| 1. |
- Fagman, Johan Bourghardt, 1980, et al.
(author)
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EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.
- 2019
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In: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:6, s. 5361-5368
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Journal article (peer-reviewed)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.
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| 2. |
- Cervantes-Madrid, Diana Lizeth, 1987, et al.
(author)
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DNA alterations in Cd133+ and Cd133- tumour cells enriched from intra-operative human colon tumour biopsies.
- 2017
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:1
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Journal article (peer-reviewed)abstract
- Tumour stem cells are considered important to promote disease progression, recurrence and treatment resistance following chemotherapy in colon cancer. However, genomic analyses of colorectal cancer have mainly been performed on integrated tumour tissue consisting of several different cell types in addition to differentiated tumour cells. The purpose of the present study was to compare genomic alterations in two cell fractions enriched of CD133+ and CD133-/EpCAM+ cells, respectively, obtained from fresh intraoperative human tumour biopsies.The tumour biopsies were fractionated into CD133+ and CD133-/EpCAM+ cells by immunomagnetic separation, confirmed by immunocytochemistry and Q-PCR. DNA were extracted and used for array comparative genome hybridization (aCGH) after whole genome amplification. Frozen tumour tissue biopsies were used for DNA/RNA extraction and Q-PCR analyses to check for DNA alterations detected in the cell fractions.The number and size of DNA alterations were equally distributed across the cell fractions; however, large deletions were detected on chromosome 1, 7 and 19 in CD133-/EpCAM+ cells. Deletions were frequent in both cell fractions and a deletion on chromosome 19p was confirmed in 90% of the patients.Isolation of enriched cells derived from tumour tissue revealed mainly genomic deletions, which were not observed in tumour tissue DNA analyses. CD133+ cells were genetically heterogeneous among patients without any defined profile compared to CD133-/EpCAM+ cells.
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| 3. |
- Falk, Peter, 1962, et al.
(author)
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An ex vivo model using human peritoneum to explore mesh-tissue integration.
- 2017
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In: Biology open. - : The Company of Biologists. - 2046-6390. ; 6:9, s. 1391-1395
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Journal article (peer-reviewed)abstract
- Biological compatibility, in terms of implantation of foreign mesh material in hernia surgery, still needs experimental investigation. Present study develops an experimental model using human peritoneum to study the integration between tissue and different mesh material. The ex vivo model using peritoneal tissue was studied with different mesh material, and integration was monitored over time using microscopy.It could be demonstrated that the peritoneal model may be kept viable in culture for several weeks. Cell migration was seen after 7-10 days in culture and could be further monitored over several weeks. The use of a human artificial model environment enabling the investigation of tissue/mesh integration has, to our knowledge, not been described previously.This proof-of-concept model was developed, for the investigation of peritoneal biology and the integration between tissue and different mesh material. It has the potential to be useful in studies on other important biological mechanisms involving the peritoneum.
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| 4. |
- Falk, Peter, 1962, et al.
(author)
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Colorectal Cancer Cells Adhere to Traumatized Peritoneal Tissue in Clusters, An Experimental Study.
- 2018
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In: Journal of investigative surgery. - : Informa UK Limited. - 0894-1939 .- 1521-0553. ; 31:4, s. 349-356
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Journal article (peer-reviewed)abstract
- Purpose/Aim: Colorectal malignity is one of the most common forms of cancer. The finding of free intraperitoneal colorectal cancer cells during surgery has been shown to be associated with poor outcome. The aim of this study was to develop an experimental model designed to investigate adhesion of colorectal cancer cells to the peritoneal surface.Two human experimental models were developed, the first using cultured mesothelial cells and the second consisting of an ex vivo model of peritoneal tissue. Both models were subjected to standardized trauma, following which labeled colorectal cancer cells (Colo205) were introduced. Adhesion of tumor cells was monitored using microscopy and detection of fluorochromes.The mesothelial cell layers and peritoneal membranes remained viable in culture medium for several weeks. In our experimental model, the tumor cells added were seen to adhere to the edges of the traumatized area in cluster formations.The use of human peritoneal tissue in an ex vivo model would appear to be a potentially useful tool for the study of interaction between human peritoneal membrane and free tumor cells. Experimental surgical trauma increases the ability of tumor cells to adhere to the peritoneal membrane. This ex vivo model should be useful in future studies on biological interactions between peritoneum and tumor cells in the search for novel forms of peritoneal cancer therapy.
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| 5. |
- Falk, Peter, 1962, et al.
