| 1. |
- Falk, Kristina, 1972, et al.
(författare)
-
Antifibrinolytic proCPU is present in the peritoneal cavity during surgery.
- 2003
-
Ingår i: Scandinavian journal of clinical and laboratory investigation. - 0036-5513. ; 63:4, s. 287-96
-
Tidskriftsartikel (refereegranskat)abstract
- The fibrinolytic capacity of the peritoneum plays a pivotal role in peritoneal wound healing. During surgery the balance between fibrin deposition and degradation is tilted towards deposition, leading to the formation of adhesions. In blood, carboxypeptidase U (CPU) stabilizes clots by retarding fibrinolysis. The purpose of this study was to investigate whether the more stable zymogen, proCPU, is also present in the peritoneal cavity and, if so, to examine its origin. Levels of proCPU were measured in plasma and serosal peritoneal fluid collected during surgery. Peritoneal biopsies were stained for proCPU. Two-dimensional gel electrophoresis was performed to study the protein composition of the serosal fluid compared to plasma and Western blotting to identify differences in glycosylation of proCPU, indicating possible different cellular origin. Cultured human mesothelial cells were examined for proCPU production under normal conditions and conditions mimicking surgery. We found comparable and correlating levels of proCPU in serosal fluid and plasma. ProCPU was also found where fibrin covered the injured peritoneal surface. A protein composition very similar in serosal fluid and plasma was shown by two-dimensional gel electrophoresis, and the proCPU pattern did not indicate a different origin. No proCPU production was found in cultured mesothelial cells. This is the first study to report on the presence of proCPU in the peritoneal cavity, which seems to be the result of plasma oozing out during the inflammatory reaction to the surgical trauma. This is likely to be important for the balance between fibrin deposition and degradation and thereby in the formation of postoperative adhesions.
|
|
| 2. |
- Angenete, Eva, 1972, et al.
(författare)
-
Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation
- 2007
-
Ingår i: International journal of colorectal disease. - 0179-1958. ; 22:6, s. 667-74
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In rectal cancer treatment, preoperative radiotherapy has led to reduction of local recurrence, but it is associated with morbidity and increased risk for secondary tumours. Matrix metalloproteinases (MMPs) are associated with tumour progression through tissue remodeling. The aim of this study was to investigate tissue remodeling after preoperative radiotherapy and to explore possible correlations with clinical outcome. MATERIALS AND METHODS: Ninety-one patients scheduled for rectal cancer surgery were included; 49% received preoperative radiotherapy three-field treatment, 5 x 5 Gy. Blood samples and biopsies from tumour and adjacent mucosa were taken during surgery. Biopsies and plasma were assayed with ELISA for MMP-1, MMP-2 and MMP-9. Clinical outcome was reviewed focusing on infections, perineal healing, fistula formation, anastomotic dehiscence, small bowel obstruction, local recurrence and distant metastases. RESULTS: Compared to non-irradiated mucosa, MMP-2 (p < 0.0001), MMP-1 (p = 0.03) and MMP-9 (p = 0.04) were significantly higher in irradiated normal mucosa. Tumour tissue had higher levels of MMP-2 if irradiated (p < 0.0001). A correlation between MMP-2 levels and wound infection (p = 0.02) as well as fistula formation (p = 0.04) was found. MMP-1 in mucosa (p = 0.02) and tumour (p = 0.04) were higher in patients developing distant metastases. Plasma levels were not influenced by irradiation, but MMP-2 was higher in patients who were later developing distant metastases (p = 0.007). CONCLUSIONS: Extracellular matrix remodeling after radiotherapy seems to be correlated to postoperative morbidity; MMP-2 is associated with both wound infections and fistula formation. High levels of MMP-1 in tumour and mucosa as well as MMP-2 in plasma may be correlated to risk of developing distant metastases.
|
|
| 3. |
- Angenete, Eva, 1972, et al.
(författare)
-
Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components.
- 2009
-
Ingår i: Acta oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:8, s. 1144-1151
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. Materials and methods. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. Results. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. Conclusions. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.
|
|
| 4. |
- Angenete, Eva, 1972, et al.
