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1.	Falk, Kristina, 1972, et al. (author) Antifibrinolytic proCPU is present in the peritoneal cavity during surgery. 2003 In: Scandinavian journal of clinical and laboratory investigation. - 0036-5513. ; 63:4, s. 287-96 Journal article (peer-reviewed)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.
2.	Angenete, Eva, 1972, et al. (author) Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation 2007 In: International journal of colorectal disease. - 0179-1958. ; 22:6, s. 667-74 Journal article (peer-reviewed)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.
3.	Angenete, Eva, 1972, et al. (author) Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components. 2009 In: Acta oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:8, s. 1144-1151 Journal article (peer-reviewed)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.
4.	Angenete, Eva, 1972, et al. (author) Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients 2007 In: Int J Colorectal Dis. - 0179-1958. ; 11, s. 1331-8 Journal article (peer-reviewed)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.
5.	Angenete, Eva, 1972, et al. (author) uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome. 2009 In: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 153:1, s. 46-53 Journal article (peer-reviewed)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.
6.	Boiso, Samuel, et al. (author) ABCB1 gene polymorphisms are associated with suicide in forensic autopsies 2013 In: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 23:9, s. 463-469 Journal article (peer-reviewed)abstract Background Polymorphisms in ABCB1 have the ability to affect both the function and the expression of the transporter protein P-glycoprotein and may lead to an altered response for many drugs including some antidepressants and antipsychotics.Objective The aim of this study was to examine the impact of the ABCB1 polymorphisms 1199Gandgt;A, 1236Candgt;T, 2677Gandgt;T/A, and 3435Candgt;T in deaths by suicide.Patients and methods A total of 998 consecutive Swedish forensic autopsies performed in 2008 in individuals 18 years of age or older, where femoral blood was available and a toxicological screening had been performed, were investigated. Genotypes were assessed with pyrosequencing and information on the cause and manner of each death was obtained from the forensic pathology and toxicology databases.Results There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases.Conclusion Our result from forensic cases suggests that ABCB1 polymorphisms are associated with an increased risk for completed suicides. The biological mechanisms involved and the clinical implications for these findings are largely unknown and need to be examined further.
7.	Brinton, Louise A, et al. (author) Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results. 2014 In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 106:3, s. 465-465 Journal article (peer-reviewed)abstract The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.
8.	Cederkrantz, Elin, et al. (author) Evaluation of Effects on the Peritoneum After Intraperitoneal α-Radioimmunotherapy with (211)At. 2012 In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:6, s. 353-364 Journal article (peer-reviewed)abstract Abstract The introduction of the short-lived α-emitter (211)At to intraperitoneal radioimmunotherapy has raised the issue of the tolerance dose of the peritoneum. The short range of the α-particles (70μm) and the short half-life (7.21h) of the nuclide yield a dose distribution in which the peritoneum is highly irradiated compared with other normal tissues. To address this issue, mice were injected with (211)At-trastuzumab to irradiate the peritoneum to absorbed doses ranging between 0 and 50 Gy and followed for up to 34 weeks. The peritoneum-to-plasma clearance of a small tracer, (51)Cr-ethylenediamine tetraacetic acid, was measured for evaluation of the small solute transport capacity of the peritoneal membrane. The macroscopic status of the peritoneum and the mesenteric windows was documented when the mice were sacrificed. Biopsies of the peritoneum were taken for morphology and immunohistochemical staining against plasminogen activator inhibitor-1 and calprotectin. Peritoneum-to-plasma clearance measurements indicated a dose-dependent decrease in peritoneal transport capacity in irradiated mice. However, macroscopic and microscopic evaluations of the peritoneal membrane showed no difference between irradiated mice versus controls. The results imply that the peritoneal membrane tolerates absorbed doses as high as 30-50 Gy from α-particle irradiation with limited response.
9.	Clendenen, Tess V., et al. (author) Breast Cancer Risk Factors and Circulating Anti-Müllerian Hormone Concentration in Healthy Premenopausal Women 2021 In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 106:11, s. E4542-E4553 Journal article (peer-reviewed)abstract Context: We previously reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.Objective: This study assessed whether risk factors for breast cancer are correlates of AMH concentration.Methods: This cross-sectional study included 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49) from 10 cohort studies among the general population.Results: Adjusting for age and cohort, AMH positively associated with age at menarche (P < 0.0001) and parity (P = 0.0008) and inversely associated with hysterectomy/partial oophorectomy (P = 0.0008). Compared with women of normal weight, AMH was lower (relative geometric mean difference 27%, P < 0.0001) among women who were obese. Current oral contraceptive (OC) use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, P < 0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, P = 0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40 vs ≥40), associations of AMH with body mass index and OCs were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (P-interaction < 0.05).Conclusion: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and it suggests that most associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
10.	Clendenen, Tess V., et al. (author) Breast cancer risk prediction in women aged 35-50 years : impact of including sex hormone concentrations in the Gail model 2019 In: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 21 Journal article (peer-reviewed)abstract Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Mullerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.Methods: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.Results: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.Conclusions: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
11.	Cook, Michael B, et al. (author) Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium. 2015 In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531 Journal article (peer-reviewed)abstract Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
12.	Delsing, Louise, et al. (author) Barrier properties and transcriptome expression in human iPSC-derived models of the blood-brain barrier 2018 In: Stem Cells. - : AlphaMed Press, Inc.. - 1066-5099 .- 1549-4918. ; 36:12, s. 1816-1827 Journal article (peer-reviewed)abstract Cell-based models of the blood-brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of inter-species differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC-derived model of the BBB that includes endothelial cells in co-culture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our co-culture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non-permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in co-culture, including upregulation of tight junction proteins such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF and PI3K-Akt pathways upon co-culture. Our data suggests that co-culture of iPSC-derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in co-culture can be used to further improve iPSC-derived BBB models through selective pathway manipulation.
