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Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid-and long-term prediction of hepatocellular carcinoma among cirrhotic patients

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World Journal of Gastroenterology 2021年第48期27卷 8343-8356页

作者： Antonio Gil-Gómez Ángela Rojas Chang-Hai Liu rocio Gallego-Duran rocio Muñoz-Hernandez Giorgio Fassina Patrizia Pontisso Javier Ampuero Manuel Romero-Gómez SeLiver Group Institute of Biomedicine of SevilleSeville 41013Spain CIBERehd Instituto de Salud Carlos IIIMadrid 28029Spain Mucosal Immunity Lab IRCCS Humanitas Research HospitalMilan 20089Italy Center of Infectious Diseases West China Hospital of Sichuan UniversityChengdu 610017Sichuan ProvinceChina State Key Laboratory of Biotherapy and Center of Infectious Diseases West China HospitalChengdu 610017Sichuan ProvinceChina Life Biotechnology Padua UniversityVenice 30175Italy Department of Clinical and Experimental Medicine University of PadovaPadova 35123Italy UCM Digestive Diseases Virgen del Rocío University HospitalSeville 41014Spain

BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine *** To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of *** Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver *** estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at *** were followed-up for 60 mo,being censored at the time of the appearance of *** There were 10.8%and 23.1%of HCC development at two-and five-years *** with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear *** multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year *** We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,esp

关键词： Squamous cell carcinoma antigen Hepatocellular carcinoma prediction Precision medicine Stratification of cirrhotic patient

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Solid Tumor Inhibitory and other Constituents of Casimiroa tetrameria

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中国天然药物 2011年第5期9卷 334-337页

作者： XU Ya-Ming maria del C. Ramirez-Ahumada Frederick A. Valenote A. A. Leslie Gunatilaka Southwest Center for Natural Products Research and Commercialization School of Natural Resources and the Environment The University of Arizona 250 E Valencia Road Tucson Arizona 85706-6800 USA Division of Hematology & Oncology Henry Ford Hospital Detroit Michigan 48202 USA

AIM:To isolate and characterize solid tumor inhibitory and other constituents from a bioactive extract of Casimiroa tetrameria((Rutaceae).METHODS:A crude extract of *** obtained from the US National Cancer Institute Natural Product Repository and found to exhibit selective toxicity to solid tumor cells was subjected bioactivity-guided fractionation involving solvent-solvent partitioning,gel filtration,and *** structures of all isolated compounds were elucidated by spectroscopic analysis(NMR and MS) and/or by comparison with the reported *** 1 and 4-9 were evaluated for their solid tumor selective ***:Nine metabolites,including a new furanocoumarin,5-methoxy-8-(4'-acetoxy-3'-methylbut-2-eny-loxy)-psoralen(1),and the previously known compounds 2-9 were *** these the flavonoid zapotin(6),and N-benzoyltyramide derivatives 7 and 8 were found to be the active ***:Zapotin(6) is the most potent constituent of *** with solid tumor selectivity.

关键词： Casimiroa tetrameria Rutaceae Solid tumor selectivity Flavonoids Zapotin Furanocoumarins N-benzoyltyramides

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Expression of HER2 and bradykinin B_1 receptors in precursor lesions of gallbladder carcinoma

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World Journal of Gastroenterology 2012年第11期18卷 1208-1215页

作者： Cesar Toledo Carola E Matus Ximena Barraza Pamela Arroyo Pamela Ehrenfeld Carlos D Figueroa Kanti D Bhoola Maeva del Pozo maria T Poblete Laboratorio de Patologia Celular Instituto de AnatomiaHistologia y PatologiaUniversidad Austral de ChileValdivia Box 567Chile Servicio de Anatomia Patologica Hospital Base Lung Institute of Western AustraliaCentre for Asthma and Allergy Research InstituteUniversity of Western Australia

