{"entity": "researcher", "timestamp": "2026-07-22T16:19:26.495Z", "family": "Halvorsen", "given": "Bente", "initials": "B", "orcid": "0000-0002-6529-6485", "affiliations": ["Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.", "Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/83218278a90c41609ea44fcd6315d395.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/83218278a90c41609ea44fcd6315d395"}}, "publications": [{"entity": "publication", "iuid": "e423aa4f3d3743ffa8ead1c41ea5a808", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e423aa4f3d3743ffa8ead1c41ea5a808.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e423aa4f3d3743ffa8ead1c41ea5a808"}}, "title": "Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.", "authors": [{"family": "Thulin", "given": "Malin Hagberg", "initials": "MH"}, {"family": "Ramberg", "given": "H\u00e5kon", "initials": "H"}, {"family": "Nielsen", "given": "Heidi Kristin", "initials": "HK"}, {"family": "Grytli", "given": "Helene Hartvedt", "initials": "HH"}, {"family": "Sivanesan", "given": "Shivanthe", "initials": "S"}, {"family": "Pandya", "given": "Abhilash D", "initials": "AD"}, {"family": "Seip", "given": "Kotryna", "initials": "K"}, {"family": "Andressen", "given": "Kjetil Wessel", "initials": "KW"}, {"family": "Linder", "given": "Anna", "initials": "A", "orcid": "0000-0002-9444-1346", "researcher": {"href": "https://publications.scilifelab.se/researcher/38b4f1c441ff49b891db4d7fb8163491.json"}}, {"family": "\u00d8ijordsbakken", "given": "Miriam", "initials": "M"}, {"family": "Poutanen", "given": "Matti", "initials": "M"}, {"family": "Katz", "given": "Betina", "initials": "B"}, {"family": "Halvorsen", "given": "Bente", "initials": "B", "orcid": "0000-0002-6529-6485", "researcher": {"href": "https://publications.scilifelab.se/researcher/83218278a90c41609ea44fcd6315d395.json"}}, {"family": "M\u00e6landsmo", "given": "Gunhild Mari", "initials": "GM"}, {"family": "Task\u00e9n", "given": "Kristin Austlid", "initials": "KA", "orcid": "0000-0001-5530-4915", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c58b6542626483697216077c630309a.json"}}], "type": "journal article", "published": "2025-06-17", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "23", "issue": "1", "pages": "672", "issn-l": "1479-5876"}, "abstract": "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.\n\nAn 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.\n\nA 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.\n\nThe 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.", "doi": "10.1186/s12967-025-06644-7", "pmid": "40528241", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12175445"}, {"db": "pii", "key": "10.1186/s12967-025-06644-7"}], "notes": [], "created": "2025-07-08T13:57:28.735Z", "modified": "2025-11-04T11:53:28.029Z"}, {"entity": "publication", "iuid": "85067a3ac4764a808733b9d4d4adc266", "links": {"self": {"href": "https://publications.scilifelab.se/publication/85067a3ac4764a808733b9d4d4adc266.json"}, "display": {"href": "https://publications.scilifelab.se/publication/85067a3ac4764a808733b9d4d4adc266"}}, "title": "Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow.", "authors": [{"family": "Svedlund Eriksson", "given": "Elin", "initials": "E", "orcid": "0009-0006-0169-6929", "researcher": {"href": "https://publications.scilifelab.se/researcher/afb8b198881944a28e575e8ca8a2cc1d.json"}}, {"family": "Lantero Rodriguez", "given": "Marta", "initials": "M", "orcid": "0000-0002-9912-6716", "researcher": {"href": "https://publications.scilifelab.se/researcher/bee7c52fd83149fbbb01ced1cf5fa79d.json"}}, {"family": "Halvorsen", "given": "Bente", "initials": "B", "orcid": "0000-0002-6529-6485", "researcher": {"href": "https://publications.scilifelab.se/researcher/83218278a90c41609ea44fcd6315d395.json"}}, {"family": "Johansson", "given": "Inger", "initials": "I", "orcid": "0009-0008-3579-9031", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc07dcc5a824676a0f788ebe060ca02.json"}}, {"family": "M\u00e5rtensson", "given": "Anna K F", "initials": "AKF", "orcid": "0000-0002-8786-4965", "researcher": {"href": "https://publications.scilifelab.se/researcher/13ca4b04916d4318b8e00f1f5f4ca6d3.json"}}, {"family": "Wilhelmson", "given": "Anna