| 1. |
- Andersson, Claes, et al.
(författare)
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Assessment in vitro of interactions between anti-cancer drugs and noncancer drugs commonly used by cancer patients
- 2023
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Ingår i: Anti-Cancer Drugs. - : Lippincott Williams & Wilkins. - 0959-4973 .- 1473-5741. ; 34:1, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients often suffer from cancer symptoms, treatment complications and concomitant diseases and are, therefore, often treated with several drugs in addition to anticancer drugs. Whether such drugs, here denoted as 'concomitant drugs', have anticancer effects or interact at the tumor cell level with the anticancer drugs is not very well known. The cytotoxic effects of nine concomitant drugs and their interactions with five anti-cancer drugs commonly used for the treatment of colorectal cancer were screened over broad ranges of drug concentrations in vitro in the human colon cancer cell line HCT116wt. Seven additional tyrosine kinase inhibitors were included to further evaluate key findings as were primary cultures of tumor cells from patients with colorectal cancer. Cytotoxic effects were evaluated using the fluorometric microculture cytotoxicity assay (FMCA) and interaction analysis was based on Bliss independent interaction analysis. Simvastatin and loperamide, included here as an opioid agonists, were found to have cytotoxic effects on their own at reasonably low concentrations whereas betamethasone, enalapril, ibuprofen, metformin, metoclopramide, metoprolol and paracetamol were inactive also at very high concentrations. Drug interactions ranged from antagonistic to synergistic over the concentrations tested with a more homogenous pattern of synergy between simvastatin and protein kinase inhibitors in HCT116wt cells. Commonly used concomitant drugs are mostly neither expected to have anticancer effects nor to interact significantly with anticancer drugs frequently used for the treatment of colorectal cancer.
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| 2. |
- Andersson, Claes, et al.
(författare)
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Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
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| 3. |
- Andersson, Matilda L., et al.
(författare)
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The interaction between metabolic rate, habitat choice, and resource use in a polymorphic freshwater species
- 2022
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- 1. Resource polymorphism is common across taxa and can result in alternate ecotypes with specific morphologies, feeding modes, and behaviours that increase performance in a specific habitat. This can result in high intraspecific variation in the expression of specific traits and the extent to which these traits are correlated within a single population. Although metabolic rate influences resource acquisition and the overall pace of life of individuals it is not clear how metabolic rate interact with the larger suite of traits to ultimately determine individual fitness.2. We examined the relationship between metabolic rates and the major differences (habitat use, morphology, and resource use) between littoral and pelagic ecotypes of European perch (Perca fluviatilis) from a single lake in Central Sweden.3. Standard metabolic rate (SMR) was significantly higher in pelagic perch but did not correlate with resource use or morphology. Maximum metabolic rate (MMR) was not correlated with any of our explanatory variables or with SMR. Aerobic scope (AS) showed the same pattern as SMR, differing across habitats, but contrary to expectations was lower in pelagic perch.4. This study helps to establish a framework for future experiments further exploring the drivers of intraspecific differences in metabolism. In addition, since metabolic rates scale with temperature and determine predator energy requirements, our observed differences in SMR across habitats will help determine ecotype-specific vulnerabilities to climate change and differences in top-down predation pressure across habitats.
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| 4. |
- Berg, Matilda, et al.
(författare)
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The Role of Learning Support and Chat-Sessions in Guided Internet-Based Cognitive Behavioral Therapy for Adolescents With Anxiety: A Factorial Design Study
- 2020
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background Increased awareness of anxiety in adolescents emphasises the need for effective interventions. Internet-based cognitive behavioural therapy (ICBT) could be a resource-effective and evidence-based treatment option, but little is known about how to optimize ICBT or which factors boost outcomes. Recently, the role of knowledge in psychotherapy has received increased focus. Further, chat-sessions are of interest when trying to optimize ICBT for youths. This study aimed to evaluate the role of learning support and chat-sessions during ICBT for adolescent anxiety, using a factorial design. Method A total of 120 adolescents were randomised to one of four treatment groups, in a 2x2 design with two factors: with or without learning support and/or chat-sessions. Results Anxiety and depressive symptoms were reduced (Beck Anxiety Inventory- BAI; Cohensd=0.72; Beck Depression Inventory- BDI;d=0.97). There was a main effect of learning support on BAI (d=0.38), and learning support increased knowledge gain (d =0.42). There were no main effects or interactions related to the chat-sessions. Treatment effects were maintained at 6-months, but the added effect of learning support had by then vanished. Conclusion ICBT can be an effective alternative when treating adolescents with anxiety. Learning support could be of importance to enhance short-term treatment effects, and should be investigated further.
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| 5. |
- Bergström, Sara, et al.
