| 1. |
- Thålin, Charlotte, et al.
(författare)
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Elevated Troponin Levels in Acute Stroke Patients Predict Long-term Mortality
- 2015
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 10, s. 285-286
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Forskningsöversikt (refereegranskat)abstract
- Background: Elevated plasma levels of troponin in acute stroke patients are common and have in several studies been shown to predict in-hospital and short-term mortality. Little is, however, known about the long-term prognosis of these patients. The aim of this study was to determine patient characteristics and 5-year mortality in patients with acute stroke and troponin elevation on admission. Methods: A retrospective cohort study of all consecutive patients with acute stroke and a plasma troponin I (TnI) analyzed on admission to Danderyd Hospital between January 1, 2005, and January 1, 2006 (n = 247). Patient characteristics were obtained from the Swedish National Stroke Register, Riksstroke, as well as hospital records. Mortality data were obtained from the Swedish Cause of Death Register. Results: There were 133 patients (54%) with TnI less than .03 mu g/L (normal), 74 patients (30%) with TnI .03-.11 mu g/L (low elevation), and 40 patients (16%) with TnI greater than .11 mu g/L (high elevation). TnI elevations were associated with a higher age, prior ischemic stroke, chronic heart failure, renal insufficiency, stroke severity, and ST segment elevation or depression on admission. The rate of hyperlipidemia decreased with increasing TnI. Adjusted for age and comorbidity, elevated TnI values on admission had a significantly and sustained increased mortality over the 5-year follow-up, with a hazard ratio of 1.90 (95% confidence interval, 1.33-2.70). Conclusions: Troponin elevation in patients with acute stroke, even when adjusted for several possible confounders, is associated with an almost 2-fold increased risk of 5-year mortality.
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| 2. |
- Danared, Håkan, et al.
(författare)
-
Preface
- 2017
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Ingår i: IPAC 2018 : Proceedings of the 8th International Particle Accelerator Conference - Proceedings of the 8th International Particle Accelerator Conference. - 9783954501823
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Ansell, Anna, et al.
(författare)
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Epidermal growth factor is a biomarker for poor cetuximab response in tongue cancer cells
- 2016
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley-Blackwell. - 0904-2512 .- 1600-0714. ; 45:1, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidermal growth factor receptor (EGFR) is a target for treatment in tongue cancer. Here, EGFR ligands were evaluated for their potential uses as predictive biomarkers of cetuximab treatment response.Methods: In three tongue cancer cell lines the influences of epidermal growth factor (EGF), amphiregulin (AR), and epiregulin (EPR) on tumour cell proliferation and cetuximab response were evaluated by the addition of recombinant human (rh) proteins or the siRNA-mediated downregulation of endogenous ligand production.Results: EGF or AR downregulation suppressed the proliferation of all investigated cell lines. Furthermore, all cell lines displayed increased cetuximab resistance upon the addition of rhEGF, whereas EGF silencing resulted in an improved cetuximab response in one cell line.Conclusions: Our data suggest that EGF and AR are critical components of the EGFR signalling network required for full proliferative potential. Moreover, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.
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| 4. |
- Bergh, Jonas C. S., et al.
(författare)
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Docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer : results from the Swedish PREDIX HER2 trial identifying a new potential de-escalation standard?
