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Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

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World Journal of Gastroenterology 2005年第44期11卷 7001-7006页

作者： Wolfgang Kruis Axel Dignass Elisabeth Steinhagen-Thiessen Julia Morgenstern Joachim M(o|¨)ssner Stephan Schreiber Maurizio Vecchi Alberto Malesci Max Reinshagen Robert L(o|¨)fberg Evangelisches Krankenhaus Kalk Medizinische Klinik für Hepatologie und Gastroenterologie Medizinische Klinik und Poliklinik Ⅱ Medizinische Klinik Dep of Int Medicine irccs Ospedale Policlinico istituto Clinico Humanitas Innere Medizin Karolinska Institute at the IBD unit

AIM： To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS： An open label multicenter study was carried out in 39 patients with active ulcerative colitis （CAI 6-8） despite continuous use of steroids （a minimum total dose of 400 mg prednisone within the last 4 wk）. Patients received a total of five aphereses using a granulocyte adsorptive technique （Adacolumn, Otsuka Pharmaceutical Europe, UK）. Assessments at wk 6 and during follow-up until 4 mo comprised clinical （CAI） and endoscopic （EI） activity index, histology, quality of life （IBDQ）, and laboratory tests. RESULTS： Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 （37.1%） patients achieved clinical remission and 10/35 （28.6%） patients had endoscopic remission （CAI〈4, EI〈4）. Quality of life （IBDQ） increased significantly （24 points, P〈0.01） at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION： In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

关键词： Steroid Refractory colitis Ulcerative colitis Granulocyte Apheresis

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Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

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World Journal of Gastroenterology 2013年第46期19卷 8659-8670页

作者： Martina Galatola Erasmo Miele Caterina Strisciuglio Lorella Paparo Daniela Rega Paolo Delrio Francesca Duraturo Massimo Martinelli Giovanni Battista Rossi Annamaria Staiano Paola Izzo Marina De Rosa Department of Molecular Medicine and Medical Biotechnology and CEINGE Biotecnologie Avanzate University of Naples"FedericoⅡ" Department of Translational Medical Sciences Section of PediatricsUniversity of Naples"FedericoⅡ" Colorectal Surgical Oncology-Abdominal Oncology Department Istituto Nazionale per lo studio e la cura dei tumori"Fondazione Giovanni Pascale"IRCCS-80131 NaplesItaly Endoscopy Unit Istituto Nazionale per lo studio e la cura dei tumori"Fondazione Giovanni Pascale"IRCCS-80131 NaplesItaly

AIM: To investigated the molecular cause of very early-onset ulcerative colitis (UC) in an 18-mo-old affected child.

关键词： Inflammatory bowel disease, Ulcerative colitis, Interleukin 10 receptors, Tumour necrosis factor α receptors, Beta catenin

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Future Directions in Metastatic Castration Resistant Prostate Cancer (mCRPC): Clinical Rationale and Use of New-Generation Hormonal Therapies

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Journal of Cancer Therapy 2013年第3期4卷 698-703页

作者： Paolo Grassi Elena Verzoni Rosanna Montone Isabella Testa Enrico Garanzini Pamela Biondani Sara Pusceddu Filippo de Braud Giuseppe Procopio Department of Medical Oncology Fondazione IRCCS Istituto Nazionale Tumori Milan Italy

Several recent studies in mCRPC have identified the mechanisms of tumoral growth after the disease becomes unresponsive to standard hormonal therapy. These studies have highlighted the importance of residual intratumoral androgens in maintaining androgen receptor (AR) transcriptional activity in mCRPC [1]. Based on this findings, it has been possible to develop drugs, blocking the key enzyme in the biosynthesis of androgens through the inhibition of cytochrome p450 17 (CYP17) such as Abiraterone Acetate (AA) and drugs which directly target the AR including Enzalutamide (E) and Orteronel. Before this new knowledge, mCRPC treatment benefited from chemotherapy with taxanes. Recently a new taxane, Cabazitaxel (C), was approved in second line setting in association with prednisone. Retrospective analyses have tried to clarify the current role of chemotherapy in mCRPC patients and the right chemotherapy sequence of use of chemotherapy compared to new hormonal agents. Moreover, it would be important to address changes in the endpoints used in clinical trials, based on the stage of disease including the presence tumor-related symptoms, in order to identify the right therapeutic strategy.

