| 1. |
- Andersson, Ulrika, et al.
(författare)
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MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.
- 2009
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 125:4, s. 968-972
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Tidskriftsartikel (refereegranskat)abstract
- The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations.
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| 2. |
- Andersson, Ulrika, et al.
(författare)
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Telomere length, allergies and risk of Glioma
- 2017
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 19:S3, s. 23-23
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Tidskriftsartikel (refereegranskat)abstract
- Background: In glioma, a malignant brain tumour with poor prognosis, the etiology is largely unkown. Rare inherited syndromes, and high doses of ionising radiation are associated with increased risk of glioma. Common genetic variants have been associated with risk of glioma, and familial glioma have been associated with genetic variants in genes functionally important in telomere regulation (e.g. RTEL, TERT and POT1). The association between telomere length and risk of cancer is complex and seems to be tumour type dependent. Patients with asthma have significantly shorter telomeres than those of control subjects, and a protective effect has been observed with an inverse association with allergies and asthma and glioma risk. Methods: We investigated population based glioma case-control series (431 cases and 672 controls) from Sweden at diagnosis with a quantitative PCR method for relative leukocyte telomere length measured in blood confirming with direct measurement of the association between telomere length and risk of glioma. We also explored the relationship between, age, gender, allergies and asthma, as these are established factors associated both with telomere length and glioma.Results: Longer relative leukocyte telomere length was significantly associated with increased risk of glioma, adjusting for age and gender (OR=2.23, CI: 1.11–4.47). As expected, for patients with allergies there was a protective effect with an inverse association with glioma risk, adjusting for age and gender (OR=0.64, CI; 0.48–0.85). Nevertheless, when analysing specific types of allergy, eczema (OR=0.66, CI; 0.41–1.08) and water eyes (OR=0.52, CI; 0.31–0.88) appeared to be more protective against glioma, compared to asthma (OR=0.92, CI; 0.59–1.41), and respiratory symptoms (OR=1.14, CI; 0.71–1.84) which showed no protective effect against glioma. Additionally adjusting for allergies did not markedly change the OR between relative leukocyte telomere length and glioma risk, indicating that the protective effect having allergies seems not to be coupled to telomere length. Conclusions: The adverse association of longer telomere and risk of glioma displays the complexity in understanding the biological role of telomere length and risk of developing cancer.
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| 3. |
- Björkander, Sophia, et al.
(författare)
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Staphylococcus aureus-derived factors induce IL-10, IFN-gamma and IL-17A-expressing FOXP3(+)CD161(+) T-helper cells in a partly monocyte-dependent manner
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus (S. aureus) is a human pathogen as well as a frequent colonizer of skin and mucosa. This bacterium potently activates conventional T-cells through superantigens and it is suggested to induce T-cell cytokine-production as well as to promote a regulatory phenotype in T-cells in order to avoid clearance. This study aimed to investigate how S. aureus impacts the production of regulatory and pro-inflammatory cytokines and the expression of CD161 and HELIOS by peripheral CD4(+)FOXP3(+) T-cells. Stimulation of PBMC with S. aureus 161:2-cell free supernatant (CFS) induced expression of IL-10, IFN-gamma and IL-17A in FOXP3(+) cells. Further, CD161 and HELIOS separated the FOXP3(+) cells into four distinct populations regarding cytokine-expression. Monocyte-depletion decreased S. aureus 161:2-induced activation of FOXP3(+) cells while pre-stimulation of purified monocytes with S. aureus 161:2-CFS and subsequent co-culture with autologous monocyte-depleted PBMC was sufficient to mediate activation of FOXP3(+) cells. Together, these data show that S. aureus potently induces FOXP3(+) cells and promotes a diverse phenotype with expression of regulatory and pro-inflammatory cytokines connected to increased CD161-expression. This could indicate potent regulation or a contribution of FOXP3(+) cells to inflammation and repression of immune-suppression upon encounter with S. aureus.
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| 4. |
- Borssén, Magnus, et al.
(författare)
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DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia
- 2016
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:7, s. 1185-1192
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Tidskriftsartikel (refereegranskat)abstract
- Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.
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| 5. |
- Borssen, Magnus, et al.
(författare)
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hTERT promoter methylation and telomere length in childhood acute lymphoblastic leukemia-associations with immunophenotype and cytogenetic subgroup
- 2011
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Ingår i: Experimental Hematology. - New York : Elsevier. - 0301-472X .- 1873-2399. ; 39:12, s. 1144-1151
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Tidskriftsartikel (refereegranskat)abstract
- Telomere maintenance, important for long-term cell survival and malignant transformation, is directed by a multitude of factors, including epigenetic mechanisms, and has been implicated in outcomes for patients with leukemia. In the present study, the objective was to investigate the biological and clinical significance of telomere length and promoter methylation of the human telomerase reverse transcriptase gene in childhood acute lymphoblastic leukemia. A cohort of 169 childhood acute lymphoblastic leukemias was investigated for telomere length, human telomerase reverse transcriptase gene promoter methylation status, genomic aberrations, immunophenotype, and clinical outcomes. Methylation of the core promoter of the human telomerase reverse transcriptase (hTERT) gene was demonstrated in 24% of diagnostic samples, with a significant difference between B-cell precursor (n = 130) and T-cell acute lymphoblastic leukemia (ALL) (n = 17) cases (18% and 72%, respectively; p < 0.001). No remission sample demonstrated hTERT promoter methylation (n = 40). Within the B-cell precursor group, t(12;21)(p13;q22) [ETV6/RUNX1] cases (n = 19) showed a much higher frequency of hTERT methylation than high-hyperdiploid (51 61 chromosomes) ALL (n = 44) (63% and 7%, respectively; p < 0.001). hTERT messenger RNA levels were negatively associated with methylation status and, in the t(12;21) group, methylated cases had shorter telomeres (p = 0.017). In low-risk B-cell precursor patients (n = 101), long telomeres indicated a worse prognosis. The collected data from the present study indicate that the telomere biology in childhood ALL has clinical implications and reflects molecular differences between diverse ALL subgroups. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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| 6. |
- Brohede, Ulrika, et al.
(författare)
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Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release
- 2009
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 20:9, s. 1859-1867
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Tidskriftsartikel (refereegranskat)abstract
- The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO2 composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO2 to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.
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| 7. |
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| 8. |
- Dezfouli, Mahya, et al.
(författare)
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Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies
- 2020
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
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| 9. |
- Eggers, Jeannette, et al.
(författare)
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Adapted forest management to improve the potential for reindeer husbandry in Northern Sweden
- 2024
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Ingår i: AMBIO: A Journal of the Human Environment. - 0044-7447 .- 1654-7209. ; 53, s. 46-62
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Tidskriftsartikel (refereegranskat)abstract
- In northern Sweden, improvements of grazing conditions are necessary for the continuation of traditional, natural pasture-based reindeer husbandry. Ground and tree lichen constitute the main fodder resource for reindeer during winter but have reached critically low levels. Using a forest decision support system, we prescribe adapted forest management to improve the preconditions for reindeer husbandry and compare outcomes with the continuation of current forest management. We found that adapted management increases the forest area with ground lichen habitat by 22% already within 15 years, while a continuation of current management would result in a further decrease in ground lichen. Tree lichen habitat can be retained and increased in all scenarios, which is important in a changing climate. Compared to a continuation of current practices, adapted management with significantly improved conditions for lichen resulted in a decrease in net revenues from wood production by 11-22%.
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| 10. |
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