| 1. |
- Dimberg, Jan, et al.
(författare)
-
Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitis
- 2020
-
Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 35, s. 277-284
-
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.
|
|
| 2. |
- Dimberg, Jan, et al.
(författare)
-
Polymorphisms of Fractalkine receptor CX3CR1 and plasma levels of its ligand CX3CL1 in colorectal cancer patients
- 2007
-
Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 22:10, s. 1195-1200
-
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.
|
|
| 3. |
- Fiehn, Anne-Marie Kanstrup, et al.
(författare)
-
Distribution of histopathological features along the colon in microscopic colitis
- 2021
-
Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 36, s. 151-159
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. Methods Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. Results In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. Conclusion Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.
|
|
| 4. |
- Lewander, Andreas, et al.
(författare)
-
NF-kappa B p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients
- 2012
-
Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 27:4, s. 447-452
-
Tidskriftsartikel (refereegranskat)abstract
- The NF-kappa B transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-kappa B p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. In this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p < 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). The NF-kappa B p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.
|
|
| 5. |
- Meng, Wen-Jian, et al.
(författare)
-
Correlation of SATB1 overexpression with the progression of human rectal cancer
- 2012
-
Ingår i: International Journal of Colorectal Disease. - : Springer Verlag (Germany). - 0179-1958 .- 1432-1262. ; 27:2, s. 143-150
-
Tidskriftsartikel (refereegranskat)abstract
- To date, the association between special AT-rich sequence-binding protein 1 (SATB1) and colorectal cancer (CRC) has not been reported. This study was aimed at investigating the expression and potential role of SATB1 in human rectal cancers. less thanbrgreater than less thanbrgreater thanNinety-three paired samples of rectal cancer and distant normal rectal tissue were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and the correlations between SATB1 expression and clinicopathological parameters were evaluated. The expression profiles of SATB1 were also investigated in a panel of five human colon carcinoma cell lines. less thanbrgreater than less thanbrgreater thanThe general level of SATB1 mRNA in rectal cancer tissues was statistically significantly higher than that in normal mucosa (P = 0.043). The rate of positive SATB1 protein expression in rectal cancers (44.1%) was significantly higher than that in normal tissues (25.8%) by IHC analysis (P = 0.009). Overexpression of SATB1 mRNA was more predominant in patients with earlier onset of rectal cancer (P = 0.033). SATB1 expression correlated with invasive depth and tumor node metastasis (TNM) stage at both protein and mRNA levels (P andlt; 0.05). Furthermore, SATB1 expression in the poorly metastatic KM12C cells was significantly lower than the highly metastatic KM12SM and KM12L4A cells and higher than the HCT116 and SW480 cells (P = 0.001). These results were further confirmed by Western blotting. less thanbrgreater than less thanbrgreater thanOur results indicate that SATB1 may play an important role in the progression of human rectal cancer, which represents a possible new mechanism underlying CRC.
|
|
| 6. |
- Moparthi, Satish Babu, et al.
(författare)
-
pRb2/p130 protein in relation to clinicopathological and biological variables in rectal cancers with a clinical trial of preoperative radiotherapy
- 2009
-
Ingår i: INTERNATIONAL JOURNAL OF COLORECTAL DISEASE. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 24:11, s. 1303-1310
-
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.
|
|
| 7. |
- Pasternak, Björn, et al.
(författare)
-
Doxycycline-coated sutures improve mechanical strength of intestinal anastomoses.
- 2008
-
Ingår i: International journal of colorectal disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 23:3, s. 271-6
-
Forskningsöversikt (refereegranskat)abstract
- BACKGROUND AND AIMS: After resection and repair of the intestines, tissue degradation leads to weakening of the repair site and risk of postoperative leakage. Matrix metalloproteinases (MMPs) are thought to be responsible for collagenolysis in the direct vicinity of surgical sutures in many tissues. Several experimental studies show that MMP inhibitors administered systemically alleviate postoperative weakening of intestinal anastomoses. We hypothesised that local delivery of MMP inhibitors would achieve a similar effect. MATERIALS AND METHODS: Implementing a novel method for the coating of biomaterials, we coated sutures with a cross-linked fibrinogen film and bound the MMP inhibitor doxycycline into this film. The sutures were then used in a standard rat model for evaluating mechanical properties of colonic anastomoses 3 days after surgery. RESULTS: The breaking strength of the anastomoses on the critical third day after operation was 17% higher with doxycycline-coated sutures compared to controls (P = 0.026). Energy uptake at failure was enhanced by 20% (P = 0.047). CONCLUSION: Drug delivery by means of MMP-inhibitor-coated sutures appears to improve tissue integrity during anastomotic repair and may reduce postoperative complications.
