| 1. |
- Bergh, Jonas, et al.
(författare)
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Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer : A randomised trial
- 2000
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 356:9239, s. 1384-1391
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. Methods: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. Findings: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. Interpretation: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.
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| 2. |
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| 3. |
- Colwill, Karen, et al.
(författare)
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A roadmap to generate renewable protein binders to the human proteome
- 2011
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Ingår i: Nature Methods. - : Nature America Inc.. - 1548-7091 .- 1548-7105. ; 8:7, s. 551-8
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Tidskriftsartikel (refereegranskat)abstract
- Despite the wealth of commercially available antibodies to human proteins, research is often hindered by their inconsistent validation, their poor performance and the inadequate coverage of the proteome. These issues could be addressed by systematic, genome-wide efforts to generate and validate renewable protein binders. We report a multicenter study to assess the potential of hybridoma and phage-display technologies in a coordinated large-scale antibody generation and validation effort. We produced over 1,000 antibodies targeting 20 SH2 domain proteins and evaluated them for potency and specificity by enzyme-linked immunosorbent assay (ELISA), protein microarray and surface plasmon resonance (SPR). We also tested selected antibodies in immunoprecipitation, immunoblotting and immunofluorescence assays. Our results show that high-affinity, high-specificity renewable antibodies generated by different technologies can be produced quickly and efficiently. We believe that this work serves as a foundation and template for future larger-scale studies to create renewable protein binders.
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| 4. |
- Eggertsen, Robert, 1948, et al.
(författare)
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Att finna dold urininkontinens
- 2002
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Ingår i: Jordemodern. ; 115, s. 24-25
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Hultborn, Ragnar, 1946, et al.
(författare)
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Radiosensitivity: Gender and Order of Administration of G-CSF, An Experimental Study in Mice
- 2019
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Ingår i: Radiation Research. - : Radiation Research Society. - 0033-7587. ; 191:4, s. 335-341
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the potential influence of stimulating bone marrow before cell-cycle-dependent irradiation, we sought to determine overall survival in mice receiving total-body irradiation (TBI) when administered granulocyte stimulating factor (G-CSF) at different time points. Gender differences were also studied. C57/BL/6J mice, aged 9-14 weeks, received 8 Gy TBI in a perspex cage using a linear accelerator. In each of five different experiments, three groups were studied: 1. one control group receiving TBI only; 2. one group treated with filgrastim [500 mu g/kg subcutaneously/intraperitoneally (s.c./i.p.)] the day before TBI, followed by daily filgrastim injections postirradiation (1-5 days); and 3. one group treated with daily filgrastim injections only post-TBI (1-5 days). Each experimental group included male and female mice. Survival of the mice was monitored daily, and mice were euthanized when their condition deteriorated. A total of 293 mice were monitored for at least 37 days post-TBI. Control mice that received 8 Gy TBI showed a significant gender difference, with a median survival of 22 days in females and 17 days in males. Addition of G-CSF, irrespective of pre- or postirradiation, significantly improved survival, but in males the improvement was significantly better when G-CSF was not given before TBI. Improved survival in females was independent of the order of administration of G-CSF. Multiple filgrastim injections were more effective than a single injection, and s.c. administration was not better than i.p. In conclusion, these findings indicate that male mice are more sensitive to TBI than females. Filgrastim improved survival in both genders irrespective of whether given pre- orpostirradiation, but in males the improvement was significantly less if an injection was given before irradiation. These results suggest that, to prevent toxicity most effectively, G-CSF should not be given before cytotoxic therapy. While a completely different experimental model was used here, these results may also be extrapolated to indicate that endocrine cell-cycle suppression therapy should not be given before or during cytotoxic therapy of hormone-dependent tumors (e.g., breast and prostate cancer), thus a reduction in the efficacy of cell-cycle-dependent therapy can be prevented. (C) 2019 by Radiation Research Society
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| 6. |
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IVIM reveals increased blood perfusion of liver metastases after oral intake of Salovum®
- 2015
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661.
