Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin

BackgroundAcute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs.MethodsThis study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse.ResultsUnivariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality.ConclusionsA higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome.Trial registration numberUMIN000014969.

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Platelet-Derived Growth Factor C in Alcoholics

Alcohol and Alcoholism ◽

10.1093/alcalc/agz094 ◽

2020 ◽

Vol 55 (2) ◽

pp. 157-163 ◽

Cited By ~ 1

Author(s):

C Martín-González ◽

L González-Navarrete ◽

I Ribot-Hernández ◽

V Vera-Delgado ◽

J Alvisa-Negrín ◽

...

Keyword(s):

Multivariate Analysis ◽

Platelet Count ◽

Growth Factor ◽

Serum Levels ◽

Muscle Disease ◽

Platelet Derived Growth Factor ◽

Laboratory Evaluation ◽

Prothrombin Activity ◽

Factor C ◽

Factor Α

Abstract Aims Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics. Methods In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on. Results Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = −0.39; P = 0.002), IL-6 (ρ = −0.33; P = 0.016), IL-8 (ρ = −0.47; P < 0.001), and MDA levels (ρ = −0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF. Conclusion PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

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Prognostic value of Serum miR-217 Level in Osteosarcoma Patients

10.21203/rs.3.rs-16386/v1 ◽

2020 ◽

Author(s):

Jia Ye ◽

Zhi-Hui Jin ◽

Ren Chen ◽

Sen Chen ◽

Yi-Jun Ren ◽

...

Keyword(s):

Multivariate Analysis ◽

Poor Prognosis ◽

Prognostic Significance ◽

Serum Levels ◽

High Serum ◽

Rt Pcr ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Polymerase Chain ◽

Low Serum

Abstract Background MicroRNA (miR)-217 is a tumor suppressor significantly associated with osteosarcoma. We try to evaluate serum levels miR-217 in osteosarcoma patients and evaluate its prognostic significance. Methods A total of 163 consecutive osteosarcoma patients and 96 healthy participates were enrolled. Serum miR-217 levels were evaluated by using real-time quantitative reverse transcription polymerase chain reactions(RT-PCR). The association between serum miR-217 level and survival outcomes was evaluated by univariate and multivariate analysis. Results Serum miR-217 levels in osteosarcoma patients was significantly lower than healthy volunteers (P<0.05). Low serum miR-217 was significantly related to advanced cancer and metastasis (both P<0.05). Moreover, patients with a low serum miR-217 had a poorer overall survival than those with a high serum miR-217 levels (P<0.05). Serum miR-217 level also been showed as independent risk factor for osteosarcoma in multivariate analysis (HR, 0.42; 95%CI: 0.12–0.98; p<0.01). Conclusions Serum miR-217 levels was significantly downregulated in osteosarcoma patients and remarkably associated with poor prognosis, indicating that serum miR-217 might serve as a useful diagnostic and prognostic indictor for osteosarcoma.

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Angiogenic Cytokines Are Increased in the Serum of Patients with Waldenastrom’s Macroglobulinemia (WM): Correlations with Clinical Data.

Blood ◽

10.1182/blood.v108.11.5006.5006 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5006-5006

Author(s):

Athanasios Anagnostopoulos ◽

Evangelos Terpos ◽

Konstantinos Zervas ◽

Efstathios Kastritis ◽

Vangelis Eleftherakis-Papaiakovou ◽

...

Keyword(s):

