Kristin Austlid Tasken

• Desiati, Indri; Forsell, Selma Bozorgpana; Ramberg, Håkon; Berge, Viktor; Tasken, Kristin Austlid & Giskeødegård, Guro F. [Vis alle 8 forfattere av denne artikkelen] (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. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Sivanesan, Shivanthe; Ramberg, Håkon; Kristiansen, Thomas; Thapa, Suraj; Bjøre, Marthe & Berge, Viktor [Vis alle 15 forfattere av denne artikkelen] (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.
• Mohammad, S.F. Haj; Pol, H. van der; Vrdoljak, E.; Lassen, U.; Ojamaa, K. & Jalkanen, K. [Vis alle 19 forfattere av denne artikkelen] (2025). A comprehensive assessment of the existing landscape of personalized cancer medicine in the European Union, on behalf of the PCM4EU consortium. ESMO Open. 10(11), s. 105872–105872. doi: 10.1016/j.esmoop.2025.105872. Fulltekst i vitenarkiv
• Ramberg, Håkon; Zucknick, Manuela; Barletta, Francesco; Davik, Petter; Nybøen, Åsmund & Eri, Lars Magne [Vis alle 15 forfattere av denne artikkelen] (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, s. 1446–1454. doi: 10.2340/1651-226x.2025.43970. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Thulin, Malin Hagberg; Ramberg, Håkon; Nielsen, Heidi Kristin; Grytli, Helene Hartvedt; Sivanesan, Shivanthe & Pandya, Abhilash D. [Vis alle 15 forfattere av denne artikkelen] (2025). Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis. Journal of Translational Medicine. 23(1). doi: 10.1186/s12967-025-06644-7. Fulltekst i vitenarkiv Vis sammendrag

  Background The therapeutic impact of beta-blockers (BB), beta-adrenergic receptor antagonists, on prostate cancer remains controversial. The underlying health conditions of BB users complicate the ability to isolate and evaluate the specific effects of these drugs on the tumour cells. This study investigated whether BBs, by inhibiting sympathetic nerve signalling, extended the duration of androgen deprivation therapy (ADT) effectiveness in patients with de novo metastatic hormone sensitive prostate cancer and in prostate cancer xenograft models, while also uncovering the molecular mechanisms involved. Methods An analysis was conducted on prospectively collected data from the Cancer Registry of Norway, Norwegian Prescription Database, and Norwegian Cause of Death Registry focusing on patients with de novo metastatic prostate cancer undergoing ADT using the commencement of second-line treatment as the endpoint. In addition, the causal effect of BB treatment was studied in two different hormone-sensitive prostate cancer xenograft mouse models. Prior to treatment, mice were surgically castrated, to mimic ADT, and tumour progression was tracked by measuring serum PSA levels. RNA sequencing was performed on xenografted orthotopic tumours to investigate the underlying mechanisms, utilizing annotation based on human data and protein levels were validated by the Protein Simple Immunoassay. Immune-related effects were evaluated using immunohistochemistry on tumour tissue and measuring neopterin levels, along with 92 analytes, using the OLINK proximity extension assay on serum samples from xenografted mice and prostate cancer patients, both BB users and non-users. Results A competitive risk analysis indicated that BB treatment postponed the initiation of second-line treatment in prostate cancer patients on ADT. Additionally, in both prostate cancer xenograft models, BB treatment reduced tumour burden and delayed progression to castration-resistant prostate cancer. Mechanistically, BB treatment suppressed androgen receptor signalling and induced a metabolic shift by up-regulating oxidative phosphorylation transcripts and down-regulating those involved in fatty acid synthesis and the PI3K/AKT/mTOR pathway. Additionally, BB treatment increased serum pro-inflammatory cytokines, such as the IL23/IL17 axis, in both xenografted mice and in patient samples. Enhanced intra-tumoral CD68+ immune cell infiltration was also observed in the tumours. Conclusion The data suggest that BB combined with ADT delay the progression to castration-resistant prostate cancer. This may be achieved by influencing androgen receptor activity, adjusting energy metabolism and fostering a pro-inflammatory antitumoral microenvironment

• Blilie, Anders; Giskeødegård, Guro F.; Nybøen, Åsmund; Krossa, Sebastian; Midtbust, Elise & Gudlaugsson, Einar [Vis alle 12 forfattere av denne artikkelen] (2025). Biobanking after Radical Prostatectomy: Comparison of Slice and Punch Protocols. Biopreservation and Biobanking. ISSN 1947-5535. 23(5), s. 421–430. doi: 10.1089/bio.2024.0175. Fulltekst i vitenarkiv Vis sammendrag

