| 1. |
- Börjesson, Anna E, et al.
(författare)
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Roles of transactivating functions 1 and 2 of estrogen receptor-alpha in bone.
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 108:15, s. 6288-6293
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Tidskriftsartikel (refereegranskat)abstract
- The bone-sparing effect of estrogen is primarily mediated via estrogen receptor-α (ERα), which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand binding domain. To evaluate the role of ERα AF-1 and ERα AF-2 for the effects of estrogen in bone in vivo, we analyzed mouse models lacking the entire ERα protein (ERα(-/-)), ERα AF-1 (ERαAF-1(0)), or ERα AF-2 (ERαAF-2(0)). Estradiol (E2) treatment increased the amount of both trabecular and cortical bone in ovariectomized (OVX) WT mice. Neither the trabecular nor the cortical bone responded to E2 treatment in OVX ERα(-/-) or OVX ERαAF-2(0) mice. OVX ERαAF-1(0) mice displayed a normal E2 response in cortical bone but no E2 response in trabecular bone. Although E2 treatment increased the uterine and liver weights and reduced the thymus weight in OVX WT mice, no effect was seen on these parameters in OVX ERα(-/-) or OVX ERαAF-2(0) mice. The effect of E2 in OVX ERαAF-1(0) mice was tissue-dependent, with no or weak E2 response on thymus and uterine weights but a normal response on liver weight. In conclusion, ERα AF-2 is required for the estrogenic effects on all parameters evaluated, whereas the role of ERα AF-1 is tissue-specific, with a crucial role in trabecular bone and uterus but not cortical bone. Selective ER modulators stimulating ERα with minimal activation of ERα AF-1 could retain beneficial actions in cortical bone, constituting 80% of the skeleton, while minimizing effects on reproductive organs.
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| 2. |
- Börjesson, Anna E, et al.
(författare)
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The role of activation functions 1 and 2 of estrogen receptor-alpha for the effects of estradiol and selective estrogen receptor modulators in male mice
- 2013
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 28:5, s. 1117-1126
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Tidskriftsartikel (refereegranskat)abstract
- Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ER had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ER for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERAF-1 (ERAF-10), ERAF-2 (ERAF-20), or the total ER (ER/) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ER/ or ERAF-20 mirx ERAF-10 mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERAF-1 for the effects of SERMs, we treated orx WT and ERAF-10 mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERAF-10 mice. In conclusion, ERAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERAF-1. Our findings might contribute to the development of bone-specific SERMs in males. (c) 2013 American Society for Bone and Mineral Research.
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| 3. |
- Corsini, Christian, et al.
(författare)
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Patient-reported side effects 1 year after radical prostatectomy or radiotherapy for prostate cancer : a register-based nationwide study
- 2024
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts.OBJECTIVE: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot-assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient-reported outcome measures in the Swedish prostate cancer database.DESIGN, SETTING, AND PARTICIPANTS: This was a nationwide, population-based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics.RESULTS AND LIMITATIONS: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19-0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61).CONCLUSIONS: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP.PATIENT SUMMARY: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects.
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| 4. |
- Corsini, Christian, et al.
(författare)
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Patient-reported Side Effects 1 Year After Radical Prostatectomy or Radiotherapy for Prostate Cancer : A Register-based Nationwide Study
- 2024
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, populationbased cohorts. Objective: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot -assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient -reported outcome measures in the Swedish prostate cancer database. Design, setting, and participants: This was a nationwide, population -based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020. Outcome measurements and statistical analysis: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics. Results and limitations: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19- 0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61). Conclusions: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP. Patient summary: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 5. |
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| 6. |
- Hard, Joanna, et al.
(författare)
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Conbase : a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing
- 2019
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Ingår i: Genome Biology. - : BMC. - 1465-6906 .- 1474-760X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Accurate variant calling and genotyping represent major limiting factors for downstream applications of single-cell genomics. Here, we report Conbase for the identification of somatic mutations in single-cell DNA sequencing data. Conbase leverages phased read data from multiple samples in a dataset to achieve increased confidence in somatic variant calls and genotype predictions. Comparing the performance of Conbase to three other methods, we find that Conbase performs best in terms of false discovery rate and specificity and provides superior robustness on simulated data, in vitro expanded fibroblasts and clonal lymphocyte populations isolated directly from a healthy human donor.
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| 7. |
- Jellvert, Åsa, et al.
(författare)
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Effective oral combination metronomic chemotherapy with low toxicity for the management of castration-resistant prostate cancer.
- 2011
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Ingår i: Experimental and therapeutic medicine. - : Spandidos Publications. - 1792-1015 .- 1792-0981. ; 2:4, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) was previously believed to be a chemoresistant disease. In recent years taxane-based chemotherapy has been shown to prolong survival in patients with castration-resistant prostate cancer (CRPC). It remains to be shown, however, which type of chemotherapy provides the most beneficial effect with the least amount of side effects. Seventeen patients with chemonaive CRPC were enrolled in a pilot study evaluating an orally administered chemo-hormonal treatment regimen using a weekly sequential combination called KEES; consisting of ketoconazole in combination with cyclophosphamide or etoposide in combination with estramustine administered on alternate weeks. Prednisone was administered throughout the treatment period. Prostate-specific antigen (PSA) response and acute and chronic toxicities were evaluated. Seventeen patients with CRPC were treated; eleven patients demonstrated a median reduction in PSA of 87% (range 26-99%). Ten (59%) patients responded with a decrease in PSA >50%. Thrombocytopenia and anaemia were the most common side effects. One study fatality was reported, however, it was unclear whether this was treatment related. In conclusion, KEES may be a promising option for patients with CRPC, resulting in a clear reduction in PSA with limited toxicity. Further clinical evaluation of this metronomic chemohormonal combination is underway.