13.	Delsing, Louise, et al. (author) Models of the blood-brain barrier using iPSC-derived cells 2020 In: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 107 Journal article (peer-reviewed)abstract The blood-brain barrier (BBB) constitutes the interface between the blood and the brain tissue. Its primary function is to maintain the tightly controlled microenvironment of the brain. Models of the BBB are useful for studying the development and maintenance of the BBB as well as diseases affecting it. Furthermore, BBB models are important tools in drug development and support the evaluation of the brain-penetrating properties of novel drug molecules. Currently used in vitro models of the BBB include immortalized brain endothelial cell lines and primary brain endothelial cells of human and animal origin. Unfortunately, many cell lines and primary cells do not recreate physiological restriction of transport in vitro. Human-induced pluripotent stem cell (iPSC)-derived brain endothelial cells have proven a promising alternative source of brain endothelial-like cells that replicate tight cell layers with low paracellular permeability. Given the possibility to generate large amounts of human iPSC-derived brain endothelial cells they are a feasible alternative when modelling the BBB in vitro. iPSC-derived brain endothelial cells form tight cell layers in vitro and their barrier properties can be enhanced through co-culture with other cell types of the BBB. Currently, many different models of the BBB using iPSC-derived cells are under evaluation to study BBB formation, maintenance, disruption, drug transport and diseases affecting the BBB. This review summarizes important functions of the BBB and current efforts to create iPSC-derived BBB models in both static and dynamic conditions. In addition, it highlights key model requirements and remaining challenges for human iPSC-derived BBB models in vitro.
14.	Falk, John, et al. (author) Immersion freezing ability of freshly emitted soot with various physico-chemical characteristics 2021 In: Atmosphere. - : MDPI AG. - 2073-4433. ; 12:9 Journal article (peer-reviewed)abstract The immersion freezing ability of soot particles has in previous studies been reported in the range of low/insignificant to very high. The aims of this study were to: (i) perform detailed physico-chemical characterisation of freshly produced soot particles with very different properties, (ii) investigate the immersion freezing ability of the same particles, and (iii) investigate the potential links between physico-chemical particle properties and ice-activity. A miniCAST soot generator was used to produce eight different soot samples representing a wide range of physico-chemical properties. A continuous flow diffusion chamber was used to study each sample online in immersion mode over the temperature (T) range from −41 to −32◦C, at a supersaturation of about 10% with respect to liquid water. All samples exhibited low to no heterogeneous immersion freezing. The most active sample reached ice-activated fractions (AF) of 10−3 and 10−4 at temperatures of 1.7 and 1.9 K, respectively, above the homogeneous freezing temperature. The samples were characterized online with respect to a wide range of physico-chemical properties including effective particle density, optical properties, particle surface oxidation and soot maturity. We did observe indications of increasing immersion freezing ice-activity with increasing effective particle density and increasing particulate PAH fraction . Hence, those properties, or other properties co-varying with those, could potentially enhance the immersion freezing ice-activity of the studied soot particle types. However, we found no significant correlation between the physico-chemical properties and the observed ice-nucleating ability when the particle ensemble was extended to include previously published results including more ice-active biomass combustion soot particles. We conclude that it does not appear possible in general and in any straightforward way to link observed soot particle physico-chemical properties to the ice-nucleating ability using the online instrumentation included in this study. Furthermore, our observations support that freshly produced soot particles with a wide range of physico-chemical properties have low to insignificant immersion freezing ice-nucleating ability.
15.	Falk, John, et al. (author) Relating ice nucleating ability of soot particles to their physico-chemical properties 2019 Conference paper (peer-reviewed)
16.	Falk, Peter, 1962, et al. (author) Effect of a DACC dressing on the growth properties and proliferation rate of cultured fibroblasts. 2012 In: Journal of wound care. - 0969-0700. ; 21:7 Journal article (peer-reviewed)abstract To study the morphology and proliferation of cultured fibroblasts in combination with an experimental wound-healing model using cultured fibroblasts, with and without the presence of a hydrophobic, dialkyl carbamoyl chloride (DACC) dressing (Sorbact; Abigo Medical AB).
