6 results on '"Caporali, C."'
Search Results
2. Angiopoietin-2/Tie2 Inhibition by Regorafenib Associates With Striking Response in a Patient With Aggressive Hepatocellular Carcinoma.
- Author
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Todesca P, Marzi L, Critelli RM, Cuffari B, Caporali C, Turco L, Pinelli G, Schepis F, Carulli L, de Maria N, Casari F, Scaglioni R, and Villa E
- Subjects
- Carcinoma, Hepatocellular pathology, Humans, Liver Neoplasms pathology, Male, Middle Aged, Treatment Outcome, Angiopoietin-2 antagonists & inhibitors, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Phenylurea Compounds pharmacology, Phenylurea Compounds therapeutic use, Pyridines pharmacology, Pyridines therapeutic use, Receptor, TIE-2 antagonists & inhibitors
- Published
- 2019
- Full Text
- View/download PDF
3. Liver Angiopoietin-2 Is a Key Predictor of De Novo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct-Acting Antivirals.
- Author
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Faillaci F, Marzi L, Critelli R, Milosa F, Schepis F, Turola E, Andreani S, Vandelli G, Bernabucci V, Lei B, D'Ambrosio F, Bristot L, Cavalletto L, Chemello L, Sighinolfi P, Manni P, Maiorana A, Caporali C, Bianchini M, Marsico M, Turco L, de Maria N, Del Buono M, Todesca P, di Lena L, Romagnoli D, Magistri P, di Benedetto F, Bruno S, Taliani G, Giannelli G, Martinez-Chantar ML, and Villa E
- Subjects
- Aged, Carcinoma, Hepatocellular blood, Female, Hepatitis C complications, Humans, Hypertension, Portal complications, Liver Cirrhosis complications, Liver Cirrhosis virology, Liver Neoplasms blood, Male, Middle Aged, Neoplasm Recurrence, Local metabolism, Neovascularization, Pathologic, Prospective Studies, Tumor Microenvironment, Vascular Endothelial Growth Factor A blood, Angiopoietin-2 blood, Antiviral Agents adverse effects, Carcinoma, Hepatocellular chemically induced, Hepatitis C drug therapy, Liver Neoplasms chemically induced, Neoplasm Recurrence, Local chemically induced
- Abstract
Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA-treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin-2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C-reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo-Doppler work-up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = -0.412, P = 0.037 and r = -0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3-month follow-up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044-1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080-2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395-16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127-13.203; P = 0.032) were independent predictors of de novo HCC., Conclusion: Our study indicates that DAA-mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo-angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000-000)., (© 2018 by the American Association for the Study of Liver Diseases.)
- Published
- 2018
- Full Text
- View/download PDF
4. Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study.
- Author
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Critelli R, Milosa F, Faillaci F, Condello R, Turola E, Marzi L, Lei B, Dituri F, Andreani S, Sighinolfi P, Manni P, Maiorana A, Caporali C, di Benedetto F, Del Buono M, De Maria N, Schepis F, Martinez-Chantar ML, Giannelli G, and Villa E
- Subjects
- Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Female, Humans, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Prospective Studies, Signal Transduction, Survival Analysis, Tumor Microenvironment, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics
- Abstract
In HCC, tumor microenvironment, heavily influenced by the underlying chronic liver disease, etiology and stage of the tissue damage, affects tumor progression and determines the high heterogeneity of the tumor. Aim of this study was to identify the circulating and tissue components of the microenvironment immune-mediated response affecting the aggressiveness and the ensuing clinical outcome. We analyzed the baseline paired HCC and the surrounding tissue biopsies from a prospective cohort of 132 patients at the first diagnosis of HCC for immunolocalization of PD-1/PD-L1, FoxP3, E-cadherin, CLEC2 and for a panel of 82 microRNA associated with regulation of angiogenesis, cell proliferation, cell signaling, immune control and autophagy. Original microarray data were also explored. Serum samples were analyzed for a panel of 19 cytokines. Data were associated with biochemical data, histopathology and survival. Patients with a more aggressive disease and shorter survival, who we named fast-growing accordingly to the tumor doubling time, at presentation had significantly higher AFP levels, TGF-β1 and Cyphra 21-1 levels. Transcriptomic analysis evidenced a significant downregulation of CLEC2 and upregulation of several metalloproteinases. A marked local upregulation of both PD-1 and PD-L1, a concomitant FoxP3-positive lymphocytic infiltrate, a loss of E-cadherin, gain of epithelial-mesenchymal transition (EMT) phenotype and extreme poor differentiation at histology were also present. Upregulated microRNA in fast-growing HCCs are associated with TGF-β signaling, angiogenesis and inflammation. Our data show that fast HCCs are characterized not only by redundant neo-angiogenesis but also by unique features of distinctively immunosuppressed microenvironment, prominent EMT, and clear-cut activation of TGFβ1 signaling in a general background of long-standing and permanent inflammatory state.
- Published
- 2017
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5. Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study.
