Transcriptomics,Genomics

Dataset Information

38

Antitumoral actions of 9-cis retinoic acid and mitotane in an adrenocortical xenograft model


ABSTRACT: The actual drug treatment options for adrenocortical carcinoma (ACC) are rather narrow and intensive efforts are going on to find novel effective agents. In our previous functional genomics study, retinoid signaling via the retinoid X receptor (RXR) was detected as a major pathogenic pathway in ACC and we have demonstrated the in vitro activity of 9-cis retinoic acid (9-cisRA) acting via the RXR on NCI-H295R cells and also found that 9-cisRA has antitumoral effects in a small pilot xenograft study. In the present study our aim was to confirm the antitumoral effect of 9-cisRA on adrenocortical cancer in a large xenograft study involving both mitotane and 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control – corn oil vehicle, ii. 5 mg/kg 9-cisRA, iii. 200 mg/kg mitotane, iv. 5 mg/kg 9-cisRA + 200 mg/kg mitotane) for 28 days. Regular tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray have been performed. Quantitative real-time-PCR was used for the validation of the microarray results and to detect circulating and tissue microRNAs. To examine the proteome proteomics and Western-blot analysis were executed. We have found that both 9-cisRA and mitotane reduced tumor growth relative to control, but only the combination of the two agents resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Gene expression analysis revealed 483 genes with significant differences in expression, but only without Benjamini-Hochberg correction (APOA4 and PDE4A were validated). Overall design: 43 SCID mice in four groups: 1) control, 2)mitotane, 3)9-cisRA, 4)combined treated. Treatment time: 28 days. Per os treatment

INSTRUMENT(S): Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)

SUBMITTER: Zoltan Nagy MD 

PROVIDER: GSE73417 | GEO | 2016-06-07

SECONDARY ACCESSION(S): PRJNA296912

REPOSITORIES: GEO

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Publications

Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model.

Nagy Zoltán Z   Baghy Kornélia K   Hunyadi-Gulyás Éva É   Micsik Tamás T   Nyírő Gábor G   Rácz Gergely G   Butz Henriett H   Perge Pál P   Kovalszky Ilona I   Medzihradszky Katalin F KF   Rácz Károly K   Patócs Attila A   Igaz Peter P  

American journal of cancer research 20151115 12


The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9-cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four gr  ...[more]

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