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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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Ulcerated intussuscepted jejunal lipoma-uncommon cause of obscure gastrointestinal bleeding: A case report

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World Journal of Clinical Cases 2019年第22期7卷 3765-3771页

作者： Tudor Cuciureanu laura Huiban Stefan Chiriac ana-Maria Singeap Mihai Danciu Florin Mihai Carol Stanciu Anca Trifan Nutu Vlad Department of Gastroenterology “Grigore T.Popa”University of Medicine and Pharmacy“St.Spiridon”Emergency HospitalIasi 700115Romania Department of Pathology “Grigore T.Popa”University of Medicine and Pharmacy“St.Spiridon”Emergency HospitalIasi 700115Romania Department of Radiology “Grigore T.Popa”University of Medicine and Pharmacy“St.Spiridon”Emergency HospitalIasi 700115Romania Department of General Surgery “Grigore T.Popa”University of Medicine and Pharmacy“St.Spiridon”Emergency HospitalIasi 700115Romania

BACKGROUND Intestinal lipomas are rare benign gastrointestinal(GI)tumors,usually asymptomatic,but may become symptomatic as the result of some complications such as intussusception,intestinal obstruction,volvulus or *** can occur at any site along the entire GI tract,more frequent in colon and rarely in small *** patient reported here is a very rare case of jejunal lipoma,ulcerated and intussuscepted,diagnosed in an adult investigated for a chronic iron deficiency anemia(IDA),and successfully managed by segmental jejunal *** SUMMARY A 63-year-old male was referred to“***”Hospital,Institute of Gastroenterology and Hepatology,Iasi,to investigate an obscure GI bleeding with an *** upper GI endoscopy and colonoscopy were performed,excluding potentially bleeding lesions,videocapsule endoscopy was then carried out,revealing fresh blood and a protruding lesion in proximal jejunum,findings confirmed by a single-balloon *** biopsies were taken from the lesion,but histological results were ***,contrast-enhanced computed tomography was performed showing jejunal polypoid mass with homogenous fat density,suggestive for lipoma.A week later a laparotomy was performed revealing the intussuscepted jejunal segment which was resected enbloc,and sent for further histopathologic *** patient made an uneventful recovery and was discharged seven days later,and at six months follow-up he had no complains and his hemoglobin returned to normal *** Lipomas are very rarely located in the jejunum,usually asymptomatic,but they may lead to complications such as intussusception and *** resection remains the treatment of choice.

关键词： Lipoma Intussusception Computed tomography Video capsule endoscopy Gastrointestinal bleeding Case report

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Recent advances in gastric cancer early diagnosis

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World Journal of Gastroenterology 2019年第17期25卷 2029-2044页

作者： laura Necula Lilia Matei Denisa Dragu ana I Neagu Cristina Mambet Saviana Nedeianu Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu Department of Cellular and Molecular Pathology Stefan S.Nicolau Institute of Virology Faculty of Medicine Titu Maiorescu University

Gastric cancer(GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva,stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

关键词： Biomarkers Gastric cancer Early diagnosis Genetic and epigenetic alterations Circulating molecules

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Predictive clinical features of cardioembolic infarction in patients aged 85 years and older

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Journal of Geriatric Cardiology 2019年第11期16卷 793-799页

作者： ana Maria Carbajo-García Jonatan Cortés AdriàArboix Joan Massons laura Díez Enric Vergés Jordi Arboix-Alió Luís García-Eroles Cerebrovascular Division Department of NeurologyHospital Universitari del Sagrat CorUniversitat de BarcelonaBarcelonaCataloniaSpain Department of Sports Sciences Ramon Llull UniversityFPCEE BlanquernaBarcelonaCataloniaSpain Director d’Organitzaciói Sistemes d’Informació Gerència Territorial Metropolitana NordInstitut Catalàde la SalutBarcelonaCataloniaSpain

