| 1. |
- 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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| 2. |
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| 3. |
- 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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| 4. |
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| 5. |
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| 6. |
- Ebenå, G., et al.
(författare)
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A comparison of methods for mine tailings sterilisation
- 2003
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Ingår i: Proc. ICARD 2003, 6th Int. Conf. on Acid Rock Drainage, Cairns, Australia, July 14 – 17, 2003. ; , s. 1013-
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Konferensbidrag (refereegranskat)abstract
- The study of microbial sulfide oxidation and oxidation rates of tailings requires the use of sterile control samples in laboratory experiments for comparison purposes. The need for sterile tailings sand is also apparent in the study of microbial communities and processes. This study compares six different methods with regard to sterilisation efficiency and investigates chemical and mineralogical changes in the samples as the result of sample treatment. In addition, the effect of sterilisation on mineral weathering rates is also studied. The efficiency of the different methods with regard to sterility is estimated by most probable numbers (MPN) of both sulfur and iron oxidising bacteria. The sterilisation methods that were compared are: washing with sterile water, washing with ethanol, applying antibiotics, repeated heating to 70°C, autoclaving, and γ-irradiation. There are several possible drawbacks with the different methods, including the risk of an applied chemical acting as a substrate for micro-organisms in the system, and the risk of altering the tailings. The results show a substantial difference in sterilisation efficiency between the treatments. For example, autoclaving, repeated heating, ethanol and irradiation efficiently kill micro-organisms, rendering an undetectable amount of bacteria after one month of incubation, whilst washing with water exhibits virtually no microbiological effect, with a bacterial content comparable to the control. The use of antibiotics for sterilisation ranks intermediate: the lag-phase was twice as long in the antibiotics treatment compared with the controls. X-ray diffraction, optical and electron microscopy, Mössbauer spectroscopy, and mineral magnetism indicate no significant change in the bulk mineralogical composition. However, X-ray photoelectron spectroscopy analyses show that with some of the treatments, sulfides are partially oxidised, as indicated by the formation of sulfate and partially – oxidised sulfur species at the tailings surfaces. Aerated batch weathering experiments performed on sterilised tailings samples and untreated controls indicated that while the initial rates of element (S, Fe, Cu, Zn, Mg, Na, K, Ca) release may differ between the samples, over the course of ~100 days of experiment at pH 2 and room temperature, the rates declined toward a similar value for all samples. To conclude, there does not appear to be one perfect method for tailings sterilisation. Autoclaving and heating damage the mineral grain structure and oxidise the sulfide surfaces. Ethanol, antibiotics and rinsing greatly alter the pore water chemistry through the washing procedure. In addition, ethanol and denatured antibiotics might serve as a substrate and also, in the case of antibiotics, adhere to mineral surfaces thus obstructing chemical reactions. Irradiation seems to be the preferable method on an overall basis, although the formation of surface Fe3+ was suggested by Mössbauer spectroscopy.
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| 7. |
- Ekman-Ordeberg, G, et al.
(författare)
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Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro
- 2009
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Ingår i: Acta Obstet Gynecol Scand. - : Wiley. ; 88:9, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The low molecular weight heparin, Dalteparin, shortens human labor time. The aim of this study was to investigate if the mechanism behind this effect involves myometrial contractility and cervical ripening and if the anticoagulative activity is necessary for its effect. DESIGN: Experimental in vitro study. SETTING: Lund University and Karolinska Institute, Sweden. METHODS: The effect of low molecular weight heparins with or without anticoagulative properties on myometrial contractility was measured in vitro on smooth muscle strips from biopsies obtained at elective cesarean sections. The effects on cervical ripening were assessed in cervical fibroblasts cultured from explants of cervical biopsies obtained at delivery. MAIN OUTCOME MEASURES: Mean force and number of contractions in uterine smooth muscle strips and interleukin-8 (IL-8) secretion in cervical fibroblasts. RESULTS: Myometrial smooth muscle strips pretreated with low molecular weight heparins showed increased contractile activity compared to untreated smooth muscle strips. Secretion of IL-8 from cultured cervical fibroblasts was significantly increased after treatment with low molecular weight heparin. Both these effects were independent of anticoagulative activity of the low molecular weight heparin. CONCLUSIONS: A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Gleisner, M., et al.
