Role of periostin in esophageal, gastric and colon cancer.

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.

Profile of exoglycosidases in synovial cell cultures derived from human synovial membrane.

OBJECTIVE: Determining the activity of lysosomal exoglycosidases in tissue cultures of synoviocytes derived from the knee joints of patients with injured anterior cruciate ligaments (ACL), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA). METHODS: The following exoglycosidases in cultured synoviocytes were analyzed with p-nitrophenyl derivatives of appropriate sugars as substrates: hexosaminidase (HEX) and its isoenzyme A (HEX-A), beta-glucuronidase (GluA), beta-galactosidase (GAL), alpha-mannosidase (MAN), and alpha-fucosidase (FUC). RESULTS: In our cell cultures, fibroblast-like synovial cells (FLS) dominated. In the group of patients with ACL-injuries, and in the groups of patients with JIA and RA, the activity of the investigated exoglycosidases was significantly higher in the intra- rather than in the extracellular compartment. Hexosaminidase was the predominant exoglycosidase. Stimulation of synoviocytes by IL-1beta in cell cultures significantly increased the activity of HEX, HEX-A, and GluA in both compartments, as well as of GAL, MAN, and FUC in the intracellular compartment. Stimulation by IL-1beta rheumatoidal synoviocytes increased by 128-201% the activity of HEX and HEX A in intracellular compartments and 33-72% in extracellular compartment. CONCLUSIONS: The profile of lysosomal exoglycosidases in a cell culture of human synoviocytes is similar, but not identical, to those in the knee joint. Hexosaminidase is the dominant glycosidase in cultured unstimulated and IL-1beta-stimulated human synoviocytes. The HEX inhibitors may be new drugs for the treatment of inflamed knee joints.

[Concentration of IL-10, IL-13 and IFN-gamma cytokines in supernatants of microcultured CD4+ and NK cells in patients with non-allergic bronchial asthma]. / Stezenie cytokin IL-10, IL-13 i IFN-gamma w nadsaczach hodowli komórek CD4+ i NK u chorych na niealergiczna astme oskrzelowa.

UNLABELLED: THE AIM OF THIS STUDY was the evaluation of T lymphocytes and NK function in patients with non-allergic asthma. MATERIAL AND METHODS: Three groups: patients with non-allergic asthma (n = 30), patients with non-allergic asthma with concomitant recurrent infections (n = 24) and group of healthy adult volunteers (n = 20) were examined. CD4+ and NK cells were isolated from peripheral blood by magnetic separation method. Cells were cultured and level of cytokine IL-10, IL-13, IFN-gamma in medium were measured. RESULTS: In patients with non-allergic asthma with recurrent infections mean value of IFN-gamma in medium from IL-15 + IL-12 stimulated NK cells was significantly lower compared with control group (p < 0.01). Mean value of IL-10 and IL-13 in medium from Con A stimulated CD4+ cells in patients with non-allergic asthma with recurrent infections were significantly higher than in control group (p < 0.05). CONCLUSIONS: Multitudes of cell and humoral factors interactions overlap dysfunction of immunological system in patients with non-allergic asthma. It causes higher susceptibility to infections factors especially viruses. Viruses give feedback for escalation of infection and worsening of clinical course of disease. Knowing mechanisms of inflammation intensification would let us specific prophylaxis use (specific antinflammatory or immunomodulatory drugs).

Levels of VE-cadherin increase independently of VEGF in preoperative sera of patients with colorectal cancer.

AIMS AND BACKGROUND: Vascular endothelial cadherin (VE-cadherin) preserves the tightness of the mature vascular network as a component of endothelial adherens junctions. Vascular endothelial growth factor (VEGF) makes VE-cadherin dissociate from complexes with beta-catenin, so that endothelial cells can loosely proliferate and migrate. We searched for relationships between VEGF and VE-cadherin levels in preoperative sera of patients with colorectal cancer (CRC). We also compared VE-cadherin levels of control and preoperative CRC sera in relation to clinicopathological features. METHODS: We measured with an ELISA kit the serum levels of the proteins in preoperative samples from 125 CRC patients and in samples from 16 healthy volunteers. RESULTS: Serum VE-cadherin was about fourfold higher in CRC patients than in controls (P < 0.00001), with similar results being found in subgroups with different clinicopathological features versus controls. VE-cadherin was not correlated with VEGF in the entire group of CRC patients nor in the subgroups of node-positive and node-negative patients, different grades of histological differentiation (G2 or G3), extent of tumor growth (pT1+pT2 or pT3+pT4), histopathological type (adenocarcinoma or mucinous carcinoma), sex, age, and tumor site (colon or rectum). However, the serum levels of VE-cadherin and VEGF in CRC patients, which were higher than the mean values of controls, tended towards a negative correlation in node-positive patients (P = 0.078, r = -0.279). CONCLUSIONS: VEGF and VE-cadherin seem to be independent markers of angiogenesis in CRC with no significant correlation between their serum levels.