  Background: Biobanking of prostate cancer tissue is crucial for advancing biomarker-guided precision medicine. However, there is no standardized optimal protocol for biobanking prostatectomy specimens. This study aims to compare the representativeness and sustainability of two biobanking protocols—“Punch” and “Slice”—currently used in Norway. Methods: Fresh frozen tissue from 40 radical prostatectomy specimens was biobanked using both the Punch and Slice protocols. Following macroscopic evaluation, a 2 mm thick transverse slice of the prostate (Slice protocol) was collected and stored in an ultra-freezer for future drill biopsy subsampling, guided by histopathological assessment of adjacent formalin-fixed, paraffin-embedded tissue sections. After the slice was collected, five cylindrical tissue samples were punched from the cut surfaces (Punch protocol). Statistical analyses were conducted to compare the sampling precision and time consumption of both protocols. Results: Cancerous tissue was successfully sampled in 87.5% of cases using the Punch protocol and 75% of cases using the Slice protocol. Both methods yielded comparable results in terms of the number of cancerous cores and the ability to sample tissue representing the highest Gleason grade. The mean biobanking time of tissue slices was 4.9 minutes compared to 15.1 minutes for the ready-to-use tissue punches. Both methods have previously been shown to provide high-quality RNA extracts. Conclusion: Both biobanking protocols are effective for sampling prostate cancer tissue, with no significant difference in precision or quality. The choice between protocols should consider factors such as resource availability, tissue quantity, and specific research needs. The Punch protocol is less resource-intensive overall, while the Slice protocol collects vastly more tissue, has a shorter period of ischemia, and provides detailed mapping of biobanked components, allowing for further subsampling at multiple time points.

• Guldvik, Ingrid Jenny; Ramberg, Håkon; Kristensen, Gitte; Røder, Andreas; Mills, Ian Geoffrey & Lilleby, Wolfgang [Vis alle 7 forfattere av denne artikkelen] (2024). Systemic interrogation of immune-oncology-related proteins in patients with locally advanced prostate cancer undergoing androgen deprivation and intensity-modulated radiotherapy. World Journal of Urology. ISSN 0724-4983. 42(1). doi: 10.1007/s00345-024-04787-8. Fulltekst i vitenarkiv Vis sammendrag

  Purpose The primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting. Methods Baseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics. Statistical analyses using Kaplan–Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins. Results High baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints. Conclusion LRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data.

• Korsnes, Monica Suarez; Ramberg, Håkon; Tasken, Kristin Austlid & Korsnes, Reinert (2024). Video tracking of single cells to identify clustering behavior. Frontiers in Imaging. 3. doi: 10.3389/fimag.2024.1443142. Fulltekst i vitenarkiv Vis sammendrag

  Cancer cell clustering is a critical factor in metastasis, with cells often believed to migrate in groups as they establish themselves in new environments. This study presents preliminary findings from an in vitro experiment, suggesting that co-culturing cells provides an effective method for observing this phenomenon, even though the cells are grown as monolayers. We introduce a novel single-cell tracking approach based on graph theory to identify clusters in PC3 cells cultivated in both monoculture and co-culture with PC12 cells, using 66-h time-lapse recordings. The initial step consists of defining “linked” pairs of PC3 cells, laying the foundation for the application of graph theory. We propose two alternative definitions for cell pairings. The first method, Method 1, defines cells as “linked” at a given time t if they are close together within a defined time period before and after t. A second potential alternative method, Method 2, pairs cells if there is an overlap between the convex hulls of their respective tracks during this time period. Pairing cells enables the application of graph theory for subsequent analysis. This framework represents a cell as a vertex (node) and a relation between two cells as an edge. An interconnected set of high-degree nodes (nodes with many connections or edges) forms a subgraph, or backbone, that defines a patch (cluster) of cells. All nodes connected to this backbone are part of the subgraph. The backbone of high-degree nodes functions as a partition (or cut) of the initial graph. Two consecutive clusters in the video are considered to share the same identity if the following cluster contains at least p = 75 % of the cells from the preceding cluster, and the mean positions of their cells are within △r = 75μm. PC3 cells grown in co-culture appear to form persistent clusters exceeding 10 cells after 40–50 h incubation following seeding. In contrast, PC3 cells cultured alone (mono-culture) did not exhibit this behavior. This approach is experimental and requires further validation with a broader dataset.

• Ouellet, Véronique; Erickson, Andrew; Wiley, Kathy; Morrissey, Colm; Berge, Viktor & Moreno, Carlos S. [Vis alle 31 forfattere av denne artikkelen] (2022). The movember global action plan 1 (GAP1): Unique prostate cancer tissue microarray resource. Cancer Epidemiology, Biomarkers and Prevention. ISSN 1055-9965. 31(4), s. 715–727. doi: 10.1158/1055-9965.EPI-21-0600. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Nunes-Xavier, Caroline Elisabeth; Emaldi, Maite; Guldvik, Ingrid Jenny; Ramberg, Håkon; Tasken, Kristin Austlid & Mælandsmo, Gunhild Mari [Vis alle 10 forfattere av denne artikkelen] (2022). Correlation of expression of Major Vault Protein with androgen receptor and immune checkpoint protein B7-H3, and with poor prognosis in prostate cancer. Pathology, Research and Practice. ISSN 0344-0338. 241. doi: 10.1016/j.prp.2022.154243. Fulltekst i vitenarkiv Vis sammendrag