Objective To assess predictive clinical factors of cardioembolic infarction in very old patients(85 years of age and older).Methods Prospective hospital-based stroke registry("The Sagrat Cor Hospital of Barcelona Stroke Registry")is an acute-care teaching hospital in Barcelona,Catalonia,*** 956 first-ever cardioembolic stroke patients included in the stroke registry over a 24-year period,639 were younger than 85 years of age and 317 were 85 years or older(mean age:88.9 years).Demographics,clinical characteristics,risk factors and early outcome were *** of cardioembolic infarction in the oldest age group were assessed by multivariate *** In a logistic regression model based on demographics,risk factors,clinical features and complications,female gender(odds ratio[OR]=1.74,95%confidence interval[CI]:1.27–2.39),heart failure(OR=2.27,95%CI:1.46–3.56),altered consciousness(OR=1.76,95%CI:1.28–2.42),and infectious complications(OR=2.01,95%CI:1.39–2.91)were predictors of cardioembolic stroke in the oldest age *** contrast,heavy smoking,heart valve disease,hypertension,headache,early seizures,sensory deficit,and involvement of the posterior cerebral artery were independently associated with cardioembolic stroke in the younger *** Identification of a differential clinical profile of cardioembolic stroke between patients aged 85 years or more and those younger than 85 years helps clinicians to the optimal management of ischemic infarction in the oldest segment of the population.

关键词： Cardioembolic stroke Clinical features Ischemic infarction Stroke Very old patients

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Palladium-Catalyzed Carbonylation of Multifunctionalized Substituted Alkynes to Quinolinone Derivatives under Mild Conditions

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Chinese Journal of Chemistry 2023年第23期41卷 3223-3228页

作者： Aleksandr Voronov Francesco Pancrazzi ana Maria Constantin Raimondo Maggi Raffaella Mancuso Bartolo Gabriele Diego Olivieri Carla Carfagna Alessandro Casnati Francesco Rispoli laura Baldini Nicola Della Ca Department of Chemistry Life Sciences and Environmental Sustainability (SCVSA)University of ParmaParco Area delle Scienze17/A43124 Parma (PR)Italy Center for Energy and Environment (CIDEA) University of ParmaParco Area delle Scienze 181/A43124 Parma (PR)Italy Laboratory of Industrial and Synthetic Organic Chemistry (LISOC) Department of Chemistry and Chemical TechnologiesUniversity of CalabriaVia P.Bucci 12/C87036 Arcavacata di RendeCosenza (CS)Italy Department of Biomolecular Sciences University of Urbino “Carlo Bo”Piazza Rinascimento 661029 Urbino (PU)Italy Department of Industrial Chemistry “T.Montanari” University of BolognaViale Risorgimento 440136 Bologna (BO)Italy

A highly selective palladium-catalyzed carbonylation of 2-alkynylanilines bearing an amide moiety to condensed six-membered heterocyclic structures has been developed under mild conditions(room temperature and atmospheric pressure of CO).The carbonylative protocol is also compatible with CO surrogates,such as benzene-1,3,5-triyl triformate(TFBen)or the newly developed calix[6]arenes functionalized with six formate groups(CLX[6]CO),which are both capable to release CO in situ.A series of tricyclic fused heterocycles containing the important oxazino-quinolinone scaffold have been selectively obtained(only the 6-endo-dig cyclization mode has been observed)in good to excellent yields(up to 99%).

关键词： Pd-catalysis Carbonylation Alkynes CO surrogates 6-endo-dig Calixarenes C1 building blocks Domino reactions

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High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

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World Journal of Gastroenterology 2020年第22期26卷 3024-3033页

作者： laura Necula Lilia Matei Denisa Dragu Ioana Pitica ana Iulia Neagu Coralia Bleotu Simona Dima Irinel Popescu Carmen C Diaconu Mihaela Chivu-Economescu Department of Cellular and Molecular Pathology Stefan S.Nicolau Institute of VirologyBucharest 030304Romania Titu Maiorescu University Faculty of MedicineBucharest 040441Romania Fundeni Clinical Institute Bucharest 022328Romania

