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1.
  • Anand, Aseem, et al. (author)
  • Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide
  • 2016
  • In: EJNMMI Research. - : Springer. - 2191-219X. ; 6
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall's tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.RESULTS: Eighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = -0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.
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2.
  • Ivarsson, Andreas, 1984-, et al. (author)
  • Associations between physical activity and core affects within and across days: a daily diary study
  • 2021
  • In: Psychology & Health. - Abingdon : Informa UK Limited. - 0887-0446 .- 1476-8321. ; 36:1, s. 43-58
  • Journal article (peer-reviewed)abstract
    • Objective: The objective of the present study was to investigate (a) if daily physical activity at the within-person level is related to four different core affects the same evening, (b) if core affects in the evening predict physical activity the following day, and (c) if physical activity predicts core affects the following day. Design: A total of 166 university students were asked to complete the affect and physical activity measures once a day (in the evening), for seven days. Bivariate unconditional latent curve model analyses with structured residuals were performed to investigate the relations within days and across days between the core affects and physical activity. Main outcome measures: Core affects and physical activity. Results: Physical activity had positive within-day associations with pleasant-activated and pleasant-deactivated core affects and a negative within-day association with unpleasant-deactivated affective responses. There were, however, no statistically significant relations between core affects and physical activity across days. Conclusion: These results highlight that the measurement interval might be an important factor that influences the association between core affects and physical activity behaviors.
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3.
  • Josefsson, Torbjörn, 1965-, et al. (author)
  • Effects of Mindfulness-Acceptance-Commitment (MAC) on Sport-Specific Dispositional Mindfulness, Emotion Regulation, and Self-Rated Athletic Performance in a Multiple-Sport Population : an RCT Study
  • 2019
  • In: Mindfulness. - New York, NY : Springer. - 1868-8527 .- 1868-8535. ; 10:8, s. 1518-1529
  • Journal article (peer-reviewed)abstract
    • ObjectivesThe aim of the study was to examine mediating effects of emotion regulation and sport-specific dispositional mindfulness on self-rated athletic training performance, following the Mindfulness-Acceptance-Commitment (MAC) intervention, compared to a Psychological Skills Training (PST) control group.MethodsSixty-nine competitive elite athletes who did not have any prior experience with mindfulness- and acceptance-based exercises, were recruited and randomly assigned into either a MAC group or a traditional PST group. Latent growth curve analyses were performed to examine longitudinal relationships among the study variables. Mediation analyses were conducted to test if the growth trajectory of each of the proposed mediators mediated the relationship between the intervention and perceived performance (measured at T3).ResultsFindings showed that the MAC intervention had an indirect effect on self-rated athletic training performance through changes in dispositional mindfulness and emotion regulation respectively. Further, the MAC- group obtained greater post-test improvements in athletic mindfulness, emotion regulation abilities, and perceived performance compared to the PST group.ConclusionsOverall, findings suggest that dispositional athletic mindfulness and emotion regulation may function as important mechanisms in MAC, and that the MAC approach is a more effective intervention compared to the PST condition in reducing emotion regulation difficulties, as well as enhancing sport-relevant mindfulness skills and perceived athletic training performance in elite sport.
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4.
  • Josefsson, Torbjörn, 1965-, et al. (author)
  • Mindfulness Mechanisms in Sports: Mediating Effects of Rumination and Emotion Regulation on Sport-Specific Coping
  • 2017
  • In: Mindfulness. - New York, NY : Springer Science and Business Media LLC. - 1868-8527 .- 1868-8535. ; 8:5, s. 1354-1363
  • Journal article (peer-reviewed)abstract
    • The main objective of the project was to examine a proposed theoretical model of mindfulness mechanisms in sports. We conducted two studies (the first study using a cross-sectional design and the second a longitudinal design) to investigate if rumination and emotion regulation mediate the relation between dispositional mindfulness and sport-specific coping. Two hundred and forty-two young elite athletes, drawn from various sports, were recruited for the cross-sectional study. For the longitudinal study, 65 elite athletes were recruited. All analyses were performed using Bayesian statistics. The path analyses showed credible indirect effects of dispositional mindfulness on coping via rumination and emotion regulation in both the cross-sectional study and the longitudinal study. Additionally, the results in both studies showed credible direct effects of dispositional mindfulness on rumination and emotion regulation. Further, credible direct effects of emotion regulation as well as rumination on coping were also found in both studies. Our findings support the theoretical model, indicating that rumination and emotion regulation function as essential mechanisms in the relation between dispositional mindfulness and sport-specific coping skills. Increased dispositional mindfulness in competitive athletes (i.e. by practicing mindfulness) may lead to reductions in rumination, as well as an improved capacity to regulate negative emotions. By doing so, athletes may improve their sport-related coping skills, and thereby enhance athletic performance.
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5.
  • Magnusson, Cecilia, et al. (author)
  • Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients
  • 2024
  • In: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 96:18, s. 6914-6921
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.METHODS: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry.RESULTS: Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM +, Cytokeratin +, DAPI +, CD45 -/CD66b -) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogeneous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding a higher number of CTCs using acoustophoresis. CONCLUSION: Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables the sensitive label-free enrichment of cells with epithelial phenotypes in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.
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6.
