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Sökning: WFRF:(Carlsson Jessica)

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1.
  • Ahlberg, Erik, et al. (författare)
  • "Vi klimatforskare stödjer Greta och skolungdomarna"
  • 2019
  • Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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2.
  • Johansson, Ellen, et al. (författare)
  • Revising the embryonic origin of thyroid C cells in mice and humans
  • 2015
  • Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 142:20, s. 3519-3528
  • Tidskriftsartikel (refereegranskat)abstract
    • Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate-mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development implicates a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. In similarity with many gut endoderm derivatives embryonic C cells were found to co-express pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo consistent with a growth-promoting role of Foxa1. Contrasting embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment down-regulated Foxa2 foregoing epithelial-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm, and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.
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3.
  • Lundgren, Markus, et al. (författare)
  • Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
  • 2017
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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4.
  • Löfvenberg, Christian, 1978-, et al. (författare)
  • Prevalence of severe-to-Profound hearing loss in the adult Swedish population and comparison with cochlear implantation rate
  • 2022
  • Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 142:5, s. 410-414
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence of disabling hearing loss is increasing worldwide. However, previous studies on hearing loss prevalence have enrolled small populations or only provided estimates.Aim: To establish the prevalence of severe-to-profound hearing loss (STPHL) in the adult Swedish population and compare it with the cochlear implantation rate in Sweden.Material and methods: We established a database containing over 15 million audiograms obtained from regions covering > 99% of the Swedish population by extracting audiogram data from the computer software application, Auditbase. We used this database to calculate the percentage of adult patients with bilateral hearing levels >= 70 dB. We collected data regarding cochlear implantations in Sweden from the National Board of Welfare and Health.Results: The prevalence of STPHL in the adult Swedish population was 0.28%. There were regional variations in the prevalence and rate of cochlear implantation; however, there was no association between both parameters.Conclusions: This study presents an updated and reliable prevalence figure for STPHL in Sweden.Significance: Patients with STPHL have extensive rehabilitation requirements; accordingly, it is important to determine the accurate prevalence of STPHL to inform the allocation of adequate resources.
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5.
  • Rueenauver, K., et al. (författare)
  • Prognostic significance of YWHAZ expression in localized prostate cancer
  • 2014
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 17:4, s. 310-314
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa.METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were, used to assess the prognostic value of YWHAZ intensity.RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P<0.001) and PSA relapse (P=0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P=0.002) and reduced survival time (P=0.002).CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
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6.
  • Ullmark, Peter, et al. (författare)
  • Design & visuell kommunikation : examensbok 2010
  • 2010
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Publiceras i samband med den första utexamineringen från kandidatprogrammet Design & Visuell Kommunikation på Malmö högskola. Boken innehåller artiklar om designforskning såväl som personliga presentationer av programmets studenter och deras examensarbeten eller portfolios. Boken definierar vad Design & Visuell Kommunikation står för i studenternas mening.
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7.
  • Alexandersson, Nathalie, et al. (författare)
  • Determinants of variable resource use for multidisciplinary team meetings in cancer care
  • 2018
  • Ingår i: Acta Oncologica. - 0284-186X. ; 57:5, s. 675-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Multidisciplinary team meetings (MDTMs) have developed into standard of care to provide expert opinion and to grant evidence-based recommendations on diagnostics and treatment of cancer. Though MDTMs are associated with a range of benefits, a growing number of cases, complex case discussion and an increasing number of participants raise questions on cost versus benefit. We aimed to determine cost of MDTMs and to define determinants hereof based on observations in Swedish cancer care. Methods: Data were collected through observations of 50 MDTMs and from questionnaire data from 206 health professionals that participated in these meetings. Results: The MDTMs lasted mean 0.88 h and managed mean 12.6 cases with mean 4.2 min per case. Participants were mean 8.2 physicians and 2.9 nurses/other health professionals. Besides the number of cases discussed, meeting duration was also influenced by cancer diagnosis, hospital type and use of video facilities. When preparatory work, participation and post-MDTM work were considered, physicians spent mean 4.1 h per meeting. The cost per case discussion was mean 212 (range 91–595) EUR and the cost per MDTM was mean 2675 (range 1439–4070) EUR. Conclusions: We identify considerable variability in resource use for MDTMs in cancer care and demonstrate that 84% of the total cost is derived from physician time. The variability demonstrated underscores the need for regular and structured evaluations to ensure cost effective MDTM services.
