Publications
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Desiati, Indri; Forsell, Selma Bozorgpana; Ramberg, Håkon; Berge, Viktor; Tasken, Kristin Austlid & Giskeødegård, Guro F.
[Show all 8 contributors for this article]
(2026).
Pre-surgical immune-proteomic profiles in serum identify inflamed and suppressed immune states associated with biochemical recurrence and PSA persistence in prostate cancer.
Clinical Proteomics.
ISSN 1542-6416.
doi:
10.1186/s12014-026-09634-z.
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Abstract Background Prostate cancer progression is shaped by complex tumor-immune interactions and inflammatory processes. However, immune-related protein biomarkers associated with prognosis after radical prostatectomy remain limited. This study aimed to characterize pre-surgical serum immune-proteomic profiles associated with biochemical recurrence (Recurrence; prostate-specific antigen [PSA] ≥ 0.2 ng/mL) and PSA persistence (Persistence; PSA ≥ 0.1 ng/mL) after surgery, targeting proteins within immuno-oncology and inflammation. Method Pre-surgical serum from two independent prostate cancer cohorts (Trondheim, n = 136; Oslo, n = 87) was analyzed using the Olink Inflammation and Immuno-Oncology panels. The 34 proteins overlapping between panels were analyzed in the combined cohort. Group comparisons used one-way ANOVA with false discovery rate adjustment and multivariate modeling used partial least squares discriminant analysis with fivefold cross-validation and recursive feature elimination. Prognostic associations were evaluated using Cox proportional hazards for recurrence and logistic regression for PSA persistence. Result IL18 was consistently lower in patients with recurrence and PSA persistence compared to non-recurrent patients, suggesting reduced antitumor immune activity before surgery. PSA persistence group was characterized by lower TNFSF12, CCL19, and CD244 compared to non-recurrent patients. We observed a broader trend toward reduced protein levels across the panel in patients with PSA persistence in both cohorts, consistent with a more immune-deserted profile. The protein-based model discriminated recurrence and PSA persistence more accurately than the clinical-parameter model, which included age, PSA before surgery, biopsy Gleason Grade Group, clinical T stage, and Prostate Imaging-Reporting and Data System (PI-RADS) score (Trondheim: Recurrence AUC 0.73 vs. 0.64; Persistence AUC 0.83 vs. 0.81; Oslo: Recurrence AUC 0.77 vs. 0.54; Persistence AUC 0.89 vs. 0.63). Combining proteins and clinical parameters further improved discrimination (Trondheim: Recurrence AUC 0.75; Persistence AUC 0.91; Oslo: Recurrence AUC 0.75; Persistence AUC 0.88). Conclusion Pre-surgical serum immune-proteomic profiling revealed distinct immune states particularly associated with PSA persistence and recurrence. Serum protein signatures improved discrimination beyond presurgical clinical parameters, supporting their potential for presurgical risk stratification and treatment planning with further validation in larger independent cohorts.
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Sivanesan, Shivanthe; Ramberg, Håkon; Kristiansen, Thomas; Thapa, Suraj; Bjøre, Marthe & Berge, Viktor
[Show all 15 contributors for this article]
(2026).
Perioperative propranolol during robotic-assisted radical prostatectomy: A randomised, double-blind, placebo-controlled, pilot trial (PeP-RALP).
BJUI Compass.
7(9).
doi:
10.1002/bco2.70267.
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Qvigstad, Lars Fredrik; Aas, Kirsti; Tulipan, Andreas Julius; Hole, Knut Håkon; Storås, Anne Marie Holck & Hammarström, Clara Louise
[Show all 9 contributors for this article]
(2025).
Clinical Trial Protocol for prePSMA: A Multicenter, Randomized, Noninferiority Trial of Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as Triage for Extended Pelvic Lymph Node Dissection in Patients Scheduled for Robot-assisted Laparoscopic Radical Prostatectomy.
European Urology Focus.
11(6),
p. 915–920.
doi:
10.1016/j.euf.2025.07.010.
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Habberstad, Andreas Hanssønn; Stokke, Siril; Eri, Lars Magne; Diep, Lien My; Brennhovd, Bjørn & Berge, Viktor
(2025).
Oncological outcomes and complications after salvage robotic-assisted laparoscopic radical prostatectomy (sRALP).
Scandinavian Journal of Urology.
ISSN 2168-1805.
60,
p. 158–163.
doi:
10.2340/sju.v60.44585.
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Noor, Danyial; Baco, Eduard; Lauritzen, Peter Mæhre; Berge, Viktor; Galtung, Kristina Flor & Jacewicz, Maciej
[Show all 8 contributors for this article]
(2025).
The Effect of Preoperative Magnetic Resonance Imaging on Long-term Oncological Outcomes Following Radical Prostatectomy—A 12-year Follow-up of a Randomized Controlled Trial.
European Urology Open Science.
ISSN 2666-1691.
79,
p. 79–86.
doi:
10.1016/j.euros.2025.07.005.
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Background and objective
The effect of preoperative magnetic resonance imaging (MRI) on long-term oncological outcomes following robot-assisted laparoscopic prostatectomy (RALP) is uncertain. The objective was to investigate the effect of preoperative MRI on long-term oncological outcomes after RALP.
Methods
A single-institution follow-up study of a randomized controlled trial was conducted, which included 438 patients with biopsy-confirmed prostate cancer scheduled for RALP between December 2009 and June 2012 (NCT06429878). No patients underwent MRI prior to biopsy. Patients were randomized into two groups: one without MRI (n = 216) and one with preoperative MRI (n = 222). The primary endpoints were disease-free (DFS) and overall (OS) survival. The effect of MRI on these endpoints was estimated using hazard ratios (HRs) with 95% confidence intervals (CIs).
Key findings and limitations
The median age was 63 yr (interquartile range [IQR] 59–67), and the median prostate-specific antigen level was 7.9 ng/ml (IQR 5.9–11.4). Based on D’Amico risk classification, 112 patients were at a low risk, 220 at an intermediate risk, and 106 at a high risk. The median follow-up was 111 mo (95% CI: 104–118). The 12-yr DFS rate was 60% (95% CI: 54–65) and OS rate was 87% (95% CI: 84–90). Preoperative MRI did not improve DFS (HR 0.97, 95% CI: 0.71–1.34) or OS (HR 0.86, 95% CI: 0.52–1.40), with similar findings across clinical subgroups. Limitations include the following: oncological outcomes were secondary endpoints and MRI pathway has undergone changes since the trial.
