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Mouse models of pancreatic cancer

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World Journal of Gastroenterology 2012年第12期18卷 1286-1294页

作者： Marta Herreros-Villanueva elizabeth hijona Angel Cosme Luis Bujanda Schulze Center for Novel Therapeutics Division of Oncology ResearchDepartment of MedicineMayo ClinicRochesterMN 55905United States Department of Gastroenterology Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd)University of the Basque CountryDonostia HospitalSan Sebastian 20014Spain Department of Gastroenterology Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd)University of the Basque CountryDonostia Hospital

Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are *** during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and *** vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research *** the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been *** models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic *** alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic *** mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model *** models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer ***,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

关键词：小鼠模型胰腺癌胰脏治疗方案肿瘤抑制基因恶性肿瘤分子特征遗传工程

Adjuvant and neoadjuvant treatment in pancreatic cancer

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World Journal of Gastroenterology 2012年第14期18卷 1565-1572页

Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United *** resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at *** studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and *** there is no consensus around the world on what constitutes"standard"adjuvant therapy for pancreatic *** controversy derives from several studies,each fraught with its own *** of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in *** of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more *** this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

关键词：辅助治疗胰腺癌恶性肿瘤癌症治疗手术切除治疗方案化疗标准

Biochemical determination of lipid content in hepatic steatosis by the Soxtec method

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World Journal of Gastroenterology 2010年第12期16卷 1495-1499页

作者： elizabeth hijona Lander hijona Mikel Larzabal Cristina Sarasqueta Pablo Aldazabal Juan Arenas Luis Bujanda Department of Gastroenterology University of the Basque CountryDonostia HospitalCenter for Biomedical Research in Hepatic and Digestive Disease(CIBERehd) Department of Gastroenterology Basurto Hospital Department of Pathology Donostia Hospital Department of Epidemiology CIBERESPDonostia Hospital

AIM:To establish a quantitative method to measure the amount of ***:The livers of 53 male Wistar rats(225 g) with different degrees of hepatic steatosis were *** model of hepatic steatosis was based on a high carbohydrate,fat-free modified *** were classified into four grades depending on fat accumulation,using the Kleiner and Brunt *** fat was studied by the Soxtec method(SoxtecTM 2050 Auto Fat Extraction System),and agreement between both assays was assessed by calculating theκ ***:According to the histological classification,38% of rats presented grade 0,21% grade 1,22% grade 2 and 20% grade *** amount of fat per 100 g tissue was 2.60±0.64 g for grade 0,3.87±1.59 g for grade 1,5.82±1.37 g for grade 2 and 8.68± 2.30 g for grade *** significant differences were found between the mean values for each of the histological grades(P<0.05).The correlation for the quantification of fat in the liver between both assays was moderate(κ=0.60).CONCLUSION:The biochemical quantification of fat in liver tissue by the Soxtec method was correlated with the histological classification,although the agreement between the two tests was only moderate.

关键词： Liver steatosis Soxtec method Quantitative analysis Histology Biochemistry

MicroRNAs in biliary diseases

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World Journal of Gastroenterology 2012年第43期18卷 6189-6196页

作者： Patricia Munoz-Garrido Maite García-Fernández de Barrena elizabeth hijona Miguel Carracedo JoséJ G Marín Luis Bujanda Jesús M Banales Division of Hepatology and Gastroenterology Biodonostia Research InstituteDonostia Universitary Hospital20014 San SebastiánSpain Division of Oncology Research Schulze Center for Novel TherapeuticsMayo ClinicRochesterMN 55905United States Division of Hepatology and Gastroenterology Biodonostia Research InstituteDonostia Universitary Hospital20014 San SebastiánSpains Department of Liver and Gastrointestinal Diseases National Institute for the Study of Liver and Gastrointestinal Diseases(CIBERehdfunded by the Spanish CarlosⅢInstitute)08036 BarcelonaSpain Department of Physiology and Pharmacology Experimental Hepatology and Drug Targeting(HEVEFARM)Biomedical Research Institute of Salamanca(IBSAL)University of Salamanca37008 SalamancaSpain Ikerbasque Basque Foundation for Science48011 BilbaoSpain

Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRNAs, small non-coding endogenous RNAs that post-transcriptionally regulate gene expres sion, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRNAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted.