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Proceedings (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Elevated interstitial fluid pressure (IFP) of tumours impairs perfusion, which hinders anti-cancer drugs and oxygen to reach tumour cells1-3. AF-16, a 16 amino acid long sequence from the amino terminal end of the endogenous protein Antisecretory Factor (AF), supresses IFP in animal models of solid tumours4, and could improve drug delivery to tumour cells. Salovum®, a spray-dried egg yolk powder with high content of antisecretory peptides, should be tested on humans, but requires non-invasive tumour IFP/perfusion assessment methods. The IntraVoxel Incoherent Motion (IVIM) model applied to multi-b DWI enables measurement of tissue diffusion (D), pseudo-diffusion (D*) and voxel volume fraction of actively perfused capillaries (f) 5. The aim of this study was to investigate if f could be used to monitor changes induced by Salovum® in colorectal liver metastases in vivo Subjects and Methods Previously untreated patients (n=6) with colorectal liver metastases were imaged before, and 24h after intake of Salovum®, using IVIM-MRI (3T Philips, 16‐channel receiver; Single-shot, SE‐EPI (breath-hold); FOV covering liver, 3x3x5mm3 voxels; TR/TE/NSA/SENSE=1900ms/50ms/2/2; 11 b‐values (0-600); acquisition~10 min. MATLAB-based images processing comprised 1) Inter-scan image registration (volume preserving free-form deformation6); 2) Voxelwise fitting of D and A [eq.2] to S(b200-600) (for b>200, [eq.1] reduces to [eq.2], assuming D<2cm) on DWI (b=600), transfer of ROIs to corresponding f-maps for calculation of median ROI f before and after Salovum® intake and 4) Mann-Whitney U-test for statistical significance (α-level=0.05). Results Liver and metastases were well visualised on DWIs and f-maps Median f in metastatic tissue increased after intake of Salovum® in 5/6 patients, but decreased in one patient (Fig.2) (p<0.0001). Discussion/Conclusion The increased perfusion fraction on day 2 may offer a “window of opportunity” for improved transport of drugs to tumour cells. The increase in f was small, and perhaps not clinically significant, suggesting that additional time points after Salovum® intake and dose escalation be investigated, as well as intra-tumour effect heterogeneity. The proposed IVIM approach is a promising, non-invasive method for studying Salovum® induced changes in liver metastases in vivo. Further optimisation and fractionation studies should be conducted, and IVIM derived parameters should be compared to other techniques for perfusion or IFP measurements. References 1Rofstad,E.K.,et al.,Neoplasia. 2009;11(11):1243-51. 2Milosevic,M.F.,et al.,1999;43(5):1111-23. 3Wiig, H.,et al.,1982;42(2):159-64. 4Al-Olama, M.et al., 2011;50(7):1098-104. 5Le Bihan, D., et al., 1988;168(2):497-505. 6Rueckert, D., et al., 1999;18(8):712-21.
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| 7. |
- Karlsson, Per Erik, 1957, et al.
(författare)
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A cumulative ozone uptake-response relationship for the growth of Norway spruce saplings
- 2004
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 128:3, s. 405-417
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Tidskriftsartikel (refereegranskat)abstract
- Norway spruce saplings [Picea abies (L.) Karst.] were exposed during four growing seasons to different ozone treatments in open-top chambers: charcoal filtered air (CF), non-filtered air (NF) and non-filtered air with extra ozone (NF+, 1.4xambient concentrations). The CF and NF + ozone treatments were combined with phosphorous deficiency and drought stress treatments. The total biomass of the trees was harvested at different intervals during the experimental period. The ozone uptake to current-year needles of the Norway spruce saplings was estimated using a multiplicative stomatal conductance simulation model. There was a highly significant correlation between the reduction of total biomass and the estimated cumulative ozone uptake, which did not vary when different thresholds were applied for the rate of ozone uptake. The reduction of the total biomass was estimated to 1 per 10 mmol m(-2) cumulated ozone uptake, on a projected needle area basis. (C) 2003 Elsevier Ltd. All rights reserved.
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| 8. |
- Krischer, Jeffrey P, et al.
(författare)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 9. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 10. |
- Ottosson, Susanne, et al.
