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  • 1
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    Online Resource
    Reproducibility and its confounders of CMR feature tracking myocardial strain analysis in patients with suspected myocarditis
    Springer Science and Business Media LLC ; 2022
    In:  European Radiology Vol. 32, No. 5 ( 2022-05), p. 3436-3446
    Details
    In: European Radiology, Springer Science and Business Media LLC, Vol. 32, No. 5 ( 2022-05), p. 3436-3446
    Abstract: Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique for assessing myocardial strain with valuable diagnostic and prognostic potential. However, the reproducibility of biventricular CMR-FT analysis in a large cardiovascular population has not been assessed. Also, evidence of confounders impacting reader reproducibility for CMR-FT in patients is unknown and currently limits the clinical implementation of this technique. Methods From a dual-center database of patients referred to CMR for suspected myocarditis, 125 patients were randomly selected to undergo biventricular CMR-FT analysis for 2-dimensional systolic and diastolic measures, with additional 3-dimensional analysis for the left ventricle. All image analysis was replicated by a single reader and by a second reader for intra- and inter-reader analysis (Circle Cardiovascular Imaging). Reliability was tested with intraclass correlation (ICC) tests, and the impact of imaging confounders on agreement was assessed through multivariable analysis. Results Left and right ventricular ejection fractions were reduced in 34% and 37% of the patients, respectively. Good to excellent reliability was shown for 2D (all ICC  〉  0.85) and 3D (all ICC  〉  0.70) peak strain and early diastolic strain rate for both ventricles in longitudinal orientation as well as circumferential orientations for the left ventricle. An increased slice number improved agreement while the presence of pericardial effusion compromised diastolic strain rate agreement, and arrhythmia compromised right ventricular agreement. Conclusion In a large clinical cohort, we could show CMR-FT yields excellent inter-reader and intra-reader reproducibility. Multi-parametric CMR-FT of the right and left ventricles appears to be a robust tool in cardiovascular patients referred to CMR. Clinical trial registration. ClinicalTrials.gov Identifier: NCT03470571, NCT04774549. Key Points • Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique to measure myocardial strain in cardiovascular patients referred for CMR; however, the evaluation of its reproducibility in a large cohort has not yet been performed . • In a large clinical cohort, CMR-FT yields excellent inter-reader and intra-reader reproducibility for both left and right ventricular systolic and diastolic parameters . • Arrhythmia and pericardial effusion compromise agreement of select FT parameters, but poor ejection fraction does not .
    Type of Medium: Online Resource
    ISSN: 1432-1084
    URL: Article
    DOI: 10.1007/s00330-021-08416-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1472718-3
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  • 2
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    Online Resource
    Effects of Cilazapril on Vascular Structure and Function in Essential Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 1996
    In:  Hypertension Vol. 27, No. 3 ( 1996-03), p. 371-376
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 27, No. 3 ( 1996-03), p. 371-376
    Abstract: Abstract Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril (5 mg twice daily) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured minimal forearm vascular resistance (ratio of mean arterial pressure and forearm blood flow after heating, ischemia, and ischemic exercise) as an indirect estimate of vascular structure. Cilazapril decreased blood pressure (151±14/99±7 mm Hg during placebo to 138±17/89±8 mm Hg after cilazapril treatment, P 〈 .01) and baseline (42.2±12.6 to 37.1±10.6 U, P 〈 .05) and minimal (3.0±1.1 to 2.4±0.7 U, 15.9±20.2%; P 〈 .05) forearm vascular resistances. The change in minimal forearm vascular resistance was unrelated to age, duration of hypertension, or changes in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6±1.0 to 11.4±5.9 mL/min per 100 mL and acetylcholine to 21.5±17.8. Both responses did not change after cilazapril. The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Therapy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/01.HYP.27.3.371
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1996
    detail.hit.zdb_id: 2094210-2
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  • 3
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    Online Resource
    CHRDL1 Regulates Stemness in Glioma Stem-like Cells
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 23 ( 2022-12-03), p. 3917-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 23 ( 2022-12-03), p. 3917-
    Abstract: Glioblastoma (GBM) still presents as one of the most aggressive tumours in the brain, which despite enormous research efforts, remains incurable today. As many theories evolve around the persistent recurrence of this malignancy, the assumption of a small population of cells with a stem-like phenotype remains a key driver of its infiltrative nature. In this article, we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of bone morphogenic protein 4 (BMP4), which induces GSC differentiation and, hence, reduces tumorigenicity. We, therefore, employed two previously described GSCs spheroid cultures and depleted them of CHRDL1 using the stable transduction of a CHRDL1-targeting shRNA. We show with in vitro cell-based assays (MTT, limiting dilution, and sphere formation assays), Western blots, irradiation procedures, and quantitative real-time PCR that the depletion of the secreted BMP4 antagonist CHRDL1 prominently decreases functional and molecular stemness traits resulting in enhanced radiation sensitivity. As a result, we postulate CHRDL1 as an enforcer of stemness in GSCs and find additional evidence that high CHRDL1 expression might also serve as a marker protein to determine BMP4 susceptibility.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11233917
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 4
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    Online Resource
