| 1. |
- Dolatabadi, Soheila, et al.
(författare)
-
JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma
- 2019
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:2, s. 435-449
-
Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy-resistant cells in MLS remains unknown. Here, we show that MLS cell lines contained subpopulations of cells that can form spheres, efflux Hoechst dye and resist doxorubicin, all properties attributed to cancer stem cells (CSCs). By single-cell gene expression, western blot, phospho-kinase array, immunoprecipitation, immunohistochemistry, flow cytometry and microarray analysis we showed that a subset of MLS cells expressed JAK–STAT genes with active signalling. JAK1/2 inhibition via ruxolitinib decreased, while stimulation with LIF increased, phosphorylation of STAT3 and the number of cells with CSC properties indicating that JAK–STAT signalling controlled the number of cells with CSC features. We also show that phosphorylated STAT3 interacted with the SWI/SNF complex. We conclude that MLS contains JAK–STAT-regulated subpopulations of cells with CSC features. Combined doxorubicin and ruxolitinib treatment targeted both proliferating cells as well as cells with CSC features, providing new means to circumvent chemotherapy resistance in treatment of MLS patients. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
|
|
| 2. |
- Lindén, Malin, et al.
(författare)
-
FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex
- 2019
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- Members of the human FET family of RNA-binding proteins, comprising FUS, EWSR1, and TAF15, are ubiquitously expressed and engage at several levels of gene regulation. Many sarcomas and leukemias are characterized by the expression of fusion oncogenes with FET genes as 5′ partners and alternative transcription factor-coding genes as 3′ partners. Here, we report that the N terminus of normal FET proteins and their oncogenic fusion counterparts interact with the SWI/SNF chromatin remodeling complex. In contrast to normal FET proteins, increased fractions of FET oncoproteins bind SWI/SNF, indicating a deregulated and enhanced interaction in cancer. Forced expression of FET oncogenes caused changes of global H3K27 trimethylation levels, accompanied by altered gene expression patterns suggesting a shift in the antagonistic balance between SWI/SNF and repressive polycomb group complexes. Thus, deregulation of SWI/SNF activity could provide a unifying pathogenic mechanism for the large group of tumors caused by FET fusion oncoproteins. These results may help to develop common strategies for therapy. © 2019 The Authors. Published under the terms of the CC BY 4.0 license
|
|
| 3. |
- Stigson, Helena, 1979, et al.
(författare)
-
Incidence of Acute Injuries among Licensed and Non-Licensed Cyclists using Insurance Registry Data
- 2019
-
Ingår i: 2019 IRCOBI Conference Proceedings. - : International Research Council on the Biomechanics of Injury.
-
Konferensbidrag (refereegranskat)abstract
- Few previous studies have examined acute injuries in competitive cycling or training as compared to other sports. By using nationwide insurance data including all injured cyclist registered in the Swedish Cycling Federation and all reported injuries during exercise race in Sweden, the objective was to examine acute injuries during competitive cycling or training for different types of cyclists. The injury incidence and injuries leading to permanent medical impairment were examined. All cyclists that were injured during 2008-2017 were included (n=1937).Among the 2666 licensed cyclists the incidence of cyclists injured during training or competition was 44 per 1000 licensed cyclists per year. Focusing on participants in exercise races, the incidence was annually 1.5 injured cyclists per 1000 participants per year. The most commonly injured body region was the upper extremity (41%), followed by head and neck (18%). In total 9.4% of all injured cyclists sustained a permanent medical impairment. Given an injury, non-licensed participants in exercise races were slightly older, and the proportion of females were higher (30% vs. 16%), than among licensed cyclists. The injury incidence among the cyclists was high, and to maintain a healthy and physically active population it is important to make efforts to prevent injuries.
|
|
| 4. |
- Åman, Malin, et al.
(författare)
-
National injury prevention measures in team sports should focus on knee, head, and severe upper limb injuries.
- 2019
-
Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer. - 0942-2056 .- 1433-7347. ; 27:3, s. 1000-1008
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine acute injuries in licensed floorball, football, handball, and ice hockey players in all ages nationwide in Sweden, and to identify the most common and severe injuries in each body location and recommend injury prevention measures.METHODS: Using national sport insurance data from years 2006-2015 was the incidence and proportion of acute injuries, and injuries leading to permanent medical impairment (PMI), calculated in the four team sports. The most common injury type and injured body part was identified, with a particular focus of the severe injuries. Comparison between sexes was made.RESULTS: In total, there were 92,162 registered injuries in all sports together. Knee injuries were most common, and also had the highest incidence of PMI, in all ball sports and in female ice hockey players. In male ice hockey, the most common injury was a dental and face injury, and PMI injuries were mostly in the shoulder. The most severe PMI injuries were rare and most often a face/eye injury in male floorball and ice hockey, a concussion in female ice hockey, and a knee injury in female floorball, and in both sexes in football and handball.CONCLUSIONS: To achieve the greatest impact in reducing the adverse effects of acute sport injuries nationwide in Sweden, preventive measures should focus on knee injuries in all the investigated team sports. The severe head/face and upper limb injuries also need attention. Protective equipment, neuromuscular training programs, rules enforcements, and fair-play interventions may reduce the incidence of injuries.
|
|