17.	Falk, Peter, 1962, et al. (author) Examination gloves affect secretion of matrix metalloproteinases and their inhibitors from human abdominal skin fibroblasts. 2003 In: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. - 1067-1927. ; 11:3, s. 230-4 Journal article (peer-reviewed)abstract Overexpression of matrix metalloproteinases (MMPs) has been observed in chronic, compared to acute, wounds and altered levels might impair healing. During treatment of wounds, examination gloves are routinely used, and the wound environment thus gets exposed to gloves. The aim of this study was to characterize secretion of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in cultured fibroblasts with or without exposure to gloves. Cultures were exposed to glove washings from powdered or powder-free latex examination gloves and compared to untreated controls. MMP-1, -2, -3, -9 and their inhibitors TIMP-1 and -2 were assayed in conditioned media. Cells exposed to gloves reduced their release of MMP-1, -2, and -3 with no differences between the manufacturers of the gloves. The inhibitor TIMP-1 was reduced to 10-15% of untreated control values (p < 0.001), being less affected by the powder-free than by the powdered glove (p < 0.05). MMP-9 and TIMP-2 were not significantly altered. We therefore conclude that secretion of MMPs and TIMPs from cultured fibroblasts were affected by glove washings. Powdered and powder-free gloves had similar effects, except for a less pronounced reduction of TIMP-1 production by the powder-free glove. Examination gloves might therefore affect wound healing, with the least pronounced effect observed using the powder-free glove.
18.	Falk, Peter, 1962, et al. (author) Studies of TGF-beta(1-3) in serosal fluid during abdominal surgery and their effect on in vitro human mesothelial cell proliferation. 2009 In: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 154:2, s. 312-6 Journal article (peer-reviewed)abstract BACKGROUND: Increased transforming growth factor-beta (TGF-beta) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-beta response to the surgical trauma is limited. This study investigated TGF-beta(1-3) isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-beta(1-3) on human mesothelial cell proliferation. MATERIALS AND METHODS: Total as well as biologically active TGF-beta(1-3) and fibrinolytic factors: t-PA, uPA, and PAI-1 were measured in serosal fluid and plasma from 23 patients undergoing colorectal cancer surgery. In vitro proliferation of human primary mesothelial cell cultures upon TGF-beta(1-3) stimulation was also investigated. RESULTS: Total TGF-beta1 and TGF-beta2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-beta3 was higher in serosal fluid compared with plasma, while levels of active fractions did not differ. Plasminogen activators (t-PA, uPA) were elevated while the inhibitor (PAI-1) was decreased in serosal fluid compared with plasma. The in vitro mesothelial cell proliferation studies revealed that high TGF-beta(1-3) concentrations decreased cell proliferation, while lower concentrations of TGF-beta1 increased mesothelial cell proliferation. CONCLUSIONS: This human study shows increased active TGF-beta levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-beta1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-beta cytokines may be involved in postsurgical adhesion formation.
19.	Falk, Peter, 1962, et al. (author) TGF-β1 promotes transition of mesothelial cells into fibroblast phenotype in response to peritoneal injury in a cell culture model. 2013 In: International journal of surgery (London, England). - : Ovid Technologies (Wolters Kluwer Health). - 1743-9159 .- 1743-9191. ; 11:9, s. 977-982 Journal article (peer-reviewed)abstract Peritoneal adhesions are a clinical problem. A key to the understanding of peritoneal adhesions is to study the healing of mesothelial cells within the peritoneal cavity following surgery. Transforming growth factor beta (TGF-βs) affects this healing process. The aim of this study was to investigate the effects of different concentrations of TGF-β1 on the healing rate and healing properties of mesothelial cells.
20.	Fortner, Renée T., et al. (author) Anti-Mullerian hormone and endometrial cancer : a multi-cohort study 2017 In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 117:9, s. 1412-1418 Journal article (peer-reviewed)abstract Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. AntiMullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog(2): 1.07 (0.99-1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
21.	Gaudet, Mia M, et al. (author) Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies. 2017 In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 881-893 Journal article (peer-reviewed)abstract Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.
22.	Ge, Wenzhen, et al. (author) Circulating anti-Müllerian hormone and breast cancer risk : a study in ten prospective cohorts 2018 In: International Journal of Cancer. - Hoboken : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:11, s. 2215-2226 Journal article (peer-reviewed)abstract A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.What's new? To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti-Müllerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case-control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.
23.	Gergei, Ingrid, et al. (author) GWAS META-analysis followed by MENDELIAN randomisation revealed potential control mechanisms for circulating α-klotho levels. 2022 In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 31:5, s. 792-802 Journal article (peer-reviewed)abstract The protein α-Klotho acts as transmembrane the co-receptor for fibroblast growth factor 23 (FGF-23) and is a key regulator of phosphate homeostasis. However, α-Klotho also exists in a circulating form, with pleiotropic, but incompletely understood functions and regulation. Therefore, we undertook a GWAS meta-analysis followed by Mendelian randomisation (MR) of circulating α-Klotho levels.Plasma α-Klotho levels were measured by ELISA in the LURIC and ALSPAC (mothers) cohorts, followed by a GWAS meta-analysis in 4376 individuals across the two cohorts.Six signals at five loci were associated with circulating α-Klotho levels at genome-wide significance (p<5×10-8), namely ABO, KL, FGFR1, and two post-translational modification genes, B4GALNT3 and CHST9. Together, these loci explained >9% of the variation in circulating α-Klotho levels. MR analyses revealed no causal relationships between α-Klotho and renal function, FGF-23-dependent factors such as vitamin D and phosphate levels, or bone mineral density. The screening for genetic correlations with other phenotypes, followed by targeted MR suggested causal effects of liability of Crohn's disease risk [IVW beta=0.059 (95% CI 0.026, 0.093)] and low-density lipoprotein cholesterol (LDL-C) levels [-0.198, (-0.332, -0.063)] on α-Klotho.Our GWAS findings suggest that two enzymes involved in post-translational modification, B4GALNT3 and CHST9, contribute to genetic influences on α-Klotho levels, presumably by affecting protein turnover and stability. Subsequent evidence from MR analyses on α-Klotho levels suggest regulation by mechanisms besides phosphate-homeostasis and raise the possibility of cross-talk with FGF19- and FGF21-dependent pathways, respectively.