[CD28 and CTLA-4 costimulatory molecules expression on T lymphocytes and NK cells in nonallergic bronchial asthma]. / Ekspresja czasteczek kostymulujacych CD28 i CTLA-4 na limfocytach T i komórkach NK u chorych na niealergicznq astme oskrzelowa.

UNLABELLED: The aim of the study was to assess the role of costimulatory molecules in pathogenesis of nonallergic bronchial asthma. MATERIAL: The studied group consisted of 30 patients with nonallergic asthma, 24 with nonallergic asthma and recurrent respiratory tract infections and 20 healthy controls. RESULTS: In nonstimulated and lipopolysaccharide (LPS) stimulated cultures of control group the mean value of CD16+ + 56+ CD28+ subpopulation were significantly decreased compared to values in both types of asthma. Similar dependence was observed in cultures of asthmatic patients with infection and healthy person, stimulated with IL-15 and in CD4+CD28+, CD8 +CD28+ and NKCD28+ cultures from all studied groups, stimulated with LPS plus IL-15. In nonallergic asthma and infection asthma mean values of CD4 +CD152+ and CD16+ +CD56 +CD152+ from nonstimulated and IL-15 stimulated cultures were significantly increased compared to analogical values in control group. CONCLUSION: The results of our studies suggest that in nonallergic asthma the disturbed expression of costimulatory molecules may play an important role in pathomechanism of disease.

[Analysis of intracellular cytokines IFN-gamma and IL-4 in peripheral blood T cells in children with bronchospastic reaction]. / Ocena wewnatrzcytoplazmatycznych receptorów cytokinowych IFN-gamma i IL-4 u dzieci z odczynami bronchospastycznymi.

UNLABELLED: In the epidemiological study there was suggested that respiratory tract infections--were a strong risk factors for the beginning and development of bronchial asthma. The aim of the study was the evaluation of intracellular cytokine IL-4 and IFN-gamma on peripheral blood T subsets in children with atopic asthma (AA) and recurrent respiratory tract infection with bronchospasm (RRTI). METHOD: Peripheral blood T cells were stained with fluorescence-labelled antibodies specific for intracellular cytokines IFN-gamma and IL-4 and cell surface markers CD3, CD4 and CD8, and were subjected to flow-cytometric analysis. RESULTS: Comparing peripheral blood lymphocytes of atopic asthma patients with those of recurrent infections we found significantly more cells positive for IL-4 in asthma patients than in recurrent infection patients, both in the CD3+ subsets (p<0.03) and CD4+ subset (p<0.01). We have also found that percentage of CD4+ was significantly lower (p<0.007) and percentage of CD8+ cells was significantly higher (p<0.05) in RRTI group comparing to atopic asthma patients. In AA group there was a significant increase intracellular expression of IL-4 among the CD3+ (p<0.03) and CD4+ (p<0.01) subsets and no significant differences among CD8+ subset. In AA group there was a significant decrease ratio of IFN-gamma/IL-4 among all of the evaluated subsets. CONCLUSION: Basing oneself on these results we conclude that markers of atopy are: increased intracellular expression of IL-4 among CD4+ cells and decreased IFN-gamma.

CD80 and CD86 expression on LPS-stimulated monocytes and the effect of CD80 and CD86 blockade on IL-4 and IFN-gamma production in nonatopic bronchial asthma.

