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- Chadeau-Hyam, M., et al.
(författare)
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Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:5, s. 1065-1072
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.METHODS:We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.RESULTS:Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.CONCLUSIONS:This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
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- Gerdtsson, Axel, et al.
(författare)
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Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients
- 2023
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Ingår i: Bju International. - 1464-4096 .- 1464-410X. ; 132:3, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- Objective To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. Materials and methods Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alphafetoprotein; b-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and postchemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out), was analysed using decision curve analysis. Results Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. Conclusions The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.
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- Georgiadis, Panagiotis, et al.
(författare)
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DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia
- 2019
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 126, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma.METHODS: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene.RESULTS: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis.CONCLUSIONS: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.
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- Kumar, B, et al.
(författare)
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Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia.
- 2006
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Ingår i: Circulation Research. - 0009-7330. ; 98:4, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.
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- Ladfors, S. W., et al.
(författare)
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Longitudinal Follow-Up on Cardiopulmonary Exercise Capacity Related to Cardio-Metabolic Risk Factors in Children With Renal Transplants
- 2021
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Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media SA. - 2624-9367. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with chronic kidney disease, including those treated with kidney transplantation (KT), have an increased risk of cardiovascular disease. The aim of this study was to examine the cardiopulmonary exercise capacity after KT compared to matched controls, to relate the results to physical activity, blood pressure and biochemical findings and to follow exercise capacity over time. & nbsp; Methods: Patients with KT (n = 38, age 7.7-18 years), with a mean time from transplantation of 3.7 years (0.9-13.0) and mean time in dialysis 0.8 years, were examined at inclusion and annually for up to three years. Healthy controls (n = 17, age 7.3-18.6 years) were examined once. All subjects underwent a cardiopulmonary exercise test, resting blood pressure measurement, anthropometry and activity assessment. Patients also underwent echocardiography, dual-energy X-ray absorptiometry (DXA), 24-h ambulatory BP measurements (ABPM), assessment of glomerular filtration rate (GFR) and blood sampling annually. & nbsp; Results: As compared to healthy controls, KT patients showed decreased exercise capacity measured both as VO2peak (34.5 vs. 43.9 ml/kg/min, p < 0.001) and maximal load (2.6 vs. 3.5 W/kg, p < 0.0001), similarly as when results were converted to z-scores. No significant difference was found in weight, but the KT patients were shorter and had higher BMI z-score than controls, as well as increased resting SBP and DBP z-scores. The patient or parent reported physical activity was significantly lower in the KT group compared to controls (p < 0.001) In the combined group, the major determinants for exercise capacity z-scores were activity score and BMI z-score (beta = 0.79, p < 0.0001 and beta = -0.38, p = 0.007, respectively). Within the KT group, low exercise capacity was associated with high fat mass index (FMI), low activity score, low GFR and high blood lipids. In the multivariate analysis FMI and low GFR remained predictors of low exercise capacity. The longitudinal data for the KT patients showed no change in exercise capacity z-scores over time. & nbsp; Conclusion: Patients with KT showed decreased exercise capacity and increased BP as compared to healthy controls. Exercise capacity was associated to GFR, physical activity, FMI and blood lipids. It did not improve during follow-up.
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- Stein, L., et al.
(författare)
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Exploring the association between oral health literacy and alexithymia
- 2015
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Ingår i: Community Dental Health. - 0265-539X. ; 32:3, s. 143-147
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Tidskriftsartikel (refereegranskat)abstract
- Low health literacy and alexithymia have separately been emphasized as barriers to patient-practitioner communication, but the association between the two concepts has not been explored. Objective: To test the hypothesis that low oral health literacy and alexithymia are associated. Method: Adults (n=127) aged 21-80 years (56% women) participated in this cross-sectional study. Oral health literacy was assessed using the interview-based Adult Health Literacy Instrument for Dentistry (AHLID) with scores from 1-5. The self-administered Toronto Alexithymia Scale (TAS-20) was used to assess three distinct TAS-20 factors and TAS-20 total score. Results: Significant negative correlations between AHLID scores and TAS-20 factors 2, 3 and TAS-20 total score were found. Regression analyses showed that TAS-20 factor 3, externally-oriented thinking (beta=-0.21, SE=0.02, p=0.017), and TAS-20 total score (beta=-0.18, SE=0.01, p=0.036) were significant predictors of AHLID level. Conclusion: The hypothesis that low oral health literacy is associated with alexithymia was supported. This finding proposes that alexithymia may be considered as a possible factor for low oral health literacy. However, the correlations are not strong, and the results should be regarded as a first step to provide evidence with additional research on this topic being needed.
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