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| 3. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 5. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 6. |
- Johnatty, S. E., et al.
(författare)
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No evidence that GATA3 rs570613 SNP modifies breast cancer risk
- 2009
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 117:2, s. 371-379
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Tidskriftsartikel (refereegranskat)abstract
- GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P trend = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269-2275]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper-allele = 1.00, 95% CI 0.94-1.05), in ER negative BCAC cases (ORper-allele = 1.02, 95% CI 0.91-1.13), in BRCA1 mutation carriers RRper-allele = 0.99, 95% CI 0.90-1.09) or BRCA2 mutation carriers (RRper-allele = 0.93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
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| 7. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 9. |
- Blomqvist, M., et al.
(författare)
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Structural and tribological properties of cluster-assembled CNx films
- 2007
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Ingår i: Applied Physics A. - : Springer Science and Business Media LLC. - 0947-8396 .- 1432-0630. ; 87:4, s. 767-772
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Tidskriftsartikel (refereegranskat)abstract
- We report the structural and tribological characterization of nanostructured CNx thin films produced by the deposition of a supersonic carbon cluster beam assisted by nitrogen ion bombardment. The influence of the deposition parameters on the chemical composition and structure of the films has been systematically studied by X-ray photoelectron spectroscopy, elastic recoil detection analysis, transmission electron microscopy and atomic force microscopy. Depending on the deposition parameters, the films show a structure ranging from amorphous to disordered graphitic with interlinked planes. Nitrogen content depends on the nitrogen ion kinetic energy. The films have a very low density with a high surface roughness. Friction measurements at the nanoscale show a correlation between nitrogen content and mechanical properties of the system.
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| 10. |
- Cox, Angela, et al.
(författare)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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| 11. |
- Berseth, P. A., et al.
(författare)
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Carbon Nanomaterials as Catalysts for Hydrogen Uptake and Release in NaAlH4
- 2009
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 9:4, s. 1501-1505
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Tidskriftsartikel (refereegranskat)abstract
- A synergistic approach involving experiment and first-principles theory not only shows that carbon nanostructures can be used as catalysts for hydrogen uptake and release in complex metal hydrides such as sodium alanate, NaAlH4, but also provides an unambiguous understanding of how the catalysts work. Here we show that the stability of NaAlH4 originates with the charge transfer from Na to the AlH4 moiety, resulting in an ionic bond between Na+ and AlH4- and a covalent bond between Al and H. Interaction of NaAlH4 with an electronegative substrate such as carbon fullerene or nanotube affects the ability of Na to donate its charge to AlH4, consequently weakening the Al-H bond and causing hydrogen to desorb at lower temperatures as well as facilitating the absorption of H-2 to reverse the dehydrogenation reaction. In addition, based on our experimental observations and theoretical calculations it appears the curvature of the carbon nanostructure plays a role in the catalytic process. Ab initio molecular dynamics simulation further reveals the time evolution of the charge transfer process.
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| 12. |
- Blomqvist, A, et al.
(författare)
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Airways symptoms, immunological response and exposure in powder painting
- 2005
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 78:2, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Powder painting is an alternative to solvent-based spray painting. Powder paints may contain organic acid anhydrides (OAAs), which are irritants to the airways and may cause sensitisation. The aim of this study was to determine the prevalence of respiratory symptoms and immunological response among powder painters and to describe the exposure to OAAs. Methods: In all, 205 subjects in 32 enterprises participated: 93 exposed and 26 formerly exposed workers in 25 powder paint shops and 86 unexposed workers. They completed a questionnaire about working conditions and symptoms and took part in a medical examination, which included a lung function test. Urine samples, for determination of two OAAs, and blood samples, for analysis of specific antibodies against the OAAs, were taken. In addition, 33 paint samples were analysed for nine OAAs. Results: The powder painters reported more work-related respiratory symptoms than unexposed subjects did. The prevalence of three or more symptoms was 24% in subjects with low exposure, 44% in highly exposed individuals, 46% in formerly exposed subjects and 19% in unexposed workers. Asthma symptoms were frequent, 7%, 40%, 15% and 2%, respectively. Regression analyses of the lung volumes did not show any influence of exposure. IgG, but not IgE, against the OAAs and metabolites of OAAs was found in some subjects, but no associations with the exposure could be observed. OAAs were found in only small amounts in the paint samples. Conclusions: The exposure to organic acid anhydrides was estimated to be low, and yet, IgG antibodies to OAA were observed in some subjects. The prevalence of work-related symptoms from the eyes and the airways was relatively high among the powder painters, and these symptoms, but not the lung volumes, were clearly related to exposure. The symptoms were probably caused by irritative properties of the powder paint dust.