  • Magnusson, Cecilia, et al. (author)
  • Acoustic enrichment of heterogenous circulating tumor cells and clusters from patients with metastatic prostate cancer
  • 2023
  • Other publication (other academic/artistic)abstract
    • BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.METHODS: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility) resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry.RESULTS: Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM + , Cytokeratin + , DAPI + , CD45 - /CD66b - ) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogenous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC-clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding higher number of CTCs using acoustophoresis. CONCLUSION: Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC-clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables sensitive label-free enrichment of cells with epithelial phenotype in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.
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8.
  • Ahlin, Kjell, et al. (author)
  • Simulation of forced response in linear and nonlinear mechanical systems using digital filters
  • 2006
  • Conference paper (peer-reviewed)abstract
    • There exist many methods to calculate forced response in mechanical systems. Some methods are slow and the errors introduced are unknown. The paper presents a method that uses digital filters and modal superposition. It is shown how aliasing can be avoided as well as phase errors. The parameters describing the mechanical system are residues and poles, taken from FEA models, from lumped MCK systems, from analytic solutions or from experimental modal analysis. Modal damping may be used. The error in the calculation is derived and is shown to be only a function of the sampling frequency used. When the method is applied to linear mechanical systems in MATLAB it is very fast. The method is extended to incorporate nonlinear components. The nonlinear components could be simple, like hardening or stiffening springs, but may also contain memory, like dampers with hysteresis. The simulations are used to generate test data for development and evaluation of methods for identification of non-linear systems.
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9.
  • Ahlin, Rebecca, 1989, et al. (author)
  • Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial
  • 2023
  • In: Nutrients. - : MDPI. - 2072-6643 .- 2072-6643. ; 15:7
  • Journal article (peer-reviewed)abstract
    • Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.
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10.
  • Ahlin, Rebecca, 1989, et al. (author)
  • The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer : study protocol for the randomized controlled PRODICA trial
  • 2022
  • In: Trials. - : BioMed Central (BMC). - 1745-6215. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Background: A high intake of phytoestrogens, found in soy, rye, and seeds, is associated with a reduced risk of a prostate cancer diagnosis. Previously, we found that the overall decreased risk of prostate cancer diagnosis in males with a high intake of phytoestrogens was strongly modified by a nucleotide sequence variant in the estrogen receptor-beta (ERβ) gene. However, we do not know if phytoestrogens can inhibit the growth of prostate cancer in males with established diseases. If there is an inhibition or a delay, there is reason to believe that different variants of the ERβ gene will modify the effect. Therefore, we designed an intervention study to investigate the effect of the addition of foods high in phytoestrogens and their interaction with the ERβ genotype on prostate tumor proliferation in patients with prostate cancer.Method: The PRODICA trial is a randomized ongoing intervention study in patients with low- and intermediate-risk prostate cancer with a Gleason score < 8, prostate-specific antigen (PSA) < 20, and scheduled for radical prostatectomy. The study is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention consists of a daily intake of soybeans and flaxseeds (~ 200 mg of phytoestrogens) until the surgery, approximately 6 weeks. The aim is to recruit 200 participants. The primary outcome is the difference in the proliferation marker Ki-67 between the intervention and the control groups. The genotype of ERβ will be investigated as an effect-modifying factor. Secondary outcomes include, e.g., concentrations of PSA and steroid hormones in the blood.Discussion: The results of the PRODICA trial will contribute important information on the relevance of increasing the intake of phytoestrogens in patients with prostate cancer who want to make dietary changes to improve the prognosis of their cancer. If genetic factors turn out to influence the effect of the intervention diet, dietary advice can be given to patients who most likely benefit from it. Dietary interventions are cost-effective, non-invasive, and result in few mild side effects. Lastly, the project will provide basic pathophysiological insights which could be relevant to the development of treatment strategies for patients with prostate cancer.Trial registration. ClinicalTrials.gov NCT02759380. Registered on 3 May 2016.
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12.
  • Back, Jenny, 1984-, et al. (author)
  • Psychological risk factors for exercise dependence
  • 2021
  • In: International Journal of Sport and Exercise Psychology. - New York : Routledge. - 1612-197X .- 1557-251X. ; 19:4, s. 461-472
  • Journal article (peer-reviewed)abstract
    • The main aim of this study was to investigate if exercisers' personality characteristics were associated with exercise dependence. Specifically, the purpose was to examine if anxiety, obsessive passion, and physical appearance orientation were associated to an increased risk for exercise dependence. Participants were 330 exercisers from exercise groups, sport clubs and university sport science classes in the southwest of Sweden. Data were analysed using CHAID (Chi-squared Automatic Interaction Detection) analysis. The CHAID analysis indicated that anxiety was the main predictor of exercise dependence. More specifically, 12.7% more exercisers who experienced high levels of anxiety symptoms (i.e. scores above 6), were, in comparison to the exercises experiencing low levels of anxiety, classified as ?at risk for exercise dependence?. For exercisers that reported low levels of anxiety symptoms (i.e. scores below 7), obsessive passion for exercise was a positive statistically significant predictor (absolute risk difference?=?8.6%). Overall, the results highlight anxiety as a main risk factor behind exercise dependence. Also, the risk of exercise dependence may increase either from obsessive passion or as a coping strategy for anxiety. Furthermore, results may illustrate two types of exercise dependence; ?primary? exercise dependence driven mainly by an obsessive passion for exercise and ?secondary? exercise dependence where exercise function as a strategy to cope with anxiety.
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14.
