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- Dimberg, Jan, et al.
(författare)
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Polymorphisms of Fractalkine receptor CX3CR1 and plasma levels of its ligand CX3CL1 in colorectal cancer patients
- 2007
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 22:10, s. 1195-1200
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS:The chemokine Fractalkine/CX3CL1, which is expressed by epithelial cells within normal colorectal mucosa and in colorectal cancer (CRC), is thought to have a crucial role in colorectal mucosal immunity by recruiting leucocytes via the receptor CX3CR1. The purpose of this study was to investigate two single-nucleotide polymorphisms of the Fractalkine receptor/CX3CR1 gene, V249I and T280M, in CRC to find out whether they occur more often in patients with CRC than in non-CRC individuals. In the search for tumour markers, we also intended to determine whether plasma levels of Fractalkine were correlated with parameters such as Dukes' stage, tumour localisation, gender and age in CRC patients.MATERIALS AND METHODS:Genomic deoxyribonucleic acid from 223 CRC patients and 229 controls was amplified by polymerase chain reaction, and the polymorphisms were detected by the restriction fragment length polymorphism analysis. Fractalkine/CX3CL1 was analysed in plasma from 62 CRC patients and 78 controls using enzyme-linked immunosorbent assay.RESULTS:The variant V249I was significantly different in genotype and allelic distribution between CRC patients and control subjects, P = 0.028 and P = 0.048, respectively. We also found that individuals with the I249 allele in homozygote state were less frequent in the CRC group (3.1%) compared with controls (9.2%; P = 0.008). No significant difference was observed regarding Fractalkine/CX3CL1 levels in plasma between patients and the control group.CONCLUSION:Our results suggest that the lack of the allele I249 of the CX3CR1 gene may play a partial or minor role in CRC and that plasma Fractalkine/CX3CL1 does not seem to be a useful tumour marker that reflects the disease outcome of CRC.
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- Jatta, Ken, et al.
(författare)
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Lipopolysaccharide-induced cytokine and chemokine expression in human carotid lesions
- 2005
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 42:3, s. 266-271
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Tidskriftsartikel (refereegranskat)abstract
- The release of cytokines and chemokines from activated immune-competent cells plays a crucial role in determining the pathology of the atherogenic progress. We investigated the effect of bacterial lipopolysaccharide (LPS) on cytokine/chemokine expression in carotid lesions and normal renal arteries. The lesions or renal arteries were incubated for 6 h at 37 degrees C in serum-free media treated with or without LPS. After LPS treatment, increased protein levels of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and MCP-1 were observed in the culture medium from the lesions measured with cytometric bead array. We were able to detect the induction of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and MCP-1 mRNA in the lesions after stimulation with LPS using real-time PCR. In renal arteries, LPS also induces mRNA expression of all chemokines and cytokines investigated with the exception of IL-6. However, LPS induces significantly higher levels of TNF-alpha, IL-1beta and IL-10 mRNA in lesions compared to renal arteries. The results suggest that infectious agents are capable of enhancing the production of cytokines/chemokines in an already ongoing inflammatory process such as in atherosclerosis, and that low levels of circulating LPS may affect the levels of pro-inflammatory cytokines much more in atherosclerotic vessels than in normal vessels and may contribute to the development of the atherosclerotic lesion.
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- Kolak, Maria, et al.
(författare)
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Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:8, s. 1960-1968
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity.RESEARCH DESIGN AND METHODS: A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 +/- 0.3 vs. 14.4 +/- 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations.RESULTS: Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator-activated receptor-gamma and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group.CONCLUSIONS: Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.
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- Mumtaz, Melad, et al.
(författare)
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Decreased expression of the chemokine CCL21 in human colorectal adenocarcinomas
- 2009
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 21:1, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have revealed participation of chemokines in cancer by regulating leukocyte movement to modify local immunoresponse. The chemokine CCL21 has been identified to play a pivotal role in homing and localization of immune cells to lymphoid tissue and into organ of non-lymphoid origin. In the cancer biology CCL21 seems to have multifaceted roles. CCL21 attracts CCR7 bearing cells especially T and dendritic cells but also various cancer cells. Besides the antitumour role as leukocyte recruiting, CCL21 has been shown to facilitate dendritic cell functions and to exert an angiostatic effect. To gain insight into the possible influence of CCL21 oil colorectal cancer (CRC) we determined whether the CCL21 is altered in CRC tissue. Collectively, by using ELISA we noted a significant lower CCL21 level in cancer tissue compared with paired normal tissue. Patients with a tumour localized in the rectum revealed significantly lower level of CCL21 than patients with a tumour localized in the colon both compared with paired normal tissue. We used immunohistochemistry and found heterogeneous immunoreactivity predominantly within areas of stromal cells mainly in macrophages. We also used a TaqMan system to investigate two single-nucleotide polymorphisms rs 11574915 and rs 2812377 with Supposed effect on CRC. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions or associations to clinical characteristics or CCL21 tissue levels. Our study implied that lower level of CCL21 in CRC tissue supports the idea that cancer is related to immunodeficiency probably depending on regulatory factors produced by tumour cells and that the different levels of CCL21 in rectum and colon may reflect divergent mechanisms in colorectal carcinogenesis. Further studies are needed to clarify whether the CCL21 level has an impact on CRC progression and survival rate.
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- Mälarstig, Anders, et al.
(författare)
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Tumour-derived adhesion factor in colorectal cancer
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2:6, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- Tumour-derived adhesion factor (TAF) has been shown to be associated with breast, prostate and colorectal cancer (CRC), acting as tumour suppressor or tumour promoter by mechanisms not as yet understood. Here, we comparatively analyzed the expression profile of TAF in plasma, tumour and paired normal tissue from patients with CRC. In addition, we investigated the relationship between TAF and systemic inflammation, mirrored by the elevation of interleukin-6 (IL-6) and TAF levels in plasma. Levels of TAF and IL-6 were determined by ELISA. Immunohistochemistry was performed to investigate the site of TAF expression. We also used a TaqMan system to investigate a TAF single nucleotide polymorphism (rs2041437) with a potential effect on CRC. TAF protein levels were significantly (Pless than0.001) higher in colorectal tumours than in normal tissue, and were increased in patients with Dukes stages B and C compared to A. Immunohistochemistry revealed heterogeneous TAF expression mainly in the epithelial cells of the cancer and normal tissue. The plasma TAF level was reduced in CRC patients compared with the controls (P=0.002), independent of the inflammatory marker IL-6. Regarding genotype and allelic distributions, significant differences between CRC patients and control subjects or associations between clinical characteristics and TAF levels in tissue and plasma were not observed. In conclusion, altered TAF protein expression in cancer tissue may be a potential biomarker in colorectal carcinogenesis. Further research exploring the regulation of TAF is required to evaluate whether TAF is linked to clinical outcome.
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