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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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- Holmström, Tim H., et al.
(författare)
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c-Jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:11, s. 7046-7053
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanisms by which the AP-1 transcription factor c-Jun exerts its biological functions are not clearly understood. In addition to its well established role in transcriptional regulation of gene expression, several reports have suggested that c-Jun may also regulate cell behavior by non-transcriptional mechanisms. Here, we report that small interfering RNA-mediated depletion of c-Jun from mammalian cells results in inhibition of 28 S and 18 S rRNA accumulation. Moreover, we show that c-Jun depletion results in partial translocation of RNA helicase DDX21, implicated in rRNA processing, from the nucleolus to the nucleoplasm. We demonstrate that DDX21 translocation is rescued by exogenous c-Jun expression and that c-Jun depletion inhibits rRNA binding of DDX21. Furthermore, the direct interaction between c-Jun and DDX21 regulates nucleolar localization of DDX21. These results demonstrate that in addition to its transcriptional effects, c-Jun regulates rRNA processing and nucleolar compartmentalization of the rRNA processing protein DDX21. Thus, our results demonstrate a nucleolar mechanism through which c-Jun can regulate cell behavior. Moreover, these results suggest that the phenotypes observed previously in c-Jun-depleted mouse models and cell lines could be partly due to the effects of c-Jun on rRNA processing.
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- Salminen, H, et al.
(författare)
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The role of IGF-I and IGFBP-1 status and secondary hyperparathyroidism in relation to osteoporosis in elderly Swedish women
- 2008
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Ingår i: Osteoporosis International. - United Kingdom : Springer UK. - 0937-941X .- 1433-2965. ; 19:2, s. 201-209
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: IGFBP-1 showed a strong inverse relation to the BMD values. The IGF-I values had a significant positive relation to the BMD values at all sites with the exception of the lumbar spine. The use of loop diuretics was a more important cause of secondary hyperparathyroidism than vitamin D status. INTRODUCTION: Our aim was to investigate among elderly women the relationship to osteoporosis of calcium-regulating hormones and insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: A population-based cross-sectional study of 350 elderly women (mean age 73 years). Measurements of bone mineral density (BMD) of the left hip, lumbar spine and heel and risk markers for osteoporosis were studied. RESULTS: The BMD values showed significant inverse relationship with the values of IGFBP-1 at all sites of measurement and significant positive relationship with the values of IGF-I at all sites with the exception of the lumbar spine. There was no significant association between the values of BMD and the values of 25-hydroxy vitamin D (25(OH)D). The use of loop diuretics was strongly and significantly associated with elevated levels of PTH >65 pg/ml (OR 4.4, P < 0.001). CONCLUSIONS: The anabolic growth factor IGF-I and its modulating binding protein IGFBP-1 showed a stronger association with the BMD values than the calcium regulating hormones 25(OH)D and PTH. In this study the use of loop diuretics was a more important cause of secondary hyperparathyroidism than vitamin D status.
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