A5001598846- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Cell death mechanisms and regulation
- Mechanisms of cancer metastasis
- Cancer Research and Treatments
- Advanced Breast Cancer Therapies
- interferon and immune responses
- Pancreatic function and diabetes
- NF-κB Signaling Pathways
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Chemical Reactions and Isotopes
- IL-33, ST2, and ILC Pathways
- Brain Metastases and Treatment
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Renal cell carcinoma treatment
- Caveolin-1 and cellular processes
- Glycosylation and Glycoproteins Research
- Neuroendocrine Tumor Research Advances
- Prostate Cancer Treatment and Research
- Cancer-related Molecular Pathways
DKFZ-ZMBH Alliance
2012-2025
German Cancer Research Center
2016-2025
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2016-2025
Heidelberg University
2016-2025
Deutschen Konsortium für Translationale Krebsforschung
2016-2024
University Hospital Heidelberg
2023
Digital Research Alliance of Canada
2018
Friedrich Miescher Institute
2012
Oregon State University
2012
Guy's and St Thomas' NHS Foundation Trust
2012
Colon carcinoma is one of the leading causes death from cancer and characterized by a heterogenic pool cells with distinct differentiation patterns. Recently, it was reported that population undifferentiated primary tumor, so-called stem (CSC), can reconstitute original tumor on xenotransplantation. Here, we show spheroid cultures these colon CSCs contain expression CD133, CD166, CD44, CD29, CD24, Lgr5, nuclear beta-catenin, which have all been suggested to mark (cancer) cell population....
Colon cancer stem cells (CSC) can be identified with AC133, an antibody that detects epitope on CD133. However, recent evidence suggests expression of CD133 is not restricted to CSCs, but also expressed differentiated tumor cells. Intriguingly, we observed detection the AC133 cell surface decreased upon differentiation CSC in a manner correlated loss clonogenicity. this event did coincide change promoter activity, mRNA, splice variant, protein expression, or even In contrast, noted...
Article27 November 2017Open Access Transparent process Screening drug effects in patient-derived cancer cells links organoid responses to genome alterations Julia Jabs orcid.org/0000-0002-4915-9966 Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany for Quantitative Analysis Molecular and Cellular Biosystems (BioQuant), University Department Bioinformatics Functional Genomics, Institute Pharmacy Biotechnology (IPMB) BioQuant, Heidelberg...
Abstract Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance circulation, robust CTC expansion protocols are urgently needed effectively study disease progression and therapy responses. Here we present establishment long-term CTC-derived organoids from female metastatic Multiomics analysis along preclinical modeling xenografts identified neuregulin 1 (NRG1)–ERBB2 receptor tyrosine kinase 3 ( ERBB3 /HER3)...
Activating mutations in the proto-oncogene KRAS are a hallmark of pancreatic ductal adenocarcinoma (PDAC), an aggressive malignancy with few effective therapeutic options. Despite efforts to develop KRAS-targeted drugs, absolute dependence PDAC cells on remains incompletely understood. Here we model complete inhibition using CRISPR/Cas-mediated genome editing and demonstrate that is dispensable subset human mouse cells. Remarkably, nearly all deficient exhibit phosphoinositide 3-kinase...
Significance Pancreatic ductal adenocarcinoma is one of the most malignant human tumors for which there are no efficacious therapeutic strategies. This tumor type characterized by an abundant desmoplastic stroma that promotes progression. Yet recent studies have shown physical or genetic elimination leads to more aggressive development. Here, we decided reprogram stromal tissue identifying and subsequently targeting genes responsible their protumorigenic properties. Comparative transcriptome...
The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase which catalyses generation of linkages
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis and poor therapeutic response to current chemotherapy regimens in unselected patient populations. Recently, it has been shown that PDAC may be stratified into functionally therapeutically relevant molecular subgroups some of these subtypes can recapitulated by IHC for KRT81 [quasi-mesenchymal (QM)/squamous/basal-like] HNF1A (non-QM, overlap exocrine/ADEX subtype).Experimental Design: We validated the...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas derived their genome-wide transcriptome DNA methylome landscapes. Clustering based on methylation revealed two distinct groups displaying different patterns at regions encoding repeat elements. Methylationlow tumors are higher expression endogenous retroviral...
Formation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death by binding to death-receptor-bound FADD. By elucidating function caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, reveal reduces DISC association activation caspase-8. Furthermore, extend our co-operative/hierarchical model caspase-8/cFLIP show does not compete with for Utilizing...
Purpose: The devastating prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDA) presents an urgent need for the development therapeutic strategies targeting disseminated tumor cells. Until now, T-cell therapy has been scarcely pursued in PDA, due to prevailing view that it represents a poorly immunogenic tumor. Experimental design: We systematically analyzed infiltrates biopsies from 127 PDA by means immunohistochemistry, flow cytometry, receptor (TCR) deep-sequencing...
Circulating tumor cells (CTCs) hold immense promise for unraveling heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to patients, enabling the screening of larger blood volumes. To leverage DLA's full potential, introduces a novel approach enrichment from DLAs.
Abstract Purpose: Malignant gliomas are the most aggressive human brain tumors without any curative treatment. The antitumor effect of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in has thus far only been thoroughly established cell lines. In present study, we investigated therapeutic potential TRAIL primary glioma cells. Experimental Design: We isolated cells from 13 astrocytoma and oligoastrocytoma patients all four WHO grades malignancy compared levels TRAIL-induced...
Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a novel promising anticancer biotherapeutic. However, TRAIL-resistant tumor cells require combinatorial regimens to sensitize but not normal for TRAIL-induced apoptosis. Here, we investigated the mechanism of synergistic antitumor effect bortezomib in combination with TRAIL hepatoma, colon, and pancreatic cancer comparison toxicity primary human hepatocytes (PHH). cotreatment at high clinically relevant...