  • Bovinder Ylitalo, Erik, et al. (author)
  • Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens
  • 2020
  • In: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 80:1, s. 214-224
  • Journal article (peer-reviewed)abstract
    • Background Taxane treatment may be a suitable therapeutic option for patients with castration-resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR-Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR-V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored. Methods Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm(3). Two cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole-genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis. Results Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, both showed upregulation of the ATP-binding cassette sub-family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR-antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1-CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment. Conclusions Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR-V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti-androgens.
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15.
  • Bratt, Ola, et al. (author)
  • The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
  • 2013
  • In: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
  • Research review (peer-reviewed)abstract
    • Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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16.
  • Bratt, Ola, 1963, et al. (author)
  • The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)
  • 2019
  • In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 76:4, s. 461-466
  • Journal article (peer-reviewed)abstract
    • Background: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown. Objective: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance. Design, setting, and participants: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75 yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included. Intervention: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores). Outcome measurements and statistical analysis: Primary outcome measure: Gleason grade group >= 2 cancer. Secondary outcomes: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied. Results and limitations: Gleason grade group >= 2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p = 0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p = 0.004) and for Gleason grade group >= 2 cancer 2.3 (95% CI 1.2-4.4, p = 0.015) per 0.1-ng/ml/cm(3) increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used. Conclusions: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy. Patient summary: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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17.
  • Carlsson, Andreas, et al. (author)
  • Prediction of designer drugs: synthesis and spectroscopic analysis of synthetic cannabinoid analogues of 1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone
  • 2016
  • In: Drug Testing and Analysis. - : WILEY-BLACKWELL. - 1942-7603 .- 1942-7611. ; 8:10, s. 1015-1029
  • Journal article (peer-reviewed)abstract
    • In this work, emergence patterns of synthetic cannabinoids were utilized in an attempt to predict those that may appear on the drug market in the future. Based on this information, two base structures of the synthetic cannabinoid analogues - (1H-indol-3-yl (2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone) - together with three substituents butyl, 4-fluorobutyl and ethyl tetrahydropyran - were selected for synthesis. This resulted in a total of six synthetic cannabinoid analogues that to the authors knowledge have not yet appeared on the drug market. Spectroscopic data, including nuclearmagnetic resonance (NMR), mass spectrometry (MS), and Fourier transforminfrared (FTIR) spectroscopy (solid and gas phase), are presented for the synthesized analogues and some additional related cannabinoids. In this context, the suitability of the employed techniques for the identification of unknowns is discussed and the use of GC-FTIR as a secondary complementary technique to GC-MS is addressed. Examples of compounds that are difficult to differentiate by their mass spectra, but can be distinguished based upon their gas phase FTIR spectra are presented. Conversely, structural homologueswhere mass spectra aremore powerful than gas phase FTIR spectra for unambiguous assignments are also exemplified. This work further emphasizes that a combination of several techniques is the key to success in structural elucidations. Copyright (C) 2015 John Wiley amp; Sons, Ltd.
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18.
  • Carlsson, Andreas, et al. (author)
  • Prediction of designer drugs: Synthesis and spectroscopic analysis of synthetic cathinone analogs that may appear on the Swedish drug market
  • 2018
  • In: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611. ; 10:7, s. 1076-1098
  • Journal article (peer-reviewed)abstract
    • The use of hyphenated analytical techniques in forensic drug screening enables simultaneous identification of a wide range of different compounds. However, the appearance of drug seizures containing new substances, mainly new psychoactive substances (NPS), is steadily increasing. These new and other already known substances often possess structural similarities and consequently they exhibit spectral data with slight differences. This situation has made the criteria that ensure indubitable identification of compounds increasingly important. In this work, 6 new synthetic cathinones that have not yet appeared in any Swedish drug seizures were synthesized. Their chemical structures were similar to those of already known cathinone analogs of which 42 were also included in the study. Hence, a total of 48 synthetic cathinones making up sets of homologous and regioisomeric compounds were used to challenge the capabilities of various analytical techniques commonly applied in forensic drug screening, ie, gas chromatography-mass spectrometry (GC-MS), gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR), nuclear magnetic resonance (NMR), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Special attention was paid to the capabilities of GC-MS and GC-FTIR to distinguish between the synthetic cathinones and the results showed that neither GC-MS nor GC-FTIR alone can successfully differentiate between all synthetic cathinones. However, the 2 techniques proved to be complementary and their combined use is therefore beneficial. For example, the structural homologs were better differentiated by GC-MS, while GC-FTIR performed better for the regioisomers. Further, new spectroscopic data of the synthesized cathinone analogs is hereby presented for the forensic community. The synthetic work also showed that cathinone reference compounds can be produced in few reaction steps.
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19.