- 2019
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 37:15, s. 501-501
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neoadjuvant therapy produces high rates of pathological complete response (pCR) and is the standard of care in HER2 positive breast cancer; however, the optimal treatment regimen remains to be established. Methods: In this randomized phase II study patients ≥18 years with HER2 positive breast cancer > 20mm or verified lymph node metastases were randomized to 6 courses of docetaxel, trastuzumab and pertuzumab (DTP, group A) or trastuzumab emtansine (T-DM1, group B), q 21 days. The protocol allowed switch to the competing treatment upon lack of response or drug-related severe toxicity. Patients received postoperative epirubicin+cyclophosphamide, trastuzumab for a total of one year and endocrine therapy. Accrual was completed in October 2018 after randomization of 202 patients, data on pCR were available for 190 at the time for this abstract submission. Median age, 52 years (26-74), menopausal status, histological type and grade were well balanced between the treatment groups. 62.6% of the tumors were hormone receptor (HR) positive. Results: Primary endpoint was pathological objective response. 190 patients completed the protocol-specified preoperative treatment. pCR was achieved in 45.3% of patients, 46.4% in patients treated with DTP and 44.1% with T-DM1 (chi-sq., p = 0.75). In HR-positive tumors, pCR was obtained in 35.3% of patients, 35.9% in group A vs. 34.6% in group B (p = 0.87); in HR-negative tumors, the overall pCR rate was 62.0%, 66.7% in group A vs. 57.9% in group B (p = 0.45). Severe (grade 3/4) toxicity was reported at 68 occasions related to DTP, compared with 16 related to T-DM1, 26 vs. 3 caused by febrile neutropenia. Significantly better quality of life was reported by patients treated with T-DM1. Conclusions: Our data on TDM-1 demonstrates similar efficacy and less toxicity, in particular for patients with HER2 and HR positive cancers, being a potential new standard for neoadjuvant therapy. Clinical trial information: NCT02568839.
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| 5. |
- Brandberg, Yvonne, et al.
(författare)
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Health-related quality of life in the Swedish PREDIX HER2 trial, evaluating docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer.
- 2019
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 37:15, s. 583-583
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neoadjuvant therapy combining docetaxel, trastuzumab and pertuzumab (DTP) was compared to trastuzumab emtansine (T-DM1) in the randomized phase 2 PREDIX HER2 trial. Patients, ≥18 years with HER2 positive breast cancer, ≥20mm or with verified lymph node metastases, were randomized to six courses of DTP (Standard arm) or T-DM1 (Experimental arm). Primary endpoint was pathological objective response to primary medical therapy at post-treatment surgery. Health related quality of life (HRQoL) was a secondary outcome, and is of specific interest as there was no difference between the randomization groups regarding the main endpoint (results presented in a separate abstract sent to ASCO 2019, Bergh et al.). Methods: Of 202 randomized patients, 190 are available for evaluation at this point. HRQoL was measured, using EORTC QLQ-C30 + EORTC QLQ-BR23, at baseline before randomization and after six courses. Results: No differences between the randomization arms were found at baseline. Results after six courses, based on 163 patients (86%) and adjusted to baseline values, revealed statistical significant differences (p≤0.01), favoring the experimental T-DM1 arm on 7 out of 15 of the EORTC QLQ-C30 variables (Physical functioning, Role functioning, Social functioning, Global quality of Life, Fatigue, Dyspnea, and Diarrhea). For the breast cancer specific questionnaire (EORTC-BR23), the experimental arm scored statistically significantly better on 5 out of 7 subscales (Body image, Sexual functioning, Sexual enjoyment, Systemic therapy side effects and Upset by hair loss). All of the statistical significant differences were of moderate or large clinical significance (≥10 scale scores). No differences between the randomization arms were found for the remaining HRQoL variables. Conclusions: The experimental arm reported better HRQoL than the control arm after six courses. Trastuzumab emtansine may be a useful treatment alternative due to better HRQoL and lower toxicity. Clinical trial information: NCT02568839.
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| 6. |
- Brandström, Josef, et al.
(författare)
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Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents
- 2019
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 49:10, s. 1328-1341
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peanut oral immunotherapy (pOIT) has showed good short-term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut.Objective: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab.Methods: This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD-sens and allergen-binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study.Results: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full-dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment.Conclusions and clinical relevance: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased.
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| 7. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 8. |
- Ewerhard, Ann Charlotte, et al.
(författare)
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Consumer decision-making of slow moving consumer goods in the age of multi-channels
- 2019
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Ingår i: International Review of Retail, Distribution and Consumer Research. - : Informa UK Limited. - 0959-3969 .- 1466-4402. ; 29:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Currently, consumer decision-making is influenced by the spread of technology that has made multi-channel retailing possible. Multi-channel retailing can be defined as a retailer using a combination of separate and independent channels without any overlap for promoting and selling products and services. This study contributes to three research streams: consumer decision-making, multi-channel retailing and slow-moving consumer goods (SMCG). A theoretical framework is developed to examine the decision-making processes of two groups of consumers, Millennials and Mothers. As the aim of the study was to gain insight into consumer decision-making in the context of multi-channels it was designed to be exploratory and used an abductive approach. The empirical material was mainly collected via interviews in store and consumers’ homes. The interview data are complemented by in-store observations. Our findings show that multi-channels influence consumers’ decision-making and that there are differences between Millennials and Mothers. Different devices and channels are used at different stages of the decision-making process and we claim that they complement, rather than conflict with each other. Retailers need to understand that customers expect omni-channelling, which has a positive impact on brand and sales. We argue that retailers who want to remain competitive will need to move toward omni-channelling.
