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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 chemotherapy.There are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the literature.In this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization.Methods:In the first step,we conducted a clinical-pathological characterization of the patients.Afterwards,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 samples.Results:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of 0-1.We 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)families.Finally,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

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Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

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World Journal of Methodology 2024年第2期14卷 107-126页

作者： Jacobo Trébol Ana Carabias-Orgaz María Carmen Esteban-Velasco Asunción García-Plaza Juan Ignacio González-munoz Ana Belén Sánchez-Casado Felipe Carlos Parreno-Manchado marta Eguía-Larrea José Antonio Alcázar-Montero Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain Cirugía Universidad de SalamancaSalamanca 37007SalamancaSpain Oftalmología Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50

关键词： COVID-19 SARS-CoV-2 Colon cancer Rectal cancer Breast cancer Liver cancer Pancreatic cancer Gastric cancer Oesophageal cancer Surgery

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Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study

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World Journal of Gastroenterology 2016年第47期22卷 10432-10439页

作者： marta Maia Bosca-Watts Xavier Cortes Marisa Iborra Jose Maria Huguet Laura Sempere Gloria Garcia Rafa Gil Mari Fe Garcia Marga munoz Pedro Almela Nuria Maroto Jose Maria Paredes Inflammatory Bowel Disease Unit Digestive Disease DepartmentUniversity of ValenciaUniversity Clinic Hospital of Valencia46010 ValenceiaSpain Digestive Disease department Hospital of Sagunto46010 ValenciaSpain Gastroenterology department and CIBEREHD Hospital Universitari i Politecnic La Fe46026 ValenciaSpain Digestive Disease department General Hospital of Valencia46014 ValenciaSpain Digestive Disease department General Hospital of Alicante03010 AlacantSpain Digestive Disease department San Juan University Hospital of Alicante46015 ValenciaSpain Digestive Disease department Arnau Hospital of Valencia Digestive Disease department General University Hospital of Elche03203 AlicaneSpain Digestive Disease department General Hospital of Castellon12004 Castellón de la PlanaSpain Digestive Disease department Hospital of Manises46940 ManisesSpain Digestive Disease department Peset University Hospital of Valencia46017 ValenciaSpain

AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis(UC) and to identify predictors of response.METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at wk 0 and 14 with the physician's global clinical assessment(PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database.RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC(E2) and 70% had extensive UC(E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor(TNF) treatment na?ve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at wk 14(a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at wk 14. Being anti-TNF treatment na?ve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of followup. Only three adverse effects(AEs) were observed during the study; all were mild and golimumab was not interrupted.CONCLUSION This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.

关键词： Golimumab Ulcerative 大肠炎真实结果

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局部麻醉剂引起的眼压改变(英文)

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国际眼科杂志 2006年第6期6卷 1255-1257页

作者： Javier A Montero Jose M Ruiz-Moreno marta fernandez-munoz M.Isabel Rodriguez-Palacios 西班牙Alicante眼科研究所视网膜科西班牙Valladolid Pio del Rio Hortega医院视网膜科

目的:确定局麻药,年龄和角膜中央厚度对非接触眼压计眼压测量值的影响。方法:记录47例93眼滴局麻药前后角膜中央厚度和非接触眼压计眼压测量值。结果:在47例中女31例,男16例;平均年龄66.4岁(标准差16,范围34～88岁);平均基础眼压16.0mm... 详细信息

目的:确定局麻药,年龄和角膜中央厚度对非接触眼压计眼压测量值的影响。方法:记录47例93眼滴局麻药前后角膜中央厚度和非接触眼压计眼压测量值。结果:在47例中女31例,男16例;平均年龄66.4岁(标准差16,范围34～88岁);平均基础眼压16.0mmHg(标准差4.0,范围8.5～26.1mmHg)。滴局麻药后1min平均眼压16.0mmHg(标准差3.8,范围7.7～26.7mmHg),5min平均眼压14.9mmHg(标准差3.9,范围7.6～26.3)。0～1min(P=0.0007)和0～5min(P=0.0003)的数值差异有统计学意义,1～5min(P=0.27)的数值差异无统计学意义(配对资料t检验)。滴局麻药前的平均角膜中央厚度为565.4μm。直线回归分析认为年龄和眼压之间以及角膜中央厚度和眼压之间无直线关系。结论:我们的研究证实,滴局麻药后前5min内引起的眼压降低是进行性的,降低值与角膜中央厚度和年龄无关。

关键词：眼内压局麻剂年龄角膜中央厚度

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Mesenchymal stromal cell therapy for damaged retinal ganglion cells, is gold all that glitters?

