| 1. |
- Dimberg, Jan, et al.
(författare)
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Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients
- 2013
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- The tumour suppressor gene adenomatous polyposis coli (APC) is a key component that drives colorectal carcinogenesis. The reported DNA methylation in the promoter of APC varies greatly among studies of colorectal cancer (CRC) in different populations. Insulin-like growth factor binding protein 7 (IGFBP7), also known as IGFBP‑related protein 1 (IGFBP-rP1), is expressed in various tissue types, including the lung, brain, prostate and gastrointestinal tract, and has been suggested to play a tumour suppressor role against colorectal carcinogenesis. Studies have indicated that IGFBP7 is inactivated by DNA methylation in human colon, lung and breast cancer. In the present study, we used the methylation‑specific polymerase chain reaction to study the methylation status of the APC and IGFBP7 gene promoters in cancerous and paired normal tissue to evaluate its impact on clinical factors and association with ethnicity, represented by Swedish and Vietnamese CRC patients. We also investigated the distribution of CpG islands and the CpG dinucleotide density of each CpG island in the regions which were the subject of our investigation. Overall, normal tissue from Swedish patients exhibited a significantly higher frequency of IGFBP7 gene methylation in comparison with that of Vietnamese patients. Moreover, a significantly higher number of cancer tissues from Vietnamese individuals showed higher levels of methylation versus the paired normal tissue compared with that of Swedish patients. When we studied the methylation in cancer compared with the matched normal tissue in individuals, we found that a significantly higher number of Vietnamese patients had a higher degree of IGFBP7 gene methylation in cancer versus matched normal tissue in comparison with Swedish patients. Taken together, our results suggest that the methylation of the APC and IGFBP7 gene promoter region in cancerous tissue, in combination with the predominance of methylation in normal tissue, may serve as a prognostic factor in CRC patients.
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| 2. |
- Dimberg, Jan, et al.
(författare)
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Detection of Cytomegalovirus DNA in Colorectal Tissue from Swedish and Vietnamese Patients with Colorectal Cancer
- 2013
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:11, s. 4947-4950
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human cytomegalovirus (HCMV) has been implicated as a factor, which might be associated with colorectal cancer (CRC) progression. Data from studies with HCMV-infected tumour cell lines have highlighted an oncomodulatory potential of HCMV. In the present study, we aimed to evaluate the prevalence of HCMV DNA in CRC tissue compared to matched normal tissue, and its association with clinical factors.Patients and Methods: We used quantitative real-time polymerase chain reaction assay to detect HCMV DNA in 202 cancerous and paired normal tissue from Swedish (n=119) and Vietnamese (n=83) CRC patients.Results: Overall, the HCMV DNA rate was significantly higher in cancerous in relation to paired normal tissue. Furthermore, a significantly higher frequency (39.8%) of HCMV DNA was observed in cancer tissues from the Vietnamese patients compared to the Swedish patients (15.1%). The prevalence of HCMV DNA in CRC tissue of 50% of those with disseminated disease tended to be higher compared to those with localized disease, with a prevalence of 33.3% in Vietnamese patients.Conclusion: Our observations indicate that the prevalence of HCMV DNA differs significantly between cancer and matched normal tissues. Thus, these data support a possible role of CMV in CRC. Moreover, we noted differences between Swedish and Vietnamese patients, indicating a role of ethnicity.
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| 3. |
- Dimberg, Jan, et al.
(författare)
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DNA promoter methylation status and protein expression of interleukin-8 in human colorectal adenocarcinomas
- 2012
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 27:6, s. 709-714
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Tidskriftsartikel (refereegranskat)abstract
- Background Interleukin-8 (IL-8) also referred to as CXCL8, a member of the CXC chemokine family that attracts neutrophils and other leukocytes, has been associated with cancer. Angiogenesis is a prime regulator of tumour expansion and data support that IL-8 is a potent angiogenic factor. Epigenomic instability has been postulated to play a role for the development of multiple neoplasias including colorectal cancer (CRC). DNA methylation of cytosine residues in CpG dinucleotides leads to transcriptional silencing of associated genes.Method In this study, we comparatively analysed the protein expression of IL-8 in plasma, tumour and paired normal tissue and methylation status of the IL-8 gene to evaluate its impact on CRC.Results Collectively, by using Luminex technology, we noted a significantly higher IL-8 level in cancer tissue compared to paired normal tissue and that CRC patients exhibit significantly higher plasma levels than healthy controls. Analysed by methylation-specific polymerase chain reaction, we detected IL-8 hypomethylation in 64% of the cancerous tissue cases but no hypomethylation was found in paired normal tissue. We noted that the CRC patients with IL-8 hypomethylation revealed a significant higher level of IL-8 protein in cancerous tissue, which tended to be associated with distant metastasis. We also observed that patients with distant metastasis showed a significantly higher plasma level of IL-8 in relation to patients without distant metastasis.Conclusion Our results suggest that the predominance of high plasma levels of IL-8 in patients with distant metastasis in combination with the hypomethylation of the IL-8 promoter region might be a useful marker of the disease advancement.
