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3. Serological and Molecular Characterization of Hepatitis C Virus-Related Cryoglobulinemic Vasculitis in Patients without Cryoprecipitate

Author

Napodano, Cecilia, primary, Ciasca, Gabriele, additional, Chiusolo, Patrizia, additional, Pocino, Krizia, additional, Gragnani, Laura, additional, Stefanile, Annunziata, additional, Gulli, Francesca, additional, Lorini, Serena, additional, Minnella, Gessica, additional, Fosso, Federica, additional, Di Santo, Riccardo, additional, Romanò, Sabrina, additional, Basile, Valerio, additional, De Stefano, Valerio, additional, Rapaccini, Gian Ludovico, additional, Zignego, Anna Linda, additional, Di Stasio, Enrico, additional, Marino, Mariapaola, additional, and Basile, Umberto, additional

Published
2023
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5. Urinary lithogenic profile of patients with non-alcoholic fatty liver disease

Author

Bargagli, Matteo, primary, Liguori, Antonio, additional, Napodano, Cecilia, additional, Baroni, Silvia, additional, Tomasello, Lidia, additional, Pizzolante, Fabrizio, additional, De Matthaeis, Nicoletta, additional, De Ninno, Grazia, additional, Grieco, Antonio, additional, Gasbarrini, Antonio, additional, Gambaro, Giovanni, additional, Ferraro, Pietro Manuel, additional, and Miele, Luca, additional

Published
2023
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6. Laboratory and Clinical Settings of Heavy/Light Chain (HLC) Assays in the Management of Monoclonal Gammopathies and Multiple Myeloma

Author

Napodano, Cecilia, primary, Ioannilli, Laura, additional, Basile, Valerio, additional, Gulli, Francesca, additional, Carnazzo, Valeria, additional, Pignalosa, Stefano, additional, Di Biase, Luigi, additional, Cavaleri, Erica, additional, Racco, Cosimo, additional, Equitani, Francesco, additional, Marino, Mariapaola, additional, and Basile, Umberto, additional

Published
2023
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8. Cytokines and Hepatocellular Carcinoma: Biomarkers of a Deadly Embrace

Author

Pocino, Krizia, primary, Stefanile, Annunziata, additional, Basile, Valerio, additional, Napodano, Cecilia, additional, D’Ambrosio, Francesca, additional, Di Santo, Riccardo, additional, Callà, Cinzia Anna Maria, additional, Gulli, Francesca, additional, Saporito, Raffaele, additional, Ciasca, Gabriele, additional, Equitani, Francesco, additional, Basile, Umberto, additional, and Marino, Mariapaola, additional

Published
2022
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10. Circulating and Salivary NGF and BDNF Levels in SARS-CoV-2 Infection: Potential Predictor Biomarkers of COVID-19 Disease—Preliminary Data

Author

Biamonte, Filippo, primary, Re, Agnese, additional, Balzamino, Bijorn Omar, additional, Ciasca, Gabriele, additional, Santucci, Daniela, additional, Napodano, Cecilia, additional, Nocca, Giuseppina, additional, Fiorita, Antonella, additional, Marino, Mariapaola, additional, Basile, Umberto, additional, Micera, Alessandra, additional, and Callà, Cinzia Anna Maria, additional

Published
2022
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11. PMON255 Inflammation and Oxidative Stress in Seminal Plasma: Role of Free Light Chains of Immunoglobulins and Antioxidants as Biomarkers in Male Infertility

Author

Bruno, Carmine, primary, Vergani, Edoardo, additional, Oliva, Alessandro, additional, Basile, Umberto, additional, Napodano, Cecilia, additional, Gulli, Francesca, additional, Silvestrini, Andrea, additional, Meucci, Elisabetta, additional, Orlando, Patrick, additional, Silvestri, Sonia, additional, Tiano, Luca, additional, and Mancini, Antonio, additional

Published
2022
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13. Inflammation and Oxidative Stress in Seminal Plasma: Search for Biomarkers in Diagnostic Approach to Male Infertility

Author

Bruno, Carmine, primary, Basile, Umberto, additional, Vergani, Edoardo, additional, Napodano, Cecilia, additional, Oliva, Alessandro, additional, Gulli, Francesca, additional, Meucci, Elisabetta, additional, Silvestrini, Andrea, additional, Orlando, Patrick, additional, Silvestri, Sonia, additional, Tiano, Luca, additional, and Mancini, Antonio, additional

Published
2022
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14. Cytokines and Hepatocellular Carcinoma: Biomarkers of a Deadly Embrace.

