| 1. |
- Nilchian, Azadeh, et al.
(author)
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CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial-Mesenchymal Plasticity in Breast Cancer.
- 2019
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 79:1, s. 47-60
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Journal article (peer-reviewed)abstract
- Tight junctions (TJ) act as hubs for intracellular signaling pathways controlling epithelial cell fate and function. Deregulation of TJ is a hallmark of epithelial-mesenchymal transition (EMT), which contributes to carcinoma progression and metastasis. However, the signaling mechanisms linking TJ to the induction of EMT are not understood. Here we identify a TJ-based signalosome, which controls AKT signaling and EMT in breast cancer. The coxsackie- and adenovirus receptor (CXADR), a TJ protein with an essential yet uncharacterized role in organogenesis and tissue homeostasis, was identified as a key component of the signalosome. CXADR regulated the stability and function of the phosphatases and AKT inhibitors PTEN and PHLPP2. Loss of CXADR led to hyper-activation of AKT and sensitized cells to TGF-β1-induced EMT. Conversely, restoration of CXADR stabilized PHLPP2 and PTEN, inhibited AKT, and promoted epithelial differentiation. Loss of CXADR in luminal A breast cancer correlated with loss of PHLPP2 and PTEN and poor prognosis. These results show that CXADR promotes the formation of an AKT-inhibitory signalosome at TJ and regulates epithelial-mesenchymal plasticity in breast cancer cells. Moreover, loss of CXADR might be used as a prognostic marker in luminal breast cancer.
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| 2. |
- Ekblom Bak, Elin, 1981-, et al.
(author)
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Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis : cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.DESIGN: Cross-sectional.SETTING: Multisite study at university hospitals.PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.
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| 5. |
- Forestier, Erik, et al.
(author)
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Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome - an iBFM-SG study.
- 2007
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020.
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Journal article (peer-reviewed)abstract
- Children with Down syndrome (DS) have a markedly increased risk of acute lymphoblastic and myeloid leukemias (ALL+AML). To identify chromosomal changes cooperating with +21 that may provide information on the pathogenesis of these leukemias, we analyzed 215 DS-ALL and 189 DS-AML. Unlike previous smaller series, a significant proportion of DS-ALL had the typical B-cell precursor ALL abnormalities high hyperdiploidy (HeH; 11%) and t(12;21)(p13;q22) (10%). The HeH DS-ALL were characterized by gains of the same chromosomes as non-DS-HeH, suggesting the same etiology/pathogenesis. In addition, specific genetic subtypes of DS-ALL were suggested by the significant overrepresentation of cases with +X, t(8;14)(q11;q32), and del(9p). Unlike DS-ALL, the common translocations associated with non-DS-AML were rare in DS-AML, which instead were characterized by the frequent presence of dup(1q), del(6q), del(7p), dup(7q), +8, +11, del(16q), and +21. This series of DS leukemias - the largest to date - reveals that DS-ALL is a heterogeneous disorder that comprises both t(12;21) and HeH as well as DS-related abnormalities. Furthermore, this analysis confirms that DS-AML is a distinct entity, originating through other genetic pathways than do non-DS-AML, and suggests that unbalanced changes such as dup(1q), +8, and +21 are involved in the leukemogenic process.
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| 6. |
- Fröbert, Ole, et al.
(author)
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Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction
- 2013
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In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 369:17, s. 1587-1597
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Journal article (peer-reviewed)abstract
- BackgroundThe clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. MethodsWe conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. ResultsNo patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. ConclusionsRoutine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.)
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| 7. |
- Jacobson, Sara, et al.
(author)
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Hyperglycemia as a risk factor in pancreatic cancer : A nested case-control study using prediagnostic blood glucose levels
- 2021
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In: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:6, s. 1112-1118
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.
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| 8. |
- Johansson, Helena, et al.
(author)
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10-årsrisken för fraktur. Stöd i behandlingen av osteoporos, enligt preliminära svenska riktlinjer.