24.	Gren, Louise, et al. (author) Effects of renewable fuel and exhaust aftertreatment on primary and secondary emissions from a modern heavy-duty diesel engine 2021 In: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 156 Journal article (peer-reviewed)abstract Compared to petroleum diesel, renewable diesel fuels and exhaust aftertreatment systems can reduce primary exhaust emissions that are hazardous to human health and the environment. Secondary aerosol emissions which form upon atmospheric processing have, however, been less studied. This study aimed to quantify the impacts of replacing petroleum diesel with renewable fuels (hydrotreated vegetable oil [HVO] and rapeseed methyl ester [RME]) on primary and secondary aerosol emissions from a heavy-duty diesel engine at different stages of an exhaust aftertreatment system. Emission characterization was obtained by combining a battery of physical characterization techniques with chemical characterization using aerosol mass spectrometry. At engine-out measurements, RME and HVO reduced primary particulate matter (PM) emissions (for example equivalent black carbon [eBC]) and secondary aerosol production (studied with an oxidation flow reactor [OFR]) by mass compared to petroleum diesel. The diesel oxidation catalyst (DOC) reduced primary nucleation mode emissions, reduced the effective density of soot mode emissions, and reduced secondary particle production by mass. The DOC + a diesel particulate filter removed >99% of the particle number and eBC emissions. Volatile PM emissions (for example organic aerosol) were found to be distributed between the nucleation mode and soot mode for both primary and secondary emissions, to a degree that depends on both fuel type and aftertreatment. A high mass concentration of condensable species and a low condensation sink in the soot mode led to increased fractions of condensable species present in the nucleation mode. Aging in the OFR led to increases in particle effective density. Motoring the engine (running without combustion) showed that the nucleation mode originated primarily from lubricating oil, and nonvolatile nanoparticle emissions were identified down to 1.2 nm in particle size. In conclusion, replacing petroleum diesel with HVO and RME changes emission characteristics and can help reduce key aerosol emissions of relevance for adverse health and climate impact, especially for diesel engines with no or limited exhaust aftertreatment.
25.	Holmdahl, Lena, 1954, et al. (author) Overproduction of transforming growth factor-beta1 (TGF-beta1) is associated with adhesion formation and peritoneal fibrinolytic impairment. 2001 In: Surgery. - : Elsevier BV. - 0039-6060. ; 129:5, s. 626-32 Journal article (peer-reviewed)abstract Reduction in peritoneal fibrinolytic capacity and increased transforming growth factor-beta1 (TGF-beta1) production are associated with adhesion development. This study investigated the expression of TGF-beta1 in peritoneal tissue, and possible correlation with components of the fibrinolytic system locally in peritoneal tissue.
26.	Ivarsson, Marie-Louise, 1956, et al. (author) Characterization and fibrinolytic properties of mesothelial cells isolated from peritoneal lavage. 1998 In: Scandinavian journal of clinical and laboratory investigation. - 0036-5513. ; 58:3, s. 195-203 Journal article (peer-reviewed)abstract Human peritoneal mesothelial cells were harvested from patients undergoing open or laparoscopic surgery for non-septic conditions using three different approaches: (1) from a peritoneal biopsy, (2) from peritoneal fluid, and (3) from lavage fluid collected from peritoneal cavity. When these different methods were compared, cells derived from peritoneal fluid or lavage were more likely to result in established cultures than those obtained from biopsies. The cells displayed morphological, immunohistochemical and ultrastructural characteristics of mesothelial cells. The cultured mesothelial cells produced tissue type plasminogen activator (t-PA), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor type-1 and type-2 (PAI-1 and PAI-2) during unstimulated conditions. Treatment with the proinflammatory mediators LPS and TNF-alpha resulted in an overall decreased fibrinolytic capacity with a decrease in the release of t-PA and an increase in plasminogen activator inhibitors PAI-1 and PAI-2. TNF-alpha had a more profound effect than LPS, especially on the release of t-PA. This may be an important mechanism by which inflammatory mediators disrupt the fibrin degradation. In conclusion, peritoneal lavage is a convenient and reproducible source of mesothelial cells for culture.
