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Verfasst von:Ansari, Shariq S. [VerfasserIn]   i
 Sharma, Ashwini Kumar [VerfasserIn]   i
 Bergmann, Frank [VerfasserIn]   i
Titel:Upregulation of cell cycle genes in head and neck cancer patients may be antagonized by erufosine's down regulation of cell cycle processes in OSCC cells
Verf.angabe:Shariq S. Ansari, Ashwini K. Sharma, Michael Zepp, Elizabet Ivanova, Frank Bergmann, Rainer König, Martin R. Berger
Jahr:2018
Jahr des Originals:2017
Umfang:14 S.
Fussnoten:Published: December 20, 2017 ; Gesehen am 19.06.2018
Titel Quelle:Enthalten in: OncoTarget
Ort Quelle:[S.l.] : Impact Journals LLC, 2010
Jahr Quelle:2018
Band/Heft Quelle:9(2018), 5, Seite 5797-5810
ISSN Quelle:1949-2553
Abstract:The TCGA database was analyzed to identify deregulation of cell cycle genes across 24 cancer types and ensuing effects on patient survival. Pan-cancer analysis showed that head and neck squamous cell carcinoma (HNSCC) ranks amongst the top four cancers showing deregulated cell cycle genes. Also, the median gene expression of all CDKs and cyclins in HNSCC patient samples was higher than that of the global gene expression. This was verified by IHC staining of CCND1 from HNSCC patients. When evaluating the quartiles with highest and lowest expression, increased CCND1/CDK6 levels had negative implication on patient survival. In search for a drug, which may antagonize this tumor profile, the potential of the alkylphosphocholine erufosine was evaluated against cell lines of the HNSCC subtype, oral squamous cell carcinoma (OSCC) using in-vitro and in-vivo assays. Erufosine inhibited growth of OSCC cell lines concentration dependently. Initial microarray findings revealed that cyclins and CDKs were down-regulated concentration dependently upon exposure to erufosine and participated in negative enrichment of cell cycle processes. These findings, indicating a pan-cdk/cyclin inhibition by erufosine, were verified at both, mRNA and protein levels. Erufosine caused a G2/M block and inhibition of colony formation. Significant tumor growth retardation was seen upon treatment with erufosine in a xenograft model. For the decreased cyclin D1 and CDK 4/6 levels found in tumor tissue, these proteins can serve as biomarker for erufosine intervention. The findings demonstrate the potential of erufosine as cell cycle inhibitor in HNSCC treatment, alone or in combination with current therapeutic agents.
DOI:doi:10.18632/oncotarget.23537
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.

Kostenfrei: Volltext: http://dx.doi.org/10.18632/oncotarget.23537
 DOI: https://doi.org/10.18632/oncotarget.23537
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cyclins and CDKs
 erufosine
 G2/M block
 head and neck cancer
 OSCC xenograft mouse model
K10plus-PPN:1576507300
Verknüpfungen:→ Zeitschrift

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