- 2011
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In: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 108:7, s. 336-339
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Journal article (other academic/artistic)abstract
- Risken för fraktur beräknas med FRAX för män och kvinnor, för olika åldrar, för olika BMI och med följande riskvariabler: tidigare osteoporotisk fraktur, höftfraktur hos föräldrar, aktuell rökning, längre tids peroral behandling med kortison någon gång i livet, förekomst av reumatoid artrit, förekomst av andra sjukdomstillstånd som orsakar osteoporos, aktuell alkoholkonsumtion ≥3 enheter och bentäthetsmätning.FRAX finns fritt tillgängligt på Internet.I denna artikel beskrivs bakgrunden till FRAX och dess användning vid diagnostik och behandling av osteoporos.
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| 9. |
- Johansson, Linda, et al.
(author)
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Complement activation prior to symptom onset in myeloperoxidase ANCA-associated vasculitis but not proteinase 3 ANCA associated vasculitis : a Swedish biobank study
- 2022
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In: Scandinavian Journal of Rheumatology. - : Taylor & Francis Group. - 0300-9742 .- 1502-7732. ; 51:3, s. 214-219
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Journal article (peer-reviewed)abstract
- Objective: Increased soluble levels of complement effectors have been demonstrated in active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the timing of complement activation in the autoimmune inflammation remains elusive. This study investigated whether the complement system is activated before onset of symptoms in AAV.Method: The Swedish National Patient Register and Cause of Death register were linked to registers of five biobanks to identify individuals sampled before AAV symptom onset. Diagnosis of AAV and time-point for symptom onset were confirmed by reviewing medical records. We identified 64 presymptomatic individuals with serum samples > 1 month < 10 years from AAV symptom onset and 122 matched controls. Complement factors (C2, C5) and activation markers (C5a, C4b) were measured using Luminex technology.Results: Presymptomatic individuals had higher levels of C5 up to 6.5 years before symptom onset, compared with controls [median (IQR) 80.7 (131.9) vs 46.6 (63.4) µg/mL, p = 0.05]. Levels of C5a increased significantly during the pre-dating time (p = 0.033) until symptom onset. The complement levels were significantly higher in presymptomatic myeloperoxidase (MPO)-ANCA+ individuals versus MPO-ANCA− and proteinase-3-ANCA+ individuals. C5 was significantly increased in cases with renal involvement at diagnosis versus controls (p = 0.022), whereas levels of both C5 and C5a were significantly increased in presymptomatic individuals diagnosed with microscopic polyangiitis after onset compared with controls (C5: p = 0.027; C5a: p = 0.027).Conclusion: Activation of the complement system is an early event in the pathogenesis of AAV and is mainly associated with MPO-ANCA+ AAV and with microscopic polyangiitis.
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| 10. |
- Jönsson, Oskar, et al.
(author)
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Air pollution episodes in Stockholm regional background air due to sources in Europe and their effects on human population
- 2013
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In: Boreal environment research. - 1239-6095 .- 1797-2469. ; 18:3-4, s. 280-302
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Journal article (peer-reviewed)abstract
- Using air quality measurements, we categorized air pollution according to source sectors in a rural background environment in southern Sweden based on hourly air-mass backward trajectories during 1997-2010. Concentrations of fine (PM2.5) and sum of fine and coarse particulate matter (PM10), accumulation mode particle number, black carbon and surface ozone were 4.0, 3.9, 4.5, 6.8 and 1.3 times higher, respectively, in air masses from the southeast as compared with those in air masses from the cleanest sector in the northwest, consistent with air-mass transport over areas with relatively high emissions of primary particulate matter (PM) and secondary PM precursors. The highest ultrafine particle numbers were associated with clean air from the northwest. We estimate that almost 7.8% and 0.6% higher premature human mortality is caused by PM2.5 and ozone exposure, respectively, when air originates from the southeast as compared with that when air originates from the northwest. Reductions of emissions in eastern Europe would reduce the highest air pollution concentrations and associated health risks. However, since air masses from the southwest are more frequent, emissions in the western part of Europe are more important for annual mean premature mortality.
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