Stefania Cannito

Stefania Cannito
University of Turin | UNITO · Dipartimento di Scienze Cliniche e Biologiche

PhD

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116
Publications
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Publications

Publications (116)
Article
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Background Metabolic dysfunction-associated steatotic liver disease (MASLD), previously non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide. In 20%–30% of MASLD patients, the disease progresses to metabolic dysfunction-associated steatohepatitis (MASH, previously NASH) which can lead to fibrosis/cirrhosi...
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Background SerpinB3 is a cysteine protease inhibitor involved in liver disease progression due to its proinflammatory and profibrogenic properties. The polymorphic variant SerpinB3‐PD (SB3‐PD), presents a substitution in its reactive centre loop, determining the gain of function. Aims To disclose the clinical characteristics of a cohort of patient...
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The most common form of primary liver malignancy is hepatocellular carcinoma (HCC) [...].
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Cholangiocarcinoma (CCA) is an extremely aggressive malignancy characterized by a very limited prognosis and scarce treatment options. The majority of patients are diagnosed at an advanced stage and do not qualify for potentially curative surgical treatments, making CCA an increasingly prevalent global challenge. CCA is characterized by a highly re...
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Chronic liver disease (CLD) is a major global health threat and has emerged as a leading cause of human death [...]
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Abnormal activation of the Wnt-β-catenin signaling cascade is involved in tumor growth and dissemination. SerpinB3 has been shown to induce β-catenin, and both molecules are overexpressed in tumors, particularly in those with poor prognoses. The aim of this study was to evaluate the ability of SerpinB3 to modulate the Wnt pathway in liver cancer an...
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Hepatocellular carcinoma is the most common primary liver cancer, ranking third among the leading causes of cancer-related mortality worldwide and whose incidence varies according to geographical area and ethnicity. Metabolic rewiring was recently introduced as an emerging hallmark able to affect tumor progression by modulating cancer cell behavior...
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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. In the recent years nonalcoholic fatty liver disease (NAFLD) is becoming a growing cause of HCCs and the incidence of NAFLD-related HCCs is expected to further dramatically increase by the next decade. Chronic inflammation is regarded as the driving force...
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Primary liver cancers represent the third-most-common cause of cancer-related mortality worldwide, with an incidence of 80–90% for hepatocellular carcinoma (HCC) and 10–15% for cholangiocarcinoma (CCA), and an increasing morbidity and mortality rate. Although HCC and CCA originate from independent cell populations (hepatocytes and biliary epithelia...
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Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide. In 20-30% of patients, NAFLD can progress into non-alcoholic steatohepatitis (NASH), eventually leading to fibrosis, cirrhosis and hepatocellular carcinoma development. SerpinB3 (SB3), a hypoxia-inducible factor-2α dependent cysteine protease inhi...
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During chronic liver disease (CLD) progression, hepatic myofibroblasts (MFs) represent a unique cellular phenotype that plays a critical role in driving liver fibrogenesis and then fibrosis. Although they could originate from different cell types, MFs exhibit a rather common pattern of pro-fibrogenic phenotypic responses, which are mostly elicited...
Article
GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein Coupled Receptors (GPCRs). GPR21 couples to the Gq family of G proteins and is markedly expressed in macrophages. Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration. The aim of this study was to evaluat...
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Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and is characterized by poor clinical outcomes, with the majority of patients not being eligible for curative therapy and treatments only being applicable for early-stage tumors. CD44 is a receptor for hyaluronic acid (HA) and is involved in HCC progression. The aim of this wo...
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Oncostatin M (OSM) is a pleiotropic cytokine of the interleukin (IL)‐6 family that contributes to the progression of chronic liver disease. Here we investigated the role of OSM in the development and progression of hepatocellular carcinoma (HCC) in NAFLD/NASH. The role of OSM was investigated in: a) selected cohorts of NAFLD/NASH HCC patients; b) l...
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GPR21 is a constitutively active, orphan, G-protein-coupled receptor, with in vivo studies suggesting its involvement in the modulation of insulin sensitivity. However, its precise contribution is not fully understood. As the liver is both a major target of insulin signalling and critically involved in glucose metabolism, the aim of this study was...
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Background & Aims Hypoxia and HIFs (hypoxia inducible factors) are involved in chronic liver disease progression. We previously showed that hepatocyte HIF-2α activation significantly contributed to NAFLD progression in experimental animals and human patients. In this study we investigated mechanistically, using an appropriate genetic murine model,...