(författare)
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Comparison of sulfide oxidation in unweathered pyretic mine tailings
- 2003
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Ingår i: Proc. ICARD 2003, 6th Int. Conf. on Acid Rock Drainage, Cairns, Australia, July 14 – 17, 2003. ; , s. 1027-1030
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Konferensbidrag (refereegranskat)abstract
- The study focuses on sulfide oxidation processes in unweathered pyrite-rich mine tailings from a soil-covered impoundment in northern Sweden. To simulate the oxygen-limited conditions in water saturated tailings two long-term column experiments were performed. Results are presented for the first 11 months of the experiments at room temperature. The tailings used in the experiments were of two different grain sizes (one coarse grained, in the range 0.02 - 0.6 mm with a grain surface area of 1.86 m2 g-1, and one fine-grained, in the range 0.0015 - 0.06 mm with a grain surface area of 10.00 m2 g-1) and with slightly different mineralogical composition. The S:Fe molar ratio in the leachates (1.0 - 1.5) indicates either that pyrrhotite is the main iron sulfide undergoing oxidation in our experiments, or, alternatively that the S:Fe molar ratio in the leachate is determined by pyrite weathering in conjunction with other processes releasing iron or immobilising sulfate. However, speciation modelling of the leachates indicates that ferrihydrite was close to saturation, suggesting that a ferric oxyhydroxide may have dissolved/ precipitated during the experimental period, thereby affecting the S:Fe molar ratio. Pyrite oxidation rates obtained from the two column experiments during ‘steady-state’ were 2.25 × 10-13 and 8.45 × 10-14 mol m-2 s-1 in the coarse and fine tailings, respectively. Pyrrhotite oxidation rates, as an alternative, were 2.31 × 10-12 and 1.24 × 10-11 mol m-2 s-1 in the coarse and fine tailings, respectively. Natural microbial activity was confirmed in both the tailings and the leachates; therefore, the obtained oxidation rates are not strictly abiotic. It is thus concluded, based on the experimental results, that tailing heterogeneity will result in zones with different oxidation rates, related to their physical and chemical properties.
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| 13. |
- Hakamies-Blomqvist, Liisa, et al.
(författare)
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Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil : A multicentre randomised phase III trial by the Scandinavian breast group
- 2000
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 36:11, s. 1411-7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%. QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed some improvement in emotional functioning during treatment, with a significant difference favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other functional scales remained stable throughout the first six cycles. There were significant differences favouring the MF group on the social functioning scale at treatment cycle 6 and on the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales there were no statistically significant differences between the groups. However, at baseline, the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of fatigue, dyspnoea and insomnia. There were no statistically significant differences between the groups in the mean change scores of the functional and symptom scales. Interindividual variance was, however, larger in the T group. Differences in QoL between the two treatment groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of treatment should be made on the basis of the expected clinical effect.
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| 14. |
- Hao, X. J., et al.
(författare)
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Dendrimers as scaffolds for multifunctional reversible addition-fragmentation chain transfer agents : Syntheses and polymerization
- 2004
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 42:23, s. 5877-5890
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and characterization of novel first- and second-generation true dendritic reversible addition-fragmentation chain transfer (RAFT) agents carrying 6 or 12 pendant 3-benzylsulfanylthiocarbonylsulfanylpropionic acid RAFT end groups with Z-group architecture based on 1,1,1-hydroxyphenyl ethane and trimethylolpropane cores are described in detail. The multifunctional dendritic RAFT agents have been used to prepare star polymers of poly(butyl acrylate) (PBA) and polystyrene (PS) of narrow polydispersities (1.4 < polydispersity index < 1.1 for PBA and 1.5 < polydispersity index < 1.3 for PS) via bulk free-radical polymerization at 60 degreesC. The novel dendrimer-based multifunctional RAFT agents effect an efficient living polymerization process, as evidenced by the linear evolution of the number-average molecular weight (M.) with the monomer-polymer conversion, yielding star polymers with molecular weights of up to M-n = 160,000 g mol(-1) for PBA (based on a linear PBA calibration) and up to M. = 70,000 g mol(-1) for PS (based on a linear PS calibration). A structural change in the chemical nature of the dendritic core (i.e., 1,1,1-hydroxyphenyl ethane vs trimethylolpropane) has no influence on the observed molecular weight distributions. The star-shaped structure of the generated polymers has been confirmed through the cleavage of the pendant arms off the core of the star-shaped polymeric materials.
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| 15. |
- Harth, E. M., et al.