Conclusions and clinical implications
During a 12-yr follow-up after RALP, we did not observe a statistically significant difference in DFS or OS between patients who underwent preoperative MRI and those who did not. These findings highlight the need to assess the long-term impact of prebiopsy MRI.
Patient summary
We studied whether having a magnetic resonance imaging (MRI) scan before prostate cancer surgery improves long-term outcomes. A total of 438 men with prostate cancer were included in this study and they were divided into two groups: one without MRI and one with MRI before surgery. The patients were followed for up to 12 yr, and we found no clear reduction in the risk of cancer recurrence or improved survival in patients who had undergone MRI. Today, MRI is performed routinely before biopsy, and more research is needed to evaluate whether this change has improved long-term outcomes.
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Ramberg, Håkon; Zucknick, Manuela; Barletta, Francesco; Davik, Petter; Nybøen, Åsmund & Eri, Lars Magne
[Show all 15 contributors for this article]
(2025).
Development and evaluation of a lymph node invasion risk prediction model in intermediate- and high-risk prostate cancer patients.
Acta Oncologica.
ISSN 0284-186X.
64,
p. 1446–1454.
doi:
10.2340/1651-226x.2025.43970.
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Background and purpose:
Many prostate cancer patients undergoing pelvic lymph node dissection (PLND) have no sign of lymph node invasion (LNI) during final pathological assessment. To improve preoperative staging accuracy, we developed the Oslo model, which estimates the risk of LNI based on clinical, histopathological, and magnetic resonance imaging (MRI) variables.
Patients/materials and methods:
We utilized data from 903 prostate cancer patients treated at Oslo University Hospital (OUS) to develop the model using Bayesian logistic regression. The Oslo model was validated with data from 189 patients at IRCCS Ospedale San Raffaele (HRS), 157 from St. Olav’s Hospital, and 231 from OUS. We assessed its performance against the Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti 2019 nomograms using metrics like AUC, R², decision curve analysis, and calibration plots.
Results:
The Oslo model outperformed Briganti 2019, demonstrating a higher net benefit and a 10% reduction in interventions at a 7% cutoff. Key variables included clinical T stage on MRI, Prostate Specific Antigen (PSA), prostate volume, International Society of Urological Pathology grade group, and maximum lesion length on MRI. Validation showed strong reliability in the OUS and HRS cohorts but weaker performance in the St. Olav’s cohort. The AUCs were 77% for the Oslo model, 74% for Briganti 2019, and 66% for MSKCC. Limitations include small and heterogeneous validation cohorts.
Interpretation:
The Oslo model enhances predictive performance in intermediate- and high-risk patients using easily accessible clinical and MRI data, potentially reducing unnecessary PLND interventions and assisting clinicians in treatment decision-making.
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Qvigstad, Lars Fredrik; Eri, Lars Magne; Diep, Lien My; Fosså, Sophie Dorothea; Aas, Kirsti & Berge, Viktor
(2024).
Reduction of lower urinary tract symptoms in prostate cancer patients treated with robot assisted laparoscopic prostatectomy.
Scandinavian Journal of Urology.
ISSN 2168-1805.
59,
p. 121–125.
doi:
10.2340/sju.v59.40070.
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Problem: The aim of this study was to evaluate the change in LUTS in patients treated with RALP and to assess factors that may predict an improvement of LUTS. Materials and method: In our institutional prospective research registry, 1935 patients operated in the period between 2009 and 2021 with complete baseline- and 12-month EPIC-26 questionnaire were eligible for the study. Also SF-12 data estimating general quality of life (QoL) were analyzed. A LUTS summary score was constructed from the two questions concerning voiding stream/residual and frequency, and transformed linearly to a 0-100 scale with higher scores representing less symptoms A change of 6 points or more were considered Meaningful Clinical Differences (MCD). Two summary scores were calculated from the SF-12 – a mental component score (MCS-12) and a physical component score (PCS-12). Multivariate regression was used to estimate covariates associated with postoperative MCD, MCS-12 and PCS-12. Results: Mean change of LUTS-score showed an increase of 10 points 12-months post-RALP. 52% of patients achieved MCD. In multivariate logistic regression, preoperative LUTS was statistically significant associated with MCD. Reduction of LUTS was associated improved mean score of MCS-12 and PCS-12. Discussion and conclusion: Along with information about risk for urinary incontinence after RALP, patients with LUTS at baseline must be informed that these symptoms may be reduced after RALP. In our study, this LUTS reduction was associated with better general QoL.
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Møller, Christina Tanem; Tafjord, Gunnar; Blindheim, Augun Jodis; Berge, Viktor; Fosså, Sophie Dorothea & Kulle, Bettina
(2023).
Initial management and survival of patients with primary metastatic bladder cancer before the immunotherapy era: a population-based study from Norway.
Scandinavian Journal of Urology.
ISSN 2168-1805.
58,
p. 101–108.
doi:
10.2340/sju.v58.5923.
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Before immunotherapy became part of the management of metastatic bladder cancer (mBC), systemic anti-cancer treatment comprised primarily of platinum-based chemotherapy. The objective of this study was to describe the characteristics, the initial management, overall survival (OS) and hospitalisations of patients with mBC before 2018 when immunotherapy for mBC was introduced in Norway. Material and methods: It is a nationwide population-based study of primary mBC patients (diagnosed 2008-16). Descriptive statistics were applied and stratified for four initial management options (≤150 days after BC diagnosis): chemotherapy, major local treatment (cystectomy/pelvic radiotherapy), multimodal treatment (chemotherapy and local) and no anti-cancer treatment beyond transurethral resection of bladder tumour (untreated). Group differences were evaluated by Chi-square and Kruskal–Wallis test; OS was estimated with Kaplan–Meier. Results: Of the 305 patients included, 76 (25%) patients had chemotherapy, 46 (15%) patients had major local treatment, 21 (7%) patients had multimodal treatment and 162 (53%) patients were untreated. Median OS ranged from 2.3 months (untreated) to 9.8 months (chemotherapy). Patients who received treatment had a higher rate of hospitalisation, with a median stay of three to four times that of untreated patients. Conclusion: Before immunotherapy, more than 50% of patients with primary mBC did not receive any initial anti-cancer therapy and had a poor survival. Patients treated with chemotherapy had inferior median OS compared to those treated with comparable systemic strategies in contemporary trials. Our results provide a basis for future research on treatment and survival after the introduction of immunotherapy for mBC, aiming to improve the care and outcome of patients with mBC.
