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challenges of advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第34期22卷 7645-7659页

作者： Stefano Colagrande Andrea l Inghilesi Sami Aburas Gian G Taliani Cosimo Nardi Fabio marra Dipartimento di Scienze Biomediche Sperimentali e Cliniche University of Florence Dipartimento di Medicina Sperimentale e Clinica Centro di Ricerca DenotheUniversity of Florence

Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

关键词： Barcelona Clinic liver Cancer Portal vein thrombosis Modified Response Evaluation Criteria in Solid Tumors Advanced hepatocellular carcinoma management Advanced hepatocellular carcinoma second line therapies Sorafenib

Relevance of Spike/Estrogen Receptor-αinteraction for endothelial-based coagulopathy induced by SARS-CoV-2

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2459-2462页

作者： Silvia Stella Barbieri Franca Cattani leonardo Sandrini Magda Maria Grillo Alessandra Amendola Carmen Valente Carmine Talarico Daniela Iaconis Gabriele Turacchio Miriam lucariello lucia lione Erika Salvatori Patrizia Amadio Gloria Garoffolo Mariano Maffei Francesca Galli Andrea Rosario Beccari Giuseppe Sberna Emanuele marra Marica Zoppi Michael Michaelides Giuseppe Roscilli luigi Aurisicchio Riccardo Bertini Marcello Allegretti Maurizio Pesce Centro Cardiologico Monzino IRCCSMilanoItaly Dompéfarmaceutici S.p.A. L’AquilaItaly Istituto Nazionale per le Malattie Infettive lazzaro Spallanzani RomaItaly Institute of Experimental Endocrinology and Oncology“G.Salvatore”(IEOS) National Research CouncilNaplesItaly EXSCAlATE DompéFarmaceutici S.p.ANapoliItaly Takis S.r.l. RomeItaly National Institute on Drug Abuse Intramural Research Program Baltimore21224MDUSA Johns Hopkins School of Medicine BaltimoreMDUSA Atreius S.a.s. L’AquilaItaly

Dear Editor,The severe coagulation syndrome in numerous organs is the major life-threatening conditions characterizing the acute infection by *** inflammation/dysfunction,platelet hyper-reactivity,generation of neutro... 详细信息

关键词： organs infection acute

Endoscopic ultrasonography-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer: An update

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World Journal of Gastrointestinal Endoscopy 2021年第10期13卷 460-472页

作者： Guillermo Pérez-Aguado Diego Martinez-Acitores de la Mata Carlos marra-lópez Valenciano Ignacio Fernandez-Urien Sainz Department of Gastroenterology Complejo Hospitalario Insular Materno Infantil de Gran CanariaLas Palmas de Gran CanariaLas Palmas 35016Spain Department of Gastroenterology Endoscopy UnitComplejo Hospitalario de Navarra CHNPamplona Navarra 31008Spain Department of Gastroenterology Endoscopy UnitAgencia Sanitaria Costa del SolMálaga 29603Spain

Pancreatic cancer produces disabling abdominal pain,and the pain medical management for pancreatic cancer is often challenging because it mainly relies on the use of narcotics(major opioids).However,opioids often provide suboptimal pain relief,and the use of opioids can lead to patient tolerance and several side effects that considerably reduce the quality of life of pancreatic cancer ***-guided celiac plexus neurolysis(EUS-CPN)is an alternative for pain control in patients with nonsurgical pancreatic cancer;EUS-CPN consists of the injection of alcohol and a local anesthetic into the area of the celiac plexus to achieve chemical ablation of the nerve ***-CPN via the transgastric approach is a safer and more accessible technique than the percutaneous *** have reviewed most of the studies that evaluate the efficacy of EUSCPN and that have compared the different approaches that have been performed by *** efficacy of EUS-CPN varies from 50%to 94%in the different studies,and EUS-CPN has a pain relief duration of 4–8 *** factors are involved in its efficacy,such as the onset of pain,previous use of chemotherapy,presence of metastatic disease,EUS-CPN technique,type of needle or neurolytic agent used,*** to this review,injection into the ganglia may be the best technique,and a good visualization of the ganglia is the best predictor for a good EUS-CPN response,although more studies are ***,any of the 4 different techniques could be used to perform EUS-CPN effectively with no differences in terms of complications between the techniques,but more studies are *** effect of EUS-CPN on pain improvement,patient survival and patient quality of life should be evaluated in well-designed randomized clinical *** research also needs to be performed to clarify the best time frame in performing a EUS-CPN.

