| 1. |
- Assarsson, Malin, et al.
(författare)
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Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin
- 2019
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Ingår i: Archives of Dermatological Research. - : SPRINGER. - 0340-3696 .- 1432-069X. ; 311:7, s. 535-544
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Tidskriftsartikel (refereegranskat)abstract
- WNT/beta-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohns disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.
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| 2. |
- 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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| 3. |
- Dimberg, Jan, et al.
(författare)
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Common 4977 bp deletion and novel alterations in mitochondrial DNA in Vietnamese patients with breast cancer
- 2015
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 4, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and ageing. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in breast cancer (BC). The aim of this study was to investigate the frequency of mtDNA 4977 bp deletion in BC tissue and its association with clinical factors.We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 106 Vietnamese patients with BC by sequencing PCR products.The mtDNA 4977 bp deletion was significantly more frequent in normal tissue in comparison with paired cancer tissue. Moreover, the incidence of the 4977 bp deletion in BC tissue was significantly higher in patients with estrogen receptor (ER) positive as compared with ER negative BC tissue. Preliminary results showed, in cancerous tissue, a significantly higher incidence of novel deletions in the group of patients with lymph node metastasis in comparison with the patients with no lymph node metastasis.We have found 4977 bp deletion in mtDNA to be a common event in BC and with special reference to ER positive BC. In addition, the novel deletions were shown to be related to lymph node metastasis. Our finding may provide complementary information in prediction of clinical outcome including metastasis, recurrence and survival of patients with BC.
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| 4. |
- 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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| 5. |
- Dimberg, Jan, et al.
(författare)
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Gene polymorphism in DNA repair genes XRCC1 and XRCC6 and association with colorectal cancer in Swedish patients
- 2016
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY-BLACKWELL. - 0903-4641 .- 1600-0463. ; 124:9, s. 736-740
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Tidskriftsartikel (refereegranskat)abstract
- The DNA repair genes XRCC1 and XRCC6 have been proposed to participate in the pathological process of cancer by modulating the DNA repair capacity. This study evaluated the susceptibility of the single-nucleotide polymorphisms (SNPs) XRCC1 (rs25487, G amp;gt; A) and XRCC6 (rs2267437, C amp;gt; G) to colorectal cancer (CRC) and their association with clinical parameters in Swedish patients with CRC. Using the TaqMan system, these SNPs were screened in 452 patients and 464 controls. No significant difference in genotype distribution was found between the patients and controls, or any significant association with cancer-specific or disease-free survival in patients. However, we showed that the carriers of allele A in XRCC1 (rs25487, G amp;gt; A) were connected with a higher risk of disseminated CRC (Odds Ratio = 1.64; 95% Confidence Interval = 1.12-2.41, p = 0.012).
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| 6. |
- Dimberg, Jan, et al.
(författare)
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Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitis
- 2020
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 35, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The pathogenesis of appendicitis is not well understood. Environmental factors are regarded most important, but epidemiologic findings suggest a role of inflammatory and genetic mechanisms. This study determines the association of single nucleotide polymorphisms (SNPs) of inflammatory genes with appendicitis.METHODS: As part of a larger prospective study on the diagnostic value of inflammatory variables in appendicitis, the genotype frequency of 28 polymorphisms in 26 inflammatory response genes from the appendicitis and control patients was analyzed in blood samples from 343 patients, 100 with appendicitis, and 243 with non-specific abdominal pain, using TaqMan SNP genotyping assays.RESULTS: Associations with appendicitis were found for SNPs IL-13 rs1800925 with odds ratio (OR) 6.02 (95% CI 1.52-23.78) for T/T versus C/C + T/T, for IL-17 rs2275913 with OR 2.38 (CI 1.24-4.57) for A/A vs G/G + GA, for CCL22 rs223888 with OR 0.12 (0.02-0.90), and for A/A vs G/G + GA. Signs of effect modification of age for the association with appendicitis were found for IL-13 rs1800925 and CTLA4 rs3087243. Stratified analysis showed difference in association with severity of disease for IL-17 rs2275913 and CD44 rs187115.CONCLUSIONS: The association of gene variants on risk of appendicitis and its severity suggest an etiologic role of genetically regulated inflammatory response. This may have implications for understanding the prognosis of untreated appendicitis as a possible self-limiting disorder and for understanding the inverse association of appendicitis with ulcerative colitis.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- Duvetorp, Albert, et al.
(författare)
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Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin
- 2017
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Ingår i: Experimental dermatology. - : WILEY. - 0906-6705 .- 1600-0625. ; 26:11, s. 1033-1038
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Tidskriftsartikel (refereegranskat)abstract
- Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.
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