Abstract. Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer.
Our study shows that, besides a rapid suppression of disease activity, serum sCAM and VEGF concentrations are downregulated following anti-tumour necrosis factor alpha (TNFalpha) therapy combined with MTX. Prolonged treatment with etanercept sustained or even more remarkably diminished the sCAM and VEGF serum concentrations.
Objective. Chemokines promote leukocyte traffic into the synovium, leading to the initiation and progression of the rheumatoid arthritis (RA). The aim of the study was to determine the effects of etanercept, a soluble tumour necrosis factor receptor (sTNFr), on the serum chemokines levels in patients with active RA.
Methods
In patients with rheumatoid arthritis the serum profile of transferrin isoforms is altered. We predict that the levels of trisialylated isoforms of transferrin will serve as a useful biochemical marker of the rheumatoid arthritis activity.
In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20+ B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20–30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.Electronic supplementary materialThe online version of this article (doi:10.1007/s00296-014-3112-1) contains supplementary material, which is available to authorized users.
Coexistence of systemic sclerosis, scleroderma-like syndromes and neoplastic diseases 119 REVIEW ARTICLES Neoplastic diseases and rheumatic syndromes A number of rheumatic diseases coexisting with neoplasm of various origins have been reported. Neoplastic lesions changes may evoke the paraneoplastic rheumatic syndromes. Moreover, they may be a complication of chronic rheumatic disease [1]. Paraneoplastic syndrome is defined as a sign or a constellation of signs and symptoms which are secondary to the presence of a malignancy. These symptoms may be induced to the substances secreted by the neoplasm (hormones and other biologically active substances) or to the immune system response to tumor cells (autoimmunological reactions, immune complexes, immune system suppression) and may involve many organs and systems. Paraneoplastic syndromes are not related to
Background
In patients with active rheumatoid arthritis (RA) decrease of galactosylation of IgG is observed. It has been shown that agalactosylation is correlated with disease activity (1, 3, 4).
Objectives
The aim of our study was to evaluate an effect of methotrexate (MTX) therapy on glycosylation disturbances of IgG in RA patients.
Methods
40 patients with active RA was treated with MTX for 12 months in dosage 15-25 mg per week (2). All patients were in remission based on DAS 28 (≤2.6) at the end of the study. The control group was consisted of 20 healthy volunteers in the same age. IgG was isolated from patients sera and analysis of IgG galactosylation by biotinylated lectins was performed. Immunosorbent assay ELISA was used for this purpose. For galactose specifity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue (Areulia auranta) AAA lectin was used (5).
Results
Our data demonstrated that N-glycan galactosylation and sialylation of IgG in untreated (naive) RA patients was significantly lower than in control group (for DSA, MAA lectins p<0.001 and SNA p<0.05). Furthermore we showed significant increase of IgG galactosylation and sialylation in RA patients after twelve months of MTX therapy (for DSA,MAA and SNA lectin p<0.05) compared to those before treatment. Moreover the glycosylation disturbances of N-glycan IgG were strongly associated with changes of disease activity based on DAS 28 (p<0.001). For fucose residues significantly higher absorbancy of AAA lectin in RA patients before MTX treatment was observed compared to control group (p<0.05). There were no correlation between absorbancy of this lectins before and after treatment but in RA treated patients still higher level of fucosylation was observed. There were no correlation between lectins absorbancy and ACPA and RF titer.
Conclusions
Defect of glycosylation of IgG in RA can be detected by simple lectin method. Assessment of disturbances of glycosylation of IgG might be a useful marker of disease activity and effectiveness of treatment.
References
Watson M, Rudd PM, Bland M et al. Sugar printing rheumatic diseases. Arthritis and Rheum. Vol.42, No 8, Aug 1999, pp 1682-1690
Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1998, 31: 315-324
Axford JS, Sumar N, Alavi A et al. Changes in normal glycosylation mechanisms in autoimmune rheumatic disease. J. Clin. Invest., 1992; 89: 1021-1031
Gindzienska-Sieskiewicz E, Klimiuk PA, Kisiel DG et al. The changes In monosaccharide composition of immunoglobulin G in the course of rheumatoid arthritis. Clin Rheumatol. 2007 May;26(5):685-90.
Radziejewska I, Borzym-Kluczyk M, Namiot Z et al. Glycosylation of mucins present In gastrin juice: the effect of Helicobacter pylori eradication treatment. Clin Exp Med. 2011, 11:81-88
Disclosure of Interest
None declared
DOI
10.1136/annrheumdis-2014-eular.2100
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