| 31. |
- Solberg, Anna, 1961, et al.
(författare)
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Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1.
- 2009
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:5, s. 579-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Serine proteases and the matrix metalloproteinases (MMPs) are key factors in the proteolytic cascade and participate in extracellular matrix (ECM) degradation. Fibrinolytic activators and inhibitors may have an effect on inflammatory cells, thereby modulating the inflammatory response. It is reasonable to assume that they may be implicated in the tissue injury in acute appendicitis that subsequently leads to appendix perforation. The purpose of this study was to investigate the expression and distribution of urokinase-type plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in appendicitis. MATERIAL AND METHODS: Expression of uPA and expression of PAI-1 were measured in tissue specimens from patients with appendicitis (n=30) and in control specimens (n=9), using the quantitative ELISA technique. Distribution of enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the subgroups of appendicitis and controls were compared. RESULTS: The overall expressions of uPA and PAI-1 were greater in appendicitis than in control specimens (p <0.001 and p<0.0001, respectively). Expressions of uPA and PAI-1 in phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all higher than those in controls (n=9), (p<0.01). Moreover, the PAI-1 level was elevated in perforated appendicitis compared with phlegmonous appendicitis (p<0.01). uPA staining was observed in connection with vascular endothelial cells and the serosa stained intensely in specimens from perforated appendicitis. CONCLUSIONS: The expression of uPA and especially the over-expression of PAI-1 seem to correlate to the progression of local inflammatory response in acute appendicitis.
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| 32. |
- Solberg, Anna, 1961, et al.
(författare)
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Tissue Proteolysis in Appendicitis with Perforation
- 2011
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 169:2, s. 194-201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation. MATERIALS AND METHODS: Biopsies were taken at the sites of perforation (n = 15) and with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique. RESULTS: MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P < 0.01). MMP-9 showed a similar pattern being highest at the sites of perforation (P < 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforation. PAI-1 was highest at the sites of perforation (P < 0.01) and the uPA expression was similarly elevated close to and at the perforation. CONCLUSIONS: These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforation may also contribute to tissue damage.
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| 33. |
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| 34. |
- Wang, Xin, et al.
(författare)
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Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice
- 2000
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 44:9, s. 2452-2457
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of carotenoids and vitamin C has been proposed to prevent development of gastric malignancies. The aim of this study was to explore if the microalga Haematococcus pluvialis rich in the carotenoid astaxanthin and vitamin C can inhibit experimental H. pylori infection in a BALB/cA mouse model. Six-week-old BALB/cA mice were infected with the mouse-passaged H. pylori strain 119/95. At 2 weeks postinoculation mice were treated orally once daily for 10 days (i) with different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively), (ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the cessation of treatment, and the other five animals were sacrificed 10 days after the cessation of treatment. Culture of H. pylori and determination of the inflammation score of the gastric mucosae were used to determine the outcome of the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Lipid peroxidation was significantly decreased in mice treated with the astaxanthin-rich algal meal and vitamin C compared with that of animals not treated or treated with the control meal. Both astaxanthin-rich algal meal and vitamin C showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.
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| 35. |
- Wang, Xin, et al.
(författare)
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Development of high-grade lymphoma in Helicobacter pylori-infected C57BL/6mice
- 2000
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 108:7-8, s. 503-508
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. Mice with H. pylori infection develop severe gastritis and atrophic changes in their stomachs after 6 months. We followed H. pylori -infected animals for 13 months to find out whether dysplasia, carcinoma or lymphoma developed. Six-week-old C57BL/6 mice were infected with the CagA-positive and VacA-positive H. pylori mouse-passaged strain 119/95, fed a low antioxidant diet, and kept in microisolated cages. Histopathological changes were examined after 13 months' infection. All H. pylori -inoculated mice (n=5) developed a gastric squamous papilloma with nagging of the lamina muscularis after 13 months. Three out of five animals developed high-grade B-cell lymphoma derived from a MALT lymphoma at the squamous-corpus border with manifestations also in the liver, spleen and kidney. There was a suspicion of local gastric lymphoma in the two remaining mice but with no significant changes in the liver, spleen or kidney. The normal control mice showed no pathological changes in any of these organs. It is concluded that this mouse model with infection by the CagA-positive, vac-toxin-producing H. pylori strain 119/95 is suitable for use in the study of lymphoma development and also development of squamous cell papilloma with proliferative features.
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| 36. |
- Wang, Xin, et al.
(författare)
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Two-year follow-up of Helicobacter pylori infection in C57BL/6 and Balb/cA mice.
- 2003
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 111:4, s. 514-522
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. We previously found high-grade lymphoma after 13 months' H. pylori infection in C57BL/6 mice. In this study we followed H. pylori infection by three different isolates in C57BL/6 and Balb/cA mice for 23 months. Six-week-old C57BL/6 and Balb/cA mice were infected with H. pylori strains 119p (CagA+, VacA+), SS1 (CagA+, VacA+) and G50 (CagA-, VacA-). Mice were followed at 2 weeks, 10 weeks and 23 months post-inoculation (p.i.) by culture, histopathology and serology. Strain G50 was only reisolated from mice 2 weeks p.i. There was no difference in colonization between strain 119p and SS1 at 10 weeks p.i., whereas SS1 gave 100% colonization versus 119p gave 50% 23 months p.i.. Interestingly, the inflammation score was higher in mice infected with strain 119p than with SS1 10-week p.i., and there were lymphoepithelial lesions in mice infected with strain 119p and G50 but not with SS1 at 23 months post-infection. Eight mice infected with strains 119p and G50 developed gastric lymphoma (grade 5 and 4). One C57BL/6 mouse infected with strain 119p developed hepatocellular carcinoma after 23 months. Immunoblot showed specific bands of 2633 kDa against H. pylori in infected mice, and two mice infected with strain SSI reacted with antibodies to the 120 kDa CagA toxin. Conclusion: A reproducible animal model for H. pylori-induced lymphoma and possibly hepatocellular carcinoma is described. Strain diversity may lead to different outcomes of H. pylori infection.
