- Liver Diseases and Immunity
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Amino Acid Enzymes and Metabolism
- Diet and metabolism studies
- Cancer, Hypoxia, and Metabolism
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Systemic Lupus Erythematosus Research
- Metabolism, Diabetes, and Cancer
- Organ Transplantation Techniques and Outcomes
- Peroxisome Proliferator-Activated Receptors
- MicroRNA in disease regulation
- Neuroendocrine Tumor Research Advances
- Diabetes and associated disorders
- Drug Transport and Resistance Mechanisms
- Systemic Sclerosis and Related Diseases
- Immunodeficiency and Autoimmune Disorders
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Gallbladder and Bile Duct Disorders
- Inflammatory Bowel Disease
- Immune Cell Function and Interaction
- Mast cells and histamine
- Polyamine Metabolism and Applications
University of Milano-Bicocca
2016-2020
Humanitas University
2008-2020
Japan Breast Cancer Research Group
2017
University of Milan
2006-2016
Canon (Japan)
2016
European Foundation for the Study of Chronic Liver Failure
2016
Istituti di Ricovero e Cura a Carattere Scientifico
2008-2013
Fondazione Humanitas per la Ricerca
2011
Ospedale San Paolo
2009
The cross-talk of cluster differentiation (CD)40/CD40 ligand (CD40L) plays a key role in CD4(+) T-cell priming, B-cell terminal maturation, and immunoglobulin (Ig) class-switch recombination. Genetic defects the CD40L lead to disorder characterized by elevated concentrations serum IgM immunodeficiency. Patients with primary biliary cirrhosis (PBC) characteristically show circulating antimitochondrial antibodies (AMAs), liver-infiltrating autoreactive T lymphocytes against mitochondrial...
Summary The altered expression of micro-RNA (miRNA) has been associated with Crohn's disease (CD) and ulcerative colitis (UC). aim this study was to establish specific miRNA patterns in the serum mucosa inflammatory bowel (IBD) patients (UC CD colonic involvement) at different stages disease. Serum biopsies from nine active (aCD), inactive (iCD), UC (aUC) (iUC) 33 healthy subjects were collected. Up 700 miRNAs evaluated by TaqMan® human array. ΔCt values obtained using mean all expressed a...
The secretin/secretin receptor (SR) axis is up‐regulated by proliferating cholangiocytes during cholestasis. Secretin stimulates biliary proliferation down‐regulation of let‐7a and subsequent up‐regulation the growth‐promoting factor, nerve growth factor (NGF). It not known whether secretin/SR plays a role in subepithelial fibrosis observed Our aim was to determine activation animal models human primary sclerosing cholangitis (PSC). Studies were performed wild‐type (WT) mice with bile duct...
Background and objectives Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. The growth factor, progranulin, overexpressed in number tumours. study aims were to assess the expression progranulin cholangiocarcinoma determine its effects on tumour growth. Methods secretion evaluated multiple cell lines clinical samples from patients cholangiocarcinoma. role interleukin 6 (IL-6)-mediated signalling was assessed using combination specific inhibitors...
Abstract Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. Symptoms are usually evident after blockage the bile duct by tumor, and at this late stage, they relatively resistant to chemotherapy radiation therapy. Therefore, it imperative that alternative options explored. We present novel data indicating metabolism serotonin dysregulated in cholangiocarcinoma cell lines, compared normal cholangiocytes, tissue from patients. Specifically, there was an...
Although the etiology of primary biliary cirrhosis (PBC) remains enigmatic, there are several pieces data supporting thesis that a strong genetic predisposition and environmental factors interact to produce selective loss tolerance. The striking female predominance PBC has suggested this sex may be secondary epigenetic alterations on X chromosome. In present study, we rigorously defined chromosome methylation profile CD4, CD8, CD14 cells from 30 patients controls. Genomic DNA sorted...
The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack sensitive and specific biomarkers, as early cholangiocarcinoma (CC), a complication PSC. aim this study was identify serum miRNAs diagnostic biomarkers for PSC CC. levels 667 were evaluated in 90 human samples (30 PSC, 30 CC control subjects) disease-associated candidate (discovery phase). deregulated validated an independent cohort 140 [40 40 CC, 20 biliary cirrhosis (PBC) controls]. Receiver operating...
