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The challenge of drug resistance in pancreatic ductal adenocarcinoma:a current overview

Cancer Biology & Medicine 2019年第4期16卷 688-699页

作者： Francisco Quinonero Cristina Mesas Kevin Doello Laura Cabeza Gloria Perazzoli Cristina Jimenez-Luna ana rosa rama Consolación Melguizo Jose Prados Institute of Biopathology and Regenerative Medicine(IBIMER) Center of Biomedical Research(CIBM)University of Gran adaz Gran ada 18100Spain Department of An atomy and Embryology Faculty of Medici neUn iversity of Gran adaGranada 18071Spain Instituto Biosanitario de Granada(ibs.GRanaDA) Granada 18014Spain Medical Oncology Service Virgen de las Nieves HospitalGranada 1812Spain Department of Oncology Ludwig Institute for Cancer ResearchUniversity of LausanneEpalinges 1066Switzerland Department of Health Scienee University of JaenJa6n 23071Spain

Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer *** delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and ***,these strategies are insufficient to improve its poor *** the advances made in chemotherapy(***-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug ***,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and ***,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(***-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and ***,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage *** the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.

关键词： Pancreatic ductal adenocarcinoma chemotherapy drug resistance cancer stem cells therapeutic strategies

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Development of a warning score for early detection of colorectal anastomotic leakage:Hype or hope?

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World Journal of Gastrointestinal Surgery 2022年第11期14卷 1297-1309页

作者： Nuno J G rama Óscar Lourenço Patrícia C Motta Lima Maria Pedro S Guarino Diana Parente Ricardo Castro ana Bento anabela Rocha Fernando Castro-Poças João Pimentel Division of Colorectal Surgical Leiria Hospital CentreLeiria 2410-021Portugal Abel Salazar Biomedical Institute University of OportoOporto 4099-002Portugal Center for Innovative Care and Health Technology(ciTechCare) Polytechnic of LeiriaLeiria 2410-541Portugal Faculty of Economics CeBERUniversity of CoimbraCoimbra 3000-137Portugal Division of Clinical Pathology Leiria Hospital CentreLeiria 2410-541Portugal Division of Surgical Oporto Hospital CentreOporto 4099-001Portugal Department of Gastroenterology Santo António HospitalPorto Hospital CenterOporto 4099-001Portugal Institute of Biomedical Sciences Abel Salazar University of OPortoOporto 4099-001Portugal Faculty of Medicine University of CoimbraCoimbra 3004-531Portugal Division of Surgical Montes Claros HospitalCoimbra 3030-320Portugal

BACKGROUND Colorectal anastomotic leakage(CAL),a severe postoperative complication,is associated with high morbidity,hospital readmission,and overall healthcare *** detection of CAL remains a challenge in clinical ***,some decision models have been developed to increase the diagnostic accuracy of this *** To develop a score based on easily accessible variables to detect CAL *** Based on the least absolute shrinkage and selection operator method,a predictive classification system was developed[Early ColoRectAL Leakage(E-CRALL)score]from a prospective observational,single center cohort,carried out in a colorectal division from a non-academic *** score performance and CAL threshold from postoperative day(POD)3 to POD5 were *** on a precise analytical decision model,the standard clinical practice was compared with the E-CRALL adoption on POD3,POD4,or POD5.A cost-minimization analysis was conducted,on the assumption that all alternatives delivered similar health-related *** In this study,396 patients who underwent colorectal resection surgery with anastomosis,and 6.3%(n=25)developed *** of the patients who developed CAL(n=23;92%)were diagnosed during the first hospital admission,with a median time of diagnosis of 9.0±6.8 *** POD3 to POD5,the area under the receiver operating characteristic curve of the E-CRALL score was 0.82,0.84,and 0.95,*** POD5,if a threshold of 8.29 was chosen,87.4%of anastomotic failures were identified with E-CRALL ***,score usage could anticipate CAL diagnosis in an average of 5.2 d and 4.1 d,if used on POD3 and POD5,*** of score adoption,episode comprehensive costs were markedly greater(up to four times)in patients who developed CAL in comparison with patients who did not develop ***,the use of the E-CRALL warning score was associated with cost savings of€421442.20,with most(92.9%)of the savings from patients