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Neural Regeneration Research 2019年第11期14卷 1851-1857页

作者： Fernando Lucas-Ruiz Caridad Galindo-Romero David García-Bernal María Norte-munoz Kristy T. Rodríguez-Ramírez Manuel Salinas-Navarro Jose E. Millán-Rivero Manuel Vidal-Sanz marta Agudo-Barriuso Grupo de Oftalmologia Experimental Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain department of Talmologia Universidad de MurciaMurciaSpain Unidad de Terapia Celular y Trasplante Hematopoyetico Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain department of Medicina Interna Universidad de MurciaMurciaSpain

Mesenchymal stromal cells are an excellent source of stem cells because they are isolated from adult tissues or perinatal derivatives, avoiding the ethical concerns that encumber embryonic stem cells. In preclinical models, it has been shown that mesenchymal stromal cells have neuroprotective and immunomodulatory properties, both of which are ideal for central nervous system treatment and repair. Here we will review the current literature on mesenchymal stromal cells, focusing on bone marrow mesenchymal stromal cells, adipose-derived mesenchymal stromal cells and mesenchymal stromal cells from the umbilical cord stroma, i.e.,Wharton’s jelly mesenchymal stromal cells. Finally, we will discuss the use of these cells to alleviate retinal ganglion cell degeneration following axonal trauma.

关键词： stem cells adipose stem cells umbilical cord bone marrow Wharton's jelly optic nerve axotomy neuroprotection

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Washback of an Oral Assessment System in the EFL Classroom

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英语考试研究 2011年第5期 50-59页

作者： Ana P. munoz marta E. Alvarez

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S-adenosyl-L-methionine modifies antioxidant-enzymes,glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells

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World Journal of Gastroenterology 2016年第14期22卷 3746-3757页

作者： Sonia Amelia Lozano-Sepulveda Eduardo Bautista-Osorio Jose Angel Merino-Mascorro marta Varela-Rey Linda Elsa munoz-Espinosa Paula Cordero-Perez María Luz Martinez-Chantar Ana Maria Rivas-Estilla department of Biochemistry and Molecular Medicine School of Medicine Autonomous University of Nuevo Leon Monterrey Metabolomic Unit CIC bio GUNE CIBERehd Parque Tecnológico de Bizkaia Liver Unit School of Medicine and Hospital Universitario Autonomous University of Nuevo Leon

AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5 A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROS) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent.RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon SAM treatment at both the transcriptional and translational lev

关键词： Hepatitis C virus S-adenosyl-L-methionine Superoxide dismutase 1 Superoxide dismutase 2 Replication Hepatitis C virus-RNA NS5A Oxidative stress Antioxidants Viral proteins Reactive oxygen species Pyrrolidine dithiocarbamate

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胸腰段脊柱骨折定量影像学

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临床与病理杂志 2017年第4期37卷 649-660页

作者： Fernando Ruiz Santiago Pablo Tomas munoz Elena Moya Sanchez marta Revelles Paniza Alberto Martinez Martinez Antonio Luis Perez Abela Radiology department Hospital of TraumatologyCarretera de Jaen SNGranada 18014Spain Radiology department Ciudad Sanitaria Virgen de las NievesHospital Complex University of GranadaAvenida de las Fuerzas Armadas 2Granada 18014Spain Traumatology department Hospital of TraumatologyCarretera de Jaen SNGranada 18014Spain 温州医科大学附属第二医院育英儿童医院骨科医院脊柱外科浙江省脊柱外科中心浙江省骨科学重点实验室

