Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma

Mg, Alexandrakis; Fh, Passam; Boula, Anna; Christophoridou, Anna V.; Aloizos, Georgios; Roussou, Parascevi; Ds, Kyriakou

doi:10.1007/s00277-002-0558-0

Cited by 52 publications

(19 citation statements)

References 27 publications

(22 reference statements)

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“…As an example of our proteomic penetration, IL6-R has been recorded at a concentration of 453 pg/mL in serum (about 9 pM). 22 Supplementary Table 2 (and references therein, Supporting Information) highlights examples of some of the proteins identified together with their relative abundance in plasma.…”

Section: Resultsmentioning

confidence: 99%

Statistical Considerations of Optimal Study Design for Human Plasma Proteomics and Biomarker Discovery

et al. 2012

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A mass spectrometry-based plasma biomarker discovery workflow was developed to facilitate biomarker discovery. Plasma from either healthy volunteers or patients with pancreatic cancer was 8-plex iTRAQ labeled, fractionated by 2-dimensional reversed phase chromatography and subjected to MALDI ToF/ToF mass spectrometry. Data were processed using a q-value based statistical approach to maximize protein quantification and identification. Technical (between duplicate samples) and biological variance (between and within individuals) were calculated and power analysis was thereby enabled. An a priori power analysis was carried out using samples from healthy volunteers to define sample sizes required for robust biomarker identification. The result was subsequently validated with a post hoc power analysis using a real clinical setting involving pancreatic cancer patients. This demonstrated that six samples per group (e.g., pre- vs post-treatment) may provide sufficient statistical power for most proteins with changes >2 fold. A reference standard allowed direct comparison of protein expression changes between multiple experiments. Analysis of patient plasma prior to treatment identified 29 proteins with significant changes within individual patient. Changes in Peroxiredoxin II levels were confirmed by Western blot. This q-value based statistical approach in combination with reference standard samples can be applied with confidence in the design and execution of clinical studies for predictive, prognostic, and/or pharmacodynamic biomarker discovery. The power analysis provides information required prior to study initiation.

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Section: Resultsmentioning

confidence: 99%

Statistical Considerations of Optimal Study Design for Human Plasma Proteomics and Biomarker Discovery

et al. 2012

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“…In SCCHN and multiple myeloma, p38 is constitutively active and promotes tumor growth, survival and invasion by modulating secretion of multiple cytokines and pro-inflammatory mediators (14) but its role in angiogenesis is unexplored.…”

Section: Introductionmentioning

confidence: 99%

The G Protein–Coupled Receptor GALR2 Promotes Angiogenesis in Head and Neck Cancer

Banerjee

Tubergen

Scanlon

et al. 2014

Molecular Cancer Therapeutics

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Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor patient survival. Galanin Receptor 2 (GALR2) is a G-protein coupled receptor (GPCR) that induces aggressive tumor growth in SCCHN. The objective of this study was to investigate the mechanism by which GALR2 promotes angiogenesis, a critical oncogenic phenotype required for tumor growth. The impact of GALR2 expression on secretion of pro-angiogenic cytokines in multiple SCCHN cell lines was investigated by ELISA and in-vitro angiogenesis assays. Chemical inhibitor and genetic knockdown strategies were used to understand the key regulators. The in-vivo impact of GALR2 on angiogenesis was investigated in mouse xenograft, chick chorioallantoic membrane (CAM) and the clinically-relevant mouse orthotopic floor-of-mouth models. GALR2 induced angiogenesis via p38-MAPK-mediated secretion of pro-angiogenic cytokines, VEGF and IL-6. Moreover, GALR2 activated small-GTP-protein, RAP1B, thereby inducing p38-mediated inactivation of tristetraprolin (TTP), which functions to destabilize cytokine transcripts. This resulted in enhanced secretion of pro-angiogenic cytokines and angiogenesis in-vitro and in-vivo. In SCCHN cells overexpressing GALR2, inactivation of TTP increased secretion of IL-6 and VEGF, whereas inhibition of p38 activated TTP and decreased cytokine secretion. Here we report that GALR2 stimulates tumor angiogenesis in SCCHN via p38-mediated inhibition of TTP with resultant enhanced cytokine secretion. Given that p38 inhibitors are in clinical use for inflammatory disorders, GALR2/p38-mediated cytokine secretion may be an excellent target for new adjuvant therapy in SCCHN.

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“…There is increased evidence that significantly elevated levels of bone marrow angiogenesis in MM and several pro-angiogenic cytokines (e.g. vascular endothelial growth factor—VEGF, basic fibroblast growth factor—bFGF, hepatocyte growth factor—HGF and platelet-derived growth factor—PDGF) are present in higher concentrations in myelomatous BM and peripheral blood and decrease after successful treatment [5, 6]. …”

Section: Introductionmentioning

confidence: 99%

BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression of human multiple myeloma

et al. 2013

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Tumour necrosis factor alpha (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the TNF-α family. Vascular endothelial growth factor (VEGF), on the other hand, is one of the most characteristic pro-angiogenic cytokines produced by multiple cell types in multiple myeloma (MM). We have analysed BAFF and APRIL concentrations in parallel with pro-angiogenic cytokines in serum and trephine biopsy, and the bone marrow microvascular density (MVD) in 50 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of BAFF, APRIL and TNF-α, as well as VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. A statistically positive correlation between the concentration of TNF-α and the expression of VEGF was demonstrated, and so was a positive link between BAFF, APRIL, MVD and lactate dehydrogenase (LDH). Furthermore, we observed a significant decrease in all studied cytokines after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with stable disease. It was also established that APRIL, but not BAFF, correlated with pro-angiogenic cytokines such as VEGF with its receptor, MVD and syndecan-1. Finally, our results showed that serum BAFF and APRIL levels could be useful biomarkers of MM disease activity and its progression which suggests that APRIL could be a possible novel therapeutic target in MM.

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Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma

Cited by 52 publications

References 27 publications

Statistical Considerations of Optimal Study Design for Human Plasma Proteomics and Biomarker Discovery

Statistical Considerations of Optimal Study Design for Human Plasma Proteomics and Biomarker Discovery

The G Protein–Coupled Receptor GALR2 Promotes Angiogenesis in Head and Neck Cancer

BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression of human multiple myeloma

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