Author

Pocino, Krizia, Stefanile, Annunziata, Basile, Valerio, Napodano, Cecilia, D'Ambrosio, Francesca, Di Santo, Riccardo, Callà, Cinzia Anna Maria, Gulli, Francesca, Saporito, Raffaele, Ciasca, Gabriele, Equitani, Francesco, Basile, Umberto, and Marino, Mariapaola

Subjects
HEPATOCELLULAR carcinoma, SOMATIC mutation, CYTOKINES, GROWTH factors, ANGIOPOIETINS
Abstract

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC. [ABSTRACT FROM AUTHOR]

Published
2023
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19. The diagnostic performance of PIVKA-II in metabolic and viral hepatocellular carcinoma: a pilot study

Author

Basile, Umberto, Miele, Luca, Napodano, Cecilia, Ciasca, Gabriele, Gulli, F., Pocino, Krizia, De Matthaeis, Nicoletta, Liguori, Antonio, DE MAGISTRIS, A., Marrone, Giuseppe, Biolato, Marco, Marino, Mariapaola, Di Giacinto, Flavio, Gasbarrini, Antonio, Grieco, Antonio, and Rapaccini, Gian Ludovico

Subjects
Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Liver Neoplasms, Pilot Projects, Metabolic Hepatocellular carcinoma, Settore MED/05 - PATOLOGIA CLINICA, α-fetoprotein, PIVKA-II, Biomarkers, Tumor, Viral Hepatocellular carcinoma, Humans, Prothrombin, alpha-Fetoproteins, Protein Precursors, Biomarkers
Abstract

Hepatocellular carcinoma (HCC) is a primary liver tumor derived from metabolic or viral chronic hepatitis, with few treatment options in advanced cases. New biomarkers that allow improving diagnosis and staging are widely desired. Here, we aim to evaluate the performance of Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) in combination with α-fetoprotein (AFP), in the diagnosis of HCC in patients with metabolic or viral hepatitis.We enrolled 60 HCC patients (20 metabolic and 40 viral) and 20 healthy subjects (HS) as negative controls. PIVKA-II, AFP, Matrix metalloproteinase-9 (MMP-9) and Fibroblast growth factor (FGF) serum levels were assessed by immunoassays.AFP and PIVKA-II levels were obviously higher in patients than in HS. AFP displayed a better diagnostic performance than PIVKA-II for viral HCC while PIVKA-II was better for metabolic HCC. The combination of the two biomarkers did not improve the discriminating ability.PIVKA-II may be considered an independent predictor of macrovascular invasion from HCC cells and it can be used to better stratify HCC patients and should be evaluated in prospective studies for early detection of advanced HCC in metabolic subjects.

Published
2020

20. Salivary Biomarkers in COVID-19 Patients: Towards a Wide-Scale Test for Monitoring Disease Activity

Author

Napodano, Cecilia, primary, Callà, Cinzia, additional, Fiorita, Antonella, additional, Marino, Mariapaola, additional, Taddei, Eleonora, additional, Di Cesare, Tiziana, additional, Passali, Giulio Cesare, additional, Di Santo, Riccardo, additional, Stefanile, Annunziata, additional, Fantoni, Massimo, additional, Urbani, Andrea, additional, Paludetti, Gaetano, additional, Rapaccini, Gian Ludovico, additional, Ciasca, Gabriele, additional, and Basile, Umberto, additional

Published
2021
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22. Cryoglobulins: Identification, classification, and novel biomarkers of mysterious proteins

Author

Napodano, Cecilia, Gulli, F., Rapaccini, Gian Ludovico, Marino, Mariapaola, and Basile, Umberto

Subjects
Vasculitis, Cryoglobulin, COVID-19, Rheumatoid factor, Hepatitis C, Article, Mixed cryoglobulin, Settore MED/05 - PATOLOGIA CLINICA, Cryoglobulinemia, Animals, Chemical Precipitation, Humans, Cryoglobulins, Biomarkers, Autoantibodies
Abstract

Cryoglobulins consist of serum immunoglobulins that precipitate below 37°C and resolubilize upon warming. The clinical triad of cryoglobulinemia usually includes purpura, weakness, and arthralgia. Cryoglobulinemic syndrome, clinically defined as a systemic vasculitis, is associated with chronic infection with hepatitis C virus (HCV) and autoimmune disorders and can evolve into B-cell malignancies. While the current literature about HCV-associated cryoglobulinemia is not very limited, little is known about the immunologic and serologic profiles of affected patients. Therefore, comprehension of the pathogenetic mechanisms underlying cryoprecipitation could be very helpful. Due to the persistence of viral antigenic stimulation, biomarkers to use after the worsening progression of HCV infection to lymphoproliferative and/or autoimmune diseases are widely needed. Laboratory methods used to detect and characterize low concentrations of cryoprecipitates and immunotyping patterns could improve patient management. The most critical factor affecting cryoglobulin testing is that the pre-analytical phase is not fully completed at 37°C.

