| 1. |
- Attner, Bo, et al.
(författare)
-
Cancer among patients with diabetes, obesity and abnormal blood lipids: a population-based register study in Sweden.
- 2012
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 23:5, s. 769-777
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study how the incidence of cancer is related to diabetes, obesity or abnormal blood lipids. METHODS: Diagnosis of diabetes, obesity or abnormal blood lipids was studied 0-10 years prior to the diagnosis of cancer in 19,756 cases of cancer and in 147,324 controls matched regarding age, sex and domicile. RESULTS: Diabetes was significantly more common prior to diagnosis in patients with liver, pancreatic, colon and urinary tract/bladder cancer and in patients with breast cancer diagnosed with diabetes 0-4 years prior to the cancer diagnosis. A lower risk of diabetes was seen in patients with prostate carcinoma among individuals with diabetes diagnosed 5-10 years prior to the cancer diagnosis. The findings remained after adjusting for obesity and high blood lipids. Obesity was significantly more common in patients with endometrial, colon and kidney cancer and with breast cancer above the age of 60 years in those where obesity was diagnosed close to the diagnosis of cancer. High blood lipids were significantly more common in patients with ovarian cancer and less common in patients with breast cancer. CONCLUSIONS: The study confirms some previous findings concerning comorbidity and cancer and highlights some new ones.
|
|
| 2. |
|
|
| 3. |
- Björner, Sofie, et al.
(författare)
-
Epithelial and Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation
- 2014
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor alpha (ER alpha) expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs are key regulators of several biological processes, acting by influencing the post-transcriptional regulation of numerous targets, thus making miRNAs potential candidates in cancer initiation. Here we have defined novel epithelial as well as stromal miRNA signatures from columnar cell hyperplasia lesions compared to normal terminal duct lobular units by using microdissection and miRNA microarrays. Let-7c were among the identified downregulated epithelial miRNAs and its functions were delineated in unique CCH derived cells and breast cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to effects on Myb and ER alpha. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding normal terminal duct lobular units (TDLUs), and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co-cultured with epithelial CCH cells caused substantial expression changes of genes involved in metabolism, DNA damage and cell motility. The miRNA signatures identified in CCH indicate early changes in the epithelial and stromal compartment of CCH and could represent early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules.
|
|
| 4. |
- Callaghan, Terry, et al.
(författare)
-
Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
-
Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
|
|
| 5. |
- Harbst, Katja, et al.
(författare)
-
Molecular and genetic diversity in the metastatic process of melanoma.
- 2014
-
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 233:1, s. 39-50
-
Tidskriftsartikel (refereegranskat)abstract
- Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using targeted deep sequencing of 1697 cancer genes and DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes between tumour lesions within a patient in 50% of the cases. In 18 of 22 patients (where matched normal tissue was available), we found that the multiple lesions within a patient were genetically divergent, with one or more melanoma tumours harbouring 'private' somatic mutations. In one case, the distant subcutaneous metastasis of one patient occurring 3 months after an earlier regional lymph node metastasis had acquired 37 new coding sequence mutations, including mutations in PTEN and CDH1. However, BRAF and NRAS mutations, when present in the first metastasis, were always preserved in subsequent metastases. The patterns of nucleotide substitutions found in this study indicate an influence of UV radiation but possibly also DNA alkylating agents. Our results clearly demonstrate that metastatic melanoma is a molecularly highly heterogeneous disease that continues to progress throughout its clinical course. The private aberrations observed on a background of shared aberrations within a patient provide evidence of continued evolution of individual tumours following divergence from a common parental clone, and might have implications for personalized medicine strategies in melanoma treatment. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk.
|
|
| 6. |
- Jönsson, Göran B, et al.
(författare)
-
The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
- 2012
-
Ingår i: Cancer Research. - 1538-7445. ; 72:16, s. 4028-4036
-
Tidskriftsartikel (refereegranskat)abstract
- Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
|
|
| 7. |
- Lindqvist, Pelle G., et al.
