| 1. |
- Hallqvist, Andreas, 1973, et al.
(author)
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Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial
- 2018
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In: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 122, s. 180-186
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Journal article (peer-reviewed)abstract
- Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
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| 2. |
- Alexandrov, Ludmil B, et al.
(author)
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The repertoire of mutational signatures in human cancer
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 94-101
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Journal article (peer-reviewed)abstract
- Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.
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| 3. |
- Bager, Jessica, et al.
(author)
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Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults
- 2021
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In: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 51:11, s. 1429-1437
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Journal article (peer-reviewed)abstract
- Background Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. Methods We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. Results Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. Conclusions In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Bornelöv, Susanne, et al.
(author)
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Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80080-
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Journal article (peer-reviewed)abstract
- Both genetic and environmental factors are important for the development of allergic diseases. However, a detailed understanding of how such factors act together is lacking. To elucidate the interplay between genetic and environmental factors in allergic diseases, we used a novel bioinformatics approach that combines feature selection and machine learning. In two materials, PARSIFAL (a European cross-sectional study of 3113 children) and BAMSE (a Swedish birth-cohort including 2033 children), genetic variants as well as environmental and lifestyle factors were evaluated for their contribution to allergic phenotypes. Monte Carlo feature selection and rule based models were used to identify and rank rules describing how combinations of genetic and environmental factors affect the risk of allergic diseases. Novel interactions between genes were suggested and replicated, such as between ORMDL3 and RORA, where certain genotype combinations gave odds ratios for current asthma of 2.1 (95% CI 1.2-3.6) and 3.2 (95% CI 2.0-5.0) in the BAMSE and PARSIFAL children, respectively. Several combinations of environmental factors appeared to be important for the development of allergic disease in children. For example, use of baby formula and antibiotics early in life was associated with an odds ratio of 7.4 (95% CI 4.5-12.0) of developing asthma. Furthermore, genetic variants together with environmental factors seemed to play a role for allergic diseases, such as the use of antibiotics early in life and COL29A1 variants for asthma, and farm living and NPSR1 variants for allergic eczema. Overall, combinations of environmental and life style factors appeared more frequently in the models than combinations solely involving genes. In conclusion, a new bioinformatics approach is described for analyzing complex data, including extensive genetic and environmental information. Interactions identified with this approach could provide useful hints for further in-depth studies of etiological mechanisms and may also strengthen the basis for risk assessment and prevention.
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| 8. |
- Challis, Pontus, et al.
(author)
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Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
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In: Archives of Disease in Childhood. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109:1, s. 87-93
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Journal article (peer-reviewed)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
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| 9. |
- Herlitschke, M., et al.
(author)
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Spin disorder in maghemite nanoparticles investigated using polarized neutrons and nuclear resonant scattering
- 2016
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In: International Conference On Polarised Neutrons For Condensed Matter Investigations (PNCMI 2014).
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Conference paper (peer-reviewed)abstract
- The manuscript reports the investigation of spin disorder in maghemite nanoparticles of different shape by a combination of polarized small -angle neutron scattering (SANSPOL) and nuclear forward scattering (NFS) techniques. Both methods are sensitive to magnetization on the nanoscale. SANSPOL allows for investigation of the particle morphology and spatial magnetization distribution and NFS extends this nanoscale information to the atomic scale, namely the orientation of the hyperfine field experienced by the iron nuclei. The studied nanospheres and nanocubes with diameters of 7.4nm and 10.6 nm, respectively, exhibit a significant spin disorder. This effect leads to a reduction of the magnetization to 44 % and 58% of the theoretical maghemite bulk value, observed consistently by both techniques.
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| 10. |
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| 11. |
- Lehnert, O., et al.
(author)
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New Ordovician-Silurian drill cores from the Siljan impact structure in central Sweden: an integral part of the Swedish Deep Drilling Program
- 2012
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In: Gff. - : Informa UK Limited. - 1103-5897 .- 2000-0863. ; 134:2, s. 87-98
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Journal article (peer-reviewed)abstract
- New drill cores from the largest known impact structure in Europe, the relict of the Siljan meteorite crater, provide new possibilities to reconstruct Early Palaeozoic marine environments and ecosystems, and to document changes in sedimentary facies, sea level and palaeoclimate in Baltoscandia. The impact crater is an important target of the project "Concentric Impact Structures in the Palaeozoic" within the framework of the "Swedish Deep Drilling Program". Two core sections, Mora 001 and Solberga 1, have been analysed. The sedimentary successions of these core sections include strata of late Tremadocian through late Wenlock ages. Our preliminary studies show not only that several of the classical Palaeozoic units of Sweden are represented in the area, but also that other significantly different facies are preserved in the Siljan district. An erosional unconformity representing a substantial hiatus occurs between Middle Ordovician limestone and a Llandovery-Wenlock (Silurian) shale succession in the western part of the Siljan structure and suggests an extended period of uplift and erosion. This may be related to forebulge migration due to flexural loading by the Caledonian thrust sheet to the west. Thus, this part of Sweden, previously regarded as a stable cratonic area, presumably was affected by the Caledonian collision between Baltica and Laurentia.
