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  • 1
    In: Cancer Medicine, Wiley, Vol. 9, No. 10 ( 2020-05), p. 3574-3583
    Abstract: Targeting fibroblast growth factor receptor 1 ( FGFR1 ) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response. Furthermore, former studies have revealed contrasting results regarding the impact of FGFR1 amplification and expression on patient's prognosis. Aims Here, we analyzed prevalence and correlation of FGFR1 gene amplification and protein expression in human lung cancer and their impact on overall survival. Materials &  Methods FGFR1 gene amplification and protein expression were analyzed by fluorescence in situ hybridization and immunohistochemistry (IHC) in 208 SQCLC and 45 small cell lung cancers (SCLC). Furthermore, FGFR1 protein expression was analyzed in 121 pulmonary adenocarcinomas (ACs). Amplification and expression were correlated to each other, clinicopathological characteristics, and overall survival. Results FGFR1 was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males ( P  = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 FGFR1 knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females ( P  = .0187) and to the absence of lymph node metastasis in SQCLC ( P  = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected. Discussion FGFR1 gene amplification does not seem to correlate to protein expression. Conclusion We believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2659751-2
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  • 2
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  European Journal of Inorganic Chemistry Vol. 2020, No. 29 ( 2020-08-09), p. 2809-2815
    In: European Journal of Inorganic Chemistry, Wiley, Vol. 2020, No. 29 ( 2020-08-09), p. 2809-2815
    Abstract: In order to gain information about the behavior of tin sulfide clusters with bio‐organic ligand shells under acidic conditions, such as found in undesirable cells for instance, we systematically treated amino acid‐functionalized tin sulfide clusters with different acids. For Boc‐protected amino acid derivatives, we could show that this treatment causes either cleavage of the protecting group of the amino acid or protolysis of the tin sulfide core under release of H 2 S and formation of the correspondingly functionalized organotin trichloride, depending on the nature of the acid. This points towards a potential future use of such species for targeted cytotoxic applications.
    Type of Medium: Online Resource
    ISSN: 1434-1948 , 1099-0682
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1475009-0
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  • 3
    In: The Journal of Clinical Pharmacology, Wiley
    Abstract: Vancomycin's widespread use as the mainstay antibiotic against methicillin‐resistant Staphylococcus aureus infections is complicated by its narrow therapeutic index. Therapeutic drug monitoring (TDM) using area‐under the concentration curve (AUC)‐guided dosing is recommended to optimise therapy and prevent vancomycin‐associated nephrotoxicity (VAN). In 2018, a consultative TDM Advisory Service (the Service) was piloted at an Australian hospital to enable AUC‐guided vancomycin dosing. This study sought to compare the incidence of VAN pre‐ and post‐Service implementation. A 4‐year retrospective observational study of intravenous vancomycin therapy ( 〉 48 hours) in adults (≥18 years), spanning 3‐years pre‐ and 1‐year post‐implementation of the Service was undertaken. Nephrotoxicity was defined as an increase in serum creatinine concentrations of ≥26.5 μmol/L or ≥50% from baseline, on ≥2 consecutive days. Univariate analysis was performed to compare patients pre‐ and post‐implementation, and with and without VAN. Independent factors associated with VAN were identified using a multivariate model. In total, 971 courses of vancomycin therapy, administered to 781 patients, were included; 764 courses (603 patients) pre‐implementation and 207 courses (163 patients) post‐implementation. The incidence of VAN decreased by 5% post‐Service implementation [15% pre‐implementation vs 10% post‐implementation; p = 0.075). Independent factors associated with VAN were sepsis, heart failure, solid organ transplant, concomitant piperacillin‐tazobactam, and average vancomycin AUC during therapy. In conclusion, there was a non‐significant trend towards a reduced incidence of VAN after the Service. Larger, prospective studies are needed to confirm the efficacy of the Service. This article is protected by copyright. All rights reserved
    Type of Medium: Online Resource
    ISSN: 0091-2700 , 1552-4604
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2010253-7
    SSG: 15,3
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