关键词： anastomotic leakage Colorectal Surgery Biomarkers Score Costs

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Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage:A prospective observational study

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World Journal of Gastroenterology 2022年第24期28卷 2758-2774页

作者： Nuno J G rama Marlene C C Lages Maria Pedro S Guarino Óscar Lourenço Patrícia C Motta Lima Diana Parente Cândida S G Silva Ricardo Castro ana Bento anabela Rocha Fernando Castro-Pocas João Pimente Colorectal Surgical Division Leiria Hospital CentreLeiria 2410-021Portugal Abel Salazar Biomedical Institute(ICBAS) University of OportoOporto 4099-002Portugal Center for Innovative Care and Health Technology(ciTechCare) Polytechnic of LeiriaLeiria 2410-541Portugal Faculty of Economics CeBERUniversity of CoimbraCoimbra 3000-137Portugal Clinical Pathology Division Leiria Hospital CentreLeiria 2410-541Portugal Surgical Division Oporto Hospital CentreOporto 4099-001Portugal Department of Gastroenterology Santo António HospitalPorto Hospital CenterPorto 4099-001Portugal Institute of Biomedical Sciences Abel Salazar University of PortoPorto 4099-001Portugal Faculty of Medicine University of CoimbraCoimbra 3004-531Portugal Surgical Division Montes Claros HospitalCoimbra 3030-320Portugal

BACKGROUND Colorectal anastomotic leakage(CAL)is one of the most dreaded complications after colorectal surgery,with an incidence that can be as high as 27%.This event is associated with increased morbidity and mortality;therefore,its early diagnosis is crucial to reduce clinical consequences and *** biomarkers have been suggested as laboratory tools for the diagnosis of *** To assess the usefulness of plasma C-reactive protein(CRP)and calprotectin(CLP)as early predictors of *** A prospective monocentric observational study was conducted including patients who underwent colorectal resection with anastomosis,from March 2017 to August *** were divided into three groups:G1–no complications;G2–complications not related to CAL;and G3–*** biomarkers were measured and analyzed in the first 5 postoperative days(PODs),namely white blood cell(WBC)count,eosinophil cell count(ECC),CRP,CLP,and procalcitonin(PCT).Clinical criteria,such as abdominal pain and clinical condition,were also *** correlation between biomarkers and CAL was *** operating characteristic(ROC)curve analysis was used to compare the accuracy of these biomarkers as predictors of CAL,and the area under the ROC curve(AUROC),specificity,sensitivity,positive predictive value,and negative predictive value(NPV)during this period were *** In total,25 of 396 patients developed CAL(6.3%),and the mean time for this diagnosis was 9.0±6.8 *** operative characteristics,such as surgical approach,blood loss,intraoperative complications,and duration of the procedure,were notably related to the development of *** length of hospital stay was markedly higher in the group that developed CAL compared with the group with complications other than CAL and the group with no complications(median of 21 d vs 13 d and 7 d respectively;P<0.001).For abdominal pain,the best predictive performance was on POD4 and POD5,with the largest AUROC of 0.84 on ***

关键词： anastomotic leakage Colorectal Surgery Biomarkers C-reactive protein Calprotectin

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Li2SnO3 branched nano- and microstructures with intense and broadband white-light emission

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Nano Research 2019年第2期12卷 441-448页

作者： Miguel Garcia-Tecedor Javier Bartolome David Maestre Achim Trampert ana Cremades Dpt. Fisica de Materials Facultad de CC. Fisicas Universidad Complutense de Madrid Madrid 28040 Spain Paul-Drude-Institut fur Festkorperelektronik Hausvogteiplatz 5-7 Berlin 10117 Germany Institute of Advanced Materials (INAM) Universitat Jaume I Castello 12006 Spain Dpt. Fisica de Materiales Facultad de CC. Ftsicas Universidad Complutense de Madrid Madrid 28040 Spain