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8.
  • Andersson, Louise, 1979, et al. (författare)
  • Role of EphA4 receptor signaling in thyroid development: regulation of folliculogenesis and propagation of the C-cell lineage.
  • 2011
  • Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 152:3, s. 1154-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptome analysis revealed that the tyrosine kinase receptor EphA4 is enriched in the thyroid bud in mouse embryos. We used heterozygous EphA4-EGFP knock-in mice in which enhanced green fluorescent protein (EGFP) replaced the intracellular receptor domain (EphA4(+/EGFP)) to localize EphA4 protein in thyroid primordial tissues. This showed that thyroid progenitors originating in the pharyngeal floor express EphA4 at all embryonic stages and when follicles are formed in late development. Also, the ultimobranchial bodies developed from the pharyngeal pouch endoderm express EphA4, but the ultimobranchial epithelium loses the EGFP signal before it merges with the median thyroid primordium. Embryonic C cells invading the thyroid are exclusively EphA4-negative. EphA4 expression continues in the adult thyroid. EphA4 knock-out mice and EphA4-EGFP homozygous mutants are euthyroid and have a normal thyroid anatomy but display subtle histological alterations regarding number, size, and shape of follicles. Of particular interest, the pattern of follicular abnormality differs between EphA4(-/-) and EphA4(EGFP/EGFP) thyroids. In addition, the number of C cells is reduced by >50% exclusively in animals lacking EphA4 forward signaling (EphA4(EGFP/EGFP)). Heterozygous EphA4 mutants have no apparent thyroid phenotype. We conclude that EphA4 is a novel regulator of thyroid morphogenesis that impacts on postnatal development of the two endocrine cell lineages of the differentiating gland. In this process both EphA4 forward signaling (in the follicular epithelium) and reverse signaling mediated by its cognate ligand(s) (A- and/or B-ephrins expressed in follicular cells and C cells, respectively) are probably functionally important.
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9.
  • Beaulieu, Luc, et al. (författare)
  • AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy
  • 2023
  • Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405. ; 50:8, s. E946-E960
  • Tidskriftsartikel (refereegranskat)abstract
    • The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for Ir-192-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.
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10.
  • Bergtagen
  • 2020. - 200
  • Samlingsverk (redaktörskap) (populärvet., debatt m.m.)
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11.
  • Brady, Lauren, et al. (författare)
  • Correlation of integrated ERG/PTEN assessment with biochemical recurrence in prostate cancer
  • 2021
  • Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 29
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Prostate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy.METHODS: Tissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups - Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared.RESULTS: Pathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066).CONCLUSION: In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.
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12.
  • Braegelmann, Johannes, et al. (författare)
  • Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer
  • 2017
  • Ingår i: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 23:7, s. 1829-1840
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.
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13.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • A miRNA expression signature that separates between normal and malignant prostate tissues
  • 2011
  • Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; :11, s. 14-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMicroRNAs (miRNAs) constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues.ResultsNine miRNAs were found to be differentially expressed (p <0.00001). With the exception of two samples, this expression signature could be used to separate between the normal and malignant tissues. A cross-validation procedure confirmed the generality of this expression signature. We also identified 16 miRNAs that possibly could be used as a complement to current methods for grading of prostate tumor tissues.ConclusionsWe found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85%) could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.
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14.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
  • 2013
  • Ingår i: BMC Cancer. - London, United Kingdom : BioMed Central (BMC). - 1471-2407. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.
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15.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ) and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation to the difference in propensity of tumors in the zones of the prostate.Methods:The expression of 667 unique miRNAs was investigated in normal and malignant transition zone and peripheral zone prostate tissues using TaqMan low density arrays for miRNAs. Student’s t-test was used in order to identify differentially expressed miRNAs and hierarchical clustering and principal component analyses were used to note the separation of the tissues. A cross-validation test using the ADtree algorithm was used to test the generality of the identified miRNA signatures.Results:The Student’s t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentiallyexpressed miRNAs between normal and malignant tissues showed a perfect separation between samples while analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmedt hese results and several potential miRNA markers were identified.Conclusions:The results of this study indicate that the major differences in the transcription programme are those arising during tumor development, rather than during normal tissue development. In conclusion, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ, indicating that the PZ are more prone to tumor development than the TZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the transition- or peripheral zone.