Published
2020

23. Solving the mystery of HBV-related mixed cryoglobulinemia: potential biomarkers of disease progression

Author

Pocino, Krizia, primary, Napodano, Cecilia, additional, Gragnani, Laura, additional, Ciasca, Gabriele, additional, Colantuono, Stefania , additional, Marri, Silvia, additional, Vantaggio, Lorenzo, additional, Gulli, Francesca, additional, Lorini, Serena, additional, Barini, Antonella, additional, Stefanile, Annunziata, additional, Miele, Luca, additional, Casato, Milvia, additional, Zignego, Anna Linda, additional, Rapaccini, Gian Ludovico, additional, Marino, Mariapaola, additional, Visentini, Marcella, additional, and Basile, Umberto, additional

Published
2021
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24. Biomarkers in HCV-related mixed cryoglobulinemia patients withnon-Hodgkin lymphoma

Author

Gulli, F., Marino, Mariapaola, Napodano, Cecilia, Pocino, Krizia, Pandolfi, Franco, Gasbarrini, Antonio, Rapaccini, Gian Ludovico, and Basile, Umberto

Subjects
Male, Hepatitis C virus, Lymphoma, Non-Hodgkin, Settore MED/12 - GASTROENTEROLOGIA, Hepacivirus, Middle Aged, B cell non-Hodgkin's lymphoma, Mixed cryoglobulins, Syndecan-1 (CD138), Settore MED/05 - PATOLOGIA CLINICA, FLC, Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Cryoglobulinemia, Biomarkers, Tumor, Humans, Female, Immunoglobulin Light Chains, Syndecan-1, Biomarkers, Retrospective Studies
Abstract

Chronic Hepatitis C virus (HCV) infection can cause severe extrahepatic manifestations, such as mixed cryoglobulins (MC), up to the development of B cell nonHodgkin's lymphoma (B-NHL). Mechanisms transforming of HCV infection into lymphoproliferative and/or autoimmune disorders are still poorly understood. In course of HCV infection, the sustained virus-driven antigenic stimulation may probably induce a B-cell clonal expansion. Measurements of serum free light chains (FLCs) levels, considered as a direct marker of B cell activity, are analyzed with increasing interest in clinical practice, for diagnosis, monitoring and follow-up of plasma cell dyscrasia. Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed and actively shed by most myeloma cells. Membrane CD138 represents the major receptor protein for HCV attachment to the hepatocyte surface and high levels of circulating sCD138 levels are detected in patients at early stage of B-cell chronic lymphocytic leukemia. This study is aimed to evaluate sCD138 and FLC levels as diagnostic biomarkers of HCV-related MC with B-NHL.We enrolled 35 HCV-MC-NHL patients, characterized for the specific type of cryoglobulins, and 25 healthy blood donors (HBD) as negative control. Serum sCD138 levels were determined using ELISA kits specific for human sCD138. Serum FLCs were assessed by means of the turbidimetric assay.We found that serum levels of sCD138, as well as FLCs, were significantly higher in patients than in HBD (p0.001).In agreement with the definition of HCV-driven lymphoproliferative disorders as the consequence of a multifactorial and multistep pathogenetic process, we suggest that sCD138 and FLCs could be considered putative independent markers of worsening progression of the disease.

