The serum levels of soluble interleukin-2 receptor α and lactate dehydrogenase but not of B2-microglobulin correlate with selected clinico-pathological prognostic factors and response to therapy in childhood soft tissue sarcomas

Bień, Ewa; Rąpała, Małgorzata; Krawczyk, Małgorzata; Balcerska, Anna

doi:10.1007/s00432-009-0661-x

Cited by 14 publications

(14 citation statements)

References 67 publications

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“…Log 10 sCD25 concentrations did not differ by batch ( p = 0.98; type 1 diabetes status was not taken into account because we randomised cases and controls across the two batches). It has been previously shown that sCD25 concentrations are stable in adults [18]. Therefore, we tested this in the 1,600 UKBS control samples and confirmed that sCD25 concentrations in individuals over 18 years of age were not associated with age ( p = 0.66).…”

Section: Methodssupporting

confidence: 66%

“…Inhibition of these proteases decreases CD25 cleavage, thus increasing the stability of surface CD25 in vitro [17]. The concentration of sCD25 is age dependent in healthy children, who have high circulating sCD25 concentrations that fall to normal adult concentrations (∼2,000 pg/ml) by age 16–18 years [18]. Elevated sCD25 concentrations in adults are associated with activation of lymphocytes during infection and inflammation, and with autoimmune disease [19–22].…”

Section: Introductionmentioning

confidence: 99%

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Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

et al. 2013

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Aims/hypothesisType 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function of these proteins is likely to be causal. We aimed to investigate if circulating concentrations of the soluble form of CD25, sCD25, an established marker of immune activation and inflammation, were increased in individuals with type 1 diabetes and if this was associated with the concentration of C-peptide, a measure of insulin production that reflects the degree of autoimmune destruction of the insulin-producing beta cells.MethodsWe used immunoassays to measure sCD25 and C-peptide in peripheral blood plasma from patient and control samples.ResultsWe identified that sCD25 was increased in patients with type 1 diabetes compared with controls and replicated this result in an independent set of 86 adult patient and 80 age-matched control samples (p = 1.17 × 10−3). In 230 patients under 20 years of age, with median duration-of-disease of 6.1 years, concentrations of sCD25 were negatively associated with C-peptide concentrations (p = 4.8 × 10−3).Conclusions/interpretationThe 25% increase in sCD25 in patients, alongside the inverse association between sCD25 and C-peptide, probably reflect the adverse effects of an on-going, actively autoimmune and inflammatory immune system on beta cell function in patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-3113-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Section: Methodssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

et al. 2013

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“…Sarcomas are highly inflammatory and therefore may be associated with worse health status and therefore higher CL of mAbs. Inflammatory markers have been shown to correlate with some clinical variables known to have an important prognostic role (stage, histological subtype, and response to therapy) in soft‐tissue sarcoma patients . The percentage of children with primary CNS tumours with albumin below the normal level (35 g l –1 ) appeared lower than in children with sarcomas: 8% vs .…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation

Han¹,

Peyret²,

Quartino³

et al. 2015

Brit J Clinical Pharma

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AimThe aim of the present study was to evaluate the pharmacokinetics of bevacizumab and various dosing strategies for this agent in paediatric patients.MethodsData were collected from 232 paediatric patients (1971 concentrations) in five studies, with a wide range of age (0.5 – 21 years), body weight (BWT; 5.9 – 125 kg), and regimens (5 – 15 mg kg–1 biweekly or triweekly). Data from 152 patients (1427 concentrations) and 80 patients (544 concentrations) were used for model building and external validation, respectively. Steady‐state exposure was simulated under BWT‐based, body surface area (BSA)‐based, ideal body weight (IBW)‐based, and tier‐based doses. NONMEM and R were used for analyses.ResultsTypical estimates of clearance, central volume of distribution (V1), and median half‐life were 9.04 ml h–1, 2851 ml, and 19.6 days, respectively. Clearance decreased with increasing albumin. Clearance and V1 increased with BWT and were higher in male patients. Clearance and V1 were lower in children with primary central nervous system (CNS) tumours than in children with sarcomas, resulting in 49% higher trough (Cmin) and 29% higher peak (Cmax) concentrations. BWT‐adjusted clearance and V1 remained unchanged across ages. Paediatric Cmin was similar to adult Cmin under all dosing strategies. Paediatric Cmax exceeded adult Cmax under tier‐based doses.ConclusionsBWT‐adjusted pharmacokinetic parameter estimates in paediatric patients were similar to those in adults, and similar across ages. Bevacizumab exposure was higher in children with primary CNS tumours than in children with sarcomas. BSA‐based, IBW‐based, and tier‐based doses offered no substantial advantage over the BWT‐based dose currently used in adults for bevacizumab. Given the similarity in pharmacokinetics among many monoclonal antibodies, this may help to develop practical paediatric dosing guidelines for other therapeutic antibodies.

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“…In the literature there is a gap of approximately ten years in publications about sIL-2Ra in ovarian cancer patients, but recently sIL-2Ra has been investigated as a prognostic marker in the case of head and neck cancer (Meyer et al, 2010), soft tissue sarcomas (Bien et al, 2010) in patients with Non-Hodgkin's lymphomas (Jo et al, 2010) and there is a lately published article in which ovarian cancer stage was associated with tryptophan degradation and a subsequent strong correlation with sIL-2Ra was observed (Sperner-Unterweger et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Role of a combined soluble interleukine-2 receptor alpha (sIL-R2α) and CA-125 serum marker assay for detection of ovarian cancer

Macuks¹,

Baidekalna²,

Nuķe³

et al. 2011

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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Role of a combined soluble interleukine-2 receptor alpha (sIL-R2α) and CA-125 serum marker assay for detection of ovarian cancer Detection of ovarian cancer can be improved using a combined diagnostic test consisting of Ca-125 and serum interleukine-2 receptor alpha (sIL-R2α) at a particular threshold. The objective of the study was to evaluate the accuracy of a diagnostic marker assay that combined Ca-125 and serum interleukine-2 receptor alpha. A case-control study of 38 patients with ovarian cancer, 40 patients with benign ovarian diseases and 31 age-matched healthy controls was designed. Ca-125 and sIL-2Rα were detected in patients' serum by standardized chemiluminescent immunometric assays. For Ca-125, a standard cutoff level of 21 U/ml was applied and for sIL-R2α — two cutoff levels were calculated from women included in the control group — one as a mean concentration and the other as an upper limit of a 95% confidence interval. Mean serum concentrations among ovarian cancer patients for CA125 and sIL-2Rα were 265.9 ± 40.2 U/ml and 651.0 ± 50.5 U/ml, respectively. The upper limit of the 95% confidence interval for a healthy control group of women was 304.5 U/ml for sIL-2Rα. Sensitivity and specificity of 89.4% and 85.9% was achieved when CA125 was combined together with sIL-2Rα at a threshold of 304.5U/ml with the condition that both markers are elevated. Sensitivity and specificity of 92.5% and 88.4% was observed when both biomarkers were applied to menopausal women. Serum sIL-2Rα in combination with CA125 can be used as a differential diagnostic test for ovarian cancer at a specific threshold, especially among menopausal women.

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The serum levels of soluble interleukin-2 receptor α and lactate dehydrogenase but not of B2-microglobulin correlate with selected clinico-pathological prognostic factors and response to therapy in childhood soft tissue sarcomas

Cited by 14 publications

References 67 publications

Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation

Role of a combined soluble interleukine-2 receptor alpha (sIL-R2α) and CA-125 serum marker assay for detection of ovarian cancer

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