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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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- Egesten, Arne, et al.
(författare)
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The proinflammatory CXC-chemokines GRO-α/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids
- 2007
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Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 22:12, s. 1421-1427
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Tidskriftsartikel (refereegranskat)abstract
- Background Ulcerative colitis is characterized by relapsing mucosal inflammation where the lesions include tissue-damaging granulocytes. In addition, T cells and natural killer (NK) cells play important pathophysiologic roles. Chemokines are a large family of peptides that play key roles in the regulation of inflammation. The CXC-chemokines, growth-related oncogene (GRO)-α/CXCL1 and interleukin (IL)-8/CXCL8, both recruit neutrophils and possess mitogenic properties, whereas the interferon-dependent CXC-chemokines monokine induced by gamma-interferon (MIG)/CXCL9, interferon-γ inducible protein of 10 kD/CXCL10, and IFN-inducible T cell alpha chemoattractant/CXCL11 recruit and activate T cells and NK cells. Materials and methods The expression of CXC-chemokines was studied in eight controls and in 11 patients suffering from ulcerative colitis in the distal part of the colon, before and during topical treatment with corticosteroids. Perfusates (obtained before, after 7 days, and after 28 days of treatment) and pinch biopsies (obtained before and after 28 days of treatment) were collected by colonoscopy. The rectal release of GRO-α and MIG was determined by enzyme-linked immunosorbent assay (ELISA), and tissue expression of the chemokines was detected in colonic tissue by immunohistochemistry. Results In perfusates, high levels of GRO-α, IL-8, and MIG were detected compared with controls (p = 0.02, 0.005, and p = 0.03, respectively). During treatment with corticosteroids, both GRO-α and MIG decreased. In clinical nonresponders, characterized by sustained inflammation, the levels of GRO-α and MIG remained elevated. Both epithelial cells and granulocytes, present in the submucosa, expressed GRO-α and MIG as detected by immunohistochemistry. Conclusions CXC-chemokines are likely to be important in the pathophysiology of ulcerative colitis and may become targets for novel treatment strategies. In addition, GRO-α may serve as a marker of disease activity.
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- Lampinen, Maria, 1965-, et al.
(författare)
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Accumulation, activation and survival of neutrophils in ulcerative colitis : regulation by locally produced factors in the colon and impact of steroid treatment
- 2008
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Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 23:10, s. 939-946
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Neutrophil granulocytes infiltrate the intestinal mucosa in active ulcerative colitis (UC), and may contribute to tissue damage and inflammation. The aim of this investigation was to study the importance of locally produced factors and the impact of steroid treatment on neutrophil functions in UC. PATIENTS AND METHODS: Intestinal perfusion fluids from 11 patients with active distal UC before and after seven and 28 days of treatment with prednisolone and from seven control patients were used in the study. Neutrophil migration towards perfusion fluid was measured in a microchemotaxis chamber. The effect of perfusion fluids on neutrophil activation was assessed as the surface expression of CD66b by flow cytometry. Neutrophil survival was evaluated by staining with propidium iodide, annexin V, and fluorescein di-acetate. We also assessed the viability of freshly isolated tissue neutrophils from rectal biopsy samples. RESULTS: Perfusion fluids from untreated patients caused increased migration, activation, and survival of neutrophils. Perfusion fluids collected after treatment had no effect on neutrophil migration, but some of the activation and anti-apoptotic effects remained after 7 days. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited the anti-apoptotic effect of perfusion fluids. Rectal tissue neutrophils from patients with active proctitis had increased viability compared to patients with inactive proctitis and control subjects. CONCLUSIONS: These data show that mediators in the colon of patients with active UC stimulate the migration, activation, and survival of neutrophils. The activities were partly neutralized by topical steroid treatment. We also identified GM-CSF as an anti-apoptotic factor for neutrophils in inflamed colon.
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- Moparthi, Satish Babu, et al.
(författare)
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pRb2/p130 protein in relation to clinicopathological and biological variables in rectal cancers with a clinical trial of preoperative radiotherapy
- 2009
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Ingår i: INTERNATIONAL JOURNAL OF COLORECTAL DISEASE. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 24:11, s. 1303-1310
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Tidskriftsartikel (refereegranskat)abstract
- pRb2/p130 plays a key role in cell proliferation and is a considerable progress about expression patterns of pRb2/p130 in number of malignancies. However, pRb2/p130 expression and its significance in rectal cancer remain unknown. The purpose of the present study was to investigate pRb2/p130 protein patterns and their correlations with clinicopathological and biological factors in rectal cancer patients with or without preoperative radiotherapy (RT). pRb2/p130 protein was examined by immunohistochemistry in 130 primary tumors, along with the corresponding 61 distant normal mucosa specimens, 85 adjacent normal mucosa specimens, 34 lymph node metastases, and 93 primary tumor biopsies from rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. The pRb2/p130 protein was mainly localized in the cytoplasm of tumor cells. In nonradiated cases, the lack of pRb2/p130 was related to advanced tumor-node-metastases stage, poorer differentiation, weak fibrosis, less inflammatory infiltration, higher Ki-67, and positive Cox-2 expression (p andlt; 0.05). In radiated cases, the lack of pRb2/p130 was related to nonstaining of Cox-2 and survivin (p andlt; 0.05). pRb2/p130 protein in primary tumors tended to be increased after RT (27% vs 16%, p = 0.07). pRb2/p130 was mainly localized in the cytoplasm rather than in the nucleus in rectal cancer. After RT, pRb2/p130 protein seems to be increased in primary tumors, and further the relationship of the pRb2/p130 with the clinicopathological and biological variables changed compared to the nonradiated cases. However, we did not find that the pRb2/p130 was directly related to RT, tumor recurrence, and patients survival.
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