Phosphospecific flow cytometry for pharmacodynamic drug monitoring: Analysis of the JAK-STAT signaling pathway

Vafadari, Ramin; Weimar, Willem; Baan, Carla C.

doi:10.1016/j.cca.2011.12.023

Cited by 21 publications

(20 citation statements)

References 43 publications

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“…JAKs phosphorylate the γ c receptor of the IL-2R that subsequently serves as docking molecule for the STAT signaling molecules. Vafadari et al published a comprehensive review on this topic [131]. For other cytokines e.g.…”

Section: Phosphospecific Flow Cytometrymentioning

confidence: 99%

“…IL-6, IL-10, IL-17 and interferons, JAK-STAT activation is also critical for signaling. Phosphospecific flow cytometry measures activation-induced changes of signaling molecules and can be used to monitor the effect of immunosuppressive drugs on intracellular signaling pathways and how molecules are activated in response to stimuli [131].…”

Section: Phosphospecific Flow Cytometrymentioning

confidence: 99%

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Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Andrews

Winter

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

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115

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Introduction: Tacrolimus (Tac) is the cornerstone of immunosuppressive therapy after solid organ transplantation and will probably remain so. Excluding belatacept, no new immunosuppressive drugs were registered for the prevention of acute rejection during the last decade. For several immunosuppressive drugs, clinical development halted because they weren't sufficiently effective or more toxic. Areas covered: Current methods of monitoring Tac treatment, focusing on traditional therapeutic drug monitoring (TDM), controversies surrounding TDM, novel matrices, pharmacogenetic and pharmacodynamic monitoring are discussed. Expert opinion: Due to a narrow therapeutic index and large interpatient pharmacokinetic variability, TDM has been implemented for individualization of Tac dose to maintain drug efficacy and minimize the consequences of overexposure. The relationship between predose concentrations and the occurrence of rejection or toxicity is controversial. Acute cellular rejection also occurs when the Tac concentration is within the target range, suggesting that Tac whole blood concentrations don't necessarily correlate with pharmacological effect. Intracellular Tac, the unbound fraction of Tac or pharmacodynamic monitoring could be better biomarkers/tools for adequate Tac exposure -research into this has been promising. Traditional TDM, perhaps following pre-emptive genotyping for Tac-metabolizing enzymes, must suffice for a few years before these strategies can be implemented in clinical practice. ARTICLE HISTORY

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Section: Phosphospecific Flow Cytometrymentioning

confidence: 99%

Section: Phosphospecific Flow Cytometrymentioning

confidence: 99%

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Andrews

Winter

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

Self Cite

115

View full text Add to dashboard Cite

show abstract

“…Analysis of the transplant patients per group showed that in the CNI (tacrolimus)-treated control patients, IL-2Y activated (15), IL-7Yactivated, and IL-15Yactivated P-STAT5 was not inhibited (Fig. 3).…”

Section: Stat5 Phosphorylation In Whole-blood T-cell Subsets Of Kidnementioning

confidence: 88%

Pharmacodynamic Analysis of Tofacitinib and Basiliximab in Kidney Allograft Recipients

et al. 2012

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“…Upon antigenic activation of T cells, IL-2/IL-2R binding triggers a variety of signaling cascades such as JAK/STAT and PI3K pathways (Fung et al 2003). Of four members of JAK family, JAK1 and JAK3 are activated by IL-2 (Vafadari et al 2012). In JAK/STAT pathway, JAK1 and JAK3 phosphorylate STAT3 and STAT5.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs Signature in IL-2-Induced CD4+ T Cells and Their Potential Targets

et al. 2015

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MicroRNAs (miRNAs) are a class of small non-coding RNAs regulated gene expression at the post-transcriptional level. Many studies have investigated role of miRNAs in the biological processes such as proliferation, apoptosis, differentiation, and development. To evaluate role of miRNAs in proliferation and death of T cell, we performed miRNA profiling in activated CD4+ T cells after IL-2 induction and depletion. Proliferation rate of IL-2-induced cells was measured by MTT assay. Then quantitative RT-PCR arrays on 739 miRNAs revealed up- and down-regulation of 170 miRNAs in IL-2-induced CD4+ T cells relative to IL-2-depleted ones. In addition, in silico analysis predicted miRNA's potential targets in pathways such as JAK/STAT and PI3K pathways. JAK1 expression, a potential target of modulated miRNAs, was decreased in IL-2-depleted cells. This study suggests that clonal expansion is regulated by miRNAs in the absence or presence of IL-2 by targeting genes implicated in JAK/STAT and PI3K pathways.

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Phosphospecific flow cytometry for pharmacodynamic drug monitoring: Analysis of the JAK-STAT signaling pathway

Cited by 21 publications

References 43 publications

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Pharmacodynamic Analysis of Tofacitinib and Basiliximab in Kidney Allograft Recipients

MicroRNAs Signature in IL-2-Induced CD4+ T Cells and Their Potential Targets

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