| 1. |
- Safavi, Setareh, et al.
(författare)
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HSP90 inhibition blocks ERBB3 and RET phosphorylation in myxoid/round cell liposarcoma and causes massive cell death in vitro and in vivo
- 2016
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Ingår i: OncoTarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 433-445
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid sarcoma (MLS) is one of the most common types of malignant soft tissue tumors. MLS is characterized by the FUS-DDIT3 or EWSR1-DDIT3 fusion oncogenes that encode abnormal transcription factors. The receptor tyrosine kinase (RTK) encoding RET was previously identified as a putative downstream target gene to FUS-DDIT3 and here we show that cultured MLS cells expressed phosphorylated RET together with its ligand Persephin. Treatment with RET specific kinase inhibitor Vandetanib failed to reduce RET phosphorylation and inhibit cell growth, suggesting that other RTKs may phosphorylate RET. A screening pointed out EGFR and ERBB3 as the strongest expressed phosphorylated RTKs in MLS cells. We show that ERBB3 formed nuclear and cytoplasmic complexes with RET and both RTKs were previously reported to form complexes with EGFR. The formation of RTK hetero complexes could explain the observed Vandetanib resistence in MLS. EGFR and ERBB3 are clients of HSP90 that help complex formation and RTK activation. Treatment of cultured MLS cells with HSP90 inhibitor 17-DMAG, caused loss of RET and ERBB3 phosphorylation and lead to rapid cell death. Treatment of MLS xenograft carrying Nude mice resulted in massive necrosis, rupture of capillaries and hemorrhages in tumor tissues. We conclude that complex formation between RET and other RTKs may cause RTK inhibitor resistance. HSP90 inhibitors can overcome this resistance and are thus promising drugs for treatment of MLS/RCLS.
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| 2. |
- Hansson, Emma, 1975-
(författare)
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Optionsprogram för anställda : en studie av svenska börsföretag
- 2001
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An important strategic question for companies today is how to recruit, motivate and retain employees. It is becoming more important to consider the incentive programs in the valuation process of companies. Recent studies show that employee stock option plans are more commonly used in Swedish companies than earlier. However, there are few studies about how employee stock options influence company performance and affect employees.The purpose of this thesis is to increase the awareness of what the introduction of an employee stock option plan means, both from a management perspective and from the employees’ perspective. There are many different kinds of stock option plans and the plans can vary in terms of type of options, time to expiry, exercise price and tax consequences. This study started with a pre-study of which types of employee stock option plans that are used in Swedish companies. A closer study was then carried out in four companies in different industries with different stock option plans.The motives for introducing employee stock option plans can be divided into five categories: personnel motives, incentive motives, salary motives, accounting motives and tax motives. The case studies show how motives for option plans can be dependent on different circumstances within the companies. Further, the study also shows that the consequences of the stock option plans varies according to factors such as motives, design of the stock option plan, share price performance and other context factors. Context factors that could have an effect are the company’s business, organisational structure, corporate culture and experiences from employee stock options in the industry, employees’ education and tax rules. The consequences for the company are also dependent on how the employees react to the options.To be able to estimate what an employee stock option plan means for the company, all these factors must be taken under consideration. Further one must take into account the costs for the stock options such as dilution effects, hedging costs, personnel costs and costs for designing the program.
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| 3. |
- Lindgren, Martin, et al.
(författare)
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Beta blockers and long-term outcome after coronary artery bypass grafting: a nationwide observational study.
- 2022
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Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 8:5, s. 529-36
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Tidskriftsartikel (refereegranskat)abstract
- Beta blockers are associated with improved outcomes for selected patients with cardiovascular disease. We assessed long-term utilization of beta blockers after coronary artery bypass grafting (CABG) and its association with outcome.All 35,184 patients in Sweden who underwent first-time isolated CABG between 1 January 2006 and 31 December 2017 and were followed for at least 6 months were included in a nationwide observational study. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between different types of beta blockers and outcome. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause mortality, stroke and myocardial infarction (MI). Subgroup analyses were performed in patients with and without previous MI, heart failure, and reduced left ventricular ejection fraction (LVEF). Median follow-up was 5.2 years (range 0-11).At baseline, 33,159 (94.2%) of the patients were dispensed beta blockers, 32,225 (91.6%) of which were cardioselective beta blockers. After 10 years, the dispense of cardioselective beta blockers had declined to 73.7% of all patients. Ongoing treatment with cardioselective beta blockers was associated with a slight reduction in MACE (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.98, p = 0.0063). The reduction was largely driven by a reduced risk of MI (HR 0.83, 95% CI 0.75-0.92, p = 0.0003), while there was no significant reduction in all-cause mortality (HR 0.99, 95% CI 0.93-1.05) and stroke (HR 0.96, 95% CI 0.87-1.05). The reduced risk for MI was consistent in all investigated subgroups.Ongoing treatment with cardioselective beta blockers after CABG is associated with a reduction in MACE, mainly because of reduced long-term risk for MI. The association between cardioselective beta blockers and MI was consistent in patients with and patients without previous MI, heart failure, atrial fibrillation, or reduced LVEF.
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| 4. |
- Perrotta, Sossio, 1975, et al.
(författare)
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Short- and long-term outcome after surgical aortic valve replacement in patients on dialysis.
- 2022
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Ingår i: Journal of thoracic disease. - : AME Publishing Company. - 2072-1439 .- 2077-6624. ; 14:2, s. 269-277
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Tidskriftsartikel (refereegranskat)abstract
- There is no consensus on the choice of aortic valve prosthesis for patients with end-stage renal failure. We analyzed short- and long-term complications in dialysis patients who underwent aortic valve replacement (AVR) with either a biological (bAVR) or a mechanical (mAVR) prosthesis.All patients on dialysis who underwent bAVR or mAVR in Sweden from 1995 to 2017 (n=335) were included in a nationwide, population-based, observational, cohort study. Short and long-term complications were compared. Long-term mortality was compared with multivariable Cox regression analysis adjusted for age, sex, comorbidities, and a propensity score-matched model. Median follow-up was 2.8 (range, 0-16) years.Biological and mechanical valves were implanted in 253 (75.5%) and 82 (24.5%) patients, respectively. The bAVR patients were older and had more comorbidities. There was no significant difference in early complication rate. Thirty-day mortality was 9.1% in bAVR and 7.3% in mAVR patients (P=0.62). The multivariable Cox regression model did not show significant difference in mortality risk between bAVR and mAVR patients [adjusted hazard ratio (aHR) 1.33; 95% CI: 0.84-2.13; P=0.22]. The results were confirmed in the propensity-score matched model. The rate of aortic valve reoperations did not differ significantly between the bAVR and mAVR group.The short- and long-term complication rate is high, and the expected life expectancy limited, in dialysis patients undergoing AVR, without significant difference between biological and mechanical prostheses. The results suggest that biological valve prosthesis, avoiding systemic anticoagulation, is appropriate in most dialysis patients.
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