| 1. |
- Lindmark, Fredrik, et al.
(författare)
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Analysis of the macrophage scavenger receptor 1 gene in Swedish hereditary and sporadic prostate cancer.
- 2004
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 59:2, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS: DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS: A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5'- or 3'-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P = 0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION: Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology.
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| 2. |
- Wahlin, Anders, et al.
(författare)
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Results of risk-adapted therapy in acute myeloid leukaemia. A long-term population-based follow-up study
- 2009
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 83:2, s. 99-107
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Tidskriftsartikel (refereegranskat)abstract
- In 1997-2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18-60 yr were assigned to one of three risk groups. In this report we account for the long-term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high-dose cytarabine. Allogeneic stem cell transplantation (allo-SCT) from an human leucocyte antigen-identical sibling was recommended in standard and poor-risk patients, whereas unrelated donor transplant was reserved for poor-risk patients. Autologous (auto-SCT) was optional for standard or poor risk patients not eligible for allo-SCT. Two hundred seventy-nine patients with de novo or secondary (9%) AML, median age 51 (18-60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard- and poor-risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow-up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4-yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4-yr OS rates were 60, 57 and 24%, respectively. Median relapse-free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four-year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred-ten transplantations were performed in CR1; 74 allo-SCT (50 sibling, 24 unrelated donor), and 36 auto-SCT. Non-relapse mortality was 16% for allo-SCT patients. Outcome after relapse was poor with median time to death 163 d and 4-yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population-based cohort of adult AML patients <60 yr old; (ii) a risk-adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.
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| 3. |
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| 4. |
- Ageberg, Malin, et al.
(författare)
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Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis.
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- The t(6;9)(p22;q34) chromosomal translocation is found in a subset of patients with acute myeloid leukemia (AML). The translocation results in a fusion between the nuclear phosphoprotein DEK and the nucleoporin NUP214 (previously CAN). The mechanism by which the fusion protein DEK-NUP214 contributes to leukemia development has not been identified, and disruptions of normal cellular functions by DEK-NUP214 have previously not been described. In the present study, a novel effect of the DEK-NUP214 fusion protein is demonstrated. Our findings reveal a substantial increase in global protein synthesis in DEK-NUP214 expressing cells. Furthermore, we conclude that this effect is not the result of dysregulated transcription but merely due to increased translation. Consistent with the association with AML, the increased protein synthesis mediated by DEK-NUP214 is restricted to cells of the myeloid lineage. Analysis of potential mechanisms for regulating protein synthesis shows that expression of DEK-NUP214 correlates to the phosphorylation of the translation initiation protein, EIF4E. The present data provide evidence that increase of translational activity constitutes a mechanism by which the leukemogenic effect of DEK-NUP124 may be mediated. (c) 2008 Wiley-Liss, Inc.
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| 5. |
- Ageberg, Malin, et al.
(författare)
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The involvement of cellular proliferation status in the expression of the human proto-oncogene DEK
- 2006
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Ingår i: Haematologica. - 1592-8721. ; 91:2, s. 268-269
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The role of the DEK protein, involved in the leukemia-associated fusion protein DEK-CAN, is not yet known. In this study, we show a higher expression of DEK mRNA in immature cells than in mature cells. Furthermore, a correlation between DEK expression and cell proliferation was demonstrated, suggesting that DEK plays a role in the proliferation of hematopoietic cells and raising the question of whether the DEK-CAN fusion protein might perturb regulation of proliferation in leukemic cells.
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| 6. |
- Ahonen, Hanna, et al.
(författare)
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Applying World Dental Federation Theoretical Framework for Oral Health in a General Population
- 2021
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Ingår i: International Dental Journal. - : Elsevier. - 0020-6539 .- 1875-595X. ; 72:4, s. 536-544
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The World Dental Federation (FDI) has recently proposed a new definition and theoretical framework of oral health. The theoretical framework includes 4 main components and describes the relationships amongst them. In 2020, an international work group proposed the minimum Adult Oral Health Standard Set (AOHSS) of variables to measure oral health, which was mapped onto the FDI's theoretical framework. By using an empirical data set, the proposed variables in the AOHSS and the potential interactions amongst the components of the FDI's theoretical framework can be tested. The purpose of this research was to investigate structural relations of the components of the FDI's theoretical framework of oral health based on data from a general adult population. Methods: Data from a previously conducted Swedish cross-sectional study focusing on oral health were utilised (N = 630; women, 55.2%; mean age, 49.7 years [SD, 19.2]). Variable selection was guided by the AOHSS. Structural equation modeling was used to analyse relationships amongst the components of the FDI's theoretical model (core elements of oral health, driving determinants, moderating factors, and overall health and well-being). Results: The Oral Health Impact Profile (OHIP)-14, xerostomia, and aesthetic satisfaction had statistically significant direct effects on overall health and well-being (p < .05). Driving determinants and moderating factors had statistically significant direct effects on all core elements of oral health (p < .05) except aesthetic satisfaction (p = .616). The predictors explained 24.1% of the variance of the latent variable overall health and well-being. Based on several indices, the proposed model showed acceptable model fit. Conclusions: The FDI's theoretical framework can be used to describe different components of oral health and the relationship amongst them in an adult general population. Further research based on the FDI's theoretical framework in other populations and settings is needed to explore complex interactions and possible relationships that form oral health and to investigate other or additional important social determinants.
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| 7. |
- Ahonen, Hanna, et al.
(författare)
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Clinical and self-reported measurements to be included in the core elements of the World Dental Federation's theoretical framework of oral health
- 2021
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Ingår i: International Dental Journal. - : Elsevier. - 0020-6539 .- 1875-595X. ; 71:1, s. 53-62
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Oral health is part of general health, and oral diseases share risk factors with several non-communicable diseases. The World Dental Federation (FDI) has published a theoretical framework illustrating the complex interactions between the core elements of oral health (CEOHs): driving determinants, moderating factors, and general health and well-being. However, the framework does not specify which self-reported or clinical measurements to be included in the CEOHs. Objectives To explore oral health measurements relevant for a general adult population to be included in the CEOHs in the FDI's theoretical framework of oral health. Materials and methods A psychometric study was performed, using cross-sectional data from Sweden (N = 630, 54% women, mean age 49.7 years). The data set initially consisted of 186 self-reported and clinical measurements. To identify suitable measurements, the selection was discussed in different settings, including both experts and patients. Principal component analyses (PCAs) were performed to explore, reduce and evaluate measurements to be included in the three CEOHs. Internal consistency was estimated by Cronbach's Alpha. Results The validation process yielded 13 measurements (four clinical, nine self-reported) in concordance with the CEOHs. PCAs confirmed robust validity regarding the construction, predicting 60.85% of variance, representing psychosocial function (number of measurements = 5), disease and condition status (number of measurements = 4), and physiological function (number of measurements = 4). Cronbach's Alpha indicated good to sufficient internal consistency for each component in the constructs (alpha = 0.88, 0.68, 0.61, respectively). Conclusion In a Swedish general adult population, 13 self-reported and clinical measurements can be relevant to include to operationalise CEOHs in the FDI's theoretical framework.
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