Growth Factor ◽

Clinical Data ◽

Serum Levels ◽

Hematologic Malignancies ◽

Sample Collection ◽

Serum Samples ◽

Symptomatic Disease ◽

Endothelial Growth Factor ◽

Angiogenic Cytokines ◽

Angiopoietin 1

Abstract Angiogenesis is essential step of disease progression in several hematologic malignancies including multiple myeloma (MM). Bone marrow (BM) angiogenesis, assessed by microvessel density (MVD), is increased in 30% of patients with WM and showed only weak correlation with BM infiltration. Two major classes of angiogenic factors, namely the vascular endothelial growth factor (VEGF and mainly its A component (VEGF-A)) and angiopoietins 1 and 2 (Ang-1, Ang-2), has been shown to play pivotal role in tumor angiogenesis. Angiogenin is member of the ribonuclease family, which participates in angiogenesis by influencing the migration and proliferation of endothelial cells. Basic fibroblast growth factor (bFGF) is another cytokine, which is produced by stromal cells and plays significant role in MM pathogenesis. Aim of the study was the evaluation of angiogenesis, as assessed by the measurement of the above angiogenic cytokines, in pts with WM and its correlation with clinical data of the pts. We studied serum samples of 67 pts with serum monoclonal IgM (SMIgM) (44M/23F; median age: 71 years, range: 39–85 years) in various phases of their disease. Fifty-three pts had overt WM (21 untreated, 20 in relapse and 12 in remission). Furthermore, 14 pts with IgM MGUS (N=11) or asymptomatic WM (N=3) were also included. VEGF, VEGF-A, angiogenin, angiopoietin-1 and 2 and bFGF were measured using ELISA methodology (Diaclone, France for VEGF-A and R&D Systems, MN, USA for other cytokines). In all pts, we also evaluated hemoglobin, PLT count, β2-microglobulin (β2m) and albumin levels as well as the presence of splenomegaly, hepatomegaly and lymphadenopathy at the time of sample collection. The same cytokines were also measured in 30 gender- and age-matched controls. All pts with SMIgM had increased serum levels of all cytokines except angiopoietin-1 compared to controls: mean ±SD for VEGF was 299±228 vs. 106±76 pg/ml in pts and controls, respectively (p<0.0001); for VEGF-A 105±102 vs. 6.7±13.6 pg/ml (p<0.0001), for angiogenin 442.9±216.5 ng/ml vs. 239.5±58.5 ng/ml (p<0.0001); for Ang-1 25.1±22 vs. 21±13.5 ng/ml (p=0,4), for Ang-2 3,212±2,110 vs. 1,746±1,023 pg/ml (p=0.0004) and for bFGF 10.2±17.1 vs. 1.3±3.15 pg/ml (p=0.005). However, pts with IgM MGUS or asymptomatic WM (N=14) had elevated values of Ang-1 (40.16±21.66 ng/ml) compared with controls (p=0.002) and pts with symptomatic WM (p=0.003). Pts with active WM (untreated and relapsed) had increased levels of angiogenin compared with asymptomatic WM-MGUS pts and with pts in remission. At the time of sample collection, 16 pts had anemia (Hb<10 g/dl), while 14 pts had increased levels of β2m (>3.5 mg/l), and 11 pts had reduced albumin levels (<3.5 g/dl). Pts with high VEGF-A had higher β2m (r=0.28, p=0.03), high angiogenin was correlated with low albumin (r=−0.39, p=0.001), while high Ang-1 was correlated with low β2m (r=−0.47, p=0.0009) and high Hb levels (r=0.27, p=0.04). Our study suggests that angiogenic cytokines increase in pts with SMIgM supporting a possible paracrine role of these molecules. Ang-1 is the only cytokine which is increased in pts with IgM-MGUS and asymptomatic WM but returns to normal in pts with symptomatic disease. Our results, if confirmed, may provide the basis for clinical trials in WM, which involve anti-angiogenic agents.

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Monokine Induced by Interferon-γ (MIG) Serum Levels Are a Marker of Disease Load and Correlate with Prognosis in Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.5040.5040 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5040-5040

Author(s):

Martin Schreder ◽

Gudrun Koch ◽

Daniel Heintel ◽

Kathrin Strasser-Weippl ◽

Katrin Frischmuth ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Prognostic Significance ◽

Serum Levels ◽

Interferon Γ ◽

Serum Samples ◽

Myeloma Cells ◽

Autocrine Loop ◽

Protein Levels

Abstract Background and Aims: Monokine-induced by interferon-γ (MIG) is a chemokine that is produced by monocytes and macrophages in response to interferon-γ and acts as a chemoattractant mainly to T-lymphocytes in inflammatory processes. MIG has also been suggested to act in an autocrine loop to stimulate tumour cells through its receptor CXCR3, which is known to be expressed in myeloma cells. However, it is presently unclear if MIG is of biologic significance in myeloma in vivo. We have recently shown that multiple myeloma oncogene 1 (MUM1) expression in myeloma cells correlates with prognosis in this disease (Heintel D et al., ASH 2005), and MUM1 was found to upregulate MIG gene expression in B cell malignancies (Uranishi M et al., Leukemia 2005). This led us to evaluate the potential prognostic significance of MIG serum levels in a series of well characterized myeloma patients. Methods: 105 newly diagnosed multiple myeloma patients (median age 69.3 years, range 39.4–90.5) were enrolled. 18 patients presented with Durie/Salmon stage I disease, 9 had stage II and 78 had stage III. MIG serum levels were determined by a commercially available ELISA (R&D Systems). Serum samples from 17 MGUS patients and 37 age-matched healthy volunteers were used as controls. Results: MIG serum levels were elevated in multiple myeloma patients (median 161.3 pg/ml, range 9.37–1966.0) compared to MGUS patients (median 92.7 pg/ml, range 6.29–1303.1) and healthy controls (median 106.2 pg/ml, range 51.0–390.6). For analysis of myeloma cases, a cut-off level for MIG of 200pg/ml (=95th percentile of MIG in controls) was chosen to identify low and high MIG expressers. Using the cut-off as defined above, 63 patients with low MIG serum levels and 42 high MIG expressers were identified in a population of 105 myeloma patients. MIG serum levels in myeloma patients showed strong correlations with several markers of tumour load including low albumin and high β2-microglobulin. Interestingly, no correlation was found with C-reactive protein levels, indicating that MIG is not associated with an inflammatory response in myeloma. Median survival was significantly shorter in patients with high MIG serum levels compared to patients with low MIG expression (median not reached vs. 17.0 months, p<0.001; see figure). Conclusions: MIG serum levels correlate with markers of disease burden in myeloma and high MIG levels are associated with a poor outcome in this disease. Overall Survival: low vs. high MIG serum levels Overall Survival: low vs. high MIG serum levels