Published
2020

27. Free light chains a novel biomarker of cardiovascular disease. A pilot study

Author

Basile, Umberto, La Rosa, Giulio, Napodano, Cecilia, Pocino, Krizia, Cappannoli, Luigi, Gulli, F, Cianfrocca, C, Di Stasio, Enrico, and Biasucci, Luigi Marzio

Subjects
Male, FLC, Acute coronary syndromes, Diabetes mellitus, Pilot Projects, Stroke Volume, Acute coronary syndromes, Middle Aged, FLC, Diabetes mellitus, Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, C-Reactive Protein, Cardiovascular Diseases, Echocardiography, Case-Control Studies, Humans, Female, Immunoglobulin Light Chains, Biomarkers, Aged
Abstract

Atherosclerosis and ischemic heart disease (IHD) are the major cause of morbidity and mortality but their inflammatory pathogenesis is still unclear. In this scenario, the role of serum free light chains (sFLC) has never been fully evaluated. The aim of the present study is to assess the clinical and pathogenetic role of sFLC in patients with IHD and to propose their use as a new biomarker for cardiovascular disease.We enrolled 117 patients, divided into 5 cohorts: 15 healthy controls, non-diabetic and without ischemic heart disease; 19 patients with type 2 diabetes (T2DM), without ischemic heart disease at recruitment; 39 patients with stable chronic angina; 27 patients with NSTEMI, 17 patients with acute STEMI. Serum sFLC and high-sensitive C-reactive protein (hs-CRP) were measured. Patients also underwent a transthoracic echocardiographic study.sFLC were higher in patients with IHD and T2DM. However, we did not find statistically significant differences in sFLC concentration among subgroups. No correlation resulted between sFLC and hs-CRP levels. The median value of the sFLC κ/λ ratio in the population was 0.63, therefore stratifying it into two groups according to their levels. We found that an increase in left ventricular ejection fraction at 12 months was detected in 77% of patients with κ/λ ratio higher than 0.63 and 25% of patients with κ/λ ratio lower of 0.63 (p=0.016, OR=10.0 [1.8-55.6]).Our study suggests that the sFLC, produced by the B-lymphocytes in the context of generalized immune activation, could play a pathogenetic role in acute coronary syndromes and that they could represent a novel risk biomarker of cardiovascular disease.

Published
2019

28. MON-448 Inflammatory and Oxidative Stress Parameters as Criteria of Classification of Metabolic Phenotypes of Insulin Resistance

Author

Bruno, Carmine, primary, Vergani, Edoardo, additional, Brunetti, Alessandro, additional, Ricerca, Bianca Maria, additional, Silvestrini, Andrea, additional, Meucci, Elisabetta, additional, Napodano, Cecilia, additional, Pocino, Krizia, additional, Gulli, Francesca, additional, Santini, Stefano Angelo, additional, Basile, Umberto, additional, and Mancini, Antonio, additional

Published
2019
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30. Autoimmunity and lymphoproliferation markers in naïve HCV-RNA positive patients without clinical evidences of autoimmune/lymphoproliferative disorders

Author

Gulli, Francesca, Basile, Umberto, Gragnani, Laura, Fognani, Elisa, Napodano, Cecilia, Colacicco, Luigi, Miele, Luca, De Matthaeis, Nicoletta, Cattani, Paola, Zignego, Anna Linda, and Rapaccini, Gian Ludovico

Subjects
Antinuclear antibodies (ANA), Cryoglobulins (CGs), Hepatitis C virus (HCV), Rheumatoid factor (RF), Hepatology, Gastroenterology
Published
2016

33. Cryoglobulin Test and Cryoglobulinemia Hepatitis C-Virus Related.

Author

Gulli, Francesca, Santini, Stefano Angelo, Napodano, Cecilia, Bottoni, Patrizia, Pocino, Krizia, Rapaccini, Gian Ludovico, and Basile, Umberto

Subjects
CRYOGLOBULINS, CRYOGLOBULINEMIA, HEPATITIS C virus
Abstract

Cryoglobulins are immunoglobulins that precipitate in serum at temperatures below 37°C and resolubilize upon warming. The clinical syndrome of cryoglobulinemia usually includes purpura, weakness, and arthralgia, but the underlying disease may also contribute other symptoms. Blood samples for cryoglobulin are collected, transported, clotted and spun at 37°C, before the precipitate is allowed to form when serum is stored at 4°C in a Wintrobe tube for at least seven days. The most critical and confounding factor affecting the cryoglobulin test is when the preanalytical phase is not fully completed at 37°C. The easiest way to quantify cryoglobulins is the cryocrit estimate. However, this approach has low accuracy and sensitivity. Furthermore, the precipitate should be resolubilized by warming to confirm that it is truly formed of cryoglobulins. The characterization of cryoglobulins requires the precipitate is several times washed, before performing immunofixation, a technique by which cryoglobulins can be classified depending on the characteristics of the detected immunoglobulins. These features imply a pathogenic role of these molecules which are consequently associated with a wide range of symptoms and manifestations. According to the Brouet classification, Cryoglobulins are grouped into three types by the immunochemical properties of immunoglobulins in the cryoprecipitate. The aim of this paper is to review the major aspects of cryoglobulinemia and the laboratory techniques used to detect and characterize cryoglobulins, taking into consideration the presence and consequences of cryoglobulinemia in Hepatitis C Virus (HCV) infection. [ABSTRACT FROM AUTHOR]

Published
2017
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34. A Comparative Study of Serum Angiogenic Biomarkers in Cirrhosis and Hepatocellular Carcinoma.

