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- Al-Ramadan, Afkar, et al.
(författare)
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Analysis of radiation effects in two irradiated tumor spheroid models
- 2018
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 15:3, s. 3008-3016
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Tidskriftsartikel (refereegranskat)abstract
- Multicellular spheroids have proven suitable as three-dimensional in vivo-like models of non-vascularized micrometastases. Unlike monolayer-based models, spheroids mirror the cellular milieu and the pathophysiological gradients inside tumor nodules. However, there is limited knowledge of the radiation effects at the molecular level in spheroids of human origin. The present study is a presentation of selected cell biological processes that may easily be analyzed with methods available at routine pathology laboratories. Using gamma irradiated pancreatic neuroendocrine BON1 and colonic adenocarcinoma HCT116 spheroids as model systems, the present study assessed the radiobiological response in these models. Spheroid growth after irradiation was followed over time and molecular responses were subsequently assessed with immunohistochemistry (IHC) staining for descriptive analyses and semi-automatic grading of apoptosis, G(2)-phase and senescence in thin sections of the spheroids. Growth studies demonstrated the BON1 spheroids were slower growing and less sensitive to radiation compared with the HCT116 spheroids. IHC staining for G2-phase was primarily observed in the outer viable P-cell layers of the spheroids, with the 6 Gy irradiated HCT116 spheroids demonstrating a very clear increase in staining intensity compared with unirradiated spheroids. Apoptosis staining results indicated increased apoptosis with increasing radiation doses. No clear association between senescence and radiation exposure in the spheroids were observed. The present results demonstrate the feasibility of the use of multicellular spheroids of human origin in combination with IHC analyses to unravel radiobiological responses at a molecular level. The present findings inspire further investigations, including other relevant IHC-detectable molecular processes in time-and radiation dose-dependent settings.
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| 3. |
- Carlsson, Axel C, et al.
(författare)
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10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease : A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
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- Carlsson, Anna K, 1966, et al.
(författare)
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Acute injuries resulting from accidents involving powered mobility devices (PMDs)-Development and outcomes of PMD-related accidents in Sweden
- 2019
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Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-9588 .- 1538-957X. ; 20:5, s. 484-491
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Powered mobility devices (PMDs) are commonly used as aids for older people and people with disabilities, subgroups of vulnarable road users (VRUs) who are rarely noted in traffic safety contexts. However, the problem of accidents involving PMD drivers has been reported in many countries where these vehicles have become increasingly popular.The aim of this study is to extract and analyze national PMD-related accident and injury data reported to the Swedish Traffic Accident Data Acquisition (STRADA) database. The results will provide valuable insight into the risks and obstacles that PMD drivers are exposed to in the traffic environment and may contribute to improving the mobility of this group in the long term.Methods: The current study is based on data from 743 accidents and 998 persons. An analysis was performed on a subset of data (N=301) in order to investigate the development of accidents over a period of 10 years. Thereafter, each accident in the whole data set was registered as either single (N=427) or collision (N=315).Results: The results show that there was a 3-fold increase in the number of PMD-related accidents reported to STRADA during the period 2007-2016.With regard to single accidents, collisions, as well as fatalities, the injury statistics were dominated by males. Single accidents were more common than collisions (N=427 and N=316, respectively) and the level of injury sustained in each type of accident is on par. The vast majority of single accidents resulted in the PMD driver impacting the ground (87%), due to either PMD turnover (71%) or the driver falling out of the PMD (16%). The reason for many of the single accidents was a difference in ground level (34%, typically a curb).Cars, trucks, or buses were involved in 67% of collision events; these occured predominantly at junctions or intersections (70%).Abbreviated Injury Scale (AIS) 3+ injuries were dominated by hip and head injuries in both single accidents and collision events.Conclusions: The present study shows that further research on PMD accidents is required, with regard to both single accidents and collision events. To ensure that appropriate decisions are made, future work should follow up on injury trends and further improve the quality of PDM-related accident data. Improved vehicle stability and design, increased usage of safety equipment, proper training programs, effective maintenance services, and development of a supporting infrastructure would contribute to increased safety for PMD drivers.
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| 10. |
- Carlsson, Jörgen, et al.
(författare)
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EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides
- 2015
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Ingår i: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 49:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.
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