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17.
  • Carlsson, Jessica, 1984- (författare)
  • Identification of miRNA expression profiles for diagnosis and prognosis of prostate cancer
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cancer of the prostate (CaP) is the most common malignancy diagnosed in men in the Western society. During the last years, prostate specific antigen (PSA) has been used as a biomarker for CaP, although a high PSA value is not specific for CaP. Thus, there is an urgent need for new and improved diagnostic markers for CaP.In this thesis, the aim was to find a miRNA signature for diagnosis of CaP and to elucidate if differences in behavior between transition zone and peripheral zone tumors are reflected in miRNA expression. One of the major findings is anexpression signature based on nine miRNAs that with high accuracy (85%) could classify normal and malignant tissues from the transition zone of the prostate. The results furthermore show that the major differences in miRNA expression are found between normal and malignant tissues, rather than between the different zones. In addition, tumors arising in the peripheral zone have fewer changes in miRNA expression compared to tumors in the transition zone, indicating that the peripheral zone is more prone to tumor development compared to the transition zone of the prostate.A crucial step in pre-processing of expression data, in order to differentiate true biological changes, is the normalization step. Therefore, an additional aim of this thesis was to compare different normalization methods for qPCR array data in miRNA expression experiments. The results show that data-driven methods based on quantile normalization performs the best. The results also show that in smaller miRNA expression studies, only investigating a few miRNAs, RNU24 is the most suitable endogenous control gene for normalization.Taken together, the results in this thesis show the importance of miRNAs and the possibility of their future use as biomarkers in the field of prostate cancer.
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20.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma
  • 2020
  • Ingår i: Applied immunohistochemistry & molecular morphology (Print). - : Lippincott Williams & Wilkins. - 1541-2016 .- 1533-4058. ; 28:3, s. 213-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.
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21.
  • Carlsson, Jessica, 1987-, et al. (författare)
  • Physical activity and music to support pre-school children’s mathematics learning in Sweden
  • 2016
  • Ingår i: Education 3-13. - : Routledge. - 0300-4279 .- 1475-7575. ; 46:5, s. 483-493
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to give all children equal opportunities in school, methods to prevent early differences are needed. The overall aim of this study was to investigate the effectiveness of two structured teaching methods: Math in Action, characterised by physical activity and music, and common numerical activities. Children (28 girls, 25 boys) were assigned to 1 of the 2 conditions during a period of 3 weeks (2 times a week for a 30-minute session). The results show that children who learn mathematics in an environment characterised by physical activity and music develop their mathematical abilities significantly more than children who learn mathematics through common number activities. We have also shown that children with different motor skill abilities benefit from learning mathematics in an environment characterised by physical activity and music.
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22.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • Prostate cancer and inflammation : The role of miRNAs
  • 2013
  • Ingår i: European Medical Journal Oncology. - United Kingdom : Gorely New Media Ltd.. - 2054-619X. ; , s. 56-60
  • Forskningsöversikt (refereegranskat)abstract
    • Approximately 15-20% of all human cancers are assumed to be a result of infection and chronic inflammation due to a constant supply of cytokines and reactive oxygen species, giving rise to genomic instability and a subsequent tumour development. In recent years, chronic inflammation has also been hypothesised to influence prostate carcinogenesis, since both acute and chronic inflammation is commonly seen in prostatic tissues. The signalling pathways involved in the immune response and tumour development are overlapping with each other, and it has been proposed that miRNAs are a possible link between the two processes. In this review, we are describing some of the miRNAs which could constitute a conceivable link between inflammation and prostate cancer.
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23.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • Quantity and quality of nucleic acids extracted from archival formalin fixed paraffin embedded prostate biopsies
  • 2018
  • Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.METHODS: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.RESULTS: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.CONCLUSIONS: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.
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24.
