| 1. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
-
EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.
- 2019
-
Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:6, s. 5361-5368
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed. Tissue slides were evaluated for membrane wild-type EGFR and cytoplasmic COX-2 staining using a histoscore system. Statistical associations between EGFR and COX-2 staining and clinicopathological characteristics were examined to predict survival. In a cohort of 32 resected PDAC patients, high EGFR protein expression in tumor cells was significantly associated with shorter median overall survival (7.9 vs. 39.2 months, P=0.0038). The corresponding hazard ratio (HR) for patients with high EGFR protein expression in tumor cells was 3.12 [95% confidence interval (CI): 1.39-7.00, P=0.006]. COX-2 protein expression was not associated with survival (22.6 vs. 24.5 months P=0.60; HR 1.22 95% CI: 0.59-2.51, P=0.60). Following multivariate Cox regression analysis, high EGFR protein expression in tumor cells (P=0.043) remained as significant independent prognostic factor for survival. In conclusion, high wild-type EGFR protein expression, but not COX-2 protein expression, in tumor cells is a prognostic factor for reduced overall survival following pancreatic tumor resection, supporting a role for EGFR in identifying resected patients that may benefit from EGFR-targeted therapy.
|
|
| 2. |
- Falk, Kristina, 1972, et al.
(författare)
-
Antifibrinolytic proCPU is present in the peritoneal cavity during surgery.
- 2003
-
Ingår i: Scandinavian journal of clinical and laboratory investigation. - 0036-5513. ; 63:4, s. 287-96
-
Tidskriftsartikel (refereegranskat)abstract
- The fibrinolytic capacity of the peritoneum plays a pivotal role in peritoneal wound healing. During surgery the balance between fibrin deposition and degradation is tilted towards deposition, leading to the formation of adhesions. In blood, carboxypeptidase U (CPU) stabilizes clots by retarding fibrinolysis. The purpose of this study was to investigate whether the more stable zymogen, proCPU, is also present in the peritoneal cavity and, if so, to examine its origin. Levels of proCPU were measured in plasma and serosal peritoneal fluid collected during surgery. Peritoneal biopsies were stained for proCPU. Two-dimensional gel electrophoresis was performed to study the protein composition of the serosal fluid compared to plasma and Western blotting to identify differences in glycosylation of proCPU, indicating possible different cellular origin. Cultured human mesothelial cells were examined for proCPU production under normal conditions and conditions mimicking surgery. We found comparable and correlating levels of proCPU in serosal fluid and plasma. ProCPU was also found where fibrin covered the injured peritoneal surface. A protein composition very similar in serosal fluid and plasma was shown by two-dimensional gel electrophoresis, and the proCPU pattern did not indicate a different origin. No proCPU production was found in cultured mesothelial cells. This is the first study to report on the presence of proCPU in the peritoneal cavity, which seems to be the result of plasma oozing out during the inflammatory reaction to the surgical trauma. This is likely to be important for the balance between fibrin deposition and degradation and thereby in the formation of postoperative adhesions.
|
|
| 3. |
- Ahnström, Ulrika, et al.
(författare)
-
Detection and direction-finding of spread spectrum signals using correlation and narrowband interference rejection
- 2003
-
Ingår i: Nordic Matlab Conference 2003.
-
Konferensbidrag (refereegranskat)abstract
- An algorithm for correlation-based detection of direct sequence spread spectrum signals with direction finding, including direction-filtering and narrow-band interference rejection, is implemented and evaluated in MATLAB. An analog noise-free signal is generated and sampled by a test-bed system. Numerical simulations are run based on data corrupted by mutually uncorrelated white Gaussian noise sequences, and also with recorded noise from two spatially separated HF radio receivers. The simulations and measurements show promising results for detection and direction-finding of covert wideband signals in low SNR and in presence of narrowband interferers. Direction filtering is shown to improve the results.
|
|
| 4. |
- Angenete, Eva, 1972, et al.
(författare)
-
Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation
- 2007
-
Ingår i: International journal of colorectal disease. - 0179-1958. ; 22:6, s. 667-74
-
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.
|
|
| 5. |
- Angenete, Eva, 1972, et al.
