| 1. |
- Devarakonda, Sravani, et al.
(författare)
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Low-grade intestinal inflammation two decades after pelvic radiotherapy.
- 2023
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Ingår i: EBioMedicine. - 2352-3964. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
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| 2. |
- Gliga, Anda R., et al.
(författare)
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Short and long-term associations between serum proteins linked to cardiovascular disease and particle exposure among constructions workers
- 2023
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 49:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Construction workers are exposed to respirable dust, including respirable crystalline silica (RCS), which is a potential risk factor for cardiovascular disease (CVD). The aim of this study was to evaluate whether exposure to particles among construction workers is associated with short-and long-term alterations in CVD-related serum proteins. Methods Using proximity extension assay, we measured 92 serum proteins linked to CVD among active male construction workers (N=65, non-smokers) sampled on two occasions: during work and after vacation. First, we used linear models to identify short-term changes in proteins associated with particle exposure (assessed as respirable dust and RCS) during work. Secondly, we used linear mixed models to evaluate whether these associations were long-term, ie, persistent after vacation. Results The median exposure to respirable dust and RCS during work were 0.25 mg/m3 and 0.01 mg/m3, respec-tively. Respirable dust was associated with short-term changes in six proteins (tissue factor, growth hormone, heme oxygenase-1, dickkopf-related protein-1, platelet-derived growth factor-B, stem cell factor); long-term associations were observed for the former three proteins. RCS was associated with short-term changes in five proteins (carcinoembryonic antigen-related cell adhesion molecule-8, hydroxyacid oxidase-1, tissue factor, car-bonic anhydrase-5A, lectin-like oxidized LDL receptor-1); long-term associations were observed for the former four proteins. Conclusions Moderate exposure to particles in the construction industry is associated with both short-and long-term changes in circulating CVD-related proteins. Further studies are needed to evaluate if these changes are predictors of occupationally induced clinical CVD.
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| 3. |
- Grahn, Karin, et al.
(författare)
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Occupational exposure to particles and biomarkers of cardiovascular disease – during work and after vacation
- 2022
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 95, s. 1537-1548
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Tidskriftsartikel (refereegranskat)abstract
- Objective Ambient particle matter is a risk factor for cardiovascular disease (CVD). However, little is known about associations between particles in occupational settings and risk of CVD. We investigated associations between occupational dust exposure and biomarkers of CVD, and potential recovery effects after vacation.Methods Personal dust exposure measurements (respirable silica, respirable dust < 4 mu m, and particles of 0.1-10 mu m (PM 0.1-10) were conducted once, and biological sampling were performed twice on non-smoking, male construction workers in Stockholm county, Sweden; during work and immediately after summer vacation. Linear regressions with adjustments for confounders and covariates were performed evaluating associations between occupational dust exposure and biomarkers. Paired t tests were performed evaluating changes before and after vacation.Results Sixty-five workers participated. Homocysteine concentrations were significantly higher with increasing concentrations (mg/m(3)) of respirable silica, respirable dust, and PM 0.1-10, and pulse rate with higher levels of respirable dust and dust of PM 0.1-10. Homocysteine levels were also positively correlated to number of years of dust exposure, as were low-density lipoprotein (LDL) levels. A clear recovery effect was present for LDL after vacation, but not for homocysteine.Conclusions Occupational dust exposure was associated with some CVD risk markers, even at mean exposure concentrations below the Swedish occupational exposure limits for respirable silica and respirable dust, respectively. Vacation resulted in recovery for some risk markers. However, the change of the homocysteine and LDL levels suggest a long-term effect. Reduction of occupational exposure to dust may decrease the risk of CVD among exposed workers.
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| 4. |
- Grahn, Karin, et al.
(författare)
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Occupational noise exposure and acute effects on pulse rate and blood pressure
- 2022
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Ingår i: Proceedings of the International Congress on Acoustics.
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Konferensbidrag (refereegranskat)abstract
- Environmental exposure to noise and particle matter (PM) are risk factors for cardiovascular disease (CVD). Although there are often higher levels in occupational settings, little is known about noise and particle exposures at work and CVD risks. We investigated occupational noise and particle exposures and acute effects on pulse rate and blood pressure. 46 active, non-smoking, male construction workers were included in the study. Continuously logged personal exposure measurements of noise (LAmax, LCpeak) and dust of PM 0.1-10, continuously logged pulse rate and blood pressure measurements were performed for one working day on each participant. Significant associations were seen between these three exposures and acute changes in pulse rate. The effects were seen below the Swedish occupational exposure limits for LAmax and LCpeak, indicating that these limits may not protect from adverse cardiovascular effects. Also, an additive effect on pulse rate was seen if simultaneously exposed to noise and dust. No association were found between these exposures and blood pressure.