(författare)
-
Are active sun exposure habits related to lowering risk of type 2 diabetes mellitus in women, a prospective cohort study?
- 2010
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 90:1, s. 109-114
-
Tidskriftsartikel (refereegranskat)abstract
- Aim An inverse relationship exists between vitamin D levels and diabetes mellitus However, little is known about the correlation of sun exposure habits and type 2 diabetes mellitus (DM) Methods A South Swedish cohort study comprising 1000 women from each age group between 25 and 64 (n = 40,000) drawn from the Southern Swedish population registry 1990-1992 At the inception of the study 74% answered the inquiry (n = 29,518) and provided detailed information on their sun exposure habits and other variables A follow-up inquiry was sent 2000-2002 which 24,098 women answered The mean follow-up time was 11 years Logistic regression analysis was used and the main outcome was the relationship between type 2 DM and sun exposure habits. Results Our findings indicated that women with active sun exposure habits were at a 30% lower risk of having DM, as compared to those with non-active habits. There was an inverse relation between this risk reduction and BMI Conclusion Our investigation gives possible epidemiological explanation to ethnic and seasonal differences in type 2 DM and metabolic control The study supports that sunlight is involved in the glucose metabolism (C) 2010 Elsevier Ireland Ltd All rights reserved.
|
|
| 8. |
- Lindqvist, P. G., et al.
(författare)
-
Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort
- 2014
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 77-86
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. Methods. We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. Results. There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. Conclusion. The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.
|
|
| 9. |
- Lövkvist, Håkan, et al.
(författare)
-
A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene
- 2012
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 20:7, s. 783-789
-
Tidskriftsartikel (refereegranskat)abstract
- Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmo Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants <55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10 500 patients and 10 102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR=0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age <55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR=0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P=0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either. European Journal of Human Genetics (2012) 20, 783-789; doi: 10.1038/ejhg.2012.4; published online 25 January 2012
|
|
| 10. |
- Lövkvist, Håkan, et al.
(författare)
-
Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?
- 2013
-
Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101. ; 20:9, s. 1284-1291
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease (CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke (IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes. Methods: We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores (GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease (LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment (TOAST)] separately. Results: SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.04-1.20; P = 0.002] as well as LVD (OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect. Conclusions: Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Adolfsson, Emelie, et al.
(författare)
-
A system for remote dosimetry audit of 3D-CRT, IMRT and VMAT based on lithium formate dosimetry
- 2014
-
Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 113:2, s. 279-282
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to develop and test a remote end-to-end audit system using lithium formate EPR dosimeters. Four clinics were included in a pilot study, absorbed doses determined in the PTV agreed with TPS calculated doses within ±5% for 3D-CRT and ±7% (k=1) for IMRT/VMAT dose plans.
|
|
| 14. |
- Adolfsson, Emelie, et al.
(författare)
-
Investigation of signal fading in lithium formate EPR dosimeters using a new sensitive method
- 2012
-
Ingår i: Physics in Medicine and Biology. - : Institute of Physics (IOP). - 0031-9155 .- 1361-6560. ; 57:8, s. 2209-2217
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate signal fading in lithium formate electron paramagnetic resonance (EPR) dosimeters used for clinical applications in radiotherapy. A new experimental method for determination of signal fading, designed to resolve small changes in signal from slowly decaying unstable radicals, was used. Possible signal fading in lithium formate due to different storage temperatures was also tested. Air humidity was kept at a constant level of 33% throughout the experiments. The conclusion drawn from the investigations was that the EPR signal from lithium formate is stable during at least 1 month after irradiation and is not sensitive to variations in storage temperature andlt;40 degrees C when kept at a relative air humidity of 33%. This makes lithium formate a suitable dosimeter for transfer dosimetry in clinical audits.
