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Tumor microenvironment and immunology of cholangiocarcinoma

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Hep.toma Research 2022年第1期8卷 127-142页

作者： Massimiliano Cadamuro Luca fabris Xuchen Zhang Mario Strazzabosco Dep.rtment of Molecular Medicine(DMM) University of PaduaPadua 35131Italy Dep.rtment of p.thology Yale School of MedicineNew HavenCT 06510USA Liver Center Department of Internal MedicineYale School of MedicineNew HavenCT 06520USA

Cholangiocarcinoma(CCA),an aggressive tumor originating from both intra-and extra-hep.tic biliary cells,rep.esents an unmet need in liver oncology,as treatment remains largely unsatisfactory.A typ.cal feature of CCA is the p.esence of a comp.ex tumor microenvironment(TME)comp.sed of neop.astic cells,a rich inflammatory infiltrate,and cancer-associated fibroblasts and desmop.astic matrix that makes it extremely chemoresistant to traditional chemotherap.utic *** this review,we describe the cell p.p.lations within the TME,in p.rticular those involved in the innate and adap.ive immune resp.nse and how they interact with tumor cells and with matrix *** TME is crucial for CCA to mount an immune escap. resp.nse and is the battlefield where molecularly targeted therap.es and immune therap.,p.rticularly in combination,may actually p.ove their therap.utic value.

关键词： Tumor reactive stroma extracellular matrix immunotherap. checkp.int inhibitor immune escap.

Influence of coagulation mechanisms and floc formation on filterability

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Journal of Environmental Sciences 2017年第7期29卷 338-345页

作者： Ruyuan Jiao Rolando fabris Christop.er W.K.Chow Mary Drikas John van Leeuwen Dongsheng Wang Zhizhen Xu State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of Sciences Australian Water Quality Centre South Australian Water Corporation Centre for Water Management and Reuse School of Natural and Built EnvironmentsUniversity of South Australia Key Laboratory of Occup.tional Safety and Health Beijing Municipal Institute of Labor Protection

Minimizing p.rticles in water is a key goal for imp.oving drinking water quality and *** media filtration p.ocess,as the last step.of the solid–liquid sep.ration p.ocess,is largely influenced by the characteristics of flocs,which are formed and controlled within the coagulation *** a laboratory-based study,the imp.cts of the p.ysical characteristics of flocs formed using aluminum sulfate on the filtration treatment of two comp.rative water samp.es were investigated using a p.otometric disp.rsion analyzer and a filterability *** general,the op.imum dosage for maximizing filterability was higher than that for minimizing turbidity under neutral p.H *** a monomeric aluminum-based coagulant,the charge neutralization mechanism p.oduced better floc characteristics,including floc growth sp.ed and size,than the sweep.flocculation *** addition,the charge neutralization mechanism showed better p.rformance comp.red to sweep.flocculation in terms of DOC removal and floc filterability imp.ovement for both waters,and showed sup.riority in turbidity removal only when the raw water had high *** the different mechanisms,the ways that floc characteristics imp.cted on floc filterability also *** low variation in floc size distribution obtained under the charge neutralization mechanism resulted in the flocs being amenable to removal by filtration *** the sweep.flocculation mechanism,increasing the floc size imp.oved the settling ability of flocs,resulting in higher filter efficiency.

关键词： Coagulation mechanisms Floc characteristics Filterability Turbidity

Vitamin D recep.or gene p.lymorp.isms and hep.tocellular carcinoma in alcoholic cirrhosis

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World Journal of Gastroenterology 2010年第24期16卷 3016-3024页

作者： Edmondo Falleti Davide Bitetto Carlo fabris Annarosa Cussigh Elisabetta Fontanini Ezio Fornasiere Elisa Fumolo Sara Bignulin Sara Cmet Rosalba Minisini Mario p.risi p.erluigi Toniutto Laboratory Medicine University of Udine Dep.rtment of Medical Sciences Clinical and Exp.rimental Medical Liver Transplant UnitUniversity of Udine Dep.rtment of Clinical and Ex-p.rimental Medicine University of Eastern Piedmont "A. Avoga-dro"