  • Carlsson, Andreas (author)
  • Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones
  • 2016
  • Licentiate thesis (other academic/artistic)abstract
    • The application of different analytical techniques is fundamental in forensic drug analysis. In the wake of the occurrence of large numbers of new psychoactive substances possessing similar chemical structures as already known ones, focus has been placed on applied criteria for their univocal identification. These criteria vary, obviously, depending on the applied technique and analytical approach. However, when two or more substances are proven to have similar analytical properties, these criteria no longer apply, which imply that complementary techniques have to be used in their differentiation.This work describes the synthesis of some structural analogues to synthetic cannabinoids and cathinones based on the evolving patterns in the illicit drug market. Six synthetic cannabinoids and six synthetic cathinones were synthesized, that, at the time for this study, were not as yet found in drug seizures. Further, a selection of their spectroscopic data is compared to those of already existing analogues; mainly isomers and homologues. The applied techniques were mass spectrometry (MS), Fourier transformed infrared (FTIR, gas phase) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. In total, 59 different compounds were analyzed with the  selected techniques.The results from comparison of spectroscopic data showed that isomeric substances may in some cases be difficult to unambiguously identify based only on their GC-MS EI spectra. On the other hand, GC-FTIR demonstrated more distinguishable spectra. The spectra for the homologous compounds showed however, that the GC-FTIR technique was less successful compared to GC-MS. Also a pronounced fragmentation pattern for some of the cathinones was found.In conclusion, this thesis highlights the importance of using complementary techniques for the univocal identification of synthetic cannabinoids and cathinones. By increasing the number of analogues investigated, the more may be learnt about the capabilities of different techniques for structural differentiations, and thereby providing important identification criteria leading to trustworthy forensic evidence.
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20.
  • Cheng, Tuck Seng, et al. (author)
  • Circulating free insulin-like growth factor-I and prostate cancer : a case-control study nested in the European prospective investigation into cancer and nutrition
  • 2024
  • In: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 24:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk.METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics.RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade.CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.
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21.
  • Chung, Sui Chu, et al. (author)
  • A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer
  • 2009
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:1, s. 174-182
  • Journal article (peer-reviewed)abstract
    • In the light of findings indicating that cannabinoids can affect the proliferation of a number of cancer cell types and that cannabinoid receptor expression is higher in prostate cancer cell lines than in non-malignant cells, we investigated whether the level of cannabinoid 1 receptor immunoreactivity (CB(1)IR) in prostate cancer tissues is associated with disease severity and outcome. Formalin-fixed paraffin-embedded non-malignant and tumour tissue samples from patients who were diagnosed with prostate cancer at a transurethral resection for voiding problems were used. CB(1)IR, which was scored in a total of 399 cases, was associated with the epithelial cell membranes, with little staining in the stroma. Patients with a tumour CB(1)IR score greater or equal to the median (2) had a significantly higher proportion of Gleason scores 8-10, metastases at diagnosis, tumour size and rate of cell proliferation at diagnosis than patients with a score<2. For 269 cases, tumour CB(1)IR was measured for patients who only received palliative therapy at the end stages of the disease, allowing the influence of CB(1)IR upon the disease outcome to be determined. Receiver operating characteristic (ROC) curves showed an area under the curve of 0.67 (95% confidence limits 0.59-0.74) for CB(1)IR in the tumour. CB(1)IR in non-malignant tissue was not associated with disease outcome. A tumour CB(1)IR score >or=2 was associated with a significantly lower disease specific survival. A Cox proportional hazards regression indicated that the tumour CB(1)IR score and the Gleason score were independent prognostic variables. It is concluded that a high tumour CB(1)IR score is associated with prostate cancer severity and outcome.
  •  
22.
  • Dorsch, Sven, et al. (author)
  • Heat Driven Transport in Serial Double Quantum Dot Devices
  • 2021
  • In: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 21:2, s. 988-994
  • Journal article (peer-reviewed)abstract
    • Studies of thermally induced transport in nanostructures provide access to an exciting regime where fluctuations are relevant, enabling the investigation of fundamental thermodynamic concepts and the realization of thermal energy harvesters. We study a serial double quantum dot formed in an InAs/InP nanowire coupled to two electron reservoirs. By means of a specially designed local metallic joule-heater, the temperature of the phonon bath in the vicinity of the double quantum dot can be enhanced. This results in phonon-assisted transport, enabling the conversion of local heat into electrical power in a nanosized heat engine. Simultaneously, the electron temperatures of the reservoirs are affected, resulting in conventional thermoelectric transport. By detailed modeling and experimentally tuning the interdot coupling, we disentangle both effects. Furthermore, we show that phonon-assisted transport is sensitive to excited states. Our findings demonstrate the versatility of our design to study fluctuations and fundamental nanothermodynamics.
  •  
23.
  • Ekström, Maria, 1988, et al. (author)
  • Towards phonon routing: controlling propagating acoustic waves in the quantum regime
  • 2019
  • In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 21:12
  • Journal article (peer-reviewed)abstract
    • We explore routing of propagating phonons in analogy with previous experiments on photons. Surface acoustic waves (SAWs) in the microwave regime are scattered by a superconducting transmon qubit. The transmon can be tuned on or off resonance with the incident SAW field using an external magnetic field or the Autler-Townes effect, and thus the reflection and transmission of the SAW field can be controlled in time. We observe 80% extinction in the transmission of the low power continuous signal and a 40 ns rise time of the router. The slow propagation speed of SAWs on solid surfaces allows for in-flight manipulations of the propagating phonons. The ability to route short, 100 ns, pulses enables new functionality, for instance to catch an acoustic phonon between two qubits and then release it in a controlled direction.
  •  
24.
  • Fowler, Christopher J., et al. (author)
  • Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer
  • 2013
  • In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1831:10, s. 1579-1587
  • Journal article (peer-reviewed)abstract
    • Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide. Here we have investigated whether the expression levels of FAAH and CB1 receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB1 receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB1IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB1IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB1IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15 year of disease-specific survival (%) of 68 +/- 7 (low endoglin, low FAAH), 45 +/- 11 (high endoglin, low FAAH), 77 +/- 6 (low endoglin, high FAAH) and 21 +/- 10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a-1b relative to stages 2-4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
  •  
25.
