Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes – Findings from two community based cohorts of elderly

Carlsson, Axel C.; Juhlin, C. Christofer; Larsson, Tobias E.; Larsson, Anders; Ingelsson, Erik; Sundström, Johan; Lind, Lars; Ärnlöv, Johan

doi:10.1016/j.atherosclerosis.2014.09.005

Cited by 29 publications

(27 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More importantly, both cathepsins were associated with both sTNFR1 and sTNFR2, which may be of clinical importance since the role of these biomarkers have been shown to be of importance for different stages of CKD and mortality [37][38][39][40]. Yet, the association between endostatin as well as cathepsins S and L levels with mortality and inflammatory biomarkers may be only associative, and do not clearly demonstrate a role of these molecules in the pathogenesis of diseases associated with CKD and dialysis.…”

Section: Discussionmentioning

confidence: 90%

Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 90%

Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, sTNF-RI has been linked to downregulation of cell surface adhesion molecules and reduction of lymphocyte infiltration into tissues [25,26]. Moreover, circulating TNF has been shown to be elevated in nonresponders to sunitinib [27]; however, research on the clinical significance of the sTNF-R is very limited [28]. Our finding linking sTNF-RI to a poor prognosis and low response to sunitinib in nccRCC is novel and suggests that, despite the biological heterogeneity of nccRCC, TNF signaling has relevance to the clinical outcomes in this group of diseases.…”

Section: Discussionmentioning

confidence: 99%

Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial

Bilen

Zurita²,

Ilias-Khan³

et al. 2015

The Oncologist

View full text Add to dashboard Cite

Background. We evaluated the significance of hypertension developing during vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (VEGFR‐TKI) treatment and a group of cytokines and angiogenic factors (CAFs) in advanced non‐clear cell renal cell carcinoma (nccRCC) patients treated with sunitinib in a phase II study. Materials and Methods. Using multiplex assays, we analyzed the levels of 38 CAFs in plasma at baseline and after 4 weeks of sunitinib therapy. Sunitinib benefit was defined as a partial response or stable disease using the Response Evaluation Criteria in Solid Tumors lasting ≥4 months. Cox proportional hazards regression models were used to assess the associations among hypertension, CAFs, and progression‐free (PFS) and overall survival (OS). Results. Fifty‐seven patients were evaluable; 53 had baseline CAF levels available. The median PFS and OS were 2.9 months (95% confidence interval [CI], 1.4–5.5) and 16.8 months (95% CI, 10.7–27.4), respectively. Sunitinib benefit was observed in 21 patients (37%). However, 33 patients (60%) developed hypertension during treatment, although no association was found with survival or response. Elevated baseline soluble tumor necrosis factor (TNF) receptor I, interleukin‐8, growth‐regulated oncogene, transforming growth factor‐α, and VEGFR‐2 levels were associated with an increased risk of death on multivariate analysis. Conclusion. We found no association between the development of hypertension and survival or sunitinib benefit in advanced nccRCC. TNF and angiogenic/immunomodulatory mediators were identified for evaluation as markers of prognosis and VEGFR‐TKI benefit in future studies. Implications for Practice: The present study describes the first analysis of hypertension and a relatively large set of circulating cytokines and angiogenic factors in patients with advanced non‐clear cell renal cell carcinoma (nccRCC) treated with sunitinib. No association was found between hypertension and patient outcomes. However, a group of candidate circulating biomarkers was identified, in particular, those associated with tumor necrosis factor and CXCR1/2 signaling, with probable biological and clinical significance in nccRCC, warranting confirmation in future studies.

show abstract

“…Yet, additional unique physiological responses of sTNFRs are present that are independent of TNF-α [2]. Moreover, sTNFR1 has repeatedly been shown to be associated with mortality in elderly individuals [3,4]. …”

Section: Introductionmentioning

confidence: 99%

Soluble Tumor Necrosis Factor Receptor 1 Is Associated with Glomerular Filtration Rate Progression and Incidence of Chronic Kidney Disease in Two Community-Based Cohorts of Elderly Individuals

Carlsson

Nordquist²,

Larsson

et al. 2015

Cardiorenal Med

Self Cite

View full text Add to dashboard Cite

Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes. Research Design and Methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as ≥60, 30-60, and <30 ml/min/1.73 m². Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR ≥60 ml/min/1.73 m² at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes. Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.

show abstract

Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes – Findings from two community based cohorts of elderly

Abstract: Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly. Atherosclerosis

Cited by 29 publications

References 37 publications

Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial

Soluble Tumor Necrosis Factor Receptor 1 Is Associated with Glomerular Filtration Rate Progression and Incidence of Chronic Kidney Disease in Two Community-Based Cohorts of Elderly Individuals

Contact Info

Product

Resources

About