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Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer.

ABSTRACT: Pro-inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro-inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]), and coagulation (D-dimer) factors were associated with pre-chemotherapy functional status in women with stage I-III breast cancer.Prior to chemotherapy initiation in patients with stage I-III breast cancer, the following was captured: IL-6, CRP, D-dimer blood levels, and physical function measures including activities of daily living (ADL, subscale of Medical Outcomes Study Physical Health); instrumental activities of daily living (IADL, subscale of the Older Americans Resources and Services Program); Timed Up and Go (TUG); physician-rated Karnofsky Performance Status (KPS); and self-rated KPS. The association of these biomarkers with physical function measures was evaluated.One hundred sixty patients (mean age 58.3 years, range 30-81 years) with stage I-III breast cancer (stages I [n?=?34; 21.5%], II [n?=?88; 55.7%], III [n?=?36; 22.8%]) were enrolled. The group with poorest physical function (defined by ADL <70, IADL <14, and TUG ?10 seconds) had higher levels of IL-6 (p?=?.05), D-dimer (p?=?.0004), and CRP (p?=?.05). There was no significant association between these biomarkers and KPS. Patients with at least two biomarkers in the highest quartile were more likely to have poorer physical function (odds ration [OR] 18.75, p?

SUBMITTER: Yuan Y

PROVIDER: S-EPMC5634764 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer.

Yuan Yuan Y Vora Nilesh N Sun Can-Lan CL Li Daneng D Smith David D Mortimer Joanne J Luu The-Hang TH Somlo George G Waisman James J Chao Joseph J Katheria Vani V Synold Timothy T Tran Vivi V Mi Shu S Feng Tao T Levi Abrahm A Arsenyan Anait A Choi Jennifer J Zavala Laura L Yost Susan S Hurria Arti A

The oncologist 20170530 10

<h4>Background</h4>Pro-inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro-inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]), and coagulation (D-dimer) factors were associated with pre-chemotherapy functional status in women with stage I-III breast cancer.<h4>Patients and methods</h4>Prior to chemotherapy initiation in patients with stage I-III breast cancer, the following was captured: IL-6, CRP, ...[more]

PMID: 28559409

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Project description:Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI?<?85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I-III BC.This study enrolled women with stage I-III BC. Prior to adjuvant or neoadjuvant chemotherapy, peripheral blood was collected for biomarker measurement. Dose reductions and delays were captured and utilized to calculate the RDI delivered. Univariate and multivariate analyses were performed to describe the association between pre-chemotherapy IL-6, CRP, and D-dimer levels and an RDI?<?85%, controlling for relevant tumor and patient factors (age, stage, receptor status, chemotherapy regimen, and pre-chemotherapy physical function and comorbidity).A total of 159 patients (mean age 58 years, range 30-81, SD 11.3) with stage I-III BC were enrolled. An RDI?<?85% occurred in 22.6% (N?=?36) of patients and was associated with higher pre-chemotherapy IL-6 (OR 1.14, 95% CI 1.04-1.25; p?=?0.006) and D-dimer (OR 2.32, 95% CI 1.27-4.24; p?=?0.006) levels, increased age (p?=?0.001), increased number of comorbidities (p?=?0.01), and decreased physical function by the Medical Outcomes Survey Activities of Daily Living (ADL) Scale (p?=?0.009) in univariate analysis. A multivariate model, including two biomarkers (IL-6 and D-dimer), age, ADL, BC stage, and chemotherapy regimen, demonstrated a significant association between the increased biomarkers and reduced RDI?<?85% (OR 2.54; p?=?0.04).Increased pre-chemotherapy biomarkers of aging (IL-6 and D-dimer) are associated with reduced RDI (<85%). Future studies are underway to validate these findings.ClinicalTrials.gov, NCT01030250 . Registered on 3 November 2016.

Project description:ObjectivesMacrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI).Methods and resultsWe recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in cultured peripheral blood mononuclear cells (PBMCs) and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1? which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI.ConclusionMI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests that MIF could be a potential therapeutic target following MI.