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| 5. |
- Gustavsson, Helene, 1977, et al.
(författare)
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ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer.
- 2009
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Ingår i: BJU international. - 1464-410X .- 1464-4096. ; 104:11, s. 1786-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the expression of 'ADAM metallopeptidase with thrombospondin type I motif, 1' (ADAMTS1) in human prostate cancer, and to study its relationship to microvessel density (MVD) and metastasis. ADAMTS1 has been described as an anti-angiogenic and antitumour factor, but its function in prostate cancer is unknown. PATIENTS AND METHODS: ADAMTS1 expression was evaluated by immunohistochemistry in specimens obtained by transurethral resection of the prostate from patients with hormone-naïve and hormone-refractory prostate tumours, including adjacent benign tissue. A semiquantitative scoring system was used for evaluating the staining. MVD was quantified by counting the number of CD34-positive blood vessels. RESULTS: ADAMTS1 was strongly expressed in the luminal epithelial cells in benign prostate glands, whereas expression was significantly lower in prostate cancer cells. There was no obvious difference between hormone-naïve and hormone-refractory tumours, and ADAMTS1 expression did not correlate with Gleason score. However, in hormone-refractory tumours from patients with metastatic disease, the expression of ADAMTS1 was significantly lower than in tumours from patients without metastases. Furthermore, the MVD was higher in hormone-refractory than in hormone-naïve tumours and benign tissue, and MVD correlated with Gleason score. There was no association between ADAMTS1 and MVD in the hormone-naïve tumours, while hormone-refractory tumours with low ADAMTS1 expression had a higher MVD than those with moderate/high expression. CONCLUSION: ADAMTS1 expression is decreased in prostate cancer, and might be involved in the early steps of prostate cancer development. Further, ADAMTS1 might have an anti-angiogenic and antimetastatic role in hormone-refractory prostate cancer, where low ADAMTS1 expression is associated with a high MVD and metastasis.
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| 6. |
- Gustavsson, Helene, 1977, et al.
(författare)
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ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors.
- 2010
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this study was to investigate the function of ADAMTS1 in prostate tumors.
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| 7. |
- Gustavsson, Helene, 1977, et al.
(författare)
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Altered expression of genes regulating angiogenesis in experimental androgen-independent prostate cancer.
- 2008
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Ingår i: Prostate. - : Wiley. - 1097-0045. ; 68:2, s. 161-170
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The aim of this study was to investigate how the expression of genes regulating angiogenesis is altered when prostate cancer cells progress into androgen-independency. METHODS A gene array specific for angiogenesis was used to compare the human prostate cancer cell line LNCaP (androgen-dependent) with its more angiogenic and tumorigenic subline LNCaP-19 (androgen-independent). Results were verified with real-time RT-PCR, and further investigations were focused on the angiogenesis inhibitor a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Expression of ADAMTS1 was investigated in vitro as well as in subcutaneous tumors with real-time RT-PCR and Western blotting. Microvessel density (MVD), versican proteolysis and protein levels of TIMP-2 and TIMP-3, known as ADAMTS1 inhibitors, were also analyzed in tumor xenografts. RESULTS The gene array revealed decreased expression of ADAMTS1, ephrin-A5, fibronectin 1, and neuropilin 1 in LNCaP-19 compared to LNCaP, while expression of midkine and VEGF were increased. Further studies showed that mRNA and protein levels of ADAMTS1 were significantly lower in LNCaP-19 compared to LNCaP, both in vitro and in subcutaneous tumors. The amount of ADAMTS1 correlated negatively with MVD, but no relation was found between ADAMTS1 and versican proteolysis. CONCLUSIONS Expression of several genes associated with angiogenesis was altered during transition into androgen-independency. Among these, a significant decrease was found for ADAMTS1, whose expression inversely correlated with MVD. Its role in progression of prostate cancer needs further investigation, but this inhibitor of angiogenesis could be an interesting candidate for future anti-angiogenic therapy.
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| 8. |
- Gustavsson, Karin, et al.
(författare)
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1920-talets by- och bebyggelsedokumentationer
- 2009
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Ingår i: Kring Kärnan : Helsingborgs museums publikation. 37. , Museum i 100 år : Helsingborgs museum från 1909. - 0440-663X. - 9789187274343 ; 37, s. 105-132
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Bokkapitel (populärvet., debatt m.m.)
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| 9. |
- Hedlund Lindberg, Julia, et al.
(författare)
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Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid
- 2024
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Ingår i: iScience. - 2589-0042. ; 27:2
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Tidskriftsartikel (refereegranskat)abstract
- Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence–based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91–1.00) at a specificity of 0.67 (0.40–0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples.
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| 10. |
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