  • Carlsson, Jessica, 1984- (författare)
  • The Potential Role of miR-126 as a Prognostic Biomarker in Renal Cell Carcinoma
  • 2018
  • Konferensbidrag (refereegranskat)abstract
    • Renal cell carcinoma (RCC) is the most common renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk for recurrence at an early stage could improve the outcome for the patient. The factors used in the clinics today cannot reliably predict the natural history of the disease, thus there is a need for finding new biomarkers that can aid in predicting patient outcome. Several studies indicate that miRNAs are potential candidates as prognostic biomarkers for patients suffering from RCC. The aim of this study was to validate the potential of miR-126 to predict prognosis in a Swedish cohort of RCC patients. Methods: The expression of miR-126 was measured using quantitative PCR (qPCR) in formalin-fixed paraffin-embedded (FFPE) tumor tissue from 116 patients diagnosed with RCC between 1987 and 2010. Results: miR-126 was found to be differentially expressed between malignant and adjacent benign tissue. The expression of miR-126 was also differentially expressed between tumor grades, and stages of RCC. We could furthermore show that in a univariate model, a low expression of miR-126 was associated with shorter time to recurrence of the disease. Conclusion: Our results indicate that miR-126 expression has a potential to be used as a prognostic biomarker for patients suffering from RCC. However, further studies are needed in order to confirm these results.
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25.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma
  • 2019
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:5, s. 4566-4574
  • Tidskriftsartikel (refereegranskat)abstract
    • Renal cell carcinoma (RCC) is the most commonly diagnosed renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk of recurrence at an early stage of disease may improve patient outcome. The factors presently used in a clinical setting cannot reliably predict the natural history of the disease. Therefore, there is a requirement to identify novel biomarkers that can aid in predicting patient outcome. Previous studies have indicated that microRNAs (miRNAs/miRs) are potential candidates as prognostic biomarkers for patients suffering from RCC. Consequently, the aims of the present study were to validate the potential of 3 of these miRNAs to predict the prognosis of patients with RCC, and to investigate the stability of endogenous control genes for miRNA studies in RCC tissues. The expression of 7 endogenous controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in formalin-fixed paraffin-embedded tumor and benign tissues from patients suffering from clear cell RCC (ccRCC). The analyses identified RNU48 and U47 as the most stable endogenous controls. The expression of miR-126, miR-21 and miR-10b was analyzed using RT-qPCR in renal tissues from 116 patients diagnosed with ccRCC. All three investigated miRNAs were differentially expressed between malignant and benign tissues. miR-126 and miR-10b were also differentially expressed between grades and stages of ccRCC. In a univariate, but not in a multivariate model, low expression of miR-126 was associated with shorter time to recurrence of the disease. The results of the present study indicate that of the 3 miRNAs investigated, the expression of miR-126 has the strongest potential as a prognostic biomarker for patients suffering from ccRCC.
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26.
  • Carlsson, Jessica, et al. (författare)
  • Validation of suitable endogenous control genes for expression studies of miRNA in prostate cancer tissues
  • 2010
  • Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier Inc.. - 0165-4608 .- 1873-4456. ; 202:2, s. 71-75
  • Tidskriftsartikel (refereegranskat)abstract
    • When performing quantitative polymerase chain reaction analysis, there is a need for correction of technical variation between experiments. This correction is most commonly performed by using endogenous control genes, which are stably expressed across samples, as reference genes for normal expression in a specific tissue. In microRNA (miRNA) studies, two types of control genes are commonly used: small nuclear RNAs and small nucleolar RNAs. In this study, six different endogenous control genes for miRNA studies were investigated in prostate tissue material from the Swedish Watchful Waiting cohort. The stability of the controls was investigated using two different software applications, NormFinder and BestKeeper. RNU24 was the most suitable endogenous control gene for miRNA studies in prostate tissue materials.
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27.
  • Carlsson, Jessica, et al. (författare)
  • Validation of suitable endogenous control genes for expression studies of miRNA in prostate cancer tissues
  • 2010
  • Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608 .- 1873-4456. ; 202:2, s. 71-75
  • Tidskriftsartikel (refereegranskat)abstract
    • When performing quantitative polymerase chain reaction analysis, there is a need for correction of technical variation between experiments. This correction is most commonly performed by using endogenous control genes, which are stably expressed across samples, as reference genes for normal expression in a specific tissue. In microRNA (miRNA) studies, two types of control genes are commonly used: small nuclear RNAs and small nucleolar RNAs. In this study, six different endogenous control genes for miRNA studies were investigated in prostate tissue material from the Swedish Watchful Waiting cohort. The stability of the controls was investigated using two different software applications, NormFinder and BestKeeper. RNU24 was the most suitable endogenous control gene for miRNA studies in prostate tissue materials. (C) 2010 Elsevier Inc. All rights reserved.
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28.
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29.
