A5051813236- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Cancer Immunotherapy and Biomarkers
- NF-κB Signaling Pathways
- Genetic factors in colorectal cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer-related molecular mechanisms research
- Colorectal and Anal Carcinomas
- Cancer therapeutics and mechanisms
- Gallbladder and Bile Duct Disorders
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- Liver Diseases and Immunity
- Cancer Mechanisms and Therapy
- Cell death mechanisms and regulation
- Colorectal Cancer Treatments and Studies
- Liver Disease Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Cytokine Signaling Pathways and Interactions
- Pediatric Hepatobiliary Diseases and Treatments
- Patient-Provider Communication in Healthcare
- Radiation Therapy and Dosimetry
Heidelberg University
2016-2025
National Center for Tumor Diseases
2015-2025
University Hospital Heidelberg
2017-2025
Hopp Children's Cancer Center Heidelberg
2019-2025
Deutschen Konsortium für Translationale Krebsforschung
2020-2024
German Cancer Research Center
2020-2024
German Primate Center
2004
A major molecular pathway of genetic instability in cancer is DNA mismatch repair deficiency. High-level microsatellite (MSI-H) currently the best predictor responsiveness towards immune checkpoint blockade. Data about prevalence high-level cholangiocarcinoma (CCA) has been conflicting. We employed a cohort comprising 308 Western-world, non-liver fluke-associated CCAs (159 intrahepatic, 106 perihilar, and 43 distal). analysed mononucleotide marker panel consisting BAT25, BAT26, CAT25...
Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, has an incidence rate equal to mortality. Over 80% of HCC cases occur within a high‐risk population, mainly patients with both cirrhosis and chronic hepatitis B or C. With 5‐year survival ranging from <16% for advanced >90% early stage HCC, there is high medical need detection HCC. In this study, we systematically evaluated biomarkers mentioned in international guidelines peer‐reviewed literature surveillance...
Objective A detailed understanding of the molecular alterations in different forms cholangiocarcinogenesis is crucial for a better cholangiocarcinoma (CCA) and may pave way to early diagnosis treatment options. Design We analysed clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions biliary tract correlated results an independent non-IPNB/ITPN associated CCA (n=294). The triplet...
Liver cancers, which are mostly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), very aggressive tumors with poor prognosis. Therapeutic options curative intent largely limited to surgery available systemic therapies show benefit. Signal transducer activator of transcription 1 (STAT1) 3 (STAT3) key factors activated by pro-inflammatory cytokines such as interferon-γ (IFN-γ) interleukin-6 (IL-6). In this study, we combined in vitro cell culture experiments immunohistochemical...
Abstract Background and aims Liver cancer is the third leading cause of related death due to treatment resistance late onset symptoms (Rumgay in J Hepatol 77: 1598–1606, 2022). The role external beam radiotherapy (EBRT) unresectable liver needs be defined. use particle therapy such as carbon ion radiation (CIRT) with high linear energy transfer (LET) could increase efficacy EBRT while limiting toxic effects on non-cancerous tissue. Promising CIRT have been described several studies during...
Abstract Background: Incidence rates of early-onset colorectal cancer (EO-CRC) are increasing in high-income countries, yet the underlying causes and optimal clinical management strategies remain unclear. Methods: Comprehensive molecular profiling was conducted on patients enrolled DKTK MASTER program, which includes with fresh tumor material, age &lt;50 years, and/or rare types. Profiling utilized RNA sequencing (RNA-seq) whole-exome (WES) or whole-genome (WGS). WES data analyzed for...
Cholangiocarcinoma (CCA) may arise in the intra- or extrahepatic biliary tract and is associated with a poor prognosis. Despite recent advances, to date there still no established targeted therapeutic approach available. Non-surgical agents are urgently needed, as most patients non-eligible surgical resection. Anti-PD-L1 therapy prevents cancer cells from evading immune system has emerged new treatment option several entities. Recently, PD-L1 expression been analyzed comparably small CCA...