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| 37. |
- Wettergren, Yvonne, 1957, et al.
(författare)
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Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients
- 2005
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Ingår i: Cancer Detect Prev. - : Elsevier BV. - 0361-090X .- 1525-1500. ; 29:4, s. 348-55
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cellular folate deficiency leads to DNA strand breaks, mutations, and aberrant methylation and might be a risk factor for colorectal cancer (CRC). The putative tumor suppressor gene deleted in colorectal carcinoma (DCC) is one of several genes the expression of which seems to be affected by the folate concentration at the tissue level. Decreased expression of DCC may be caused by LOH or hypermethylation, i.e. by events that might be linked to folate deficiency. The purpose of this study was to analyze if the folate level and the gene expression levels of reduced folate carrier (RFC-1) and folylpolyglutamate synthase (FPGS) had impact on the expression of DCC splice variants. METHODS: Quantification of RFC-1 and FPGS expression in mucosa of 53 CRC patients was performed using real-time PCR whereas DCC splicing variants were detected by automated capillary gel electrophoresis. Total reduced folate concentration was measured with the FdUMP-binding assay (n = 22). RESULTS: Significantly higher expression levels of RFC-1 (p = 0.026) and FPGS (p = 0.05) were found in mucosa expressing the splice variant DCC342 compared to mucosa that did not. Furthermore, multivariate analysis showed that RFC-1 and FPGS (r = 0.49, p = 0.01) as well as folate and RFC-1 (r = 0.56, p = 0.023) were correlated only in mucosa expressing DCC342. CONCLUSIONS: In conclusion, the present study points to a potential influence of folates in regulating DCC expression at multiple levels involving post-transcriptional pathways. The results may provide a basis for a detailed investigation of molecular mechanisms involved in folate regulation of DCC expression.
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| 38. |
- Willén, Linda, 1979-
(författare)
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Factors influencing management and outcome in non-small cell lung cancer : the role of socioeconomic status, age, geographic region of origin and aspects of quality of life
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Yearly, 4,200 individuals in Sweden are diagnosed with lung cancer, of which 85 % are non-small cell lung cancer (NSCLC). The aims of this thesis were to investigate aspects of equality of care and outcomes in patients with NSCLC and to examine indicators of quality of life. All studies used data in Lung Cancer Database Sweden (LCBaSe), a research database generated by record linkages between the National Lung Cancer Register and other population-based registers. We identified 40,000 patients with NSCLC diagnosed between 2002 and 2016.Paper I examined influence of socioeconomic status. Patients with a high educational level were more often offered PET-CT, assessed in a multidisciplinary team setting, treated with stereotactic body radiotherapy and had better survival in early-, but not in late-stage disease.Paper II investigated elderly NSCLC patients. No difference in stage was seen in patients ≤ 84 years, nor in diagnostic intensity <80 years. Treatment intensity was adapted according to age. Survival differed across age groups in early-, but not late-stage disease.Paper III examined immigrants. We found evidence of a “healthy migrant effect”. There were only small differences in management and outcome. If anything, non-Nordic immigrants had better survival in early-stage disease. Paper IV assessed psychological impact following a NSCLC diagnosis. Higher rates of depression, anxiety, intoxication and suicide were seen in NSCLC patients compared to lung cancer free individuals. The risk of depression, anxiety and suicide decreased over time but the increased risk of intoxication remained throughout the follow-up period.In summary, we found equal access of care and only minor differences in patterns of management and outcomes according to socioeconomic status, age and geographic region of origin. New diagnostics and treatment modalities need to be quickly introduced to enable equal access across socioeconomic groups. A careful assessment of older patients is important to avoid age-biased clinical decision-making. A diagnosis of NSCLC impacts psychological aspects of quality of life and active measures to identify and treat depression and anxiety as well as to identify patients at risk of intoxication and suicide is necessary.
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| 39. |
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| 40. |
- Willén, Roger, 1939, et al.
(författare)
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Prophylactic surgery for patients with longstanding ulcerative colitis. Which option? Histopathological and clinical implications.
- 2007
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Ingår i: Upsala journal of medical sciences. - 2000-1967 .- 0300-9734. ; 112:1, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Patients with longstanding chronic ulcerative proctocolitis are at risk to develop colorectal cancer Conflicting views as regards surveillance, the indications for surgery and type of preventive procedure exist. For permanent prevention of cancer development complete removal of all potential malignant colorectal mucosa has to be done. Panprocto-colectomy with a conventional ileostomy or continent ileostomy removing all colorectal mucosa should therefore eliminate further risks of colorectal cancer. Colectomy and ileorectal anastomosis is a controversial issue. While many surgeons today are reluctant to use the technique, emphasising the persistent cancer risk, others consider the operation a viable alternative when used on a selective basis. The long-term risk of cancer in the rectal stump is the main strong argument . In restorative proctocolectomy, i.e. proctocolectomy with construction of an ileopouch anal anastomosis residual rectal mucosa is left behind irrespective of technique used and is therefore at risk for cancer development. Quite a few cancers have been reported to occur in these patients but controversy exists as regards the origin of these tumours but the risk for cancer development is very low. Biopsies from ileal pouches demonstrate various histopathological changes from nearly normal mucosa, to inflammation and atrophy, inflammatory cell changes, dysplasia as well as development of carcinoma. Grading of type and atypia is a challenge to reproduce and requires the participation of experienced gastrointestinal histopathologists.
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