  • Carlsson, Liesel, et al. (författare)
  • School Gardens : Cultivating Food Security in Nova Scotia Public Schools?
  • 2016
  • Ingår i: Canadian journal of dietetic practice and research. - Toronto : DIETITIANS CANADA. - 2292-9592 .- 1486-3847. ; 77:3, s. 119-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: A small but growing body of peer-reviewed research suggests that school gardens can play a role in building community food security (CFS); however, to date little research exploring the role of school gardens in supporting CFS is available. This paper begins to address this gap in the literature. Methods: A qualitative, exploratory, single-case study design was used. The focus of this case study was the school food garden at an elementary school in the River Valley, Nova Scotia, school community. Results: Results provide useful information about potential CFS effects of school gardens in addition to the environmental effects on school gardens important to their effectiveness as CFS tools. Findings suggest children gained food-related knowledge, skills, and values that support long-term CFS. A local social and political landscape at the community, provincial, and school board level were key to strengthening this garden's contributions to CFS. Conclusions: We support Dietitians of Canada's nomination of school gardens as an indicator of CFS with theoretical and practical evidence, underscore the importance of a supportive environment, and need for further research in this area. Health professionals and community organizations provide critical support, helping to weave gardens into a greater movement towards building CFS.
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30.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer
  • 2021
  • Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p ,0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression. 
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31.
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32.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer
  • 2018
  • Ingår i: The Prostate. - Hoboken, USA : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 78:1, s. 40-47
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs ). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.METHODS: Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.RESULTS: In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart.CONCLUSIONS: Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established.
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33.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
  • 2016
  • Ingår i: Infectious Agents and Cancer. - London, United Kingdom : BioMed Central (BMC). - 1750-9378. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.
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34.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
  • 2020
  • Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 62-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome. Background: It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective: To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants: A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis: Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations: We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions: Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary: The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.
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35.
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36.
  • Davidsson, Sabina, et al. (författare)
  • PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes
  • 2019
  • Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 2:2, s. 214-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity.Objective: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer.Design, setting, and participants: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry.Outcome measurements and statistical analysis: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.Results and limitations: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1–positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation.Conclusions: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes.Patient summary: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.
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37.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue
  • 2017
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes.
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38.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Soluble Levels of CD163, PD-L1, and IL-10 in Renal Cell Carcinoma Patients
  • 2022
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • CD163+ M2 macrophages have been suggested to counteract tumor immunity by increasing immunosuppressive mechanisms including PD-L1 and IL-10 expression. Soluble levels of PD-L1, IL-10, and CD163 have been reported as potential biomarkers in various cancers, although the prognostic value in renal cell carcinoma (RCC) has to be further elucidated. In the present study, we measured the levels of sPD-L1, sIL-10, and sCD163 in 144 blood samples from patients with RCC. The levels were determined by using enzyme linked immunosorbent assays. Soluble PD-L1 and CD163 were detectable in 100% of the serum samples, and sCD163 in 22% of the urine samples, while only a minority of the samples had detectable sIL-10. Significantly higher serum levels of sPD-L1 and sCD163 were observed in patients with metastatic disease (p < 0.05). The results also showed that patients with high levels of sPD-L1 in serum had shorter cancer-specific survival compared with patients with low levels (p = 0.002). The results indicate that sPD-L1 most significantly reflects tumor progression in RCC.
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39.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • The presence of PD-L1 in men with localized prostate cancer
  • 2017
  • Ingår i: Medical research archives. - Walnut CA, USA : KEI Journals. - 2375-1916 .- 2375-1924. ; 4:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent therapeutic strategies for different cancer types have focused on targeting immune check-points, such as programmed death-1 (PD-1) and its ligand PD-L1. However, it was recently reported that men with castration-resistant prostate cancer did not respond to PD-1 blockade as monotherapy. The unresponsiveness could potentially be explained by low expression of PD-L1 on prostate tumor cells. This study investigated the expression of PD-L1 on tumor cells and tumor infiltrating lymphocytes (TILs) in men with primary prostate cancer.Material and Methods: Immunohistochemical analysis of PD-L1 expression was performed in a cohort of men undergoing transurethral resection of the prostate and diagnosed with prostate cancer. The expression was evaluated in tissue microarrays from 522 patients with at least 25 years of follow-up.Results: Only four of the 522 evaluated cases were positive for PD-L1, positivity on tumor cells were found in three of the cases, of which one case also had positivity on TILs, while a fourth case only had positivity on TILs.Conclusion: Our data suggest that treatments targeting the PD-1/PD-L1 interaction may not be successful as monotherapy in patients diagnosed with localized prostate cancer due to low expression of PD-L1.