|
|
| 15. |
- Adolfsson, Emelie, 1985-
(författare)
-
Lithium formate EPR dosimetry for accurate measurements of absorbed dose in radiotherapy
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lithium formate has shown to be a material with properties suitable for electron paramagnetic resonance (EPR) dosimetry, among them up to 7 times higher sensitivity compared to alanine, which is a well-established EPR detector material for dose determinations in radiotherapy.The aim of this thesis was to further investigate the properties of lithium formate and develop the dosimetry system towards applications in radiotherapy. The intrinsic efficiency for energies of relevance to brachytherapy and the signal stability were investigated. The dosimetry system was expanded to include a smaller dosimeter model, suitable for measurements in dose gradient regions. An individual sensitivity correction method was applied to the smaller dosimeters to be able to perform dose determinations with the same precision as for the larger ones. EPR dosimetry in general is time consuming and effort was spent to optimize the signal readout procedure regarding measurement time and measurement precision.The system was applied in two clinical applications chosen for their high demands on the dosimetry system: 1) a dosimetry audit for external photon beam therapy and 2) dose verification measurements around a low energy HDR brachytherapy source.The conclusions drawn from this thesis were: dose determinations can be performed with a standard uncertainty of 1.8-2.5% using both the original size dosimeters and the new developed smaller ones. The dosimetry system is robust and useful for applications when high measurement precision and accuracy is prioritized. It is a good candidate for dosimetry audits, both in external beam therapy and brachytherapy.
|
|
| 16. |
|
|
| 17. |
- Alejano, L. R., et al.
(författare)
-
Rock engineering design and the evolution of Eurocode 7
- 2013
-
Ingår i: ISRM International Symposium - EUROCK 2013. - : International Society for Rock Mechanics. - 9781138000803 ; , s. 777-782
-
Konferensbidrag (refereegranskat)abstract
- The Eurocode for Geotechnical Design, EN-1997-1:2004, informally known as Eurocode 7 or EC7, was fully implemented within the European Union in 2010. This Eurocode is intended to apply to all geotechnical engineering design, including rock engineering. In recognition that all codes must continue to evolve in order to remain applicable, and the long time that such evolution takes, work is already underway under the auspices of the European Committee for Standardisation, CEN, to identify how the code should develop for future revisions. This paper presents a summary of the maintenance procedures for Eurocodes in general and the specific maintenance work currently being undertaken on EC7 in respect of rock engineering design. It also highlights potential future development of EC7, and the need for enthusiastic involvement by the European rock engineering community to direct these developments.
|
|
| 18. |
- Ambrosi, Aurelie, et al.
(författare)
-
Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
-
Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
|
|
| 19. |
- Amos, Christopher I, et al.
(författare)
-
Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
- 2011
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:24, s. 23-5012
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Antoniou, Antonis C., et al.
(författare)
-
Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
-
Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
|
|
| 23. |
|
|
| 24. |
- Attner, Bo, et al.
(författare)
-
Low Cancer Rates among Patients with Dementia in a Population-Based Register Study in Sweden.
- 2010
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 30:1, s. 39-42
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Some studies have suggested a lower incidence of cancer in patients with dementia. We studied this further for 18 cancer types in population-based registers. Methods: In 19,756 cases and in 147,324 age- and sex-matched controls a diagnosis of dementia was studied 9-45 months prior to the diagnosis of cancer. Results: Overall a diagnosis of dementia was significantly less common among the cancer cases (risk ratio, RR = 0.60; 95% CI = 0.52-0.69). Conclusion: The study confirms previous findings that patients with dementia have a lower risk of cancer. Because the effect was seen for all tumour types and especially for patients older than 70 years and since the deficit was more pronounced for patients with tumours situated within the body, the data suggest that malignancies are underdiagnosed for persons with dementia.
|
|
| 25. |
|
|
| 26. |
- Baldetorp, Bo, et al.
(författare)
-
Analysis of protein expression in pure cell nuclei populations isolated from human breast cancer tissue by DNA flow cytometric sorting.