|
|
| 8. |
- Rolny, P., et al.
(författare)
-
Longer term outcome of steroid refractory ulcerative colitis treated with intravenous cyclosporine without subsequent oral cyclosporine maintenance therapy
- 2002
-
Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 17:2, s. 67-69
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Intravenous cyclosporine (Cy) is increasingly used in patients with severe ulcerative colitis who fail to respond to corticosteroids. However, in spite of subsequent oral Cy maintenance therapy almost one-half of the initial responders need colectomy within a year. In light of the drug's limited efficacy and potential toxicity use of oral long-term Cy can be questioned. Patients and methods: Nineteen patients with steroid refractory severe ulcerative colitis were treated intravenously with Cy. Results: Of the 19 patients 14 (76%) achieved remission. Six of the patients (46%) remained in remission for 12-61 months. Eight patients experienced one to four flares during the year after treatment. However, except for one patient who needed another course of intravenous Cy, all responded to corticosteroids. The duration of remission since the last flare in these patients (five received azathioprin) was 10-36 months. None of the patients needed colectomy because of symptoms. Conclusion: These preliminary data suggest that a course of intravenous Cy can turn corticosteroid-refractory ulcerative colitis to corticosteroids responsive. The outcome of patients not receiving oral Cy maintenance therapy appears to be satisfactory. Azathioprin maintenance therapy can probably be reserved for select patients.
|
|
| 9. |
- Shen, Xiao-Gang, et al.
(författare)
-
Downregulation of caspase-10 predicting poor survival after resection of stage II colorectal cancer
- 2011
-
Ingår i: International Journal of Colorectal Disease. - : Springer Verlag (Germany). - 0179-1958 .- 1432-1262. ; 26:12, s. 1519-1524
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to evaluate the prevalence and clinical significance of caspase-10 mRNA expression in stage II colorectal cancer. less thanbrgreater than less thanbrgreater thanMethods Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze caspase-10 expression in cancer tissue and corresponding normal mucosa from 120 patients with stage II colorectal cancer. Variables were analyzed by Chi-square test or Fishers exact test. Survival was evaluated with method of Kaplan-Meier. Multivariate analysis was performed with Coxs proportional hazards model. less thanbrgreater than less thanbrgreater thanResults The expression of caspase-10 mRNA was found to be downregulated in cancer tissue compared to normal mucosa (P = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation (P = 0.031). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between caspase-10 expression and both overall survival (P = 0.012) and disease-free survival (P = 0.021). A multivariate analysis, performed by Coxs proportional hazards regression model, confirmed that a low caspase-10 expression was the only significant factor to predict poor prognosis in patients with stage II colorectal cancer. less thanbrgreater than less thanbrgreater thanConclusion Our data indicate that caspase-10 expression, measured by quantitative real-time RT-PCR, is a possible prognostic factor in patients with stage II colorectal cancer.
|
|
| 10. |
- Slind Olsen, Renate, et al.
(författare)
-
CD93 gene polymorphism is associated with disseminated colorectal cancer
- 2015
-
Ingår i: International Journal of Colorectal Disease. - : Springer Verlag (Germany). - 0179-1958 .- 1432-1262. ; 30:7, s. 883-890
-
Tidskriftsartikel (refereegranskat)abstract
- Cluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC). Tissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed. Total CD93 levels were 82 % higher (P less than 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30 % lower (P less than 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95 % confidence interval (CI) = 1.11-2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22-3.51, P = 0.007). We showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.
|
|
