| 1. |
- Ashton, Susan, et al.
(författare)
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Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:325
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans.
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| 2. |
- Lissner, Lauren, 1956, et al.
(författare)
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OPEN about obesity: recovery biomarkers, dietary reporting errors and BMI
- 2007
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Ingår i: International Journal of Obesity. ; 31, s. 956-961
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Tidskriftsartikel (refereegranskat)abstract
- Department of Public Health and Community Medicine, Sahlgrenska Academy at Göteborg University, Sweden, and Research Unit for Dietary Studies at Institute of Preventive Medicine, Copenhagen University Hospital, Denmark. Lauren.lissner@medfak.gu.se OBJECTIVE: Obesity-related under-reporting of usual dietary intake is one of the most persistent sources of bias in nutrition research. The aim of this paper is to characterize obese and non-obese individuals with respect to reporting errors observed with two common dietary instruments, using energy and protein recovery biomarkers as reference measures. POPULATION AND METHODS: This report employs data from the Observing Protein and Energy Nutrition (OPEN) study. Analyses are based on stratified samples of 211 (57 obese) men and 179 (50 obese) women who completed 24-h recalls (24HR), food frequency questionnaires (FFQ), doubly labelled water (DLW) and urinary nitrogen (UN) assessments. RESULTS: In obese and non-obese subgroups, FFQ yielded lower energy and protein intake estimates than 24HR, although biomarker-based information indicated under-reporting with both dietary instruments. Gender differences in obesity-related bias were noted. Among women, the DLW-based energy requirement was 378 kcal greater in obese than in non-obese groups; the FFQ was able to detect a statistically significant portion of this extra energy, while the 24HR was not. Among men, the DLW-based energy requirement was 485 kcal greater in the obese group; however, neither FFQ nor 24HR detected this difference in energy requirement. Combining protein and energy estimates, obese men significantly over-reported the proportion of energy from protein using the 24HR, but not with the FFQ. In obese women, no significant reporting error for energy percent protein was observed by either method. At the individual level, correlations between energy expenditure and reported energy intake tended to be weaker in obese than non-obese groups, particularly with the 24HR. Correlations between true and reported protein density were consistently higher than for protein or energy alone, and did not vary significantly with obesity. CONCLUSION: This work adds to existing evidence that neither of these commonly used dietary reporting methods adequately measures energy or protein intake in obese groups. The 24HR, while capturing more realistic energy distributions for usual intake, may be particularly problematic in the obese. PMID: 17299385 [PubMed - indexed for MEDLINE]
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| 3. |
- Lissner, Lauren, 1956, et al.
(författare)
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Recall of physical activity in the distant past: the 32-year follow-up of the Prospective Population Study of Women in Göteborg, Sweden
- 2004
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Ingår i: American Journal of Epidemiology. ; 159 (3):Feb 1, s. 304-307
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Tidskriftsartikel (refereegranskat)abstract
- Institute of Community Medicine, Primary Health Care, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. Lauren.Lissner@medfak.gu.se It has been of interest to researchers in chronic disease epidemiology to determine whether elderly subjects can accurately recall their physical activity patterns in the distant past. As part of a 32-year follow-up of the Prospective Population Study of Women in Göteborg, Sweden, 433 participants currently aged 70-92 years recalled their leisure-time physical activity at the original examination in 1968, when they had been 38-60 years of age. Using a four-point scale, subjects were originally asked to describe leisure-time activity during the previous 12 months. Identical questions were asked in 2000 describing levels in 1968 and current levels. Subjects were more likely to overestimate their previous activity level than to underestimate it: 43.9% of women classified themselves consistently at both examinations; 48.7% overestimated and 7.4% underestimated their previous activity levels. Using current activity as a proxy for recalled levels did not improve the moderate agreement with activity as originally reported in 1968. The average magnitude of the recall bias (recalled minus original values) amounted to one half of a unit on the four-point scale and was not significantly associated with age or body mass index. In summary, systematic errors were observed in remote physical activity recalls by elderly women, who generally remembered being more active 32 years earlier than they had originally reported. Physical activity recall questionnaires for the distant past should be used with caution, particularly in older populations. PMID: 14742291 [PubMed - indexed for MEDLINE]
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