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Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP

Neonatology ◽

10.1159/000512282 ◽

2021 ◽

Vol 118 (1) ◽

pp. 18-27

Author(s):

Gunnel Hellgren ◽

Pia Lundgren ◽

Aldina Pivodic ◽

Chatarina Löfqvist ◽

Anders K. Nilsson ◽

...

Keyword(s):

Platelet Count ◽

Growth Factor ◽

Serum Levels ◽

Clinical Indication ◽

Serum Concentrations ◽

Serum Samples ◽

Platelet Counts ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Underlying Mechanisms

Introduction: Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated. Methods: Data for 78 infants born at gestational age (GA) <28 weeks were included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. Results: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05–0.001). With adjustment for GA, low platelet counts and low serum concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p < 0.001). Conclusion: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.

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Prognostic value of Serum miR-217 Level in Osteosarcoma Patients

10.21203/rs.3.rs-111272/v2 ◽

2021 ◽

Author(s):

Jia Ye ◽

Zhi-Hui Jin ◽

Ren Chen ◽

Sen Chen ◽

Yi-Jun Ren ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Significance ◽

Serum Levels ◽

Prognostic Indicator ◽

High Serum ◽

Rt Pcr ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Polymerase Chain ◽

Low Serum

Abstract Background: MicroRNA (miR)-217 is a tumor suppressor significantly associated with osteosarcoma. We try to evaluate serum levels miR-217 in osteosarcoma patients and evaluate its prognostic significance.Methods: A total of 163 consecutive osteosarcoma patients and 96 healthy participates were enrolled. Serum miR-217 levels were evaluated by using real-time quantitative reverse transcription polymerase chain reactions(RT-PCR). The association between serum miR-217 level and survival outcomes was evaluated by univariate and multivariate analysis. Results: Serum miR-217 levels in osteosarcoma patients was significantly lower than healthy volunteers (P<0.05). Low serum miR-217 was significantly related to advanced cancer and metastasis (both P<0.05). Moreover, patients with a low serum miR-217 had a poorer overall survival than those with a high serum miR-217 levels (P<0.05). Serum miR-217 level also been showed as independent risk factor for osteosarcoma in multivariate analysis (HR, 0.42; 95%CI: 0.12–0.98; p<0.01). Conclusions: Serum miR-217 levels was significantly downregulated in osteosarcoma patients and remarkably associated with poor prognosis, indicating that serum miR-217 might serve as a useful diagnostic and prognostic indicator for osteosarcoma.

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Prognostic Significance of Angiogenic Growth Factor Serum Levels in Patients With Acute Coronary Syndromes

Circulation ◽

10.1161/01.cir.0000048183.37648.1a ◽

2003 ◽

Vol 107 (4) ◽

pp. 524-530 ◽

Cited By ~ 77

Author(s):

Christopher Heeschen ◽

Stefanie Dimmeler ◽

Christian W. Hamm ◽

Eric Boersma ◽

Andreas M. Zeiher ◽

...