  • Habib, Iman, et al. (author)
  • DGTS: Integrated Typing and Pointing
  • 2009
  • In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 9783642036576 ; , s. 232-235
  • Conference paper (peer-reviewed)abstract
    • Capacitive sensing is used in many different fields of application. Ithas been implemented in such devices as mobile phones and remote controls. However, up until now the physical sensing area has remained limited despite the widespread use of larger input devices such as keyboards. We present DGTS, which seamlessly integrates keyboard typing and cursor pointing. This input device offers multi-finger operation for scrolling and other specialized input commands. The objective of this work is to replace computer mice and touchpads by integrating capacitive sensing into a layer within the keyboard thereby reducing the space required for pointing devices. This paper gives the technical background, shows our contribution, and concludes with initial tests.
  •  
26.
  • Halin Bergström, Sofia, et al. (author)
  • High-grade tumours promote growth of other less-malignant tumours in the same prostate
  • 2021
  • In: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 253:4, s. 396-403
  • Journal article (peer-reviewed)abstract
    • Prostate cancer is a multifocal disease, but if and how individual prostate tumours influence each other is largely unknown. We therefore explored signs of direct or indirect tumour–tumour interactions in experimental models and patient samples. Low‐metastatic AT1 and high‐metastatic MatLyLu (MLL) Dunning rat prostate cancer cells were injected into separate lobes of the ventral prostate of immunocompetent rats. AT1 tumours growing in the same prostate as MLL tumours had increased tumour size and proliferation compared to AT1 tumours growing alone. In addition, the vasculature and macrophage density surrounding the AT1 tumours were increased by MLL tumour closeness. In patient prostatectomy samples, selected to contain an index tumour [tumour with the highest grade, International Society of Urological Pathology (ISUP) grade 1, 2, 3 or 4] and a low‐grade satellite tumour (ISUP grade 1), cell proliferation in low‐grade satellite tumours gradually increased with increasing histological grade of the index tumour. The density of blood vessels and CD68+ macrophages also increased around the low‐grade satellite tumour if a high‐grade index tumour was present. This suggests that high‐grade tumours, by changing the prostate microenvironment, may increase the aggressiveness of low‐grade lesions in the organ. Future studies are needed to explore the mechanisms behind tumour–tumour interactions and their clinical importance.
  •  
27.
  • Hammarsten, Peter, et al. (author)
  • Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome
  • 2019
  • In: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 32, s. 1310-1319
  • Journal article (peer-reviewed)abstract
    • Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975–1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts. © 2019, The Author(s).
  •  
28.
  • Hammarsten, Peter, et al. (author)
  • Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.
  • 2010
  • In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:4, s. 1245-1255
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients. EXPERIMENTAL DESIGN: We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR. The staining pattern was scored and related to clinicopathologic parameters and to outcome. RESULTS: Low phosphorylation of EGFR in prostate epithelial cells, both in the tumor and surprisingly also in the surrounding nonmalignant tissue, was associated with significantly longer cancer-specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR immunoreactivity was significantly correlated to tumor cell proliferation, tumor vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients with metastases had significantly higher immunoreactivity for tumor and nonmalignant epithelial pEGFR compared with patients without metastases. CONCLUSIONS: Low pEGFR immunoreactivity is associated with the favorable prognosis in prostate cancer patients and may provide information about which patients with Gleason score 6 and 7 tumors that will survive their disease even without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors give prognostic information.
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29.
  • Hammarsten, Peter, et al. (author)
  • Phospho-Akt Immunoreactivity in Prostate Cancer : Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression
  • 2012
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e47994-
  • Journal article (peer-reviewed)abstract
    • Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms. Methodology/Principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8-10, but not for patients with Gleason score 6-7. Conclusions/Significance: Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6-7.
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30.
  • Huang, Junchi, et al. (author)
  • Osteoclasts directly influence castration-resistant prostate cancer cells
  • 2022
  • In: Clinical and Experimental Metastasis. - : Springer Nature. - 0262-0898 .- 1573-7276. ; 39:5, s. 801-814
  • Journal article (peer-reviewed)abstract
    • Metastasis to bone is the leading cause of death from prostate cancer. Interaction between tumor cells and bone cells can promote progression and influence tumor phenotype. It is known that prostate cancer cells support osteoclast differentiation, and degradation of bone matrix by osteoclasts releases growth factors stimulating tumor cell proliferation and invasion. In the present study osteolytic (PC-3) and osteoblastic (LNCaP-19) castration-resistant prostate cancer (CRPC) cells were co-cultured with mature osteoclasts or their precursor cells (RAW 264.7) to characterize direct effects of mature osteoclasts on CRPC cells. Osteoclasts increased proliferation and decrease apoptosis of CRPC cells as assessed with flow cytometry. RNA sequencing revealed that osteolytic CRPC cells were more responsive to osteoclast stimulation regarding gene expression, but the overall induced expression patterns were similar between the prostate cancer cell lines. Genes related to DNA repair were upregulated by osteoclasts, while genes related to endoplasmic reticulum stress-induced apoptosis and cholesterol synthesis were downregulated. The results of this study shows that osteoclasts directly influence CRPC cells, increasing proliferation, decreasing apoptosis, and affecting gene expression pathways that can affect sensitivity to DNA damage and endoplasmic reticulum function. This suggests targeting of osteoclasts to be a possible way to affect efficacy of other drugs by combination regimens in treating prostate cancer metastases.