(författare)
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The effect of macromolecular architecture in nanomaterials : A comparison of site isolation in porphyrin core dendrimers and their isomeric linear analogues
- 2002
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 124:15, s. 3926-3938
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Forskningsöversikt (refereegranskat)abstract
- The influence of macromolecular architecture on the physical properties of polymeric materials has been studied by comparing poly(benzyl ether) dendrons with their exact linear analogues. The results clearly confirm the anticipation that dendrimers are unique when compared to other architectures. Physical properties, from hydrodynamic volume to crystallinity, were shown to be different, and in a comparative study of core encapsulation in macromolecules of different architecture, energy transduction from the polymer backbone to a porphyrin core was shown to be different for dendrimers as compared to that of isomeric four- or eight-arm star polymers. Fluorescence excitation revealed strong, morphology dependent intramolecular energy transfer in the three macromolecular isomers investigated, Even at high generations, the dendrimers exhibited the most efficient energy transfer, thereby indicating that the dendritic architecture affords superior site isolation to the central porphyrin it surrounds.
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| 16. |
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| 17. |
- Jesberger, M., et al.
(författare)
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Hyperbranched polymers as scaffolds for multifunctional reversible addition-fragmentation chain-transfer agents : A route to polystyrene-core-polyesters and polystyrene-block-poly(butyl acrylate)-core-polyesters
- 2003
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 41:23, s. 3847-3861
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Tidskriftsartikel (refereegranskat)abstract
- Polydisperse hyperbranched polyesters were modified for use as novel multifunctional reversible addition-fragmentation chain-transfer (RAFT) agents. The polyester-core-based RAFT agents were subsequently employed to synthesize star polymers of n-butyl acrylate and styrene with low polydispersity (polydispersity index < 1.3) in a living free-radical process. Although the polyester-core-based RAFT agent mediated polymerization of n-butyl acrylate displayed a linear evolution of the number-average molecular weight (M.) up to high monomer conversions (>70%) and molecular weights [M-n > 140,000 g mol(-1), linear poly(methyl methacrylate) equivalents)], the corresponding styrene-based system reached a maximum molecular weight at low conversions (approximate to30%, M-n = 45,500 g mol(-1), linear polystyrene equivalents). The resulting star polymers were subsequently used as platforms for the preparation of star block copolymers of styrene and n-butyl acrylate with a polyester core with low polydispersities (polydispersity index < 1.25). The generated polystyrene-based star polymers were successfully cast into highly regular honeycomb-structured microarrays.
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| 18. |
- Liedberg, Fredrik, et al.
(författare)
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Bladder cancer and the sentinel node concept
- 2003
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Ingår i: Aktuelle Urologie. - : Georg Thieme Verlag KG. - 0001-7868 .- 1438-8820. ; 34, s. 115-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Lymph node status is one of the most important prognostic factors in muscle-invasive bladder cancer. The extent of lymphadenectomy performed in conjunction with cystectomy and the question as to whether this is a staging or therapeutic intervention are matters of discussion. The aim of this study was to evaluate the sentinel node (SN) concept and to correlate findings with tumour status in excised regional lymph nodes. Material and method: 26 patients scheduled for cystectomy were investigated with preoperative lymphoscintigraphy, peroperative dye detection (Patent Blue) and dynamic lymphoscintigraphy (Nanocoll or Albures 50 MBq/ml). The substances were injected adjacent to the tumour in the detrusor muscle. Results: Sentinel nodes were detected in 21 of the 26 of the investigated patients. 7/21 SN were located outside the obturator fossa. Of the eight patients with lymph node metastasis, five displayed metastasis in lymph nodes outside the obturator fossa. There was one false negative SN in a patient with multifocal tumour, while in the other seven patients with lymph node metastasis, these were detected in the SN. Conclusion: Sentinel node detection is possible in most cases of bladder cancer scheduled for cystectomy. The significance of utilizing this method to detect lymph node metastasis outside the obturator fossa warrants further investigation.
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| 19. |
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| 20. |
- Malmström, Helena, et al.
