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- Solberg, Anna, 1961, et al.
(författare)
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A local imbalance between MMP and TIMP may have an implication on the severity and course of appendicitis.
- 2008
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Ingår i: International journal of colorectal disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 23:6, s. 611-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) have been demonstrated to be involved in inflammatory conditions in the intestine. The purpose of this study was to investigate whether the alterations of the MMP/TIMP balance might reflect the course of the inflammatory process in acute appendicitis and if the expression and localisation of MMPs and TIMP is variable in the various clinical manifestations of appendicitis. MATERIALS AND METHODS: The study comprises 40 patients (26 men and 14 women) having emergency appendectomy and a control group constituting of 10 patients (5 men and 5 women) having a hemicolectomy for other reasons. MMP and TIMP expressions were assessed and compared in tissue specimens from phlegmonous (n = 15), gangrenous (n = 7), perforated appendicitis (n = 11) and controls with noninflamed appendices (n = 10) by means of enzyme-linked immunosorbent assay technique. Localisation of the enzymes was performed by immunohistochemistry. RESULTS: MMP-1 was significantly higher in gangrenous and perforated appendicitis compared with phlegmonous appendicitis and controls (p < 0.05) while MMP-2 was significantly lower in gangrenous appendicitis compared with phlegmonous appendicitis and controls. MMP-2 was also lower in perforated appendicitis when compared with controls (p < 0.01). Elevated expression of MMP-9 was demonstrated in all groups of appendicitis compared with the controls (p < 0.001). CONCLUSIONS: MMP-9 is the most abundantly expressed MMP of those investigated in inflamed appendix. We postulate that a local imbalance between MMP-9 and TIMP-1 may trigger a perforation. These results suggest that MMPs might be useful as biomarkers of appendices prone to perforation.
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| 2. |
- Angenete, Eva, 1972, et al.
(författare)
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Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation
- 2007
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Ingår i: International journal of colorectal disease. - 0179-1958. ; 22:6, s. 667-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In rectal cancer treatment, preoperative radiotherapy has led to reduction of local recurrence, but it is associated with morbidity and increased risk for secondary tumours. Matrix metalloproteinases (MMPs) are associated with tumour progression through tissue remodeling. The aim of this study was to investigate tissue remodeling after preoperative radiotherapy and to explore possible correlations with clinical outcome. MATERIALS AND METHODS: Ninety-one patients scheduled for rectal cancer surgery were included; 49% received preoperative radiotherapy three-field treatment, 5 x 5 Gy. Blood samples and biopsies from tumour and adjacent mucosa were taken during surgery. Biopsies and plasma were assayed with ELISA for MMP-1, MMP-2 and MMP-9. Clinical outcome was reviewed focusing on infections, perineal healing, fistula formation, anastomotic dehiscence, small bowel obstruction, local recurrence and distant metastases. RESULTS: Compared to non-irradiated mucosa, MMP-2 (p < 0.0001), MMP-1 (p = 0.03) and MMP-9 (p = 0.04) were significantly higher in irradiated normal mucosa. Tumour tissue had higher levels of MMP-2 if irradiated (p < 0.0001). A correlation between MMP-2 levels and wound infection (p = 0.02) as well as fistula formation (p = 0.04) was found. MMP-1 in mucosa (p = 0.02) and tumour (p = 0.04) were higher in patients developing distant metastases. Plasma levels were not influenced by irradiation, but MMP-2 was higher in patients who were later developing distant metastases (p = 0.007). CONCLUSIONS: Extracellular matrix remodeling after radiotherapy seems to be correlated to postoperative morbidity; MMP-2 is associated with both wound infections and fistula formation. High levels of MMP-1 in tumour and mucosa as well as MMP-2 in plasma may be correlated to risk of developing distant metastases.
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| 3. |
- Angenete, Eva, 1972, et al.
(författare)
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Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients
- 2007
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Ingår i: Int J Colorectal Dis. - 0179-1958. ; 11, s. 1331-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-beta1 (TGF-beta1) acts both as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels of TGF-beta1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy and clinical outcome. MATERIALS AND METHODS: One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field treatment 5 x 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent assay for total TGF-beta1 and active TGF-beta1. Patients were then followed for 3 years. RESULTS: Total and active TGF-beta1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-beta1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-beta1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-beta1 in plasma were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-beta1 in the rectal mucosa (p = 0.038). CONCLUSIONS: Higher levels of total TGF-beta1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active TGF-beta1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-beta1 in rectal mucosa may influence risk of local recurrence. Measurement of TGF-beta1 in rectal cancer patients may be of clinical use in the future.
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| 4. |
- Langenskiöld, Marcus, 1972, et al.
(författare)
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Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer
- 2005
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Ingår i: International journal of colorectal disease. - 0179-1958. ; 20:3, s. 245-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Degradation of the extracellular matrix plays an important part during the invasion of cancer cells into the surrounding tissue. The matrix metalloproteinases (MMPs) have a central role in this process as demonstrated in different malignancies. The aim of this study was to investigate the presence of several MMPs from tumour, adjacent tumour-free colon segment and from plasma, in order to evaluate how these factors might be used as predictors in colorectal malignancy. METHODS: Seventy-two patients who underwent surgery because of a colorectal carcinoma were included. Biopsies from the tumour, macroscopically tumour-free bowel and plasma samples were analysed with enzyme-linked immunosorbent assay tests (ELISAs) quantifying protein expression of several MMPs. RESULTS: We found highly elevated concentrations of MMP-1, MMP-2, MMP-3 and MMP-9 protein expression in tumour tissue compared with tumour-free tissue (p<0.0001). Elevated MMP-1 tumour levels were found in patients with Dukes' C cancers (p=0.02). Lymph node status correlated with the expression of MMP-2 in plasma, which was significantly increased in patients with lymph node metastasis compared with those without (p=0.002). MMP-2 in plasma was higher in T3 and T2 tumours than in T4 tumours (p=0.0083). CONCLUSION: The MMPs we investigated were strongly elevated in tumour tissue compared with tumour-free bowel wall. Our results indicate that MMP-2 in plasma may possibly be used as a predictor in colorectal malignancy. The use of MMP-2 as a predicting tool in combination with different imaging techniques may give important preoperative information in patients with colorectal cancer.
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