| 1. |
- Cruz, Rodrigo G.B., et al.
(författare)
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Human epidermal growth factor receptor-3 expression is regulated at transcriptional level in breast cancer settings by junctional adhesion molecule-a via a pathway involving beta-catenin and foxa1
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- The success of breast cancer therapies targeting the human epidermal growth factor receptor-2 (HER2) is limited by the development of drug resistance by mechanisms including upregulation of HER3. Having reported that HER2 expression and resistance to HER2-targeted therapies can be regulated by Junctional Adhesion Molecule-A (JAM-A), this study investigated if JAM-A regulates HER3 expression. Expressional alteration of JAM-A in breast cancer cells was used to test expressional effects on HER3 and its effectors, alongside associated functional behaviors, in vitro and semi-in vivo. HER3 transcription factors were identified and tested for regulation by JAM-A. Finally a patient tissue microarray was used to interrogate connections between putative pathway components connecting JAM-A and HER3. This study reveals for the first time that HER3 and its effectors are regulated at gene/protein expression level by JAM-A in breast cancer cell lines; with functional consequences in in vitro and semi-in vivo models. In bioinformatic, cellular and patient tissue models, this was associated with regulation of the HER3 transcription factor FOXA1 by JAM-A via a pathway involving β-catenin. Our data suggest a novel model whereby JAM-A expression regulates β-catenin localization, in turn regulating FOXA1 expression, which could drive HER3 gene transcription. JAM-A merits investigation as a novel target to prevent upregulation of HER3 during the development of resistance to HER2-targeted therapies, or to reduce HER3-dependent tumorigenic signaling.
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| 2. |
- Kilic, Aysenur, et al.
(författare)
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A 12-month longitudinal study examining the shared and unique contributions of self-compassion and psychological inflexibility to distress and quality of life in people with Type 2 Diabetes
- 2022
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Ingår i: Journal of Psychosomatic Research. - : Elsevier. - 0022-3999 .- 1879-1360. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Self-compassion and psychological flexibility appear to benefit wellbeing and quality of life (QoL) in the general population and in people with long-term conditions like Type 2 Diabetes (T2D). However, both variables share similarities and their unique roles in relation to distress and QoL in people with diabetes over time are not clear.Design: This was a longitudinal study with online assessments of self-compassion, psychological inflexibility, distress (depression, anxiety, diabetes-distress), and QoL at baseline (T1) and six (T2) and 12 months (T3). Methods: In total, 173 UK adults with T2D completed baseline questionnaires; T2 and T3 follow-ups were completed by 82 and 52 participants, respectively. Correlations were conducted to understand the relationships between variables at each time point. Hierarchical regressions were conducted to understand the unique predictive role of baseline self-compassion and psychological inflexibility in relation to distress and QoL at T2 and T3, controlling for age and baseline distress and QoL.Results: There were large significant negative correlations between self-compassion and psychological inflexibility (r >-0.50), and both had significant large correlations with distress (r >-0.50) but not QoL across time points. Regressions indicated that psychological inflexibility uniquely predicted depression (T2) and anxiety symptoms (T2 and T3) and QoL (T3). Self-compassion did not uniquely predict any of the outcomes.Conclusions: Psychological inflexibility may play an important role in distress in T2D, but prospective studies with larger samples are needed to replicate these findings. Given the overlap between psychological inflexibility and self-compassion, treatments targeting either variable may be useful.
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| 3. |
- Kilic, Aysenur, et al.
(författare)
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A Systematic Review of the Effectiveness of Self-Compassion-Related Interventions for Individuals With Chronic Physical Health Conditions
- 2021
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Ingår i: Behavior Therapy. - : Elsevier. - 0005-7894 .- 1878-1888. ; 52:3, s. 607-625
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Forskningsöversikt (refereegranskat)abstract
- Self-compassion, defined as a mindful way of coping with pain and suffering by showing kindness, care, and concern towards the self, may improve psychological adjustment in people living with a chronic physical health condition (CPHC). Various studies illustrate that self-compassion is associated with positive outcomes in general. The aim of this systematic review is to establish the effect of compassion-related therapies on self-compassion specifically in people with CPHCs. Secondary aims are to (a) establish the effect on other psychological and physiological outcomes and (b) explore the relative effectiveness of different therapy types among those identified. Cochrane, Embase, Medline, Psy-cINFO, and CINAHL databases were searched using & ldquo;compassion & rdquo; AND & ldquo;chronic disease & rdquo; AND & ldquo;psychological outcomes & rdquo; and their synonyms, from 2004 to March 2019. Eligible studies had an experimental design using a self-compassion scale with an adult population. Risk of bias (RoB)& nbsp;was assessed using the Cochrane RoB tool. Effect sizes were calculated for study outcomes. Fifteen studies, including a total of 1,190 participants, 7 different CPHCs, and 11 types of therapies, were included in the review. Nearly all included therapies significantly increased self-compassion with medi-um to large effect sizes, and reported positive outcomes, such as decreased depression. None of the therapy types appeared clearly superior to the others. Findings from this review show that included therapies increased self-compassion and im -proved various outcomes, which may represent clinically significant benefits for patients. However, there is a need to further understand how self-compassion exerts its benefits and determine the best methods to increase self-compassion.
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| 4. |
- Kilic, Aysenur, et al.
(författare)
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An online acceptance, commitment, and self-compassion based treatment to decrease psychological distress in people with type 2 diabetes : A feasibility randomised-controlled trial
- 2023
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThis study explored the feasibility and acceptability of conducting a larger trial of a self-guided, online self-compassion and acceptance and commitment therapy (ACT) focused treatment among people with type 2 diabetes (T2D) to decrease psychological distress.Materials and methodsThis study was a two-arm, parallel, feasibility randomised controlled trial with nested qualitative methods. UK adults with T2D were randomly (1:1) allocated to a five-week online self-compassion and ACT treatment or waitlist control. Information regarding recruitment, trial retention, and treatment completion was collected, and post-treatment semi-structured interviews were conducted to assess feasibility and acceptability. Self-report measures of psychological distress (depression, anxiety, diabetes distress) and potential treatment processes (self-compassion and psychological flexibility) were completed as secondary feasibility outcomes.ResultsFifty-five (60.44 %) out of 91 people who accessed the study link were eligible to participate. Of these, 33 eligible participants (60 %) were randomly assigned to treatment (n = 19) or control arms (waitlist; n = 14). While treatment completion was 47.37 %, trial retention rates were 39.39 % (5-week follow-up) and 21.2 % (9-week follow-up). Secondary feasibility outcomes of treatment effect estimates are difficult to interpret in light of low treatment completion and trial retention rates.ConclusionA larger trial of the self-guided, online self-compassion treatment to decrease psychological distress in people with T2D may be beneficial, but it has limited feasibility in its current form. Further efforts are needed to improve treatment acceptability of online self-compassion and ACT focused treatment and trial procedures.
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| 5. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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