(författare)
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More on contamination : The use of asymmetric molecular behavior to identify authentic ancient human DNA
- 2007
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 24:4, s. 998-1004
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Tidskriftsartikel (refereegranskat)abstract
- Authentication of ancient human DNA results is an exceedingly difficult challenge due to the presence of modern contaminant DNA sequences. Nevertheless, the field of ancient human genetics generates huge scientific and public interest, and thus researchers are rarely discouraged by problems concerning the authenticity of such data. Although several methods have been developed to the purpose of authenticating ancient DNA (aDNA) results, while they are useful in faunal research, most of the methods have proven complicated to apply to ancient human DNA. Here, we investigate in detail the reliability of one of the proposed criteria, that of appropriate molecular behavior. Using real-time polymerase chain reaction (PCR) and pyrosequencing, we have quantified the relative levels of authentic aDNA and contaminant human DNA sequences recovered from archaeological dog and cattle remains. In doing so, we also produce data that describes the efficiency of bleach incubation of bone powder and its relative detrimental effects on contaminant and authentic ancient DNA. We note that bleach treatment is significantly more detrimental to contaminant than to authentic aDNA in the bleached bone powder. Furthermore, we find that there is a substantial increase in the relative proportions of authentic DNA to contaminant DNA as the PCR target fragment size is decreased. We therefore conclude that the degradation pattern in aDNA provides a quantifiable difference between authentic aDNA and modern contamination. This asymmetrical behavior of authentic and contaminant DNA can be used to identify authentic haplotypes in human aDNA studies.
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| 21. |
- Mazzucato, M, et al.
(författare)
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Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation
- 2002
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Ingår i: FASEB Journal. - 1530-6860. ; 16:14, s. 1903-1916
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Tidskriftsartikel (refereegranskat)abstract
- We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions. A purification scheme was devised to obtain vascular versicans, which by biochemical, immunochemical, and ultrastructural means were asserted to be 1) composed primarily of isoforms V1 and V2; 2) free of contaminants; 3) prevalently substituted with chondroitin-4-sulfate and dermatan sulfate (DS) chains; and 4) capable of binding hyaluronan to form link protein-stabilized ternary complexes. Real-time analysis of human platelet perfused under diverse shear forces showed that they largely failed to bind to several vascular and nonvascular proteoglycans (PGs). In contrast, they bound in a dose- and shear rate-dependent manner to vascular versicans, exhibiting a unique attachment-detachment kinetics and establishing a firm substrate tethering characterized with no significant aggregation. Digestion of these PGs with lyases and competition experiments with purified glycosaminoglycans revealed that platelet adhesion to vascular versicans was primarily mediated by their DS chains. Incorporation of the versicans into fibrillar collagen substrates augmented their adhesive activity and strongly promoted platelet aggregation at low and high shear rates. Affinity chromatography of platelet surfaces on DS columns identified a 120-140 kDa polypeptide complex that behaved as a specific vascular versican binding membrane ligand in solid-phase binding assays. These findings indicate that selective versican variants of the subendothelium may serve as ancillary GPIbalpha/integrin/selectin-independent platelet ligands in healthy and diseased vascular beds and may be directly responsible for the platelet accruing after rupture of atherosclerotic plaques., versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation.
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| 22. |
- Parola, S., et al.
(författare)
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Hybrid materials for non linear absorption
- 2005
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Ingår i: Nonlinear Optical Transmission and Multiphoton Processes in Organics III. - : SPIE - International Society for Optical Engineering. ; , s. 1-5
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Konferensbidrag (refereegranskat)abstract
- Alkynyl platinum derivatives and thiacalixarenes were trapped in solid transparent matrices prepared by the sol-gel process. By using functionalyzed silicon alkoxides, molecular species were grafted to the gel matrix giving a high doping concentration and chemically stable materials. In this communication we present broadband optical limiting performance in the visible wavelength region observed in the prepared materials.
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| 23. |
- Saal, Lao, et al.
(författare)
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PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma
- 2005
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Ingår i: Cancer Research. - 1538-7445. ; 65:7, s. 2554-2559
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Tidskriftsartikel (refereegranskat)abstract
- Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate WIN is critical for tumorigenesis in a significant fraction of breast cancers and that loss Of PIP3 homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications.
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| 24. |
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| 29. |
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| 30. |
- Campa, A., et al.