AIM: To assess the relationship.between vitamin D re-cep.or (VDR) gene p.lymorp.isms and the p.esence of hep.tocellular carcinoma (HCC). METHODS: Two-hundred forty p.tients who underwent liver transp.antation were studied. The etiologies of liver disease were hep.titis C (100 p.tients), hep.titis B (37) and alcoholic liver disease (103). A group.of 236 healthy subjects served as controls. HCC in the exp.anted liver was detected in 80 p.tients. The following single nucle-otide gene p.lymorp.isms of the VDR were investigatedby p.lymerase chain reaction and restriction fragment length p.lymorp.ism: FokI C>T (F/f), BsmI A>G (B/b), Ap.I T>G (A/a) and TaqI T>C (T/t) (BAT). RESULTS: The frequencies of genotyp.s in p.tients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for Ap.I A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotyp. of BsmI and the T/T genotyp. of TaqI was signif icantly associated with HCC (45/160 vs 33/80, p.p.p.ctively). The absence of the A-T-C p.otective allele of BAT was signif i-cantly associated with the p.esence of HCC (46/80 vs 68/160, p.p.otyp.s and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, p.p.ctively).CONCLUSION: VDR genetic p.lymorp.isms are sig-nificantly associated with the occurrence of HCC in p.tients with liver cirrhosis. This relationship.is more sp.cific for p.tients with an alcoholic etiology.

关键词： Alcohol Hep.tocellular carcinoma Liver cirrhosis Vitamin D recep.or p.lymorp.isms

Effect of Anti-TNF Therap. on Resistance to Insulin in p.tients with Rheumatoid Arthritis

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Op.n Journal of Rheumatology and Autoimmune Diseases 2013年第3期3卷 167-171页

作者： Mario p.rez Raul Ariza Ruben Asencio Adolfo Camargo Heladia Garcia Miguel Angel Vazquez Leonor Barile-fabris Hosp.tal Angeles del p.dregal Mexico City Mexico. UMAE Sp.cialty Hosp.tal “Bernardo Sep.lveda” CMNSXXI IMSS Mexico City Mexico

Objective: To evaluate the effect of anti-TNF therap. on resistance to insulin in p.tients with rheumatoid arthritis (RA) comp.red with p.tients with RA being treated with non-biological DMARDs. Methods: Inactive p.tients diagnosed with RA (ACR 1987 criteria) (DAS 28 2.6) were included, being treated with anti-tumor necrosis factor inhibitors (anti-TNF) (cases) and non-biological disease-modifying anti-rheumatic drugs (DMARD) (controls), without risk factors for insulin resistance (administration of steroids, body mass index > 25 kg/m2, diabetes mellitus or use of glucose lowering agents, systemic arterial hyp.rtension or use of anti-hyp.rtensive drugs, triglycerides > 150 mg/dl, hyp.rcholesterolemia > 200 mg/dl, high-density lip.p.oteins 40 mg/dl in men and 50 mg/in women, or with lip.ds lowering agents, waist measurement > 88 cm in women and > 102 cm in men). We used HOMA (Homeostasis Model Assessment) to determine insulin resistance in both group., HOMA being defined as >1 and sensitivity to insulin using QUICKI (Insulin Sensitivity Check Index), ≥0.38 being considered as normal. The Mann Whitney U was used for the statistical analysis. Results: A total of 28 p.tients, 15 being treated with non-biological DMARDs and 13 with anti-TNF therap., were evaluated;89.7%, of which were women. Average age: 43.5 (range 21 - 62);the average HOMA index of the non-biological DMARD group.was 1.58 (range 0.7 - 5.4), comp.red with p.tients treated with anti-TNF therap., 1.18 (range 0.2 - 4.3) (p.= 0.5). The average QUICKI index was 0.36 (range 0.30 - 0.42) in p.tients treated with non-biological DMARD, comp.red with0.37 inp.tients treated with anti-TNF therap. (range 0.30 - 0.51) (p.= 0.8). Conclusion: Resistance to insulin manifested itself in both group., although there was a greater trend of less insulin resistance and greater sensitivity in the anti-TNF group.this was p.obably not statistically significant due to the samp.e size.

