A5048806639- Cancer Cells and Metastasis
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Cancer Research and Treatments
- interferon and immune responses
- Hepatitis B Virus Studies
- Mesenchymal stem cell research
- Liver physiology and pathology
- Cancer-related molecular mechanisms research
- Pancreatic function and diabetes
- Wind Turbine Control Systems
- Wind Energy Research and Development
- Cancer, Hypoxia, and Metabolism
- 3D Printing in Biomedical Research
- Immune cells in cancer
- Protein Tyrosine Phosphatases
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Real-time simulation and control systems
- Cancer-related Molecular Pathways
- Stress Responses and Cortisol
- Animal Virus Infections Studies
- Pluripotent Stem Cells Research
- Gut microbiota and health
- Plant and Fungal Interactions Research
University of Basel
2013-2022
University Hospital of Basel
2013-2022
Polytechnic University of Bari
2004-2020
Novartis (Switzerland)
2012
Freiwillige Akademische Gesellschaft
2011
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and second frequent cause of cancer-related mortality worldwide. The multikinase inhibitor sorafenib only treatment option for advanced HCC. Due to tumor heterogeneity, its efficacy greatly varies between patients limited due adverse effects drug resistance. Current in vitro models fail recapitulate key features HCCs. We report generation long-term organoid cultures from needle biopsies HCC with various etiologies stages....
// Silvio Däster 1, * , Nunzia Amatruda 2, Diego Calabrese 2 Robert Ivanek Eleonora Turrini 3 Raoul A. Droeser 1 Paul Zajac Carmela Fimognari Giulio C. Spagnoli Giandomenica Iezzi Valentina Mele ** Manuele G. Muraro Department of Surgery, University Hospital Basel, Switzerland Biomedicine, for Life Quality Studies, Bologna, Rimini, Italy These authors have contributed equally to this work Shared senior authorship Correspondence to: Mele, email: valentina.mele@usb.ch Muraro,...
Approximately 50% of patients with chronic hepatitis C (CHC) have ongoing expression interferon stimulated genes (ISGs) in the liver. It is unclear why this endogenous antiviral response inefficient eradicating infection. Several viral escape strategies been identified vitro, including inhibition (IFN) induction and ISG messenger RNA (mRNA) translation. The vivo relevance these mechanisms unknown, because reliable methods to identify virus (HCV)-infected cells human liver are lacking. We...
•A unique set of liver biopsies from patients with HBeAg-negative chronic hepatitis B infection was studied.•HBV RNA and antigen expression are ubiquitous in the despite low viremia.•Levels viral transcriptional template cccDNA not sufficient for HBV expression.•Ubiquitous is associated virus-host chimeric transcription.•Intrahepatic DNA levels consistent widespread integration. Background & AimsLoss serum HBsAg a hallmark spontaneous therapy induced resolution infection, since it generally...
The molecular repertoire promoting cancer cell plasticity is not fully elucidated. Here, we propose that glycosphingolipids (GSLs), specifically the globo and ganglio series, correlate promote transition between epithelial mesenchymal cells. character of ovarian remains stable throughout disease progression, spatial glycosphingolipidomics reveals elevated globosides in tumor compartment compared with ganglioside-rich stroma. CRISPR-Cas9 knockin mediated truncation endogenous E-cadherin...
The prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate over 1,600 using two independent tissue microarrays immunohistochemistry. Survival time was assessed Kaplan-Meier method Cox proportional hazards regression analysis a multivariable setting. Spearman's rank correlation tested association between lymphocyte infiltration. Basel study included 1,400...
Background Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key transcription regulating plethora of detoxifying enzymes and antioxidant genes involved in drug metabolism defence against oxidative stress. The glucocorticoid receptor (GR) ligand-induced the regulation energy supply for metabolic needs to cope with various stressors. GR activity controlled by glucocorticoids, which are synthesized adrenal glands regenerated mainly liver from inactive cortisone 11β-hydroxysteroid...
Background and aims HCV infection is a leading risk factor of hepatocellular carcinoma (HCC). However, even after viral clearance, HCC remains elevated. perturbs host cell signalling to maintain infection, derailed circuitry key driver carcinogenesis. Since protein phosphatases are regulators events, we aimed identify that respond with relevance for hepatocarcinogenesis. Methods We assessed mRNA microRNA (miRNA) expression profiles in primary human hepatocytes, liver biopsies resections...
The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset peritoneal cavity remains unexplored. Here, we suggest a new route metastasis through interaction integrin alpha 2 (ITGA2) with collagens enriched coinciding poor outcome patients ovarian cancer. Using multiple gene-edited cell lines patient-derived samples, demonstrate that ITGA2 triggers cancer adhesion collagen, promotes migration,...
Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home primary and metastatic tumor sites, where they can integrate into tumor-associated stroma. However, molecular mechanisms outcome of their interaction cancer have not been fully clarified. In this study, we investigated effects mediated by bone marrow-derived MSC on human colorectal (CRC) in vitro vivo. We found that triggered epithelial-to-mesenchymal transition (EMT) vitro, as indicated...