(författare)
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The potential of textured front ZnO and flat TCO/metal back contact to improve optical absorption in thin Cu(In,Ga)Se2 solar cells
- 2007
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 515:15, s. 5968-5972
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Tidskriftsartikel (refereegranskat)abstract
- The role of additionally textured front transparent conductive oxide − TCO (ZnO:Al) and flat TCO/metal contact on optical improvements in thin Cu(In,Ga)Se2 (CIGS) solar cells are investigated by means of numerical simulations. A de-coupled analysis of two effects related to additional texturing of front surface of ZnO:Al TCO − (i) enhancement of light scattering and (ii) decreased total reflectance (antireflective effect) − reveals that the improvements in quantum efficiency, QE, and short-circuit current, JSC, of the solar cell originate from an antireflective effect only. In order to improve optical properties of the back contact the introduction of a TCO layer (undoped ZnO) between CIGS and back metal contact is investigated from the optical point of view. In addition to ZnO/Mo, a highly reflective ZnO/Ag contact (ZnO is also assumed to work as a protection layer for Ag) is also included in simulations. Results show significant increase in reflectance related to introduced ZnO in front of Mo. Drastically increased reflectance is obtained if ZnO/Mo is substituted with ZnO/Ag. The improvements in QE and JSC of a thin CIGS solar cell, related to ZnO/metal contacts are presented.
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| 31. |
- Claesson, Hans, et al.
(författare)
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Rheological behaviour during UV-curing of a star-branched polyester
- 2002
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Ingår i: Progress in organic coatings. - 0300-9440 .- 1873-331X. ; 44:1, s. 63-67
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Tidskriftsartikel (refereegranskat)abstract
- Using a rheometer coupled with an UV-light generator, the viscoelastic behaviour during the fast cure of star-branched polyester is investigated. The 32 arm star polymers consist of a hyperbranched polyester core, Boltorn(TM) and linear grafts of poly(E-caprolactone) (degree of polymerisation: 20-52) with methacrylate end groups. The resins are crystalline and the melting points range from 34 to 50degreesC; films can be formed and cured below 80degreesC. The crossover of G' and G was used as the gel point. The time to reach the gel point, a few seconds, increases linearly with molecular weight.
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| 32. |
- Clarke, M, et al.
(författare)
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Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials
- 2008
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Ingår i: The Lancet. - 0140-6736. ; 371:9606, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982).FINDINGS: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0.73, 2p<0.00001), breast cancer mortality 24% versus 32% (ratio 0.73, 2p=0.0002), and death from any cause 25% versus 33% (ratio 0.75, 2p=0.0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0.82, 2p<0.00001), breast cancer mortality 36% versus 42% (ratio 0.86, 2p=0.0004), and death from any cause 39% versus 45% (ratio 0.87, 2p=0.0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy.INTERPRETATION: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.
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| 33. |
- Dubicke, A., et al.
(författare)
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Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts
- 2008
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407 .- 1360-9947. ; 14:11, s. 641-647
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT-PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10(-13)-10(-6) M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3.
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| 34. |
- Dyrskjøt, Lars, et al.
(författare)
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Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma : a multicenter validation study
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:12, s. 3545-3551
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression. Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome. Results: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (P < 0.001). Furthermore, the classifier added information regarding disease progression of Ta or T1 tumors (P < 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (P < 0.001) and cancer-specific survival (P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; P < 0.001) in multivariate logistic regression analysis. Conclusion: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.
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| 35. |
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| 36. |
- Gode, Peter, et al.
(författare)
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A novel sulfonated dendritic polymer as the acidic component in proton conducting membranes
- 2006
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Ingår i: Solid State Ionics. - : Elsevier BV. - 0167-2738 .- 1872-7689. ; 177:7-8, s. 787-794
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Tidskriftsartikel (refereegranskat)abstract
- The present study involves the synthesis of sulfonated poly(3-ethyl-3-(hydroxymethyl)oxetane), sPTMPO, by end-capping the hydroxy-groups in the PTMPO with 1,4-butane sultone. A series of the polymer with different degrees of substitution was investigated. Furthermore, the subsequent use of the sulfonated PTMPO as the acidic component in proton conducting membranes was explored. The membranes were prepared by either a) mixing the partly sulfonated PTMPO with hexamethoxymethyl melamine (HMMM) to form cross-links by ether formation between the methylol groups on HMMM and the remaining hydroxyl groups on the hyperbranched polyether or b) using the sulfonated polyether in conjunction with a pyridine functionalised polysulfone, PSU-pyridine, to produce acid-base blend membranes. Membrane properties such as proton conductivity, water uptake and mechanical properties are discussed.
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| 37. |
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| 38. |
- Hakamies-Blomqvist, Liisa, et al.