  Prostate cancer diagnosis and early stratification is an important aspect to avoid undertreatment of high-risk prostate cancer patients. Major Vault Protein (MVP) has been proposed as a prognostic biomarker in prostate cancer. PTEN and the immune checkpoint protein B7-H3 interact with MVP and are important in prostate cancer progression and therapy response. We evaluated the expression of MVP by immunohistochemistry of tissue microarray samples from a retrospective cohort consisting of 119 prostate cancer patients. We correlated the protein expression of MVP with clinicopathological characteristics, and protein expression of androgen receptor (AR), PTEN, immune checkpoint proteins B7-H3 and PD-L1. We found MVP to be expressed in 53 % of prostate tumors, and correlated positively with biochemical recurrence (ρ = 0.211/p = 0.021). Furthermore, we found positive correlation of MVP expression with expression of AR (ρ = 0.244/p = 0.009) and the immune checkpoint protein B7-H3 (ρ = 0.200/p = 0.029), but not with PD-L1 (ρ = 0.152/p = 0.117) or PTEN expression (ρ = − 0.034/p = 0.721). Our findings support the notion that expression of MVP is associated with poor prognosis in prostate cancer. The correlation between MVP and immune checkpoint protein B7-H3 in prostate cancer suggests a role for MVP in immunoregulation and drug resistance.

• Sivanesan, Shivanthe; Tasken, Kristin Austlid & Grytli, Helene Hartvedt (2022). Association of β-Blocker Use at Time of Radical Prostatectomy with Rate of Treatment for Prostate Cancer Recurrence. JAMA Network Open. 5(1), s. E2145230–E2145230. doi: 10.1001/jamanetworkopen.2021.45230. Fulltekst i vitenarkiv Vis sammendrag

  Importance The perioperative period has gained attention as a window of opportunity to prevent cancer recurrence. Evidence in support of a role for nonselective β-blockers (nsBBs) in cancer treatment is increasing, and counteracting cancer recurrence associated with perioperative stress and catecholamine is one of the suggested mechanisms of action. Objective To explore whether use of nsBBs at the time of radical prostatectomy is associated with a lower rate of treatment for prostate cancer recurrence. Design, Setting, and Participants This cohort study analyzed prospectively collected data from the Cancer Registry of Norway, Norwegian Patient Registry, Norwegian Prescription Database, and Norwegian Cause of Death Registry. Of 12 298 eligible patients, this study included 11 117 treatment-naive patients with prostate cancer (ie, no prior hormonal therapy, radiotherapy, or chemotherapy) who underwent radical prostatectomy in Norway from January 1, 2008, to December 31, 2015, with a minimum progression-free follow-up of 6 months. Data analysis was performed from April 20, 2020, to April 30, 2021. Exposures Use of nsBBs and selective β-blockers (sBBs) at time of radical prostatectomy. Main Outcomes and Measures Treatment for cancer recurrence after radical prostatectomy (defined as initiation of hormonal therapy, radiotherapy, or chemotherapy) or, if no treatment was identified, cancer-specific mortality. Results The study included 11 117 men with prostate cancer (median [IQR] age at radical prostatectomy, 64.8 [60.4-68.3] years). Of these, 1622 (14.6%) later received treatment for cancer recurrence during a median follow-up of 4.3 years (IQR, 2.4-6.3 years). Use of nsBBs at time of surgery among 209 patients was significantly associated with a lower risk of treatment for cancer recurrence (adjusted hazard ratio [aHR], 0.64; 95% CI, 0.42-0.96; P = .03). No such association was observed for use of sBBs (aHR, 0.96; 95% CI, 0.84-1.11; P = .62). Subanalyses with (1) relaxed inclusion criteria allowing for inclusion also of patients with early progression (within 6 months) and (2) only the healthiest patients (Eastern Cooperative Oncology Group performance status of 0) supported the main findings. Conclusions and Relevance In this cohort study, use of nsBB but not sBBs at the time of radical prostatectomy was associated with less treatment initiation for cancer recurrence. This finding, together with accumulated preclinical and clinical evidence, provides a foundation for initiation of an interventional study.

• Guldvik, Ingrid Jenny; Braadland, Peder Rustøen; Sivanesan, Shivanthe; Ramberg, Håkon Andre; Kristensen, Gitte & Tennstedt, Pierre [Vis alle 13 forfattere av denne artikkelen] (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, s. 68–75. doi: 10.1016/j.euros.2022.09.002. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Moghaddam, Shirin; Jalali, Amirhossein; O’neill, Amanda; Murphy, Lisa; Gorman, Laura & Reilly, Anne-Marie [Vis alle 16 forfattere av denne artikkelen] (2021). Integrating serum biomarkers into prediction models for biochemical recurrence following radical prostatectomy. Cancers. 13(16), s. 1–11. doi: 10.3390/cancers13164162. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Ramirez, Manuel; Bajo-Santos, Cristina; Line, Aija; Martens-Uzunova, Elena S.; Fuente, Jesus Martinez de la & Moros, Maria [Vis alle 9 forfattere av denne artikkelen] (2021). Extracellular vesicles as a source of prostate cancer biomarkers in liquid biopsies: a decade of research. British Journal of Cancer. ISSN 0007-0920. 126. doi: 10.1038/s41416-021-01610-8. Fulltekst i vitenarkiv Vis sammendrag