(författare)
-
Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients
- 2007
-
Ingår i: Int J Colorectal Dis. - 0179-1958. ; 11, s. 1331-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-beta1 (TGF-beta1) acts both as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels of TGF-beta1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy and clinical outcome. MATERIALS AND METHODS: One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field treatment 5 x 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent assay for total TGF-beta1 and active TGF-beta1. Patients were then followed for 3 years. RESULTS: Total and active TGF-beta1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-beta1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-beta1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-beta1 in plasma were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-beta1 in the rectal mucosa (p = 0.038). CONCLUSIONS: Higher levels of total TGF-beta1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active TGF-beta1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-beta1 in rectal mucosa may influence risk of local recurrence. Measurement of TGF-beta1 in rectal cancer patients may be of clinical use in the future.
|
|
| 5. |
- Angenete, Eva, 1972, et al.
(författare)
-
uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.
- 2009
-
Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 153:1, s. 46-53
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors. MATERIALS AND METHODS: Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo). RESULTS: Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01). CONCLUSIONS: There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.
|
|
| 6. |
- Boiso, Samuel, et al.
(författare)
-
ABCB1 gene polymorphisms are associated with suicide in forensic autopsies
- 2013
-
Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 23:9, s. 463-469
-
Tidskriftsartikel (refereegranskat)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. |
|
|
| 8. |
- Cederkrantz, Elin, et al.
(författare)
-
Evaluation of Effects on the Peritoneum After Intraperitoneal α-Radioimmunotherapy with (211)At.
- 2012
-
Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:6, s. 353-364
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Breast Cancer Risk Factors and Circulating Anti-Müllerian Hormone Concentration in Healthy Premenopausal Women
- 2021
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 106:11, s. E4542-E4553
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Breast cancer risk prediction in women aged 35-50 years : impact of including sex hormone concentrations in the Gail model
- 2019
-
Ingår i: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 21
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium.
- 2015
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Barrier properties and transcriptome expression in human iPSC-derived models of the blood-brain barrier
- 2018
-
Ingår i: Stem Cells. - : AlphaMed Press, Inc.. - 1066-5099 .- 1549-4918. ; 36:12, s. 1816-1827
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Models of the blood-brain barrier using iPSC-derived cells
- 2020
-
Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 107
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Immersion freezing ability of freshly emitted soot with various physico-chemical characteristics
- 2021
-
Ingår i: Atmosphere. - : MDPI AG. - 2073-4433. ; 12:9
-
Tidskriftsartikel (refereegranskat)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. |
|
|
| 16. |
|
|
| 17. |
- Falk, Peter, 1962, et al.
(författare)
-
Examination gloves affect secretion of matrix metalloproteinases and their inhibitors from human abdominal skin fibroblasts.
- 2003
-
Ingår i: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. - 1067-1927. ; 11:3, s. 230-4
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Studies of TGF-beta(1-3) in serosal fluid during abdominal surgery and their effect on in vitro human mesothelial cell proliferation.
- 2009
-
Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 154:2, s. 312-6
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
TGF-β1 promotes transition of mesothelial cells into fibroblast phenotype in response to peritoneal injury in a cell culture model.
- 2013
-
Ingår i: International journal of surgery (London, England). - : Ovid Technologies (Wolters Kluwer Health). - 1743-9159 .- 1743-9191. ; 11:9, s. 977-982
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Anti-Mullerian hormone and endometrial cancer : a multi-cohort study
- 2017
-
Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 117:9, s. 1412-1418
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies.
- 2017
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 881-893
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Circulating anti-Müllerian hormone and breast cancer risk : a study in ten prospective cohorts
- 2018
-
Ingår i: International Journal of Cancer. - Hoboken : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:11, s. 2215-2226
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
GWAS META-analysis followed by MENDELIAN randomisation revealed potential control mechanisms for circulating α-klotho levels.
- 2022
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 31:5, s. 792-802
-
Tidskriftsartikel (refereegranskat)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.
(författare)
-
Effects of renewable fuel and exhaust aftertreatment on primary and secondary emissions from a modern heavy-duty diesel engine
- 2021
-
Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 156
-
Tidskriftsartikel (refereegranskat)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. |
|
|