(författare)
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Timing of quality of life (QoL) assessments as a source of error in oncological trials
- 2001
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 35:5, s. 709-16
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Tidskriftsartikel (refereegranskat)abstract
- AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of the error produced by incorrect timing quality of life (QoL) measurements in patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients were randomized to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). The QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in both treatment arms. At baseline, there were statistically significant differences in the MF group on the nausea/vomiting scale, with ill-timed assessment showing more symptoms, and in the T group on the physical functioning scale with ill-timed assessments indicating better QoL. The mean scores of correct vs. incorrect timings over the first 14 cycles showed statistically significant differences on several scales. In the MF group, ill-timed assessments indicated significantly worse physical functioning and global QoL, and significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia, appetite loss, and constipation. In the T group, ill-timed assessment showed better physical functioning, less dyspnoea and more insomnia than correctly timed assessments. The reasons for erroneous timing were not always detectable retrospectively. However, in some cases the MF group, being in standard treatment, seemed to have followed a clinical routine not involving the active participation of the study nurse responsible, whereas patients in the experimental T group were more consistently taken care of by the study nurses. CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials jeopardises both the reliability of the QoL findings within treatment and the validity of QoL outcome comparisons between treatments. This issue should be emphasized in the planning of both the study design and clinical routines.
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| 39. |
- Hao, X. J., et al.
(författare)
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Dendrimers as scaffolds for reversible addition fragmentation chain transfer (RAFT) agents : A route to star-shaped block copolymers
- 2005
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Ingår i: Australian journal of chemistry (Print). - 0004-9425 .- 1445-0038. ; 58:6, s. 483-491
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Tidskriftsartikel (refereegranskat)abstract
- Star-shaped block copolymers of styrene and n-butyl acrylate having three, six, and twelve pendent arms were successfully synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. Dendritic cores ( based on 1,1,1-trimethylolpropane) of generation 0, 1, and 2 have been functionalized with 3-benzylsulfanylthiocarbonylsulfanylpropionic ester groups and have subsequently been employed to mediate the polymerization of styrene and n-butyl acrylate to generate macro-star-RAFT agents as starting materials for chain extension. The chain extension of the macro-star-RAFT agents with either styrene or n-butyl acrylate by bulk free radical polymerization at 60 degrees C gives narrowly distributed polymer (final polydispersities close to 1.2) increasing linearly in molecular weight with increasing monomer-to-polymer conversion. However, with an increasing number of arms (i.e., when going from three- to twelve-armed star polymers), the chain extension becomes significantly less efficient. The molecular weight of the generated block copolymers was assessed using H-1 NMR spectroscopy as well as size exclusion chromatography calibrated with linear polystyrene standards. The hydrodynamic radius, R-h, of the star block copolymers as well as the precursor star polymers was determined in tetrahydrofuran by dynamic light scattering (90 degrees) at 25 degrees C. Interestingly, the observed R-h-M-n relationships indicate a stronger dependence of R-h on M-n for poly(butyl acrylate) stars than for the corresponding styrene polymers. R-h increases significantly when the macro-star-RAFT agent is chain extended with either styrene or n-butyl acrylate.
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| 40. |
- Hedenqvist, Mikael S., et al.
(författare)
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Transport properties of hyperbranched and dendrimer-like star polymers
- 2000
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Ingår i: Polymer. - 0032-3861 .- 1873-2291. ; 41:5, s. 1827-1840
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Tidskriftsartikel (refereegranskat)abstract
- Moisture transport properties were assessed by sorption and desorption measurements on hydroxyl-functional hyperbranched polyesters based on 2,2-bis(methylol) propionic acid (bis-MPA) as AB(2)-monomer with ethoxylated pentaerythritol. A series of these polymers with different molar masses were studied. For the first time, it is reported that sigmoidal sorption curves were successfully modelled using a time-dependent surface boundary concentration, where the relaxation time was obtained from the mechanical stress relaxation data. The zero concentration diffusivities were very small and comparable with the values of fully amorphous poly(vinyl alcohol). Both the diffusivity data and the stress relaxation data indicated that these materials were plasticized by moisture. Ethylene glycol transport properties were measured on a hexadecanoate(C16)-terminated bis-MPA hyperbranched polymer. The replacement of the hydroxyl groups with C16 paraffin tails resulted in an increase in solute diffusivity despite the fact that these polymers became semicrystalline. The shape of the desorption curves indicated that continuous micropores were present and facilitated mass transport. The moisture transport properties were also measured on a series of semicrystalline dendrimer-like star poly(epsilon-caprolactone(s)). The low measured densities of these highly crystalline dendrimers confirmed that the porosity, as indicated by the shape of the desorption curves, had to be discontinuous. The porosity in the (C16)-terminated and the poly(epsilon-caprolactone(s)) was impossible to eliminate by applying a high external pressure during crystallization. A collective view of all the results obtained confirm that the transport properties are primarily controlled by the hydroxyl group concentration.