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| 8. |
- Kindblom, Jon, 1969, et al.
(författare)
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High precision transponder localization using a novel electromagnetic positioning system in patients with localized prostate cancer.
- 2009
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140. ; 90:3, s. 307-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The Micropos 4DRT system is being developed to provide accurate, precise, objective, and continuous target localization during radiotherapy. This study involves the first in vivo use of the system, aiming to evaluate the localization accuracy of this electromagnetic positioning technique compared with radiographic localization and to assess its real-time tracking ability. MATERIAL AND METHODS: An active positioning marker was inserted in the prostatic urethra of 10 patients scheduled to receive radiotherapy for localized prostate cancer. A receiving sensor plate (antennae system) was placed at a known position in the treatment tabletop. Initial in vivo system calibrations were performed in three subjects. Ten additional patients were then enrolled in a study arm that compared radiographic transponder location to radiotransponder location simultaneously acquired by the Micropos 4DRT system. Frontal and side radiographs were taken with the radiopaque transponder located at three different positions within the prostatic urethra. RESULTS: The transponder insertions were all successful and without complications. Comparison of the transponder location as per the Micropos 4DRT system with the radiographic transponder localization showed an average (+/-SD) absolute and relative 3D difference of 2.7+/-1.2 and 1.7+/-1.0mm, respectively. Continuous transponder tracking capability was also demonstrated. CONCLUSIONS: Electromagnetic positioning using the Micropos transponder system is feasible in vivo. Evaluation of this novel non-ionizing localization system, in this study using a transponder positioned in the prostatic urethra, indicates transponder localization accuracy to isocenter comparable with X-ray localization of a radiopaque marker.
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| 9. |
- Kindblom, Jenny, 1971, et al.
(författare)
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Increased adipogenesis in bone marrow but decreased bone mineral density in mice devoid of thyroid hormone receptors.
- 2005
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 36:4, s. 607-16
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient for all known thyroid hormone receptors, TRalpha1-/-beta-/- mice, display a clear skeletal phenotype characterized by growth retardation, delayed maturation of long bones and decreased trabecular and total bone mineral density (BMD; -14.6 +/- 2.8%, -14.4 +/- 1.5%). The aim of the present study was to investigate the molecular mechanisms behind the skeletal phenotype in TRalpha1-/-beta-/- mice. Global gene expression analysis was performed on total vertebrae from wild-type (WT) and TRalpha1-/-beta-/- mice using DNA microarray and the results were verified by real-time PCR. The mRNA levels of six genes (AdipoQ, Adipsin, Fat-Specific Protein 27 (FSP 27), lipoprotein lipase (LPL), retinol-binding protein (RBP) and phosphoenolpyruvate carboxykinase (PEPCK)) expressed by mature adipocytes were increased in TRalpha1-/-beta-/- compared with WT mice. An increased amount of fat (225% over WT) due to an increased number but unchanged mean size of adipocytes in the bone marrow of TRalpha1-/-beta-/- mice was revealed. Interestingly, the mRNA levels of the key regulator of osteoclastogenesis, receptor activator of NF-varkappab ligand (RANKL), were dramatically decreased in TRalpha1-/-beta-/- mice. In conclusion, TRalpha1-/-beta-/- mice demonstrated increased expression of adipocyte specific genes and an increased amount of bone marrow fat. Thus, these mice have increased adipogenesis in bone marrow associated with decreased trabecular bone mineral density (BMD). One may speculate that these effects either could be caused by an imbalance in the differentiation of the osteoblast and the adipocyte lineages at the expense of osteoblastogenesis, or by independent effects on the regulation of both osteoblastogenesis and adipogenesis.
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| 10. |
- Kindblom, Kristina, et al.
(författare)
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A learning process towards person-centred care : A second-year follow-up of guideline implementation
- 2021
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Ingår i: International Journal of Older People Nursing. - : John Wiley & Sons. - 1748-3735 .- 1748-3743. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Research claims that ‘learning by doing’ creates new thinking, often leading to new practice.Objectives: The aim was to explore and describe the staff learning process from the first to the second year when adopting person-centred care into clinical practice in a nursing home for persons with dementia.Method: The data consisted of poster texts from staff and written notes by researchers obtained from the group discussions. The study involved 24 care units (200 staff). Content analysis was chosen as method to explore the learning process.Result: The staff described the actions that they took during year 1 and year 2, in which five categories emerged, activities, environment, information, priorities and staff routines. With researchers' analysis the categories together created the learning process and formed a sub-theme. They further formed an overarching theme from simplicity to complexity and consensus. Staff changes year 1 pertained more to planning and doing, while year 2 changes constituted a larger complexity of person-centred care with reflection, collaborative learning and a mind-set change.Conclusion: Staff chose the development area, and the learning process was illuminated by the researchers. This underscores the value to visualise and verbalise the steps of change as well as include these steps in the design of an implementation process. The concept of person-centred care could be viewed on different levels. The findings may contribute to a more comprehensive understanding of staff learning process when implementation of person-centred care. Implications for practice: Making staff's learning process visible can be a guide for improvement and change from a generic care towards person-centred care. The Regional Board of Research Ethics approved the study (Reg no. 2010/1234-31/5).
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