Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.

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.

Biobanking after Radical Prostatectomy: Comparison of Slice and Punch Protocols.

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.

Systemic interrogation of immune-oncology-related proteins in patients with locally advanced prostate cancer undergoing androgen deprivation and intensity-modulated radiotherapy.

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.

Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer.

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.

Association of β-Blocker Use at Time of Radical Prostatectomy With Rate of Treatment for Prostate Cancer Recurrence.

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.

Extracellular vesicles as a source of prostate cancer biomarkers in liquid biopsies: a decade of research.

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.

The β-Adrenergic Receptor Is a Molecular Switch for Neuroendocrine Transdifferentiation of Prostate Cancer Cells.

The incidence of treatment-related neuroendocrine prostate cancer (t-NEPC) is rising as more potent drugs targeting the androgen signaling axis are clinically implemented. Neuroendocrine transdifferentiation (NEtD), an putative initial step in t-NEPC development, is induced by androgen-deprivation therapy (ADT) or anti-androgens, and by activation of the β-adrenergic receptor (ADRB2) in prostate cancer cell lines. Thus, understanding whether ADRB2 is involved in ADT-initiated NEtD may assist in developing treatment strategies that can prevent or reverse t-NEPC emergence, thereby prolonging therapeutic responses.

Role of serum response factor expression in prostate cancer biochemical recurrence.

Background: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment.

Observed correlation between the expression levels of catalytic subunit, Cβ2, of cyclic adenosine monophosphate-dependent protein kinase and prostate cancer aggressiveness.

Background: Today overtreatment of indolent prostate cancers and undertreatment of aggressive prostate cancer are a major concern for patients, their families, and the health care system. New biomarkers distinguishing indolent and aggressive prostate cancer are needed to improve precision medicine. In prostate cancer, protein kinase A (PKA) is known to activate the androgen receptor and published data indicate that PKA subunits can act as predictive markers for response to radiation and chemotherapy.

PBX3 is a putative biomarker of aggressive prostate cancer.

There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis.

Low β₂-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism.

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.

β-Adrenergic Receptor Signaling in Prostate Cancer.

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.

TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells.

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.

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.

Background: We recently reported reduced prostate cancer (PCa)-specific mortality for β-blocker users among patients receiving androgen-deprivation therapy in a health survey cohort including 655 PCa patients. Information on clinical characteristics was limited.

Objective: To assess the association between β-blockers and PCa-specific mortality in a cohort of 3561 prostate cancer patients with high-risk or metastatic disease, and to address potential confounding from the use of statins or acetylsalicylic acid (ASA).

Use of β-blockers is associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy.

Background: Experimental evidence suggests a role for the β(2) -adrenergic receptor pathway in prostate cancer (PCa). We have investigated the association of β-blocker use with PCa incidence and survival in a Norwegian cohort.

Methods: Data from the Oslo II study in 2000 (n = 6515) were linked with information from the Cancer Registry of Norway and Statistics Norway.

Regulation of PBX3 expression by androgen and Let-7d in prostate cancer.

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.

Hormonal regulation of beta2-adrenergic receptor level in prostate cancer.

Background: Androgen deprivation is the only effective systemic therapy available for patients with prostatic carcinoma, but is associated with a gradual transition to a hormone-refractory prostate cancer (HRCAP) in which ligand-independent activation of the androgen receptor has been implicated. The beta(2)-adrenergic receptor (beta(2)-AR) is a well-known activator of the androgen receptor.

Methods: Prostatic cell lines were analyzed using cDNA micro-array, real time RT-PCR, radioligand binding assay, cAMP measurements, transfection and thymidine incorporation assay.

Androgen dependent regulation of protein kinase A subunits in prostate cancer cells.

Neuroendocrine (NE) cells may play a role in prostate cancer progression. Both androgen deprivation and cAMP are well known inducers of NE differentiation (NED) in the prostate. Gene-expression profiling of LNCaP cells, incubated in androgen stripped medium, showed that the Cbeta isoform of PKA is up-regulated during NE differentiation.

[Markers for diagnosis, prediction and prognosis of prostate cancer].

Background: Prostate cancer is the most frequent new cancer diagnosis in the western world today. There is an urgent need to obtain validated molecular markers that can identify clinically significant prostate cancer.

Material And Methods: The article represents our view of the current status of molecular markers in diagnosis of prostate cancer based on literature searches (PubMed).

USF2 inhibits C/EBP-mediated transcriptional regulation of the RIIbeta subunit of cAMP-dependent protein kinase.

Background: Cyclic AMP-dependent protein kinase (PKA) plays a central role in regulation of energy metabolism. Upon stimulation of testicular Sertoli cells by follicle stimulating hormone (FSH), glycolysis is activated to increase the production of nutrients for the germ cells, and a new regulatory subunit of cAMP-dependent protein kinase, RIIbeta, is induced. We have previously shown that production of the transcription factor C/EBPbeta is rapidly increased by FSH and cAMP in primary Sertoli cell cultures, and that C/EBPbeta induces the RIIbeta promoter.