A5080874150- Cholangiocarcinoma and Gallbladder Cancer Studies
- Hippo pathway signaling and YAP/TAZ
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Cancer Mechanisms and Therapy
- Peroxisome Proliferator-Activated Receptors
- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Liver Disease Diagnosis and Treatment
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Renal and related cancers
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Liver physiology and pathology
- Lipid metabolism and biosynthesis
- Pancreatic function and diabetes
- Cholesterol and Lipid Metabolism
- Ubiquitin and proteasome pathways
- Pancreatitis Pathology and Treatment
Universität Greifswald
2016-2025
Universitätsmedizin Greifswald
2016-2025
Taipei Institute of Pathology
2021
Memorial Sloan Kettering Cancer Center
2014
Cold Spring Harbor Laboratory
2014
University of Veterinary Medicine Hannover, Foundation
2014
Intrahepatic cholangiocarcinomas (ICCs) are primary liver tumors with a poor prognosis. The development of effective therapies has been hampered by limited understanding the biology ICCs. Although ICCs exhibit heterogeneity in location, histology, and marker expression, they currently thought to derive invariably from cells lining bile ducts, biliary epithelial (BECs), or progenitor (LPCs). Despite lack experimental evidence establishing BECs LPCs as origin ICCs, other cell types have not...
Objective Increased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC). Design We investigated the functional contribution of synthase (Fasn)-mediated FA a murine HCC model induced by loss Pten overexpression c-Met (sgPten/c-Met) using liver-specific Fasn knockout mice. Expression arrays lipidomic analysis were performed to characterise global gene expression lipid profiles,...
Amplification and/or activation of the c‐Myc proto‐oncogene is one leading genetic events along hepatocarcinogenesis. The oncogenic potential has been proven experimentally by finding that its overexpression in mouse liver triggers tumor formation. However, molecular mechanism whereby exerts activity remains poorly understood. Here, we demonstrate mammalian target rapamycin complex 1 (mTORC1) cascade activated and necessary for c‐Myc‐dependent Specifically, found ablation Raptor , unique...
Abstract Activation of the AKT/mTOR cascade and overexpression c-Met have been implicated in development human hepatocellular carcinoma (HCC). To elucidate functional crosstalk between two pathways, we generated a model characterized by combined expression activated AKT mouse liver. Co-expression triggered rapid liver tumor mice required to be euthanized within 8 weeks after hydrodynamic injection. At molecular level, tumors induced AKT/c-Met display activation Ras/MAPK cascades as well...
•A novel mouse model of intrahepatic cholangiocarcinoma (ICC) was established.•Hydrodynamic transfection activated forms AKT and Yap used to induce ICC.•This recapitulates many morphological molecular features human ICC.•MLN0128 may be superior gemcitabine/oxaliplatin based chemotherapy treat ICC.•The efficacy MLN0128 is mainly attributed induction apoptosis ICC cells. Background & AimsIntrahepatic a lethal malignancy without effective treatment options. MLN0128, second generation pan-mTOR...
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one hallmarks Fatty acid synthase (FASN) catalyzes synthesis long‐chain fatty acids from acetyl‐coenzyme A malonyl‐coenzyme A. Increased FASN expression has been reported multiple tumor types, inhibition shown to...
Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with limited treatment options. The c‐Myc transcription factor pivotal player in hepatocarcinogenesis, but the mechanisms underlying oncogenic activity remain poorly delineated. Mammalian target rapamycin complex 2 (mTORC2) has been implicated by regulating multiple AGC kinases, especially AKT proteins. In liver, AKT1 and AKT2 are widely expressed. While major isoform downstream activated phosphoinositide 3‐kinase loss...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and projected to be second leading cause cancer-related death by 2030. Despite extensive knowledge insights into biological properties genetic aberrations PDAC, therapeutic options remain temporary ineffective. One plausible explanation for futile response therapy an insufficient non-specific delivery anticancer drugs tumour site.Superparamagnetic iron oxide nanoparticles (SPIONs) coupled with siRNA directed...
The morphology of podocyte foot processes is obligatory for renal function. Here we describe a method the superresolution-visualization using structured illumination microscopy slit diaphragm, which before has only been achieved by electron microscopy. As proof principle, measured mean process width 0.249 ± 0.068 µm in healthy kidneys and significant higher 0.675 0.256 minimal change disease patients indicating effacement processes. We then hypothesized that length per glomerular capillary...
Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer type, lacking effective therapies and associated with a dismal prognosis. Palbociclib selective CDK4/6 inhibitor, which has been shown to suppress cell proliferation in many experimental models. Recently, we demonstrated that pan-mTOR inhibitors, such as MLN0128, effectively induce apoptosis, although have limited efficacy restraining of ICC cells. Here, tested the hypothesis palbociclib, due its antproliferative properties types,...
// Xiaolei Li 1,2 , Junyan Tao 2,3 Antonio Cigliano 4 Marcella Sini Julien Calderaro 5,6 Daniel Azoulay 7 Chunmei Wang 2 Yan Liu 1 Lijie Jiang Katja Evert Maria I. Demartis 8 Silvia Ribback Kirsten Utpatel Frank Dombrowski Matthias Diego F. Calvisi 4,8 and Xin Chen Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China Bioengineering Therapeutic Sciences Liver Center, University California, San Francisco, CA, U.S.A 3 School...
Abstract Background & Aims Although it is well established that fatty acids ( FA ) are indispensable for the proliferation and survival of cancer cells in hepatocellular carcinoma HCC ), inhibition Fatty Acid Synthase FASN cannot completely repress cell growth culture. Thus, we hypothesized uptake exogenous by might play an important role development progression . Lipoprotein lipase LPL enzyme catalyses hydrolysis triglycerides into free FFA increases cellular Methods We used...
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, early tumor resection (neo)adjuvant chemotherapy fails improve poor prognosis. In transgenic mouse model of resectable PDAC, we investigated the coordinated activation T natural killier (NK) cells in addition gemcitabine prevent recurrence. Only neoadjuvant, but not adjuvant treatment with PD-1 antagonist effectively supported suppressed local...
Abstract Intrahepatic cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. An altered expression and/or activation of NOTCH1–3 receptors has been shown to play role in iCCA development progression. In this study, we established new CCA patient-derived xenograft model, which was validated by immunohistochemistry transcriptomic analysis. The effects Notch pathway suppression the Crenigacestat (LY3039478)-specific inhibitor were evaluated human cell...
Hepatocellular carcinoma (HCC), the most frequent primary tumor of liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression fatty acid synthase (FASN), major enzyme responsible for lipogenesis, highly detrimental in vitro growth HCC cell lines. To assess whether lipogenesis required liver carcinogenesis,...