4 results on '"Lotsch, Catharina"'
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2. The Molecular and Immunological Landscape of Meningiomas.
- Author
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Lotsch, Catharina, Warta, Rolf, and Herold-Mende, Christel
- Subjects
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INTRACRANIAL tumors , *BRAIN tumors , *IMMUNE checkpoint proteins , *DNA methylation , *MENINGIOMA - Abstract
Meningiomas are the most common primary intracranial tumors in adults and typically have a slow-growing and benign nature. However, there is also a substantial subset of meningiomas that shows aggressive clinical behavior and is refractory to standard treatment modalities, which are still limited to surgery and/or radiotherapy. Despite intensive research, no systemic treatment options are yet available in the clinic for these challenging tumors, resulting in poor patient outcome. Intensive research on the molecular pathogenesis of meningiomas has led to improved diagnostic tools, but so far there is no standardized implementation for the molecular profiling of these tumors for clinical practice. Recent research advances have also focused on the immunophenotyping of meningiomas, leading to several clinical trials examining the use of immune checkpoint blockade therapy in patients with clinically aggressive subtypes. In this review, we aim to summarize the current knowledge on the molecular and immunological landscape of meningiomas in detail and provide current and progressive ideas for future directions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells.
- Author
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Rehbein, Sarah, Possmayer, Anna-Lena, Bozkurt, Süleyman, Lotsch, Catharina, Gerstmeier, Julia, Burger, Michael, Momma, Stefan, Maletzki, Claudia, Classen, Carl Friedrich, Freiman, Thomas M., Dubinski, Daniel, Lamszus, Katrin, Stringer, Brett W., Herold-Mende, Christel, Münch, Christian, Kögel, Donat, and Linder, Benedikt
- Subjects
DISEASE progression ,CALCITRIOL ,CANCER invasiveness ,GLIOMAS ,GENETIC polymorphisms ,CELL receptors ,CHOLECALCIFEROL ,MOLECULAR biology ,CELLULAR signal transduction ,PROTEOMICS ,CELL motility ,STEM cells ,SYMPTOMS ,PHENOTYPES - Abstract
Simple Summary: Glioblastoma is one of the worst cancer types and the most common cancer originating within the brain. Patients afflicted by glioblastoma suffer from poor prognosis, a lack of specific therapies and frequent tumor recurrences. Many researchers are confident that glioblastoma cells can display traits of stem cells and that these attributes lead to an aggressive growth and high rate of recurrence. Based on our previous work that demonstrates that the "sun hormone" vitamin D
3 can block these stem cell traits, we have now gained additional insights into the effects of the active form of vitamin D3 , calcitriol. We can show that specific gene variants of the vitamin D3 receptor might be responsible for the sensitivity towards calcitriol and that sensitive cells are blocked in their stemness attributes as well as migratory potential. Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis. These and other factors are hypothesized to be largely due to the fact that glioblastoma cells are known to be able to obtain stem-like traits, thereby driving these phenotypes. Recently, we have shown that the in vitro and ex vivo treatment of glioblastoma stem-like cells with the hormonally active form of vitamin D3 , calcitriol (1α,25(OH)2 -vitamin D3 ) can block stemness in a subset of cell lines and reduce tumor growth. Here, we expanded our cell panel to over 40 different cultures and can show that, while half of the tested cell lines are sensitive, a quarter can be classified as high responders. Using genetic and proteomic analysis, we further determined that treatment success can be partially explained by specific polymorphism of the vitamin D3 receptor and that high responders display a proteome suggestive of blockade of stemness, as well as migratory potential. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
4. Effective Reprogramming of Patient-Derived M2-Polarized Glioblastoma-Associated Microglia/Macrophages by Treatment with GW2580.
- Author
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Fermi V, Warta R, Wöllner A, Lotsch C, Jassowicz L, Rapp C, Knoll M, Jungwirth G, Jungk C, Dao Trong P, von Deimling A, Abdollahi A, Unterberg A, and Herold-Mende C
- Subjects
- Humans, Microglia pathology, Macrophages metabolism, Glioblastoma drug therapy, Glioblastoma genetics, Glioblastoma metabolism, Brain Neoplasms drug therapy, Brain Neoplasms genetics, Brain Neoplasms metabolism
- Abstract
Purpose: Targeting immunosuppressive and pro-tumorigenic glioblastoma (GBM)-associated macrophages and microglial cells (GAM) has great potential to improve patient outcomes. Colony-stimulating factor-1 receptor (CSF1R) has emerged as a promising target for reprograming anti-inflammatory M2-like GAMs. However, treatment data on patient-derived, tumor-educated GAMs and their influence on the adaptive immunity are lacking., Experimental Design: CD11b+-GAMs freshly isolated from patient tumors were treated with CSF1R-targeting drugs PLX3397, BLZ945, and GW2580. Phenotypical changes upon treatment were assessed using RNA sequencing, flow cytometry, and cytokine quantification. Functional analyses included inducible nitric oxide synthase activity, phagocytosis, transmigration, and autologous tumor cell killing assays. Antitumor effects and changes in GAM activation were confirmed in a complex patient-derived 3D tumor organoid model serving as a tumor avatar., Results: The most effective reprogramming of GAMs was observed upon GW2580 treatment, which led to the downregulation of M2-related markers, IL6, IL10, ERK1/2, and MAPK signaling pathways, while M1-like markers, gene set enrichment indicating activated MHC-II presentation, phagocytosis, and T-cell killing were substantially increased. Moreover, treatment of patient-derived GBM organoids with GW2580 confirmed successful reprogramming, resulting in impaired tumor cell proliferation. In line with its failure in clinical trials, PLX3397 was ineffective in our analysis., Conclusions: This comparative analysis of CSF1R-targeting drugs on patient-derived GAMs and human GBM avatars identified GW2580 as the most powerful inhibitor with the ability to polarize immunosuppressive GAMs to a proinflammatory phenotype, supporting antitumor T-cell responses while also exerting a direct antitumor effect. These data indicate that GW2580 could be an important pillar in future therapies for GBM., (©2023 American Association for Cancer Research.)
- Published
- 2023
- Full Text
- View/download PDF
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