关键词：小分子RNA 疾病 miRNA 胆道细胞类型发病机理免疫相关调控基因

Effects of resveratrol and other polyphenols in hepatic steatosis

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World Journal of Gastroenterology 2014年第23期20卷 7366-7380页

作者： Leixuri Aguirre Maria Puy Portillo elizabeth hijona Luis Buja Nutrition and Obesity Group Department of Nutrition and Food ScienceUniversity of Basque Country (UPV/EHU) and Centro de Investigación Lucio Lascaray01006 VitoriaSpain Centro de Investigación Biomédica en Fisiopatología de la Obesidad y Nutrición (CIBERobn) Instituto de Salud Carlos Ⅲ01006 VitoriaSpain Department of Gastroenterology University of the Basque Country (UPV/EHU)Donostia Hospital and Biodonostia Institute20014 San SebastiánSpain Centro de Investigación Biomédica en Enfermedades Hepáticas (CIBERehd) Instituto de Salud Carlos Ⅲ20014 San SebastianSpain

Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic *** are members of a very large family of plant-derived compounds that can have beneficial effects on human health,and thus their study has become an increasingly important area of human nutrition *** aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts,on hepatocyte and liver fat accumulation under different steatosis-inducing *** results reported clearly show that this group of biomolecules is able to reduce fat accumulation,but further studies are needed to establish the optimal dose and treatment period *** regard to the potential mechanisms of action,there is a good *** anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis,increased in fatty acid oxidation,and reduced of oxidative stress and *** a general conclusion,it can be stated that polyphenols are biomolecules which produce hepatoprotective *** date,these beneficial effects have been demonstrated in cultured cells and animal ***,studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.

关键词： Polyphenols Resveratrol Quercetin liver Steatosis

Alcohol consumption on pancreatic diseases

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World Journal of Gastroenterology 2013年第5期19卷 638-647页

作者： Marta Herreros-Villanueva elizabeth hijona Jesus Maria Baales Angel Cosme Luis Bujanda Schulze Center for Novel Therapeutics Division of Oncology ResearchDepartment of MedicineMayo ClinicRochesterMA 55905United States Department of Gastroenterology Center for Biomedical Research in Digestive and Liver Diseases Network(CIBERehd)Donostia HospitalUniversity of the Basque UPV/EHU20010 San SebastianSpain

Although the association between alcohol and pancreatic diseases has been recognized for a long time,the impact of alcohol consumption on pancreatitis and pancreatic cancer(PC)remains poorly *** there is not consensus about the epidemiology and the beverage type,dose and duration of alcohol consumption causing these *** objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior trying to understand the association between dose,type and frequency of alcohol consumption and risk of pancreatitis and *** majority of the studies conclude that high alcohol intake was associated with a higher risk of pancreatitis(around 2.5%-3% between heavy drinkers and 1.3%between non drinkers).About 70%of pancreatitis are due to chronic heavy alcohol *** this incidence rate differs between countries,it is clear that the risk of developing pancreatitis increases with increasing doses of alcohol and the average of alcohol consumption vary since 80 to 150 g/d for 10-15 *** regard to PC, the role of alcohol consumption remains less clear,and low to moderate alcohol consumption do not appear to be associated with PC risk,and only chronic heavy drinking increase the risk compared with lightly *** a population of 10%-15%of heavy drinkers, 2%-5%of all PC cases could be attributed to alcohol ***,as only a minority(less than 10%for pancreatitis and 5%for PC)of heavily drinkers develops these pancreatic diseases,there are other predisposing factors besides alcohol *** variability and environmental exposures such as smoking and diet modify the risk and should be considered for further investigations.