- 2010
-
Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 73, s. 1111-1116
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, cell nuclei from aneuploid breast cancer samples were sorted with respect to DNA content into pure diploid and aneuploid fractions using flow cytometry. The nuclear proteins were then separated by one-dimensional gel electrophoresis (1D-PAGE) and differences in protein expression patterns, between diploid and aneuploid nuclei from the same tumours, were compared. Using a combination of peptide finger printing and peptide identification by MALDI-TOF mass spectrometry, we identified proteins and confirmed that the proteins were of nuclear origins. The results in this study add further information to the knowledge about the breast cancer disease complexity and heterogeneity at molecular level. For some of the tumours studied different nuclei protein patterns were obtained, in the diploid respective aneuploid nuclei populations, whilst other tumours did not show these differences.
|
|
| 27. |
|
|
| 28. |
- Barrett, Jennifer H., et al.
(författare)
-
Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
-
Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
|
|
| 29. |
- Beral, V., et al.
(författare)
-
Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
- 2012
-
Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 9:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade.
|
|
| 30. |
- Beral, V., et al.
(författare)
-
Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
- 2012
-
Ingår i: The Lancet Oncology. - 1474-5488. ; 13:9, s. 946-956
-
Tidskriftsartikel (refereegranskat)abstract
- Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
|
|
| 31. |
- Berggren, Cathrine, et al.
(författare)
-
Att utvärdera och använda resultaten – vilka avtryck ger bibliotekens utvärderingar i samhället?
- 2013
-
Konferensbidrag (populärvet., debatt m.m.)abstract
- Det har blivit allt viktigare för biblioteken att kunna visa på sin betydelse i samhället. Mätetal och utvärderingar är nödvändiga instrument för att kunna jämföra satsningar på biblioteken med satsningar på andra områden. Men finns det en synergi mellan mätetalen och verksamhetens planer och mål? Hur mäter vi måluppfyllese i biblioteksverksamheten? Finns det kvalitetsindikatorer som vi har gemensamma oavsett bibliotekstyp? Hur kan biblioteksstatistiken användas? Vad gör bibliotekens utvärderingar för avtryck i beslutsprocessen? Vad gör bibliotekens utvärderingar för avtryck i samhället?För att svara på frågorna ovan har expertgruppen påbörjat ett arbete med att kartlägga hur svenska bibliotek arbetar med utvärdering. I det arbetet har vi bland annat sett vikten av ett gemensamt språk mellan bibliotekstyperna i arbetet med utvärderingar och kvalitetsutveckling. Gruppen kommer att under år 2014 publicera ett utvärderingsverktyg för bibliotek. Där kan bibliotek finna vägledning och stöd i valet av utvärderingsmetod, i genomförandet och i nyttjandet av utvärderingars resultat i syfte att utveckla och synliggöra biblioteksverksamheten.I det här papret presenterar vi syftet med vårt arbete och den metod vi har använt samt mer ingående berättar om hur vi har tänkt kring det verktyg som vi i slutet av papret ger en beskrivning av – ett verktyg som går under namnet "Utvärderingshjälpen".Vid konferensen kommer vi att presentera hur en årscykel kan se ut vid ett bibliotek som väljer att använda sig av utvärderingsarbete och systematiskt kvalitetsutveckling i nära relation till måluppfyllelse och till dialog med beslutsfattare samt omgivande samhälle. Vi presenterar också hur "Utvärderingshjälpen" skall kunna användas som stöd i det arbetet.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Bertolotto, Corine, et al.
(författare)
-
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 480:7375, s. 94-98
-
Tidskriftsartikel (refereegranskat)abstract
- So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes(1); risk factors associated with RCC include smoking, obesity and hypertension(2). A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers(3). The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene(4); it also stimulates the transcription of hypoxia inducible factor(5) (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes(6). We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (Psi KXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
|
|
| 35. |
- Bohlin, Jonas, et al.