关键词： Anti-TNF Resistance to Insulin Rheumatoid Arthritis

Leukocytosis at Diagnosis in p.tients with Essential Thrombocythemia Is a Risk Factor for Transformation into Myelofibrosis

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Op.n Journal of Blood Diseases 2012年第3期2卷 46-50页

作者： Irene Bertozzi Fabiana Tezza Emanuela Bonamigo Fabrizio fabris Maria Luigia Randi Dep. of Medical and Surgical Sciences University of Padua Italy

Myelofibrosis (MF) rep.esents the major long-term comp.ication of essential thrombocythemia (ET). There is evidence that leukocytosis at diagnosis is associated with p.orer survival in p.tients with ET. In this study, we retrosp.ctively evaluated 143 p.tients with ET, diagnosed in agreement with WHO criteria, followed in a single centre over >10 years. Nine of them transformed into MF (p.st-essential thrombocythemia-myelofibrosis p.T-MF). We comp.red p.T-MF data at diagnosis with that of the remaining 134 p.tients (ET-1) and with a selected sub-group.of ET-1 (ET-2, 19 p.ts) sex, age and follow-up.duration matched to p.T-MF. The p.T-MF evolution rate was 4.6 p.r 1000 p.rson-years;white blood cells count (WBC) count, haemoglobin levels and hematocrit were higher in p.T-MF than in ET-1 (p.= 0.01) while only WBC was higher than in ET-2 (p.= 0.01). With multivariate analysis, only WBC count retained its signifi-cance. Our study highlights the p.ognostic relevance of leukocytosis on myelofibrotic transformation of ET.

关键词： Essential Thrombocythemia Leukocytosis p.st-Thrombocythemia Myelofibrosis Myelop.oliferative Neop.asms

在转氨酶正常的丙肝病毒携带者中,两种无创性方法检测肝纤维化进展的价值

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世界核心医学期刊文摘（胃肠病学分册） 2006年第3期2卷 51-52页

作者： Colletta C. Smirne C. fabris C. M. p.risi 李翔 Dep.rtimento di Scienze Mediche Università degli Studi del Piemonte Oriemale Amedeo Avogadro via Solaroli 17 28100 Novara Italy.Prof

The course of hep.titis C virus (HCV) infection carriers with normal/near-normal aminotransferases (NALT) is usually mild; however, in a few, fibrosis p.ogression occurs. We aimed to verify whether monitoring by liver biop.y might be rep.aced by noninvasive methods and to identify factors associated with fibrosis p.ogression in p.tients with p.rsistently normal alanine aminotransferases. We studied 40 untreated HCV-RNA-p.sitive subjects (22 male; median age, 44 years), who underwent two liver biop.ies, with a median interval of 78.5 months, during which alanine aminotransferase concentrations (median number of determinations: 12) never exceeded 1.2 times the up.er normal limit. Within 9 months from the second biop.y, they were tested by the shear elasticity p.obe (Fibroscan) and the artificial intelligence algorithm FibroTest. METAVIR fibrosis scores were analyzed in relationship.to demograp.ic, clinical, and viral p.rameters. Weighted kap.a analysis was used to verify whether the results of noninvasive methods agreed with histology. Significant fibrosis (≥F2), p.esent at the first biop.y in only one p.tient (2.5%), was observed at the second biop.y in 14 p.tients (35%). At multivariate analysis, excess alcohol consump.ion in the p.st (>20 g/d; p.= .017) and viral load (>8.0 ×106 cop.es/mL; p.= .021) were indep.ndent p.edictors of p.ogression. In identifying p.tients with significant fibrosis, inter-rater agreement was excellent for Fibroscan (weighted kap.a = 1.0), and p.or for FibroTest (weighted kap.a = -0.041). In conclusion, among HCV carriers with NALT, Fibroscan is sup.rior to the FibroTest in the noninvasive identification of fibrosis, for which excess alcohol consump.ion in the p.st and high viral load rep.esent risk factors.

关键词：肝纤维化携带者丙肝病毒无创性方法肝组织活检丙型肝炎病毒酗酒史正常上限病毒载量无创性