关键词： Pancreatic cancer Endosonography Celiac plexus neurolysis Opioids Echoendoscopy

Soybean Flour Improves Fatty Acid Profile and Decreases Hepatic Triglyceride Deposition in Rats Fed with Normocaloric and Hypercaloric Diet

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Food and Nutrition Sciences 2015年第14期6卷 1245-1257页

作者： Gabriela S. Razzeto Viviana R. lucero lópez Carlos A. marra luis A. Scardapane Nora l. Escudero María S. Gimenez Department of Biochemistry and Biological Sciences Faculty of Chemistry Biochemistry and Pharmacy National University of San Luis San Luis Argentina INIBIOlP CONICET-UNLP Faculty of Medical Sciences National University of La Plata La Plata Argentina

This study investigated the effects of replacing casein with soy flour on the fatty acids profile and triglycerides metabolism in the liver of rats that were previously fed with normocaloric and hypercaloric diets based on casein. Wistar male rats were used;one group was fed with control diet (AIN-93) and another with hypercaloric diet (AIN-93 with 34.15% sucrose, 42% fat calories) for 9 weeks. Each group was then divided into two subgroups and casein was replaced with soybean in one of them, obtaining CC (control casein), CS (control soy), HC (hypercaloric casein) and HS (hypercaloric soy), which were fed for 6 weeks. We measured triglycerides in serum, and triglycerides, total lipids, fatty acids profile, the expression of apolipoprotein B (Apo B), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element-binding protein 1c (SREBP-1c), mitochondrial glycerol-3-phosphate acyltransferase (mGPAT), diacylglycerol acyltransferase 2 (DGAT-2), carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptors alpha (PPARα) in liver. Histological studies were also performed. When comparing HS vs. HC, a positive effect of soybean flour on hepatic triglycerides deposits was found, possibly through the reduction in DGAT-2 expression (P lour also decreased fat deposits in control diets when compared with casein, decreasing the DGAT-2 (P lipid droplets in HS, whereas a fat deposit in HC was observed. These results suggest that replacing casein with soybean flour in normocaloric and hypercaloric diets reduces triglycerides and improves fatty acids profile in rat liver.

关键词： Soybean Flour Normocaloric and Hypercaloric Diets Fatty Acids Triglyceride Metabolism Rat liver

Application of Trichoderma harzianum (T22) and Trichoderma atroviride (P1) as plant growth promoters, and their compatibility with copper oxychloride

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 425-425页

作者： Francesco Vinale Gaetano D'Ambrosio Khalid Abadi Felice Scala Roberta marra David Turrà Sheridan l Woo Matteo lorito Department Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) ItalyDepartment Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) ItalyDepartment Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) Italy Department Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) Italy Department Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) Italy Department Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) Italy Department Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) Italy Department Ar.Bo.Pa.Ve. Section of Plant Pathology University of Naples "Federico II" Portici. 80055 (NA) Italy

Trichoderma strains are used in agriculture because they provide to the plants the following benefits: i) are rhizosphere competence and establish stable rhizosphere microbial communities; ii) control plant disease caused by pathogenic and competitive microflora, by using a variety of mechanisms; iii) improve vegetative growth, root development and yield; iv) make nutrients more available to the plant. In this work we have investigated the ability of T. harzianum T22 and T. atroviride P1 to improve plant growth of locally important horticultural crops: lettuce, tomatoes and peppers and to prevent disease in the greenhouse and field. The effect of the Trichoderma treatment was evaluated by determining the weight of fresh and dry roots and above ground plant biomass, measuring plants height, counting the number of emerged leaves (lettuce, tomatoes and peppers) and quantifying production (tomatoes and peppers). No disease symptoms were found during production, although Fusarium sp. strains pathogenic to tomato were detected in the soil. Compounds containing copper oxychloride are frequently used for fungal disease control in agriculture. In order to investigate the compatibility of T. harzianum T22 and T. atroviride P1 with copper oxychloride applications, the effect on mycelia growth was monitored in both liquid and solid medium. In general, the tests indicated a high level of tolerance of the Trichoderma strains to concentrations of copper oxychloride varying from 0.1 to 5 mmol/l.

关键词：园艺作物真菌病害防治木霉属植物生长促进剂氯化铜

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Extracellular proteome of Trichoderma harzianum to identify proteins with biotechnological value

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 452-452页

作者： Ambrosino P Scala V marra R Vinale F Soriente I Ferraioli S Carbone V Ruocco M Woo S l lorito M Dep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyISA-CNR Avellino ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples ItalyDep. Ar.Bo.Pa.Ve.-Plant Pathology University of Naples "Federico II"-80055 Portici Naples Italy