27.	Ivarsson, Marie-Louise, 1956, et al. (author) Plasminogen activator/plasminogen activator inhibitor-1 and cytokine modulation by the PROACT System. 2003 In: Fertility and sterility. - 0015-0282. ; 79:4, s. 987-92 Journal article (peer-reviewed)abstract To examine the effects of the PROACT treatment on the fibrinolytic system and inflammatory cytokines in human peritoneum.
28.	Ivarsson, Marie-Louise, 1956, et al. (author) Response of visceral peritoneum to abdominal surgery. 2001 In: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 88:1, s. 148-51 Journal article (peer-reviewed)abstract Postoperative adhesion formation has been associated with a reduced capacity to degrade fibrin within the peritoneal cavity. Peritoneal fibrinolytic capacity has been shown to decrease during the course of a surgical operation. The aim of this study was to investigate whether tissue-type plasminogen activator (tPA), a key fibrinolytic enzyme, is released into the peritoneal cavity during operation.
29.	Iveson, Timothy J., et al. (author) 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT) : an international, randomised, phase 3, non-inferiority trial 2018 In: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 19:4, s. 562-578 Journal article (peer-reviewed)abstract Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1: 1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1.13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76.7% (95% CI 75.1-78.2) for the 3 month group and 77.1% (75.6-78.6) for the 6 month group, giving a hazard ratio of 1.006 (0.909-1.114, test for non-inferiority p=0.012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
30.	Iveson, Timothy, et al. (author) Toxicity and quality of life data from SCOT : An international phase III randomized (1:1) noninferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy. 2015 In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 33:15 Journal article (other academic/artistic)
31.	Jones, Robert P., et al. (author) Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial 2019 In: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048 Journal article (peer-reviewed)abstract Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
32.	Jung, Seungyoun, et al. (author) Alcohol consumption and breast cancer risk by estrogen receptor status : in a pooled analysis of 20 studies. 2016 In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:3, s. 916-928 Journal article (peer-reviewed)abstract BACKGROUND: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts.METHODS: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model.RESULTS: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status.CONCLUSIONS: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.
33.	Jung, Seungyoun, et al. (author) Anti‐Müllerian hormone and risk of ovarian cancer in nine cohorts 2018 In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:2, s. 262-270 Journal article (peer-reviewed)abstract Animal and experimental data suggest that anti‐Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case‐control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme‐linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable‐adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable‐adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59–1.67) (Ptrend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity: ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity: ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
34.	Jung, Seungyoun, et al. (author) Demographic, lifestyle, and other factors in relation to antimullerian hormone levels in mostly late premenopausal women 2017 In: Fertility and Sterility. - : ELSEVIER SCIENCE INC. - 0015-0282 .- 1556-5653. ; 107:4 Journal article (peer-reviewed)abstract Objective: To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimullerian hormone (AMH) concentrations in mostly late premenopausal women. Design: Cross-sectional study. Setting: Not applicable. Patient(s): A total of 671 premenopausal women not known to have cancer. Intervention(s): None. Main Outcome Measure(s): Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. Result(s): Older women had significantly lower AMH concentrations (>= 40 [n = 444] vs. < 35 years [n = 64], multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (< 12 [n = 96] vs. >= 14 years [n = 200]: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). Conclusion(s): Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.
35.	Karlsson, Louise, et al. (author) ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram 2013 In: International journal of legal medicine. - : Springer Verlag (Germany). - 0937-9827 .- 1437-1596. ; 127:3, s. 579-586 Journal article (peer-reviewed)abstract P-glycoprotein (P-gp), encoded by the ABCB1/MDR1 gene, is a drug transporter at the blood–brain barrier. Several polymorphisms in the ABCB1 gene are known to affect the activity and/or expression of P-gp, thereby influencing the treatment response and toxicity of P-gp substrates like citalopram and venlafaxine. In this study, we aimed to investigate the frequency of ABCB1 genotypes in forensic autopsy cases involving these two antidepressants. Further, the distribution of ABCB1 genotypes in deaths related to intoxication was compared to cases not associated to drug intoxication. The study included 228 forensic autopsy cases with different causes and manners of deaths. The ABCB1 single nucleotide polymorphisms (SNPs) G1199A, C1236T, C3435T and G2677T/A for these individuals were determined. The SNPs C1236T and C3435T in venlafaxine-positive cases were significantly different between the intoxication cases and non-intoxications. This was not seen for cases involving citalopram, indicating that the effect of genetic variants might be substrate specific. This novel finding should, however, be confirmed in future studies with larger number of cases.