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Ouellet, Véronique; Erickson, Andrew; Wiley, Kathy; Morrissey, Colm; Berge, Viktor & Moreno, Carlos S.
[Show all 31 contributors for this article]
(2022).
The movember global action plan 1 (GAP1): Unique prostate cancer tissue microarray resource.
Cancer Epidemiology, Biomarkers and Prevention.
ISSN 1055-9965.
31(4),
p. 715–727.
doi:
10.1158/1055-9965.EPI-21-0600.
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Abstract Background: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations. Methods: Three separate TMA sets were built that differ by purpose and disease state. Results: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases. Conclusions: The GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation. Impact: This resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.
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Møller, Christina Tanem; Støer, Nathalie Charlotte; Blindheim, Augun; Berge, Viktor; Tafjord, Gunnar & Fosså, Sophie Dorothea
[Show all 7 contributors for this article]
(2022).
Downstaging and survival after Neoadjuvant chemotherapy for bladder cancer in Norway; a population-based study.
BMC Cancer.
22(1).
doi:
10.1186/s12885-022-10394-w.
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Background
Neoadjuvant chemotherapy (NAC) before radical cystectomy is associated with pathological downstaging (DS) and improved overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC). Population-based studies have not unequivocally shown improved survival. The aim of this population-based study was to evaluate the effect of NAC on DS and OS in Norwegian patients with MIBC.
Methods
Patients in the Cancer Registry of Norway undergoing radical cystectomy (2008–2015) with or without NAC diagnosed with MIBC between 2008 and 2012 were included. Follow-up data were available until 31 December 2019. Logistic regression estimated the odds of DS with NAC, and a Cox model investigated the effect of DS on OS. Cox models, a mediator analysis and an instrumental variable approach were used to investigate the effect of NAC on OS.
Results
A total of 575 patients were included. NAC was administered to 82 (14%) patients. Compared to cystectomy only, NAC increased the proportion (43% vs. 22%) and the odds of DS (OR 2.51, CI 1.37–4.60, p = 0.003). Independent of NAC, the proportion of pN0 was higher in patients with DS (89% vs. 60%) and DS yielded a 78% mortality risk reduction (HR 0.22, CI 0.15–0.34, p = 1.9∙10–12), compared to patients without DS. We did not find an association between NAC and OS, neither by Cox regression (HR 1.16, CI 0.80–1.68, p = 0.417) nor by an instrumental variable approach (HR = 0.56, CI = 0.07–4.57, p = 0.586). The mediation analysis (p = 0.026) confirmed an indirect effect of NAC on OS through DS. Limitations include limited information of the primary tumour, details of NAC treatment and treatment indications.
Conclusions
NAC increases the probability of DS and is indirectly associated to OS. DS is related to the absence of regional lymph node metastases and is associated with an OS benefit. Improved staging and biomarkers are needed to identify patients most likely to achieve DS and to benefit from NAC.
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Luiting, Henk Benjamin; Remmers, Sebastiaan; Boevé, Egbert R.; Valdagni, Riccardo; Chiu, Peter K. & Semjonow, Axel
[Show all 11 contributors for this article]
(2022).
A Multivariable Approach Using Magnetic Resonance Imaging to Avoid a Protocol-based Prostate Biopsy in Men on Active Surveillance for Prostate Cancer-Data from the International Multicenter Prospective PRIAS Study.
European Urology Oncology (EUO).
5(6),
p. 651–658.
doi:
10.1016/j.euo.2022.03.007.
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Møller, Christina Tanem; Fosså, Sophie Dorothea; Tafjord, Gunnar; Babigumira, Ronnie; Berge, Viktor & Kulle, Bettina
(2022).
Primary versus secondary muscle-invasive bladder cancer: survival after curative treatment.
Scandinavian Journal of Urology.
ISSN 2168-1805.
56(3),
p. 214–220.
doi:
10.1080/21681805.2022.2056633.
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Purpose To assess if cancer-specific survival (CSS) following curative intent treatment (CIT) for muscle-invasive bladder cancer (MIBC) differs between patients presenting with MIBC (primary) and patients presenting with non-muscle-invasive bladder cancer who progress to MIBC (secondary). Methods This study uses data from the Cancer Registry of Norway on patients initially diagnosed with bladder cancer in 2008–2012 and treated with radical cystectomy (RC) or radiotherapy (RT). To ensure a clinically relevant population, we selected patients with a pre-treatment histology confirming muscle-invasion. Survival models were applied to evaluate differences in observed and adjusted CSS by type of MIBC and stratified by type of CIT. Adjustment was made for age group, sex, previous cancer, diagnostic hospital’s academic status and geographical region, and type of CIT. Results We identified 650 eligible patients: 589 (91%) primary MIBC and 61 (9%) secondary MIBC. A total of 556 (86%) patients underwent RC and 94 (14%) RT. The 5-year CSS for primary MIBC was 56% and 59% for secondary MIBC (p = 0.68). The type of MIBC did not impact the risk of bladder cancer death (HR = 0.85, CI = 0.55–1.33, p = 0.48), nor when stratified for CIT (RC: HR = 0.93, CI = 0.57–1.53, p = 0.78); RT: HR = 0.71, CI = 0.24–2.16, p = 0.55). Conclusion This first nation-wide population-based study comparing CSS between primary and secondary MIBC showed no significant difference in survival regardless of type of CIT. Continued surveillance of patients with non-muscle-invasive bladder cancer is necessary to detect early progression to MIBC. Future studies should include molecular and genetic characteristics in addition to detailed clinicopathologic information.
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Guldvik, Ingrid Jenny; Braadland, Peder Rustøen; Sivanesan, Shivanthe; Ramberg, Håkon Andre; Kristensen, Gitte & Tennstedt, Pierre
[Show all 13 contributors for this article]
(2022).
Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer.