关键词： Metastatic Castration Resistant Prostate Cancer Abiraterone Cabazitaxel Enzalutamide

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The epigenetics of autoimmunity

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Cellular & Molecular Immunology 2011年第3期8卷 226-236页

作者： Francesca Meda Marco Folci Andrea Baccarelli Carlo Selmi Department of Medicine and Hepatobiliary Immunopathology Unit IRCCS Istituto Clinico HumanitasRozzanoMilanItaly Department of Translational Medicine University of MilanRozzanoMilanItaly Harvard School of Public Health ExposureEpidemiology&Risk ProgramBostonMAUSA

The etiology of autoimmune diseases remains largely *** rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of *** lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt *** in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune *** recent years,several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and *** specifically,data support the impact of epigenetic changes in systemic lupus erythematosus,rheumatoid arthritis,multiple sclerosis and other autoimmune diseases,in some cases based on mechanistical *** herein discuss what we currently know and what we expect will come in the next ***,epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases.

关键词： DNA methylation histone modification microRNA tolerance breakdown

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Loss of CDKN1B induces an age-related clonal hematopoietic disorder via Notch2 activity dysregulation

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Cancer Communications 2023年第7期43卷 844-849页

作者： Ilenia Segatto Gian Luca Rampioni Vinciguerra Ilenia Pellarin Alessandra Dall’Acqua Stefania Berton Francesca Citron Sara D’Andrea Giorgia Mungo Davide Viotto Lorena Musco Arianna Di Napoli Maria Antonietta Aloe Spiriti Vincenzo Canzonieri Valter Gattei Andrea Vecchione Barbara Belletti Gustavo Baldassarre Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano(PN)Italy Department of Clinical and Molecular Medicine University of Rome“La Sapienza”Santo Andrea HospitalRomeItaly Division of Pathology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano(PN)Italy Division of Clinical and Experimental Onco-Hematology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano(PN)Italy

Dear Editor,The tumor suppressor gene CDKN1B,encoding for the p27^(Kip1)(p27)protein,defines the smallest region of deletion on chromosome 12p13 described in clonal hematopoietic disorders(CHDs)[1].Among them,myelodysplastic syndromes(MDSs)display typical onset in the elderly and an indolent behavior that may evolve in acute myeloid leukemia(AML)[2].Recent evidences support a model of parallel clonal evolution at the stem or progenitor cell level and implicate the need of more preclinical,translational and clinical research to identify better ways to timely target clones that may evolve toward malignancy[3,4].

关键词： hematopoietic clinical acute

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Seafood loss prevention and waste reduction

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Food Quality and Safety 2024年第2期8卷 239-267页

作者： Andrea Conz Enrico Davoli Carlotta Franchi Luisa Diomede Department of Molecular Biochemistry and Pharmacology Istituto di Ricerche Farmacologiche Mario Negri IRCCSMilanoItaly Department of Environmental Health Istituto di Ricerche Farmacologiche Mario Negri IRCCSMilanoItaly Department of Health Policy Istituto di Ricerche Farmacologiche Mario Negri IRCCSMilanoItaly Italian Institute for Planetary Health(IIPH) MilanItaly

Despite its high demand,the seafood processing industry grapples with a substantial challenge:generating signifcant waste,encompassing edible and inedible *** leads to considerable fnancial losses and raises socioecological concerns regarding managing and disposing of such *** addressing this issue,implementing sustainable seafood preservation methods becomes *** study provides a comprehensive summary of chemical and physical approaches proposed in the literature to prevent seafood loss and diminish waste.A literature search from 2000 to January 2023 yielded 49 publications meeting the inclusion criteria,revealing a fragmented landscape of studies conducted on various fsh products under diverse *** methods include organic acids and bio-derived preservatives;physical approaches comprise cold plasma,high hydrostatic pressure,and UV-C *** advantages and disadvantages of each technique were considered and *** chitosans,derived from natural sources and Generally Recognized As Safe,has emerged as the most promising ***,the discourse on fsh preservation methods remains an evolving topic,weaving between the complexities of food safety,consumer satisfaction,and economic and environmental *** research is needed to investigate spoilage during production and critically evaluate the waste generated at different stages of the industrial process.

关键词： Seafood spoilage Shelf-life extension Microbial control Quality control Quality maintenance Non-thermal technologies Food safety

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Prediction of hepatocellular carcinoma biological behaviorin patient selection for liver transplantation

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World Journal of Gastroenterology 2016年第1期22卷 232-252页

作者： Umberto Cillo Tommaso Giuliani Marina Polacco Luz Maria Herrero Manley Gino Crivellari Alessandro Vitale Hepatobiliary Surgery and Liver Transplantation Unit Department of General Surgery and Organ TransplantationUniversity Hospital of Padua35128 PadovaItaly UnitàOperativa di Oncologia Medica Istituto Oncologico Veneto(IOV)IRCCS35128 PadovaItaly

Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma(HCC)patients for liver transplantation(LT).These criteria,which are often inappropriate to express the tumor’s biological behavior and aggressiveness,offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after ***-fetoprotein(AFP)and its progression as well as AFP-m RNA,AFP-L3%,des-γ-carboxyprothrombin,inflammatory markers and other serological tests appear to be correlated with post-transplant *** other markers for patient selection including functional imaging studies such as18F-FDG-PET imaging,histological evaluation of tumor grade,tissue-specific biomarkers,and molecular signatures have been outlined in the *** growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC *** AFP,its progression,and HCC response to pretransplant therapy have already been used as a part of an integrated prognostic model for selecting patients,the utility of other markers in the transplant setting is still under *** article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.