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40.
  • Davies, Lindsay C., et al. (författare)
  • Type 1 Diabetes Mellitus Donor Mesenchymal. Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro
  • 2016
  • Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 5:11, s. 1485-1495
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone marrow mesenchymal stromal cells (BM-MSCs) have been characterized and used in many clinical studies based on their immunomodulatory and regenerative properties. We have recently reported the benefit of autologous MSC systemic therapy in the treatment of type 1 diabetes mellitus (T1D). Compared with allogeneic cells, use of autologous products reduces the risk of eliciting undesired complications in the recipient, including rejection, immunization, and transmission of viruses and prions; however, comparable potency of autologous cells is required for this treatment approach to remain feasible. To date, no analysis has been reported that phenotypically and functionally characterizes MSCs derived from newly diagnosed and late-stage T1D donors in vitro with respect to their suitability for systemic immunotherapy. In this study, we used gene array in combination with functional in vitro assays to address these questions. MSCs from T1D donors and healthy controls were expanded from BM aspirates. BM mononuclear cell counts and growth kinetics were comparable between the groups, with equivalent colony-forming unit-fibroblast capacity. Gene microarrays demonstrated differential gene expression between healthy and late-stage T1D donors in relation to cytokine secretion, immunomodulatory activity, and wound healing potential. Despite transcriptional differences, T1D MSCs did not demonstrate a significant difference from healthy controls in immunosuppressive activity, migratory capacity, or hemocompatibility. We conclude that despite differential gene expression, expanded MSCs from T1D donors are phenotypically and functionally similar to healthy control MSCs with regard to their immunomodulatory and migratory potential, indicating their suitability for use in autologous systemic therapy.
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41.
  • Deo, Ameya, et al. (författare)
  • How to Choose a Normalization Strategy for miRNA Quantitative Real-Time (qPCR) Arrays
  • 2011
  • Ingår i: Journal of Bioinformatics and Computational Biology. - : Imperial College Press. - 0219-7200 .- 1757-6334. ; 9:6, s. 795-812
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-density arrays for quantitative real-time PCR (qPCR) are increasingly being used as an experimental technique for miRNA expression profiling. As with gene expression profiling using microarrays, data from such experiments needs effective analysis methods to produce reliable and high-quality results. In the pre-processing of the data, one crucial analysis step is normalization, which aims to reduce measurement errors and technical variability among arrays that might have arisen during the execution of the experiments. However, there are currently a number of different approaches to choose among and an unsuitable applied method may induce misleading effects, which could affect the subsequent analysis steps and thereby any conclusions drawn from the results. The choice of normalization method is hence an important issue to consider. In this study we present the comparison of a number of data-driven normalization methods for TaqMan low-density arrays for qPCR and different descriptive statistical techniques that can facilitate the choice of normalization method. The performance of the normalization methods was assessed and compared against each other as well as against standard normalization using endogenous controls. The results clearly show that the data-driven methods reduce variation and represent robust alternatives to using endogenous controls.
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42.
  • Dorofte, Luiza, 1982-, et al. (författare)
  • Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care
  • 2022
  • Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 480:4, s. 879-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors. 
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43.
  • Edstorp, Jessica, et al. (författare)
  • Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?
  • 2024
  • Ingår i: Diabetes/Metabolism Research and Reviews. - 1520-7552. ; 40:3, s. e3758-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods: We used data from a population-based Swedish case-control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results: Individuals who developed LADA did not have a higher prevalence of infectious disease 1–10 years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1–3 years. Similar results were seen for LADA with high-risk HLA genotypes (OR 0.95 [0.64, 1.42]) or high GADA levels (OR 1.10 [0.79, 1.55]), ≥2 episodes (OR 0.89 [0.56, 1.40]), and in infections treated using antibiotics (OR 1.03 [0.73, 1.45]). The only significant association was observed with lower respiratory disease the year preceding LADA diagnosis (OR 1.67 [1.06, 2.64]). Conclusions: Our findings do not support the idea that exposure to infections increases the risk of LADA. A higher prevalence of respiratory infection in the year before LADA diagnosis could reflect increased susceptibility to infections due to hyperglycemia.