Trichoderma harzianum strain T22 parasitizes and controls many phytopatogenic fungi and is applied commercially as biological control agent. The production of hydrolitic enzymes appears to be a key factor in the parasitic process. We tested the endo-esochitinolitic and glucanolitic activities of culture filtrates of T22 grown under carbon and nitrogen starvation or in presence of biomass or cell walls of the phytopathogenic fungi Botrytis cinerea, Rhizoctonia solani and Pythium ultimum. The highest level of enzimatic activities was found in culture where the mycoparasite interacted with a phytopathogenic fungus. Therefore we used a proteomic approach to investigate changes in the complex mixture of extracellular proteins secreted by T. harzianum strain T22 in order to identify proteins of potential biotechnology value for commercial and industrial *** technology has greatly enhanced our ability to conduct functional genomics studies. Nevertheless only a few studies have been published so far on the fungal extracellular proteome. Sample preparation remains the most critical step in analyses based on two-dimensional gel electrophoresis (2-DE), and it requires to be optimized for each specific application. In this study, our first aim was to set up the extraction protocol of the extracellular proteins secreted by T . harzianum strain T22 when it was grown in vitro .The secreted proteins were analysed by two-dimensional electrophoresis (2-DE) and substantial changes in the extracellular proteome of the mycoparasite have been observed. Comparing the 2D maps of the fungus grown in minimal medium with glycerol as carbon source (used as control condition) with those obtained in inducing conditions, a lot of novel proteins appeared. The higher number of novel and up-regulated spots was obtained in the presence of Rhizoctonia solani biomass. Other spots were specifically up-regulated by the interaction with different plant pathogens. Differentially expressed proteins

关键词：木霉属真菌蛋白质鉴定生物技术植物病原体水解酶

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Use of Trichoderma spp. for biological control of the livestock feed contaminant fungus Fusarium proliferatum

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 414-414页

作者： Ruocco M Pane F Ritieni A lanzuise S Ambrosino P marra R Woo S l Ciliento R Soriente I Ferraioli S Scala F lorito M Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 ItalyDip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Università di Napoli "Federico II" and CNR-IPP Via Università 100 Portici (NA) 80055 Italy Dip. Arboricoltura Botanica e Patologia Vegetale-Sez. Patologia Vegetale Lab. di Lotta Biologica Uni

Fusarium spp. are pathogens of many important agricultural crops, and are often strong mycotoxin producers. Fusarium proliferatum, in particular, causes disease in cereals and secretes the toxin Beauvaricin that contaminates livestock feed and cereals, producing a variety of toxicity symptoms ranging from poor weight gain to mortality. Beauvaricin is a cyclodepsipeptide and acts as a potent mycotoxin known to have insecticidal properties. This compound is highly toxic to human cell lines, where it induces apoptosis and specifically inhibits cholesterol acetyltransferase. Nothing is known about the role of this mycotoxin during the interaction of F. proliferatum with other microorganisms, including the fungal antagonists Trichoderma spp. In vitro tests have demonstrated that the antagonistic and mycoparasitic activity of Trichoderma is not inhibited by the presence of Beauvaricin at concentrations up to 10 mg/kg in the substrate. In vivo biocontrol assays on barley and wheat with Trichoderma against F. proliferatum isolates, producing and non-producing Beauvaricin, confirmed the ability of the antagonist to control this pathogen in all cases. Also Trichoderma culture filtrates obtained in conditions that promote Cell Wall Degrading Enzyme (CWDE) secretion, were able to inhibit. spore. germination. of. different. F.. proliferatum. isolates.. These. results. suggest. the. possibility. of. using. Trichoderma. and/or. its. metabolites. to. control. contaminants. of. livestock. feed. by. mycotoxin-producing. Fusarium..

关键词：家畜霉菌饲料污染物镰刀霉木霉属生物防治

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Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea l Inghilesi Donatella Gallori lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni luca Boni Giacomo laffi Francesco Di Costanzo Fabio marra Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Oncologia Medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established ***:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively *** to the Barcelona Clinic liver Cancer(BClC)classification,patients were in the advanced stage(BClC-C)or in the intermediate stage(BClC-B)but unfit or unresponsive to other therapeutic *** was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid *** was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall ***:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of *** caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,PlC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 *** 16 wk of treatment,18 patients(41%)had stable disease or partial *** with viral infection or BClC-C were at higher risk of disease ***,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall ***:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment *** invasion and extrahepatic spread condition early response to treatment and *** biochemical parameters may be helpful

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adver

Steroid-refractory ulcerative colitis and associated primary sclerosing cholangitis treated with infliximab

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World Journal of Gastroenterology 2013年第4期19卷 590-593页

作者： Ileana Duca Patricia Ramírez de la Piscina Silvia Estrada Rosario Calderón Katerina Spicakova leire Urtasun Carlos marra-lópez Salvador Zabaleta Raquel Bengoa María Asunción Marcaide Francisco García-Campos Service of Gastroenterology Hospital Universitario de álava-Sede TxagorritxuUniversidad del País VascoE-01009 Vitoria-GasteizSpain

Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative *** to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually *** describe a patient with long-standing ulcerative colitis,which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis(biochemical stage Ⅱ/Ⅳ) in the course of his *** with infliximab(5 mg/kg as an induction dose followed by maintenance doses every two months) was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprinerelated hepatic *** present,after two years of follow-up,the patient is asymptomatic with normal liver tests and complete resumption of daily life *** case draws attention to the usefulness of antitumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease.

关键词： Ulcerative colitis Infliximab Monoclonal antibodies Sclerosing cholangitis Bile duct diseases Tumor necrosis factor-alpha