Substance P (SP) is involved in the proliferation of cholangiocytes bile duct–ligated (BDL) mice and human cholangiocarcinoma growth by interacting with neurokinin‐1 receptor (NK‐1R). To identify whether SP regulates liver fibrosis during cholestasis, wild‐type or NK‐1R knockout (NK‐1R –/– ) that received BDL sham surgery multidrug resistance protein 2 ( Mdr2 treated either an antagonist (L‐733,060) saline were used. Additionally, intraperitoneally. In vivo , there was increased expression...
Hepatic fibrosis is marked by activation of hepatic stellate cells (HSCs). Cholestatic injury precedes liver fibrosis, and cholangiocytes interact with HSCs promoting fibrosis. Mast (MCs) infiltrate following release histamine, increasing biliary proliferation. We evaluated if inhibition MC-derived histamine decreases proliferation Wild-type multidrug resistance 2 knockout mice (9-11 weeks) were treated cromolyn sodium for 1 week to block histamine. Biliary mass immunohistochemistry...
Abstract Background & Aims Biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis ( PSC ) have not been firmly established. Enhanced liver fibrosis ELF test was previously reported to predict outcome . We aimed validate the prognostic utility of an independent, multi‐centre, retrospective study population. Methods collected serum samples from patients seven countries. estimated rates transplant‐free survival by Kaplan‐Meier method, used Cox proportional...
Primary sclerosing cholangitis (PSC) patients are at risk of developing cholangiocarcinoma (CCA). We have shown that (1) histamine increases biliary hyperplasia through H1/H2 receptors (HRs) and (2) levels increase mast cells (MCs) infiltrate during PSC CCA. examined the effects chronic treatment with H1/H2HR antagonists on Wild-type multidrug-resistant knockout (Mdr2-/- ) mice were treated by osmotic minipumps saline, mepyramine, or ranitidine (10 mg/kg body weight/day) a combination...
Cholestasis is a condition that leads to chronic hepatobiliary inflammation, fibrosis, and eventually cirrhosis. Many microRNAs (miRs) are known have role in fibrosis progression; however, the of miR-21 during cholestasis remains unknown. Therefore, aim this study was elucidate cholestasis-induced biliary hyperplasia hepatic fibrosis. Wild-type (WT) miR-21-/- mice underwent Sham or bile duct ligation (BDL) for 1 week, before evaluating liver histology, proliferation, stellate cell (HSC)...
Melatonin therapy or prolonged exposure to complete darkness reduces biliary hyperplasia and liver fibrosis in bile-duct-ligated (BDL) rats; however, no information exists primary sclerosing cholangitis (PSC). Thus, we aimed determine the therapeutic effects of dark melatonin administration on hepatic multidrug resistance gene 2-knockout (Mdr2-/-) mouse model PSC. levels, mass, fibrosis, angiogenesis miR-200b expression were evaluated wild-type Mdr2-/- mice exposed treatment male patients...
Biliary‐committed progenitor cells (small mouse cholangiocytes; SMCCs) from small bile ducts are more resistant to hepatobiliary injury than large cholangiocytes (LGCCs) ducts. The definitive endoderm marker, forkhead box A2 (FoxA2), is the key transcriptional factor that regulates cell differentiation and tissue regeneration. Our aim was characterize translational role of FoxA2 during cholestatic liver injury. Messenger RNA expression in SMCCs LGCCs assessed by polymerase chain reaction...
Cholangiocarcinoma (CCA) is a devastating biliary cancer. Melatonin synthesized in the pineal gland and peripheral organs from serotonin by two enzymes, N-acetyltransferase (AANAT) acetylserotonin O-methyltransferase (ASMT). Cholangiocytes secrete neuroendocrine factors, including serotonin-regulating CCA growth autocrine mechanisms. exerts its effects interaction with melatonin receptor type 1A/1B (MT1/MT2) receptors. We propose that 1) CCA, there decreased expression of AANAT ASMT...