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| 12. |
- Lemonnier, Nathanaël, et al.
(author)
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A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
- 2020
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
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Journal article (peer-reviewed)abstract
- Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
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| 13. |
- Lim, Che Kang, et al.
(author)
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Reversal of Immunoglobulin. A Deficiency in Children
- 2015
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In: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 35:1, s. 87-91
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Journal article (peer-reviewed)abstract
- Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.
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| 14. |
- Madsen, Lynette D, et al.
(author)
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Texture of Al thin films deposited by magnetron sputtering onto epitaxial W(001)
- 2000
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 87:1, s. 168-171
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Journal article (peer-reviewed)abstract
- Highly textured epitaxial metallizations will be required for the next generation of devices with the main driving force being a reduction in electromigration. Herein a model system of 190 nm of Al on a 140 nm layer of W grown on MgO less than 00l greater than substrates was studied. The W layer was less than 00l greater than oriented and rotated 45 degrees with respect to the MgO substrate to minimize the misfit; the remaining strain was accommodated by dislocations, evident in transmission electron microscopy images. From high-resolution x-ray diffraction (XRD) measurements, the out-of-plane lattice parameter was determined to be 3.175 Angstrom, and the in-plane parameter was 3.153 Angstrom, i.e., the W film sustained a strain resulting in a tetragonal distortion of the lattice. XRD pole figures showed that the Al had four fold symmetry and two dominant orientations, less than 016 greater than and less than 3 9 11 greater than, which were twinned with multiple placements on the epitaxial W layer. The driving force for the tilted less than 001 greater than and less than 011 greater than orientations of Al on W is due to strain minimization through lattice matching. These results show that less than 00l greater than Al deposited at ambient conditions onto W is difficult to achieve and implies that electromigration difficulties are inherent.
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| 15. |
- Norman, M., et al.
(author)
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Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016
- 2019
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In: Jama-Journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 321:12, s. 1188-1199
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Journal article (peer-reviewed)abstract
- IMPORTANCE Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. OBJECTIVE To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. DESIGN, SETTING AND PARTICIPANTS All births at 22-26weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. EXPOSURES Delivery at 22-26 weeks' gestational age. MAIN OUTCOMES AND MEASURES The primary outcomewas infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). RESULTS During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P =.61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7%[95% CI, -11% to -2.2%], P =.003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6%[95% CI, -11% to -1.7%], P =.008). CONCLUSIONS AND RELEVANCE Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.
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| 16. |
- Owen, Christopher G, et al.
(author)
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Does initial breastfeeding lead to lower blood cholesterol in adult life? A quantitative review of the evidence.
- 2008
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In: American Journal of Clinical Nutrition. - 0002-9165 .- 1938-3207. ; 88:2, s. 305-14
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Journal article (peer-reviewed)abstract
- BACKGROUND: Earlier studies have suggested that infant feeding may program long-term changes in cholesterol metabolism. OBJECTIVE: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood. DESIGN: The study consisted of a systematic review of published observational studies relating initial infant feeding status to blood cholesterol concentrations in adulthood (ie, aged >16 y). Data were available from 17 studies (17 498 subjects; 12 890 breastfed, 4608 formula-fed). Mean differences in total cholesterol concentrations (breastfed minus formula-fed) were pooled by using fixed-effect models. Effects of adjustment (for age at outcome, socioeconomic position, body mass index, and smoking status) and exclusion (of nonexclusive breast feeders) were examined. RESULTS: Mean total blood cholesterol was lower (P = 0.037) among those ever breastfed than among those fed formula milk (mean difference: -0.04 mmol/L; 95% CI: -0.08, 0.00 mmol/L). The difference in cholesterol between infant feeding groups was larger (P = 0.005) and more consistent in 7 studies that analyzed "exclusive" feeding patterns (-0.15 mmol/L; -0.23, -0.06 mmol/L) than in 10 studies that analyzed nonexclusive feeding patterns (-0.01 mmol/L; -0.06, 0.03 mmol/L). Adjustment for potential confounders including socioeconomic position, body mass index, and smoking status in adult life had minimal effect on these estimates. CONCLUSIONS: Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.
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| 17. |
- Rosén, Jacob, et al.
(author)
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Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19 : the PROFLO multicenter randomized clinical trial
- 2021
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In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1
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Journal article (peer-reviewed)abstract
- Background: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. Methods: We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO(2) ratio <= 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. Results: Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8-8.4] in the control group compared with 9.0 h per day [IQR 4.4-10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference - 18% (95% CI - 2 to - 33%); P = 0.032). There were no other differences in secondary outcomes between groups. Conclusions: The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care.
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| 18. |
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| 19. |
- Sooman, Linda, et al.