(författare)
-
Species-specific forest variable estimation using non-parametric modeling of multi-spectral photogrammetric point cloud data
- 2012
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The recent development in software for automatic photogrammetric processing of multispectral aerial imagery, and the growing nation-wide availability of Digital Elevation Model (DEM) data, are about to revolutionize data capture for forest management planning in Scandinavia. Using only already available aerial imagery and ALS-assessed DEM data, raster estimates of the forest variables mean tree height, basal area, total stem volume, and species-specific stem volumes were produced and evaluated. The study was conducted at a coniferous hemi-boreal test site in southern Sweden (lat. 58° N, long. 13° E). Digital aerial images from the Zeiss/Intergraph Digital Mapping Camera system were used to produce 3D point-cloud data with spectral information. Metrics were calculated for 696 field plots (10 m radius) from point-cloud data and used in k-MSN to estimate forest variables. For these stands, the tree height ranged from 1.4 to 33.0 m (18.1 m mean), stem volume from 0 to 829 m3 ha-1 (249 m3 ha-1 mean) and basal area from 0 to 62.2 m2 ha-1 (26.1 m2 ha-1 mean), with mean stand size of 2.8 ha. Estimates made using digital aerial images corresponding to the standard acquisition of the Swedish National Land Survey (Lantmäteriet) showed RMSEs (in percent of the surveyed stand mean) of 7.5% for tree height, 11.4% for basal area, 13.2% for total stem volume, 90.6% for pine stem volume, 26.4 for spruce stem volume, and 72.6% for deciduous stem volume. The results imply that photogrammetric matching of digital aerial images has significant potential for operational use in forestry.
|
|
| 36. |
- Bolton, Kelly L., et al.
(författare)
-
Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
-
Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
-
Tidskriftsartikel (refereegranskat)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
|
|
| 37. |
- Botermans, Jos, et al.
(författare)
-
Comparison between air inlet via channels under the building and air inlets via the ceiling for growing-finishing pigs
- 2014
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the studies was to compare the indoor climate between two different ventilation systems for growing-finishing pigs. In one housing system the air came into the pig house via channels under the lying area of the pigs. The air came into the compartment close to the lying area of the pigs. The first part of the exhaust air was via another channel along the manure channel (pit ventilation). The rest of the exhaust air was via two fans in the ceiling (farm 1). In the other housing system the air came into the pig house via air inlets in the ceiling. The exhaust air was via two fans in the ceiling (farm 2). Measurements were done during one summer batch and one winter batch. Air temperature was measured for 5-8 weeks with mini-loggers. Ammonia concentration, carbon dioxide concentration, air speed and differences in air pressure between in and outside the pig house, were registered at 4 occasions. During summer time, the temperature of incoming air via the channels under the building (farm 1) was almost the same as the temperature of the air outside. So the cooling effect in the channels was very small. However, on the farm with air inlets in the ceiling (farm 2), the incoming air, during the afternoon, was about 3 0C above the temperature outside. So during the warmest period of the day, the air was heated on the ceiling. On the farm with channels under the lying area, the pigs continued to lie on the concrete lying area instead of the slatted flooring and the cleanliness of the pens was good (farm 1). During winter time, the temperature of the incoming air via the channels under the building was about 4 0C above the air temperature outside. On the farm with air inlets in the ceiling, the air temperature of the incoming air was the same as the temperature of the air outside.
|
|
| 38. |
|
|
| 39. |
- Branstrom, Richard, et al.