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| 19. |
- Dafnis, G, et al.
(författare)
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Patient factors influencing the completion rate in colonoscopy
- 2005
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Ingår i: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. - : Elsevier BV. - 1590-8658. ; 37:2, s. 113-118
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Hadinia, Baharak, et al.
(författare)
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First identification of gamma-rays in Te-106 using recoil decay tagging technique
- 2006
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Ingår i: Frontiers in Nuclear Structure Astrophysics, and Reactions: FINUSTAR. - MELVILLE, NY : AMER INST PHYSICS. - 0735403236 - 9780735403239 ; , s. 457-459
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Konferensbidrag (refereegranskat)abstract
- Gamma-ray transitions from excited states in Te-106 have been identified using the recoil decay tagging technique. The experiment which was the reaction Fe-54(Fe-54,2n)Te-106* was performed at the JYFL accelerator facility at the University of Jyvaskyla, Finland. The production cross section was estimated at 25 nb, a new limit for in-beam gamma-ray spectroscopy. A tentative level structure for the ground state band of Te-106 is proposed.
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| 25. |
- Janson, Staffan, 1945-, et al.
(författare)
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Äldre i Värmland : Om hälsa, levnadsvanor och livssituation 2006
- 2007
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Landstinget har i samarbete med Karlstads universitet gjort flera befolkningsundersökningar i Värmland och publicerat rapporter om både den vuxna befolkningens och barns hälsa, senast med rapporten Värmlänningarnas Liv och Hälsa 2004. Någon befolkningsstudie av de äldres hälsa och livsvillkor har dock inte gjorts tidigare.Efter tre års förarbeten och samråd mellan landstinget, Värmlands kommuner och flera institutioner vid Karlstads universitet genomfördes den föreliggande studien av de äldres hälsa under senhösten 2006, i form av en omfattande postenkät. Urvalet utgjordes av 2500 slumpmässigt uttagna kvinnor och män som var 80 år eller äldre. Svarsfrekvensen var 60 procent, vilket får betraktas som mycket bra med tanke på att cirka 15 procent i denna åldersgrupp lever i särskilda boenden.Studien avspeglar således hälsan och livsvillkoren för de äldre. Överlag visar det sig att de äldre mår bra och har stor kapacitet att fungera som aktiva samhällsmedborgare. Samtidigt är det många som har kroniska besvär, med värk, syn- och hörselnedsättning, inkontinensbesvär etc. Det föreligger också en klar social gradient, där särskilt äldre kvinnor med arbetarbakgrund har både mer sjukdom och större ekonomiska problem än de övriga.
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| 29. |
- Morein, Bror, et al.
(författare)
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Immune responsiveness in the neonatal period
- 2007
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Ingår i: Journal of Comparative Pathology. - : Elsevier BV. - 0021-9975 .- 1532-3129. ; 137, s. S27-S31
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Tidskriftsartikel (refereegranskat)abstract
- The maintenance of pregnancy requires suppression of the maternal immune system which would naturally recognize the developing fetus as an allograft and seek to destroy it by mounting a Th1 regulated Cytotoxic immune response. During pregnancy a range of soluble factors are produced by the placenta which switch maternal immune regulation towards a protective Th2 phenotype. These factors also influence the developing fetal immune system and all newborns initially have an immunological milieu skewed towards Th2 immunity. Vaccination during the neonatal period must therefore overcome the dual challenge of the inhibitory effect of maternally derived antibody and this natural Th2 regulatory environment. One means of overcoming these obstacles is by the use of adjuvant systems that can redirect the neonatal immune response towards an appropriate Th1 regulated reaction that affords protection from infectious disease. In this overview, experiments are described in which viral antigens incorporated into immune stimulatory complexes (ISCOMs) are able to induce immune responses with balanced Th1 and Th2 regulation in neonatal mice, as evidenced by the nature of the IgG subclass response and cytokine profile, and the induction of cytotoxic lymphocytes. ISCOM adjuvanted vaccines are able to induce similar protective immunity in the newborn of larger animal species including cattle, horses and dogs.
