| 21. |
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| 22. |
- Dimberg, Jan, et al.
(författare)
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Novel and Differential Accumulation of Mitochondrial DNA Deletions in Swedish and Vietnamese Patients with Colorectal Cancer
- 2014
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:1, s. 147-152
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and aging. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in colorectal cancer (CRC). In the present study, we aimed to evaluate the frequency of mtDNA 4977 bp deletion in CRC tissues and its association with clinical factors. Patients and Methods: We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 105 Swedish and 88 Vietnamese patients with CRC using polymerase chain reaction (PCR) assays. Results: The mtDNA 4977 bp deletion was shown to be significantly more frequent in normal tissues in comparison with paired cancer tissues in both Swedish and Vietnamese patients. The 4977 bp common deletion was significantly more frequent in cancer tissues of the Vietnamese patients compared to the Swedish patients, and in Vietnamese cancer tissues, the 4977 bp deletion was significantly over represented in those with localized disease compared to those with disseminated disease. Moreover, we detected nine novel mtDNA deletions and found a significantly higher rate of these in CRC tissues in Swedish in comparison to Vietnamese patients. Conclusion: The mtDNA 4977 bp deletion seems to have an impact on the clinical outcome of CRC in Vietnamese patients, that the Swedish patients accumulate more of the detected novel deletions in CRC tissue compared to Vietnamese patients probably indicates divergent mechanisms in colorectal carcinogenesis.
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| 23. |
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| 24. |
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| 25. |
- Dimberg, Jan, et al.
(författare)
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Polymorphism of the p38 beta gene in patients with colorectal cancer
- 2014
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8, s. 1093-1095
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Tidskriftsartikel (refereegranskat)abstract
- The p38 mitogen‑activated protein kinase (MAPK) signaling pathways have been proposed to participate in the pathological process of cancer by affecting inflammation, proliferation, metastasis and cell survival. A single nucleotide polymorphism (SNP; rs2235356, ‑1628A→G) in the promoter region of the p38β gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a Chinese population. The present study evaluated the susceptibility of patients possessing this SNP to CRC, in addition to determining its association with clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping assay, this SNP was screened in 389 patients with CRC and 517 control subjects. No significant difference in the genotype distribution or in the allelic frequencies was identified between the two groups nor was any association identified with the clinical parameters. These findings indicate that the ‑1628A→G polymorphism of the p38β gene is not significantly associated with a susceptibility to CRC in a Swedish population.
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| 26. |
- 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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| 27. |
- Dimberg, Jan, et al.
(författare)
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Protein expression and gene polymorphism of CXCL10 in patients with colorectal cancer
- 2014
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Ingår i: Biomedical Reports. - : Spandidos Publications. - 2049-9442 .- 2049-9434. ; 2:3, s. 340-343
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Tidskriftsartikel (refereegranskat)abstract
- Chemokines (chemotactic cytokines) promote leukocyte attraction to sites of inflammation and cancer. Certain chemokines promote and regulate neoplastic progression, including metastasis and angiogenesis. One such chemokine, CXCL10, was found to be expressed in colorectal cancer (CRC) tissue. To gain insight into the prognostic significance of CXCL10, we investigated whether the levels of this chemokine were altered in the colorectal tissue or plasma of CRC patients. Using Luminex technology for protein analyses, we observed a significantly higher CXCL10 protein level in cancer tissue compared to that in paired normal tissue. Moreover, significantly higher plasma levels of CXCL10 were detected in patients compared to those in control subjects and the plasma levels of CXCL10 in disseminated disease were found to be significantly higher compared to those in localized disease. The single‑nucleotide polymorphism rs8878, which has been described in exon 4 in the 3'‑untranslated region of the CXCL10 gene, was investigated using a TaqMan system. There were significant differences in genotype distribution and allelic frequencies between CRC patients and control subjects. In conclusion, altered CXCL10 protein concentrations in CRC tissues or plasma and the rs8878 genotype variant of CXCL10 may contribute to the prediction of clinical outcome.
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| 28. |
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| 29. |
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| 30. |
- Dimberg, Jan
(författare)
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Studies on expression and regulation of phospholipase A2 and cyclooxygenase 2 in gastrointestinal tissues with special reference to colorectal cancer
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The phospholipases A2 (PLA2s) are phospholipid hydrolyzing enzymes that in mammalian cells exist in several different isoform including cytosolic PLA2 (cPLA2), group I PLA2 (PLA2-I) and group II PLA2 (PLA2-ll). PLA2 is involved in production of inflammatory mediators, membrane remodelling, digestive functions and stimulation of prolifemtion. In addition. PLA2 supplies cyclooxygenase COX-1 and COX-2 with arachidonic acid for production of eicosanoids.Increased COX-2 expression and high concentrations of prostaglandins have been found in human colorectal adenocarcinomas and in rat colonic twnours. Studies implicate that there is a link between the tumourigenic effect of the tumour suppressor gene adenomatous polyposis coli (APC) and COX-2 up-regulation in mouse intestinal neoplasms. Mutations of the human APC gene are frequent in both sporadic and familial colorectal cancer and result in activation of p-catenin!T cell factor-4 (Tcf-4) mediated transcription of target genes which may contribute to colorectal tumourigenesis.The ontogenic development of rat gastrointestinal PLA2-I and PLA2-II and the influence of the exogenous glucocorticoid cortisone acetate were studied. The ontogeny of rat glandular stomach PLA2-I and PLA2-II gene expression is similar and seems to follow the general postnatal development of the gastrointestinal tract PLA2-II gene expression is different in the glandular stomach compared to ileum and forestomach during the neonatal period. Administration of the cortisone acetate, during the neonatal period, induced PLA2-I and PLA2-II gene expression in glandular stomach and ileum, respectively, au effect that may be related to maturation of the gastrointestinal tract.Gene expression of PLA2-II, cPLA2 and COX-2, protein levels of COX-2 and mutational analysis of APC were investigated in human colorectal tumours. COX-2 was dramatically up-regulated in tumours located in rectum and associated with the presence of APC mutations. Tcf-4 consensus sequences found in the COX-2 promoter were activated but APC/P-catenin/fcf-4 pathway may partly be involved in transcriptional regulation of the COX-2 gene. Neither induction of PLA2-II nor correlation in gene expression between cPLA2 and COX-2 were observed. 'These observations imply that other enzymes than PLA2 contribute to generate arachidonic acid for COX-2 mediated eicosanoid metabolism aud that PLA2-II seems to play a minor or no role in hllltlan colorectal cancer.
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