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- 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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- Wootton, P. T., et al.
(författare)
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Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2-IIA: results from the UDACS study
- 2007
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Ingår i: Hum Mol Genet. ; 16:12, s. 1437-44
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Tidskriftsartikel (refereegranskat)abstract
- Animal and human studies suggest that both secretory PLA2 (sPLA2)-V and sPLA2-IIA (encoded, respectively, by the neighbouring PLA2G5 and PLA2G2A genes) contribute to atherogenesis. Elevated plasma sPLA2-IIA predicts coronary heart disease (CHD) risk, but no mass assay for sPLA2-V is available. We previously reported that tagging single nucleotide polymorphism (tSNP) haplotypes of PLA2G2A are strongly associated with sPLA2-IIA mass, but not lipid levels. Here, we use tSNPs of the sPLA2-V gene to investigate the association of PLA2G5 with CHD risk markers. Seven PLA2G5 tSNPs genotypes, explaining >92% of the locus genetic variability, were determined in 519 patients with Type II diabetes (in whom PLA2G2A tSNP data was available), and defined seven common haplotypes (frequencies >5%). PLA2G5 and PLA2G2A tSNPs showed linkage disequilibrium (LD). Compared to the common PLA2G5 haplotype, H1 (frequency 34.9%), haplotypes H2-7 were associated with overall higher plasma LDL (P < 0.00004) and total cholesterol (P < 0.00003) levels yet lower oxLDL/LDL (P = 0.006) and sPLA2-IIA mass (P = 0.04), probably reflecting LD with PLA2G2A. Intronic tSNP (rs11573248), unlikely itself to be functional, distinguished H1 from LDL-raising haplotypes and may mark a functional site. In conclusion, PLA2G5 tSNP haplotypes demonstrate an association with total and LDL cholesterol and oxLDL/LDL, not seen with PLA2G2A, thus confirming distinct functional roles for these two sPLA2s.
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- Duggan, D., et al.
(författare)
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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP
- 2007
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 99:24, s. 1836-1844
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Tidskriftsartikel (refereegranskat)abstract
- Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
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- Eriksson Wiklund, Ann-Kristin, et al.
(författare)
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Contaminants and habitat choice in the Baltic Sea: Behavioural experiments with the native species, Monoporeia affinis, and the invasive genus, Marenzelleria
- 2009
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Ingår i: Estuarine, Coastal and Shelf Science. - : Elsevier BV. - 0272-7714 .- 1096-0015. ; 81, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- The invasive polychaete genus, Marenzelleria and the native amphipod, Monoporeia affinis are food and habitat competitors in the Baltic Sea. Previous studies have shown that moderate densities of Marenzelleria can affect the behaviour of M. affinis. To examine the short-term interactive effects of interspecific habitat choice and environmental contaminants a series of habitat colonisation experiments were performed. The contaminants examined included harbor sediments and sediment spiked with the antifouling substances, Cu, Zn and Irgarol. Polychaetes and amphipods were exposed to contaminants in single-species and two-species experiments. In spiked-sediment experiments, M. affinis showed clear dose-dependent response. These experiments verified that behavioural response of M. affinis to different habitats is a sensitive method for testing toxicity under controlled conditions. In experiments with three different harbor sediments and reference sediment both species showed the lowest preference for the reference sediment. This sediment also had the lowest content of quality food, indicating that factors such as food quality and quantity may override the disturbing effects of contaminants in natural sediments. The presence of Marenzelleria spp. did not affect amphipod habitat choice, indicating no short-term effects, which implies that both species can co-exist provided sufficient food is available.
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- Larsson, C., et al.
(författare)
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Estimation of blood loss after cesarean section and vaginal delivery has low validity with a tendency to exaggeration
- 2006
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 85:12, s. 1448-1452
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Tidskriftsartikel (refereegranskat)abstract
- Background. Excessive bleeding is one of the major threats to women at childbirth. The aim of this study was to validate estimation of blood loss during delivery. Methods. Bleeding was estimated after 29 elective cesarean sections and 26 vaginal deliveries and compared to blood loss measured by extraction of hemoglobin using the alkaline hematin method, according to Newton. Results. Inter-individual agreement of estimation showed good results. Estimated loss in comparison with measured loss resulted in an over-estimation. In vaginally delivered women, there was no correlation between estimated and measured blood loss (r2=0.13), and in women delivered by elective cesarean section, the correlation was moderate (r2=0.55). Agreement, according to Bland and Altman, indicated that measured blood loss could vary from 570 ml less to 342 ml more than estimated blood loss. Conclusions. The standard procedure of estimation of obstetric bleeding was found to be unreliable. In this study, blood loss was over-estimated in cesareans. In vaginal deliveries, there seemed to be no correlation. Estimated blood loss as a quality indicator or as a variable in studies comparing complications must be used with caution. For clinical purposes, estimation of blood loss and measurement of post partum hemoglobin is of low value and may lead to the wrong conclusions. © 2006 Taylor & Francis.
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- Malmer, Beatrice, et al.
(författare)
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GLIOGENE an International Consortium to Understand Familial Glioma
- 2007
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 16:9, s. 1730-1734
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Tidskriftsartikel (refereegranskat)
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