(author)
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SHP1 expression is epigenetically regulated and influences the sensitivity to chemotherapeutic agents in glioblastoma cells
- 2012
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In: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 14:suppl 3, s. iii18-iii18
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Journal article (other academic/artistic)abstract
- INTRODUCTION: Glioblastoma is characterized by chemoresistance. One factor than can contribute to chemoresistance is aberrant DNA methylation of specific genes relevant for drug response, e.g. tumor suppressor genes. AIM: The aim of this study was to investigate whether the tumor suppressor gene SHP1 is epigenetically regulated and if its overexpression affects the sensitivity to chemotherapeutic drugs with different mechanisms of action in glioblastoma cell lines.METHODS: Differences in methylation levels in the SHP1 promoter and SHP1 protein expressions between untreated cells and cells treated with the demethylating agent decitabine were analyzed with bisulfite Pyrosequencing and Western blotting. Differences in drug sensitivity to a panel of chemotherapeutic drugs with different mechanisms of action between SHP1 overexpressing clones and control clones were analyzed with the fluorometric microculture cytotoxicity assay.RESULTS: We demonstrated that SHP1 promoter methylation was correlated to SHP1 expression and that the expression was increased upon demethylation. Overexpression of SHP1 resulted in lower (p < 0.05) sensitivity to the proteasome inhibitor bortezomib and the alkylating agents cisplatin and melphalan.CONCLUSION: SHP1 expression may be epigenetically regulated and its overexpression influences the sensitivity to chemotherapeutic drugs in glioblastoma derived cells.
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| 20. |
- Thacher, Jesse D., et al.
(author)
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Pre- and Postnatal Exposure to Parental Smoking and Allergic Disease Through Adolescence
- 2014
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 134:3, s. 428-434
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To examine the role of prenatal and postnatal second-hand tobacco smoke (SHS) exposure on asthma, rhinitis, and eczema development up to 16 years of age. METHODS: A birth cohort of 4089 children was followed for 16 years. Information on parental smoking habits, lifestyle factors, and symptoms of allergic disease was gathered using repeated parental questionnaires. Generalized estimating equations assessed the overall and age-specific associations between SHS exposure and allergic disease at ages 1 to 16 years. RESULTS: Exposure to SHS in utero was associated with an overall elevated risk of developing asthma up to 16 years (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.15-1.83) but not for rhinitis or eczema. After additional adjustment for parental smoking throughout childhood, excess overall risks for asthma remained statistically significant. Moreover, a dose-dependent pattern with SHS was observed. Exposure to SHS during infancy was associated with an overall elevated risk of asthma (OR = 1.23; 95% CI, 1.01-1.51), rhinitis (OR = 1.18; 95% CI, 1.01-1.39), and eczema (OR = 1.26; 95% CI, 1.09-1.45) up to 16 years. When age-specific associations were examined, the elevated risks related to SHS exposure in utero or during infancy were mostly confined to early childhood for asthma and rhinitis, whereas the excess risk of eczema appeared greatest at later ages. CONCLUSIONS: Our findings indicate that early SHS exposure, in utero or during infancy, influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages.
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| 21. |
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| 22. |
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| 23. |
- Zettergren, Anna, et al.
(author)
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Assessing tobacco use in Swedish young adults from self-report and urinary cotinine : A validation study using the BAMSE birth cohort
- 2023
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In: BMJ Open. - 2044-6055. ; 13:7
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Journal article (peer-reviewed)abstract
- Objectives Studies on health effects of tobacco often rely on self-reported exposure data, which is subjective and can lead to misclassification. The aim of this study was to describe the prevalence of cigarette smoking, snus and e-cigarette use, as well as to validate self-reported tobacco use among young adults in Sweden. Method Participants of a population-based Swedish cohort (n=3052), aged 22-25 years, assessed their tobacco use in a web questionnaire. Urinary cotinine was analysed in a subsample of the study population (n=998). The agreement between self-reported tobacco use and urinary cotinine was assessed using Cohen's Kappa coefficient (κ) at a cut-off level of 50 ng/mL. Results Patterns of tobacco use differed between men and women. Among men, 20.0% reported daily snus use, 5.8% daily cigarette smoking and 5.6% any e-cigarette use. In contrast, 3.2% of the women reported daily snus use, 9.0% daily cigarette smoking and 2.4% any e-cigarette use. Among the tobacco use categories, daily snus users had the highest levels of cotinine. Of reported non-tobacco users, 3.5% had cotinine levels above the cut-off, compared with 68.0% among both occasional cigarette smokers and snus users, 67.5% among all e-cigarette users and 94.7% and 97.8% among daily cigarette smokers and snus users, respectively. Agreement between self-reported tobacco use and urinary cotinine was classified as strong for daily use of cigarettes (κ=0.824) and snus (κ=0.861), while moderate to weak for occasional smoking (κ=0.618), occasional snus use (κ=0.573) and any e-cigarette use (κ=0.576). Conclusions We found high validity of self-reported tobacco use in our study population, particularly for daily tobacco use. Further, we found that daily snus users were exposed to high levels of cotinine. Together with previous findings, our results indicate good validity of self-reported tobacco use among young adults.
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