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| 9. |
- Gånemo, Agneta, et al.
(författare)
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Usefulness of Rajka and Langeland Eczema Severity Score in Clinical Practice.
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 96:4, s. 521-524
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Tidskriftsartikel (refereegranskat)abstract
- Simple, validated eczema severity scores are required for the evaluation of interventions. The Rajka and Langeland (R and L) scale is based on 3 domains (extent, course, and intensity); however, its validity is not yet confirmed. The aim of this study was to investigate the quality aspects of the R and L scale in clinical practice. In the first part of the study, experts and consumers judged the content validity of the scale. The second part of the study was performed with 87 children during a 4-month eczema school. Construct validity, internal consistency, sensitivity to change, time consumption and health-related quality of life variables were investigated. The content of the R and L scale was considered valid by 45 panellists. Inter- and intra-observer reliability was very good. Divergent construct validity was adequate, while convergent construct validity and internal consistency were inadequate. The R and L scale was able to define a significant improvement in eczema during the eczema school. The time required for completing the R and L assessment was significantly shorter than for objective Severity Scoring of Atopic Dermatitis (SCORAD). The R and L scale is a simple, fast, valid, reliable and sensitive tool for scoring of atopic dermatitis in everyday clinical practice.
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| 10. |
- Indira Chandran, Vineesh, et al.
(författare)
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Global extracellular vesicle proteomic signature defines U87-MG glioma cell hypoxic status with potential implications for non-invasive diagnostics
- 2019
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Ingår i: Journal of Neuro-Oncology. - : SPRINGER. - 0167-594X .- 1573-7373. ; 144:3, s. 477-488
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Glioblastoma multiforme (GBM) is the most common and lethal of primary malignant brain tumors. Hypoxia constitutes a major determining factor for the poor prognosis of high-grade glioma patients, and is known to contribute to the development of treatment resistance. Therefore, new strategies to comprehensively profile and monitor the hypoxic status of gliomas are of high clinical relevance. Here, we have explored how the proteome of secreted extracellular vesicles (EVs) at the global level may reflect hypoxic glioma cells. Methods We have employed shotgun proteomics and label free quantification to profile EVs isolated from human high-grade glioma U87-MG cells cultured at normoxia or hypoxia. Parallel reaction monitoring was used to quantify the identified, hypoxia-associated EV proteins. To determine the potential biological significance of hypoxia-associated proteins, the cumulative Z score of identified EV proteins was compared with GBM subtypes from HGCC and TCGA databases. Results In total, 2928 proteins were identified in EVs, out of which 1654 proteins overlapped with the ExoCarta EV-specific database. We found 1034 proteins in EVs that were unique to the hypoxic status of U87-MG cells. We subsequently identified an EV protein signature, "HYPSIGNATURE", encompassing nine proteins that strongly represented the hypoxic situation and exhibited close proximity to the mesenchymal GBM subtype. Conclusions We propose, for the first time, an EV protein signature that could comprehensively reflect the hypoxic status of high-grade glioma cells. The presented data provide proof-of-concept for targeted proteomic profiling of glioma derived EVs, which should motivate future studies exploring its utility in non-invasive diagnosis and monitoring of brain tumor patients.
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| 11. |
- Indira Chandran, Vineesh, et al.
(författare)
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Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 25:10, s. 3115-3127
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma.Experimental Design: PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay-based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82).Results: Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II; area under the ROC curve (AUC): 0.81; sensitivity: 71%; specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased postoperatively depending on the extent of surgery.Conclusions: Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.