    Dexamethasone Treatment Limits Efficacy of Radiation, but Does Not Interfere With Glioma Cell Death Induced by Tumor Treating Fields
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-7-30)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-30)
    Abstract: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive. Methods Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/- concomitant Dex and analysed its impact on progression-free (PFS) and overall survival (OS). Results The addition of Dex significantly reduced the efficacy of RT in U251, but not in MZ54 cells. TTFields (200 kHz/250 kHz) induced massive cell death in both cell lines. Concomitant treatment of TTFields and Dex did not reduce the overall efficacy of TTFields. Further, in our retrospective clinical analysis, we found that the addition of Dex to TTFields therapy did not influence PFS nor OS. Conclusion Our translational investigation indicates that the efficacy of TTFields therapy in patients with GBM and GBM cell lines is not affected by the addition of Dex.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.715031
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 5
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    A New Pentafluorothio-Substituted Curcuminoid with Superior Antitumor Activity
    MDPI AG ; 2021
    In:  Biomolecules Vol. 11, No. 7 ( 2021-06-25), p. 947-
    Details
    In: Biomolecules, MDPI AG, Vol. 11, No. 7 ( 2021-06-25), p. 947-
    Abstract: A new and readily available pentafluorothiophenyl-substituted N-methyl-piperidone curcuminoid 1a was prepared and investigated for its anti-proliferative, pro-apoptotic and cancer stem cell-differentiating activities against a panel of human tumor cell lines derived from various tumor entities. The compound 1a was highly anti-proliferative and reached IC50 values in the nanomolar concentration range. 1a was superior to the known anti-tumorally active curcuminoid EF24 (2) and its known N-ethyl-piperidone analog 1b in all tested tumor cell lines. Furthermore, 1a induced a noticeable increase of intracellular reactive oxygen species in HT-29 colon adenocarcinoma cells, which possibly leads to a distinct increase in sub-G1 cells, as assessed by cell cycle analysis. A considerable activation of the executioner-caspases 3 and 7 as well as nuclei fragmentation, cell rounding, and membrane protrusions suggest the triggering of an apoptotic mechanism. Yet another effect was the re-organization of the actin cytoskeleton shown by the formation of stress fibers and actin aggregation. 1a also caused cell death in the adherently cultured glioblastoma cell lines U251 and Mz54. We furthermore observed that 1a strongly suppressed the stem cell properties of glioma stem-like cell lines including one primary line, highlighting the potential therapeutic relevance of this new compound.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom11070947
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2701262-1
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  • 6
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    Online Resource
    Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic–Induced Apoptosis
    American Association for Cancer Research (AACR) ; 2017
    In:  Molecular Cancer Therapeutics Vol. 16, No. 1 ( 2017-01-01), p. 156-168
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 16, No. 1 ( 2017-01-01), p. 156-168
    Abstract: Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here, we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101–induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, whereas these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels. KRIBB11 decreased protein levels of HSP70, BAG3, and the antiapoptotic Bcl-2 protein Mcl-1, and both KRIBB11 and YM-1 elicited significantly increased mitochondrial dysfunction, effector caspase activity, and apoptotic cell death after combined treatment with AT-101 and ABT-737. Depletion of BAG3 also led to a pronounced loss of cell–matrix adhesion, FAK phosphorylation, and in vivo tumor growth in an orthotopic mouse glioma model. Furthermore, it reduced the plating efficiency of U251 cells in three-dimensional clonogenic assays and limited clonogenic survival after short-term treatment with AT-101. Collectively, our data suggest that the HSF1/HSP70/BAG3 pathway plays a pivotal role for overexpression of prosurvival Bcl-2 proteins and cell death resistance of glioma. They also support the hypothesis that interference with BAG3 function is an effective novel approach to prime glioma cells to anoikis. Mol Cancer Ther; 16(1); 156–68. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.MCT-16-0262
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 7
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    Online Resource
    Synthesis of Novel Lithium Salts containing Pentafluorophenylamido-based Anions and Investigation of their Thermal and Electrochemical Properties
    Walter de Gruyter GmbH ; 2012
    In:  Zeitschrift für Physikalische Chemie Vol. 226, No. 5-6 ( 2012-6-1), p. 377-390
    Details
    In: Zeitschrift für Physikalische Chemie, Walter de Gruyter GmbH, Vol. 226, No. 5-6 ( 2012-6-1), p. 377-390
    Abstract: Three novel lithium salts, lithium bis(pentafluorophenyl)amide LiN(Pfp) 2 , lithium pentafluorphenyl(trifluormethylsulfonyl)imide LiN(Pfp)(Tf) and lithium pentafluorphenyl(nonafluorbutylsulfonyl)imide LiN(Pfp)(Nf) were synthesized and characterized with respect to their thermal and electrochemical properties. LiN(Pfp) 2 decomposes at 108 ºC, whereas Li-N(Pfp)(Tf) and Li-N(Pfp)(Nf) show a much higher thermal stability of 307 ºC and 316 ºC, respectively. The ionic conductivity at 100 ºC measured by means of impedance spectroscopy decreases in the order LiN(Pfp)(Tf) 〉 LiN(Tf) 2 〉 LiN(Pfp)(Nf). Both, the activation energy and entropy for ion conduction in the new salts are lower than in LiN(Tf) 2 (LiTFSI), most likely due to the lower symmetry of the new anions. The electrochemical stability and ionic conductivity of LiN(Pfp)(Tf) and LiN(Pfp)(Nf) solutions (0.1 mol/l) in ethylene carbonate/dimethyl carbonate ( 1:3 w/w) are slightly lower than those of the LiTFSI solution, but still sufficient for application in lithium ion batteries. The high thermal stability of the novel salts and their stability towards hydrolysis makes them attractive candidates for overcoming the drawbacks of LiPF 6 -based electrolytes at elevated temperatures.