36.	Karlsson, Louise, et al. (author) ABCB1 gene polymorphisms in forensic autopsy cases positive for citalopram and venlafaxine Other publication (other academic/artistic)abstract P-glycoprotein (P-gp), encoded by the ABCB1/MDR1 gene, is a drug transporter expressed on e.g. the endothelial cells of the blood-brain barrier which regulates the efflux of many drugs. Several polymorphisms in the ABCB1 gene are known to affect the activity and/or expression of P-gp, thereby influencing the treatment response and toxicity of P-gp substrates. It has previously been shown that the antidepressant drugs citalopram and venlafaxine are actively transported out of the brain by P-gp using a mouse model. In the present study we aimed to investigate the frequency of ABCB1 genotypes in forensic autopsy cases positive for these two antidepressants. Further, the distribution of ABCB1 genotypes in deaths related to intoxication was compared to cases not associated to drug intoxication. The present study included 228 forensic autopsy cases positive for venlafaxine and citalopram with different causes of deaths. The ABCB1 single nucleotide polymorphisms (SNPs) G1199A, C1236T, C3435T and G2677T/A for these individuals were determined by Pyrosequencing. The SNPs C1236T, G2677T and C3435T in venlafaxine positive cases were significantly different between the intoxication cases and non-intoxications. The latter novel finding should, however, be confirmed in future studies with larger number of cases.
37.	Korhonen, Kimmo, et al. (author) Particle emissions from a modern heavy-duty diesel engine as ice nuclei in immersion freezing mode: a laboratory study on fossil and renewable fuels 2022 In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 22:23, s. 1615-1631 Journal article (peer-reviewed)abstract We studied ice-nucleating abilities of particulate emissions from a modern heavy-duty diesel engine using three different types of fuel. The polydisperse particle emissions were sampled during engine operation and introduced to a continuous-flow diffusion chamber (CFDC) instrument at a constant relative humidity RHwater=110 %, while the temperature was ramped between −43 and −32 ∘C (T scan). The tested fuels were EN 590 compliant low-sulfur fossil diesel, hydrotreated vegetable oil (HVO), and rapeseed methyl ester (RME); all were tested without blending. Sampling was carried out at different stages in the engine exhaust aftertreatment system, with and without simulated atmospheric processing using an oxidation flow reactor. In addition to ice nucleation experiments, we used supportive instrumentation to characterize the emitted particles for their physicochemical properties and presented six parameters. We found that the studied emissions contained no significant concentrations of ice-nucleating particles likely to be of atmospheric relevance. The substitution of fossil diesel with renewable fuels, using different emission aftertreatment systems such as a diesel oxidation catalyst, and photochemical aging of total exhaust had only minor effect on their ice-nucleating abilities.
38.	Langenskiöld, Marcus, 1972, et al. (author) Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer. 2009 In: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380. ; 30:4, s. 210-220 Journal article (peer-reviewed)abstract Background and Objectives: Degradation of extracellular matrix is important for tumour growth and invasion, which in part is regulated by the plasminogen activation system. The aim of the study was to evaluate the protein expression of urokinase plasminogen activator (uPA) and plasminogen-activating inhibitor-1 (PAI-1) in plasma, tumour-free mucosa and tumour tissue regarding their prognostic value in colon and rectal cancer. Methods: Patients (n = 221) undergoing surgery for colorectal cancer were prospectively included. Samples were assayed by ELISA technique. Results: PAI-1 in tumour tissue (p = 0.006), plasma (<0.0001) and uPA in tumour-free mucosa (p = 0.006) were associated with survival in rectal cancer in univariate analysis. An uPA expression level below 1.1 ng/mg (log rank test, p < 0.0001) in tumour-free mucosa was associated with poor survival in rectal cancer. This was true also for patients without disseminated disease (M(0), p = 0.02). PAI-1 in plasma correlated with metastatic disease (p < 0.0001). uPA and PAI-1 were not associated with survival in either tumour tissue, mucosa or plasma in patients with colon cancer. Conclusions: uPA and PAI-1 have a differential prognostic impact in colon and rectal cancer. Preoperative mucosal uPA and plasma PAI-1 protein expression could possibly be used as prognostic factors in rectal cancer.
39.	Langenskiöld, Marcus, 1972, et al. (author) Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer 2005 In: International journal of colorectal disease. - 0179-1958. ; 20:3, s. 245-52 Journal article (peer-reviewed)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.
40.	Langenskiöld, Marcus, 1972, et al. (author) Increased TGF-beta 1 protein expression in patients with advanced colorectal cancer. 2008 In: Journal of surgical oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 97:5, s. 409-15 Journal article (peer-reviewed)abstract INTRODUCTION: There is evidence that TGF-beta 1 plays a role as a tumor suppressor in early disease and has pro-oncogenic effects in advanced tumor stage. The aim of the study was to correlate TGF-beta 1 in plasma and tissue to clinical and pathological parameters in patients with various stages of disease progression. METHODS: One hundred sixty-nine patients who underwent surgery for a colorectal carcinoma were prospectively included. Blood samples, tumor free mucosa and tumor biopsies were assayed. RESULTS: TGF-beta 1 protein expression in tumors increased with increasing T-stage regardless of whether patients with metastatic disease were included or not (P = 0.0006). Patients with metastatic disease showed elevated TGF-beta 1 protein expression in both tumor tissue (P = 0.004) and plasma (P = 0.001) compared to those without metastatic disease. TGF-beta 1 protein expression was higher in the colon compared with the rectum in both tumor tissue and tumor-free bowel (P = 0.03), regardless of whether patients with metastatic disease were included or not. This difference was mainly attributable to a higher TGF-beta 1 protein expression in non-metastatic patients with lymph node positivity (P = 0.005). CONCLUSIONS: Higher TGF-beta 1 protein expression is associated with increasing T-stage and metastatic disease, indicating that TGF-beta 1 is of importance in tumor progression. The localization of the tumor seems to influence the TGF-beta 1 protein expression in patients with tumor cell-positive lymph nodes.