(författare)
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Miljöbedömning och miljöbeskrivning i väg- och järnvägsprojekt : Vägledning
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna vägledning förmedlar Trafikverkets syn på hur de båda processerna miljöbedömning och miljöbeskrivning bör tillämpas i planläggning och projektering av väg- och järnvägsprojekt, med utgångspunkt från lagkrav, praxis och Trafikverkets erfarenheter. Den tar även upp innehållet i de båda dokumenten miljökonsekvensbeskrivning och miljöbeskrivning som kommer ut av de båda processerna. Vägledningen syftar till att bidra till integrering av miljöaspekter i planläggning och projektering av vägar och järnvägar samt till en god kvalitet på genomförande och redovisning. Den syftar även till att miljöbedömningar och miljöbeskrivningar ska genomföras på ett likartat sätt i hela Trafikverket och få en jämn kvalitet. Vägledningen riktar sig främst till Trafikverkets konsulter och egna miljöspecialister som gör miljöbedömningar och miljöbeskrivningar i Trafikverkets väg- och järnvägsprojekt. Vägledningen ersätter Trafikverkets Handbok om metodik för miljökonsekvensbeskrivning för vägar och järnvägar (Trafikverket 2011:090). Den ersätter också texter om MKB och miljöbeskrivning i Trafikverkets Rapport planläggning av vägar och järnvägar. Vägledningen innehåller bland annat:relevant lagstiftning och målbeskrivning om hur miljö integreras samt miljöbedömningens roll och moment i planläggningens olika skedensamråd, samrådsunderlag, utredning om betydande miljöpåverkan och miljökonsekvensbeskrivningens (MKB) innehåll Trafikverkets syn på hantering av miljöaspekter, behov av att koppla dessa till miljöintressen för vilka konsekvenser beskrivs
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| 6. |
- Bjersand, Kathrine, et al.
(författare)
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Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome
- 2022
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 61:4
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short-term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross-resistance and association with progression-free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment-naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross-resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.
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| 7. |
- Borland, Maria, 1967, et al.
(författare)
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Effects of 3months of detraining following cardiac rehabilitation in patients with atrial fibrillation.
- 2022
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Ingår i: European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity. - : Springer Science and Business Media LLC. - 1813-7253. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation negatively impacts physical fitness and health-related quality of life. We recently showed that 3months of physiotherapist-led exercise-based cardiac rehabilitation improves physical fitness and muscle function in elderly patients with permanent atrial fibrillation and concomitant diseases. Little is, however, known about the consequences for physical fitness, physical activity level, and health-related quality of life after ending the rehabilitation period.Prospective 3months follow-up study of 38 patients out of 40 eligible (10 women) who, as part of a randomized controlled trial, had completed a 3months physiotherapist-led cardiac rehabilitation resulting in improved physical fitness,. In the current study, the participants were instructed to refrain from exercise for 3months after completion of the rehabilitation period. Primary outcome measure was physical fitness measured as highest achieved workload using an exercise tolerance test. Secondary outcome measures were muscle function (muscle endurance tests), physical activity level (questionnaire and accelerometer), and health-related quality of life, (Short Form-36), as in the preceding intervention study. We used the Wilcoxon Signed Rank test to analyse differences between the end of rehabilitation and at follow-up. The effect size was determined using Cohen's d .Exercise capacity and exercise time significantly decresead between end of rehabilitation and at follow-up (p<.0001 for both). A significant reduction in shoulder flexion repetitions (p=.006) was observed as well as reduced health-related quality of life in the Short Form-36 dimensions Physical Function (p=.042), Mental Health (p=.030), and Mental Component Score (p=.035). There were, however, no changes regarding objective and subjective physical activity measurements.In older patients with permanent atrial fibrillation, previously achieved improvements from physiotherapist-led exercise-based cardiac rehabilitation in physical fitness and muscle function were lost, and health-related quality of life was impaired after ending the rehabilitation period. A strategy for conserving improvements after a rehabilitation period is essential.
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| 8. |
- Cashin, Peter, 1984-, et al.
(författare)
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Ex vivo assessment of chemotherapy sensitivity of colorectal cancer peritoneal metastases
- 2023
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 110:9, s. 1080-1083
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Tidskriftsartikel (refereegranskat)abstract
- Patients with peritoneal metastasis from colorectal cancer (PMCRC) may have a chance of cure when treated with cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC)1–5.Choice of chemotherapy for HIPEC has been based on knowledge of its systemic effects, pharmacokinetics, technical feasibility, hyperthermic efficacy enhancement, and tolerance6–8. Selection of cancer drugs for treatment based on phenotypical assessment of patient cancer cell drug sensitivity ex vivo is one approach to personalized cancer treatment. One technique for this is the fluorometric microculture cytotoxicity assay (FMCA) that has been used in drug development and for the development of personalized cancer medicine9–16.This study investigated whether ex vivo assessment of drug sensitivity by the FMCA provides predictive information in terms of peritoneal recurrence-free survival (PRFS) and overall survival (OS) in patients treated with CRS and HIPEC for isolated PMCRC.
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| 9. |
- Ekelöf, Katarina, et al.
(författare)
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Depressive symptoms postpartum is associated with physical activity level the year prior to giving birth – A retrospective observational study
- 2021
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Ingår i: Sexual and Reproductive Healthcare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine physical activity level prior to pregnancy, during pregnancy and postpartum and investigate the association with depressive symptoms postpartum among women in Sweden. Study design: Retrospective observational study including 532 women on self-assessment of physical activity level before pregnancy, during pregnancy and postpartum, depressive symptoms postpartum as well as stressful life events in the past two years. Main outcome measures: Level and change of physical activity before pregnancy, during pregnancy and postpartum and depressive symptoms postpartum. Results: Almost two-thirds of the women in the study reported that they were inactive or performed light physical activity (62.9%; n = 331) in the year prior to giving birth. Women with a sedentary lifestyle or performing light physical activity level reported depressive symptoms postpartum to a greater extent than active women. Conclusions: A higher level of physical activity during pregnancy was associated with a lower level of depressive symptoms postpartum. Physical activity is a contributing factor to promote a healthier lifestyle and can contribute to improve mental health for pregnant women, newly become mothers and their children. © 2021 The Authors
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| 10. |
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