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Liver fibrosis is a potentially reversible pathophysiological event, leading to excess deposition of extracellular matrix (ECM) components and taking place as the net result of liver fibrogenesis, a dynamic and highly integrated process occurring during chronic liver injury of any etiology. Liver fibrogenesis and fibrosis, together with chronic inf...
Article
Liver fibrogenesis is defined as a dynamic and highly integrated process occurring during chronic injury to liver parenchyma that can result in excess deposition of extracellular matrix (ECM) components (i.e., liver fibrosis). Liver fibrogenesis, together with chronic inflammatory response, is then primarily involved in the progression of chronic l...
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Background: Hepatic myofibroblasts (MFs) can originate from hepatic stellate cells, portal fibroblasts, or bone marrow-derived mesenchymal stem cells and can migrate towards the site of injury by aligning with nascent and established fibrotic septa in response to several mediators. Oncostatin M (OSM) is known to orchestrate hypoxia-modulated hepat...
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Background: SerpinB3 (SB3) is a hypoxia and hypoxia-inducible factor (HIF)-2α-dependent cysteine-protease inhibitor up-regulated in hepatocellular carcinoma (HCC), released by cancer cells and able to stimulate proliferation and epithelial-to-mesenchymal-transition. Methods: In the study we employed transgenic and knock out SerpinB3 mice, liver ca...
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Fibrogenic progression of chronic liver disease, whatever the etiology, is characterized by persistent chronic parenchymal injury, chronic activation of inflammatory response, and sustained activation of liver fibrogenesis, and of pathological wound healing response. A critical role in liver fibrogenesis is played by hepatic myofibroblasts (MFs), a...
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The cholangipathies are a class of liver diseases that specifically affects the biliary tree. These pathologies may have different etiologies (genetic, autoimmune, viral, or toxic) but all of them are characterized by a stark inflammatory infiltrate, increasing overtime, accompanied by an excess of periportal fibrosis. The cellular types that mount...
Article
Human HT-29 and HepG2 cell lines were employed to test the effects of increasing concentrations of two rare earth elements (REEs), namely cerium (Ce) and lanthanum (La), alone or in combination. Effects on cell proliferation were measured using MTT assay, luciferase-based assays and proliferating cell nuclear antigen expression, while cell mortalit...
Article
We have prepared and evaluated the physico-chemical and biological properties of four different hyaluronated mesoporous silica nanoparticles (MSNs) samples (MSN/HA). Hyaluronic acid (HA) with two different molecular weights (200 and 6.4 kDa) was used for the conjugation of aminopropyl-functionalized MSN (NH2-MSN), following two different procedures...
Article
Mechanisms underlying progression of nonalcoholic fatty liver disease (NAFLD) are still incompletely characterized. Hypoxia and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of chronic liver diseases, but the actual role of HIF-2α in the evolution of NAFLD has never been investigated in detail. In this study, we show tha...
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Iron overload results in cellular toxicity, tissue injury, organ fibrosis and increased risk of neoplastic transformation. SerpinB3 is a serine protease inhibitor overexpressed in the liver in oxidative stress conditions, able to induce fibrosis and increased risk of malignant transformation. Aim of the present study was to assess the effect of iro...
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SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth f...
Article
Myofibroblasts (MFs) play a critical role in the progression of chronic inflammatory and fibroproliferative diseases in different tissues/organs, whatever the etiology. Fibrosis is preceded and sustained by persistent injury and inflammatory response in a profibrogenic scenario involving mutual interactions, operated by several mediators and pathwa...
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Non-Alcoholic Fatty Liver Disease (NAFLD) is a major form of chronic liver disease in the general population in relation to its high prevalence among overweight/obese individuals and patients with diabetes type II or metabolic syndrome. NAFLD can progress to steatohepatitis (NASH), fibrosis and cirrhosis and end-stage of liver disease but mechanism...
Data
Characterization of microvesicles (MVs) obtained from fat-laden HepG2 cells. (A). Representative TEM micrograph of HepG2-derived MVs released after 24 hrs of 0.25 mM palmitic acid (PA) treatment. Scale bar 200 nm. (B) Flow cytometry analysis (Whisker plot) of Calcein+ MVs per mL of media isolated from fat-laden HepG2 cells at the end of 24 hrs expo...