AIM:To determine the expression of HER2 and bradykinin B 1 receptors(B 1 R) in the two pathogenic models of gallbladder cancer:the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma ***:Receptor proteins were visualized by immunohistochemistry on 5-μm sections of paraffin-embedded *** of both receptors was studied in biopsy samples from 92 patients(6 males and 86 females;age ranging from 28 to 86 years,mean 56 years).High HER2 expression in specimens was additionally investigated by fluorescence in situ *** proliferation in each sample was assessed by using the Ki-67 proliferation ***:HER2 receptor protein was absent in adenomas and in normal gallbladder *** the contrary,there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia(22/24;91.7%) and carcinoma in situ(9/10;90%),the lesions that displayed a significantly high proliferation *** up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification.A similar result was observed in invasive carcinomas(0/12).The B 1 R distribution pattern mirrored that of HER2 except that B 1 R was additionally observed in the *** B 1 R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia(24/24;100%) and carcinoma in situ(10/10;100%) and in the epithelial cells of *** contrast,both HER2(4/12;33%) and B 1 R(1/12;8.3%) showed a low expression in invasive gallbladder ***:The up-regulation of HER2 and B1R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.

关键词：受体表达胆囊癌病变肽

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HVEM,a cosignaling molecular switch,and its interactions with BTLA,CD160 and LIGHT

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Cellular & Molecular Immunology 2019年第7期16卷 679-682页

作者： Jose Ignacio Rodriguez-Barbosa Pascal Schneider Andreas Weigert Kyung-Mi Lee Tae-Jin Kim Jose-Antonio Perez-Simon maria-Luisa del Rio Transplantation Immunobiology Section Research Institutes of the University of LeonCampus of Vegazana s/n24071 LeonSpain leon Regional Transplantation Coordination Center Leon University HospitalLeonSpain Acción Estratégica en Salud Consorcio CIBER-ONCSevilleSpain Department of Biochemistry University of Lausanne1066 EpalingesSwitzerland Institute of Biochemistry I Faculty of MedicineGoethe-University Frankfurt60590 FrankfurtGermany Department of Biochemistry and Molecular Biology Korea University College of MedicineSeoul 02841Republic of Korea Department of Biomedical Engineering Center for Bio-Integrated ElectronicsSimpson Querrey Institute for BioNanotechnologyNorthwestern UniversityEvanstonIL 60208USA Department of Hematology Virgen del Rocio University HospitalBiomedical Institute of SevillaSevillaSpain

Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T *** the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T *** expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.

关键词： stimulation homeostasis inflammation

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Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer:A focus on biological mechanisms and therapeutic opportunities

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World Journal of Gastroenterology 2023年第18期29卷 2764-2783页

作者： Federico Selvaggi Teresa Catalano Rossano Lattanzio Roberto Cotellese Gitana maria Aceto Department of Surgical ASL2 Lanciano-Vasto-ChietiOspedale Clinicizzato SS Annunziata of ChietiChieti 66100Italy Department of Clinical and Experimental Medicine University of MessinaMessina 98125Italy Department of Innovative Technologies in Medicine&Dentistry University“G.d’Annunzio”Chieti-PescaraChieti 66100Italy Department of Medical Oral and Biotechnological SciencesUniversity“G.d’Annunzio”Chieti-PescaraChieti 66100Italy Villa Serena Foundation for Research Villa Serena-Del Dott.L.PetruzziCittàSant’Angelo 65013PescaraItaly Department of Medical Oral and Biotechnological Sciences“G.d’Annunzio”University of Chieti-PescaraChieti 66100Italy

The liver is the most common site of metastases in patients with colorectal *** liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver *** aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition *** liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and *** of CRLMs is challenging due to its variability and *** in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in *** the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may *** this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was *** addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.