Keyword(s):

Growth Factor ◽

Acute Coronary Syndromes ◽

Prognostic Significance ◽

Serum Levels ◽

Angiogenic Growth Factor ◽

Coronary Syndromes

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Serum Cytokines Correlated with The Disease Severity of Generalized Pustular Psoriasis

Disease Markers ◽

10.1155/2013/702763 ◽

2013 ◽

Vol 34 (3) ◽

pp. 153-161 ◽

Cited By ~ 15

Author(s):

Masaaki Yamamoto ◽

Yasutomo Imai ◽

Yoshiko Sakaguchi ◽

Takashi Haneda ◽

Kiyofumi Yamanishi

Keyword(s):

Serum Levels ◽

Pustular Psoriasis ◽

Clinical Markers ◽

Serum Samples ◽

Protein Levels ◽

Serum Cytokines ◽

Cell Counts ◽

Severity Scores ◽

Generalized Pustular Psoriasis ◽

White Blood Cell Counts

To characterize serum biomarkers reflecting the severity of generalized pustular psoriasis (GPP), we measured multiple cytokine/chemokine levels in 39 serum samples from 6 cases with GPP during the course of the disease. Serum levels of IL-4, IL-8, CXCL1 and CCL3 were positively correlated with the severity scores of GPP, white blood cell counts and serum C-reactive protein levels. Serum levels of IL-1β, IL-1ra, IL-6, IL-10, IL-12p70, IL-18, IL-22, IFN-γand VEGF showed strong positive correlations (r> 0.4,p< 0.01) with all those 3 clinical markers. Of those, IL-10 and IL-22 were significantly decreased after treatment in parallel with the GPP score and therefore those two serum cytokines might be useful to evaluate the efficacy of treatment for GPP.

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Prognostic value of Serum miR-217 Level in Osteosarcoma Patients

10.21203/rs.3.rs-111272/v1 ◽

2020 ◽

Author(s):

Jia Ye ◽

Zhi-Hui Jin ◽

Ren Chen ◽

Sen Chen ◽

Yi-Jun Ren ◽

...

Keyword(s):

Multivariate Analysis ◽

Poor Prognosis ◽

Prognostic Significance ◽

Serum Levels ◽

High Serum ◽

Rt Pcr ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Polymerase Chain ◽

Low Serum

Abstract Background: MicroRNA (miR)-217 is a tumor suppressor significantly associated with osteosarcoma. We try to evaluate serum levels miR-217 in osteosarcoma patients and evaluate its prognostic significance.Methods: A total of 163 consecutive osteosarcoma patients and 96 healthy participates were enrolled. Serum miR-217 levels were evaluated by using real-time quantitative reverse transcription polymerase chain reactions (RT-PCR). The association between serum miR-217 level and survival outcomes was evaluated by univariate and multivariate analysis. Results: Serum miR-217 levels in osteosarcoma patients was significantly lower than healthy volunteers (P<0.05). Low serum miR-217 was significantly related to advanced cancer and metastasis (both P<0.05). Moreover, patients with a low serum miR-217 had a poorer overall survival than those with a high serum miR-217 levels (P<0.05). Serum miR-217 level also been showed as independent risk factor for osteosarcoma in multivariate analysis (HR, 0.42; 95%CI: 0.12–0.98; p<0.01). Conclusions: Serum miR-217 levels was significantly downregulated in osteosarcoma patients and remarkably associated with poor prognosis, indicating that serum miR-217 might serve as a useful diagnostic and prognostic indictor for osteosarcoma.

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Serial Analysis of Multiple Serum Cytokine Responses to Adrenocorticotropic Hormone Therapy in Patients With West Syndrome

Journal of Child Neurology ◽

10.1177/0883073818770764 ◽

2018 ◽

Vol 33 (8) ◽

pp. 528-533

Author(s):

Gaku Yamanaka ◽

Natsumi Morishita ◽

Shinichiro Morichi ◽

Mika Takeshita ◽

Urabe Tomomi ◽

...

Keyword(s):

Growth Factor ◽

Adrenocorticotropic Hormone ◽

Japanese Patients ◽

Serum Levels ◽

Underlying Mechanism ◽

West Syndrome ◽

Serum Samples ◽

Chemokine Ligand ◽

Ifn Γ ◽

Inducible Protein

Adrenocorticotropic hormone (ACTH) therapy is effective for West syndrome; however, the underlying mechanism of action remains unknown. This study explored this mechanism in 5 Japanese patients with West syndrome, injected with ACTH for 28 days. Serum samples were obtained before and 30, 120, and 720 minutes after ACTH injection divided into an “early” (1-4 days) and a “late” (10-28 days) group. Responses to ACTH over time were analyzed by measuring the levels of 27 cytokines. In the early group, serum levels of interleukins-5, -9, and -17, basic fibroblast growth factor, interferon (IFN-γ), IFN-γ-inducible protein 10, chemokine ligand (CCL) 3 and 4, and platelet-derived growth factor were higher in all patients before ACTH administration than in the 720-minute time point. In the late group, no definite trend was observed except for decreased CCL2 levels after ACTH administration. These changes may correlate with mechanisms underlying the anticonvulsant effects of ACTH.

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