  Prostate cancer is a global cancer burden and considerable effort has been made through the years to identify biomarkers for the disease. Approximately a decade ago, the potential of analysing extracellular vesicles in liquid biopsies started to be envisaged. This was the beginning of a new exciting area of research investigating the rich molecular treasure found in extracellular vesicles to identify biomarkers for a variety of diseases. Vesicles released from prostate cancer cells and cells of the tumour microenvironment carry molecular information about the disease that can be analysed in several biological fluids. Numerous studies document the interest of researchers in this field of research. However, methodological issues such as the isolation of vesicles have been challenging. Remarkably, novel technologies, including those based on nanotechnology, show promise for the further development and clinical use of extracellular vesicles as liquid biomarkers. Development of biomarkers is a long and complicated process, and there are still not many biomarkers based on extracellular vesicles in clinical use. However, the knowledge acquired during the last decade constitutes a solid basis for the future development of liquid biopsy tests for prostate cancer. These are urgently needed to bring prostate cancer treatment to the next level in precision medicine.

• Guerriero, Ilaria; Ramberg, Håkon Andre; Sagini, Krizia; Ramirez, Manuel; Tasken, Kristin Austlid & Llorente, Alicia (2021). Implication of β2-adrenergic receptor and miR-196a correlation in neurite outgrowth of LNCaP prostate cancer cells. PLOS ONE. 16:e025828(6), s. 1–11. doi: 10.1371/journal.pone.0253828. Fulltekst i vitenarkiv Vis sammendrag

  The β2-adrenergic receptor has been shown to be involved in neuroendocrine differentiation and to contribute to the development of aggressive prostate cancer. In this study we have investigated whether miR-196a plays a role in the regulation of the β2-adrenergic receptor in the LNCaP prostate cancer cell line. Our results show that the expression of miR-196a is elevated in LNCaP prostate cancer cells with reduced levels of β2-adrenergic receptor after stably transfection with three different shRNAs. Furthermore, treatment with β-blockers showed that this upregulation is strictly related to the low levels of β2-adrenergic receptor and not to the inhibition of the receptor signaling activity. Finally, we found that the reduced ability of LNCaP cells with low levels of β2-adrenergic receptor to initiate neuroendocrine differentiation under androgen depletion conditions is mediated by miR-196a. In conclusion, this study provides the rational for a role of miR-196a in the β2-adrenergic receptor mediated neuroendocrine differentiation of LNCaP prostate cancer cells.

• Ramberg, Håkon Andre; Richardsen, Elin; Souza, Gustavo Antonio De; Rakaee, Mehrdad; Stensland, Maria & Braadland, Peder Rustøen [Vis alle 13 forfattere av denne artikkelen] (2021). Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer. Carcinogenesis. ISSN 0143-3334. 42(5), s. 685–693. doi: 10.1093/carcin/bgab015. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Guldvik, Ingrid Jenny; Zuber, Verena; Braadland, Peder Rustøen; Grytli, Helene Hartvedt; Ramberg, Håkon Andre & Lilleby, Wolfgang [Vis alle 18 forfattere av denne artikkelen] (2020). Identification and Validation of Leucine-rich alpha-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification. European Urology Open Science. ISSN 2666-1691. 21, s. 51–61. doi: 10.1016/j.euros.2020.08.007. Fulltekst i vitenarkiv Vis sammendrag

  Background More accurate risk assessments are needed to improve prostate cancer management. Objective To identify blood-based protein biomarkers that provided prognostic information for risk stratification. Design, setting, and participants Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015. Outcome measurements and statistical analysis The primary outcome objectives were progression-free survival, prostate cancer–specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed. Results and limitation Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today’s clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management. Conclusions High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients. Patient summary High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.

• Arstad, Christian; Tasken, Kristin Austlid; Refinetti, Paulo; Axcrona, Ulrika; Giercksky, Karl-Erik & Ekstrøm, Per Olaf (2020). Somatic Mitochondrial DNA Point Mutations Used as Biomarkers to Demonstrate Genomic Heterogeneity in Primary Prostate Cancer. Prostate Cancer. ISSN 2090-3111. 2020. doi: 10.1155/2020/7673684. Fulltekst i vitenarkiv
• Nyakas, Marta Sølvi; Aamdal, Elin; Jacobsen, Kari Dolven; Guren, Tormod Kyrre; Aamdal, Steinar & Hagene, Kirsten Thorin [Vis alle 13 forfattere av denne artikkelen] (2019). Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma. Clinical and Experimental Immunology. ISSN 0009-9104. 197(1), s. 74–82. doi: 10.1111/cei.13283. Fulltekst i vitenarkiv Vis sammendrag

