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  • 1
    Online Resource
    Online Resource
    Mesothelial mobilization in the developing lung and heart differs in timing, quantity, and pathway dependency
    American Physiological Society ; 2019
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 316, No. 5 ( 2019-05-01), p. L767-L783
    Details
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 316, No. 5 ( 2019-05-01), p. L767-L783
    Abstract: The mesothelial lining of the lung, the visceral pleura, and of the heart, the epicardium, derive from a common multipotent precursor tissue, the mesothelium of the embryonic thoracic cavity that also contributes to organ-specific mesenchymal cell types. Insight into mesothelial mobilization and differentiation has prevailedin the developing heart while the mesenchymal transition and fate of the visceral pleura are poorly understood. Here, we use the fact that the early mesothelium of both the lung and the heart expresses the transcription factor gene Wt1, to comparatively analyze mesothelial mobilization in the two organs by a genetic cre-loxP-based conditional approach. We show that epicardial cells are mobilized in a large number between E12.5 and E14.5, whereas pleural mobilization occurs only sporadically and variably in few regions of the lung in a temporally highly confined manner shortly after E12.5. Mesothelium-specific inactivation of unique pathway components using a Wt1 creERT2 line excluded a requirement for canonical WNT, NOTCH, HH, TGFB, PDGFRA, and FGFR1/FGFR2 signaling in the mesenchymal transition of the visceral pleura but indicated a deleterious effect of activated WNT, NOTCH, and HH signaling on lung development. Epicardial mobilization was negatively impacted on by loss of HH, PDGFRA, FGFR1/2 signaling. Epicardial overactivation of WNT, NOTCH, and HH disturbed epicardial and myocardial integrity. We conclude that mesothelial mobilization in the developing lung and heart differs in timing, quantity and pathway dependency, indicating the organ specificity of the program.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    URL: Article
    DOI: 10.1152/ajplung.00212.2018
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2019
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    RUNX3 Transcript Variants Have Distinct Roles in Ovarian Carcinoma and Differently Influence Platinum Sensitivity and Angiogenesis
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 3 ( 2021-01-26), p. 476-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 3 ( 2021-01-26), p. 476-
    Abstract: The prognosis of late-stage epithelial ovarian cancer (EOC) patients is affected by chemotherapy response and the malignant potential of the tumor cells. In earlier work, we identified hypermethylation of the runt-related transcription factor 3 gene (RUNX3) as a prognostic biomarker and contrary functions of transcript variants (TV1 and TV2) in A2780 and SKOV3 cells. The aim of the study was to further validate these results and to increase the knowledge about RUNX3 function in EOC. New RUNX3 overexpression models of high-grade serous ovarian cancer (HGSOC) were established and analyzed for phenotypic (IC50 determination, migration, proliferation and angiogenesis assay, DNA damage analysis) and transcriptomic consequences (NGS) of RUNX3 TV1 and TV2 overexpression. Platinum sensitivity was affected by a specific transcript variant depending on BRCA background. RUNX3 TV2 induced an increased sensitivity in BRCA1wt cells (OVCAR3), whereas TV1 increased the sensitivity and induced a G2/M arrest under treatment in BRCA1mut cells (A13-2-12). These different phenotypes relate to differences in DNA repair: homologous recombination deficient A13-2-12 cells show less γH2AX foci despite higher levels of Pt-DNA adducts. RNA-Seq analyses prove transcript variant and cell-line-specific RUNX3 effects. Pathway analyses revealed another clinically important function of RUNX3—regulation of angiogenesis. This was confirmed by thrombospondin1 analyses, HUVEC spheroid sprouting assays and proteomic profiling. Importantly, conditioned media (CM) from RUNX3 TV1 overexpressing A13-2-12 cells induced an increased HUVEC sprouting. Altogether, the presented data support the hypothesis of different functions of RUNX3 transcript variants related to the clinically relevant processes—platinum resistance and angiogenesis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13030476
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 3
    Online Resource
    Online Resource
    The placebo effect in allergen‐specific immunotherapy trials
    Wiley ; 2013
    In:  Clinical and Translational Allergy Vol. 3, No. 1 ( 2013-01)
    Details
    In: Clinical and Translational Allergy, Wiley, Vol. 3, No. 1 ( 2013-01)
    Abstract: Double‐blind, placebo‐controlled (DBPC) trials are the gold standard for demonstrating clinical efficacy and tolerability. The placebo effect, although an important feature in placebo‐controlled studies, has never been systematically investigated in allergen‐specific immunotherapy (SIT) studies. This study was performed to examine the placebo response in SIT trials that employed a baseline observational period and two treatment years using a symptom‐medication‐score (SMS) as the primary endpoint. Methods The placebo effect was evaluated in six DBPC SIT studies (five studies using subcutaneous SIT (SCIT) and one sublingual (SLIT)), two grass, two birch and two house dust mite (HDM) SIT, including a total of 472 adult patients treated with a placebo. The results were reported as changes from baseline of the SMS area under the curve after two years of perennial placebo therapy during the respective evaluation periods. Pollen counts and IgG 4 levels were additionally analysed. Results Subcutaneously treated placebo patients displayed a marked decrease in the SMS. The mean placebo effect in the SCIT trials with comparable allergen exposure was up to 41% in the second treatment year and, in contrast, reached only 1% in the SLIT trial. Allergen exposure had an inverse influence on the placebo effect. No changes from baseline in allergen specific IgG 4 antibodies were observed in the placebo‐treated patients. Conclusions SIT studies display a significant placebo effect, mainly observed in subcutaneous immunotherapy, with high variability depending on the route of application and allergen exposure. Our findings indicate the differential role of the placebo effect in SIT efficacy depending on the route of administration and pollen exposure.
    Type of Medium: Online Resource
    ISSN: 2045-7022 , 2045-7022
    URL: Article
    DOI: 10.1186/2045-7022-3-42
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2630865-4
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  • 4
    Online Resource
    Online Resource
    Fgfr2 is required for the expansion of the early adrenocortical primordium
    Elsevier BV ; 2015
    In:  Molecular and Cellular Endocrinology Vol. 413 ( 2015-09), p. 168-177
    Details
    In: Molecular and Cellular Endocrinology, Elsevier BV, Vol. 413 ( 2015-09), p. 168-177
    Type of Medium: Online Resource
    ISSN: 0303-7207
    URL: Article
    DOI: 10.1016/j.mce.2015.06.022
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 1500651-7
    SSG: 12
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