scholarly journals Levels of Circulating Fibroblast Growth Factor 23 (FGF23) and Prognosis in Cancer Patients with Bone Metastases

2019 ◽  
Vol 20 (3) ◽  
pp. 695 ◽  
Author(s):  
André Mansinho ◽  
Arlindo R. Ferreira ◽  
Sandra Casimiro ◽  
Irina Alho ◽  
Inês Vendrell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Metastases ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Patients With Cancer ◽  
Skeletal Related Events ◽  
Baseline Characteristics ◽  
The Impact

The fibroblast growth factor (FGF) signaling pathway plays a key role in tumorigenesis and is recognized as a potential therapeutic target. In this study, the authors aimed to assess the impact of serum FGF23 levels in the prognosis of patients with cancer and bone metastases from solid tumors. A cohort of 112 patients with cancer and metastatic bone disease were treated with bone-targeted agents (BTA). Serum baseline FGF23 was quantified by ELISA and dichotomized in FGF23high and FGF23low groups. Additionally, the association between FGF23 and overall survival (OS) and time to skeletal-related events (TTSRE) was investigated. Baseline characteristics were balanced between groups, except for the median urinary N-terminal telopeptide (uNTX) level. After a median follow-up of 26.0 months, a median OS of 34.4 and 12.2 months was found in the FGF23low and FGF23high groups, respectively (multivariate HR 0.18, 95% CI 0.07–0.44, p = 0.001; univariate HR 0.27, p = 0.001). Additionally, TTSRE was significantly longer for patients with FGF23low (13.0 vs 2.0 months, p = 0.04). Overall, this study found that patients with FGF23low at baseline had longer OS and TTSRE. Further studies are warranted to define its role as a prognostic biomarker and in the use of drugs targeting the FGF axis.

Abstract P050: Serum Fibroblast Growth Factor 23 and Incident Hypertension: The Atherosclerosis Risk in Communities Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Amber L Fyfe-Johnson ◽  
Alvaro Alonso ◽  
Elizabeth Selvin ◽  
Sunil K Agarwal ◽  
James S Pankow ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Interval Censoring ◽  
Fibroblast Growth ◽  
Incident Hypertension ◽  
Increased Risk ◽  
Wall Stiffness

Background: Elevated serum fibroblast growth factor-23 (FGF23), an endogenous hormone, is associated with endothelial dysfunction, chronic kidney disease, arterial wall stiffness, and inflammation. These factors may contribute to an increased risk of hypertension. To date, the association of FGF23 with incident hypertension has not been examined. Hypothesis: Elevated serum FGF23 will be positively associated with risk of incident hypertension. Methods: The ARIC study measured intact FGF23 in stored serum from 7,948 middle-aged men and women without hypertension at baseline (1990-92). Participants were examined during two follow-up visits, in 1993-95 and 1996-98. Incident hypertension was determined by measured blood pressure (DBP 90 mm Hg, or SBP140 mm Hg) and/or hypertension medication use during the follow-up exams. Multivariate Cox proportional hazards regression models and complementary log-log models were used to adjust for potential confounding variables. Results: During a median follow-up of 5.9 years, 27% (2,152/7,948) participants developed hypertension. A nonlinear association between serum FGF23 and incident hypertension was observed; only the highest decile of serum FGF23 was positively associated with incident hypertension (Table). After adjustment for demographics, the hazard ratio for incident hypertension was 1.37 (95% CI: 1.17, 1.60) for the highest decile of FGF23 compared to the lowest quintile. After adjustment for behaviors and adiposity the HR was 1.25 (95% CI: 1.07, 1.46). The association was further attenuated in the final model after adjusting for renal function (HR: 1.20, 95% CI: 1.03, 1.41). Complementary log-log models that accounted for interval censoring did not alter results. Conclusions: High levels ( 60.6 pg/mL) of FGF23 are associated with a modestly increased risk of incident hypertension in the general population. Next steps include replication of these findings in other cohorts, and examining the association with a longer follow-up period.

Differential Impacts of Intravenous Iron Administration and Iron-Containing Phosphate Binders on Serum Intact Fibroblast Growth Factor 23 Levels

2019 ◽  
Vol 47 (Suppl. 2) ◽  
pp. 63-69 ◽  
Author(s):  
Hirokazu Honda ◽  
Kenji Tanaka ◽  
Tetsuo Michihata ◽  
Keigo Shibagaki ◽  
Toshitaka Yuza ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iron Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Intravenous Iron ◽  
Phosphate Binders ◽  
Fibroblast Growth ◽  
Iron Administration ◽  
Iron Treatment ◽  
The Impact

Aims: This study assessed the impact of iron administration on serum fibroblast growth factor 23 (FGF23) levels. Methods: Of 123 hemodialysis (HD) patients treated with erythropoiesis-stimulating agents, 22 received once-weekly intravenous iron and 17 received daily oral iron with iron-containing phosphate binders. Intact FGF23 and biomarkers of iron metabolism were measured from blood samples drawn before each HD session, at baseline and on days 3, 5, 7, and 14. Results: Phosphate levels did not differ among the 3 groups during the 14-day period. Ferritin levels were significantly increased in both iron treatment groups compared with the non-iron treatment group, but changes in transferrin saturation levels were similar in the intravenous iron and non-iron groups. However, intact FGF23 levels were continuously higher in the intravenous iron group than those in the other groups. Conclusion: Intravenous iron administration may influence intact FGF23 levels in HD patients independently of phosphate and iron metabolism.