(författare)
-
Perceptions of genetic research and testing among members of families with an increased risk of malignant melanoma
- 2012
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:16, s. 3052-3062
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several melanoma susceptibility genes have been identified. As part of the international genetic research programme of the GenoMEL consortiums research on genetic mutations in melanoma families, the aim of this study was to examine family members' views about their risk of melanoma, gene testing and genetic research. Methods: Self-report data were gathered using online and paper-based surveys available in four languages among 312 individuals (62% from Europe, 18% from Australia, 13% from the United States of America (USA) and 7% from Israel). Results: Fifty three percent had been diagnosed with a melanoma, and 12% had a positive susceptibility gene test result. Respondents with many moles and freckles were more likely to perceive themselves at risk for developing melanoma (odds ratio [OR](Freckles) = 2.24 with 95% confidence interval [CI] = 1.18-4.26; ORMany (moles) = 6.92, 95% CI = 2.37-20.23). Respondents who had received a non-informative (negative) genetic test result were much less likely to perceive themselves at increased risk (OR = 0.17, 95% CI = 0.04-0.73). Safe-guards were perceived as important to protect genetic information, but there was also support for the storage and exchange of such information. Overall, respondents were in favour of genetic testing, even if current knowledge about melanoma risk genes is still limited. Contrary to previous studies, participants reported that a non-informative (negative) genetic test result, although not necessarily indicative of lower risk of melanoma, would be likely to reduce their practise of preventive behaviours. Conclusions: Participants were influenced by their phenotype and test results in risk estimations. They expressed positive views on genetic research and towards genetic testing, but reported that a non-informative (negative) test result might be associated with an (erroneous) perception of reduced risk and fewer preventive behaviours. These results highlight the urgency of improving the quality of genetic counselling and increasing the effectiveness of communication regarding genetic test results. (C) 2012 Elsevier Ltd. All rights reserved.
|
|
| 40. |
|
|
| 41. |
- Bulut, Sanja, et al.
(författare)
-
Fusion of Nonionic Vesicles
- 2010
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5421-5427
-
Tidskriftsartikel (refereegranskat)abstract
- We present an experimental study of vesicle fusion using light and neutron scattering to monitor fusion events. Vesicles are reproducibly formed with an extrusion procedure using an single amphiphile triethylene glycol mono-n-decyl ether in water. They show long-term stability for temperatures around 20 C, but at temperatures above 26 C we observe an increase in the scattered intensity due to fusion. The system is unusually well suited for the study of basic mechanisms of vesicle fusion. The vesicles are flexible with a bending rigidity of only a few k(H)T. The monolayer spontaneous curvature, Ho, depends strongly on temperature in a known way and is thus tunable. For temperatures where H-0 > 0 vesicles tyre long-term stable, while in the range H-0 < 0 the fusion rate increases the more negative the Spontaneous curvature Through a quantitative;analysis of the fusion rate we arrive tit a barrier to fusion changing from 15 k(B)T at T = 26 degrees C to 10k(H) T at T = 35 degrees C. These results are compatible with the theoretical predictions using the stalk model of vesicle fusion.
|
|
| 42. |
- Bulut, Sanja, et al.
(författare)
-
Lamellar phase separation in a centrifugal field. A method for measuring interbilayer forces
- 2010
-
Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 6:18, s. 4520-4527
-
Tidskriftsartikel (refereegranskat)abstract
- We present a novel method for measuring interbilayer forces in lamellar liquid crystals of amphiphile-water systems. In a centrifuge the gravitational effect is easily strong enough to produce clearly observable concentration gradients. During the experiment the concentration profile in the test-tube is monitored using NMR imaging of the deuterium quadrupole splitting in the lamellar phase, by temporarily transferring the sample into a NMR spectrometer. We also present a theoretical analysis of the experiment, where interactions dominate over entropy of mixing effects. For a system at sedimentation equilibrium one obtains a direct measurement of the interbilayer force, or equivalently chemical potential of the components over a substantial concentration range. It requires long times to obtain equilibrium in the centrifuge but very useful information about equilibrium and dynamic parameters is also obtained through an analysis of the sedimentation process. Experiments were performed on samples of a dilute lamellar phase of the non-ionic surfactant C10E3. After a few days of centrifugation a consistent concentration pattern was observed. At the bottom of the sample there appears a pure water-phase. The concentration profiles stabilize after a long centrifugation time. If they are related to the phase boundary the different profiles superimpose. This observation is consistent with the theory and the observation allows for a determination of how the chemical potentials vary with composition. The observed profiles are consistent with a dominating undulation force with a bilayer bending rigidity of 4.8-5.1 kT.
|
|
| 43. |
- Carlsson, Anders, et al.