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31.
  •  
32.
  • Hägglöf, Christina, et al. (author)
  • TMPRSS2-ERG Expression Predicts Prostate Cancer Survival and Associates with Stromal Biomarkers
  • 2014
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
  • Journal article (peer-reviewed)abstract
    • The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFR beta and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.
  •  
33.
  • Jakobsen, Lasse H., et al. (author)
  • Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy : an international study of 264 real-world patients
  • 2020
  • In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:4, s. 661-671
  • Journal article (peer-reviewed)abstract
    • Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: −0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.
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34.
  • Jonsson, Linus, 1986, et al. (author)
  • Self-Determination Theory in Pratice
  • 2013
  • In: Book of Abstract. ENYSSP 9th Annual International Workshop. ; 9
  • Conference paper (other academic/artistic)
  •  
35.
  •  
36.
  • Josefsson, Andreas, et al. (author)
  • Bias errors due to leakage effects when estimating frequency response functions
  • 2012
  • In: Shock and Vibration. - : IOS Press. - 1070-9622 .- 1875-9203. ; 19:6, s. 1257-1266
  • Journal article (peer-reviewed)abstract
    • Frequency response functions are often utilized to characterize a system's dynamic response. For a wide range of engineering applications, it is desirable to determine frequency response functions for a system under stochastic excitation. In practice, the measurement data is contaminated by noise and some form of averaging is needed in order to obtain a consistent estimator. With Welch's method, the discrete Fourier transform is used and the data is segmented into smaller blocks so that averaging can be performed when estimating the spectrum. However, this segmentation introduces leakage effects. As a result, the estimated frequency response function suffers from both systematic (bias) and random errors due to leakage. In this paper the bias error in the H 1 and H2-estimate is studied and a new method is proposed to derive an approximate expression for the relative bias error at the resonance frequency with different window functions. The method is based on using a sum of real exponentials to describe the window's deterministic autocorrelation function. Simple expressions are derived for a rectangular window and a Hanning window. The theoretical expressions are verified with numerical simulations and a very good agreement is found between the results from the proposed bias expressions and the empirical results.
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37.
  • Josefsson, Andreas, 1979, et al. (author)
  • Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer
  • 2017
  • In: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 77:8, s. 849-858
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC). METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study. CTCs were analysed for expression of PSA prostate specific membrane antigen (PSMA) and epidermal growth factor receptor (EGFR) before and three months after ADT and related to progression. RESULTS: At inclusion, 46 out of 53 patients (87%) were CTC-positive with a sensitivity and specificity for distant metastases (M1) of 98% and 75%, respectively. In patients with M1-disease, EGFR-detection in CTC was an independent prognostic marker for progression-free survival, whereas PSA and alkaline phosphatase serum levels, Gleason score, or T-stage were not. EGFR-positive patients had significantly shorter time to progression (5 months) compared to EGFR-negative patients (11 months) (P < 0.05). CONCLUSIONS: In this explorative study, CTCs were detected in 98% of M1 patients and detection of EGFR in CTCs was strongly associated with poor outcome, which indicated that phenotypical analysis of CTC could be a promising prognostic marker of ADT-response in castration-naïve metastatic PC patients. Prostate 77:849–858, 2017.
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38.
  • Josefsson, Andreas, 1979, et al. (author)
  • Circulating tumor cells mirror bone metastatic phenotype in prostate cancer
  • 2018
  • In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9, s. 29403-29413
  • Journal article (peer-reviewed)abstract
    • © Josefsson A et al. Circulating tumor cells (CTCs) are promising biomarkers in prostate cancer (PC) because they derive from primary tumor and metastatic tissues. In this study, we used quantitative real-time PCR (qPCR) to compare the expression profiles of 41 PC-related genes between paired CTC and spinal column metastasis samples from 22 PC patients that underwent surgery for spinal cord compression. We observed good concordance between the gene expression profiles in the CTC and metastasis samples in most of the PC patients. Expression of nine genes (AGR2, AKR1C3, AR, CDH1, FOLH1, HER2, KRT19, MDK, and SPINK1) showed a significant correlation between the CTC and metastasis samples. Hierarchical clustering analysis showed a similar grouping of PC patients based on the expression of these nine genes in both CTC and metastasis samples. Our findings demonstrate that CTCs mirror gene expression patterns in tissue metastasis samples from PC patients. Although low detection frequency of certain genes is a limitation in CTCs, our results indicate the potential for CTC phenotyping as a tool to improve individualized therapy in metastatic prostate cancer.
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39.
  • Josefsson, Andreas, et al. (author)
  • Control Algorithm For Sine Excitation On Nonlinear Systems
  • 2006
  • Conference paper (other academic/artistic)abstract
    • When using electrodynamic vibration exciters to excite structures, the actual force applied to the structure under test is the reaction force between the exciter and the structure. The magnitude and phase of the reaction force is dependent upon the characteristics of the structure and exciter. Therefore the quality of the reaction force i.e. the force applied on the structure depends on the relationship between the exciter and structure under test. Looking at the signal from the force transducer when exciting a structure with a sine wave, the signal will appear harmonically distorted within the regions of the resonance frequencies. This phenomenon is easily observed when performing tests on lightly damped structures. The harmonic distortion is a result of nonlinearities produced by the shaker when undergoing large amplitude vibrations, at resonances. When dealing with non-linear structures, it is of great importance to be able to keep a constant force level as well as a non-distorted sine wave in order to get reliable results within the regions of the resonance frequencies. This paper presents theoretical methods that can be used to create a non-distorted sinusoidal excitation signal with constant force level.