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| 12. |
- Jedlinski, Adam, 1978-, et al.
(författare)
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Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction in EGFR, pEGFR, and pSrc.
- 2017
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Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 46:9, s. 717-724
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aims of this study were to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC) cell lines in an in vivo xenograft model and to identify treatment-induced changes in the epidermal growth factor receptor (EGFR) signaling pathway that could be used as markers for cetuximab treatment response.MATERIALS AND METHODS: The in vitro and in vivo cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UT-SCC-45, was assessed using a crystal violet assay and xenografts in nude mice, respectively. The expression of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki-67 was investigated by immunohistochemistry. To verify these results, the in vitro expression of EGFR and pEGFR was analyzed with ELISA in a panel of 10 HNSCC cell lines.RESULTS: A close correlation was found between in vitro and in vivo cetuximab sensitivity data in the two investigated HNSCC cell lines. In treatment sensitive UT-SCC-14 xenografts, there was a decrease in EGFR, pEGFR, and pSrc upon cetuximab treatment. Interestingly, in insensitive UT-SCC-45 xenografts, an increased expression of these three proteins was found. The change in EGFR and pEGFR expression in vivo was confirmed in cetuximab-sensitive and cetuximab-insensitive HNSCC cell lines using ELISA.CONCLUSION: High sensitivity to cetuximab was strongly associated with a treatment-induced reduction in pEGFR both in vivo and in vitro in a panel of HNSCC cell lines, suggesting that EGFR and pEGFR dynamics could be used as a predictive biomarker for cetuximab treatment response.
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| 13. |
- Jedliński, Adam
(författare)
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Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck squamous cell carcinoma (HNSCC) originates from the epithelial lining of the upper aerodigestive tract. It accounts for over 90 % of the malignancies found in the head and neck region. 600,000 new cases of HNSCC occur each year worldwide. Apart from causing painful lesions, HNSCC directly impacts the patient’s fundamental functions such as breathing and eating and also can disrupt the patient’s senses such as smell, taste, speech and even vision. Most cases of HNSCC require a combination of different treatments such as surgery, chemotherapy (primarily cisplatin based), and radiotherapy. Treatment decisions are largely based on the size of the tumor, the involvement of local lymph nodes, and distant spread. Treatment resistance and local recurrence are significant problems and to date no form of clinical treatment sensitivity prediction is available.A majority of HNSCC tumors overexpresses the epidermal growth factor receptor (EGFR). This receptor is involved in proliferation and DNA repair and is the target of a monoclonal antibody named cetuximab that selectively binds and inhibits EGFR. It is the only targeted therapy available to HNSCC patients and reserved for late stage patients in Sweden.Numerous investigators have searched for predictive markers and we hypothesized that since HNSCC is a very heterogeneous disease a single factor would not be able to predict the treatment outcome. In paper I we explore a panel of predictive factors using a point system, called the number of negative points (NNP), in which we could combine both proteins and genetic variations in an attempt to find a set of markers that could predict the intrinsic cisplatin sensitivity (ICS). The expression level of EGFR, Hsp70, Bax, Bcl-XL, survivin, and COX-2 was determined in 39 HNSCC cell lines. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearson’s correlation tests showed that EGFR was the only protein that alone correlated to ICS (r=0.388, P=0.015). The strongest correlation to ICS was found when combining SNPs in XRCC3 and XPD with the expression of EGFR, Hsp70, Bax, and Bcl-2 using the NNP system (r=0.614 P≤0.001).In paper II we assess the intrinsic radiosensitivity (IR), the ICS, and the intrinsic cetuximab sensitivity (ICmabS) as well as their combinations in 25 HNSCC cell lines established from HNSCC biopsies taken at the Department of Otorhinolaryngology and Head and Neck Surgery at Linköping University Hospital. Furthermore we investigate the EGFR status (consisting of EGFR gene copy number, EGFR mRNA, EGFR protein, pEGFR), pAkt and mRNA levels of