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  • 1
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    Online Resource
    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-10-17)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-10-17)
    Abstract: The 18 kDa translocator protein (TSPO) receives growing interest as a biomarker in glioblastoma. Mouse models can serve as an important tool for the investigation of biomarkers in glioblastoma, but several glioblastoma models indicated only low TSPO-PET signals in contrast to high TSPO-PET signals of human glioblastoma. Thus, we aimed to investigate TSPO-PET imaging in the syngeneic immunocompetent SB28 mouse model, which is thought to closely represent the tumor microenvironment (TME) of human glioblastoma. Methods Dynamic TSPO-PET/CT imaging was performed for 60 min after injection of 13.6 ± 4.2 MBq [ 18 F]GE-180. Contrast enhanced CT (ceCT) was acquired prior to PET and served for assessment of tumor volumes and attenuation correction. SB28 and sham mice were imaged at an early (week-1; n = 6 SB28, n = 6 sham) and a late time-point (week-3; n = 8 SB28, n = 9 sham) after inoculation. Standard of truth ex vivo tumor volumes were obtained for SB28 mice at the late time-point. Tracer kinetics were analyzed for the lesion site and the carotid arteries to establish an image derived input function (IDIF). TSPO-PET and ceCT lesion volumes were compared with ex vivo volumes by calculation of root-mean-square-errors (RMSE). Volumes of distribution (VTmax/mean) in the lesion were calculated using carotid IDIF and standardized uptake values (SUVmax/mean) were obtained for a 40–60 min time frame. Results Higher uptake rate constants (K1) were observed for week-1 SB28 tumor lesions when compared to week-3 SB28 tumor lesions. Highest agreement between TSPO-PET lesion volumes and ex vivo tumor volumes was achieved with a 50% maximum threshold (RMSE-VT: 39.7%; RMSE-SUV: 34.4%), similar to the agreement of ceCT tumor volumes (RMSE: 30.1%). Lesions of SB28 mice had higher PET signal when compared to sham mice at week-1 (VTmax 6.6 ± 2.9 vs. 3.9 ± 0.8, p = 0.035; SUVmax 2.3 ± 0.5 vs. 1.2 ± 0.1, p & lt; 0.001) and PET signals remained at a similar level at week-3 (VTmax 5.0 ± 1.6 vs. 2.7 ± 0.8, p = 0.029; SUVmax 1.9 ± 0.5 vs. 1.2 ± 0.2, p = 0.0012). VTmax correlated with SUVmax ( R 2 = 0.532, p & lt; 0.001). Conclusion TSPO-PET imaging of immunocompetent SB28 mice facilitates early detection of tumor signals over sham lesions. SB28 tumors mirror high TSPO-PET signals of human glioblastoma and could serve as a valuable translational model to study TSPO as an imaging biomarker.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.992993
    DOI: 10.3389/fmed.2022.992993.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 2
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    Image_2.jpeg
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-4-4)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-4-4)
    Abstract: Brain metastases (BM) can present a displacing or infiltrating growth pattern, independent of the primary tumor type. Previous studies have shown that tumor cell infiltration at the macro-metastasis/brain parenchyma interface (MMPI) is correlated with poor outcome. Therefore, a pre-therapeutic, non-invasive detection tool for potential metastatic cell infiltration at the MMPI would be desirable to help identify patients who may benefit from a more aggressive local treatment strategy. The aim of this study was to identify specific magnetic resonance imaging (MRI) patterns at the MMPI in patients with BM and to correlate these patterns with patient outcome. Patients and Methods In this retrospective analysis of a prospective BM registry, we categorized preoperative MR images of 261 patients with BM according to a prespecified analysis system, which consisted of four MRI contrast enhancement (CE) patterns: two with apparently regularly shaped borders (termed “rim-enhancing” and “spherical”) and two with irregular delineation (termed “breakout” and “diffuse”). The primary outcome parameter was overall survival (OS). Additionally analyzed prognostic parameters were the Karnofsky Performance Index, tumor size, edema formation, extent of resection, and RPA class. Results OS of patients with a breakout pattern was significantly worse than OS of all other groups. Conclusion Our data show that BM with a breakout pattern have a highly aggressive clinical course. Patients with such a pattern potentially require a more aggressive local and systemic treatment strategy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.849880
    DOI: 10.3389/fonc.2022.849880.s001
    DOI: 10.3389/fonc.2022.849880.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Online Resource
    DataSheet_9.xlsx
    Frontiers Media SA ; 2024
    In:  Frontiers in Immunology Vol. 15 ( 2024-4-25)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 15 ( 2024-4-25)
    Abstract: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterize extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems. Methods Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterization was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analyzed by high-resolution mass spectrometry. Results We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR-323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer-associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response. Conclusion Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2024.1388769
    DOI: 10.3389/fimmu.2024.1388769.s001
    DOI: 10.3389/fimmu.2024.1388769.s002
    DOI: 10.3389/fimmu.2024.1388769.s003
    DOI: 10.3389/fimmu.2024.1388769.s004
    DOI: 10.3389/fimmu.2024.1388769.s005
    DOI: 10.3389/fimmu.2024.1388769.s006
    DOI: 10.3389/fimmu.2024.1388769.s007
    DOI: 10.3389/fimmu.2024.1388769.s008
    DOI: 10.3389/fimmu.2024.1388769.s009
    DOI: 10.3389/fimmu.2024.1388769.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2606827-8
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