Insulin-like growth factors and their binding proteins in pleural fluid

Bouc, Yves Le; Bellocq, A.; Philippe, C.; Périn, Laurence; Garabédian, M; Fouqueray, Bruno; Zacharias, Claudia Andrea; Cadranel, J.; Baud, Laurent

doi:10.1530/eje.0.1370467

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…The ratio of pleural:serum IGF-1 was nearly 1, suggesting local production of IGF-1 by malignant and in ammatory cells, while the total protein and albumin content of pleural uid was at least 30 to 50% lower than that in the corresponding sera. Similar observations were made by Le Bouc et al (23) in their study of tuberculous and malignant pleural effusion. In contrast, in acellular uid from patients with CHF, the ratio between serum and pleural IGF-1 was 2.7 : 1, suggesting non-speci c transport of IGF-1 from plasma to pleural space.…”

Section: Discussionsupporting

confidence: 88%

Elevated Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-2 in Malignant Pleural Effusion

Olchovsky¹,

Shimon²,

Goldberg³

et al. 2002

Acta Oncologica

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Insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBPs) are produced by many tissues and are present in serum and other biological fluids. Alterations in sera of IGF-1 and 2 and IGFBPs were demonstrated in patients with malignancy, infection and other diseases causing pleural effusion. In this study the IGF-1 and IGFBP-2 content and the specific electrophoretic patterns of IGFBPs in samples of sera and pleural effusions of 25 patients with malignancy, infection and congestive heart failure were investigated. IGF-1 levels in exudative effusions of malignant solid tumors were significantly higher [(mean +/- SD), 20.9+/-7.5 nmol/L, n = 9] than in lymphoma (11.0+/-5.2 nmol/L, n = 5; p < 0.05), infection (11.4+/-6.5 nmol/L, n = 6; p < 0.05) and transudative effusion of congestive heart failure (4.3+/-3.3 nmol/L, n = 5; p < 0.02). IGFBP-2 was markedly increased in effusions of malignant solid tumors (2.14+/-0.82 mg/L, n = 9) compared with exudates of lymphoma, infection and transudates (1.10+/-0.70, 1.22+/-0.32 and 0.93+/-0.52 nmol/L, respectively, p< 0.05). Moreover, in effusion of solid tumors, IGFBP-2 levels were higher than those in corresponding sera, which suggests local production of this binding protein. The demonstration of IGFBP-2 in solid tumor cells by immunohistochemistry further supports this possibility. This work demonstrates the existence of the IGF-1/IGFBP system in pleural fluids from different etiologies and implies possible use of IGF-1 and IGFBP-2 as a potential marker of malignant effusions.

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Section: Discussionsupporting

confidence: 88%

Elevated Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-2 in Malignant Pleural Effusion

Olchovsky¹,

Shimon²,

Goldberg³

et al. 2002

Acta Oncologica

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“…Binding proteins also provide indication of nutritional status and were down-regulated at the time of diagnosis. Examples include corticosteroid binding protein (CBG), transthyretin (TTHY), serotransferrin (TRFE), insulin-like growth factor-binding protein 3 (IGBP3) [ 56 ], albumin (ALBU) and tetranectin (TETN) and afamin (AFAM). Retinol binding protein (RET4) increased expression post-treatment might be due to retinoic acid’s ability to induce monocyte differentiation [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis

et al. 2018

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Rationale:The monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.Objective:We utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy.Methods:Serum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points.Results:A total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status.Conclusion:A comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care.

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“…The remaining two proteins in the HIV + panel, IGFBP6 and TAGLN2 have unknown roles in infectious diseases. Of note, ligands of IGFBP6 are reduced in sera and pleural fluids of subjects with tuberculous and non-tuberculous pleuritis ( Le Bouc et al, 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

et al. 2015

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Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB.

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Insulin-like growth factors and their binding proteins in pleural fluid

Cited by 5 publications

References 30 publications

Elevated Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-2 in Malignant Pleural Effusion

Elevated Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-2 in Malignant Pleural Effusion

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis

Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

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