41.	Langenskiöld, Marcus, 1972, et al. (author) Intestinal mucosal MMP-1 - a prognostic factor in colon cancer. 2013 In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:5, s. 563-569 Journal article (peer-reviewed)abstract Abstract Objective. There is evidence that transforming growth factor-β1 (TGF-β1) and matrix metalloproteinases (MMPs) play an important role in tumor invasion and progression in colorectal cancer. The aim of this study was to assess their utility in prediction of cancer-specific survival (CSS). Materials and methods. 136 patients undergoing curative surgery for colorectal carcinoma were prospectively included. Samples were taken from tumor and tumor-free intestinal mucosa and ELISA was used to assess protein levels in the tissues. Patients were followed for CSS. The median follow-up time for all included patients was 65 months (range: 45-92). The main outcome measure was CSS. Results. T stage, lymph node involvement and high levels of MMP-1 as well as MMP-9 in tumor-free mucosa tissue were significantly associated with CSS in colon cancer in univariate analysis. This prognostic strength was maintained for MMP-1 and N-status in multivariate analysis. Conclusions. The results indicate that MMP-1 is independently associated with CSS in patients with colon cancer. Furthermore, a possible clinical implication is that MMP-1 protein expression in tumor-free mucosa could identify colon cancer patients with poor CSS in need of more intensified adjuvant treatment.
42.	Lensvelt, Mare M A, et al. (author) Decreased Peritoneal Expression of Active Transforming Growth Factor {beta}1 During Laparoscopic Cholecystectomy With Heated Carbon Dioxide. 2010 In: Archives of surgery (Chicago, Ill. : 1960). - : American Medical Association (AMA). - 1538-3644 .- 0004-0010. ; 145:10, s. 968-72 Journal article (peer-reviewed)abstract BACKGROUND: Laparoscopic surgery involves the establishment of a pneumoperitoneum, mostly using carbon dioxide. Cooling of the peritoneum, due to insufflation, may traumatize the peritoneum and disturb local biological processes. The current study was performed to assess the effect of the temperature of carbon dioxide on peritoneal transforming growth factor β1 (TGF-β1) expression. DESIGN: Patients were randomized into 2 groups. In one group, a pneumoperitoneum was created with carbon dioxide at room temperature; in the other, with carbon dioxide at body temperature. Peritoneal biopsy specimens were taken at the start and end of surgery. SETTING: Community hospital. PATIENTS: Thirty patients scheduled for laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Tissue concentrations of total and active TGF-β1 were measured using enzyme-linked immunosorbent assays. RESULTS: At the start of surgery, there were no significant differences between groups in the total and active fractions of TGF-β1. At the end of the procedure, the peritoneal active TGF-β1 concentrations were significantly lower (P=.03) in patients receiving carbon dioxide at body temperature. In contrast, the concentrations of total TGF-β1 did not differ between groups. A slight, nonsignificant increase in total and active TGF-β1 levels was observed in patients receiving unheated carbon dioxide. The ratio of active to total TGF-β1 did not change during procedures, and there were no differences between groups. CONCLUSIONS: Heating of carbon dioxide, used for insufflation, to body temperature decreases the expression of active TGF-β1 in the peritoneum. Considering the broad biological effects of TGF-β1, including the regulation of peritoneal healing and oncological processes, this observation might have clinical repercussions.
43.	Lensvelt, Mare M A, et al. (author) Peritoneal transforming growth factor beta-1 expression during prolonged laparoscopic procedures. 2010 In: Journal of laparoendoscopic & advanced surgical techniques. Part A. - : Mary Ann Liebert Inc. - 1557-9034 .- 1092-6429. ; 20:6, s. 545-50 Journal article (peer-reviewed)abstract BACKGROUND: Laparoscopic surgery may affect peritoneal physiology. Short-term laparoscopic surgery does not affect peritoneal transforming growth factor beta (TGF-b1) expression. The current study was conducted to evaluate the hypothesis that prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression. STUDY DESIGN: In the first study, 24 patients scheduled for a right colonic resection were enrolled in the trial. Twelve underwent conventional surgery (CCR) and 12 were operated on laparoscopically (LCR). In the second study, 12 patients undergoing laparoscopic gastric bypass (LGB) surgery for morbid obesity were included. Biopsies of the parietal peritoneum were taken at standardized moments during the procedures. Tissue concentrations of active and total TGF-b1 were measured by using enzyme-linked immunosorbent assays. RESULTS: During the LCR, there was a significant increase in peritoneal active TGF-b1 levels (P < 0.05). A similar, but not significant, trend was observed during the CCR. A similar pattern was seen in the total TGF-b1 concentrations during both procedures. The LGB procedure did not affect peritoneal active or total TGF-b1 concentrations. During the procedure, both the active and total TGF-b1 levels were significantly higher in the LCR, when compared to the LGB, group (P < 0.05). CONCLUSIONS: Prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression, depending on the procedure performed. Considering the role of TGF-b1 in various biologic processes, including adhesiogenesis and oncology, these results may have clinical consequences.