(author)
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Role of matrix metalloproteinases in tumour invasion: immunohistochemistry of peritoneum from peritoneal carcinomatosis
- 2018
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:5
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Journal article (peer-reviewed)abstract
- Colorectal cancer is one of the most common forms of cancer. Spread of tumour to the peritoneal cavity may lead to seeding of cancer cells that adhere to and invade the peritoneal membrane causing peritoneal carcinomatosis. Matrix metalloproteinases (MMPs) play an essential role in cancer cell invasion and dissemination. The aim of this study was to evaluate the morphology and presence of matrix metalloproteinases in peritoneal carcinomatosis. Biopsy samples of the parietal peritoneum were taken from patients undergoing cytoreductive surgery for peritoneal carcinomatosis. The samples were fixed in formalin, dehydrated and embedded in paraffin prior to cutting into 4-mu m slices. Staining with haematoxylin/eosin was used for morphology studies, and MMP-1, MMP-2 and TIMP-1 levels were evaluated using immunohistochemistry and light microscopy. The microscopically tumour-free areas of the peritoneal membrane were thin compared to the peripheral invasion zone and the areas invaded by tumour. Peritoneum invaded by tumour was richly vascularised and contained inflammatory cells. MMP-1 was expressed in tumour-free peritoneum and in the invasion zone between tumour and peritoneal tissue, but not in tumour-invaded areas. MMP-2 and TIMP-1 were mostly expressed in the proximity of blood vessels and inflammatory cells in tumour-invaded areas, but was not seen in tumour-free areas. MMPs play an important role in the process of cancer cell invasion of the peritoneum in peritoneal carcinomatosis. The peripheral zone of the tumour appears to be of importance for tumour invasion.
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| 6. |
- Jonsson, Andreas, 1984, et al.
(author)
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Levels of matrix metalloproteinases differ in plasma and serum - aspects regarding analysis of biological markers in cancer.
- 2016
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 115:6, s. 703-706
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Journal article (peer-reviewed)abstract
- Background: There are inconsistencies in the use of serum or plasma when analysing the matrix metalloproteinases (MMPs) as diagnostic or prognostic markers. The purpose of this study was to compare the concentration of MMP-1, -2, -7, -8, -9 and -13 in serum vs plasma samples. METHODS: Blood samples were obtained from sixty-five men and women. Samples were analysed for levels of MMPs in corresponding citrate plasma and serum. RESULTS: All MMPs expressed higher concentration in serum compared with plasma (P<0.01). There were no differences between genders. CONCLUSIONS: Present study demonstrated significant differences regarding concentrations of some MMPs using plasma vs serum. We conclude that future studies regarding MMPs as biological markers in cancer should consider the use of citrate plasma instead of serum.
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| 7. |
- Jonsson, Andreas, 1984, et al.
(author)
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Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer.
- 2018
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In: Medical oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 35:4
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Journal article (peer-reviewed)abstract
- Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at -80°C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9years of cryopreservation (median values 9.9 and 9.7ng/mL, respectively; p>0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1ng/mL, respectively; p<0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5ng/mL, respectively; p<0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at -80°C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.
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| 8. |
- Skoglar, A., et al.
(author)
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Band adhesions not related to previous abdominal surgery – A retrospective cohort analysis of risk factors
- 2018
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In: Annals of Medicine and Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 2049-0801. ; 36, s. 185-190
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Journal article (peer-reviewed)abstract
- Background: Postoperative intra-abdominal adhesion formation is a common cause of small bowel obstruction (SBO). Adhesions causing SBO are classed as either matted adhesions or solitary band adhesions. The aim of this study was to investigate the prevalence of previous abdominal surgery in a cohort of patients operated for bowel obstruction and to analyze the causes of obstruction discovered at surgery. Materials and methods: The study was performed at a county hospital with a catchment population of 120 000 inhabitants. Records of operations performed for bowel obstruction over a period of 70 months were retrieved. Results: Of the 196 surgical procedures for intestinal obstruction included, 108 (55%) were caused by adhesions. In this group, 42 (39%) were due to solitary band adhesions and 66 (61%) were due to matted adhesions. Ten of 18 male patients (56%) with a solitary obstructing band had not undergone previous abdominal surgery (p < 0.05). In the cohort as a whole, a significant number of surgical procedures were performed for solitary band adhesions in patients without prior history of surgery (p < 0.01). Conclusion: In male patients, not only previous abdominal surgery but also other factors appear to increase the risk for bowel obstruction due to a solitary band. For intestinal obstruction caused by matted adhesions, however, previous abdominal surgery is the main risk factor in both genders. Patients with signs of SBO but without previous abdominal surgery should be managed bearing in mind that solitary band adhesion and thereby strangulation may be present regardless of previous surgery or not. © 2018 The Authors
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| 9. |
- Strigård, Karin, et al.