关键词： Hepatocellular carcinoma Liver Alphafetoprotein Transplantation Biomarkers Histopathology Recurrence Integrated prognostic tool

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Endoscopic ultrasound assessment and tissue acquisition of mediastinal and abdominal lymph nodes

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1475-1491页

作者： Giacomo Tamanini Anna Cominardi Nicole Brighi Pietro Fusaroli Andrea Lisotti Department of Gastroenterology Unit Hospital of ImolaUniversity of BolognaImola 40026BOItaly Department of Medical Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori(IRST)"Dino Amadori"Meldola 47014FCItaly

The differential diagnosis between benign and malignant lymph nodes(LNs)has a fundamental role in the characterization and staging of malignant conditions,as well as in subsequent patients’*** imaging modalities(*** tomography and magnetic resonance imaging)rely mainly on size;endoscopic ultrasound(EUS)criteria based on B-mode evaluation and Doppler features fail to adequately characterize with high specificity LNs *** introduction of EUS-elastography and contrast-enhanced harmonic EUS are useful techniques to increase the diagnostic yield in identifying metastatic LNs,to identify which suspicious LN should require pathological characterization and,finally,to target tissue ***-guided tissue acquisition(EUS-TA)is increasingly being used for diagnosing lymphadenopathy whenever the characterization modifies patients’subsequent management and when no superficial LN is *** target therapy are currently available(*** cancer,breast cancer),EUS-TA of malignant LNs could be required to identify tumor *** this field,both fine needle aspiration and biopsy needles are able to guarantee accurate results with almost perfect specificity and sub-optimal *** finally propose a diagnostic algorithm based on most recent,high-level evidence for the diagnostic approach to suspected LNs assessment.

关键词： Endoscopic ultrasound-guided tissue acquisition Endoscopic ultrasound-fine needle aspiration Endoscopic ultrasound-fine needle biopsy Biopsy Aspiration Cancer

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Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

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World Journal of Gastroenterology 2018年第36期24卷 4152-4163页

作者： Giorgia Marisi Alessandro Cucchetti Paola Ulivi Matteo Canale Giuseppe Cabibbo Leonardo Solaini Francesco G Foschi Serena De Matteis Giorgio Ercolani Martina Valgiusti Giovanni L Frassineti Mario Scartozzi Andrea Casadei Gardini Biosciences Laboratory Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Department of Medical and Surgical Sciences Alma Mater StudiorumUniversity of Bologna General and Oncologic Surgery Morgagni-Pierantoni Hospital Section of Gastroenterology DI.BI.M.I.S.University of Palermo Department of Internal Medicine Degli Infermi Hospital Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS Department of Medical Oncology University of Cagliari

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma(HCC) since 2007 and numerous studieshave investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.

关键词： Biomarker Angiopoietin Neutrophil-tolymphocyte ratio Polymorphisms Sorafenib MicroRNA Adverse events Hepatocellular carcinoma Vascular endothelial growth factor

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miRNAs in precancerous lesions of the gastrointestinal tract

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World Journal of Gastroenterology 2011年第48期17卷 5231-5239页

作者： Matteo Fassan Carlo M Croce Massimo Rugge Department of Medical Diagnostic Sciences and Special Therapies Surgical Pathology and Cytopathology Unit University of Padova Department of Oncological and Surgical Sciences General Oncology Unit University of Padova Comprehensive Cancer Center Ohio State University istituto Oncologico del Veneto-IOV-irccs

In spite of the well-established understanding of the phenotypic lesions occurring in the shift from native epithelia to invasive （adeno） carcinoma, the molecular b/ping of the precancerous changes in the gastrointes- tinal tract remains unreliable. In recent years, no biomarkers have aroused as much interest as the miRNAs, a class of non-coding RNA molecules that function as endogenous silencers of numerous target genes. Aberrant miRNA expression is a hallmark of human disease, including cancer. Unlike most mRNAs, miRNAs are both long-living in vivo and very stable in vitro. Such charac- teristics allow their testing in paraffin-embedded tissue samples, which is essential in the biological profiling of small （phenotypically characterized） preneoplastic lesions of the gastrointestinal tract （as well as in other fields of human pathology）. The upcoming challenge lies in the reliable identification of disease-specific targets of dysregulated miRNAs, to enable miRNA testing in the clinical management of the secondary prevention of gastrointestinal cancer.

关键词： miRNA Dysplasia Barrett's esophagus Atro-phic gastritis Inflammatory bowel disease

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