44.	Lindberg Falk, Monica, et al. (author) Feminism, Buddhism and Transnational Women's Movements in Thailand 2010 In: Women's Movements in Asia: Feminisms and Transnational Activism. Book chapter (other academic/artistic)
45.	Lindberg Falk, Monica, et al. (author) Women In Between: Becoming Religious Persons in Thailand. 2009 In: Women in Asia. - 0415445256 ; IV, s. 225-246 Book chapter (peer-reviewed)
46.	Lundin, Anders, et al. (author) Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models 2018 In: Stem Cell Reports. - : Cell Press. - 2213-6711. ; 10:3, s. 1030-1045 Journal article (peer-reviewed)abstract In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of biological characterization. Here, we report human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined conditions through long-term neuroepithelial-like stem (ltNES) cells. We characterized NES-Astro and astrocytic models from primary sources, astrocytoma (CCF-STTG1), and hiPSCs through transcriptomics, proteomics, glutamate uptake, inflammatory competence, calcium signaling response, and APOE secretion. Finally, we assess modulation of astrocyte biology using APOE-annotated compounds, confirming hits of the cholesterol biosynthesis pathway in adult and hiPSC-derived astrocytes. Our data show large diversity among astrocytic models and emphasize a cellular context when studying astrocyte biology.
47.	Malmborg, Agota, et al. (author) Sexual function changes attributed to hormonal contraception use : a qualitative study of women experiencing negative effects 2020 In: European journal of contraception & reproductive health care. - : Taylor & Francis. - 1362-5187 .- 1473-0782. ; 25:3, s. 169-175 Journal article (peer-reviewed)abstract Objective: To increase the understanding of women who experience negative effects on sexual function when using hormonal contraception.Methods: We performed 24 in-depth interviews with women who had previously experienced negative sexual function effects while using hormonal contraceptives. The thematic analysis method was used.Results: 'After experience comes insight', 'Lubrication and desire go hand in hand', 'Mental wellbeing comes before desire' and 'The contraceptive counsellor potentially facilitates insight and decision-making' were the main themes found in the study.Conclusions: This selected group of women described lubrication difficulties and decreased sexual desire associated with both contraceptive use and the menstrual cycle. Contraceptive use became easier with age and with better understanding. The contraceptive counsellor could facilitate the process. Further choice between hormonal or non-hormonal contraceptive methods depended primarily on experienced adverse effects on mood, and secondarily on sexual function, weighed against the advantages or disadvantages experienced during the person's own menstrual cycle.
48.	Robles-Zurita, Jose, et al. (author) SCOT : a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer 2018 In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 119:11, s. 1332-1338 Journal article (peer-reviewed)abstract BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken.RESULTS: The 3M arm is less costly (-4881; pound 95% CI: -6269; pound -3492) pound and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3M had lower QALYs than 6M (not statistically significant).CONCLUSIONS: Overall, 3M dominates 6M with no significant detrimental impact on QALYs. The results provide the economic case that a 3M treatment strategy should be considered a new standard of care.
49.	Ruiz-Jasbon, Fernando, et al. (author) Results at 3-year follow-up of totally extraperitoneal (TEP) hernia surgery with long-term resorbable mesh 2020 In: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 24, s. 669-676 Journal article (peer-reviewed)abstract © 2020, The Author(s). Introduction: Synthetic non-resorbable mesh is almost standard in hernia surgery. However, several studies have showed negative effects of permanent implants such as chronic inflammation and complications involving different organs bordering the mesh. Such complications can raise the risk of chronic post-operative pain (CPP). Recently promising results regarding CPP have been published in patients with Lateral Inguinal Hernia (LIH) using a slowly resorbable mesh in Lichtenstein technique. For this reason the aim of the present study was to find the effect of a slowly resorbable implant on the long-term rate of hernia recurrence and chronic post-operative pain in patients with LIH repaired with TEP procedure. Methods: Prospective pilot study of TEP repair using TIGR® Matrix Surgical Mesh in 35 primary LIH. At 3-year follow-up the Visual Analogue Scale (VAS) and the Inguinal Pain Questionnaire were employed to assess pain. Recurrence was determined by ultrasound and clinical examination. Results: All patients completed the pain questionnaires but one patient did not attend the planned clinical examination for the 3-year follow-up. No patients had CPP, as defined in the World Guidelines for Groin Hernia Management. Almost all patients had lower VAS score in any activity 3years following surgery in comparison to the preoperative period. Three patients (8.8%) suffered symptomatic recurrence during the 3-year follow-up. Conclusion: TEP repair in patients with LIH using a synthetic long-term resorbable mesh was found to be encouraging respecting chronic post-operative pain at 3-year follow-up but at the cost of an increased risk of recurrence.
50.	Solberg, Anna, 1961, et al. (author) A local imbalance between MMP and TIMP may have an implication on the severity and course of appendicitis. 2008 In: International journal of colorectal disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 23:6, s. 611-8 Journal article (peer-reviewed)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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