- Pancreatitis Pathology and Treatment
- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- Liver Disease Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Alcohol Consumption and Health Effects
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Intestinal and Peritoneal Adhesions
- Mitochondrial Function and Pathology
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Lipid metabolism and disorders
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Pediatric Hepatobiliary Diseases and Treatments
- Sphingolipid Metabolism and Signaling
- Cancer-related gene regulation
- Genomics, phytochemicals, and oxidative stress
- Cholesterol and Lipid Metabolism
- Cancer Cells and Metastasis
- Ginger and Zingiberaceae research
- Mesenchymal stem cell research
Heidelberg University
2015-2024
University Hospital Heidelberg
2013-2024
IRCCS Humanitas Research Hospital
2024
Humanitas University
2024
University of Milan
1994-2014
University Hospital of Zurich
2005
Ospedale Maggiore
2001-2003
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2003
University of Kentucky
2000-2001
Istituti di Ricovero e Cura a Carattere Scientifico
2001
Duchenne muscular dystrophy is a lethal recessive disease characterized by widespread muscle damage throughout the body. This increases difficulty of cell or gene therapy based on direct injections into muscles. One way to circumvent this obstacle would be use circulating cells capable homing sites lesions. Here, we showed that stem antigen 1 (Sca-1), CD34 double-positive purified from tissues newborn mice are multipotent in vitro and can undergo both myogenic multimyeloid differentiation....
Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) multiplexed immunofluorescence 122) on chemo-naive postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) define impact neoadjuvant chemotherapy. Transcriptome analysis combined high-resolution mapping whole-tissue...
The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated ability to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, evaluated cell necrosis an animal model AP human samples. Rats were fed either ethanol-containing or control diet for 14 weeks killed 3 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome...
// Yiyao Zhang 1, 2, 3, 4 , Li Liu 3 Pei Fan Nathalie Bauer Jury Gladkich Eduard Ryschich Alexandr V. Bazhin Nathalia A. Giese Oliver Strobel Thilo Hackert Ulf Hinz Wolfgang Gross Franco Fortunato Ingrid Herr 1 Molecular OncoSurgery, University of Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany 2 Section Surgical Research, Department General, Visceral Transplantation Surgery, Gastrointestinal Zhongshan Hospital Xiamen University, Xiamen, China Correspondence to:...
Chronic alcohol consumption is known to increase the susceptibility acute and chronic pancreatitis, it likely that a cofactor required initiate progression alcoholic pancreatitis. The severity complications of nonalcoholic pancreatitis may be influenced by number cofactors, including endotoxemia. To explore effect possible cofactor, we used endotoxin [lipopolysaccharide (LPS)] as tool induce cellular injury in pancreas. Single, increasing doses were injected rats fed an or control diet...
The broccoli isothiocyanate, sulforaphane (SFN), was recently identified as being capable of eliminating highly therapy-resistant pancreatic carcinoma (PC) cells without inducing toxic side effects. While SFN has been shown to stimulate autophagy or 'self-eating', it is unclear whether this catabolic process a pro- anti-tumorigenic response. To investigate the role in SFN-induced cell death, established PC lines were treated with SFN, and induction evaluated by detecting abundance autophagic...
The purpose of this study was to determine if exacerbation apoptosis precedes liver injury during chronic exposure rats alcohol. After 7 weeks feeding an alcohol‐ or dextrin‐containing liquid diet, the animals were treated with Gram‐negative bacterial lipopolysaccharide (1 mg kg ‐1 body weight, intravenously) sterile saline and sacrificed 3 hr after treatment. Alanine:2‐oxoglutarate aminotransferase (ALT) 1actate:NAD oxidoreductase [lactate dehydrogenase (LDH)] measured in plasma. caudate...
The role of apoptosis in EtOH-induced liver injury has not been investigated much. Therefore, the question whether is a contributory factor to alcoholic disease remains be answered. purpose this study was characterize apoptotic response murine model alcohol-enhanced lipopolysaccharide (LPS) hepatotoxicity.Mice were fed an alcohol-containing liquid diet for 49 days followed by acute LPS challenge. state judged on basis histological appearance, plasma enzyme activity (alanine:2-oxoglutarate...
In contrast to apoptosis, necrosis is generally viewed as a pro-inflammatory cell death mechanism. Accumulation of autophagosomes and massive acinar observed in human acute pancreatitis, severe potentially lethal inflammatory condition. We have investigated the incidence autophagy affecting cells rat model pancreatitis induced by chronic alcohol intake endotoxemia. that combination exposure endotoxemia result substantial accumulation without an increase autolysosomes, coupled depletion...
Abstract Invalidation of pancreatic autophagy entails atrophy, endocrine and exocrine insufficiency pancreatitis. The aim this study was to investigate whether depletion Rip3, which is involved in necroptotic signaling, may attenuate the atrophy pancreatitis resulting from inhibition. Autophagy necroptosis signaling were evaluated mice lacking expression Rip3 all organs Atg7 pancreas. Acinar cell death, inflammation fibrosis by using a compendium immunofluorescence methods immunoblots. Mice...