European Urology Open Science.
ISSN 2666-1691.
45,
p. 68–75.
doi:
10.1016/j.euros.2022.09.002.
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Background After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to castration-resistant PCa (CRPC). Prognostic markers herald the need for neoadjuvant, adjuvant, or multimodal treatment. Objective To evaluate the added value of blood LRG1 in predicting treatment failure in patients who have undergone radical prostatectomy (RP). Design, setting, and participants We quantified LRG1 in serum or plasma sampled before radical prostatectomy from patients from the Martini-Klinik (Martini; n = 423), the Danish CuPCa cohort (CuPCa; n = 182), and Oslo University Hospital (OUH; n = 145). Outcome measurements and statistical analysis The endpoints were BF, pHT, and CRPC. The association between LRG1 and survival outcomes was evaluated using Kaplan-Meier estimation and Cox proportional-hazards modeling. The added predictive value of LRG1 in nested models was estimated using the concordance index, time-dependent area under the receiver operating characteristic curve, and decision curve analysis. Results and limitations In multivariable Cox models using preoperative characteristics, LRG1 was associated with an estimated lower risk of BF in the Martini cohort (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.52–0.90) and in the CuPCa cohort (aHR 0.47, 95% CI 0.30–0.73). Using preoperative prognostic variables, our data showed that doubling of LRG1 was also associated with a lower risk of pHT receipt in the CuPCa cohort (aHR 0.43, 95% CI 0.20–0.93) and of CRPC development in the OUH cohort (aHR 0.32, 95% CI 0.15–0.69). Similar aHR values were observed using either preoperative or postoperative variables for all endpoints. Conclusions PCa patients with high blood LRG1 are at lower risk of BF, pHT receipt, and progression to CRPC. Since LRG1 adds value to established prognostic models, new prognostic factor combinations including LRG1 should be considered in future studies. Patient summary We measured concentrations of the blood-based protein LRG1 before surgery for prostate cancer. Patients with high LRG1 levels had better disease-free survival, suggesting that LRG1 can help in predicting prognosis.
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Aas, Kirsti; Berge, Viktor; Myklebust, Tor Åge & Fosså, Sophie Dorothea
(2021).
Comparative survival outcomes of high-risk prostate cancer ttreated with radical prostatectomy or definitive radiotherapy regimens.
European Urology Open Science.
ISSN 2666-1691.
26,
p. 55–63.
doi:
10.1016/j.euros.2021.01.011.
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Background: Observational data has indicated improved survival after radical
prostatectomy (RP) compared with definitive radiotherapy (RT) in men with
high-risk prostate cancer (PCa).
Objective: To compare PCa-specific mortality (PCSM) and overall mortality (OM) in
men with high-risk PCa treated with RP or RT, providing information on target
doses and fractionations.
Design, setting, and participants: This is an observational study from the Cancer
Registry of Norway. Patients were diagnosed with high-risk PCa during 2006–2015,
treated with RP
12 mo or RT
15 mo after diagnosis, and stratified according to RP
or RT modality; external beam radiotherapy (EBRT; 70–<74, 74–<78, or 78 Gy),
hypofractionated RT or EBRT combined with brachytherapy (BT-RT).
Outcome measurements and statistical analysis: Competing risk and Kaplan-
Meier methods estimated PCSM and OM, respectively. Multivariable Cox regression
models evaluated hazard ratios (HRs) for PCSM and OM.
Results and limitations: In total, 9254 patients were included (RP 47%, RT 53%). RT
patients were older, had poorer performance status and more unfavorable disease
characteristics. With a median follow-up time of seven and eight yrs, the overall 10-
yr PCSM was 7.2% (95% confidence interval [CI] 6.4–8.0) and OM was 22.9% (95% CI
21.8–24.1). Compared with RP, EBRT 70–<74 Gy was associated with increased (HR
1.88, 95% CI 1.33–2.65, p < 0.001) and BT-RT with decreased (HR 0.49, 95% CI 0.24–
0.96, p = 0.039) 10-yr PCSM. Patients treated with EBRT 70–78 Gy had higher
adjusted 10-yr OM than those treated with RP.
Conclusions: In men with high-risk PCa, treatment with EBRT <74 Gy was associated
with increased adjusted 10-yr PCSM and OM, and BT-RT with decreased 10-yr
PCSM, compared with RP.
Patient summary: In this study, we compared mortality after radical prostatectomy
(RP) and radiotherapy (RT) in men with high-risk prostate cancer (PCa); the results
suggest that men receiving lower-dose RT have higher, and patients receiving
brachytherapy may have lower, risk of death from PCa than patients treated with
prostatectomy.
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Moghaddam, Shirin; Jalali, Amirhossein; O’neill, Amanda; Murphy, Lisa; Gorman, Laura & Reilly, Anne-Marie
[Show all 16 contributors for this article]
(2021).
Integrating serum biomarkers into prediction models for biochemical recurrence following radical prostatectomy.
Cancers.
13(16),
p. 1–11.
doi:
10.3390/cancers13164162.
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This study undertook to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy using serum biomarkers and clinical features. Three radical prostatectomy cohorts were used to build and validate a model of clinical variables and serum biomarkers to predict BCR. The Cox proportional hazard model with stepwise selection technique was used to develop the model. Model evaluation was quantified by the AUC, calibration, and decision curve analysis. Cross-validation techniques were used to prevent overfitting in the Irish training cohort, and the Austrian and Norwegian independent cohorts were used as validation cohorts. The integration of serum biomarkers with the clinical variables (AUC = 0.695) improved significantly the predictive ability of BCR compared to the clinical variables (AUC = 0.604) or biomarkers alone (AUC = 0.573). This model was well calibrated and demonstrated a significant improvement in the predictive ability in the Austrian and Norwegian validation cohorts (AUC of 0.724 and 0.606), compared to the clinical model (AUC of 0.665 and 0.511). This study shows that the pre-operative biomarker PEDF can improve the accuracy of the clinical factors to predict BCR. This model can be employed prior to treatment and could improve clinical decision making, impacting on patients’ outcomes and quality of life.
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Hopland, Ola Andreas; Fosså, Sophie Dorothea; Ottosson, Fredrik; Brennhovd, Bjørn; Svindland, Aud & Hole, Knut Håkon
[Show all 10 contributors for this article]
(2021).
Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience.
Scandinavian Journal of Urology.
ISSN 2168-1805.
55(4).
doi:
10.1080/21681805.2021.1946135.
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Objectives To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND) Material and Methods Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. Results Sixty-nine patients underwent robotic sPLND after a median time of 47 months post- RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10–27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1 Conclusion Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.
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Ramirez, Manuel; Berge, Viktor; Linē, Aija & Llorente, Alicia
(2021).
Potential of miRNAs in urinary extracellular vesicles for management of active surveillance in prostate cancer patients.
British Journal of Cancer.
ISSN 0007-0920.
126,
p. 492–501.
doi:
10.1038/s41416-021-01598-1.
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Background: Active surveillance is an alternative to radical treatment for patients with low-risk prostate cancer, which could also benefit some patients with intermediate risk. We have investigated the use of miRNA in urinary extracellular vesicles to stratify these patients. Methods: NGS was performed to profile the miRNAs from small urinary extracellular vesicles in a cohort of 70 patients with prostate cancer ISUP Grade 1, 2 or 3. The most promising candidates were then analysed by RT-qPCR in a new cohort of 60 patients. Results: NGS analysis identified nine miRNAs differentially expressed in at least one of the comparisons. The largest differences were found with miR-1290 (Grade 3 vs. 1), miR-320a-3p (Grade 3 vs. 2) and miR-155-5p (Grade 2 vs. 1). Combinations of 2–3 miRNAs were able to differentiate between two ISUP grades with an AUC 0.79–0.88. RT-qPCR analysis showed a similar trend for miR-186-5p and miR-30e-5p to separate Grade 3 from 2, and miR-320a-3p to separate Grade 2 from 1. Conclusions: Using NGS, we have identified several miRNAs that discriminate between prostate cancer patients with ISUP Grades 1, 2 and 3. Moreover, miR-186-5p, miR-320a-3p and miR-30e-5p showed a similar behaviour in an independent cohort using an alternative analytical method. Our results show that miRNAs from urinary vesicles can be potentially useful as liquid biopsies for active surveillance.
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Thiem, Barbara; Kruszka, Dariusz; Turowska, Natalia; Sliwinska, Elwira; Berge, Viktor & Kikowska, Małgorzata
(2021).
Linnaea borealis L. Var. borealis—In vitro cultures and phytochemical screening as a dual strategy for its ex situ conservation and a source of bioactive compounds of the rare species.
Molecules.
ISSN 1431-5157.
26(22).
doi:
10.3390/molecules26226823.
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Linnaea borealis L. (Twinflower)—a dwarf shrub in the Linnaeeae tribe of Caprifoliaceae family—is distributed across the Northern Hemisphere. By means of this study, a reliable protocol for efficient micropropagation of uniform L. borealis L. var. borealis plantlets has been provided for the first time; callus culture was also established. Different initial explants, types of cultures, media systems, and plant growth regulators in Murashige and Skoog (MS) media were tested. Agitated shoot cultures in the liquid media turned out to be the best system for the production of sustainable plant biomass. After stabilization of the callus lines, the highest growth index (c.a. 526%) was gained for callus maintained on MS enriched with picloram. TLC and UHPLC-HESI-HRMS analysis confirmed the presence of phenolic acids and flavonoids, and for the first time, the presence of iridoids and triterpenoid saponins in this species. Multiplication of L. borealis shoot culture provides renewable raw material, allowing for the assessment of the phytochemical profile, and, in the future, for the quantitative analyses and the studies of the biological activity of extracts, fractions, or isolated compounds. This is the first report on in vitro cultures of traditionally used L. borealis rare taxon and its biosynthetic potential.
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Ramberg, Håkon Andre; Richardsen, Elin; Souza, Gustavo Antonio De; Rakaee, Mehrdad; Stensland, Maria & Braadland, Peder Rustøen
[Show all 13 contributors for this article]
(2021).
Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer.
Carcinogenesis.
ISSN 0143-3334.
42(5),
p. 685–693.
doi:
10.1093/carcin/bgab015.
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The demographic shift toward an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years postsurgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein (MVP) was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the MVP was verified by scoring immunohistochemical staining of a tissue microarray. High level of MVP was associated with more than 4-fold higher risk for death from prostate cancer (hazard ratio = 4.41, 95% confidence interval: 1.45–13.38; P = 0.009) in a Cox proportional hazard models, adjusted for Cancer of the Prostate Risk Assessments Post-surgical (CAPRA-S) score and perineural invasion. Decision curve analyses suggested an improved standardized net benefit, ranging from 0.06 to 0.18, of adding MVP onto CAPRA-S score. This observation was confirmed by receiver operator characteristics curve analyses for the CAPRA-S score versus CAPRA-S and MVP score (area under the curve: 0.58 versus 0.73). From these analyses, one can infer that MVP levels in combination with CAPRA-S score might add onto established risk parameters to identify patients with lethal prostate cancer.
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Aas, Kirsti; Fosså, Sophie Dorothea; Myklebust, Tor Åge; Møller, Bjørn; Kvåle, Rune & Vlatkovic, Ljiljana
[Show all 7 contributors for this article]
(2020).
Increased curative treatment is associated with decreased prostate cancer-specific and overall mortality in senior adults with high-risk prostate cancer; results from a national registry-based cohort study.
Cancer Medicine.
9(18),
p. 6646–6657.
doi:
10.1002/cam4.3297.
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Background The association between curative treatment (CurTrt) and mortality in senior adults (≥70 years) with high‐risk prostate cancer (PCa) is poorly documented. In a population‐based cohort we report temporal trends in treatment and PCa‐specific mortality (PCSM), investigating the association between CurTrt and mortality in senior adults with high‐risk PCa, compared to findings in younger men (<70 years). Methods Observational study from the Cancer Registry of Norway. Patients with high‐risk PCa were stratified for three diagnostic periods (2005‐08, 2009‐12 and 2013‐16), age (<70, vs ≥70) and primary treatment (CurTrt: Radical prostatectomy (RP), Radiotherapy (RAD) vs no curative treatment (NoCurTrt)). Competing risk and Kaplan‐Meier methods estimated PCSM and overall mortality (OM), respectively. Multivariable logistic regression models estimated odds for CurTrt, and multivariable Fine Gray and Cox regression models evaluated the hazard ratios for PCSM and OM. Results Of 19 763 evaluable patients, 54% were aged ≥70 years. Senior adults had more unfavorable PCa characteristics than younger men. Across diagnostic periods, use of CurTrt increased from 15% to 51% in men aged ≥70 and 65% to 81% in men aged < 70 years. With median five years follow‐up, PCSM decreased in all patients (P < .05), in the third period restricted to senior adults. In all patients NoCurTrt was associated with three‐fold higher 5‐year PCSM and two‐fold higher OM compared to CurTrt. Conclusions In high‐risk PCa patients, increased use of CurTrt, greatest in senior men, was observed along with decreased PCSM and OM in both senior and younger adults. CurTrt should increasingly be considered in men ≥70 years.
