Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression profiling of Jurkat cells infected with HIV-1 and treated with digoxin or DMSO

ABSTRACT: To determine changes of gene expression in human CD4+ T cells (Jurkat) infected with HIV-1 and treated with digoxin. Cells were infected (MOI 0.01) with a single cycle HIV-1 delta env expressing GFP and pseudotyoed with VSV-G in the presence of 400nM digoxin or DMSO. Cells were harvested 36 hours post-infection and processed for RNAseq

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Ariberto Fassati

PROVIDER: E-MTAB-5982 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

Zhyvoloup Alexander A Melamed Anat A Anderson Ian I Planas Delphine D Lee Chen-Hsuin CH Kriston-Vizi Janos J Ketteler Robin R Merritt Andy A Routy Jean-Pierre JP Ancuta Petronela P Bangham Charles R M CRM Fassati Ariberto A

PLoS pathogens 20170720 7

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its sele ...[more]

PMID: 28727807

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Project description:Non-medullary thyroid cancer (NMTC) is the most frequent endocrine tumor with in most cases a good prognosis. Unfortunately, 30-40% of patients with metastatic NMTC are unresponsive to 131-I radioactive iodide (RAI) treatment as a result of tumor dedifferentiation. Autophagy has emerged as an important mechanism involved in NMTC dedifferentiation. Furthermore, activation of autophagy by cardiac glycosides such as digoxin has been demonstrated to induce effective in vitro redifferentiation of poorly differentiated and anaplastic thyroid cancer cell lines, thereby restoring sensitivity to RAI treatment. However, the in vivo effects of digoxin treatment on tumor differentiation in NMTC patients remains unclear. In the present retrospective clinical study, archived tumor material obtained from NMTC patients that received digoxin as treatment of heart disease before and after NMTC diagnosis was investigated. By a national PALGA-PHARMO database search, 11 digoxin-treated NMTC patients were included encompassing all major histological NMTC subtypes. In addition, 11 control NMTC patients never treated with digoxin were included that were matched for age, gender, histological tumor type, TNM staging and genetic profile. From the collected tumor material, autophagy activity has been determined by LC3 immunofluorescent staining and RNA expression profiles have been generated by RNA sequencing to assess differential expression of thyroid-specific genes. Interestingly, the results indicate that tumor material from digoxin-treated NMTC patients exhibit significantly higher autophagy activity as compared to tumor material of matched control NMTC patients. Moreover, in all 11 tumor tissues obtained from digoxin-treated NTMC patients the differentiation status was profoundly higher as compared to the matched control NMTC patients, of which the effect size was however dependent on histological NMTC subtypes and genetic profile of the tumor. In conclusion, treatment of NMTC with digoxin before and after NMTC diagnosis is associated with a higher tumor differentiation grade as compared to tumor tissue from closely matched NMTC patients not treated with digoxin. These in vivo data confirm our previous in vitro findings and provide accumulating evidence that digoxin could represent a beneficial adjunctive treatment modality to improve RAI sensitivity in patients with RAI-refractory thyroid carcinoma.

Dataset Information

Expression profiling of Jurkat cells infected with HIV-1 and treated with digoxin or DMSO

Publications

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

Similar Datasets

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