(författare)
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Acute hematologic feasibility of G-CSF supported dose-escalated FEC therapy as adjuvant treatment after breast cancer surgery
- 1999
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Ingår i: Anticancer Res. - 0250-7005. ; 19:5C, s. 4429-34
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Tidskriftsartikel (refereegranskat)abstract
- A study of the feasibility of gradually increased epirubicin and cyclophosphamide dosage in an FEC regimen with G-CSF (granulocyte colony stimulating factor) support in 18 high-risk breast cancer patients as adjuvant treatment was carried out. The FEC regimen was initiated with 5-fluorouracil 600 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 900 mg/m2 together with G-CSF 5 micrograms/kg subcutaneously on days 2-15 q 3 weeks for nine cycles, increasing individually through four dose levels to a maximum of 5-FU 600 mg/m2 (not escalated), epirubicin 120 mg/m2 and cyclophosphamide 1800 mg/m2. Transient cytopenias were regularly observed without major clinical complications. Rapid recovery and a biphasic overshoot of granulocytes required individualization of G-CSF support. During the 6-month treatment period, a general decline in granulocytes, platelets and haemoglobin was observed, resulting in maximal dose intensity in the middle of the treatment period. Compared to a conventional FEC regimen (5-Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2, Cyclophosphamide 600 mg/m2 q 3 w) without dose reductions, it was feasible to increase the dose of epirubicin by more than 50 per cent with an increased dose intensity between 25 and 70 per cent. The dose of cyclophosphamide was increased by more than 100 per cent. All patients suffered from complete alopecia and moderate nausea, but there was no acute cardiac or severe mucosal toxicity. It was concluded that intensified, G-CSF supported FEC therapy can be safely administered in an outpatient setting, provided the patients are thoroughly informed and adequately monitored. High-risk patients are enrolled in a study comparing the described regimen and a myeloablative regimen including peripheral stem-cell support. Breast cancer seems to respond to chemotherapy in a dose dependent manner, suggesting the use of dose intensified regimens (1,8,9,11). This approach is currently under investigation in studies comparing standard regimens with myelo-ablative regimens in high-risk primary breast cancer (3,10). In a Scandinavian multicenter study (2), two high dose regimens, G-CSF supported dose-escalated FEC and myeloablative cyclophosphamide-thiotepacarboplatin with peripheral stem cell support, are compared as adjuvant therapy in operable high-risk breast cancer. This phase I study was performed to assess the feasibility and achievable dose intensity of an individually dose-escalated FEC regimen not in previous use.
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| 11. |
- Skarby, L., et al.
(författare)
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Growth of Norway spruce (Picea abies) in relation to different ozone exposure indices: a synthesis
- 2004
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Ingår i: Atmospheric Environment. - 1352-2310. ; 38:15, s. 2225-2236
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Tidskriftsartikel (refereegranskat)abstract
- In the Goteborg Ozone-Spruce Project (GOSP), two independent open-top chamber experiments were conducted during four growing seasons, using one clone of Norway spruce (Picea abies). The experiments tested the impact of ozone, alone and in combination with low phosphorus supply and in combination with drought stress, respectively, on biomass accumulation. In this paper, the results from both experiments were combined for the first time in order to analyse the relationship between relative biomass accumulation and different exposure indices (accumulated exposure over a threshold (AOT) with different cut-off concentrations, and the sum of ozone concentrations above 60 nl l(-1), referred to as SUM06). In addition, a pooled analysis was made on several European studies of Norway spruce as a first effort to synthesize independent data and test the relative growth in relation to the AOT40 index. Significant negative relationships between the relative biomass of the GOSP-clone and the different indices were obtained. AOT20 and AOT30 resulted in the highest correlations. Based on the regression model, ozone is predicted to reduce the biomass of the GOSP-clone by 1% at the critical level for forest trees in Europe, a seasonal AOT40 of 10 mul l(-1) h. A significant negative relationship between relative growth and AOT40 was obtained also with the European data set. At the present ozone critical level, the model predicted a 6% reduction in growth for the most sensitive Norway spruce trees in this data set. (C) 2004 Elsevier Ltd. All rights reserved.
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| 12. |
- Åkesson, Susanne, et al.