Exploiting the synergy between microstructure, morphology and dimensions by suitable nanomaterial engineeri ng, can effectively upgrade the physical properties and material performances. Li2SnO3 elongated nano- and microstructures in form of belts, wires, rods and branched structures have been fabricated by a vapor-solid method at temperatures ranging from 700 to 900℃ using metallic Sn and Li2CO3 as precursors. The achievement of these new morphologies can face challenging applications for Li2SnO3, not only in the field of energy storage, but also as building blocks in optoelectronic devices. The micro? and nanostructures grown at 700 and 800℃ correspond to monoclinic Li2SnO3, while at 900℃ complex Li2S nO/SnO2 core-shell microstructures are grow n, as con firmed by X-ray diffractio n and rama n spectroscopy. Transmission electron microscopy reveals structural disorder related to stacking faults in some of the branched structures, which is associated with the prese nee of the low-temperature phase of L12S nO3. The luminescent resp onse of these structures is domi nated by in tense emissi ons at 2, 2.5 and 3 eV, almost completely covering the whole range of the visible light spectrum. As a result, white-light emission is obtained without the need of phosphors or complex quantum well heterostructures. Enhanced functionality in applications such as in light-emitting devices could be exploited based on the high luminescenee intensity observed in some of the analysed Li2SnO3 structures.

关键词： lithium oxides white light emitters nanostructures luminescenee

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Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3009-3026页

作者： Saini Setua Shabia Shabir Poornima Shaji ana Martinez Bulnes Anupam Dhasmana Swathi Holla Nivesh K.Mittal Nirakar Sahoo Tripti Saini Francesco Giorgianni Mohammad Sikander Andrew E.Massey Bilal B.Hafeez Manish K.Tripathi Vincent P.Diego Meena Jaggi Junming Yue Nadeem Zafar Murali M.Yallapu Stephen W.Behrman Sheema Khan Subhash C.Chauhan Department of Pharmaceutical Sciences College of Pharmacyand College of MedicineUniversity of Tennessee Health Science Center(UTHSC)MemphisTN 36163USA Department of Computer Science Islamic University of Science and TechnologyAwantiporaJ&K 192122India Department of Immunology and Microbiology School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTX 78504USA South Texas Center of Excellence in Cancer Research School of Medicinethe University of Texas Rio Grande ValleyMcAllenTX 78504USA Himalayan School of Biosciences and Cancer Research Institute Himalayan Institute of Medical SciencesSwami Rama Himalayan UniversityDehradun 248016India Plough Center for Sterile Drug Delivery Solutions UTHSCMemphisTN 38104USA Department of Biology College of SciencesUTRGVMcAllenTX 78539USA National Institute of Biomedical Imaging and Bioengineering(NIBIB) National Institutes of HealthBethesdaMD 20892USA South Texas Diabetes and Obesity Institute UTRGVMcAllenTX 78504USA Dept.of Laboratory Medicine&Pathology University of WashingtonSeattleWA 98195USA Department of Surgery Baptist Memorial Medical EducationBaptist Memorial HospitalMemphisTN 38120USA Baptist Health Sciences University MemphisTN 38104USA

The application of extracellular vesicles,particularly exosomes(EXs),is rapidly expanding in the field of medicine,owing to their remarkable properties as natural carriers of biological *** study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues(NAF-EXs)for personalized medicine,which can be derived at the time of diagnosis by endoscopic ***,we show that exosomes(EXs)derived from NAFs demonstrate differential bio-physical characteristics,efficient cellular internalization,drug loading efficiency,pancreatic tumor targeting and delivery of ***-derived EXs(NAF-EXs)were used for loading ormeloxifene(ORM),a potent anti-cancer and desmoplasia inhibitor as a model *** found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype,which may be due to regulation of Ca^(2+) influx in fibroblast ***-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition(EMT)and repressed tumor growth in xenograft mouse *** conclusion,our data suggests preferential tropism of NAF-EXs for PDAC tumors,thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer ***,it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

关键词： Pancreatic cancer Tumor adjacent normal tissue fibroblasts(NAF) Desmoplasia Extracellular vesicles Exosomes Tumor targeting Ormeloxifene Personalized medicine

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