Prednisolone-Induced Changes in Gene-Expression Profiles in Healthy Volunteers

Toonen, Erik J. M.; Fleuren, Wilco W. M.; Nässander, U. K.; Lierop, Marie-Jose C. van; Bauerschmidt, Susanne; Dokter, Wim H.A.; Alkema, Wynand

doi:10.2217/pgs.11.34

Cited by 12 publications

(14 citation statements)

References 61 publications

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“…Rapid non-genomic effects of GR ligation occur after ligand-induced dissociation of the GR multiprotein complex in the cytoplasm (39). This diversity of regulatory processes indicates that prednisolone is likely to regulate different genes than the physiological glucocorticoid, hydrocortisone (41). …”

Section: Discussionmentioning

confidence: 99%

Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency

Quinkler¹,

Ekman

Marelli³

et al. 2017

Endocrine Connections

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Objective Prednisolone is used as glucocorticoid replacement therapy for adrenal insufficiency (AI). Recent data indicate that its use in AI is associated with low bone mineral density. Data on risk factors for cardiovascular disease in patients with AI treated with prednisolone are scarce, despite this condition being the predominant cause of excess mortality. We aimed to address this question using real-world data from the European Adrenal Insufficiency Registry (EU-AIR). Design/methods EU-AIR, comprising of 19 centres across Germany, the Netherlands, Sweden and the UK, commenced enrolling patients with AI in August 2012. Patients receiving prednisolone (3–6 mg/day, n = 50) or hydrocortisone (15–30 mg/day, n = 909) were identified and grouped at a ratio of 1:3 (prednisolone:hydrocortisone) by matching for gender, age, duration and type of disease. Data from baseline and follow-up visits were analysed. Data from patients with congenital adrenal hyperplasia were excluded. Results Significantly higher mean ± s.d. total (6.3 ± 1.6 vs 5.4 ± 1.1 mmol/L; P = 0.003) and low-density lipoprotein (LDL) cholesterol levels (3.9 ± 1.4 vs 3.2 ± 1.0 mmol/L; P = 0.013) were identified in 47 patients on prednisolone vs 141 receiving hydrocortisone at baseline and at follow-up (P = 0.005 and P = 0.006, respectively). HbA1c, high-density lipoprotein and triglyceride levels, body mass index, systolic and diastolic blood pressure and waist circumference were not significantly different. Conclusions This is the first matched analysis of its kind. Significantly higher LDL levels in patients receiving prednisolone relative to hydrocortisone could predict a higher relative risk of cardiovascular disease in the former group.

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Section: Discussionmentioning

confidence: 99%

Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency

Quinkler¹,

Ekman

Marelli³

et al. 2017

Endocrine Connections

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“…Relationships between keywords can be summarized in tables that can be sorted and filtered based on scoring schemas yielding ranked lists of genes, drugs or diseases which can be used for guiding follow up experiments [51,79,80]. It is important to link the keywords and concepts in these results back to the original text source where they can be highlighted in the text, providing the context in which they are mentioned [9,81].…”

Section: Visualizationmentioning

confidence: 99%

“…Toonen et al [79] used CoPub (Table 1) to analyze a set of genes that was differentially expressed in blood of healthy volunteers treated with prednisolone. They matched all genes against three keyword categories, i.e.…”

Section: Genome and Gene Expression Annotationmentioning

confidence: 99%

“…Genes that play a pivotal role in these processes are possible drug target candidates for therapeutic intervention. TM is an established technique in drug discovery to find automatically information in the scientific literature about how these genes are related to the disease and how they are involved in the drug induced effects [50,79,[88][89][90].…”

Section: Drug-target Discoverymentioning

confidence: 99%

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Application of text mining in the biomedical domain

Fleuren

Alkema

2015

Methods

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163

107

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“…However, for most tracers this correlation is less clear. For instance, Steffens et al have studied the correlation between the radiolabeled antibody cG250 ( 131 I-cG250) and the expression of its respective antigen carbonic anhydrase IX (CAIX) [33]. They have shown that high antigen expression was a prerequisite for high antibody uptake.…”

Section: Factors Affecting Imaging Of Drug Deliverymentioning

confidence: 99%

Radionuclide imaging of drug delivery for patient selection in targeted therapy

Heskamp

Laarhoven

Graaf

et al. 2014

Expert Opinion on Drug Delivery

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Molecular imaging of drug delivery clearly has potential for patient selection for targeted therapy. The main advantage of this technique is that not only can antigen expression be measured noninvasively but also target accessibility is taken into account. However, up to now, most of these studies have been performed in preclinical models. Therefore, future research should focus on bringing promising tracers to the clinic, preferable in an early stage of drug development in order to test their potential role as a biomarker.

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Prednisolone-Induced Changes in Gene-Expression Profiles in Healthy Volunteers

Abstract: The identified gene signatures provide new starting points for further study into GC-induced transcriptional regulation in vivo and the mechanisms underlying GC-mediated metabolic side effects.

Cited by 12 publications

References 61 publications

Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency

Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency

Application of text mining in the biomedical domain

Radionuclide imaging of drug delivery for patient selection in targeted therapy

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