Computational Drug-repositioning Approach Identifying Sirolimus as a Potential Therapeutic Option for Inflammatory Dilated Cardiomyopathy

Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 565-571 ◽  
Author(s):  
Kyoko Shibata ◽  
Toshinori Endo ◽  
Yoshikazu Kuribayashi
Keyword(s):  
Gene Expression ◽  
Dilated Cardiomyopathy ◽  
Drug Repositioning ◽  
Expression Profiles ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Antiviral Drug ◽  
Specific Treatment ◽  
Gene Expression Profiles ◽  
Connectivity Map

Abstract Objective The aim of this study was to determine promising treatment options for human inflammatory dilated cardiomyopathy using a computational drug-repositioning approach (repurposing established drug compounds for new therapeutic indications). Background If the myocardial tissue is detected to be infiltrated with inflammatory cells, primarily of lymphocytes, and if the virus is confirmed using genetic examination (PCR) or immunostaining, the infection is suspected. However, there is no specific treatment (i. e., an antiviral drug) even if the virus is identified; therefore, we used Connectivity Map to identify compounds showing inverse drug–disease signatures, indicating activity against inflammatory dilated cardiomyopathy. Results Potential drug-repositioning candidates for the treatment of inflammatory dilated cardiomyopathy were explored through a systematic comparison of the gene expression profiles induced by drugs using Gene Expression Omnibus and Connectivity Map databases. Conclusion Using a computational drug-repositioning approach based on the integration of publicly available gene expression signatures of drugs and diseases, sirolimus was suggested as a novel therapeutic option for inflammatory dilated cardiomyopathy.

scholarly journals Connecting gene expression data from connectivity map and in silico target predictions for small molecule mechanism-of-action analysis

2015 ◽  
Vol 11 (1) ◽  
pp. 86-96 ◽  
Author(s):  
Aakash Chavan Ravindranath ◽  
Nolen Perualila-Tan ◽  
Adetayo Kasim ◽  
Georgios Drakakis ◽  
Sonia Liggi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ligand Binding ◽  
Gene Expression Data ◽  
Mechanism Of Action ◽  
In Silico ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Expression Data ◽  
Connectivity Map ◽  
Action Analysis

Integrating gene expression profiles with certain proteins can improve our understanding of the fundamental mechanisms in protein–ligand binding.

scholarly journals Genome assembly and gene expression in the American black bear provides new insights into the renal response to hibernation

2018 ◽  
Author(s):  
Anuj Srivastava ◽  
Vishal Kumar Sarsani ◽  
Ian Fiddes ◽  
Susan M. Sheehan ◽  
Rita L. Seger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Assembly ◽  
Expression Profiles ◽  
Treatment Options ◽  
Gene Expression Profiles ◽  
Black Bear ◽  
Early Spring ◽  
Black Bears ◽  
American Black Bear ◽  
American Black

AbstractThe prevalence of chronic kidney disease (CKD) is rising worldwide and 10-15% of the global population currently suffers from CKD and its complications. Given the increasing prevalence of CKD there is an urgent need to find novel treatment options. The American black bear (Ursus americanus) copes with months of lowered kidney function and metabolism during hibernation without the devastating effects on metabolism and other consequences observed in humans. In a biomimetic approach to better understand kidney adaptations and physiology in hibernating black bears, we established a high-quality genome assembly. Subsequent RNA-Seq analysis of kidneys comparing gene expression profiles in black bears entering (late fall) and emerging (early spring) from hibernation identified 169 protein-coding genes that were differentially expressed. Of these, 101 genes were downregulated and 68 genes were upregulated after hibernation. Fold changes ranged from 1.8-fold downregulation (RTN4RL2) to 2.4-fold upregulation (CISH). Most notable was the upregulation of cytokine suppression genes (SOCS2, CISH, and SERPINC1) and the lack of increased expression of cytokines and genes involved in inflammation. The identification of these differences in gene expression in the black bear kidney may provide new insights in the prevention and treatment of CKD.

scholarly journals Gene Expression Profiles from Needle Biopsies Provide Useful Signatures of Non-Small Cell Lung Carcinomas

2007 ◽  
Vol 2 ◽  
pp. 117727190700200
Author(s):  
Douglas E. Paull ◽  
Kevin Kelley ◽  
Jazbieh Moezzi ◽  
Madhavi Kadakia ◽  
Steven J. Berberich
Keyword(s):  
Gene Expression ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Treatment Options ◽  
Gene Expression Profiles ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Carcinomas ◽  
Fine Needle Aspirates ◽  
Resected Tumor

Gene expression profiles from DNA microarrays can provide molecular signatures that improve tumor classification, prognosis, and treatment options. While much of this work has focused on isolation of RNA from the resected tumor, fewer studies have utilized RNA from fine needle aspirates (FNA). In this pilot study we examined whether the gene signatures obtained from FNA samples would correlate with signatures taken from the resected tumor. Based on NSCLC gene expression profiles obtained from eleven sets of FNA and tumor samples we obtained a high concordance of FNA profiles matching their matched tumor sample. These results suggest that FNA samples may provide informative gene expression signatures regarding the potential aggressiveness of non-small-cell lung carcinomas.

MLL-Rearranged ALL Cells Are Highly Dependent On the Expression of EP300-Interacting Inhibitor of Differentiation 1 (EID1)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1462-1462
Author(s):  
Marieke Hendrika van der Linden ◽  
Pauline Schneider ◽  
Rob Pieters ◽  
Ronald Stam
Keyword(s):  
Gene Expression ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Gene Expression Profiles ◽  
Pcr Analysis ◽  
Rapid Reduction ◽  
Adequate Treatment ◽  
Inhibitor Of Differentiation 1

Abstract Abstract 1462 MLL-rearranged acute lymphoblastic leukemia (ALL) remains a difficult to treat type of leukemia, for which alternative and more adequate treatment options are still urgently needed. Various genome-wide transcriptome studies, including ours, have shown that MLL-rearranged ALL patients display highly unique gene expression profiles. In search of new and valid therapeutic targets to which more adequate treatments could be developed, we constantly screen our gene expression profiling data for potential candidates. In the present study we set out to investigate EID1 (EP300-interacting inhibitor of differentiation 1), which we found highly and specifically expressed in MLL-rearranged ALL cells. Validating this observation, quantitative RT-PCR analysis confirmed that EID1 expression was significantly higher in MLL-rearranged ALL cells as compared with other ALL subtypes or healthy bone marrow samples. Next, we performed shRNA-mediated knockdown of EID1 in MLL-rearranged ALL cells, which resulted in a dramatic reduction of viable cells. Subsequently, flow cytometry analyses demonstrated that this rapid reduction of cell viability was due to massive induction of apoptosis as well as an abrupt cell cycle arrest. Consequently, it appeared difficult to study the actual function of EID1 over-expression in MLL-rearranged ALL cells. On the other hand, these features make EID1 an attractive target for therapeutic intervention in MLL-rearranged ALL. Hence, further studies on the function of EID1 in MLL-rearranged ALL and exploring the possibilities to inhibit it are warranted. Disclosures: No relevant conflicts of interest to declare.

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