A5033111453- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Barrier Structure and Function Studies
- Brain Metastases and Treatment
- Angiogenesis and VEGF in Cancer
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Mechanisms of cancer metastasis
- Chemical Reactions and Isotopes
- Cell Image Analysis Techniques
- Radiopharmaceutical Chemistry and Applications
- MRI in cancer diagnosis
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- ATP Synthase and ATPases Research
- Single-cell and spatial transcriptomics
- bioluminescence and chemiluminescence research
- DNA Repair Mechanisms
- Radiomics and Machine Learning in Medical Imaging
- 3D Printing in Biomedical Research
- Lanthanide and Transition Metal Complexes
- S100 Proteins and Annexins
- Advanced Breast Cancer Therapies
German Cancer Research Center
2013-2023
University Hospital Heidelberg
2015-2023
Heidelberg University
2015-2023
National Center for Tumor Diseases
2015-2023
Carl Zeiss (Germany)
2019-2023
Deutschen Konsortium für Translationale Krebsforschung
2013-2023
Carl Zeiss (Australia)
2021-2023
Korea Advanced Institute of Science and Technology
2018
Bellvitge University Hospital
2018
Institut d'Investigació Biomédica de Bellvitge
2018
Primary and adaptive resistance against chemo- radiotherapy local recurrence after surgery limit the benefits from these standard treatments in glioma patients. Recently we found that cells can extend ultra-long membrane protrusions, "tumor microtubes" (TMs), for brain invasion, proliferation, interconnection of single to a syncytium is resistant radiotherapy. We wondered whether TMs also convey other 2 treatment modalities. Patient-derived glioblastoma stemlike cell (GBMSC) lines were...
Significance N -myc downstream regulated gene 1 (NDRG1) is a central and druggable molecular hub integrating diverse therapy-induced microenvironmental factors to promote resistance toward alkylating chemotherapy. We suggest that NDRG1-mediated chemoprotection achieved via binding stabilizing methyltransferases, such as O 6 -methylguanine-DNA methyltransferase.
Early and progressive colonization of the healthy brain is one hallmark diffuse gliomas, including glioblastomas. We recently discovered ultralong (>10 to hundreds microns) membrane protrusions [tumor microtubes (TMs)] extended by glioma cells. TMs have been associated with capacity cells effectively invade proliferate. Moreover, are also used some tumor interconnect large, resistant multicellular network. Here, we performed a correlative gene-expression microarray <i>in vivo</i> imaging...
The role of blood-brain barrier (BBB) integrity for brain tumor biology and therapy is a matter debate.We developed new experimental approach using in vivo two-photon imaging mouse metastases originating from melanoma cell line to investigate the growth kinetics individual cells response systemic delivery two PI3K/mTOR inhibitors over time, study impact microregional vascular permeability. drugs are closely related but differ regarding minor chemical modification that greatly increases...
Intravital microscopy provides dynamic understanding of multiple cell biological processes, but its limited resolution has so far precluded structural analysis. Because it is difficult to capture rare and transient events, only few attempts were made observe specific developmental pathological processes in animal models by electron microscopy. The multimodal correlative approach that we propose here combines intravital microscopy, microscopic X-ray computed tomography three-dimensional It...
Amplification of the epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are among most common genetic alterations in glioblastoma (GBM), frequent aggressive primary brain tumor.In present work, we analyzed clonal evolution these major EGFR aberrations a small cohort GBM patients using unique surgical multisampling technique. Furthermore, overexpressed both receptors separately together 2 patient-derived stem cell lines (GSCs) to analyze their functions vivo orthotopic xenograft...
Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding mechanisms cancer cell extravasation from microcapillaries limited as underlying cellular and molecular processes cannot be adequately investigated using in vitro models endpoint vivo experiments. Using ultrastructural functional imaging, we demonstrate that dynamic changes activated promote mandatory first steps colonization. Successful arrested cells occurred when adjacent capillary...
Abstract Background Glioblastomas are characterized by aggressive and infiltrative growth, striking heterogeneity. The aim of this study was to investigate whether tumor cell proliferation invasion interrelated, or rather distinct features different populations. Methods Tumor were longitudinally determined in real-time using 3D vivo 2-photon laser scanning microscopy over weeks. Glioblastoma cells expressed fluorescent markers that permitted the identification their mitotic history cycling...
For a targeted cancer vaccine to be effective, the antigen of interest needs naturally processed and presented on MHC by target cell or an antigen-presenting (APC) in tumor stroma. The presence these characteristics is often assumed based animal models, evaluation antigen-overexpressing APCs vitro, assays material-consuming immune precipitation from fresh solid tissue. Here, we evaluated use alternative approach that uses proximity ligation assay (PLA) identify presentation class...
Rationale: Glioblastoma is the most frequent, primary brain tumor that characterized by a highly immunosuppressive microenvironment (TME). The TME plays key role for biology and effectiveness of immunotherapies. Composition correlates with overall survival governs therapy response. Non invasive assessment has been notoriously difficult. Methods: We have designed an in vivo imaging approach to non invasively visualize innate immune cell dynamics mouse glioma model correlated MRI multiphoton...
Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes subpopulation of glioma cells that becomes highly resistant integration into tumor microtube (TM)-connected multicellular networks. A novel functional approach to detect, isolate, and characterize cell subpopulations with respect in vivo network is established, combining dye staining method intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular...
Abstract Background Glioblastomas have highly infiltrative growth patterns that contribute to recurrence and poor survival. Despite infiltration being a critical therapeutic target, no clinically useful therapies exist counter glioblastoma invasion. Here, we report inhibition of ataxia telangiectasia Rad 3 related kinase (ATR) reduces invasion cells through dysregulation cytoskeletal networks subsequent integrin trafficking. Methods Glioblastoma motility were assessed in vitro vivo response...
Neoangiogenesis is a pivotal therapeutic target in glioblastoma. Tumor monitoring requires imaging methods to assess treatment effects and disease progression. Until now mapping of the tumor vasculature has been difficult. We have developed combined magnetic resonance optical toolkit study neoangiogenesis glioma models. use vivo (MRI) correlative ultramicroscopy (UM) ex cleared whole brains track neovascularization. T2* allows identification single vessels development quantification...
Abstract Specific biological properties of those circulating cancer cells that are the origin brain metastases (BM) not well understood. Here, single breast were fate-tracked during all steps metastatic cascade in mice after intracardial injection over weeks. A novel vivo two-photon microscopy methodology was developed allowed to determine specific cellular and molecular features homed brain, extravasated, successfully established a macrometastasis. Those BM-initiating (BMIC) mainly...
Abstract Glioblastoma multiforme alters healthy tissue vasculature by inducing angiogenesis and vascular remodeling. To fully comprehend the structural functional properties of resulting network, it needs to be studied collectively considering both geometric topological properties. Utilizing Single Plane Illumination Microscopy (SPIM), detailed capillary structure in entire tumor-bearing mouse brains could resolved three dimensions. At scale smallest capillaries, systems bulk U87-...
Diffuse tumor infiltration into the adjacent parenchyma is an effective dissemination mechanism of brain tumors. We have previously developed correlated high field magnetic resonance imaging and ultramicroscopy (MR-UM) to study neonangiogenesis in a glioma model. In present we used MR-UM investigate neoangiogenesis translational approach. compare patterns four models human disease: whereas U87MG model resembles metastases with encapsulated growth extensive neoangiogenesis, S24 experimental...