the seven known EGFR ligands. No correlation was found between the different treatment sensitivities. Cetuximab treatment response was significantly correlated to epiregulin (EREG) mRNA expression (r=-0.408, P=0.043). Cetuximab resistant cell lines tended to have low levels of pEGFR (P=0.13) while resistant cell lines had a significantly lower expression of EGFR protein (P=0.04) and tended to have decreased levels of pAkt (P=0.13) and amphiregulin (AREG) mRNA (p=0.18).In paper III the functional importance of EGFR ligands in relation to proliferation and cetuximab sensitivity was investigated. Here we tried to diminish the tumor heterogeneity by selecting three cell lines that are derived from the same anatomical location but display different ICmabS. Signaling through the EGFR was stimulated with recombinant EGF, AREG or EREG or reduced by siRNA-mediated silencing of the aforementioned EGFR ligands. EGF downregulation suppressed the proliferation of all investigated tumor cell lines whereas the response to an increased level of EGF differed between EGFR overexpressing and EGFR non-overexpressing cell lines. Furthermore, tumor cells consistently displayed increased cetuximab resistance upon the addition of EGF, whereas EGF silencing was associated with an improved cetuximab response. The data regarding AREG and EREG were inconclusive.In paper IV we wanted to validate in vitro drug sensitivity testing of HNSCC cell lines in an in vivo xenograft model, and to identify treatment-induced changes in the EGFR signaling pathway that could be used as markers for cetuximab treatment response. In vitro ICmabS for the HNSCC cell lines UT-SCC-14 and UT-SCC-45 was established using a crystal violet assay. In order to determine the corresponding in vivo sensitivity, UT-SCC-14 and UT-SCC-45 xenografts were generated in female BALB/c (nu/nu) nude mice. Mice were given three injections of intraperitoneal cetuximab or PBS and the tumor volume was recorded continuously. The expression of EGFR, pEGFR, pSrc, and Ki67 in the tumor tissue was investigated by immunohistochemistry. The in vitro sensitivity was reproduced in the in vivo model. Furthermore a clear reduction of EGFR, pEGFR, and pSrc after cetuximab treatment was noted in UT-SCC-14, the cetuximab sensitive cell line while the cetuximab resistant UT-SCC-45 showed a slight increase in EGFR, pEGFR and pSrc.In conclusion, the EGFR ligand EGF is a potential predictive marker of poor cetuximab response and a possible treatment target. Moreover, treatment-induced downregulation of EGFR and pEGFR is associated with a good cetuximab response.
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| 14. |
- Johansson, Ann-Charlotte, et al.
(författare)
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The relationship between EMT, CD44(high)/EGFR(low) phenotype, and treatment response in head and neck cancer cell lines
- 2016
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Ingår i: Journal of Oral Pathology & Medicine. - : WILEY-BLACKWELL. - 0904-2512 .- 1600-0714. ; 45:9, s. 640-646
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHead and neck squamous cell carcinoma (HNSCC) tumors are often therapy resistant and may originate from cancer stem cells or tumor cells with an epithelial-to-mesenchymal transition (EMT) phenotype. The aim of this study was to characterize HNSCC cell lines with regard to EMT profile and to investigate the influence of EMT on the response to treatment. MethodsmRNA expression of the EMT-associated genes CDH1 (E-cadherin), CDH2 (N-cadherin), FOXC2, TWIST1, VIM (vimentin), and FN1 (fibronectin) was determined using quantitative real-time PCR. Cell morphology and migration were investigated by phase-contrast microscopy and Boyden chamber assay, respectively. The cell surface expression of CD44 and epidermal growth factor receptor (EGFR) was examined by flow cytometry. The response to radiotherapy, cetuximab, and dasatinib was assessed by crystal violet staining. ResultsA total of 25 cell lines investigated differed greatly with regard to EMT phenotype. Cell lines with an EMT expression profile showed a mesenchymal morphology and a high migratory capacity. In addition, they exhibited a high cell surface expression of CD44 and a low expression of EGFR, a pattern previously associated with stemness. When the EMT inducer transforming growth factor- (TGF-) was added to non-EMT cells, changes in treatment responses were observed. Moreover, the expression of TWIST1 was found to correlate with radioresistance. ConclusionsThe data presented in this report suggest that EMT is associated with a CD44(high)/EGFR(low) phenotype and possibly negative impact on radiotherapy response in HNSCC cell lines.
