Constitutively active androgen receptor variants (AR-V) lacking the ligand binding domain (LBD) may promote development of castration-resistant prostate cancer (CRPC). The expression AR-Vs in clinically most important metastatic site, bone, has, however, not been well documented. Our aim was therefore to compare levels hormone-naive (HN) and CRPC bone metastases comparison primary PC non-malignant tissue, as relation AR protein expression, whole-genome transcription profiles patient...

Background and purpose — There is no consensus on the association between global femoral offset (FO) outcome after total hip arthroplasty (THA). We assessed FO patients’ reported function, quality of life, abductor muscle strength.Patients methods included 250 patients with unilateral osteoarthritis who underwent a THA. Before operation, patient’s function was evaluated Western Ontario McMaster Universities Osteoarthritis (WOMAC) index life EQ-5D. At 1-year follow-up, same scores also...

Background Metastasis to the bone is one clinically important features of prostate cancer (PCa). Current diagnostic methods cannot predict metastatic PCa at a curable stage disease. Identification metabolic pathways involved in growth metastases therefore has potential improve prognostication as well therapy. Methodology/Principal Findings Metabolomics was applied for study (n = 20) comparison with corresponding normal 14), and furthermore malignant 13) benign 17) tissue plasma samples...

Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly cancers not driven by androgen receptor (AR) activation.To identify molecular subgroups of PC bone metastases relevance therapy.Fresh-frozen metastasis samples from CRPC (n=40), treatment-naïve (n=8), or other malignancies (n=12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles...

Purpose: Bone is the most predominant site of distant metastasis in prostate cancer, and patients have limited therapeutic options at this stage.Experimental Design: We performed a system-wide quantitative proteomic analysis bone metastatic tumors from 22 operated to relieve spinal cord compression. At time surgery, had relapsed after androgen-deprivation therapy, while 5 were previously untreated. An extended cohort cancer metastases (n = 65) was used for immunohistochemical...

Abstract Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark the translocation t(12;22)(q13;q12) resulting in chimeric EWS/ATF1 gene which 3′‐terminal part of EWS at 22q replaced by ATF1 12q. To date, only 13 cases CCS have been analyzed for fusion genes transcription level, there no information about breakpoints genomic level. In present study, we describe molecular genetic characteristics from 10...

Background Intra-tumoral steroidogenesis and constitutive androgen receptor (AR) activity have been associated with castration-resistant prostate cancer (CRPC). This study aimed to examine if CRPC bone metastases expressed higher levels of steroid-converting enzymes than untreated metastases. Steroidogenic enzyme were also analyzed in relation expression constitutively active AR variants (AR-Vs) clinical pathological variables. Methodology/Principal Findings Untreated, hormone-naïve (HN, n =...

Androgen receptors (ARs) are probably of importance during all phases prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms complications (metastasis surgery, n=58), immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) chromogranin A, results...

In Brief Study Design. We retrospectively analyzed prognostic factors for survival in patients with prostate cancer operated metastatic spinal cord compression. Objective. The aim was to obtain a clinical score prediction of after surgery. Summary Background Data. Survival prognosis is important when deciding about treatment criteria identifying who may benefit from surgical are unclear. Methods. study comprised 68 consecutive compression at Umeå University Hospital, Sweden. indication...

Background and purpose The criteria for selecting patients who may benefit from surgery of spinal cord compression in metastatic prostate cancer are poorly defined. We therefore studied operated order to evaluate outcome find predictors survival.Patients methods reviewed the records 54 consecutive with were at Umeå University Hospital. indication was neurological deficit due compression. 41 had hormone-refractory 13 previously untreated, hormone-naïve cancer. 29 posterior decompression only,...

Background. Spinal cord compression is an oncological and surgical emergency. Delays in referral diagnosis may influence functional outcome. It therefore important to identify patients who will regain or maintain the ability walk after surgery. The aim of present study was examine current practice for prostate cancer with spinal prognostic factors neurological outcome Patients methods. includes 68 consecutive underwent surgery due compromise. Intervals from onset symptoms referral,...

Advanced prostate cancer frequently metastasizes to bone and induces a mixed osteoblastic/osteolytic response. Standard treatment for metastatic is androgen-deprivation therapy (ADT) that also affects biology. Treatment options patients relapsing after ADT are limited, particularly in cases where castration-resistance does not depend on androgen receptor (AR) activity. Patients with non-AR driven metastases may, however, benefit from therapies targeting the tumor microenvironment. Therefore,...

The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants steroid-converting enzymes has been poorly examined. Specific aim was to examine in PC bone metastases explore molecular functional consequences this, with the long-term goal identifying novel targets for treatment.Gene assessed by fluorescence situ hybridization cryo-sections clinical (n = 40)...

Patients with metastatic prostate cancer (PC) are treated androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related receptor (AR) activity described....

Bone metastasis is the lethal end‐stage of prostate cancer (PC), but biology bone metastases poorly understood. The overall aim this study was therefore to explore molecular variability in PC potential importance for therapy. Specifically, genome‐wide expression profiles from untreated patients ( n = 12) and treated with androgen‐deprivation therapy (ADT, 60) were analyzed relation patient outcome morphological characteristics paired primary tumors. Principal component analysis unsupervised...

Background and purpose - Metastatic spinal cord compression (MSCC) as the initial manifestation of malignancy (IMM) limits time for diagnostic workup; most often, treatment is required before final primary tumor diagnosis. We evaluated neurological outcome, complications, survival, manner diagnosing in patients who were operated MSCC IMM. Patients methods Records 69 consecutive (51 men) underwent surgery IMM reviewed. The had no history cancer when they presented with pain (n = 2) and/or...

Background and purpose — Uncemented monoblock cruciate retaining (CR) trabecular metal (TM) tibial components in total knee arthroplasty (TKA) work well the long-term perspective patients ≤ 60 years. Younger persons expect nearly normal flexion after TKA, but CR implants generally achieve less compared with posterior stabilized (PS) implants. Cemented PS implantshave higher revision rate than Can an uncemented TM implant be used safely younger patients? Patients methods 40 (49 knees) age...

Study Design.. We retrospectively analyzed Spinal Instability Neoplastic Score (SINS) in 110 patients with prostate cancer operated for metastatic spinal cord compression (MSCC). Objective.. aimed to investigate the association between SINS and clinical outcomes after surgery MSCC cancer. Summary of Background Data.. The is a useful tool assessing tumor-related instability, but its prognostic value regarding survival neurological outcome still controversial. Methods.. consecutive who...

To improve treatment of metastatic prostate cancer, the biology metastases needs to be understood. We recently described three subtypes cancer bone (MetA-C), based on differential gene expression. The aim this study was verify clinical relevance these and explore their relations genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated 21), or castration-resistant 65) from a total 67 patients. Previously published sequencing data 573...

Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized high cell cycle activity, low androgen receptor (AR) and a limited response to standard deprivation therapy (ADT). Complementary treatments should preferably introduced early on if risk developing subtype predicted behigh. In this study, we therefore examined metastatic patient outcome after ADT could...