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Berlin Brandenburg

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  • 1
    Language: English
    In: Cell Reports, 23 October 2018, Vol.25(4), pp.1027-1039.e6
    Description: , which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a mouse, which harbors an additional allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous -driven lung adenocarcinoma model, we show that mice display a cancer protection phenotype that is indistinguishable from that observed in animals. Moreover, we demonstrate that and cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our allele enabled us to assess the contribution of to -mediated tumor suppression. Torgovnick et al. create a mouse model, carrying a third copy of (p21), which shows enhanced cell-cycle arrest capacity and protection against DNA damage-induced apoptosis. The animals display delayed epithelial regeneration and a robust cancer resistance phenotype, highlighting the importance of p21 in p53-dependent tumor suppression.
    Keywords: Cdkn1a ; P21 ; P53 ; Mouse Model ; Cancer ; Tumor Suppressor ; Cell Cycle Arrest ; Apoptosis ; Cancer Protection ; Biology
    ISSN: 2211-1247
    E-ISSN: 2211-1247
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  • 2
    In: European Journal of Haematology, September 2019, Vol.103(3), pp.268-271
    Description: Follicular lymphoma is the most common subtype of the indolent non‐Hodgkin lymphomas. Treatment usually consists of immuno‐chemotherapy and results in long‐lasting remissions in most cases. Progression‐free survival with the second‐generation anti‐CD20 antibody obinutuzumab was shown to be better than with rituximab when given in combination with either bendamustine or anthracycline‐based chemotherapy. Although treatment is generally well tolerated without an excessive rate of toxicities, there appear to be slightly more adverse events with obinutuzumab than with rituximab. Here, we report the case of a 45‐year‐old female patient that was diagnosed with a disseminated enterovirus infection while undergoing maintenance therapy with obinutuzumab after induction treatment with the combination of bendamustine and rituximab. Enterovirus RNA was detected in the blood, the cerebrospinal fluid, and the colon. A therapy with intravenous immunoglobulins was initiated since the patient presented with a severe treatment‐related immunosuppression indicated by hypogammaglobulinemia. Nonetheless, she eventually died from the enterovirus infection without evidence of lymphoma progression. This case underscores that clinicians should be aware of rare but potentially fatal infectious complications related to treatment protocols containing anti‐CD20 antibodies.
    Keywords: Anti‐Cd20 Antibody ; Enterovirus ; Follicular Lymphoma ; Hypogammaglobulinemia ; Obinutuzumab
    ISSN: 0902-4441
    E-ISSN: 1600-0609
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  • 3
    Language: English
    In: Cancer Cell, 14 August 2017, Vol.32(2), pp.238-252.e9
    Description: Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92–0.96; p 〈 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83–0.95; p 〈 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources. Best et al. use particle-swarm optimization algorithms and RNA-seq of tumor-educated platelets from patients to generate RNA sets capable of identifying patients with non-small-cell lung cancer, including those having early stage, from individuals without cancer, including those having inflammatory conditions.
    Keywords: Tumor-Educated Platelets ; Blood Platelets ; RNA ; Cancer Diagnostics ; Particle-Swarm Optimization ; Splicing ; Swarm Intelligence ; Self-Learning Algorithms ; Liquid Biopsies ; Nsclc ; Medicine
    ISSN: 1535-6108
    E-ISSN: 1878-3686
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