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40.
  • Josefsson, Andreas, 1979-, et al. (author)
  • Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
  • 2023
  • In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:4, s. 372-380
  • Journal article (peer-reviewed)abstract
    • Background: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).Materials and Methods: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.Results: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.Conclusion: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
  •  
41.
  • Josefsson, Andreas, 1979, et al. (author)
  • Effect of docetaxel added to bicalutamide in Hormone-Naive non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
  • 2023
  • In: Acta Oncologica. - 0284-186X. ; 62:4, s. 372-380
  • Journal article (peer-reviewed)abstract
    • BackgroundHistorically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).Materials and MethodsPatients with hormone-naive, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m(2), q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.ResultsBetween 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.ConclusionDocetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
  •  
42.
  • Josefsson, Andreas, 1979, et al. (author)
  • Gene expression alterations during development of castration-resistant prostate cancer are detected in circulating tumor cells
  • 2020
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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43.
  • Josefsson, Andreas (author)
  • Identification and Simulation Methods for Nonlinear Mechanical Systems Subjected to Stochastic Excitation
  • 2011
  • Doctoral thesis (other academic/artistic)abstract
    • With an ongoing desire to improve product performance, in combination with the continuously growing complexity of engineering structures, there is a need for well-tested and reliable engineering tools that can aid the decision making and facilitate an efficient and effective product development. The technical assessment of the dynamic characteristics of mechanical systems often relies on linear analysis techniques which are well developed and generally accepted. However, sometimes the errors due to linearization are too large to be acceptable, making it necessary to take nonlinear effects into account. Many existing analysis techniques for nonlinear mechanical systems build on the assumption that the input excitation of the system is periodic and deterministic. This often results in highly inefficient analysis procedures when nonlinear mechanical systems are studied in a non-deterministic environment where the excitation of the system is stochastic. The aim of this thesis is to develop and validate new efficient analysis methods for the theoretical and experimental study of nonlinear mechanical systems under stochastic excitation, with emphasis on two specific problem areas; forced response simulation and system identification from measurement data. A fundamental concept in the presented methodology is to model the nonlinearities as external forces acting on an underlying linear system, and thereby making it possible to use much of the linear theories for simulation and identification. The developed simulation methods utilize a digital filter to achieve a stable and condensed representation of the linear subparts of the system which is then solved recursively at each time step together with the counteracting nonlinear forces. The result is computationally efficient simulation routines, which are particularly suitable for performance predictions when the input excitation consist of long segments of discrete data representing a realization of the stochastic excitation of the system. Similarly, the presented identification methods take advantage of linear Multiple-Input-Multiple-Output theories for random data by using the measured responses to create artificial inputs which can separate the linear system from the nonlinear parameters. The developed methods have been tested with extensive numerical simulations and with experimental test rigs with promising results. Furthermore, an industrial case study of a wave energy converter, with nonlinear characteristics, has been carried out and an analysis procedure capable of evaluating the performance of the system in non-deterministic ocean waves is presented.
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44.
  •  
45.
  • Josefsson, Andreas, 1979-, et al. (author)
  • Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance
  • 2012
  • In: Scandinavian Journal of Urology and Nephrology. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 46:4, s. 247-257
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting. Material and methods. From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf).Results: In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours.Conclusions: Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.
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46.
  • Josefsson, Andreas, et al. (author)
  • On Nonlinear Parameter Estimation with Random Noise Signals
  • 2007
  • Conference paper (peer-reviewed)abstract
    • In the field of nonlinear dynamics it is essential to have well tested and reliable tools for estimating the nonlinear parameters from measurement data. This paper presents an identification technique based on using random noise signals, as initially developed by Julius S. Bendat. With this method the nonlinearity is treated as a feedback forcing term acting on an underlying linear system. The parameter estimation is then performed in the frequency domain by using conventional MISO/MIMO techniques. To apply this method successfully it is necessary to have some pre-information about the model structure and thus methods for nonlinear characterization and localization are studied. The paper also demonstrates the various ways the method can be formulated for multiple-degree-of-freedoms. The implementation of the method is illustrated with simulated data as well as a practical application, where the method is used to create a dynamic model of a test-rig with a significant nonlinearity.
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47.
  • Josefsson, Andreas, 1979-, et al. (author)
  • Performance of 4Kscore as a Reflex Test to Prostate-specific Antigen in the GÖTEBORG-2 Prostate Cancer Screening Trial
  • 2024
  • In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560.