(författare)
-
Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components.
- 2009
-
Ingår i: Acta oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:8, s. 1144-1151
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. Materials and methods. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. Results. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. Conclusions. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.
|
|
| 6. |
- Angenete, Eva, 1972, et al.
(författare)
-
Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients
- 2007
-
Ingår i: Int J Colorectal Dis. - 0179-1958. ; 11, s. 1331-8
-
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.
|
|
| 7. |
- Angenete, Eva, 1972, et al.
(författare)
-
uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.
- 2009
-
Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 153:1, s. 46-53
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors. MATERIALS AND METHODS: Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo). RESULTS: Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01). CONCLUSIONS: There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.
|
|
| 8. |
|
|
| 9. |
- Bergström, Maria, 1964, et al.
(författare)
-
Effect of acidosis on expression of mesothelial cell plasminogen activator inhibitor type-1.
- 2006
-
Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 20:9, s. 1448-52
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Abdominal mesothelial cells are exposed to carbon dioxide during laparoscopy. Previous data indicate that carbon dioxide increases release and expression of plasminogen activator inhibitor type-1 (PAI-1) and induces acidification. METHODS: To assess the impact resulting from a range of pH, human mesothelial cells were exposed to culturing media balanced to pH levels of 6.0 to 8.0 for 90 min. Samples from cell media were withdrawn at several time points. Concentrations of PAI-1 and PAI-1 activity were measured using enzyme-linked immunoassay techniques. To focus on the effect of clinically relevant pH, cells were subjected to pH 6.4 and 7.4. Samples were withdrawn for PAI-1 assessments and for PAI-1 mRNA analyses. RESULTS: During exposure to various levels of pH, PAI-1 secretion and activity were variable. However, 5 h after exposure, greater concentration and activity of PAI-1 were observed in acidified cultures. More PAI-1 mRNA was isolated after exposure of cells to a pH of 6.4, apparently indicating transcriptional regulation. CONCLUSIONS: Mesothelial cells seem to respond to acidification by an increased release and production of PAI-1 in vitro.
|
|
| 10. |
- Bergström, Maria, 1964, et al.
(författare)
-
Peritoneal and systemic pH during pneumoperitoneum with CO(2) and helium in a pig model.
- 2008
-
Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 22:2, s. 359-364
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Local peritoneal effects of laparoscopic gases might be important in peritoneal biology during and after laparoscopic surgery. The most commonly used gas, CO(2), is known to be well tolerated, but also causes changes in acid-base balance. Helium is an alternative gas for laparoscopy. Although safe, it is not widely used. In this study a method for monitoring peritoneal pH during laparoscopy was evaluated and peritoneal pH during CO(2) and helium pneumoperitoneum was studied as well as its systemic reflection in arterial pH. METHODS: For these experiments 20 pigs were used, with ten exposed to pneumoperitoneum with CO(2), and ten to helium. Peritoneal and sub-peritoneal pH were continuously measured before and during gas insufflation, during a 30-minute period with a pneumoperitoneum and during a 30-minute recovery period. Arterial blood-gases were collected immediately before gas insufflation, at its completion, at 30 minutes of pneumoperitoneum and after the recovery period. RESULTS: Peritoneal pH before gas insufflation was in all animals 7.4. An immediate local drop in pH (6.6) occurred in the peritoneum with CO(2) insufflation. During pneumoperitoneum pH declined further, stabilising at 6.4, but was restored after the recovery period (7.3). With helium, tissue pH increased slightly (7.5) during insufflation, followed by a continuous decrease during pneumoperitoneum and recovery, reaching 7.2. Systemic pH decreased significantly with CO(2) insufflation, and increased slightly during helium insufflation. Systemic pH showed co-variation with intra-peritoneal pH at the the end of insufflation and after 30 minutes of pneumoperitoneum. CONCLUSIONS: Insufflation of CO(2) into the peritoneal cavity seemed to result in an immediate decrease in peritoneal pH, a response that might influence biological events. This peritoneal effect also seems to influence systemic acid-base balance, probably due to trans-peritoneal absorption.
|
|