Project description:BackgroundNeutrophils play crucial roles in the inflammatory response after acute cerebral infarction (ACI). Previous studies revealed neutrophils are non-homogeneous and can be divided into at least two subtypes, pro-inflammatory and anti-inflammatory, correlated with patients' prognosis.ObjectiveWe aimed to explore the correlation between disease severity and peripheral blood neutrophils in patients with ACI and determine whether remote ischemic postconditioning (RIPostC) exerts neuroprotective effects by regulating neutrophils.MethodsPatients (n = 38) with acute anterior circulation cerebral infarction were assigned to conventional treatment (n = 24; included aspirin, statins, neuro nutrition drugs, and circulation improvement drugs) or RIPostC (n = 14; 7-day ischemia adaptation [complete ischemia of both upper extremities for 5 minutes followed by remission for 5 minutes, 5 repeated cycles, twice a day, started from the morning of the second day of admission] based on conventional treatment) groups, based on their preference. General clinical data and peripheral blood samples were taken three times, in the morning before and 3 and 7 days after treatment. Fifteen adults with non-acute cerebral infarction matched for sex, age, and risk factors were recruited as controls; peripheral blood samples were only collected on the recruitment day. We used flow cytometry to detect the percentage of neutrophils and Real-Time PCR to detect the gene expression of interleukin (IL)-1β in the peripheral blood samples.ResultsThe percentage of neutrophils, pro-inflammatory neutrophils (IL-1β high expression in flow cytometry), and IL-1β mRNA expression increased after ACI (P = 0.01, P = 0.001, P < 0.001). The National Institutes of Health Stroke Scale (NIHSS) score of patients with ACI within one day of onset was positively correlated with the percentage of pro-inflammatory neutrophils (R = 0.618, P = 0.043). Pro-inflammatory neutrophils in the RIPostC group decreased compared with those in the conventional treatment group, with the most significant difference observed on Day 7 (P = 0.01). However, the percentage of neutrophils was not statistically different. IL-1β mRNA expression decreased, with the most significant difference on Day 3 (P = 0.004). The NIHSS and Modified Rankin Scale scores for RIPostC decreased more significantly than for conventional treatment (P = 0.002, P = 0.019).ConclusionMore severe cerebral infarction was associated with a higher percentage of pro-inflammatory neutrophils. The neuroprotective effect of RIPostC may partly be exerted through gene regulation to reduce pro-inflammatory neutrophils.

Project description:Hirschsprung disease (HSCR) is a rare congenital anomaly characterized by the absence of enteric ganglia in the distal intestinal tract. While classified as a multigenic disorder, the altered function of the RET tyrosine kinase receptor is responsible for the majority of the pathogenesis of HSCR. Recent evidence demonstrate a strong association between RET and the homeostasis of immune system. Here, we utilize a unique cohort of fifty HSCR patients to fully characterize the expression of RET receptor on both innate (monocytes and Natural Killer lymphocytes) and adaptive (B and T lymphocytes) human peripheral blood mononuclear cells (PBMCs) and to explore the role of RET signaling in the immune system. We show that the increased expression of RET receptor on immune cell subsets from HSCR individuals correlates with the presence of loss-of-function RET mutations. Moreover, we demonstrate that the engagement of RET on PBMCs induces the modulation of several inflammatory genes. In particular, RET stimulation with glial-cell line derived neurotrophic factor family (GDNF) and glycosyl-phosphatidylinositol membrane anchored co-receptor ?1 (GFR?1) trigger the up-modulation of genes encoding either for chemokines (CCL20, CCL2, CCL3, CCL4, CCL7, CXCL1) and cytokines (IL-1?, IL-6 and IL-8) and the down-regulation of chemokine/cytokine receptors (CCR2 and IL8-R?). Although at different levels, the modulation of these "RET-dependent genes" occurs in both healthy donors and HSCR patients. We also describe another set of genes that, independently from RET stimulation, are differently regulated in healthy donors versus HSCR patients. Among these "RET-independent genes", there are CSF-1R, IL1-R1, IL1-R2 and TGF?-1, whose levels of transcripts were lower in HSCR patients compared to healthy donors, thus suggesting aberrancies of inflammatory responses at mucosal level. Overall our results demonstrate that immune system actively participates in the physiopathology of HSCR disease by modulating inflammatory programs that are either dependent or independent from RET signaling.

Dataset Information

Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer.

Publications

Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer.

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