A5001423869- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- NF-κB Signaling Pathways
- Cancer Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immune Response and Inflammation
- Cancer Mechanisms and Therapy
- Caveolin-1 and cellular processes
- Circular RNAs in diseases
- Radiation Therapy and Dosimetry
- Nutrition, Genetics, and Disease
- Cancer therapeutics and mechanisms
- Liver Diseases and Immunity
- Cancer Cells and Metastasis
- Immune cells in cancer
- Hepatitis B Virus Studies
- Calpain Protease Function and Regulation
- Plant Micronutrient Interactions and Effects
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- Metabolomics and Mass Spectrometry Studies
Heidelberg University
2013-2024
University Hospital Heidelberg
2013-2024
National Center for Tumor Diseases
2013-2024
Institut de Biologia Evolutiva
2015
Universitat Pompeu Fabra
2015
University of Konstanz
2010
Migration and invasion of malignant cells are prerequisites for cancer progression metastasis. The Bcl-2 family proteins consists about 25 members has been extensively studied in the context apoptosis. Despite fact that small molecules targeting have already entered clinical trials, very few studies investigated a role antiapoptotic beside cell death aim this study was to dissect potential Mcl-1, Bcl-xL on migration colorectal independent their control function. We used assays as well three...
Abstract Since metastatic colorectal cancer (CRC) is a leading cause of cancer-related death, therapeutic approaches overcoming primary and acquired therapy resistance are an urgent medical need. In this study, the efficacy toxicity high-affinity inhibitors targeting antiapoptotic BCL-2 proteins (BCL-2, BCL-XL, MCL-1) were evaluated. By RNA sequencing analysis pan-cancer cohort comprising >1500 patients subsequent prediction protein activity, BCL-XL was identified as only that...
Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal cell (IEC) death and proliferation. While the disruption of several IEC regulating factors result in inflammation, loss anti-apoptotic BCL2 family members BCL2L1 has no effect mice. We investigated functions antiapoptotic protein MCL1, another member family,
Despite the fact that new treatment regimes have improved overall survival of patients challenged by colorectal cancer (CRC), prognosis in metastatic situation is still restricted. The Bcl-2 family proteins has been identified as promising anti drug target. Even though small molecules targeting are clinical trials, little known regarding their effects on CRC. aim this study was to preclinically investigate value ABT-737 and Obatoclax anticancer drugs for CRC treatment. BH3-mimetics cells...
Colorectal cancer is the third most common malignancy in humans and novel therapeutic approaches are urgently needed. Autophagy an evolutionarily highly conserved cellular process by which cells collect unnecessary organelles or misfolded proteins subsequently degrade them vesicular structures order to refuel with energy. Dysregulation of complex autophagy signaling network has been shown contribute onset progression various models. The Bcl-2 family comprises central regulators apoptosis...
Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health disease, they are tightly regulated the human body. In order to assess variability potential adaptive evolution of element homeostasis, we quantified 18 150 liver samples, together with expression 90 genes abundances 40 proteins involved their homeostasis. Additionally, genotyped 169 single nucleotide polymorphism (SNPs) same sample set. We detected significant associations for 8...
Autophagy is a catabolic process that enables cells to degrade obsolete content and refuel energy depots. In colorectal cancer (CRC) autophagy has been shown promote tumorigenesis through delivery in the condition of uncontrolled proliferation. With this study, we aimed at evaluating whether sustains CRC cell viability if it impacts therapy resistance. Initially, tissue micro array, containing mucosa (n = 10), adenoma 18) adenocarcinoma 49) spots, was stained for expression essential...
Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance PHD during spread colorectal cancer. expression analysis 124 cancer patients revealed reduced tumoral PHD3 correlated with increased frequency distant metastases and poor outcome. Tumorigenicity potential tumor cells over underexpressing were...
Avoidance of therapy-induced apoptosis is a hallmark acquired resistance towards radiotherapy. Thus, breaking still challenges modern cancer therapy. The Bcl-2 protein family known for its regulatory role in signaling, making Bcl-2, Mcl-1 and Bcl-xL promising targets. This study evaluates the effects highly specific inhibitors (WEHI-539), (ABT-199) (S63845) as radiosensitizers. Covering broad spectrum solid tumors, Non-Small-Cell Lung Cancer (NSCLC), Head Neck Squamous Cell Carcinoma (HNSCC)...
Abstract Background and Aims Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the intrahepatic (iCCA) or extrahepatic (eCCA) bile ducts with poor prognosis limited treatment options. Prior evidence highlighted a significant contribution of non‐canonical NF‐κB signalling pathway in initiation aggressiveness different tumour types. Lymphotoxin‐β (LTβ) stimulates NF‐κB‐inducing kinase (NIK), resulting activation transcription factor RelB. However, functional via LTβ/NIK/RelB...
Intrahepatic, perihilar, and distal cholangiocarcinoma (iCCA, pCCA, dCCA) are highly malignant tumours with increasing mortality rates due to therapy resistances. Among the mechanisms mediating resistance, overexpression of anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-xL , Mcl-1) is particularly important. In this study, we investigated whether antiapoptotic protein patterns prognostically relevant potential therapeutic targets in CCA. were analysed a pan-cancer cohort from NCT/DKFZ/DKTK MASTER...
Background Chronic alcohol consumption is a risk factor for colorectal cancer. The mechanisms by which ethanol (EtOH) exerts its carcinogenic effect on the mucosa are not clear and may include oxidative stress with action of reactive oxygen species ( ROS ) generated through EtOH metabolism via cytochrome P4502E1 CYP 2E1) leading to etheno‐ DNA adducts. also induce apoptosis. However, chronic 2E1, adducts as well anti‐apoptotic proteins in heavy drinkers without inflammation still known....
HCC is the most common primary liver tumor, with an increasing incidence worldwide. a heterogeneous malignancy and usually develops in chronically injured liver. The NF-κB signaling network consists of canonical noncanonical branch. Activation documented. However, functional clinically relevant role its downstream effectors not established.
Obatoclax is a very late stage autophagy inhibitor in CRC cells and allows acidification of autophagosomes. Cells were treated with either Chloroquine (30 IźM, middle) or obatoclax (0.25 lower) for 48 h. Acridine orange was applied. Green dots indicate unprotonated (left panel) red (middle protonated Orange. The right panel shows merged overlay. Pictures are representative three independent experiments. AO = (PDF 6121 kb)
Background and Aims Primary liver cancer is the third leading cause of related death with increasing incidence mortality worldwide. Recent studies demonstrate a role non-canonical nuclear factor kappa B (NF-κB) signaling in various chronic diseases. Here, we aimed to further elucidate NF-κB its key transcription RELB hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (iCCA).