Miroslaw Kornek

University of Bonn | Uni Bonn · Department of Internal Medicine and Polyclinic I

Cell-derived vesicles in particular extracellular vesicles (EVs) such as microparticles (MPs) and microvesicles besides exosomes are raising more and more attention as a novel and unique approach to detect diseases. It has recently become apparent that disease specific MP signatures or profiles might be beneficial to differentiate chronic liver dis...

Background & Aims Large extracellular vesicles, specifically AnnexinV⁺ EpCAM⁺ CD147⁺ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular...

Background Biliary cancer, comprising cholangio‐ and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary c...

Extracellular vesicles, comprising exosomes, microvesicles, and apoptotic bodies, represent an emerging field in disease diagnostics and prognosis. They can be isolated from peripheral blood of patients as well as from other body fluids and can therefore be considered a minimally invasive liquid biopsy screening tool. Especially their surface antig...

Liquid biopsies do promise a lot, but are they keeping it? In the past decade, additional novel biomarkers qualified to be called like that, of which, some took necessary hurdles resulting in FDA approval and clinical use. Some others are since a while around, well known and were once regarded to be a game changer in cancer diagnosis or cancer scre...

In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) in cancer. Thanks to advancements in molecular biology, it has been found that the fraction of EVs called exosomes or small EVs (sEVs) modulates the sensitivity of cancer cells to chemotherapeutic agents by delivering molecularly active non...

Hepatocellular carcinoma (HCC) is at the forefront of the global cancer burden, and biomarkers for HCC are constantly being sought. Interestingly, RGS (Regulators of G protein signaling) proteins, which negatively regulate GPCR signaling, have been associated with various cancers, with some members of the RGS family being associated with liver canc...

Background: The dysregulation of autophagy and immunological processes has been linked to various pathophysiological conditions, including cancer. Most notably, their particular involvement in hepatocellular carcinoma (HCC) is becoming increasingly evident. This has led to the possibility of developing a prognostic signature based on immuno-autoph...

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the m...

The clinical utility of immune checkpoint inhibitors, such as programmed cell death protein 1 (PD‑1) and programmed death‑ligand 1 (PD‑L1) inhibitors used alone or in combination with other therapies, is currently gaining attention. In this particular scenario, the inclusion of cytokine‑induced killer (CIK) cells has proven to be a novel therapeuti...

Introduction Gastrointestinal (GI) malignancies, such as cholangiocarcinoma, pancreatic carcinoma, and metastatic colorectal carcinoma, have a poor prognosis and effective therapeutic approaches are still challenging. Checkpoint inhibition with PD-1 or PDL-1 antibodies revealed promising results in different tumor entities; however, only few patien...

For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipid...

Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the third most common cause of cancer-related death. One of the major problems faced by researchers and clinicians in this area is the lack of reliable disease biomarkers, which would allow for an earlier diagnosis, follow-up or prediction of treatment response, am...

The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non‐invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any know...

Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and rele...

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...

The terms microparticles (MPs) and microvesicles (MVs) refer to large extracellular vesicles (EVs) generated from a broad spectrum of cells upon its activation or death by apoptosis. The unique surface antigens of MPs/MVs allow for the identification of their cellular origin as well as its functional characterization. Two basic aspects of MP/MV fun...

The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal...

Larger extracellular vesicles, microparticles (MPs) or microvesicles (MVs), especially their acquisition and characterization by flow cytometry (FACS), is increasingly in focus of clinical/translational research efforts. Several laboratories have shown that MPs/MVs might be suitable for the diagnosis and predicting prognosis in various diseases inc...

Background Here, we assess the diagnostic value of tumour-associated microparticles (taMPs), for the detection and therapy monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Methods FACS was applied to detect various taMP populations in patients' sera that were associated with the presence of a liver tumour. In total 172 pat...

Introduction: Considering the high lethality of liver cancer, new early detection methods are in urgent need to increase patient survival. Here, we aim to improve early diagnosis and therapy monitoring possibilities of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) by applying a minimally-invasive approach involving tumor-associated mi...

During chronic liver injuries, progenitor cells expand in a process called ductular reaction, which also entails the appearance of inflammatory cellular infiltrate and epithelial cell activation. The progenitor cell population during such inflammatory reactions has mostly been investigated using single surface markers, either by histological analys...

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagno...

Background and Aims: Recently, showed that subpopulations of microparticles (MPs) belonging to the family of extracellular vesicles (EVs) that carry immune cell specific surface antigens accurately diagnosed and correlated with histological disease severity of chronic hepatitis C vs nonalcoholic steatohepatitis and controls (Kornek M et al., Hepato...