关键词： Acute pancreatitis Chronic pancreatitis Alcohol consumption Alcohol metabolism Genetic variability Pancreatic cancer Risk

Childhood sleep:assessments,risk factors,and potential mechanisms

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World Journal of Pediatrics 2024年第2期20卷 105-121页

作者： Jianghong Liu Xiaopeng Ji elizabeth Rovit Susannah Pitt Terri Lipman School of Nursing University of Pennsylvania418 Curie Blvd.Room 426Claire M.Fagin HallPhiladelphiaPA 19104USA School of Nursing College of Health SciencesUniversity of DelawareNewarkDE 19716USA Geisinger Commonwealth School of Medicine ScrantonPA 18510USA

Background Sleep problem is a highly prevalent health issue among pediatric populations across the *** this review,we aimed to identify risk factors contributing to sleep deficiency and poor sleep hygiene in *** biological,psychosocial,and environmental mechanisms as well as research gaps in the literature are also *** sources A comprehensive search for relevant English language full-text,peer-reviewed publications was performed focusing on pediatric sleep studies from prenatal to childhood and adolescence in a variety of indexes in PubMed,SCOPUS,and Psych *** relevant data based and systematic reviews are *** This paper summarizes many risk factors for childhood sleep problems,including biological(e.g.,genetics,gender,age and puberty,prenatal factors,postnatal factors);nutritional(e.g.,macronutrients,micronutrients,omega-3 fatty acids,obesity);environmental(e.g.,heavy metals,noise,light,air pollution);interpersonal(e.g.,family,exposure to violence,screen media use,physical injury);and community/socioeconomic variables(e.g.,racial/ethnicity and cultural factors,neighborhood conditions and socioeconomic status,school factors,public health disasters/emergencies),to better understand the development of sleep problems in *** Poor childhood sleep is a multifactorial issue affected by a wide range of prenatal and early-life biological,environmental,and psychosocial risk factors and contributors.A better understanding of these risk factors and their mechanisms is an important first step to develop future research and prevention programs focusing on pediatric sleep problems.

关键词： Child sleep Pediatrics Risk factor Mechanisms

IMAGE-BUILDING AND FRAMING PROCESSES OF AN ANTI-MOTHER/-WOMAN IN CICERO’S PRO CLUENTIO

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Journal of Ancient Civilizations 2024年第1期39卷 51-72,124页

作者： Hongxia Zhang elizabeth Webster IHAC NENUChangchun

In this case study we explore Cicero’s processes of framing and image-building regarding the concept of an anti-mother/-*** this we examine Cicero’s portrayal of Sassia,a woman who features as one of the main antagonists of his speech Pro *** analyse Cicero’s depiction of Sassia’s evilness towards her son,Cluentius,through the lens of frame and framing *** doing so,this case study aims to present a deeper understanding of Cicero’s stratagems(e.g.,priming,calling for action;nudging,pushing someone towards action;and affordance,offering a frame to act outside of or within)which were employed in order to devise a negative characterisation of *** application of this methodological approach to Cicero’s framing of Sassia provides a new scope for analysing not only the classical text itself but also for the analysis of ancient human society to which it belonged.

关键词： affordance Cicero frames&framing image-building nudging&priming Roman Republic stereotypes

Ecosystem Services of Grazed Grasslands in the Flooding Pampa

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Phyton-International Journal of Experimental Botany 2024年第6期93卷 1179-1202页

作者： elizabeth J.Jacobo Adriana M.Rodríguez Facultad de Agronomía Área de AgroecologíaUniversidad de Buenos AiresBuenos Aires1417Argentina Facultad de Agronomía Departamento de Producción AnimalUniversidad de Buenos AiresBuenos Aires1417Argentina

The Flooding Pampa grasslands are the last remnant of the Rio de la Plata grasslands in ***-genic interventions have led to severe degradation and,as a result,the ecosystem services provided by the grass-lands are declining,in terms of provisioning,regulating,and supporting *** synthesized the existing literature on the ecosystem goods and services provided by these grasslands under grazing in different conditions and conservation *** found that plant and animal diversity and primary production are the most studied ecosystem services,while climate regulation,water supply,nutrient cycling,meat production and erosion control,in that order,are less *** services are *** grazing and glyphosate spraying are the main drivers of grassland *** grazing and conservative stocking rates have been shown to reverse degradation and demonstrate that livestock production is compatible with ecosystem conserva-tion by maintaining regulating and provisioning *** these management strategies are poorly integrated,improving their implementation will require important changes in farmers’decisions and the development of policies that create the economic conditions for this to *** is needed to understand the conditions that prevent the knowledge generated from being transferred to producers and translated into practices that would improve the provision of ecosystem services.

关键词： Salado basin sustainability biodiversity rangelands meat production adaptative multi paddock grazing process technologies agroecology