  New therapies, including the anti‐cytotoxic T lymphocyte antigen (CTLA)‐4 antibody, ipilimumab, is approved for metastatic melanoma. Prognostic biomarkers need to be identified, because the treatment has serious side effects. Serum samples were obtained before and during treatment from 56 patients with metastatic or unresectable malignant melanoma, receiving treatment with ipilimumab in a national Phase IV study (NCT0268196). Expression of a panel of 17 inflammatory‐related markers reflecting different pathways including extracellular matrix remodeling and fibrosis, vascular inflammation and monocyte/macrophage activation were measured at baseline and the second and/or third course of treatment with ipilimumab. Six candidate proteins [endostatin, osteoprotegerin (OPG), C‐reactive protein (CRP), pulmonary and activation‐regulated chemokine (PARC), growth differentiation factor 15 (GDF15) and galectin‐3 binding‐protein (Gal3BP)] were persistently higher in non‐survivors. In particular, high Gal3BP and endostatin levels were also independently associated with poor 2‐year survival after adjusting for lactate dehydrogenase, M‐stage and number of organs affected. A 1 standard deviation increase in endostatin gave 1·74 times [95% confidence interval (CI) = 1·10–2·78, P = 0·019] and for Gal3BP 1·52 times (95% CI = 1·01–2·29, <i>P</i> = 0·047) higher risk of death in the adjusted model. Endostatin and Gal3BP may represent prognostic biomarkers for patients on ipilimumab treatment in metastatic melanoma and should be further evaluated. Owing to the non‐placebo design, we could only relate our findings to prognosis during ipilimumab treatment.

• Richardsen, Elin; Andersen, Sigve; Al-Saad, Samer; Rakaee, Mehrdad; Nordby, Yngve & Pedersen, Mona Irene [Vis alle 14 forfattere av denne artikkelen] (2019). Low expression of miR-424-3p is highly correlated with clinical failure in prostate cancer. Scientific Reports. 9(10662), s. 1–10. doi: 10.1038/s41598-019-47234-0. Fulltekst i vitenarkiv Vis sammendrag

  Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22–0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer.

• Nome, Marianne Eikhom; Euceda, Leslie R.; Jabeen, Shakila; Debik, Julia; Bathen, Tone Frost & Giskeødegård, Guro F. [Vis alle 17 forfattere av denne artikkelen] (2019). Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers. International Journal of Cancer. ISSN 0020-7136. 146(1), s. 223–235. doi: 10.1002/ijc.32638. Fulltekst i vitenarkiv Vis sammendrag

  Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti‐vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine‐protein kinase erbB‐2‐negative breast cancers, we measured metabolites and inflammation‐related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation‐regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth‐differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy

• Braadland, Peder Rustøen; Ramberg, Håkon Andre; Grytli, Helene Hartvedt; Urbanucci, Alfonso; Nielsen, Heidi Kristin & Guldvik, Ingrid Jenny [Vis alle 13 forfattere av denne artikkelen] (2019). The β2-adrenergic receptor is a molecular switch for neuroendocrine transdifferentiation of prostate cancer cells. Molecular Cancer Research. ISSN 1541-7786. 17(11), s. 2154–2168. doi: 10.1158/1541-7786.MCR-18-0605. Fulltekst i vitenarkiv
• Berg, Janna; Halvorsen, Ann Rita; Bengtson, May-Bente; Tasken, Kristin Austlid; Mælandsmo, Gunhild Mari & Yndestad, Arne [Vis alle 11 forfattere av denne artikkelen] (2018). Levels and prognostic impact of circulating markers of inflammation, endothelial activation and extracellular matrix remodelling in patients with lung cancer and chronic obstructive pulmonary disease. BMC Cancer. 18(1). doi: 10.1186/s12885-018-4659-0. Fulltekst i vitenarkiv Vis sammendrag

  Background The development of both chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is influenced by smoking related chronic pulmonary inflammation caused by an excessive innate immune response to smoke exposure. In addition, the smoking induced formation of covalent bonds between the carcinogens and DNA and the accumulation of permanent somatic mutations in critical genes are important in the carcinogenic processes, and can also induce inflammatory responses. How chronic inflammation is mirrored by serum markers in COPD and LC and if these markers reflect prognosis in patients with LC is, however, largely unknown. Methods Serum levels of 18 markers reflecting inflammation, endothelial activation and extracellular matrix remodelling were analysed in 207 patients with non-small lung carcinoma (NSCLC) before surgery and 42 COPD patients. 56% of the LC patients also suffered from COPD. The serum samples were analysed by enzyme immunoassays. Results Serum levels of OPG, PTX3, AXL, ALCAM, sCD163, CD147, CatS and DLL1 were significantly higher in patients with COPD as compared to patients with LC. High sTNFR1 levels were associated with improved progression free survival (PFS) and overall survival (OS) in LC patients with (PFS hazard ratio (HR) 0.49, OS HR 0.33) and without COPD (OS HR 0.30). High levels of OPG were associated with improved PFS (HR 0.17) and OS (HR 0.14) for LC with COPD. CRP was significantly associated with overall survival regardless of COPD status. Conclusion Several markers reflecting inflammation, endothelial activation and extracellular matrix remodelling are elevated in serum from patients with COPD compared to LC patients. Presence of COPD might influence the levels of circulating biomarkers. Some of these markers are also associated with prognosis.

