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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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- Carlsson, Ella, et al.
(författare)
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Mass composition of the escaping plasma at Mars
- 2006
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 182:2, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- Data from the Ion Mass Analyzer (IMA) sensor of the ASPERA-3 instrument suite on Mars Express have been analyzed to determine the mass composition of the escaping ion species at Mars. We have examined 77 different ion-beam events and we present the results in terms of flux ratios between the following ion species: CO2+/O+ and O-2(+)/O+. The following ratios averaged over all events and energies were identified: CO2+/O+ = 0.2 and O-2(+)/O+ = 0.9. The values measured are significantly higher, by a factor of 10 for O-2(+)/O+, than a contemporary modeled ratio for the maximum fluxes which the martian ionosphere can supply. The most abundant ion species was found to be O+, followed by O-2(+) and CO2+. We estimate the loss of CO2+ to be 4.0 x 10(24) s(-1) (0.29 kg s(-1)) by using the previous measurements of Phobos-2 in our calculations. The dependence of the ion ratios in relation to their energy ranges we studied, 0.3-3.0 keV, indicated that no clear correlation was found.
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| 4. |
- Johnson, Magnus S.C. 1969, et al.
(författare)
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Interaction of scavenger receptor class B type I with peroxisomal targeting receptor Pex5p.
- 2003
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Ingår i: Biochemical and biophysical research communications. - 0006-291X. ; 312:4, s. 1325-34
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Tidskriftsartikel (refereegranskat)abstract
- Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective HDL lipid uptake. Peroxisomes play an important role in lipid metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p. We have previously identified a PTS1 motif in the intracellular domain of rat SR-BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the peroxisome as demonstrated by double labeling with anti-Flag IgG and anti-catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However, when an antibody against Pex5p was used for immunoprecipitation, only the 57kDa, non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in vitro.
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| 5. |
- Lehmann, O. J., et al.
(författare)
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Novel anterior segment phenotypes resulting from forkhead gene alterations: Evidence for cross-species conservation of function
- 2003
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:6, s. 2627-2633
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Mutations in murine and human Versions of an ancestrally related gene usually result in similar phenotypes. However, interspecics differences exist, and in the case of two forkhead transcription factor genes (FOXC1 and FOXC2), these differences include corneal or anterior segment phenotypes, respectively. This study was undertaken to determine whether such discrepancies provide an opportunity for identifying novel human-murine ocular phenotypes. METHODS. Four pedigrees with early-onset glaucoma phenotypes secondary to segmental chromosomal duplications or deletions encompassing FOXC1 and 18 individuals from 9 FOXC2 mutation pedigrees underwent detailed ocular phenotyping. Subsequently, mice with mutations in Foxc1 or a related forkhead gene, Foxe3, were assessed for features of the human phenotypes. RESULTS. A significant increase in central corneal thickness was present in affected individuals from the segmental duplication pedigrees compared with their unaffected relatives (mean increase 13%, maximum 35%, P < 0.05). Alterations in corneal thickness were present in mice heterozygous and homozygous for Foxe3 mutations but neither in Foxc1 heterozygotes nor the small human segmental deletion pedigree. Mutations in FOXC2 resulted in ocular anterior segment anomalies. These were more severe and prevalent with mutations involving the forkhead domain. CONCLUSIONS. Normal corneal development is dependent on the precise dose and levels of activity of certain forkhead transcription factors. The altered corneal thickness attributable to increased forkhead gene dosage is particularly important, because it may affect the clinical management of certain glaucoma subtypes and lead to excessive treatment. The FOXC1 and Foxe3 data, taken together with the novel ocular phenotypes of FOXC2 mutations, highlight the remarkable cross-species conservation of function among forkhead genes.
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| 9. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Molecular characterization of a local sulfonylurea system in human adipose tissue.
- 2004
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Ingår i: Molecular and cellular biochemistry. - 0300-8177 .- 1573-4919. ; 258:1-2, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
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| 10. |
- Johnson, Magnus S.C. 1969, et al.
(författare)
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Expression of scavenger receptor class B type I in gallbladder columnar epithelium.
- 2002
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Ingår i: Journal of gastroenterology and hepatology. - 0815-9319. ; 17:6, s. 713-20
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Tidskriftsartikel (refereegranskat)abstract
- The lipid content of bile may be modified by the gallbladder epithelium. Recent studies indicate that cholesterol can be absorbed from bile and that this can be enhanced by apolipoprotein (apo) A-I. SR-BI is a multifunctional receptor capable of binding a wide array of native or modified lipoproteins, phospholipid or bile acid micelles. As apo A-I is a ligand for scavenger receptor class B type I (SR-BI) we have characterized the expression of this receptor in murine gallbladder.Reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemistry were used to study SR-BI expression in murine gallbladders. SR-BI expression was also used to examine gallbladders from high-fat-fed wild-type and apo B-100 transgenic mice.SR-BI and SR-BII mRNA are expressed in gallbladder. SR-BI immunoreactivity was localized to the columnar epithelium of the gallbladder. Immunoreactive SR-BI in gallbladder had an estimated molecular weight of 57 kDa, in contrast to the expected 82 kDa. Deglycosylation experiments indicated that the size difference between the two forms of the receptor is due to post-translational modification. Fat feeding of apo B transgenic mice resulted in gallstone formation but had no effect on the abundance of SR-BI.Gallbladder epithelial cells express SR-BI. This opens the possibility that SR-BI may influence the modification of bile in the gallbladder.
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