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Fosså, Sophie Dorothea; Beyer, Bud; Dahl, Alv A; Aas, Kirsti; Eri, Lars Magne & Kvan, Espen
[Show all 10 contributors for this article]
(2019).
Improved patient-reported functional outcomes after nerve-sparing radical prostatectomy by using NeuroSAFE technique.
Scandinavian Journal of Urology.
ISSN 2168-1805.
p. 1–7.
doi:
10.1080/21681805.2019.1693625.
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Purpose: To explore whether prostatectomized men report improved post-operative erectile function and urinary control dependent on the application of intra-operative frozen section examination (NeuroSAFE) during nerve-sparing radical prostatectomies (NS-RPs). Methods: Pre- and post-RP responses to the sexual domain and the urinary incontinence subscale of EPIC-26 were analyzed in 95 and 312 men from a NeuroSAFEGroup (Martini-Klinik, Hamburg, Germany) and a Non-NeuroSAFE Group (Oslo University Hospital, Norway), respectively, undergoing NS-RPs for ≤ cT2 prostate cancer. All patients had intra-prostatic tumors as evaluated by Digital Rectal Examination. Statistical significance in bivariate and multi-variable analyses: p < 0.05. Results: With similar oncological outcomes and not associated with the performance of bilateral or unilateral NS-RP within each group patients from the NeuroSAFE Group had better sexuality outcomes than those from the NonNeuroSAFE Group (p < 0.01). Age and pre-RP sexual function represented significant co-variables. In pre-RP potent men, erectile function was preserved in 74% of men in the NeuroSAFE Group and in 46% in those from the NonNeuroSAFE Group (p < 0.01). Any superior continence-saving effect of NeuroSAFE was limited. The non-randomized small-sized observational study design represents the observations’ main limitation. Conclusions: Our study indicates that NeuroSAFE contributes to preservation of post-RP erectile function. If confirmed in a randomized trial the NeuroSAFE should be applied in patients undergoing NS-RP for maximal preservation of post-RP sexual function.
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Fan, Zhirui; Li, Lifeng; Li, Xiaoli; Zhang, Meng; Zhong, Yali & Li, Yaqing
[Show all 17 contributors for this article]
(2018).
Generation of an oxoglutarate dehydrogenase knockout rat model and the effect of a high-fat diet.
RSC Advances.
8(30),
p. 16636–16644.
doi:
10.1039/c8ra00253c.
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Although abnormal metabolism in metabolic syndrome and tumours has been well described, the relationship between oxoglutarate dehydrogenase (OGDH) and obesity-related diseases is still largely unknown. This study aimed to investigate whether it was possible to use transcription activator-like effector nuclease (TALEN) technology to establish OGDH−/− rats and then study the effect of a high-fat diet (HFD) on these rats. However, after OGDH+/−rats were generated, we were unable to identify any OGDH−/− rats by performing mating experiments with the OGDH+/− rats for almost one year. During the past three years, only OGDH+/− rats were stably established, and correspondingly reduced OGDH expression in the tissues of the OGDH+/− rats was verified. No significant abnormal behaviour was observed in the OGDH+/− rats compared to the wild-type (WT) control rats. However, the OGDH+/− rats were revealed to have higher body weight, and the difference was even significantly greater under the HFD condition. Furthermore, blood biochemical and tissue histological examinations uncovered no abnormalities with normal diets, but a HFD resulted in liver dysfunction with pathological alterations in the OGDH+/− rats. Our results strongly indicate that OGDH homologous knockout is lethal in rats but heterologous OGDH knockout results in vulnerable liver lesions with a HFD. Therefore, the current study may provide a useful OGDH+/− rat model for further investigations of metabolic syndrome and obesity-related hepatic carcinogenesis.
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Braadland, Peder; Giskeødegård, Guro F.; Sandsmark, Elise; Bertilsson, Helena; Euceda, Leslie R. & Hansen, Ailin Falkmo
[Show all 17 contributors for this article]
(2017).
Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.
British Journal of Cancer.
ISSN 0007-0920.
117(11),
p. 1656–1664.
doi:
10.1038/bjc.2017.346.
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Background: Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. Methods: We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan–Meier survival analyses and concordance index (C-index). Results: High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P=0.016 and C-index: 0.765; HR: 1.43; P=0.014, respectively). Conclusions: Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.
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Moen, Line Victoria; Ramberg, Håkon Andre; Zhao, Sen; Grytli, Helene Hartvedt; Sveen, Anita & Berge, Viktor
[Show all 9 contributors for this article]
(2017).
Observed correlation between the expression levels of catalytic subunit, C?2, of cyclic adenosine monophosphate-dependent protein kinase and prostate cancer aggressiveness.
Urologic Oncology.
ISSN 1078-1439.
35(3),
p. 111.e1–111.e8.
doi:
10.1016/j.urolonc.2016.10.002.
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Background
As an intracellular human pathogen, Mycobacterium tuberculosis (Mtb) is facing multiple stressful stimuli inside the macrophage and the granuloma. Understanding Mtb responses to stress is essential to identify new virulence factors and pathways that play a role in the survival of the tubercle bacillus. The main goal of this study was to map the regulatory networks of differentially expressed (DE) transcripts in Mtb upon various forms of genotoxic stress. We exposed Mtb cells to oxidative (H2O2 or paraquat), nitrosative (DETA/NO), or alkylation (MNNG) stress or mitomycin C, inducing double-strand breaks in the DNA. Total RNA was isolated from treated and untreated cells and subjected to high-throughput deep sequencing. The data generated was analysed to identify DE genes encoding mRNAs, non-coding RNAs (ncRNAs), and the genes potentially targeted by ncRNAs.
