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- Raivola, J, et al.
(författare)
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Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention
- 2022
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 13:8, s. 714-
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with ovarian cancer (OC) are diagnosed at a late stage when there are very few therapeutic options and a poor prognosis. This is due to the lack of clearly defined underlying mechanisms or an oncogenic addiction that can be targeted pharmacologically, unlike other types of cancer. Here, we identified protein tyrosine kinase 7 (PTK7) as a potential new therapeutic target in OC following a multiomics approach using genetic and pharmacological interventions. We performed proteomics analyses upon PTK7 knockdown in OC cells and identified novel downstream effectors such as synuclein-γ (SNCG), SALL2, and PP1γ, and these findings were corroborated in ex vivo primary samples using PTK7 monoclonal antibody cofetuzumab. Our phosphoproteomics analyses demonstrated that PTK7 modulates cell adhesion and Rho-GTPase signaling to sustain epithelial-mesenchymal transition (EMT) and cell plasticity, which was confirmed by high-content image analysis of 3D models. Furthermore, using high-throughput drug sensitivity testing (525 drugs) we show that targeting PTK7 exhibited synergistic activity with chemotherapeutic agent paclitaxel, CHK1/2 inhibitor prexasertib, and PLK1 inhibitor GSK461364, among others, in OC cells and ex vivo primary samples. Taken together, our study provides unique insight into the function of PTK7, which helps to define its role in mediating aberrant Wnt signaling in ovarian cancer.
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| 3. |
- Rossi, Andrea, et al.
(författare)
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Left atrial structural and mechanical remodelling in heart failure with reduced ejection fraction
- 2021
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 8:6, s. 4751-4759
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known.Methods and results: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1).Conclusions: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.
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- Seyed Hashemi, S. G., et al.
(författare)
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The mediating effect of the cyberchondria and anxiety sensitivity in the association between problematic internet use, metacognition beliefs, and fear of COVID-19 among Iranian online population
- 2020
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- With the rapid growth of the novel coronavirus disease 2019 (COVID-19), individuals may try to find related medical information using the internet to overcome their fears. Under such circumstances, individuals with the features of cyberchondria, anxiety sensitivity, and metacognitive beliefs in negative thoughts may suffer more fears than those without these features. Therefore, the present study proposed a model to understand the associations between problematic internet use (PIU), cyberchondria, anxiety sensitivity, metacognition beliefs, and fear of COVID-19. Utilizing a cross-sectional online survey, 651 Iranians completed the following psychometric scales: Metacognition Questionnaire-30 (MCQ-30), Anxiety Sensitivity Questionnaire (ASI), Cyberchondria Severity Scale-Short Form (CSS-12), Fear of COVID-19 Scale (FCV–19S), and Generalized Problematic Internet Use Scale (GPIUS). Structural equation modeling (SEM) was used to assess the proposed model via several fit indices. The indices include Tucker-Lewis index (TLI), comparative fit index (CFI), standardized root mean square residual (SRMR), and root mean square error of approximation (RMSEA). The fit indices (CFI = 0.948, TLI = 0.938, RMSEA = 0.053, and SRMR = 0.001) indicated the good fit between the data and the proposed model. Moreover, fear of COVID-19 was significantly and directly predicted by cyberchondria (β = 0.479, p <.001) and anxiety sensitivity (β = 0.286, p <.001). The relationship between PIU and cyberchondria with fear of COVID-19 was mediated significantly by anxiety sensitivity and metacognitive beliefs. Because fear of COVID-19 was found to be significantly associated with cyberchondria and anxiety sensitivity, healthcare providers may want to provide additional support for those with cyberchondria and anxiety sensitivity tendencies. © 2020 The Author(s) Psychology; COVID-19; Cyberchondria; Internet; Metacognition; Psychological distress.
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