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| 41. |
- Herbert, R. B., et al.
(författare)
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Quantification of abiotic reaction rates in mine tailings : Evaluation of treatment methods for eliminating iron- and sulfur-oxidizing bacteria
- 2005
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 39:3, s. 770-777
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Tidskriftsartikel (refereegranskat)abstract
- Effective treatment techniques for eliminating iron-oxidizing (10B) and sulfur-oxidizing bacteria (SOB) are required for the comparison of abiotic and microbial sulfide oxidation rates and mechanisms in mine tailings. This study evaluates the effect of autoclaving, repeated heating, ethanol treatment, antibiotic treatment, gamma-radiation, and washing with deionized water on tailings characteristics and concentrations of IOB and SOB. Most probable number enumeration indicates that IOB and SOB were present at very low concentrations or below detection limits following treatment with all methods except rinsing and antibiotics treatment, where higher concentrations of IOB and SOB were present. The physical, chemical, and mineralogical characterization of the tailings indicated no changes in bulk mineralogy or bulk chemical composition as a result of treatment. However, an increase in oxidized sulfur species at the tailings surface, as determined by X-ray photoelectron spectroscopy, was observed for the heating, autoclaving, and antibiotics treatments. Batch weathering experiments, used to evaluate the effect of treatment on element release rates, indicated that the final element release rates (after >30 d) were similar between treated and untreated control samples. On the basis of the results of this study, experiments over relatively long periods (>30 d) are to be recommended for the establishment of microbial and abiotic weathering rates in mill tailings samples. For the determination of abiotic reaction rates, treatment by gamma-radiation is suggested to be the most appropriate method for sulfide-rich tailings.
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| 42. |
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| 43. |
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| 44. |
- Hong, Y., et al.
(författare)
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Film blowing of linear low-density polyethylene blended with a novel hyperbranched polymer processing aid
- 2000
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Ingår i: Polymer. - 0032-3861 .- 1873-2291. ; 41:21, s. 7705-7713
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Tidskriftsartikel (refereegranskat)abstract
- The use of hyperbranched polymer (HBP) as a processing aid for linear low-density polyethylene (LLDPE) in the tubular film blowing process was investigated. Through the addition of HBP, sharkskin was successfully eliminated without significantly changing the overall physical properties of LLDPE films. Also, there was a minimum of 40% enhancement in processing rate with addition of 0.5 wt% HBP. The study showed that HBP and LLDPE are immiscible, and HBP has a tendency to migrate to the surface, subsequently, it seems to form a lubricating layer between the metal surfaces and the bulk material. This phase separation between HBP and LLDPE results in an HBP-rich surface, which has a high potential to create unique surface properties tailored to various applications. Rheological analysis indicated that excessive slip was present in HBP/LLDPE suggesting that the onset of slip is not the cause of sharkskin. On the contrary, it may be partially responsible for the elimination of sharkskin.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Krc, J., et al.
(författare)
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Optical and electrical modeling of Cu(In,Ga)Se-2 solar cells
- 2006
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Ingår i: Optical and quantum electronics. - : Springer Science and Business Media LLC. - 0306-8919 .- 1572-817X. ; 38:12-14, s. 1115-1123
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Tidskriftsartikel (refereegranskat)abstract
- In this work numerical modeling of Cu(In,Ga)Se-2 (CIGS) thin-film solar cells is presented. The main features of the optical simulator SunShine and the electrical simulator Aspin that are used for solar cell analysis are demonstrated. Modeling of light scattering at rough interfaces in the solar cell structures is described. The two descriptive scattering parameters that are used in optical simulations are the haze parameter and the angular distribution function of scattered light. The results of optical and electrical simulations of a thin CIGS solar cell with an absorber layer thickness of 360 nm are presented. The calculated external parameters of the solar cell are verified with the experimental data.
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| 50. |
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