(författare)
-
Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.
- 2011
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:34, s. 14252-14257
-
Tidskriftsartikel (refereegranskat)abstract
- The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high- versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
|
|
| 44. |
- Carlsson, Michael, et al.
(författare)
-
Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease
- 2012
-
Ingår i: Biochimica et Biophysica Acta - General Subjects. - : Elsevier. - 0304-4165 .- 1872-8006 .- 0006-3002. ; 1820:9, s. 1366-1372
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Changes in glycosylation of serum proteins are common, and various glycoforms are being explored as biomarkers in cancer and inflammation. We recently showed that glycoforms detected by endogenous galectins not only provide potential biomarkers, but also have different functions when they encounter galectins in tissue cells. Now we have explored the use of a combination of two galectins with different specificities, to further increase biomarker sensitivity and specificity. less thanbrgreater than less thanbrgreater thanMethods: Sera from 14 women with metastatic breast cancer, 12 healthy controls, 14 patients with IgA-nephritis (IgAN), and 12 patients with other glomerulonephritis were fractionated by affinity chromatography on immobilized human galectin-1 or galectin-8N, and the protein amounts of the bound and unbound fractions for each galectin were determined. less thanbrgreater than less thanbrgreater thanResults: Each galectin bound largely different fractions of the serum glycoproteins, including different glycoforms of haptoglobin. In the cancer sera, the level of galectin-1 bound glycoproteins was higher and galectin-8N bound glycoproteins lower compared to the other patients groups, whereas in IgAN sera the level of galectin-8N bound glycoproteins were higher. less thanbrgreater than less thanbrgreater thanConclusion: The ratio of galectin-1 bound/galectin-8N bound glycoproteins showed high discriminatory power between cancer patients and healthy, with AUC of 0.98 in ROC analysis, and thus provides an interesting novel cancer biomarker candidate. less thanbrgreater than less thanbrgreater thanGeneral significance: The galectin-binding ability of a glycoprotein is not only a promising biomarker candidate but may also have a specific function when the glycoprotein encounters the galectin in tissue cells, and thus be related to the pathophysiological state of the patient. This article is part of a Special Issue entitled Glycoproteomics.
|
|
| 45. |
- Carlsson, Maine, 1955-, et al.
(författare)
-
Effects of high-intensity exercise and protein supplement on muscle mass in ADL dependent older people with and without malnutrition : a randomized controlled trial
- 2011
-
Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 15:7, s. 554-560
-
Tidskriftsartikel (refereegranskat)abstract
- Background Loss of muscle mass is common among old people living in institutions but trials that evaluate interventions aimed at increasing the muscle mass are lacking. Objective, participants and intervention This randomized controlled trial was performed to evaluate the effect of a high-intensity functional exercise program and a timed protein-enriched drink on muscle mass in 177 people aged 65 to 99 with severe physical or cognitive impairments, and living in residential care facilities. Design Three-month high-intensity exercise was compared with a control activity and a protein-enriched drink was compared with a placebo drink. A bioelectrical impedance spectrometer (BIS) was used in the evaluation. The amount of muscle mass and body weight (BW) were followed-up at three and six months and analyzed in a 2 × 2 factorial ANCOVA, using the intention to treat principle, and controlling for baseline values. Results At 3-month follow-up there were no differences in muscle mass and BW between the exercise and the control group or between the protein and the placebo group. No interaction effects were seen between the exercise and nutritional intervention. Long-term negative effects on muscle mass and BW was seen in the exercise group at the 6-month follow-up. Conclusion A three month high-intensity functional exercise program did not increase the amount of muscle mass and an intake of a protein-enriched drink immediately after the exercise did not induce any additional effect on muscle mass. There were negative long-term effects on muscle mass and BW, indicating that it is probably necessary to compensate for an increased energy demand when offering a high-intensity exercise program.
|
|
| 46. |
- Carlsson, Michael, et al.