关键词： Wingless/It/β-catenin signaling Colorectal cancer Epithelial-mesenchymal transition/mesenchymal-epithelial transition Liver metastasis Markers Surgical and non-surgical therapies

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血管生成素在淀粉样沉积症中发挥作用吗?（英文）

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中国生物化学与分子生物学报 2015年第12期31卷 1276-1283页

作者： Rita del Giudice Daria maria Monti 那不勒斯菲里德里克第二大学化学科学系意大利那不勒斯80126

淀粉样沉积症是致命性的疾病,可以是神经退行性的,也可以是系统性的.该疾病以错误折叠蛋白质的堆积、缠绕成纤维为特征,最终导致受累组织、器官的渐进性坏死.目前,没有有效的治疗手段可以阻止该类疾病的进程.错误折叠蛋白质的累积诱导... 详细信息

淀粉样沉积症是致命性的疾病,可以是神经退行性的,也可以是系统性的.该疾病以错误折叠蛋白质的堆积、缠绕成纤维为特征,最终导致受累组织、器官的渐进性坏死.目前,没有有效的治疗手段可以阻止该类疾病的进程.错误折叠蛋白质的累积诱导内质网应激,被认为是退行性疾病的标志.血管生成素不仅可以调节细胞生长和增殖,也在应激条件下细胞存活中发挥作用.最近,发现血管生成素介导的应激反应可以减轻蛋白聚积造成的损伤,提示该蛋白可能在退行性疾病中具有新功能.本综述概述了血管生成素在淀粉样沉积症中的研究进展,特别是描述了血管生成素失调与该类疾病的起始和进展间的关系.我们认为,深入了解血管生成素失调的分子基础有助于发展与蛋白质错误折叠和聚积相关的退行性疾病的治疗方法.

关键词：血管生成素神经退行性疾病系统性淀粉样沉积症

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Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures

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Nano Research 2016年第3期9卷 644-662页

作者： Gianpiero Valente Nicoletta Depalo Ivan de Paola Rosa maria lacobazzi Nunzio Denora Valentino Laquintana Roberto Comparelli Emiliano Altamura Tiziana Latronico Michele Altomare Elisabetta Fanizza Marinella Striccoli Angela Agostiano Michele Saviano Annarita del Gatto Laura Zaccaro maria Lucia Curri Universita degli Studi di Bari Aldo Moro Dipartimento di Chimica Via Orabona 4 70125 - Bari Italy Istituto per i Processi Chimico-Fisici-CNR UOS Bari Via Orabona 4 70125 - Bari Italy Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone 16 80134 - Napoli Italy Universita degli Studi di Bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via Orabona 4 70125 - Bari Italy Universita degli Studi di BariAIdo Moro Dipartimento di Bioscienze Biotecnologie e Biofarmaceutica Via Orabona 4 70125 - Bari Italy lstituto di Cristallografia-CNR Via Amendola 122/0 70126 Bari Italy

Binary asymmetric nanocrystals （BNCs）, composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.

关键词： nanocrystallineheterostructures photoactive semiconductor magnetic nanostructure cyclic RGD peptide αvβ3 integrin active targeting

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Management of single pulmonary metastases from colorectal cancer:State of the art

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World Journal of Gastrointestinal Oncology 2022年第4期14卷 820-832页

作者： Marco Chiappetta Lisa Salvatore maria Teresa Congedo maria Bensi Viola De Luca leonardo PetraccaCiavarella Floriana Camarda Jessica Evangelista Vincenzo Valentini Giampaolo Tortora StefanoMargaritora Filippo Lococo Department of Thoracic Surgery Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy Oncologia Medica Comprehensive Cancer Center Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy Department of Radiation Therapy Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy

Colorectal cancer(CRC)is one of the most common causes of death from *** seeding occurs in approximately 10%of patients surgically treated for primary CRC with radical intent:the lung is the most common site of metastases after the *** surgical treatment of liver metastases is widely accepted to affect long-term outcomes,more controversial and not standardized is the therapy for CRC patients developing lung *** suggests the potential curative role of pulmonary metastasectomy,especially in oligometastatic ***,the optimal strategy of care and the definition of prognostic factors after treatment still need to be *** review focused on the uncommon scenario of single pulmonary metastases from *** explored pertinent literature and provide an overview of the epidemiology,clinical characteristics and imaging of single pulmonary metastases from ***,we identified the best available evidence for overall *** particular,we analyzed the role and results of locoregional approaches(surgery,radiotherapy or ablative procedures)and their integration with systemic therapy.