S", "initials": "AS", "orcid": "0000-0003-0640-0251", "researcher": {"href": "https://publications.scilifelab.se/researcher/73ed1ad8dfa2406081cef9eb005b3ad6.json"}}, {"family": "Huse", "given": "Camilla", "initials": "C", "orcid": "0000-0002-7694-5196", "researcher": {"href": "https://publications.scilifelab.se/researcher/1025010995224e44bae6f9c15813de38.json"}}, {"family": "Ueland", "given": "Thor", "initials": "T"}, {"family": "Aukrust", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-0919-836X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b52ec6832f0742b4be1f6dd2e455a1ed.json"}}, {"family": "Broch", "given": "Kaspar", "initials": "K", "orcid": "0000-0003-4316-805X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c4d9562e7294f849d3ff4508d353bf9.json"}}, {"family": "Gullestad", "given": "Lars", "initials": "L"}, {"family": "Amundsen", "given": "Brage H\u00f8yem", "initials": "BH", "orcid": "0000-0001-7914-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7ee62e8f93047258965bcf42bb4a475.json"}}, {"family": "Andersen", "given": "Geir \u00d8ystein", "initials": "G\u00d8", "orcid": "0000-0003-1578-6440", "researcher": {"href": "https://publications.scilifelab.se/researcher/a498990cfa894f74bd3a273a1bbaee58.json"}}, {"family": "Karlsson", "given": "Mikael C I", "initials": "MCI", "orcid": "0000-0001-5582-614X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b7a0612c55f4ab8865b6e5f59347271.json"}}, {"family": "Hagberg Thulin", "given": "Malin", "initials": "M", "orcid": "0000-0002-8673-1247", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbf6e0d2d6f748e39f32a70e1e4d597f.json"}}, {"family": "Camponeschi", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-6472-2438", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbaffafd6a24f4abed1e402219fa472.json"}}, {"family": "Trompet", "given": "Dana", "initials": "D", "orcid": "0000-0001-9472-6184", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ef4d02ec2e1427088522df2a759bf3a.json"}}, {"family": "Hammarsten", "given": "Ola", "initials": "O"}, {"family": "Redfors", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Omerovic", "given": "Elmir", "initials": "E"}, {"family": "Levin", "given": "Malin C", "initials": "MC"}, {"family": "Chagin", "given": "Andrei S", "initials": "AS", "orcid": "0000-0002-2696-5850", "researcher": {"href": "https://publications.scilifelab.se/researcher/909bca2fc68645e980a93b99dc150e4c.json"}}, {"family": "Dahl", "given": "Tuva B", "initials": "TB", "orcid": "0000-0001-7818-9411", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff93848d0aac4a9fbf8ec2bbedebadea.json"}}, {"family": "Tivesten", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-8318-0486", "researcher": {"href": "https://publications.scilifelab.se/researcher/55ade4099dfd4859970a6fe21af50870.json"}}], "type": "journal article", "published": "2025-02-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "1142", "issn-l": "2041-1723"}, "abstract": "Men develop larger infarct sizes than women after a myocardial infarction (MI), but the mechanism underlying this sex difference is unknown. Here, we demonstrated that blood neutrophil counts post-MI were higher in male than female mice. Castration-induced testosterone deficiency reduced blood neutrophil counts to the level in females and increased survival post-MI. These effects were mimicked by Osterix-directed ablation of the androgen receptor in bone marrow (BM). Mechanistically, androgens downregulated the leukocyte retention factor CXCL12 in BM stromal cells. Post-hoc analysis of clinical trial data showed that neutrophilia was greater in men than women after reperfusion of first-time ST-elevation MI, and tocilizumab, an interleukin-6 receptor inhibitor, reduced blood neutrophil counts and infarct size to a greater extent in men than women. Our work reveals a previously unknown mechanism connecting testosterone with neutrophilia and MI injury via BM and identifies the importance of considering sex when developing anti-inflammatory strategies to treat MI.", "doi": "10.1038/s41467-025-56217-x", "pmid": "39910039", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11799197"}, {"db": "pii", "key": "10.1038/s41467-025-56217-x"}], "notes": [], "created": "2025-07-08T13:56:49.778Z", "modified": "2025-11-04T11:38:37.313Z"}]}