描述影响胸腰段脊柱不同类型骨折,以及指导脊柱骨折治疗的不同分类及关键影响因素。目前脊柱骨折分类以denis三柱模型为基石,包括压缩性骨折、爆裂性骨折、屈曲牵张骨折和骨折伴脱位。骨折分类系统包括胸腰椎损伤分类和严重程度评分(Tho... 详细信息

描述影响胸腰段脊柱不同类型骨折,以及指导脊柱骨折治疗的不同分类及关键影响因素。目前脊柱骨折分类以denis三柱模型为基石,包括压缩性骨折、爆裂性骨折、屈曲牵张骨折和骨折伴脱位。骨折分类系统包括胸腰椎损伤分类和严重程度评分(Thoracolumbar Injury Classification and Severity Score,TLICS)系统和AO脊柱胸腰椎损伤分类和严重程度评分(AOSpine-TLICS)。正确分类需要定量成像方法,采用多个测量指标来评定其属于不同TLICS或AOSpine-TLICS类型。如果TLICS评分>4或者AOSpine-TLICS评分>5,则患者需要手术治疗。本文重点描述X线片、CT及MRI影像表现和测量参数,包括爆裂性骨折患者中椎体楔形变成角和压缩性骨折椎体高度丢失百分比、椎弓根间距和腰椎管狭窄程度以及一些严重骨折(如屈曲牵张骨折、骨折伴脱位)患者的椎体位移和棘突间距增加。通过图解和影像案例展现这些影像学特征和相关参数。

关键词：脊柱骨折胸腰椎创伤脊柱损伤普通X线片成像计算机断层扫描

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PKR and PP1C Polymorphisms in Alzheimer’s Disease Risk

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Neuroscience & Medicine 2011年第3期2卷 226-231页

作者： Ernest Palomer Gerard ILL-Raga marta Tajes Eva Ramos-Fernández Mònica Bosch-Morató Biuse Guivernau Jose J.Galan Jordi Clarimon Carmen Antunez Merce Boada Luis M.Real César Fandos Francisco J.munoz Laboratory of Molecular Physiology and Channelopathies Department of Experimental and Health SciencesPompeu Fabra University(UPF)BarcelonaSpain NeoCodex SevillaSpain Alzheimer Laboratory Neurology DepartmentSanta Creu and Sant Pau HospitalBiomedical Research Center on Neurodegenerative Diseases(CIBERNED)BarcelonaSpain Fundacion Alzheimur Dementia UnitVirgen de la Arrixaca HospitalMurciaSpain Memory Clinic of ACE Foundation Catalan Institute of Applied NeurosciencesBarcelonaSpain Neurology department Vall d’Hebron Universitary HospitalBarcelonaSpain

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by senile plaques and neurofibrillary tangles. Senile plaques are deposits of amyloid ?-peptide (A?) produced by the cleavage of a transmembrane protein termed Amyloid Precursor Protein (APP). The amyloidogenic cleavage of APP is performed by γ-secretase complex and ?-site APP cleaving enzyme 1 (BACE1), a key enzyme in AD that can be activated by different noxious stimuli. Interestingly, some viruses could activate double-stranded RNA-activated protein kinase (PKR), which phosphorylates Eukaryotic Initiation Factor 2 alpha (eIF2α). This phosphorylation stops global translation to avoid any synthesis of viral infective proteins, but paradoxically up-regulates BACE1 translation. One of the viral mechanisms to circumvent eIF2α phosphorylation is the recruitment of protein phosphatase 1 (PP1), to fully dephosphorylate eIF2α and allow viral protein synthesis. Due to the functional relationship between BACE1, PKR, PP1 and AD we have performed a large (1122 cases and 1191 control individuals) case-control genetic analysis using two biallelic polymorphisms rs2254958 and rs7480390, located within the genes coding for PKR and the catalytic unit A of PP1, respectively. Although a trend to association of the rs2254958 TT genotype with AD risk was found, our results show that neither rs7480390 nor rs2254958 are associated with AD susceptibility.

关键词： Alzheimer’s Disease BACE1 PKR PP1 eIF2α

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