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Verfasst von:Strowitzki, Moritz [VerfasserIn]   i
 Radhakrishnan, Praveen [VerfasserIn]   i
 Ritter, Alina [VerfasserIn]   i
 Volz, Claudia [VerfasserIn]   i
 Harnoß, Jonathan M. [VerfasserIn]   i
 Klose, Johannes [VerfasserIn]   i
 Schmidt, Thomas [VerfasserIn]   i
 Schneider, Martin [VerfasserIn]   i
Titel:High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases
Verf.angabe:Moritz J. Strowitzki, Praveen Radhakrishnan, Sandra Pavicevic, Jana Scheer, Gwendolyn Kimmer, Alina S. Ritter, Christopher Tuffs, Claudia Volz, Florian Vondran, Jonathan M. Harnoss, Johannes Klose, Thomas Schmidt and Martin Schneider
E-Jahr:2019
Jahr:27 February 2019
Umfang:14 S.
Teil:volume:120
 year:2019
 number:7
 pages:675-688
 extent:14
Fussnoten:Gesehen am 27.01.2020
Titel Quelle:Enthalten in: British journal of cancer
Ort Quelle:Edinburgh : Nature Publ. Group, 1999
Jahr Quelle:2019
Band/Heft Quelle:120(2019), 7, Seite 675-688
ISSN Quelle:1532-1827
Abstract:Patients with borderline resectable colorectal liver metastases (CRLM) frequently receive neoadjuvant chemotherapy (NC) to reduce tumour burden, thus making surgical resection feasible. Even though NC can induce severe liver injury, most studies investigating tissue-based prognostic markers focus on tumour tissue. Here, we assessed the prognostic significance of pyruvate-dehydrogenase-kinase isoenzyme 4 (PDK4) within liver tissue of patients undergoing surgical resection due to CRLM. Transcript levels of hypoxia-adaptive genes (such as PDK isoenzymes) were assessed in the tissue of healthy liver, corresponding CRLM, healthy colon mucosa and corresponding tumour. Uni- and multivariate analyses were performed. Responses to chemotherapy upon up- or down-regulation of PDK4 were studied in vitro. PDK4 expression within healthy liver tissue was associated with increased overall survival and liver function following surgical resection of CRLM. This association was enhanced in patients with NC. PDK4 expression in CRLM tissue did not correlate with overall survival. Up-regulation of PDK4 increased the resistance of hepatocytes and colon cancer cells against chemotherapy-induced toxicity, whereas knockdown of PDK4 enhanced chemotherapy-associated cell damage. Our findings suggest that up-regulated PDK4 expression reduces hepatic chemotherapy-induced oxidative stress and is associated with improved postoperative liver function in patients undergoing multimodal treatment and resection of CRLM.
DOI:doi:10.1038/s41416-019-0406-9
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1038/s41416-019-0406-9
 Verlag: https://www.nature.com/articles/s41416-019-0406-9
 DOI: https://doi.org/10.1038/s41416-019-0406-9
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1688547614
Verknüpfungen:→ Zeitschrift

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