  • Journal article (peer-reviewed)abstract
    • Background and objective: We investigated whether adding 4Kscore as a reflex test to prostate-specific antigen (PSA) could improve the screening algorithm for prostate cancer (PC). Methods: In the GÖTEBORG-2 PC screening trial, 38 000men (50–60 yr) were invited to PSA testing and, if elevated, followed by magnetic resonance imaging (MRI). For 571 men with PSA ≥3.0 ng/ml and evaluable outcomes, 4Kscore was calculated. The performance using a prespecified 4Kscore cutoff of 7.5% was evaluated. Key findings and limitations: The area under the curve for 4Kscore to identify intermediate- and high-risk PC was 0.84 (95% confidence interval 0.79–0.89), and the positive predictive value, and negative predictive value were 15% (0.12–0.20) and 99% (97–100%), respectively. Of the 54 men diagnosed with intermediate- or high-grade PC, two had a 4Kscore cutoff below 7.5%, both with organ-confined intermediate-risk PC. Per 1000 men with elevated PSA, adding 4Kscore would have resulted in avoidance of MRI for 408 (41%) men, biopsies for 95 (28% reduction) men, and diagnosis of 23 low-grade cancers (23% reduction) while delaying the diagnosis of four men with intermediate-grade cancers (4%). Conclusions and clinical implications: Including 4Kscore as a reflex test for men with elevated PSA reduces the need for MRI and biopsy markedly, and results in less overdiagnosis of low-grade PC at the cost of delaying the diagnosis of intermediate-grade PC in a few men. These results add further evidence for including new blood-based biomarkers in addition to PSA to improve the harm and benefit ratio of PC screening and reduce the need for resource-demanding MRI and biopsies. Patient summary: In this study, 4Kscore, a blood-based biomarker, as a reflex test for men with elevated prostate-specific antigen (PSA), reduces the need for magnetic resonance imaging and biopsy. These results support the inclusion of new blood-based biomarkers in addition to PSA.
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48.
  • Josefsson, Andreas, et al. (author)
  • Performance of a Wave Energy Converter with Mechanical Energy Smoothing
  • 2011
  • Conference paper (peer-reviewed)abstract
    • A wave energy converter which uses a power balancing mechanism for turning intermittent and irregular wave motion input to smoothed continuous electrical power output is studied by combined scale-model testing and numerical simulation. The studied concept consists of a moored floating device together with a moving mass which is used to store instantaneous incoming power and deliver a controllable load to an electric generator over a unidirectional rotating shaft. A mathematical model describing the vertical dynamics of the wave energy converter is presented. The wave-body interaction is modelled with linear potential theory and a nonlinear rigid-body model describes the power take-off system. Experimental data from a scale-model test is utilized to validate and update the linear hydrodynamic model. A simulation study is then carried out in order to investigate the performance characteristics of the coupled hydrodynamic and mechanical system. An efficient time-domain algorithm is developed in order to simulate the discontinuous nonlinear characteristics of the combined system in non-deterministic wave situations. The simulation result provides a prediction of the absorbed power and capture ratio which can be used to evaluate the performance in different wave situations. The developed analysis procedure demonstrates its capability to produce computationally efficient performance predictions suitable for design evaluation and optimisation.
  •  
49.
  • Josefsson, Andreas, 1979- (author)
  • Prognostic markers in prostate cancer : studies of a watchful waiting cohort with long follow up
  • 2011
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Prostate Cancer (PC) is a common and highly variable disease. Using current diagnostic methods, the prostate specific antigen (PSA) blood test and histological grading of prostate tissue needle biopsies, it is often difficult to evaluate whether the patient has a PC that requires active treatment or not. The absolute majority of all 10,000 cases of PCs diagnosed annually in Sweden have tumours graded as Gleason score (GS) 6-7 and a PSA value in blood below 10. Many of these are harmless and can be left without active treatment and hence spared problematic post-therapy side-effects, others are highly malignant and require early diagnosis and treatment. Better prognostic markers are needed and the aim of this study was to evaluate prognostic markers and to test if these markers could identify patients with indolent tumours. Methods: We have studied tumour material from 419 men consecutively diagnosed with PC at transurethral resection (1975-1990). The majority of these patients (295) had no metastasis at diagnosis and was not given any curative treatment and only hormonal treatment upon symptoms from metastatic progression. Standard histological sections and tissue microarrays (TMA) from these tumours and surrounding normal prostate tissue were stained and evaluated for cell proliferation (Ki67), blood vessels (endoglin and von Willebrand factor, vWf) and the extracellular matrix component hyaluronan (HA). An orthotopic rat PC model was used to explore hyaluronan staining, hyaluronic acid synthase (HAS)-1 mRNA levels and the effect of local HA treatment on tumour growth. Results: Tumour cell proliferation (Ki67) and the density of intra-tumoural endoglin stained blood vessels were independent prognostic markers (i.e. they added prognostic information to the conventional prognostic markers; clinical stage and GS). None of the GS 6 patients with low staining for both Ki67 and endoglin died of PC within 15 years of follow-up. High HA staining in the tumour epithelium and stroma was a negative prognostic marker of cancer specific survival but they were not independent of GS. High HA staining and high vascular density in the stroma of the surrounding morphologically normal prostate were prognostic for short cancer specific survival. Implantation of tumour cells in the normal rat prostate resulted in an increase in HA and HAS-1 mRNA levels in the prostate tissue surrounding prostate tumours. Concurrently intra-prostatic injection of HA also stimulated tumour growth. Conclusions: By evaluating both tumour cell proliferation (Ki67) and vascular density, it is possible to identify patients with very low risk of cancer specific death in the absence of active treatment. Prostate tumours influence the surrounding non-malignant prostate tissue, for example they cause an increased angiogenesis and synthesis of hyaluronan. Such responses can possibly be used to diagnose PC and to evaluate PC aggressiveness.
  •  
50.
  • Josefsson, Andreas, et al. (author)
  • Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome
  • 2011
  • In: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 179:4, s. 1961-1968
  • Journal article (peer-reviewed)abstract
    • Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome.
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