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,
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...
Abstract: Cynomolgus macaques are frequently used in biomedical research. However, contrast to their closest relative, the rhesus macaque, little is known about Mhc genes except for DQB1 locus. In this study, 33 DRB ‐sequences belonging 17 allelic lineages were detected a total of 68 macaques, 58 originating from Mauritius and 10 China. The majority sequences few China, confirming low degree genetic variation Mauritius. summary, region cynomolgus polymorphic. belong general same as macaque....
Mobile phone video call applications generally did not undergo testing in randomised controlled clinical trials prior to their implementation patient care regarding the rate of successful visits and impact on physician-patient relationship.The National Center for Tumour Diseases (NCT) MOBILE trial was a monocentric open-label patients with solid tumours undergoing systemic cancer therapy need follow-up visit consulting physician at outpatient clinics. 66 were 1:1 receive either standard...
Activation of the oncogene yes-associated protein (YAP) is frequently detected in intrahepatic cholangiocarcinoma (iCCA); however, expression pattern and functional impact its paralogue WW domain-containing transcription regulator 1 (WWTR1; synonym: TAZ) are not well described different CCA subtypes.Immunohistochemical analysis YAP TAZ iCCA extrahepatic (eCCA) cohorts was performed. YAP/TAZ shuttling their on cell lines were investigated. Target genes after combined inhibition...
DNA mismatch repair (MMR) deficiency is a major pathway of genomic instability in cancer. It leads to the accumulation numerous mutations predominantly at microsatellite sequences, phenotype known as (MSI). MSI tumors have distinct clinical behavior and commonly respond well immune checkpoint blockade, irrespective their origin. Data about prevalence among gallbladder cancer (GBC) been conflicting. We here analyzed well-characterized cohort 69 Western-world GBCs.We mononucleotide marker...
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...
Distal cholangiocarcinoma (dCCA) is a biliary tract cancer with dismal prognosis and often preceded by intraepithelial neoplasia (BilIN), representing the most common non-invasive precursor lesion. BilIN are histologically well defined but have not so far been characterised systematically at molecular level. The aim of this study was to determine miRNA-regulated genes in cholangiocarcinogenesis via BilIN. We used clinicopathologically well-characterised cohort 12 dCCA patients. Matched...
Inhibition of the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis has opened a new era in treatment solid cancers. However, there is no data on expression and relevance PD-L1 Western gallbladder cancer (GBC). We assessed immunohistochemically 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell (IC) Combined Positivity (CPS). cells expressed subset 14.7% at TPS cut-off 1%. Higher levels above 10% 25% were reached 4.7% 3.1% cases, respectively. At cut-off, was associated...
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...
Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there no published information on its interaction potential with important drug metabolizing enzymes and transporters, or efficacy in multidrug resistant (MDR) cells. We therefore scrutinized drug–drug vitro. Inhibition cytochrome P450 (CYPs) was quantified by commercial kits. transporters (P-glycoprotein (P-gp, ABCB1), breast...
Although knowledge on inflammatory signaling pathways driving cancer initiation and progression has been increasing, molecular mechanisms in hepatocarcinogenesis are still far from being completely understood. Hepatocyte-specific deletion of the MAPKKK Tak1 mice recapitulates important steps hepatocellular carcinoma (HCC) development, including occurrence cell death, steatohepatitis, dysplastic nodules, HCCs. However, overactivation upon its deubiquitinase Cyld also results steatohepatitis...
Introduction Diagnosis of cholangiocarcinoma (CCA) can be challenging due to unclear imaging criteria and difficulty obtaining adequate tissue biopsy. Although serum cancer antigen 19-9 carcinoembryonic have been proposed as potential diagnostic aids, their use remains limited by insufficient sensitivity specificity. This exploratory analysis aimed identify individual- combinations biomarkers distinguish CCA from hepatocellular carcinoma (HCC) chronic liver disease (CLD) controls using...