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| 15. |
- Johansson, Karl E., et al.
(författare)
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Shiga toxin signals via ATP and its effect is blocked by purinergic receptor antagonism
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli (EHEC), that cause gastrointestinal infection leading to hemolytic uremic syndrome. The aim of this study was to investigate if Stx signals via ATP and if blockade of purinergic receptors could be protective. Stx induced ATP release from HeLa cells and in a mouse model. Toxin induced rapid calcium influx into HeLa cells, as well as platelets, and a P2X1 receptor antagonist, NF449, abolished this effect. Likewise, the P2X antagonist suramin blocked calcium influx in Hela cells. NF449 did not affect toxin intracellular retrograde transport, however, cells pre-treated with NF449 exhibited significantly higher viability after exposure to Stx for 24 hours, compared to untreated cells. NF449 protected HeLa cells from protein synthesis inhibition and from Stx-induced apoptosis, assayed by caspase 3/7 activity. The latter effect was confirmed by P2X1 receptor silencing. Stx induced the release of toxin-positive HeLa cell- and platelet-derived microvesicles, detected by flow cytometry, an effect significantly reduced by NF449 or suramin. Suramin decreased microvesicle levels in mice injected with Stx or inoculated with Stx-producing EHEC. Taken together, we describe a novel mechanism of Stx-mediated cellular injury associated with ATP signaling and inhibited by P2X receptor blockade.
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| 16. |
- Johansson, Rose-Marie, et al.
(författare)
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Reflective team and process-oriented supervision – a case study on differences
- 2017
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Ingår i: Reflective Practice. - : Informa UK Limited. - 1462-3943 .- 1470-1103. ; , s. 737-749
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Tidskriftsartikel (refereegranskat)abstract
- To meet the Swedish healthcare legislation’s requirements for evidence-based care, a work model for reflection has been developed, called a reflective team (RT). Because this RT model can be perceived as either a competitor of or a complement to caring supervision, this case study aims to explore what distinguishes these two in psychiatric care. Five members of one RT who are psychiatric nurses with previous experiences in caring supervision were interviewed. The transcribed interviews were analysed according to phenomenography. The findings reveal three qualitatively separated categories, which describe differences in focus, competencies, and relationships between confirmation and demands. It is concluded that an RT by no means replaces supervision. Instead, both can contribute to care improvement by complementing each other and increasing the professionalism of psychiatric nurses
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| 17. |
- Karpman, Diana, et al.
(författare)
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Complement Interactions with Blood Cells, Endothelial Cells and Microvesicles in Thrombotic and Inflammatory Conditions.
- 2015
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Ingår i: Advances in Experimental Medicine and Biology. - Cham : Springer International Publishing. - 0065-2598. - 9783319186023 ; 865, s. 19-42
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Konferensbidrag (refereegranskat)abstract
- The complement system is activated in the vasculature during thrombotic and inflammatory conditions. Activation may be associated with chronic inflammation on the endothelial surface leading to complement deposition. Complement mutations allow uninhibited complement activation to occur on platelets, neutrophils, monocytes, and aggregates thereof, as well as on red blood cells and endothelial cells. Furthermore, complement activation on the cells leads to the shedding of cell derived-microvesicles that may express complement and tissue factor thus promoting inflammation and thrombosis. Complement deposition on red blood cells triggers hemolysis and the release of red blood cell-derived microvesicles that are prothrombotic. Microvesicles are small membrane vesicles ranging from 0.1 to 1 μm, shed by cells during activation, injury and/or apoptosis that express components of the parent cell. Microvesicles are released during inflammatory and vascular conditions. The repertoire of inflammatory markers on endothelial cell-derived microvesicles shed during inflammation is large and includes complement. These circulating microvesicles may reflect the ongoing inflammatory process but may also contribute to its propagation. This overview will describe complement activation on blood and endothelial cells and the release of microvesicles from these cells during hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and vasculitis, clinical conditions associated with enhanced thrombosis and inflammation.
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| 18. |
- Ståhl, Anne-lie, et al.
(författare)
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A Novel Mechanism of Bacterial Toxin Transfer within Host Blood Cell-Derived Microvesicles.
- 2015
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system.
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