BACKGROUND Gastric cancer(GC)remains an aggressive malignancy with a high rate of mortality,being the third leading cause of cancer-related *** than one million newly diagnosed cases and 782685 deaths due to GC were reported in *** is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these *** discovery of new biomarkers useful in the early diagnosis of GC is *** To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma *** Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of ***-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent *** circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma *** analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma *** Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue(P<0.05).COL10A1 seems to show an elevated expression from the beginning of carcinogenesis,in the early stages,and its increased level remains elevated during cancer progression.A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also ***,increased COL10A1 plasma level was associated with poor survival of the *** COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve(AUC)of 0.9171(P=0.0002),sensitivity of 87.76%,and specificity of 100.0%.Furthermore,this study demonstrated the potential role of plasma COL10A1 in the early detection of GC,as in the early stage,we obtained an AUC of 0.8789(P=0.00

关键词： Gastric cancer COL10A1 Circulating biomarkers Early diagnosis Poor prognosis Tumor stage

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Did the severe acute respiratory syndrome-coronavirus 2 pandemic cause an endemic Clostridium difficile infection?

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World Journal of Clinical Cases 2021年第33期9卷 10180-10188页

作者： Camelia Cojocariu Irina Girleanu Anca Trifan Andrei Olteanu Cristina Maria Muzica laura Huiban Stefan Chiriac ana Maria Singeap Tudor Cuciureanu Catalin Sfarti Carol Stanciu Department of Gastroenterology “Grigore T.Popa”University of Medicine and Pharmacy“St.Spiridon”University HospitalInstitute of Gastroenterology and HepatologyIasi 700115Romania

BACKGROUND Clostridium difficile infection(CDI)has increased in prevalence during the last *** coronavirus disease 2019(COVID-19)pandemic has negatively influenced patient *** majority of the severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)-infected patients received antibiotics during *** To analyze the factors that influenced CDI development after SARS-CoV-2 *** Between March 2020 to December 2020,we performed a prospective observational study including 447 patients diagnosed with CDI who were admitted to our tertiary referral university *** diagnosis of CDI was based on the presence of diarrhea(≥3 watery stools within 24 h)associated with Clostridium difficile toxins A or *** excluded patients with other etiology of acute *** Among the total 447(12.5%)patients with CDI,most were male(54.3%)and mean age was 59.7±10.8 ***-six(17.0%)had history of COVID-19,most being elderly(COVID-19:62.6±14.6 years vs non-COVID-19:56.8±17.6 years,P=0.007),with history of alcohol consumption(43.4%vs 29.4%,P=0.017),previous hospitalizations(81.6%vs 54.9%,P<0.001)and antibiotic treatments(60.5%vs 35.5%,P<0.001),requiring higher doses of vancomycin and prone to recurrent disease(25.0%vs 13.1%,P=0.011).Age over 60 years[odds ratio(OR):2.591,95%confidence interval(CI):1.452-4.624,P=0.001],urban residence(OR:2.330,95%CI:1.286-4.221,P=0.005),previous antibiotic treatments(OR:1.909,95%CI:1.083-3.365,P=0.025),previous hospitalizations(OR:2.509,95%CI:1.263-4.986,P=0.009)and alcohol consumption(OR:2.550,95%CI:1.459-4.459,P=0.001)were risk factors of CDI in *** CDI risk is unrelated to history of SARS-CoV-2 ***,previous COVID-19 may necessitate higher doses of vancomycin for CDI.

关键词： COVID-19 infection Clostridium difficile infection Risk factors Antibiotic use Pandemic Recurrence

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Virgin Olive Oil Acceptability in Emerging Olive Oil-Producing Countries

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Food and Nutrition Sciences 2013年第10期4卷 1060-1068页

作者： Adriana Gámbaro ana Claudia Ellis laura Raggio Sensory Evaluation Laboratory Food Science and Technology Department School of Chemistry Universidad de la República Montevideo Uruguay.