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| 4. |
- Dimberg, Jan, et al.
(författare)
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Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas
- 2011
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 2:3, s. 413-418
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Tidskriftsartikel (refereegranskat)abstract
- Proteases facilitate a number of steps in cancer progression. The serine protease inhibitors (serpins) are a protein superfamily with inhibitory activity against proteases. One of these proteases, serpinA3, appears to have a multifaceted role and is associated with inflammatory reactions, Alzheimer's disease, malignant melanoma and gastric cancer. To gain insight into the potential effect of serpinA3 on colorectal cancer (CRC) we determined whether serpinA3 is altered in colorectal tissue or plasma in CRC patients. Collectively, by using ELISA we noted a significantly lower serpinA3 level in cancer tissue compared to paired normal tissue. Moreover, the tumour serpinA3 level tended to be higher in disseminated disease as compared to localised disease. No significant difference in the plasma levels of serpinA3 was noted in the patients when compared to the controls. However, plasma serpinA3 and C-reactive protein (marker of inflammation) in the CRC patients and controls were significantly positively correlated. To confirm and detect localization of serpinA3 expression, immunohistochemistry was performed. Immunohistochemistry showed heterogeneous immunoreactivity in epithelial cells in the cancer and normal tissue and extracellular staining within bands of stroma as well as in some stromal cells. A Taq Man system was used to investigate a single nucleotide polymorphism (rs4934) in the serpinA3 signal sequence gene with supposed effect on serpinA3 secretion and expression. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions, nor were associations noted between clinical characteristics and serpinA3 levels. In conclusion, an altered serpinA3 concentration in CRC tissue may be a potential biomarker in CRC progression. SerpinA3 concentrations in plasma appear to be correlated with systemic inflammation, but do not appear to be specific to CRC patients. Further studies are warranted to improve our understanding of the role of serpinA3 in CRC.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Song Van, Nguyen, et al.
(författare)
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Gene Polymorphism of Matrix Metalloproteinase-12 and-13 and Association with Colorectal Cancer in Swedish Patients
- 2013
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33, s. 3247-3250
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been widely reported that matrix metalloproteinases (MMPs) have fundamental roles in pathological processes in cancer through degradation of basal membranes and extracellular matrix. For MMP12 and MMP13, a functional single nucleotide polymorphism (SNP) has been detected -82A -> G (rs2276109) and -77A -> G (rs2252070), respectively. These SNPs are suggested to have an influence on different diseases. The present study evaluated the association between these SNPs in patients with colorectal cancer (CRC) patients and healthy controls. Patients and Methods: Using the TaqMan system, these SNPs were screened in 385 patients with CRC and 619 controls. Results: No significant difference in genotype distribution or in allelic frequencies was found between the two groups. However, we showed that the AA MMP-12 genotype is connected with a higher risk of disseminated CRC (Odds Ratio=1.77; 95% Confidence Interval=1.11-2.81, p=0.018). Conclusion: The results of this study suggest that the -82A -> G (rs2276109) polymorphism of the MMP12 gene reflects clinical outcome of patients with CRC.
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| 9. |
- Wågsäter, Dick, et al.
(författare)
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Pigment Epithelium-Derived Factor Expression in Colorectal Cancer Patients
- 2010
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Ingår i: Cancer Investigation. - : Informa Healthcare. - 0735-7907 .- 1532-4192. ; 28:8, s. 872-877
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Tidskriftsartikel (refereegranskat)abstract
- Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis and has been proposed to be a tumor suppressor in a variety of tumors. Limited reports exist of PEDF in colorectal cancer (CRC). We noted a 55% lower plasma level (p less than .001) of PEDF in the CRC patient group (1.6 mu g/mL) than in of a healthy control group (3.6 mu g/mL). A single nucleotide polymorphism (rs1136287, Tgreater thanC) was screened. In the control group, the CC genotype showed 30% lower PEDF plasma levels compared with the TT genotype (p less than .01), whereas the CRC patients failed to show any association regarding these genotypes.
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