Abstract 14245: Fibroblast Growth Factor 23 and Long-term Cardiac Function: The Multi- Ethnic Study of Atherosclerosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ravi B Patel ◽  
Hongyan Ning ◽  
Ian H de Boer ◽  
Bryan Kestenbaum ◽  
Joao Ac Lima ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Circumferential Strain ◽  
Fibroblast Growth Factor 23 ◽  
Later Life ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Global Circumferential Strain ◽  
Ethnic Study

Background: While fibroblast growth factor 23 (FGF23) is associated with incident heart failure (HF) and atrial fibrillation (AF), the mechanisms driving these associations are unclear. FGF23 elevation leads to cardiomyocyte calcium handling abnormalities, suggesting that FGF23 may directly reduce myocardial function. Methods: In the Multi-Ethnic Study of Atherosclerosis, a cohort free of cardiovascular disease at recruitment, we evaluated the associations of serum FGF23 (2000-2002) with measures of left ventricular (LV) and left atrial (LA) mechanical function on cardiac magnetic resonance (CMR) at 10-year follow up (2010-2012). Results: Of 2,276 participants with baseline FGF23 and CMR at 10-year follow up, participants with higher FGF23 levels were more likely white race, taking anti-hypertensive medications, and had lower baseline glomerular filtration rate (GFR). After covariate adjustment, baseline FGF23 levels were independently associated with worse LV global circumferential strain, worse LV mid-wall circumferential strain, and lower LA total emptying fraction in later life ( Table ). The association of FGF23 and LV global circumferential strain was consistent across the spectrum of GFR ( Figure ). While higher FGF23 was associated with higher LV mass (β coefficient per SD higher: 1.14, 95% CI: 0.16, 2.12, P= 0.02), it was not associated with the presence of macroscopic myocardial scar (OR per SD higher: 1.12, 95% CI: 0.86-1.45, P= 0.42). Conclusions: Baseline FGF23 is independently associated with lower LV and LA systolic function in later life. These findings provide mechanistic insight driving the associations of FGF23 with development of both HF and AF.

scholarly journals Growth differentiation factor-15 and fibroblast growth factor-23 are associated with mortality in type 2 diabetes – An observational follow-up study

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0196634 ◽  
Author(s):  
Marie Frimodt-Møller ◽  
Bernt Johan von Scholten ◽  
Henrik Reinhard ◽  
Peter Karl Jacobsen ◽  
Tine Willum Hansen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Growth Differentiation Factor 15 ◽  
Follow Up Study ◽  
Differentiation Factor

Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis

2017 ◽  
Vol 44 (2) ◽  
pp. 122-128 ◽  
Author(s):  
Nicholas Carlson ◽  
Ole H. Mortensen ◽  
Mette Axelsen ◽  
Robert S. Pedersen ◽  
James G. Heaf
Keyword(s):  
Growth Factor ◽  
Bone Metabolism ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Plasma Concentrations ◽  
Fibroblast Growth ◽  
Ultrafiltration Rate ◽  
Cross Sectional ◽  
Blood Concentrations ◽  
The Impact

Introduction: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. Methods: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. Results: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. Conclusions: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged.

scholarly journals PKC regulates the production of fibroblast growth factor 23 (FGF23)

2019 ◽  
Author(s):  
Ludmilla Bär ◽  
Philipp Hase ◽  
Michael Föller
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Tyrosine Kinases ◽  
Membrane Lipids ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Pkc Isoforms ◽  
Proliferation And Differentiation ◽  
The Impact ◽  
G Protein Coupled

AbstractSerine/threonine protein kinase C (PKC) is activated by diacylglycerol that is released from membrane lipids by phospholipase C in response to activation of G protein-coupled receptors or receptor tyrosine kinases. PKC isoforms are particularly relevant for proliferation and differentiation of cells including osteoblasts. Osteoblasts/osteocytes produce fibroblast growth factor 23 (FGF23), a hormone regulating renal phosphate and vitamin D handling. PKC activates NFκB, a transcription factor complex controlling FGF23 expression. Here, we analyzed the impact of PKC on FGF23 synthesis. Fgf23 expression was analyzed by qRT-PCR in UMR106 osteoblastlike cells and in IDG-SW3 osteocytes. Phorbol ester 12-O-tetradecanoylphorbol-13-acetate (PMA), a PKC activator, up-regulated Fgf23 expression. In contrast, PKC inhibitors calphostin C, Gö6976, sotrastaurin and ruboxistaurin supressed Fgf23 gene expression. NFκB inhibitor withaferin A abolished the stimulatory effect of PMA on Fgf23. PKC is a powerful regulator of FGF23 synthesis, an effect which is at least partly mediated by NFκB.

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