![](/images/graphics-bg.png)
Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma
Joint Authors
Fletcher, Jonathan A.
Beck, Andrew H.
West, Robert B.
Edris, Badreddin
van de Rijn, Matt
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-08-05
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist.
Previously, we showed that there are three molecular subtypes of LMS.
Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells.
11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines.
We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132).
Given MG-132’s strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines.
These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS.
American Psychological Association (APA)
Edris, Badreddin& Fletcher, Jonathan A.& West, Robert B.& van de Rijn, Matt& Beck, Andrew H.. 2012. Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma. Sarcoma،Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-499478
Modern Language Association (MLA)
Edris, Badreddin…[et al.]. Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma. Sarcoma No. 2012 (2012), pp.1-9.
https://search.emarefa.net/detail/BIM-499478
American Medical Association (AMA)
Edris, Badreddin& Fletcher, Jonathan A.& West, Robert B.& van de Rijn, Matt& Beck, Andrew H.. Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma. Sarcoma. 2012. Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-499478
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-499478