CD80 and CD86 seem to play an important role in the allergen-induced secretion of interleukin (IL)-5 and IL-13. Up to now, the expressions of CD80 (B7.1) and CD86 (B7.2) on monocytes and the kinetics of the expression of these molecules on lipopolysaccharide-stimulated monocytes in nonatopic asthma have not been defined. Using monoclonal antibodies, we have compared the expressions of CD80 (B7.1) and CD86 (B7.2) on the monocytes of healthy persons and nonatopic asthmatic patients. We have also assessed the effect of CD80 and CD86 inactivation on IL-4 and interferon (IFN)-gamma production in nonatopic asthmatics and healthy subjects. We found that a low expression of CD80 (1.64 +/- 0.65 vs. 3.53 +/- 1.43%) and a moderate expression of CD86 (41.25 +/- 13.4 vs. 49.46 +/- 11.49%) on the studied monocytes were characteristic for asthma. In nonatopic asthma patients inactivation of CD80 or CD86 blockade significantly reduced IFN-gamma production by T lymphocytes (p < 0.02; p < 0.03). In both the studied groups, anti-CD80 antibodies did not diminish T lymphocyte production of IL-4. However, anti-CD86 antibodies significantly (p < 0.04) reduced the IL-4 concentration in culture supernatants. Our results confirm that both the CD80 and CD86 molecules play an important role in the maintenance and amplification of the inflammatory process. It suggests that in the inflammatory process that occurs in nonatopic bronchial asthma, Th1 as well as Th2 lymphocytes are equally important.

[The role of monocytes stimulated with LPS on CD69 expression in T lymphocytes of patients with non-atopic asthma]. / Wplyw monocytów stymulowanych LPS na ekspresje CD69 na limfocytach T u chorych na astme nieatopowa.

CD69 molecule is the earliest antigen of T lymphocytes activation. We have studied the ex-pression of CD69 on LPS-stimulated T cells in nonatopic bronchial asthma. We have found that CD69 expression on freshly isolated peripheral blood T cells in nonatopic asthma patients was increased compare to control group (4.74 +/- 1.55/3.05 +/- 1.31) and the difference was statistically significant (p < 0.01). Monocytes added to nonstimulated T cell cultures increased 3-4 times the expression of CD69 and about 10-times in LPS-stimulated T lymphocytes.

[The effect of inactivation of co-stimulated particles B7.1 (CD80), B7.2 (CD86) on T lymphocyte activity]. / Wplyw inaktywacji czastek kostymulujacych B7.1 (CD80), B7.2 (CD86) na aktywnosc limfocytów T.

We have studied the effect of CD80 (B7.1) and CD86 (B7.2) costimulatory molecules inactivation on IL-4 and IFN-gamma production by T lymphocytes. T cells were received from nonatopic asthmatic and healthy subjects. We have added anti-CD80 or anti-CD86 monoclonal antibodies to the monocyte/lymphocyte (1:5) cultures. In nonatopic asthma patients compare to control group inactivation of CD80 significantly reduced IFN-gamma production by T lymphocytes (2172/2368 pg/ml; p < 0.02). Blockade of CD86 decreased IFN-gamma production non-significantly (2858/3317 pg/ml; p < 0.3). In both studied groups anti-CD80 antibodies did not diminish T lymphocyte production of IL-4 (control: 630/725 pg/ml; nonatopic asthma: 718/742 pg/ml). Anti-CD86 antibodies reduced the IL-4 concentration in culture supernatants (630/523 pg/ml; 718/659 pg/ml), but the changes were nonsignificant.

[The effect of monocytes on early activation of lymphocytes T among children with idiopathic uveitis]. / Wplyw monocytów na wczesna aktywacje limfocytów T u dzieci z idiopatycznym zapaleniem blony naczyniowej.

PURPOSE: We have investigated T Lymphocytes ability for CD69 molecule induction in presence and absence of monocytes in idiopathic uveitis. MATERIAL AND METHODS: Twenty-five children with idiopathic uveitis were studied. The control group consisted of 12 healthy children. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinised venous blood, by density gradient centrifugation. CD69 expression was cytometrically assessed on freshly isolated and cultured T lymphocytes. RESULTS: CD69 expression on freshly isolated peripheral blood T lymphocytes was low in both studied groups. LPS-stimulated monocytes added to cultures of T lymphocytes induced increase in CD69 expression but significantly lower in children with idiopathic uveitis compare to healthy children.