Abstract Chronic pancreatitis (CP) is associated with elevated plasma levels of bacterial lipopolysaccharide (LPS) and we have demonstrated reduced acinar cell autophagy in human CP tissue. Therefore, investigated the role experimental endotoxin-induced pancreatic injury aimed to identify LPS Pancreatic Atg7-deficient mice were injected a single sub-lethal dose LPS. Expression autophagy, apoptosis, necroptosis, inflammatory markers was determined 3 24 h later utilizing immunoblotting...
Alcoholic liver disease (ALD) is the most common worldwide and its underlying molecular mechanisms are still poorly understood. Moreover, conflicting data have been reported on potentially protective autophagy, exact role of ethanol-metabolizing enzymes ROS. Expression LC3B, CYP2E1, NOX4 was studied in a mouse model acute ethanol exposure by immunoblotting immunohistochemistry. Autophagy further primary hepatocytes huh7 cells response to major intermediator acetaldehyde. Experiments were...
Several collagen subtypes are involved in pancreatic ductal adenocarcinoma (PDAC) desmoplasia, which constrains therapeutic efficacy. We evaluated type VIII alpha 1 chain (COL8A1), whose function PDAC is currently unknown. identified COL8A1 expression 7 examined cell lines by microarray analysis, western blotting, and RT‒qPCR. Higher occurred 2 gemcitabine-resistant lines; pancreas tissue (n=15) from LSL-KrasG12D/+; p48-Cre mice with advanced predisposition; parenchyma stroma of a patient...
Recent evidence suggests that cells from bone marrow can acquire neuroectodermal phenotypes in cell culture or after transplantation animal models and the human brain. However, isolation of subpopulation with neuronal differentiation potential remains a challenge. To isolate expand neural progenitors whole murine marrow, was obtained hind limb C57BL6 mice plated medium basic fibroblast growth factor epidermal factor. After 5-7 days culture, cellular spheres similar to brain neurospheres...
The functional relationship between bile acid (BA) and autophagy has not been evaluated in the context of pancreatitis. Here we investigated whether BA their nuclear farnesoid X receptor (FXR) modulate development FXR expression, autophagy, apoptosis necroptosis were determined human chronic pancreatitis (CP) tissue vivo pancreatic cells lines vitro by means real-time PCR, immunoblots immunofluorescence. Pancreatic cell exposed to most abundant BAs glycochenodeoxycholate (GCDC) taurocholic...
Background Sulforaphane (SFN), an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects cell lines such as pancreatic cancer. Antiproliferative well radiosensitizing properties were reported head neck cancer but little is known about cells combination with irradiation (RT). Methods In four established we investigated clonogenic survival, analyzed cycle distribution compared DNA damage via flow cytometry western...
Background/aims: The liver apoptotic response to chronic alcohol consumption remains poorly characterized. purpose of this study was determine in rats the effects on relative magnitude apoptosis two major targets alcohol-induced injury: hepatocyte (Hep) and sinusoidal endothelial cell (SEC). Methods: Rats were fed a liquid diet containing either or isocaloric amounts maltose-dextrin for 14 weeks. Hep SEC isolated by perfusion with collagenase followed centrifugal elutriation. state assessed...
Alcohol exposure is known to sensitize acinar cells various insults but the pathophysiological mechanisms of alcoholic pancreatitis remain unknown. abuse has been shown mediate an anti-inflammatory response and periods immune suppression seem be associated with organ injury mortality. The purpose this study was determine by which alcohol exerts transcriptional activities in rat pancreas how alters inflammatory response. Using Lieber-DeCarli alcohol/control diet, rats that were fed over 14...
Systemic complications in alcoholic pancreatitis are supposed to be aggravated by inflammatory liver damage. Resident macrophages including hepatic Kupffer cells play a pivotal role mediating systemic severe necrotizing (SNP). The aim of this study was evaluate the effects cell inhibition on damage experimental pancreatitis.Rats were fed with either alcohol or control diet for 6 weeks before induction SNP. Animals allocated into 4 groups: healthy controls, controls SNP, SNP gadolinium...
// Li Xie 1 , 2 Leizhou Xia Ulla Klaiber Milena Sachsenmaier Ulf Hinz Frank Bergmann 3 Oliver Strobel Markus W. Büchler John P. Neoptolemos Franco Fortunato * and Thilo Hackert Department of General, Visceral Transplantation Surgery, University Clinic Heidelberg, Germany Section Surgical Research, Institute Pathology, Co-senior authors Correspondence to: Fortunato, email: Franco.Fortunato@uni-heidelberg.de Keywords: autophagy; cell death; stroma; neoadjuvant therapy; prognosis Received:...