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1.
  • Höglund, Odd, et al. (author)
  • Online dosimetri för temoporfin-medierad interstitiell fotodynamisk terapi av prostata på hund
  • 2012
  • In: SUF-nytt. - 2001-3981. ; , s. 34-34
  • Other publication (peer-reviewed)abstract
    • Bakgrund: Prostatacancer är vanligt förekommande hos män och orsakar fler dödsfall än andra cancerformer, förutom lungcancer. Ca 1 av 6 män får diagnosen prostatacancer under sin livstid (1, 2). Eftersom kirurgisk behandling och strålning av prostatavävnad orsakar biverkningar, framförallt impotens och inkontinens söks alternativa behandlingsmetoder. Interstitiell fotodynamisk terapi (PDT) är ett alternativ till att behandla tumöromvandlad prostatavävnad. Vid PDT bildas cytotoxiska radikaler som orsakar vävnadsnekros. Med hjälp av Spectracures P18-system erbjuds kontrollerad dosering av energimängden som överförs till prostatan. Syftet med denna studie var att verifiera korrelationen mellan energidos, vävnadsrespons och tröskeldos för induktion av nekros i prostata.Metod: Nio destinationsuppfödda friska beaglar användes i studien. Tre dagar före PDT gavs Temoporfin (Foscan) för fotosensibilisering. Med hjälp av transrektalt ultraljud bedömdes prostatans storlek och dosberäkning utfördes. Sju brakyterapinålar fördes in i prostatan via perineum under guidning av ultraljud och dosberäknad PDT utfördes. Sju dagar efter behandlingen avlivades hundarna.Resultat: Vid histopatologisk undersökning sågs nekroser i prostatan och förändringar i periprostata-vävnaden. En dos-responskorrelation för induktion av nekros bestämdes till 20-30 J/cm2. Online-dosimetri resulterade i mer fokuserad behandling och mindre skada på omkringliggande vävnad jämfört med PDT utan dosimetri.Konklusion: Denna studie visar att temoporfin-medierad interstitiell fotodynamisk terapi kan åstadkomma nekros av prostatavävnad. Metoden är en potentiell alternativ behandling till prostatektomi och brakyterapi.1. National Cancer Institute http://www.cancer.org/Cancer/ProstateCancer/OverviewGuide/prostate-cancer-overview-key-statistics 2. American Cancer Society 2008 Cancer Facts and Figures
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  • Wu, Ping-Hsun, 1982-, et al. (author)
  • Novel biomarkers detected by proteomics predict death and cardiovascular events in hemodialysis patients
  • Other publication (other academic/artistic)abstract
    • Background. End-stage kidney disease increases mortality and the risk of cardiovascular (CV) disease. It is crucial to explore novel biomarkers to predict CV disease in the complex setting of patients receiving hemodialysis (HD). This study investigated the association between 92 targeted proteins with all-cause death, CV death, and composite vascular events (CVEs) in HD patients.Methods. From December 2010 to March 2011, 331 HD patients were included and followed prospectively for 5 years. Serum was analyzed for 92 CV-related proteins using Proseek Multiplex Cardiovascular I panel, a high-sensitivity assay based on proximity extension assay (PEA) technology. The association between biomarkers and all-cause death, CV death, and CVEs was evaluated by Cox-regression analyses.Results. Of the PEA-based proteins, we identified 20 proteins associated with risk of all-cause death, 7 proteins associated with risk of CV death, and 17 proteins associated with risk of CVEs, independent of established risk factors. Interleukin-8 (IL-8), T-cell immunoglobulin and mucin domain 1 (TIM-1), and C-C motif chemokine 20 (CCL20) were associated with increased risk of all-cause death, CV death, and CVE  in multivariable-adjusted models. Stem cell factor (SCF) and Galanin peptides (GAL) were associated with both decreased risk of all-cause death and CV death.Conclusions. IL-8, TIM-1, and CCL20 predicted death and CV outcomes in HD patients. Novel findings were that SCF and GAL were associated with a lower risk of all death and CV death. The SCF warrants further study with regards to its possible biological effect in HD patients.
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  • Wu, Ping-Hsun, 1982-, et al. (author)
  • The effect of fibroblast growth factor 23, vitamin D, and renal function on all-cause and cardiovascular mortality : The MrOS Sweden Study
  • Other publication (other academic/artistic)abstract
    • Background: Fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), estimated glomerular filtration rate (eGFR), and vitamin D have been linked to mortality and cardiovascular disease, but the limited data addressed the combined effect of these factors on mortality. We investigated these different aspects of mineral bone disease biomarkers that portray independent and prognostic information in the Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort.Methods: The baseline level of FGF23, PTH, vitamin D, and eGFR was categorized as a normal and abnormal group. The mortality risk of mineral bone markers was analyzed by Kaplan-Meier curve for group difference evaluation and restricted cubic regression spline curve for continuous values of markers. We compare the importance of markers by random forest. Cox proportional regression models were used to evaluate the mortality risk of abnormal mineral bone markers components and their independent effect.Results: The MrOS cohort included 2706 men whose mean aged 75.4±3.18 years, 9.4% had diabetes, and 36.3% had hypertension. During a mean follow-up of 4.48 years, 383 all-cause deaths and 144 cardiovascular deaths were recorded. A high intact FGF23 level, low eGFR, and vitamin D deficiency were associated with increased all-cause mortality. Participants with a combination of high FGF23 level, low eGFR, and vitamin D deficiency had a twofold increased all-cause and cardiovascular mortality risk compared to those without abnormalities after adjusting for confounders. FGF23 was the most important factor related to all-cause mortality in random forest analysis, but the association was attenuated after controlling eGFR in the Cox model. In contrast, a low vitamin D remained to predict all-cause mortality independently.Conclusions: A higher FGF23, lower renal function, and lower vitamin D level are associated with increased all-cause and cardiovascular mortality in elderly men. Renal dysfunction influenced the mortality prediction of FGF23 but not vitamin D.