    Type of Medium: Online Resource
    ISSN: 2196-7156 , 0942-9352
    URL: Article
    DOI: 10.1524/zpch.2012.0220
    RVK:
    VA 8450
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2012
    detail.hit.zdb_id: 201103-7
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  • 8
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    Online Resource
    BAG3 is a negative regulator of ciliogenesis in glioblastoma and triple‐negative breast cancer cells
    Wiley ; 2022
    In:  Journal of Cellular Biochemistry Vol. 123, No. 1 ( 2022-01), p. 77-90
    Details
    In: Journal of Cellular Biochemistry, Wiley, Vol. 123, No. 1 ( 2022-01), p. 77-90
    Abstract: By regulating several hallmarks of cancer, BAG3 exerts oncogenic functions in a wide variety of malignant diseases including glioblastoma (GBM) and triple‐negative breast cancer (TNBC). Here we performed global proteomic/phosphoproteomic analyses of CRISPR/Cas9‐mediated isogenic BAG3 knockouts of the two GBM lines U343 and U251 in comparison to parental controls. Depletion of BAG3 evoked major effects on proteins involved in ciliogenesis/ciliary function and the activity of the related kinases aurora‐kinase A and CDK1. Cilia formation was significantly enhanced in BAG3 KO cells, a finding that could be confirmed in BAG3‐deficient versus ‐proficient BT‐549 TNBC cells, thus identifying a completely novel function of BAG3 as a negative regulator of ciliogenesis. Furthermore, we demonstrate that enhanced ciliogenesis and reduced expression of SNAI1 and ZEB1, two key transcription factors regulating epithelial to mesenchymal transition (EMT) are correlated to decreased cell migration, both in the GBM and TNBC BAG3 knockout cells. Our data obtained in two different tumor entities identify suppression of EMT and ciliogenesis as putative synergizing mechanisms of BAG3‐driven tumor aggressiveness in therapy‐resistant cancers.
    Type of Medium: Online Resource
    ISSN: 0730-2312 , 1097-4644
    URL: Issue
    URL: Article
    DOI: 10.1002/jcb.v123.1
    DOI: 10.1002/jcb.30073
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1479976-5
    SSG: 12
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  • 9
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    Online Resource
    Die Unterlassenskausalität im Fall Jalloh: Ein Schritt zur Anerkennung der hypothetischen Genehmigung?
    Walter de Gruyter GmbH ; 2016
    In:  Zeitschrift für die gesamte Strafrechtswissenschaft Vol. 2016, No. 3 ( 2016-01-1)
    Details
    In: Zeitschrift für die gesamte Strafrechtswissenschaft, Walter de Gruyter GmbH, Vol. 2016, No. 3 ( 2016-01-1)
    Type of Medium: Online Resource
    ISSN: 1612-703X , 0084-5310
    URL: Article
    DOI: 10.1515/zstw-2016-0025
    RVK:
    PH 1000
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2016
    detail.hit.zdb_id: 2138296-7
    detail.hit.zdb_id: 206260-4
    SSG: 2
    SSG: 2,1
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  • 10
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    Online Resource
    Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death
    Informa UK Limited ; 2021
    In:  Autophagy Vol. 17, No. 11 ( 2021-11-02), p. 3424-3443
    Details
    In: Autophagy, Informa UK Limited, Vol. 17, No. 11 ( 2021-11-02), p. 3424-3443
    Type of Medium: Online Resource
    ISSN: 1554-8627 , 1554-8635
    URL: Article
    DOI: 10.1080/15548627.2021.1874208
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2262043-6
    SSG: 12
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