• Tasken, Kristin Austlid (2018). Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy. British Journal of Cancer. ISSN 0007-0920. 18((6). doi: 10.1038/bjc.2017.470. Fulltekst i vitenarkiv
• Prencipe, Maria; Fabre, Aurelie; Murphy, Thomas Brendan; Vargyas, Eszter; O'Neill, Amanda & Bjartell, Anders [Vis alle 13 forfattere av denne artikkelen] (2018). Role of serum response factor expression in prostate cancer biochemical recurrence. The Prostate. ISSN 0270-4137. 78(10), s. 724–730. doi: 10.1002/pros.23516. Fulltekst i vitenarkiv
• Braadland, Peder; Giskeødegård, Guro F.; Sandsmark, Elise; Bertilsson, Helena; Euceda, Leslie R. & Hansen, Ailin Falkmo [Vis alle 17 forfattere av denne artikkelen] (2017). Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy. British Journal of Cancer. ISSN 0007-0920. 117(11), s. 1656–1664. doi: 10.1038/bjc.2017.346. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Moen, Line Victoria; Ramberg, Håkon Andre; Zhao, Sen; Grytli, Helene Hartvedt; Sveen, Anita & Berge, Viktor [Vis alle 9 forfattere av denne artikkelen] (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), s. 111.e1–111.e8. doi: 10.1016/j.urolonc.2016.10.002. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Paur, Ingvild; Lilleby, Wolfgang; Bøhn, Siv Kjølsrud; Hulander, Erik; Klein, Willibrord & Vlatkovic, Ljiljana [Vis alle 19 forfattere av denne artikkelen] (2016). Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA. Clinical Nutrition. ISSN 0261-5614. 36(3), s. 672–679. doi: 10.1016/j.clnu.2016.06.014. Fulltekst i vitenarkiv Vis sammendrag

  Background & aims: The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. Methods: Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. Results: The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (−2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009). Conclusions: Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids.

• Ramberg, Håkon Andre; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Øgren, Hans Olav & Zhao, Sen [Vis alle 14 forfattere av denne artikkelen] (2016). PBX3 is a putative biomarker of aggressive prostate cancer. International Journal of Cancer. ISSN 0020-7136. 139(8), s. 1810–1820. doi: 10.1002/ijc.30220. Fulltekst i vitenarkiv
• Braadland, Peder; Grytli, Helene Hartvedt; Ramberg, Håkon Andre; Katz, Betina; Kellmann, Ralf & Gauthier-Landry, louis [Vis alle 18 forfattere av denne artikkelen] (2016). Low β2-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism. OncoTarget. 7(2), s. 1878–1894. doi: 10.18632/oncotarget.6479. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Braadland, Peder; Ramberg, Håkon Andre; Grytli, Helene Hartvedt & Tasken, Kristin Austlid (2015). β-Adrenergic Receptor Signaling in Prostate Cancer. Frontiers in Oncology. doi: 10.3389/fonc.2014.00375. Fulltekst i vitenarkiv Vis sammendrag

  Enhanced sympathetic signaling, often associated with obesity and chronic stress, is increasingly acknowledged as a contributor to cancer aggressiveness. In prostate cancer, intact sympathetic nerves are critical for tumor formation, and sympathectomy induces apoptosis and blocks tumor growth. Perineural invasion, involving enrichment of intra-prostatic nerves, is frequently observed in prostate cancer and is associated with poor prognosis. β2-adrenergic receptor (ADRB2), the most abundant receptor for sympathetic signals in prostate luminal cells, has been shown to regulate trans-differentiation of cancer cells to neuroendocrine-like cells and to affect apoptosis, angiogenesis, epithelial–mesenchymal transition, migration, and metastasis. Epidemiologic studies have shown that use of β-blockers, inhibiting β-adrenergic receptor activity, is associated with reduced prostate cancer-specific mortality. In this review, we aim to present an overview on how β-adrenergic receptor and its downstream signaling cascade influence the development of aggressive prostate cancer, primarily through regulating neuroendocrine differentiation.

• Grytli, Helene Hartvedt; Fagerland, Morten; Fosså, Sophie Dorothea & Tasken, Kristin Austlid (2014). Association between use of β-blockers and prostate cancer-specific survival: A cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. European Urology. ISSN 0302-2838. 65(3), s. 635–641. doi: 10.1016/j.eururo.2013.01.007. Fulltekst i vitenarkiv
• Grytli, Helene Hartvedt; Fagerland, Morten; Fosså, Sophie Dorothea; Tasken, Kristin Austlid & Håheim, Lise Lund (2013). Use of beta-blockers is associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy. The Prostate. ISSN 0270-4137. 73(3), s. 250–260. doi: 10.1002/pros.22564. Fulltekst i vitenarkiv
• Eide, Turid; Ramberg, Håkon Andre; Glackin, Carlotta A.; Tindall, Donald & Tasken, Kristin Austlid (2013). TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells. Cancer Cell International. 13. doi: 10.1186/1475-2867-13-4. Fulltekst i vitenarkiv Vis sammendrag

  Background TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process. Methods Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA’s and reporter constructs. Results We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate–specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells. Conclusion Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.