Background and aims: We recently showed that subpopulations of serum/plasma microparticles (MPs) belonging to the family of extracellular vesicles (EVs) that carry immune cell specific surface markers predict histological stage and grade chronic hepatitis C and nonalcoholic steatohepatitis (Kornek M et al., Hepatology 2011; Gastroenterology 2012)....

Podoplanin/gp38(+) stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38(+) cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied...

In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker...

Unlabelled: Radiofrequency ablation (RFA) is a potentially curative therapy for hepatocellular carcinoma (HCC). However, incomplete RFA can induce accelerated invasive growth at the periphery. The mechanisms underlying the RFA-induced tumor promotion remain largely unexplored. Three human HCC cell lines were exposed to 45°C-55°C for 10 minutes, si...

BACKGROUND/AIMS. After insufficient radiofrequency ablation (RFA) local recurrent HCC has been reported to spread more aggressively than pre-RFA. We previously showed that HCC cells exposed to sublethal heat undergo EMT-like transition and a higher proliferation via ERK1/2 activation both vitro and vivo (AASLD 2012: 887). However, it remained uncle...

Background and aims: We recently showed that subpopulations of serum/plasma microparticles (MPs) serve as novel diagnostic tools to stage and grade chronic hepatitis C (CHC) and nonalcoholic steatohepatitis (NASH) (Kornek M et al., Hepatology 2011; Gastroenterology 2012). Here, we studied if circulating MPs may help to identify patients with HCC or...

Background: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block endothelial activation. Here, we tested whether CD133 M...

BACKGROUND/AIMS. Insufficient radiofrequency ablation (RFA) therapy can facilitate local recurrence and recurrent HCC has been reported to spread more aggressively than pre-RFA. We previously showed that HCC cells exposed to sublethal heat undergo EMT-like transition to a progenitor-like and highly proliferative phenotype in vitro. However, how far...

Circulating microparticles (MP) are increasingly recognized as biomarkers of immune mediated and metabolic liver diseases. Apart from serving as intercellular signal transducers, their levels appear to reflect activation of specific cellular compartments in diseases as diverse as chronic viral hepatitis, non alcoholic fatty liver disease and vascul...

Microparticles released into the bloodstream upon activation or apoptosis of CD4(+) and CD8(+) T cells correlate with inflammation as determined by histologic analysis in patients with chronic hepatitis C (CHC). Patients with nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) can be differentiated from those with CHC based on ac...

BACKGROUND/AIMS. Radiofrequency ablation (RFA) is an effective therapy for hepatocellular carcinoma (HCC). However, insufficient heating can facilitate local recurrence and recurrent HCC has been reported to spread more aggressively than pre-RFA. However, the underlying mechanisms have not been explored. METHODS. To analyze a possible phenotypic ch...

Unlabelled: Microparticles (MPs) are small cell membrane vesicles that are released from cells during apoptosis or activation. Although circulating platelet MPs have been studied in some detail, the existence and functional role of T cell MPs remain elusive. We show that blood from patients with active hepatitis C (alanine aminotransferase [ALT] l...

Liver injury is a frequent complication associated with anorexia nervosa, and steatosis of the liver is thought to be the major underlying pathology. However, acute hepatic failure with transaminase levels over 1000 IU/mL and deep coma are very rare complications and the mechanism of pathogenesis is largely unknown. A 37-year-old Japanese woman sho...

Recently, increasing evidence has been found demonstrating direct effects of angiostatin on tumor cells themselves. We have applied the plasminogen derivatives K1-4 and K1-5 to a lung cancer model to analyse indirect angiostatic effects against endothelial and direct effects against tumor cells. In accordance with preceding findings both derivative...

Unlabelled: Dendritic cells (DCs) are professional antigen-presenting cells able to prime T-cells against tumor-associated antigens (TAA), but their potential to induce hepatocellular carcinoma (HCC) regression is still limited. CD40/CD40L interaction is essential for DC activation and induction of antigen-specific T-cells. In this study, transduc...

Most experimental therapy studies are performed in mice that bear subcutaneous or orthotopic hepatoma but are otherwise healthy and nonfibrotic. The majority of hepatocellular carcinoma (HCC), however, develops in patients suffering from preexisting liver fibrosis. We investigated the efficacy of a standard experimental therapeutic approach to inte...

Most experimental therapy studies are performed in mice that bear subcutaneous or orthotopic hepatoma but are otherwise healthy. We questioned whether a pre-existing fibrosis affects tumour development of implanted syngenic hepatoma cells. To further investigate a selected panel of factors involved in tumour growth, tumour organ samples were charac...

Soluble Ags devoid of inflammatory stimuli, derived for example from self-serum or food proteins, induce T cell tolerance, predominantly in the spleen. In this study, we describe an additional role of the kidney-renal LN (rLN) system in tolerogenic presentation of circulating soluble Ags. Protein below albumin molecular mass constitutively passed t...