(författare)
-
Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.
- 2011
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.
|
|
| 47. |
- Carlsson Tedgren, Åsa, 1968-, et al.
(författare)
-
Determination of absorbed dose to water around a clinical HDR 192-Ir source using LiF:Mg,Ti TLDs demonstrates an LET dependence of detector response
- 2012
-
Ingår i: Medical physics (Lancaster). - USA : American Association of Physicists in Medicine. - 0094-2405. ; 39:2, s. 1133-1140
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Experimental radiation dosimetry with thermoluminescent dosimeters (TLDs), calibrated in a (60)Co or megavoltage (MV) photon beam, is recommended by AAPM TG-43U1for verification of Monte Carlo calculated absorbed doses around brachytherapy sources. However, it has been shown by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] that for TLDs of LiF:Mg,Ti, detector response was 4% higher in a (137)Cs beam than in a (60)Co one. The aim of this work was to investigate if similar over-response exists when measuring absorbed dose to water around (192)Ir sources, using LiF:Mg,Ti dosimeters calibrated in a 6 MV photon beam.Methods: LiF dosimeters were calibrated to measure absorbed dose to water in a 6 MV photon beam and used to measure absorbed dose to water at distances of 3, 5, and 7 cm from a clinical high dose rate (HDR) (192)Ir source in a polymethylmethacrylate (PMMA) phantom. Measured values were compared to values of absorbed dose to water calculated using a treatment planning system (TPS) including corrections for the difference in energy absorption properties between calibration quality and the quality in the users' (192)Ir beam and for the use of a PMMA phantom instead of the water phantom underlying dose calculations in the TPS.Results: Measured absorbed doses to water around the (192)Ir source were overestimated by 5% compared to those calculated by the TPS. Corresponding absorbed doses to water measured in a previous work with lithium formate electron paramagnetic resonance (EPR) dosimeters by Antonovic et al. [Med. Phys. 36, 2236-2247 (2009)], using the same irradiation setup and calibration procedure as in this work, were 2% lower than those calculated by the TPS. The results obtained in the measurements in this work and those obtained using the EPR lithium formate dosimeters were, within the expanded (k = 2) uncertainty, in agreement with the values derived by the TPS. The discrepancy between the results using LiF:Mg,Ti TLDs and the EPR lithium formate dosimeters was, however, statistically significant and in agreement with the difference in relative detector responses found for the two detector systems by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] and by Adolfsson et al. [Med. Phys. 37, 4946-4959 (2010)].Conclusions: When calibrated in (60)Co or MV photon beams, correction for the linear energy transfer (LET) dependence of LiF:Mg,Ti detector response will be needed as to measure absorbed doses to water in a (192)Ir beam with highest accuracy. Such corrections will depend on the manufacturing process (MTS-N Poland or Harshaw TLD-100) and details of the annealing and read-out schemes used.
|
|
| 48. |
|
|
| 49. |
- Davies, John R, et al.
(författare)
-
Inherited variation in the PARP1 gene and survival from melanoma
- 2014
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:7, s. 1625-1633
-
Tidskriftsartikel (refereegranskat)abstract
- We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p=0.005, eleven cohorts) and MSS (HR=1.20 per allele, 95% CI 1.01-1.39, p=0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS. What's new? Although staging systems predict outcome fairly well for melanoma, survival still varies among individual patients. In this meta-analysis, the authors found that inheritance of a rare genetic variant of PARP1 was associated with improved survival of melanoma patients. Increased expression of PARP1 has been associated with poorer outcome, and depletion of PARP1 may reduce both melanoma growth and angiogenesis. The identification of this and other germline variants that affect survival may help to identify key biological pathways active in host/tumor interactions, which may lead to the discovery of new therapeutic targets for treating advanced melanoma. Epidemiology
|
|
| 50. |
|
|