(author)
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Giant ventral hernia-relationship between abdominal wall muscle strength and hernia area
- 2016
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In: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 16
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Journal article (peer-reviewed)abstract
- Background: Symptoms arising from giant ventral hernia have been considered to be related to weakening of the abdominal muscles. The aim of this study was to investigate the relationship between the area of the abdominal wall defect and abdominal wall muscle strength measured by the validated BioDex system together with a back/ abdominal unit.Methods: Fifty-two patients with giant ventral hernia (> 10 cm wide) underwent CT scan, clinical measurement of hernia size and BioDex measurement of muscle strength prior to surgery. The areas of the hernia derived from CT scan and from clinical measurement were compared with BioDex forces in the modalities extension, flexion and isometric contraction. The Spearman rank test was used to calculate correlations between area, BMI, gender, age, and muscle strength.Result: The hernia area calculated from clinical measurements correlated to abdominal muscle strength measured with the Biodex for all modalities (p-values 0.015-0.036), whereas no correlation was seen with the area calculated by CT scan. No relationship was seen between BMI, gender, age and the area of the hernia.Discussion: The inverse correlation between BioDex abdominal muscle strength and clinically assessed hernia area, seen in all modalities, was so robust that it seems safe to conclude that the area of the hernia is an important determinant of the degree of loss of abdominal muscle strength. Results using hernia area calculated from the CT scan showed no such correlation and this would seem to concur with the results from a previous study by our group on patients with abdominal rectus diastasis. In that study, defect size assessed clinically, but not that measured by CT scan, was in agreement with the size of the diastasis measured intra-operatively.The point at which the area of a hernia begins to correlate with loss of abdominal wall muscle strength remains unknown since this study only included giant ventral hernias.
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| 10. |
- Winsnes, Annika, et al.
(author)
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Evaluating full-thickness skin grafts in intraperitoneal onlay mesh position versus onlay position in mice
- 2018
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In: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 230, s. 155-163
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Journal article (peer-reviewed)abstract
- Background: Importance: Hernia surgery requires reinforcement material with few side effects when used in the intraperitoneal position. Autologous skin grafting may meet this requirement, but animal experiments are obligatory before being applied in humans. Objective: To compare survival and effects of isogeneic full-thickness skin grafts in the intraperitoneal onlay mesh (IPOM) position in mice, with a control group using the onlay position. Primary end point was graft survival and secondary end point adhesion formation and inflammation through NF-κB activity. Methods: Design: Intervention study with 8-week follow-up in accordance with ARRIVE criteria, performed between 2015 and 2016. Setting: Animal laboratory. Participants: Transgenic C57BL/6 mice with isogeneic background were used. Recipients were female wild-type phenotype mice >3 mo (n = 24). Donors were male or female mice >7 mo, with phenotype-positive for the luciferase gene (n = 20) or positive for NF-κB-luciferase gene (n = 4). Intervention: Full-thickness skin was grafted in the IPOM position and compared with grafts in the onlay position as controls. Survival was evaluated by regular longitudinal postoperative luminescence imaging over 8 wk. Adherence formation was evaluated macroscopically after sacrifice. Inflammation of full-thickness skin grafts in IPOM position of NF-κB mice was evaluated in four additional mice. Main outcome and measure: Survival of grafts, evaluated by luminescence. Results: Ten animals received grafts in the IPOM position, and 10 in the onlay position as controls. Graft survival after 8 wk was 100% (20/20). Average luminescence at the end of the 8-week period was 999,597 flux (min 162,800, max 2,521,530) in the IPOM group (n = 10) and 769,708 flux (min 76,590, max 2,164,080) in the onlay control group (n = 10). No adhesions requiring sharp dissection (Jenkins' scale >2) were seen. Four animals with grafts in the IPOM position showed peak inflammation (NF-κB activity) 5 d after surgery subsiding toward the end of follow-up. Conclusions: Full-thickness skin survives as well in the IPOM position as in the onlay control position, and few adherences develop. Further studies are required to fully characterize the tissue remodeling and repair processes associated with IPOM skin grafting. The result is relevant in the search for alternative reinforcement materials to be used in complex hernia surgery in humans. © 2018 The Author(s)
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