The molecular mechanisms that link IFN-λ3 genotypes to differential induction of interferon (IFN)-stimulated genes (ISGs) in the liver patients with chronic hepatitis C (CHC) are not known. We measured expression IFN-λ and specific receptor chain (IFN-λR1) 122 biopsies CHC 53 control samples. genotype was associated IFN-λ, but rather IFN-λR1. In a series 30 primary human hepatocyte (PHH) samples, IFN-λR1 low could be induced IFN-α. IFN-α–induced significantly stronger PHHs carrying minor...
HMGA1 is a non-histone nuclear protein that regulates cellular proliferation, invasion and apoptosis overexpressed in many carcinomas. In this study we sought to explore the expression of HCCs cirrhotic tissues, its effect vitro models.We evaluated using gene microarrays (59 HCCs, which 37 were matched with their corresponding tissue 5 normal liver donors) microarray (192 108 tissues 79 samples). was correlated clinicopathologic features patient outcome. Four cancer cell lines stable induced...
The use of pegylated interferon-α (pegIFN-α) has replaced unmodified recombinant IFN-α for the treatment chronic viral hepatitis. While superior antiviral efficacy pegIFN-α is generally attributed to improved pharmacokinetic properties, pharmacodynamic effects in liver have not been studied. Here, we analyzed pegIFN-α–induced signaling and gene regulation paired biopsies obtained prior during first week following injection 18 patients with hepatitis C. Despite sustained high concentrations...
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Treatment options for patients with advanced-stage disease are limited. A major obstacle in drug development lack an vivo model that accurately reflects broad spectrum human HCC. Patient-derived xenograft (PDX) tumor mouse models could overcome limitations cancer cell lines. PDX tumors maintain genetic and histologic heterogeneity originating used preclinical various cancers. Controversy exists...
This paper proposes a new variable structure control scheme for variable-speed, fixed-pitch ducted wind turbine, equipped with an annular, brushless permanent-magnet synchronous generator, considering back-to-back power converter topology. The purpose of this is to maximise the aerodynamic over entire speed range, mechanical safety limits turbine. ideal characteristics are achieved design laws aimed at performing maximum point tracking in low speeds region, and constant speed, power, torque...
VEGF is widely investigated for therapeutic angiogenesis, but while short-term delivery desirable safety, it insufficient new vessel persistence, jeopardizing efficacy. Here, we whether and how dose regulates nascent stabilization, to identify novel targets. Monoclonal populations of transduced myoblasts were used homogeneously express specific doses in SCID mouse muscles. was abrogated after 10 17 days by Aflibercept treatment. Vascular stabilization fastest with low VEGF, delayed or...
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Most HCCs develop in cirrhotic livers. Alcoholic liver disease, chronic hepatitis B and C are underlying diseases. Hepatitis virus (HCV)-specific mechanisms that contribute to HCC presently unknown. Transgenic expression HCV proteins mouse induces an overexpression protein phosphatase 2A catalytic subunit (PP2Ac). We have previously reported HCV-induced PP2Ac modulates histone methylation acetylation inhibits DNA...
Summary The maintenance of glucose homeostasis is a complex process in which the insulin signalling pathway plays major role. Disruption insulin‐regulated frequently observed chronic hepatitis C ( CHC ) infection and might potentially contribute to type 2 diabetes mellitus T DM development. Presently, mechanism that links HCV resistance remains unclear. Previously, we have reported protein expression transgenic mice B 6 leads an overexpression phosphatase A PP through ER stress response. In...
Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, how this impacts on NAFLD. We analyzed the pro- gene expression murine human monocytes vitro presence or absence imatinib. In a time-resolved study, we characterized metabolic manifestations such hepatic steatosis,...
Chronic liver inflammation causes continuous damage with progressive fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10‐year incidence for HCC in patients cirrhosis is approximately 20%, many of these remain tumor free their entire lives. Clarifying mechanisms that define various outcomes chronic a key aspect research. In addition wide variety contributing factors, microRNAs (miRNAs) have also been shown be engaged promoting cancer. Therefore,...
Abstract Background and Aim Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes continuous damage leading to cirrhosis eventually HCC. However, only minority of cirrhotic develop To assess possible differential impact inflammation in developing HCC versus remaining tumor‐free, we designed longitudinal study analysed tissue the same ( n = 33) at two points time: once when no was present several years later present. As control group,...
Background & aims Hepatocyte-like cells (HLCs) differentiated from induced pluripotent stem (iPSCs) have emerged as a promising cell culture model to study metabolism, biotransformation, viral infections and inherited liver diseases. iPSCs provide an unlimited supply for the generation of HLCs, but incomplete HLC differentiation remains major challenge. iPSC may carry-on tissue origin dependent expression memory influencing into different types. Whether derived (Li-iPSCs) would allow more...