 nicotinic receptors as potential theranostic targets for experimental stroke

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Neural Regeneration Research 2024年第5期19卷 939-940页

作者： Maider Garbizu Laura aguado Abraham Martín Achucarro Basque Center for Neuroscience LeioaSpain CIC biomaGUNE Basque Research and Technology AllianceSan SebastianSpain Ikerbasque Basque Foundation for Science BilbaoSpain

Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen ***,this inflammatory response is limited by rapid,localized,and adaptive anti-inflammatory responses which are crucial for maintaining ***,the loss of these responses converts a limited and protective inflammatory response into an excessive and harmful ***-inflammatory responses are integrated into the central nervous system,since the central nervous system accumulates information about harmful events,activates defenses,and builds memory for *** the same time,it has been demonstrated that hypothalamic neuronal signaling can be altered by inflammation in peripheral ***,immune cells release neuropeptides and neurotransmitters such as acetylcholine(ACh),the main neurotransmitter of the parasympathetic autonomic nervous system,evidencing the communication between the immune and nervous systems(Tracey,2002).

关键词： protective invasion Alpha

Elutriation, attrition and segregation in a conical spouted bed with a fountain confiner

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Particuology 2020年第4期18卷 35-44页

作者： Aitor Pablos Roberto aguado Jorge Vicente Mikel Tellabide Javier Bilbao Martin Olazar Department of Chemical Engineering University of the Basque Country UPV/EHUP.O.Box 644E48080 BilbaoSpain Novattia Desarrollos Ltd.Scientific and Technologic Park of BizkaiaAstondo BideaBuilding 612E48160 DerioSpain

This study examined elutriation,attrition,and segregation in a conical spouted bed with a fountain confiner and incorporating an open sided draft *** silica sand with a wide particle size distribution was employed as a model material,operating in both the batch and continuous *** use of a fountain confiner is crucial when operating with fine particles,because otherwise the bed rapidly exhibits significant *** extent of attrition was quantified using a tracing technique based on differently-coloured sand fractions as well as monitoring size distributions by *** breakage was found to be the primary attrition mechanism,and the fountain confiner was determined to limit the elutriation of fine particles resulting from ***,only a small fraction of the finest particles were entrained from the *** incorporation of a confiner increased operational stability while reducing segregation,especially in the upper half of the bed where the majority of segregation typically ***,the bed was perfectly mixed apart from very minimal segregation close to the wall and at the bottom of the *** results provide a basis for the design and operation of larger scale equipment for the continuous drying of materials.

关键词： Spouted bed Fine sand Elutriation Attrition Segregation Fountain confinement device

Selective intestinal decontamination for the prevention of early bacterial infections after liver transplantation

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World Journal of Gastroenterology 2016年第26期22卷 5950-5957页

作者： Elena Resino Rafael San-Juan Jose Maria aguado Unit of Infectious Diseases 12 de Octubre University Hospital

Bacterial infection in the first month after liver transplantation is a frequent complication that poses a serious risk for liver transplant recipients as contributes substantially to increased length of hospitalization and hospital costs being a leading cause of death in this period. Most of these infections are caused by gramnegative bacilli, although gram-positive infections, especially Enterococcus sp. constitute an emerging infectious problem. This high rate of early postoperative infections after liver transplant has generated interest in exploring various prophylactic approaches to surmount this problem. One of these approaches is selective intestinal decontamination(SID). SID is a prophylactic strategy that consists of the administration of antimicrobials with limited anaerobicidal activity in order to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract and so prevent infections caused by these organisms. The majority of studies carried out to date have found SID to be effective in the reduction of gram-negative infection, but the effect on overall infection is limited due to a higher number of infection episodes by pathogenic enterococci and coagulase-negative staphylococci. However, difficulties in general extrapolation of the favorable results obtained in specific studies together with the potential risk of selection of multirresistant microorganisms has conditioned controversy about the routinely application of these strategies in liver transplant recipients.

关键词： Selective intestinal decontamination Liver transplant Infection Gram-negative bacterial infection Gram-positive bacterial infection Multirresistant