关键词： Colorectal cancer Pulmonary metastases Oligometastases Chemotherapy Surgery Radiotherapy

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Bowman-Birk inhibitors from legumes as colorectal chemopreventive agents

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World Journal of Gastroenterology 2014年第30期20卷 10305-10315页

作者： Alfonso Clemente maria del Carmen Arques Department of Physiology and Biochemistry of Nutrition Estación Experimental del Zaidín (CSIC)18008 GranadaSpain

Aberrant functioning of serine proteases in inflammatory and carcinogenic processes within the gastrointestinal tract(GIT)has prompted scientists to investigate the potential of serine protease inhibitors,both natural and synthetic,as modulators of their proteolytic *** inhibitors of the Bowman-Birk type,a major protease inhibitor family in legume seeds,which inhibit potently and specifically trypsin-and chymotrypsin-like proteases,are currently being investigated as colorectal chemopreventive *** relevant amounts of Bowman-Birk inhibitors(BBI)can reach the large intestine in active form due to their extraordinary resistance to extreme conditions within the *** in animal models have proven that dietary BBI from several legume sources,including soybean,pea,lentil and chickpea,can prevent or suppress carcinogenic and inflammatory processes within the *** the therapeutic targets and the action mechanism of BBI have not yet been elucidated,the emerging evidence suggests that BBI exert their preventive properties via protease inhibition;in this sense,serine proteases should be considered as primary targets in early stages of *** validation of candidate serine proteases as therapeutic targets together with the identification,within the wide array of natural BBI variants,of the most potent and specific protease inhibitors,are necessary to better understand the potential of this protein family as colorectal chemopreventive agents.

关键词： Bowman-Birk inhibitors Cell proliferation Chemopre

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S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism

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World Journal of Gastroenterology 2006年第12期12卷 1895-1904页

作者： maria del Pilar Cabrales-Romero Lucrecia Márquez-Rosado Samia FatteI-Fazenda Cristina Trejo-Solis Evelia Arce-Popoca Leticia Alemán-Lazarini Saúl Villa-Trevineo Department of Cell Biology Centro de Investigacién y Estudios Avanzados IPN Av. IPN No. 2508 México DF México Department of Neuroimmunology Instituto National de Neurologia y Neurocirugia MVS Insurgentes Sur 3877 Col La Fama DF México

AIM:To determine the role of c-Jun N-terminal kinase(JNK)activity in ethanol-induced apoptosis and themodulation of this signaling cascade by S-Adenosyl-methionine(AdoMet).METHODS:Primary hepatocyte cultures werepretreated with 100 μmol/L SP600125,a selective JNKinhibitor,1 mL/L DMSO or 4 mmol/L AdoMet and thenexposed to 100 mmo/L *** apoptosiswas determined by the TUNEL and DNA ladder *** activity and its inhibition by SP600125 and AdoMetwere determined by Western blot analysis of c-junphosphorylation and Bid ***600125 andAdoMet effects on the apoptotic signaling pathway weredetermined by Western blot analysis of cytochrome crelease and pro-caspase 3 *** AdoMeteffect on glutathione levels was measured by Ellman'smethod and reactive oxygen species(ROS)generationby cell ***:The exposure of hepatocytes to ethanolinduced JNK activation,c-jun phosphorylation,Bidfragmentation,cytochrome c release and pro-caspase 3cleavage;these effects were diminished by SP600125,and caused a significant decrease in ethanol-inducedapoptosis(P<0.05).AdoMet exerted an antioxidanteffect maintaining glutathione levels and decreasing ROSgeneration,without a significant effect on JNK activity,and prevented cytochrome c release and pro-caspase 3cleavage. CONCLUSION:The JNK signaling cascade is a keycomponent of the proapoptotic signaling pathwayinduced by *** activation may be independentfrom ROS generation,since AdoMet which exertedantioxidant properties did not have a significant effect onJNK *** pathway modulator agents and AdoMetmay be components of promising therapies for alcoholicliver disease(ALD)treatment.

关键词：蛋氨酸甲硫氨酸乙醇细胞调亡肝细胞酶活性

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