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Buskbjerg Cecilie R. Zachariae Robert Agerbæk Mads Gravholt Claus H. Haldbo-Classen Lene Hosseini S. M. Hadi Amidi Ali 《Brain imaging and behavior》2022,16(1):199-210
Brain Imaging and Behavior - A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the... 相似文献
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Karin Birkenkamp-Demtröder Emil Christensen Iver Nordentoft Michael Knudsen Ann Taber Søren Høyer Philippe Lamy Mads Agerbæk Jørgen Bjerggaard Jensen Lars Dyrskjøt 《European urology》2018,73(4):535-540
Of the patients undergoing radical cystectomy, 20–80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes. Patients were prospectively recruited between 2013 and 2017. Patients with metastatic relapse had significantly higher ctDNA levels compared with disease-free patients (p < 0.001). The median positive lead time between ctDNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0–932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions.
Patient summary
Measurement of tumour-specific mutations in plasma and urine may be a powerful tool to monitor response during treatment and identify early signs of metastatic disease. 相似文献3.
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Emil Christensen Karin Birkenkamp-Demtröder Iver Nordentoft Søren Høyer Kirstin van der Keur Kim van Kessel Ellen Zwarthoff Mads Agerbæk Torben Falck Ørntoft Jørgen Bjerggaard Jensen Lars Dyrskjøt 《European urology》2017,71(6):961-969
Background
Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment.Objective
To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations.Design, setting, and participants
Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non–muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n = 216, Cx n = 27) and plasma samples (NMIBC n = 39, Cx n = 27) from patients harbouring mutations were subsequently screened using ddPCR assays.Outcome measurements and statistical analysis
Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied.Results and limitations
In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p = 0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p = 0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study.Conclusions
Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer.Patient summary
Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays. 相似文献5.
Munksgaard PP Mansilla F Brems Eskildsen AS Fristrup N Birkenkamp-Demtröder K Ulhøi BP Borre M Agerbæk M Hermann GG Orntoft TF Dyrskjøt L 《British journal of cancer》2011,105(9):1379-1387
Background:
Markers for outcome prediction in bladder cancer are urgently needed. We have previously identified a molecular signature for predicting progression in non-muscle-invasive bladder cancer. ANXA10 was one of the markers included in the signature and we now validated the prognostic relevance of ANXA10 at the protein level.Methods:
We investigated ANXA10 expression by immunohistochemistry using a tissue microarray with 249 Ta and T1 urothelial carcinomas. The expression of ANXA10 was also investigated in an additional set of 97 more advanced tumours. The functional role of ANXA10 in cell lines was investigated by siRNA-mediated ANXA10 knockdown using wound-healing assays, proliferation assays, and ingenuity pathway analysis.Results:
Low expression of ANXA10 correlated with shorter progression-free survival in patients with stage Ta and T1 tumours (P<0.00001). Furthermore, patients with more advanced tumours and low ANXA10 expression had an unfavourable prognosis (P<0.00001). We found that ANXA10 siRNA transfected cells grew significantly faster compared with control siRNA transfected cells. Furthermore, a wound-healing assay showed that ANXA10 siRNA transfected cells spread along wound edges faster than control transfected cells.Conclusion:
We conclude that ANXA10 may be a clinical relevant marker for predicting outcome in both early and advanced stages of bladder cancer. 相似文献6.
Cognitive impairment and potential biological and psychological correlates of neuropsychological performance in recently orchiectomized testicular cancer patients
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F. Andreasen H. Agerbæk P. Bjerregaard H. Gøtzsche 《European journal of clinical pharmacology》1981,19(4):293-299
Summary Seven patients with cardiac arrhythmias were given amiodarone 400 mg intravenously over 2 min, and 2–4 days later the same dose was given orally. The serum concentration of amiodarone was determined by HPLC; the sensitivity of the analysis was 0.1 µg/ml. The time sequence of the measurements of drug concentration made conventional compartemental analysis impossible. There was large individual variation but some of the curves suggested enterohepatic circulation. The time from oral intake to the peak serum concentration was estimated to be 7.3±2.9 h (SD). The amount of drug reaching the general circulation in 24 h after oral intake averaged 42% (22–80%). After oral administration of amiodarone 200 mg 8 hourly the serum concentration before the morning dose averaged 0.61 µg/ml after 24 h, 0.76 after 48 h, 1.18 after 1 week and 1.56 µg/ml after 1 month. In one patient, who had been on amiodarone therapy for 8 months, the drug was discontinued and the serum concentration was followed over the next 3 months. The drug elimination curve suggested an elimination half life of 13.7 days. Because of instability in physiological saline protein binding could not be precisely quantitated, but only characterized as strong. No unchanged amiodarone was found in urine. The urinary excretion of iodine over 2 h after intravenous administration suggested that 5% of orally administered amiodarone was eliminated in the urine after biotransformation. No effect of the drug was observed during the first 10 days of treatment. In 2 patients with supraventricular arrhythmia, an excellent response was seen, and in one with ventricular arrhythmia there was a good response. 相似文献
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Ali Amidi Mads Agerbæk Lisa M. Wu Anders D. Pedersen Mimi Mehlsen Cecilie R. Clausen Ditte Demontis Anders D. Børglum Anja Harbøll Robert Zachariae 《Brain imaging and behavior》2017,11(3):769-783
Evidence suggests that testicular cancer (TC) and its treatment are associated with cognitive impairment. However, the underlying neural substrate and biological mechanisms are poorly understood. This study aimed to investigate changes in cognition and brain grey matter (GM) morphology in TC patients undergoing treatment, and to explore associations with immune markers, endocrine markers, and genotype. Sixty-five patients with stage I-III TC underwent assessment after surgery but prior to further treatment and again 6 months after. Twenty-two patients received chemotherapy (+CT), while 43 did not (?CT). Assessments included neuropsychological testing, whole-brain magnetic resonance imaging, and blood samples. Twenty-five healthy controls (HCs) underwent neuropsychological testing with a matching time interval. A regression-based approach was used to determine cognitive changes and longitudinal voxel-based morphometry (VBM) was performed to investigate changes in GM density in the TC groups. Compared with the HCs, both TC groups showed higher rates of cognitive decline (p?<?0.05). A trend towards greater decline was observed in?+?CT (63.6 %) compared with -CT patients (39.5 %) (p?=?0.07). VBM revealed widespread GM reductions in both TC groups, but a group-by-time interaction analysis revealed prefrontal reductions specific to the?+?CT group (p?=?0.02), which were associated with poorer cognitive performance. Poorer cognitive performance was also associated with an increase in tumor necrosis factor alpha in?+?CT patients. Furthermore, an interaction effect was found between the APOE ε4 genotype and chemotherapy on cognitive performance with ε4 carriers performing significantly worse. These findings provide novel evidence of changes in cognition and brain morphology in TC patients undergoing treatment. 相似文献
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