(författare)
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Avian orientation at steep angles of inclination: experiments with migratory white-crowned sparrows at the magnetic North Pole
- 2001
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 268:1479, s. 1907-1913
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Tidskriftsartikel (refereegranskat)abstract
- The Earths magnetic field and celestial cues provide animals with compass information during migration.Inherited magnetic compass courses are selected based on the angle of inclination, making itdifficult to orient in the near vertical fields found at high geomagnetic latitudes. Orientation cage experimentswere performed at different sites in high Arctic Canada with adult and young white-crownedsparrows (Zonotrichia leucophrys gambelii) in order to investigate birds ability to use the Earths magneticfield and celestial cues for orientation in naturally very steep magnetic fields at and close to the magneticNorth Pole. Experiments were performed during the natural period of migration at night in the localgeomagnetic field under natural clear skies and under simulated total overcast conditions. The experimentalbirds failed to select a meaningful magnetic compass course under overcast conditions at themagnetic North Pole, but could do so in geomagnetic fields deviating less than 38 from the vertical.Migratory orientation was successful at all sites when celestial cues were available.
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| 13. |
- Åkesson, Susanne, et al.
(författare)
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Avian orientation: effects of cue-conflict experiments with young migratory songbirds in the high Arctic
- 2002
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Ingår i: Animal Behaviour. - : Elsevier BV. - 1095-8282 .- 0003-3472. ; 64:3, s. 469-475
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Tidskriftsartikel (refereegranskat)abstract
- The migratory orientation of juvenile white-crowned sparrows, Zonotrichia leucophrys gambelli, was investigated by orientation cage experiments in manipulated magnetic fields performed during the evening twilight period in northwestern Canada in autumn. We did the experiments under natural clear skies in three magnetic treatments: (1) in the local geomagnetic field; (2) in a deflected magnetic field (mN shifted -90degrees); and (3) after exposure to a deflected magnetic field (mN -90degrees) for 1 h before the cage experiment performed in the local geomagnetic field at dusk. Subjects showed a mean orientation towards geographical east in the local geomagnetic field, north of the expected migratory direction towards southeast. The sparrows responded consistently to the shifted magnetic field, demonstrating the use of a magnetic compass during their first autumn migration. Birds exposed to a cue conflict for 1 h on the same day before the experiment, and tested in the local geomagnetic field at sunset, showed the same northerly orientation as birds exposed to a shifted magnetic field during the experiment. This result indicates that information transfer occurred between magnetic and celestial cues. Thus, the birds' orientation shifted relative to available sunset and geomagnetic cues during the experimental hour. The mean orientation of birds exposed to deflected magnetic fields prior to and during testing was recorded up to two more times in the local geomagnetic field under natural clear and overcast skies before release, resulting in scattered mean orientations. (C) 2002 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved.
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| 14. |
- Åkesson, Susanne, et al.
(författare)
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Dramatic orientation shift of white-crowned sparrows displaced across longitudes in the high arctic
- 2005
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 15:17, s. 1591-1597
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Tidskriftsartikel (refereegranskat)abstract
- Advanced spatial-learning adaptations have been shown for migratory songbirds (1], but it is not well known how the simple genetic program encoding migratory distance and direction in young birds [2-4] translates to a navigation mechanism used by adults [2, 4-6]. A number of convenient cues are available to define latitude on the basis of geomagnetic and celestial information [7-15], but very few are useful to defining longitude [12-15]. To investigate the effects of displacements across longitudes on orientation, we recorded orientation of adult and juvenile migratory white-crowned sparrows, Zonotrichia leucophrys gambelii, after passive longitudinal displacements, by ship, of 266-2862 km across high-arctic North America. After eastward displacement to the magnetic North Pole and then across the 0 degrees declination line, adults and juveniles abruptly shifted their orientation from the migratory direction to a direction that would lead back to the breeding area or to the normal migratory route, suggesting that the birds began compensating for the displacement by using geomagnetic cues alone or together with solar cues. In contrast to predictions by a simple genetic migration program, our experiments suggest that both adults and juveniles possess a navigation system based on a combination of celestial and geomagnetic information, possibly declination, to correct for eastward longitudinal displacements.
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| 15. |
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