Data
Immunohistochemistry analysis for NLRP3 on liver specimens from NLRP3 hemizygous +/-mice (A) as well as WT mice or Casp 3-/- knockout mice fed for 6wks with MCD diet (B). Original magnification as indicated. Right panels represent histomorphometric analysis (ImageJ program) that has been performed on n = 4 liver sections obtained from three differe...
Article
Orthotopic liver transplantation (OLT) represents the standard curative treatment for human patients affected by an end-stage form of life-threatening liver disease involving, whatever the etiology (acquired or inborn) and development (acute or chronic), significant loss of hepatocytes and organ failure (1,2). The need for reliable therapeutic appr...
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SerpinB3 has been recently described as an early marker of liver carcinogenesis, but the potential mechanistic role of this serpin in tumor development is still poorly understood. Overexpression of Myc often correlates with more aggressive tumour forms, supporting its involvement in carcinogenesis. Yes-associated protein (Yap), the main effector of...
Article
Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process that during the course of a chronic liver disease (CLD) leads progressively to an excess deposition of extracellular matrix (ECM) components in an attempt to limit the consequences of chronic parenchymal injury. Irrespective of etiology, liver fibrogenesis...
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SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial...
Article
Full-text available
SerpinB3 has been recently described as an early marker of liver carcinogenesis, but the potential mechanistic role of this serpin in tumor development is still poorly understood. Overexpression of Myc often correlates with more aggressive tumour forms, supporting its involvement in carcinogenesis. Yes-associated protein (Yap), the main effector of...
Article
Full-text available
Objective: The Extracellular Signal-Regulated kinase 5 (ERK5 or BMK1) is involved in tumour development. The ERK5 gene may be amplified in hepatocellular carcinoma (HCC) but its biological role has not been clarified. In this study we explored the role of ERK5 expression and activity in HCC in vitro and in vivo. Design: ERK5 expression was evaluate...
Article
Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process, potentially reversible, that drives the progression of chronic liver diseases (CLD) towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), the pro-fibrogenic effector cells, originate mainly from activation of hepatic stellate cells and...
Article
Oncostatin M (OSM), a member of IL‐6 family of cytokines, can affect hypoxia‐modulated liver processes contributing to chronic liver disease progression and hepatocellular carcinoma (HCC) development. In this study we investigated whether OSM may induce epithelial‐to‐mesenchymal transition (EMT) in human hepatic cancer cells and increased invasiven...
Article
SERPINB3 (S‐B3), a cysteine‐proteases inhibitor up‐regulated in cirrhosis, dysplastic nodules and hepatocellular carcinoma (HCC), can trigger epithelial‐to‐mesenchymal transition (EMT) and increased invasiveness in hepatic cancer cells. In this study we have investigated whether hypoxia, through involvement of hypoxia inducible factors (HIFs), may...
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Introduction: Cyclooxygenase-2 (COX-2) is overexpressed in several malignancies and is implicated in breast cancer progression. Objectives: We investigated whether changes in COX-2 expression may affect epithelial-to-mesenchymal transition (EMT) and then invasive potential of human breast cancer cells, in relationship with hypoxia. COX-2-null MC...
Article
Fibrogenic progression of chronic liver diseases (CLDs) towards the end-point of cirrhosis is currently regarded, whatever the aetiology, as a dynamic and highly integrated cellular response to chronic liver injury. Liver fibrogenesis (i.e., the process) is sustained by hepatic populations of highly proliferative, pro-fibrogenic and contractile myo...
Article
Fibrogenic progression of chronic liver diseases (CLDs) to the end-points ofcirrhosis and hepatic failure or hepatocellular carcinoma (HCC) can be envisaged as adynamic and highly integrated cellular response to chronic liver injury. Liver fibrogenesisas a process is sustained by hepatic populations of highly proliferative, pro-fibrogenicand contra...
Article
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to exert chemopreventive and antitumor effects on colon cancer, one of the most common solid epithelial malignancy worldwide. The aim of this study was to elucidate whether celecoxib may be able to affect epithelial-mesenchymal transition (EMT), a critical process involved...
Article
Liver fibrogenesis is sustained by pro-fibrogenic myofibroblast-like cells (MFs), mainly originating from activated hepatic stellate cells (HSC/MFs) or portal (myo)fibroblasts, and is favoured by hypoxia-dependent angiogenesis. Human HSC/MFs were reported to express vascular-endothelial growth factor (VEGF) and VEGF-receptor type 2 and to migrate u...