A sample of 99 habitual consumers sensory-evaluated 2 extra virgin and 2 ordinary olive oils in terms of overall liking and willingness to purchase based on 9-point structured scales and responded to a check-all-that-apply question comprising a list of 18 positive and negative attributes. In the second session, the same consumers evaluated the same oils also based on their respective commercial specifications and sensory profiles previously prepared by a panel of 9 trained tasters. Two consumer clusters with contrasting behavior were identified. Whereas 52% of respondents gave high overall liking scores to the extra virgin oils and scores below commercially acceptable limits to those of ordinary virgin quality, 48% gave low overall liking scores to the extra virgin oils and high overall liking scores to those oils that were defective. Consumers of neither cluster were influenced by the information made available in Session 2. Although a slight majority of consumers described the oils consistently with the sensory profiles available from the tasting panel, an alarmingly large number of respondents described the two extra virgin oils in terms of defective, bad-tasting, strange-tasting, poor quality and rancid, and those oils that were defective in terms of good quality, tasty, sweet, aromatic, mild-flavored, delicious and fresh. These results highlight the need for the implementation of relevant consumer sensitization programs in emerging olive-producing countries like Uruguay, where virgin olive oils of varied quality are locally available.

关键词： Olive Oil Consumer Study Olive Oil Quality

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Noninvasive investigations for non alcoholic fatty liver disease and liver fi brosis

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World Journal of Gastroenterology 2010年第38期16卷 4784-4791页

作者： Carmen Fierbinteanu-Braticevici Ion Dina ana Petrisor laura Tribus Lucian Negreanu Catalin Carstoiu Carmen Fierbinteanu-Braticevici Ana PetrisorLaura TribusLucian NegreanuCatalin CarstoiuMedical Clinic Ⅱ and Gastroenterology University Hospital Bucharest Department of Gastroenterology St John’s Hospital 7001 Bucharest Carmen Fierbinteanu-Braticevici Ana PetrisorLaura TribusLucian NegreanuCatalin CarstoiuMedical Clinic Ⅱ and GastroenterologyUniversity Hospital Bucharest

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and f ibrosis; however, several noninvasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. These markers are currently neither available in all centers nor validated in extensive studies. Examples include high-sensitivity C reactive protein and plasma pentraxin 3, which are associated with extensive liver f ibrosis in NASH. Interleukin-6 correlates with inflammation, and cytokeratin-18 represents a marker of hepatocyte apoptosis (prominent in NASH and absent in simple steatosis). Tissue polypep-tide specif ic antigen seems to have a clinical utility in the follow-up of obese patients with NASH.

关键词： Non-alcoholic fatty liver disease Biomarkers Necroinflammation Liver fibrosis

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Function, kinetic properties, crystallization, and regulation of microbial malate dehydrogenase

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2016年第4期17卷 247-261页

作者： Toshiko TAKAHASHI-INIGUEZ Nelly ABURTO-RODRIGUEZ ana laura VILCHIS-GONZALEZ Maria Elena FLORES Departamento de Biologla Molecular y Biotecnologia lnstituto de Investigaciones BiomddicasUniversidad Nacional Autonoma de MexicoMexicoD.F.04510Mexico

Malate dehydrogenase （MDH） is an enzyme widely distributed among living organisms and is a key protein in the central oxidative pathway. It catalyzes the interconversion between malate and oxaloacetate using NAD＋ or NADP＊ as a cofactor. Surprisingly, this enzyme has been extensively studied in eukaryotes but there are few reports about this enzyme in prokaryotes. It is necessary to review the relevant information to gain a better understanding of the function of this enzyme. Our review of the data generated from studies in bacteria shows much diversity in their molecular properties, including weight, oligomeric states, cofactor and substrate binding affinities, as well as differences in the direction of the enzymatic reaction. Furthermore, due to the importance of its function, the transcription and activity of this enzyme are rigorously regulated. Crystal structures of MDH from different bacterial sources led to the identification of the regions involved in substrate and cofactor binding and the residues important for the dimer-dimer interface. This structural information allows one to make direct modifications to improve the enzyme catalysis by increasing its activity, cofactor binding capacity, substrate specificity, and thermostability. A comparative analysis of the phylogenetic reconstruction of MDH reveals interesting facts about its evolutionary history, dividing this superfamily of proteins into two principle clades and establishing relationships between MDHs from different cellular compartments from archaea, bacteria, and eukaryotes.

关键词： Malate dehydrogenase Carbon metabolism Tricarboxylic acid cycle

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