Results
The most significant transcriptomic alteration with more than 700 DE genes was seen under nitrosative stress. In addition to genes that belong to the replication, recombination and repair (3R) group, mainly found under mitomycin C stress, we identified DE genes important for bacterial virulence and survival, such as genes of the type VII secretion system (T7SS) and the proline-glutamic acid/proline-proline-glutamic acid (PE/PPE) family. By predicting the structures of hypothetical proteins (HPs) encoded by DE genes, we found that some of these HPs might be involved in mycobacterial genome maintenance. We also applied a state-of-the-art method to predict potential target genes of the identified ncRNAs and found that some of these could regulate several genes that might be directly involved in the response to genotoxic stress.
Conclusions
Our study reflects the complexity of the response of Mtb in handling genotoxic stress. In addition to genes involved in genome maintenance, other potential key players, such as the members of the T7SS and PE/PPE gene family, were identified. This plethora of responses is detected not only at the level of DE genes encoding mRNAs but also at the level of ncRNAs and their potential targets.
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Ling, Wang; Skotland, Tore; Berge, Viktor; Sandvig, Kirsten & Llorente, Alicia
(2017).
Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to immunoassay-based validation.
European Journal of Pharmaceutical Sciences.
ISSN 0928-0987.
98,
p. 80–85.
doi:
10.1016/j.ejps.2016.09.023.
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Walker, Steven M.; Knight, Laura A.; McCavigan, Andrena M.; Logan, Gemma E.; Berge, Viktor & Sherif, Amir
[Show all 27 contributors for this article]
(2017).
Molecular subgroup of primary prostate cancer presenting with metastatic biology.
European Urology.
ISSN 0302-2838.
72(4),
p. 509–518.
doi:
10.1016/j.eururo.2017.03.027.
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Background Approximately 4–25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. Objective To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Design, setting, and participants Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Outcome measurements and statistical analysis Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. Results and limitations A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13–2.33]; p = 0.0092) and metastatic recurrence (multivariable HR = 3.20 [1.76–5.80]; p = 0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR = 2.67 [1.90–3.75]; p < 0.0001 and HR = 7.53 [4.13–13.73]; p < 0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. Conclusions The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. Patient summary The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.
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Bokhorst, Leonard P.; Lepistö, Inari; Kakehi, Yoshiyuki; Bangma, Chris H.; Pickles, Tom & Valdagni, Riccardo
[Show all 13 contributors for this article]
(2016).
Complications after prostate biopsies in men on active surveillance and its effects on receiving further biopsies in the Prostate cancer Research International: Active Surveillance (PRIAS) study.
BJU International.
ISSN 1464-4096.
118(3),
p. 366–371.
doi:
10.1111/bju.13410.
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Braadland, Peder; Grytli, Helene Hartvedt; Ramberg, Håkon Andre; Katz, Betina; Kellmann, Ralf & Gauthier-Landry, louis
[Show all 18 contributors for this article]
(2016).
Low β2-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism.
OncoTarget.
7(2),
p. 1878–1894.
doi:
10.18632/oncotarget.6479.
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The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17.
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Dahl, Sigrun; Loge, Jon Håvard; Berge, Viktor; Dahl, Alv A; Småstuen, Milada C & Fosså, Sophie Dorothea
(2015).
Influence of radical prostatectomy for prostate cancer on work status and working life 3 years after surgery.
Journal of cancer survivorship.
ISSN 1932-2259.
9(2),
p. 172–179.
doi:
10.1007/s11764-014-0399-6.
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Ramberg, Håkon Andre; Alshbib, Ayham; Berge, Viktor; Svindland, Aud & Tasken, Kristin Austlid
(2011).
Regulation of PBX3 expression by androgen and Let-7d in prostate cancer.
Molecular Cancer.
10.
doi:
10.1186/1476-4598-10-50.
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Background The pre-leukemia transcription factor 3 (PBX) is part of the PBX family of transcription factors, which is known to regulate genes involved in differentiation of urogenital organs and steroidogenesis. This is of interest with regard to prostate cancer progression as regulation of steroidogenesis is one of the mechanisms involved in the development of castration-resistant prostate cancer. In light of this we wanted to investigate the possible involvement of androgen regulation of PBX3 expression in prostate cancer. Results In this study, we show that PBX3 is post-transcriptionally regulated by androgen in prostate cancer cells and that the effect might be independent of the androgen receptor. Furthermore, PBX3 was identified as a target of Let-7d, an androgen regulated microRNA. Let-7d was down-regulated in malignant compared to benign prostate tissue, whereas up-regulation of PBX3 expression was observed. Conclusions We demonstrate that PBX3 is up-regulated in prostate cancer and post- transcriptionally regulated by androgen through Let-7d.
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Berge, Viktor; Baco, Eduard; Dahl, Alv A & Karlsen, Steinar
(2011).
Health-related quality of life after salvage high-intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer.
International journal of urology.
ISSN 0919-8172.
18(9),
p. 646–651.
doi:
10.1111/j.1442-2042.2011.02815.x.
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Berge, Viktor; Baco, Eduard & Karlsen, Steinar
(2010).
A prospective study of salvage high-intensity focused ultrasound for locally radiorecurrent prostate cancer: Early results.
Scandinavian Journal of Urology and Nephrology.
ISSN 0036-5599.
44(4),
p. 223–227.
doi:
10.3109/00365591003727551.
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Berge, Viktor; Johnson, Egil & Berge, Knut Erik
(1996).
Interleukin-1 alpha, interleukin 6 and tumor necrosis factor alpha increase the synthesis and expression of the functional alternative and terminal complement pathways by human umbilical vein endothelial cells in vitro.
APMIS - Journal of Pathologiy, Microbiology and Immunology.
ISSN 0903-4641.
104,
p. 213–219.