Author

Pocino, Krizia, Napodano, Cecilia, Marino, Mariapaola, Di Santo, Riccardo, Miele, Luca, De Matthaeis, Nicoletta, Gulli, Francesca, Saporito, Raffaele, Rapaccini, Gian Ludovico, Ciasca, Gabriele, and Basile, Umberto

Subjects
*BIOMARKERS, *DISEASE progression, *CIRRHOSIS of the liver, *COMPARATIVE studies, *ENZYME-linked immunosorbent assay, *HEPATOCELLULAR carcinoma
Abstract

Simple Summary: The progression of liver disease is accompanied by pathological angiogenesis, a prerequisite for the development of HCC. In this paper, we analyzed the clinical significance of serum angiogenic markers VEGF, Ang-1, Ang-2, angiopoietin receptor Tie1/2, HGF, and PECAM-1 in 62 patients with liver disease, out of which 33 were diagnosed with HCC and 29 with liver cirrhosis without signs of neoplasia. Biomarkers levels were investigated as a function of "Model for End-Stage Liver Disease" (MELD) score and Fibrosis Index (FI). HCC patients showed higher HGF levels than ones with cirrhosis, while high Ang-1 levels appeared to have a protective role in HCC as well as prognostic significance; we also found a strong correlation between HGF levels, Ang-2, and VEGF levels, further supporting their role in tumor angiogenesis. Due to the complexity of angiogenesis and the small size of the study group, further investigations are widely desired especially in the era of immunotherapy and HCC-targeted anti-angiogenic drugs. Background: Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. Its pathogenesis varies according to the underlying etiological factors, although in most cases it develops from liver cirrhosis. The disease progression is accompanied by pathological angiogenesis, which is a prerequisite that favors the development of HCC. Aims: This study aims at contributing to our understanding of the role of angiogenic factors in the progression of liver disease. For this purpose, we evaluate the clinical significance of serum angiogenic markers (VEGF, Ang-1, Ang-2, the angiopoietin receptor Tie1/2, HGF, and PECAM-1) first in cirrhotic and HCC patients separately, and then comparing cirrhotic patients with and without HCC. Materials and Methods: We enrolled 62 patients, out of whom 33 were diagnosed with HCC and 29 with liver cirrhosis without signs of neoplasia. Patients underwent venous blood sampling before and after receiving treatments for the diagnosed disease. Serum markers were evaluated using ELISA assays for Tie1 and the Bio-Plex Multiplex system for the remaining ones. Biomarker levels were investigated as a function of clinical scores for disease staging (MELD and Fibrosis Index, FI). Results: In cirrhotic patients, Ang-1 and Ang-2 correlate with MELD (ρAng-1 = −0.73, p = 2E−5) and FI (ρAng-1 = −0.52, p = 7E−3, ρAng-2 = 0.53, p = 3E−3). A reduction of Ang-2 levels (p = 0.047) and of the Ang-2/Ang-1 ratio (p = 0.031) is observed in cirrhotic patients diagnosed with viral hepatitis after antiviral treatments. In HCC patients, Ang-1 negatively correlates with FI (ρ = −0.63, p = 1E−4), and PECAM-1 positively correlates with MELD (ρ = 0.44, p = 0.01). A significant Ang-1 reduction was observed in deceased patients during the study compared to ones who survived (p = 0.01). In HCC patients, VEGF levels were increased after tumor treatment (p = 0.037). Notably, HGF levels in cirrhotic patients with HCC are significantly raised (p = 0.017) compared to that in those without HCC. Conclusions: Our results suggest that serum angiogenic markers, with emphasis on Ang-1/2, can contribute to the development of quantitative tools for liver disease staging and therapy monitoring. The comparison between cirrhotic patients with and without HCC suggests that HGF levels are potentially useful for monitoring the insurgence of HCC after a cirrhosis diagnosis. High Ang-1 levels in HCC patients appear to have a protective role as well as prognostic significance. [ABSTRACT FROM AUTHOR]

Published
2022
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