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44.
  • Edstorp, Jessica, et al. (författare)
  • Incidence of lada and type 2 diabetes in relation to tobacco use and genetic susceptibility to type 2 diabetes and related traits : Findings from a swedish case-control study and the norwegian hunt study
  • 2023
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1028-1036
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations. RESEARCH DESIGN AND METHODS We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS. RESULTS The RR of LADA was elevated in high IR-GRS heavy smokers (‡15 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (‡15 box/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (P = 0.003; P = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D. CONCLUSIONS Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use.
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45.
  • Edstorp, Jessica, et al. (författare)
  • Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
  • 2023
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 66, s. 70-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results: Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. Data availability: Analysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA). Graphical abstract: [Figure not available: see fulltext.]
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46.
  • Erlandsson, Ann, 1968-, et al. (författare)
  • High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer
  • 2018
  • Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 52:2, s. 129-133
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa.MATERIALS AND METHODS: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category.RESULTS: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97).CONCLUSION: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.
  •  
47.
  • Erlandsson, Ann, 1968-, et al. (författare)
  • M2 macrophages and regulatory T cells in lethal prostate cancer.
  • 2019
  • Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 79:4, s. 363-369
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs ) can contribute to cancer progression by suppressing the anti-tumor immune response. This study investigated the number of CD163-positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs .METHODS: This nested case-control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163-positive M2 macrophages and FOXP3/CD4-positive Tregs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and Tregs were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.RESULTS: The number of M2 macrophages and Tregs showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.CONCLUSIONS: Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs , promote an immunosuppressive environment.
  •  
48.
  • Falck, Eva, et al. (författare)
  • Loss of Glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma
  • 2010
  • Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.
  •  
49.
  • Finnveden, Göran, et al. (författare)
  • Strategic environmental assessment methodologies : applications within the energy sector
  • 2003
  • Ingår i: Environmental impact assessment review. - 0195-9255 .- 1873-6432. ; 23:1, s. 91-123
  • Tidskriftsartikel (refereegranskat)abstract
    • Strategic Environmental Assessment (SEA) is a procedural tool and within the framework of SEA, several different types of analytical tools can be used in the assessment. Several analytical tools are presented and their relation to SEA is discussed including methods for future studies, Life Cycle Assessment, Risk Assessment, Economic Valuation and Multi-Attribute Approaches. A framework for the integration of some analytical tools in the SEA process is suggested. It is noted that the available analytical tools primarily cover some types of environmental impacts related to emissions of pollutants. Tools covering impacts on ecosystems and landscapes are more limited. The relation between application and choice of analytical tools is discussed. It is suggested that SEAs used to support a choice between different alternatives require more quantitative methods, whereas SEAs used to identify critical aspects and suggest mitigation strategies can suffice with more qualitative methods. The possible and desired degree of site-specificity in the assessment can also influence the choice of methods. It is also suggested that values and world views can be of importance for judging whether different types of tools and results are meaningful and useful. Since values and world views differ between different stakeholders, consultation and understanding are important to ensure credibility and relevance.
  •  
50.
  • Ginstman, Charlotte, et al. (författare)
  • Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux‐en‐Y gastric bypass surgery : a pharmacokinetic study
  • 2019
  • Ingår i: British Journal of Obstetrics and Gynecology. - : Blackwell Publishing. - 1470-0328 .- 1471-0528. ; 126:4, s. 486-492
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether Roux-en-Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics.Design: Single centre, open label, phase-2 pharmacokinetic study.Setting: University hospital of Linkoping, Sweden.Population: Fourteen women with planned RYGB surgery were included; nine women aged 18-45 years using 75 micrograms desogestrel completed the study.Methods: Steady-state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 6 weeks before surgery, and at 12 2 and 52 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24-hour period and etonogestrel concentrations were determined with ultra-performance liquid chromatography/tandem mass spectrometry.Main outcome measures: Area under the plasma concentration time curve of etonogestrel (AUC(0-24 hours)).Results: All women had significant postoperative weight loss. There were no significant differences in AUC(0-24 hours), terminal half-lives (t(1/2)), time to peak serum concentrations (T-max), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (C-max) increased after 52 +/- 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024).Conclusion: To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously.
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