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The proinflammatory cytokines interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) modulate the synthesis of complement factors B and C3 by endothelial cells (EC), and are considered to play an important role in the development of sepsis. By using agarose beads activating the alternative pathway of complement, we wanted to study the net effect of these cytokines on EC synthesis of the alternative and terminal pathways, measured by binding of anti-C3c and anti-TCC (terminal complement complex) antibodies to beads kept with the EC. Addition of IL-1 alpha and TNF alpha at concentrations of 50 and 100 U/ml resulted in a significant increase in binding of these antibodies to co-incubated beads, most pronounced for anti-C3c. IL-6 from 50-200 U/ml resulted in a stronger (two to fourfold) binding for both antibodies compared to experiments with IL-1 alpha and TNF. However, increased concentrations of IL-1 alpha (200 U/ml) and IL-6 (400 U/ml) resulted in a strong reduction in binding of anti-C3c and anti-TCC antibodies to the co-cultured beads. This study indicates that proinflammatory cytokines upregulate the synthesis by EC of the functional alternative and terminal pathways of complement.
Registry Numbers
EC 3-4-21-47 (Properdin Factor B). 0 (Complement Membrane Attack Complex). 0 (Complement 3). 0 (Culture Media, Serum-Free). 0 (Interleukin-1). 0 (Interleukin-6). 0 (Tumor Necrosis Factor).
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Berge, Viktor; Berge, Knut Erik & Johnson, Egil
(1996).
Vitronectin modulates the expression of the terminal complement pathway synthesized by human umbilical vein endothelial cells in vitro.
APMIS - Journal of Pathologiy, Microbiology and Immunology.
ISSN 0903-4641.
p. 523–530.
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Berge, Viktor; Berge, Knut Erik & Johnson, Egil
(1996).
Vitronectin modulates the expression of complement components of the terminal pathway synthesized by human umbilical vein endothelial cells in vitro.
APMIS - Journal of Pathologiy, Microbiology and Immunology.
ISSN 0903-4641.
104,
p. 523–530.
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Rodriguez, Marta; Bajo-Santos, Cristina; Hessvik, Nina Pettersen; Lorenz, Susanne; Fromm, Bastian & Berge, Viktor
[Show all 9 contributors for this article]
(2017).
Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes.
Molecular Cancer.
16:156,
p. 1–6.
doi:
10.1186/s12943-017-0726-4.
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The aim of this study was to identify microRNAs in urinary exosomes that are differently expressed in prostate cancer patients and healthy donors. For this purpose, RNA was extracted from urinary exosomes from 20 prostate cancer patients and 9 healthy males and the microRNAs were analyzed by next generation sequencing. Interestingly, 5 microRNAs - miR-196a-5p, miR-34a-5p, miR-143-3p, miR-501-3p and miR-92a-1-5p - were significantly downregulated in exosomes from prostate cancer patients. Furthermore, RT-qPCR analysis of an independent cohort of 28 prostate cancer patients and 19 healthy males confirmed that miR-196a-5p and miR-501-3p were downregulated in prostate cancer samples. These results suggest that specific microRNAs in urinary exosomes might serve as non-invasive biomarkers for prostate cancer. In particular, miR-196a-5p and miR-501-3p are promising biomarkers that need to be further studied in large patient cohorts.
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Lundeby, Eskild; Eri, Lars Magne; Lien, My Diep; Karlsen, Steinar & Berge, Viktor
(2013).
Functional outcomes after conventional laparoscopic radical prostatectomy (LRP); A comparison between assessment by clinician interview vs validated health related quality of life (HRQOL) questionnaires completed by the patients.
Scandinavian Journal of Urology and Nephrology.
ISSN 0036-5599.
47,
p. 6–6.
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Baco, Eduard; Rud, Erik; Boezelijn, Gro; Berge, Viktor & Eggesbø, Heidi Beate
(2013).
Hemi ablation of prostate by hifu in patients with unilateral prostate cancer: a prospective study.
Scandinavian Journal of Urology and Nephrology.
ISSN 0036-5599.
47,
p. 49–50.
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Berge, Viktor; Næss-Andresen, Thomas Fredrik; Karlsen, Steinar & Baco, Eduard
(2013).
Biochemical survival, urinary and sexual function at 29.1 months median follow up in patients treated with primary whole gland high intensity focused ultrasound (wgHIFU) for localized prostate cancer.
Scandinavian Journal of Urology and Nephrology.
ISSN 0036-5599.
47,
p. 52–52.
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Robertson, Cary N.; Ward, John Francis; Crouzet, Sebastien; Brown, Stephen C. W.; Berge, Viktor & Chaussy, Christian G.
[Show all 11 contributors for this article]
(2012).
Biochemical survival and morbidity of high-intensity focused ultrasound (HIFU) as a primary monotherapy for low-risk localized prostate cancer: Outcomes from the @-registry following the ENLIGHT trial inclusion criteria.
Journal of Clinical Oncology.
ISSN 0732-183X.
30(15).
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Baco, Eduard; Berge, Viktor & Karlsen, Steinar
(2007).
Recurrent prostate cancer etter radikal strålebehandling. "Salvage" HIFU, foreløpige korttidserfaringer ved OUU.
Vitenskapelige forhandlinger - De norske kirurgiske foreninger.
ISSN 0801-5902.
p. 74–74.
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Berge, Viktor; Baco, Eduard & Karlsen, Steinar
(2007).
Our first experience high intensity focused ultrasound treatment for localized prostate cancer.
Scandinavian Journal of Urology and Nephrology.
ISSN 0036-5599.
2007(41),
p. 21–21.
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Eri, Lars Magne; Berg, Rolf Eigil; Berge, Viktor; Hoff, Jon-Roar; Wahlqvist, Rolf & Karlsen, Steinar
(2007).
Laparoscopic radical prostatectomy. Our first four years.
European Urology.
ISSN 0302-2838.
6,
p. 254–254.
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Berge, Viktor; Baco, Eduard & Karlsen, Steinar
(2007).
HIFU ved OUU: Nytt tilbud for pasienter med cancer prostatae.
Kirurgen.
ISSN 1504-8888.
1,
p. 26–27.
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Berge, Viktor
(1997).
STUDIES ON FACTORS REGULATING THE EXPRESSION AND SYNTHESIS OF THE FUNCTIONAL COMPONENTS OF THE ALTERNATIVE AND TERMINAL COMPLEMENT PATHWAYS BY HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS IN VITRO.
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Published
May 14, 2019 12:08 PM
- Last modified
June 13, 2019 12:26 PM