- Author
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Villa E, Critelli R, Lei B, Marzocchi G, Cammà C, Giannelli G, Pontisso P, Cabibbo G, Enea M, Colopi S, Caporali C, Pollicino T, Milosa F, Karampatou A, Todesca P, Bertolini E, Maccio L, Martinez-Chantar ML, Turola E, Del Buono M, De Maria N, Ballestri S, Schepis F, Loria P, Enrico Gerunda G, Losi L, and Cillo U
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular mortality, Disease Progression, Female, Humans, Liver Neoplasms mortality, Male, Middle Aged, Neovascularization, Pathologic genetics, Prospective Studies, Survival Rate, Time Factors, Tumor Burden, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Liver Neoplasms genetics, Liver Neoplasms pathology
- Abstract
Objective: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC., Design: Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V0 and V1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of survival were assessed by multivariate Cox model., Results: Calculated tumour doubling times ranged from 30 to 621 days (mean, 107±91 days; median, 83 days) and were divided into quartiles: ≤53 days (n=19), 54-82 days (n=20), 83-110 days (n=20) and ≥111 days (n=19). Median survival according to doubling time was significantly lower for the first quartile versus the others (11 vs 41 months, 42, and 47 months, respectively) (p<0.0001). A five-gene transcriptomic hepatic signature including angiopoietin-2 (ANGPT2), delta-like ligand 4 (DLL4), neuropilin (NRP)/tolloid (TLL)-like 2 (NETO2), endothelial cell-specific molecule-1 (ESM1), and nuclear receptor subfamily 4, group A, member 1 (NR4A1) was found to accurately identify rapidly growing HCCs of the first quartile (ROC AUC: 0.961; 95% CI 0.919 to 1.000; p<0.0001) and to be an independent factor for mortality (HR: 3.987; 95% CI 1.941 to 8.193, p<0.0001)., Conclusions: The hepatic five-gene signature was able to predict HCC growth in individual patient and the consequent risk of death. This implies a role of this molecular tool in the future therapeutic management of patients with HCC., Trial Registration Number: ClinicalTrials.gov Identifier: NCT01657695., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
- Full Text
- View/download PDF
6. Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study
- Author
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Mariagrazia Del Buono, Paola Loria, Teresa Pollicino, Stefano Colopi, Elena Bertolini, Guido Marzocchi, Stefano Ballestri, Cristian Caporali, Calogero Cammà, Barbara Lei, Aimilia Karampatou, Gianluigi Giannelli, Fabiola Milosa, Erica Villa, Giuseppe Cabibbo, Marco Enea, Elena Turola, Rosina Maria Critelli, Umberto Cillo, Giorgio Enrico Gerunda, Patrizia Pontisso, Nicola De Maria, María L. Martínez-Chantar, Paola Todesca, Luisa Losi, Livia Maccio, Filippo Schepis, Villa E., Critelli R., Lei B., Marzocchi G., Camma C., Giannelli G., Pontisso P., Cabibbo G., Enea M., Colopi S., Caporali C., Pollicino T., Milosa F., Karampatou A., Todesca P., Bertolini E., Maccio L., Martinez-Chantar M.L., Turola E., Dal Buono M., De Maria N., Ballestri S., Schepis F., Loria P., Gerunda G.E., Losi L., and Cillo U.
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Carcinoma, Hepatocellular ,Time Factor ,Microarray ,Hepatocellular carcinoma ,molecular carcinogenesis ,Gastroenterology ,liver imaging ,HEPATOCELLULAR CARCINOMA ,LIVER IMAGING ,MOLECULAR CARCINOGENESIS ,MOLECULAR ONCOLOGY ,Aged ,Aged, 80 and over ,Disease Progression ,Female ,Humans ,Liver Neoplasms ,Middle Aged ,Neovascularization, Pathologic ,Prospective Studies ,Survival Rate ,Tumor Burden ,Medicine (all) ,03 medical and health sciences ,molecular oncology ,0302 clinical medicine ,Hepatocellular carcinoma, liver imaging, molecular carcinogenesis, molecular oncology ,Internal medicine ,medicine ,Carcinoma ,Doubling time ,Prospective cohort study ,Survival rate ,business.industry ,Proportional hazards model ,medicine.disease ,Prospective Studie ,030104 developmental biology ,Quartile ,Liver Neoplasm ,030220 oncology & carcinogenesis ,business ,Human - Abstract
Objective The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC.Design Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V-0 and V-1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of survival were assessed by multivariate Cox model.Results Calculated tumour doubling times ranged from 30 to 621 days (mean, 107 +/- 91 days; median, 83 days) and were divided into quartiles: = 111 days (n= 19). Median survival according to doubling time was significantly lower for the first quartile versus the others (11 vs 41 months, 42, and 47 months, respectively) (p< 0.0001). A five-gene transcriptomic hepatic signature including angiopoietin-2 (ANGPT2), delta-like ligand 4 (DLL4), neuropilin (NRP)/tolloid (TLL)-like 2 (NETO2), endothelial cell-specific molecule-1 (ESM1), and nuclear receptor subfamily 4, group A, member 1 (NR4A1) was found to accurately identify rapidly growing HCCs of the first quartile (ROC AUC: 0.961; 95% CI 0.919 to 1.000; p< 0.0001) and to be an independent factor for mortality (HR: 3.987; 95% CI 1.941 to 8.193, p< 0.0001).Conclusions The hepatic five-gene signature was able to predict HCC growth in individual patient and the consequent risk of death. This implies a role of this molecular tool in the future therapeutic management of patients with HCC.
- Published
- 2015
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