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  • Ahlberg, Mats Steinholtz, 1979- (author)
  • Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control study
  • Other publication (other academic/artistic)abstract
    • Background: What should trigger transition from active surveillance (AS) to radical treatment for prostate cancer (PC) remains an unanswered question. Objective:To examine the association between potential triggers and transition from AS to radical treatment.Design, Setting and Participants:Swedish register-based case-control study including men in the National Prostate Cancer Register in Sweden with low- or favorable intermediate-risk PC, starting AS from Jan 1st, 2008, to Dec 31st, 2020.Interventions: Triggers are: histopathological progression, MRI progression without histopathological progression, and only PSA progression.Outcomes measurements and statistical analysis: Probability of experiencing a trigger one year preceding treatment. Odds ratios (OR) of histopathological progression, MRI progression without histopathological progression, or only PSA progression, for transition to radical treatment, analyzed by logistic regression.Results and limitations: The study base included 846 patients, 99 cases 2008-2014, and 172 cases 2015-2020. For every case, 10 controls were chosen. Histopathological progression was strongly associated with transition to radical treatment (OR 2008-2014: 6.89, 95% confidence interval (CI) 3.78-12.56; 2015-2020: 65.03, 95% CI 35.11-120.44). MRI progression was associated with treatment 2015-2020 (adjusted OR 4.01, 95% CI 1.72-9.36) but PSA progression was not associated with treatment in any adjusted analyses. Absence of any progression was strongly associated with reduced probability of transition to treatment (adjusted OR 2008-2014: 0.24, 95% CI 0.15-0.39, adjusted OR 2015-2020: 0.08, 95% CI 0.05-0.12) but the probability of treated men not having experienced any trigger was still 27% 2015-2020. Limitations include small study-base.Conclusion: Histopathological progression during AS was increasingly strongly associated with transition to treatment but the probability of not having experienced any trigger before treatment was 27%.Patient summary: Reliance on objective signs of progression before discontinuing AS increase, but still about a quarter of treated men have not experienced progression.
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  • Häggström, Christel, et al. (author)
  • Competing risk analysis of metabolic factors and prostate cancer
  • Other publication (other academic/artistic)abstract
    • Background: Men at risk of prostate cancer are also at risk of competing events but this has been ignored in most studies of metabolic aberrations and prostate cancer. The aim of this study was to assess probabilities of prostate cancer and prostate cancer death by use of competing risk analysis.Methods: In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index, blood pressure, glucose, total cholesterol, and triglycerides were collected from 285 040 men. Probabilities of prostate cancer, prostate cancer death and competing events, i.e. all-cause death or death from other causes, respectively, were calculated for men with normal (bottom 84%) and high (top 16%) levels of each metabolic factor and a composite score based on all metabolic factorsResults: During follow up, 5893 men were diagnosed with prostate cancer, 1013 men died of prostate cancer, and 26 328 men died of other causes. Men with high levels of metabolic factors had decreased probability of prostate cancer, similar probability of prostate cancer death, and increased probability of other causes of death compared to men with normal levels. After 1996, when prostate specific antigen was used for detection of prostate cancer, men up to 80 years with normal levels of metabolic factors had 13% probability of prostate cancer and 37% probability of death from all causes. For men with high levels of metabolic factors, corresponding probabilities were 12% and 47%.Conclusions: Men with metabolic aberrations had a decreased probability of prostate cancer but a substantially higher probability of death from all causes.
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  • Kerzeli, Iliana Kyriaki, et al. (author)
  • Proximity Extension Assay reveals MMP12 in plasma as a predictor of outcome in urothelial bladder cancer
  • Other publication (other academic/artistic)abstract
    • Background Urothelial bladder cancer (UBC) is most-frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact quality of life. Biomarkers for patient stratification can help to avoid unnecessary interventions whilst indicating aggressive measures when required.Methods Proximity Extension Assay (PEA) was utilised to analyse plasma (n=90) and urine (n=40) samples from 90 newly-diagnosed and treatment-naïve UBC patients with an immuno-oncology protein panel. Public single-cell and bulk RNA sequencing data from patient tumour tissues and a murine OH-BBN induced UBC model were also explored. Results Plasma samples from muscle-invasive UBC patients displayed higher levels of MMP7 and CCL23 compared to NMIBC patients, whereas urine samples displayed higher levels of CD27 and CD40 in the NMIBC group. Increased MMP12 plasma levels were identified as an independent marker of poor survival outcome and this finding was further validated in an independent cohort. Moreover, scRNA-seq data analysis indicated tumour infiltrating macrophages as a putative source of MMP12. Conclusion The local production, but systemic diffusion of MMP12, suggests that MMP12 could be an important biomarker to complement histopathology-based risk stratification. Additionally, it may represent a pharmacological target in bladder cancer.
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