• Lazarevic, Bato; Hammarstrøm, Clara Louise; Yang, Jing; Ramberg, Håkon Andre; Diep, Lien My & Karlsen, Steinar [Vis alle 10 forfattere av denne artikkelen] (2012). The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy. British Journal of Nutrition. ISSN 0007-1145. 108(12), s. 2138–2147. doi: 10.1017/S0007114512000384. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Lazarevic, Bato; Boezelijn, Gro; Diep, Lien My; Kvernrød, Kristin; Øgren, Hans Olov & Ramberg, Håkon Andre [Vis alle 16 forfattere av denne artikkelen] (2011). Efficacy and Safety of Short-Term Genistein Intervention in Patients with Localized Prostate Cancer Prior to Radical Prostatectomy: A Randomized, Placebo-Controlled, Double-Blind Phase 2 Clinical Trial. Nutrition and Cancer. ISSN 0163-5581. 63(6), s. 889–898. doi: 10.1080/01635581.2011.582221. Fulltekst i vitenarkiv
• Dizeyi, Nishtman; Hedlund, Petter; Bjartell, Anders; Tinzl, Martina; Tasken, Kristin Austlid & Abrahamsson, Per-Anders (2011). Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines. Urologic Oncology. ISSN 1078-1439. 29(4), s. 436–445. doi: 10.1016/j.urolonc.2009.09.013. Fulltekst i vitenarkiv
• Røtterud, Ranveig; Malmstrom, Per-Uno; Wahlqvist, Rolf & Tasken, Kristin Austlid (2010). The star chart to Ta bladder cancer: An unsophisticated analysis of two-dimensional gel electrophoresis proteome maps. Scandinavian Journal of Urology and Nephrology. ISSN 0036-5599. 44(2), s. 76–83. doi: 10.3109/00365590903510729. Fulltekst i vitenarkiv
• Ramberg, Håkon; Eide, Turid; Krobert, Kurt Allen; Levy, Finn Olav; Dizeyi, N & Bjartell, AS [Vis alle 8 forfattere av denne artikkelen] (2008). Hormonal regulation of beta(2)-adrenergic receptor level in prostate cancer. The Prostate. ISSN 0270-4137. 68(10), s. 1133–1142. doi: 10.1002/pros.20778. Fulltekst i vitenarkiv
• Kvissel, Anne Katrine; Ramberg, Håkon; Eide, Turid; Svindland, Aud; Skålhegg, Bjørn Steen & Tasken, Kristin Austlid (2007). Androgen dependent regulation of protein kinase A subunits in prostate cancer cells. Cellular Signalling. ISSN 0898-6568. 19(2), s. 401–409. doi: 10.1016/j.cellsig.2006.07.011. Fulltekst i vitenarkiv
• Tasken, Kristin Austlid; Angelsen, A.; Svindland, Aud; Eide, Turid; Berge, V. & Wahlquist, R. [Vis alle 7 forfattere av denne artikkelen] (2005). Markører for påvisning av prostatakreft og prediksjon av prognose. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 125(23), s. 3279–82. Fulltekst i vitenarkiv
• Dizeyi, N; Bjartell, A; Hedlund, P; Tasken, Kristin Austlid; Gadaleanu, V & Abrahamsson, PA (2005). Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines. European Urology. ISSN 0302-2838. 47, s. 895–900. Fulltekst i vitenarkiv
• Eide, Turid; Tasken, Kristin Austlid; Carlson, C.; Williams, G.; Jahnsen, Tore & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2003). Protein kinase A-anchoring protein AKAP95 interacts with MCM2, a regulator of DNA replication. Journal of Biological Chemistry. ISSN 0021-9258. 278(29), s. 26750–26756. Fulltekst i vitenarkiv
• Tasken, Kristin Austlid; Jacobsen, Frede Wælgaard; Eikvar, Lars Kristian; Hansson, Vidar & Haugen, Trine B. (1995). The alpha-subunit mRNAs for Gs and Go2 are differentially regulated by protein kinase A and protein kinase C in rat Sertoli cells. Biochimica et Biophysica Acta. ISSN 0006-3002. 1260(3), s. 269–275. Fulltekst i vitenarkiv
• Tasken, Kjetil; Skålhegg, Bjørn Steen; Tasken, Kristin Austlid; Solberg, Rigmor; Levy, Finn Olav & Lea, Tor Erling [Vis alle 8 forfattere av denne artikkelen] (1994). Diversity and regulation of cAMP-dependent protein kinases. I Verhoeven, G. & Habenicht, U.-F. (Red.), Molecular and Cellular Endocrinology of the Testis. Springer. ISSN 9783662221891. s. 185–217. Fulltekst i vitenarkiv
