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  • 1
    Abstract: Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a 2-year timeframe, at 89% and 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and platinum (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP-naive patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient's disease. Collectively, this work highlights the translational potential of this strategy.Significance: Effective translational research utilizing SCLC PDX models requires both efficient generation of models from patients and fidelity of those models in representing patient tumor characteristics. We present approaches for efficient generation of PDXs from both biopsies and CTCs, and demonstrate that these models capture the mutational landscape and functional features of the donor tumors. Cancer Discov; 8(5); 600-15. (c)2018 AACR.This article is highlighted in the In This Issue feature, p. 517.
    Type of Publication: Journal article published
    PubMed ID: 29483136
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  • 2
    German Medical Science GMS Publishing House; Düsseldorf
    In:  70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie; 20190512-20190515; Würzburg; DOCV212 /20190508/
    Publication Date: 2019-05-09
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 3
    Electronic Resource
    Electronic Resource
    Marine biology 25 (1974), S. 327-333 
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung 1. Unter den marinen Makrobenthosarten der Westlichen Ostsee weisen einige Lamellibranchier, die hier auf sauerstoffarmen Weichböden vorkommen, eine besonders große Überlebensfähigkeit bei Fehlen von Sauerstoff auf. 2. Die O2-Mangelresistenz ist bei den agilen Vertretern aus dieser und aus anderen systematischen Gruppen von entsprechenden standorten geringer als bei den mehr oder weniger ständig sessilen Arten. 3. Allgemein besteht die Tendenz, daß die O2-Mangelresistenz innerhalb des ökologischen Bereichs bei sinkender Außentemperatur größer wird. Die unterschiedlich starke Abhängigkeit dieser Resistenz von der Temperatur hängt mit der geographischen Verbreitung der Formen zusammen.
    Notes: Abstract Among the macrobenthos fauna of the Western Baltic Sea, lamellibranchs occurring in poorly oxygenated soft sediments exhibit especially high tolerances to temporary oxygen deficiency. Such tolerance is less well developed in mobile species of various systematic groups than in more or less immobile forms. Commonly, tolerance to oxygen deficiency tends to increase with decreasing temperature. Different qualitative relations between tolerance to oxygen deficiency and temperature may be correlated with the distributional range of the species.
    Type of Medium: Electronic Resource
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