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| 32. |
- Pechacek, Peter, et al.
(författare)
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Classical polyandry found in the three-toed woodpecker Picoides tridactylus
- 2006
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Ingår i: Journal of Ornithology. - : Springer Science and Business Media LLC. - 0021-8375 .- 2193-7192 .- 2193-7206. ; 147:1, s. 112-114
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Tidskriftsartikel (refereegranskat)abstract
- We report two cases of simultaneous, social polyandry in the three-toed woodpecker Picoides tridactylus found in Berchtesgaden National Park, Germany during an 11-year study. The first case was between two neighbouring pairs in 2003. A female incubated both of her clutches during a period of at least 8 days. The second case was in 2004 between a widowed male and a female of a neighbouring pair. This time, a female divided parental care between her two clutches during a period of at least 27 days. We hypothesise that social polyandry in the three-toed woodpecker may be linked to the parental quality of the first male.
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| 35. |
- Pechacek, Peter, et al.
(författare)
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Monogamy with exceptions: Social and genetic mating system in a bird species with high paternal investment
- 2005
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Ingår i: Behaviour. - : Brill. - 0005-7959 .- 1568-539X. ; 142:8, s. 1093-1114
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Tidskriftsartikel (refereegranskat)abstract
- Animal mating systems are strongly linked to costs and benefits associated with parental care. A high degree of male parental care may explain the occasional occurrence of social polyandry in some monogamous birds such as woodpeckers. We examined mating and parental behaviours of 55 three-toed woodpeckers Picoides tridaclylus, and used DNA fingerprinting to study its genetic mating system over 11 years. Sexes shared nest hole guarding and parental care, but males allocated significantly more time to territory defence, cavity excavation and feeding young than females. Two (7.4%) of the 27 females were polyandrous, each paired simultaneously with two males. Four (7.3%) out of 55 chicks were extra-pair (15.4% of the broods). Two of these chicks were associated with social polyandry, and one with female parasitism. Hence, three-toed woodpeckers were socially and genetically predominantly monogamous. We propose that both social and genetic polyandry in woodpeckers are constrained by the long duration of cavity excavation, few re-mating opportunities, and by the fact that bi-parental care is important for reproductive success.
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| 37. |
- Torkzad, Michael R., 1968-, et al.
(författare)
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Morphological assessment of the interface between tumor and neighboring tissues, by magnetic resonance imaging, before and after radiotherapy in patients with locally advanced rectal cancer
- 2008
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 49:10, s. 1099-103
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Magnetic resonance imaging (MRI) in rectal cancer is sometimes performed after radiotherapy (MRI 2) to evaluate tumor response and to choose alternative forms of surgery. The accuracy of MRI 2 in distinguishing tumor delineation might be difficult due to fibrosis. PURPOSE: To evaluate the morphological changes in the interface between the tumor and neighboring organs on MRI 2 performed after radiotherapy, and to assess the accuracies of MRI before and after radiotherapy compared to histopathology after surgery. MATERIAL AND METHODS: Sixteen patients with locally advanced primary rectal cancer, with MRI before and after radiotherapy, were retrospectively studied, concerning the interface between the tumor and neighboring structures. The accuracies of MRI before and after radiotherapy were compared based on histopathology as a reference. RESULTS: The accuracies of both MRI before and after radiotherapy were moderate, with no additional value of MRI after radiotherapy compared to MRI before radiotherapy. The most predictive form of interface for involvement of a neighboring organ after radiotherapy was nodular growth of the tumor into a neighboring structure. CONCLUSION: The morphological assessment of pelvic MRI after preoperative radiotherapy does not provide any significant new information about tumor extent in patients with locally advanced rectal cancer.
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