• Tasken, Kjetil; Andersson, Kristin Brevik; Skålhegg, Bjørn Steen; Tasken, Kristin Austlid; Hansson, Vidar & Jahnsen, Tore [Vis alle 7 forfattere av denne artikkelen] (1993). Reciprocal regulation of mRNA and protein for subunits of cAMP-dependent protein kinase (RI alpha and C alpha) by cAMP in a neoplastic B cell line (Reh). Journal of Biological Chemistry. ISSN 0021-9258. 268(31), s. 23483–23489. Fulltekst i vitenarkiv
• Jahnsen, Tore; Tasken, Kristin Austlid; Landmark, Brynjar Fowels; Knutsen, HK; Solberg, R. & Foss, Kari Bente [Vis alle 10 forfattere av denne artikkelen] (1993). Multiple genes for regulatrory and catalytic subunits of cyclic-AMP dependent protein kinases are differentially expressed and regulated in testicular cells. I Mornex, René; Jaffiol, C. & Leclère, J. (Red.), Progress in endocrinology: the proceedings of the Ninth International Congress of Endocrinology, Nice 1992. Parthenon Pub. Group. ISSN 9781850704690. s. 29–33. Fulltekst i vitenarkiv
• Knutsen, Helle Katrine; Tasken, Kristin Austlid; Eskild, Winnie; Jahnsen, Tore & Hansson, Vidar (1992). Half-lives of different sized mRNAs for the PKA subunit RI alpha are regulated differently in response to inhibition of transcription and translation. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 184(1), s. 454–460. Fulltekst i vitenarkiv
• Tasken, Kristin Austlid; Knutsen, Helle Katrine; Eikvar, Lars Kristian; Tasken, Kjetil; Eskild, Winnie & Jahnsen, Tore [Vis alle 7 forfattere av denne artikkelen] (1992). Protein kinase C activation by 12-O-tetradecanoylphorbol 13-acetate modulates messenger ribonucleic acid levels for two of the regulatory subunits of 3',5'-cyclic adenosine monophosphate-dependent protein kinases (RII beta and RI alpha) via multiple and distinct mechanisms. Endocrinology. ISSN 0013-7227. 130(3), s. 1271–1280. Fulltekst i vitenarkiv
• Tasken, Kristin Austlid; Knutsen, Helle Katrine; Attramadal, Håvard; Tasken, Kjetil; Jahnsen, Tore & Hansson, Vidar [Vis alle 7 forfattere av denne artikkelen] (1991). Different Mechanisms are Involved in cAMP Mediated Induction of mRNAs for Subunits of cAMP-Dependent Protein Kinases. Molecular Endocrinology. ISSN 0888-8809. 5(1), s. 21–28. Fulltekst i vitenarkiv
• Knutsen, Helle Katrine; Tasken, Kristin Austlid; Eskild, Winnie; Jahnsen, Tore & Hansson, Vidar (1991). Adenosine 3',5'-monophosphate-dependent stabilization of messenger ribonucleic acids (mRNAs) for protein kinase-A (PKA) subunits in rat Sertoli cells: rapid degradation of mRNAs for PKA subunits is dependent on ongoing RNA and protein synthesis. Endocrinology. ISSN 0013-7227. 129(5), s. 2496–2502. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Ramberg, Håkon; Korsnes, Monica Suarez; Korsnes, Reinert; Sørensen, Vigdis; Katz, Betina & Tasken, Kristin Austlid (2023). What is the stress about cancer nerve crosstalk? Cell tracking in the tumor-neural niche. Fulltekst i vitenarkiv
• Ramberg, Håkon; Korsnes, Monica Suarez; Korsnes, Reinert & Tasken, Kristin Austlid (2023). UP09 - Single-cell tracking of prostate cancer and nerve cells in co-culture. Fulltekst i vitenarkiv
• Braadland, PR; Giskeødegård, Guro F.; Sandsmark, Elise; Bertilsson, Helena; Wood, Leslie Euceda & Hansen, Ailin Falkmo [Vis alle 15 forfattere av denne artikkelen] (2016). Distinguishing indolent from agressive prostate cancer by ex vivo metabolic fingerprinting. Fulltekst i vitenarkiv
• Grytli, Helene Hartvedt; Fagerland, Morten; Fosså, Sophie Dorothea & Tasken, Kristin Austlid (2013). Reply to Chris R. Cardwell, Samy Suissa and Liam J. Murray's Letter to the Editor re: Helene Hartvedt Grytli, Morten Wang Fagerland, Sophie D. Fossa, Kristin Austlid Tasken. Association between use of beta-blockers and prostate cancer-specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.01.007. European Urology. ISSN 0302-2838. 64(1), s. E11–E12. doi: 10.1016/j.eururo.2013.03.045. Fulltekst i vitenarkiv

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