Search Results (248)

Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood. Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation. Results: Prostate-specific antigen (PSA)—the clinically widely used blood biomarker for PCa—emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3′-untranslated region (3′-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues. Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone. Full article

Background/Objectives: Atypical cartilaginous tumours (ACTs) are intermediate, locally aggressive chondroid tumours in the appendicular skeleton. Due to the potential for transformation into high-grade chondrosarcomas, management typically consists of regular MRI follow-up and, occasionally, surgery. We primarily aimed to examine the rate of malignant transformation in ACTs in our hospital; secondarily, we aimed to identify the factors influencing management choices and outcomes. Methods: All patients referred between 2013 and 2020 with a long-bone ACT were identified from the unit database. For this retrospective study, we analysed the imaging, management, and outcomes for the patients discussed at our musculoskeletal radiological conference. Results: A total of 59 patients were included; of these, 0 cases of malignant transformation were observed with a mean follow-up time of 8.4 years. Of the presenting cases, the musculoskeletal radiological conference advised that 6 should be biopsied, 40 should receive MRI follow-up, 7 should receive X-ray follow-up, and 6 should be re-examined in clinic. Subsequently, 12 patients underwent surgery due to continued pain, diagnostic uncertainty, and historical practices. Of these, seven experienced continued post-operative pain. Conclusions: None of the encountered ACTs underwent malignant transformation, supporting previous findings that this transformation is a rare phenomenon. Furthermore, of the small sample of patients undergoing surgery, less than half were left pain-free. These findings support a more conservative approach to ACT management, with the potential to discharge after an initial review. Full article

Background/Objectives: Management of cancer treatment-induced bone loss (CTIBL) is essential for preserving quality of life among breast cancer (BC) patients receiving endocrine therapy. However, bone-modifying agents (BMAs) remain underused and delayed. In 2014, IRST launched the first bone health outpatient service in Romagna (the eastern area of the Emilia-Romagna region). A multi-centre, retrospective observational study with propensity score matching (PSM) was conducted to evaluate the impact of the IRST organisational model on bone health. Methods: The PSM matched the Emilia-Romagna patients who underwent BC surgery between 2014 and 2022 and were in follow-up in the Romagna area. Patients were grouped as follows: (1) IRST and (2) other Romagna hospitals (without bone health service, i.e., the control group). The matching was based on age, in situ/invasive cancer, and type of early-stage treatment (hormone treatment vs. chemotherapy). Logistic regression and Cox proportional-hazard models assessed factors associated with bone care treatment initiation and timings, respectively. Results: After PSM, we matched 3112 of the 8021 eligible patients into the two cohorts. IRST patients were 39% more likely to receive BMAs (OR: 1.393; 95% CI: 1.236–1.571) and initiated treatment approximately 12 months earlier. We observed that patients with invasive tumours were 77% more likely to initiate bone therapy than those with in situ tumours (OR: 1.766; 95% CI: 1.237–2.585). The early initiation of bone health therapy was influenced by age (p < 0.001) and neoadjuvant chemotherapy treatment (p < 0.001). Conclusions: The IRST model demonstrates responsiveness to bone health needs in BC patients and may be implemented elsewhere to support integrated CTIBL care. Full article

Background/Objectives: Bone reconstruction using megaprostheses is increasingly performed following bone tumour resections, including sarcomas, to enhance patient outcomes and quality of life. However, this is a complex patient group, and there is little consensus as to postoperative rehabilitation and associated outcomes. Methods: A systematic search was conducted in MEDLINE and EMBASE databases according to the Implementing Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidelines. Studies describing rehabilitation protocols and functional outcomes following bone tumour resection and modular oncologic megaprosthesis reconstruction were included. All papers were individually assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tool. Results: The search generated 105 records, 28 underwent full-text review, and 13 studies were included. Available data reflect 371 patients with a mean age of 49.17 (S.D. 21.40) years and a mean postoperative follow-up of 41.88 (S.D. 32.88) months. Surgical indications were documented as sarcomas in 9 studies, and tumour metastasis to the bone in 10 studies. Rehabilitation protocols were reported in 5 studies following proximal humerus resection with a mean dislocation rate of 14.5% (S.D. 5.26). All protocols advised brace immobilisation for a period ranging between 10 days and 6 months. Superior Constant-Murley shoulder score was reported in patients with early active isometric exercises at 6 weeks. Six studies reported proximal femur prosthesis rehabilitation and functional outcomes, with a mean dislocation rate of 10% (S.D. 9.82). Enhanced outcomes were reported in studies employing early mobilisation. Two studies assessed distal femur prosthesis; both studies reported similar protocols with full weight bearing 3 weeks following surgery. The methodological quality of the studies varied, but was overall modest, with 10/13 studies meeting at least 50% of JBI reporting criteria. Conclusions: The existing literature on rehabilitation and outcomes in orthopaedic oncology patients following arthroplasty with megaprosthesis is limited, with rehabilitative protocols variably described. However, it seems that early active mobilisation does not increase the risk of joint dislocations or infections. Full article

Osteoarthritis (OA) is a multifactorial chronic musculoskeletal disorder characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Conventional diagnostic modalities, including radiographic imaging and symptom-based assessments, primarily detect disease in its later stages, limiting the potential for timely intervention. Inflammatory biomarkers, particularly Interleukin-6 (IL-6), Tumour Necrosis Factor-alpha (TNF-α), and Myeloperoxidase (MPO), have emerged as biologically relevant indicators of disease activity, with potential applications as companion diagnostics in precision medicine. This review examines the diagnostic and prognostic relevance of IL-6, TNF-α, and MPO in OA, focusing on their mechanistic roles in inflammation and joint degeneration, particularly through the activity of fibroblast-like synoviocytes (FLSs). The influence of sample type (serum, plasma, synovial fluid) and analytical performance, including enzyme-linked immunosorbent assay (ELISA), is discussed in the context of biomarker detectability. Advanced statistical and computational methodologies, including rank-based analysis of covariance (ANCOVA), discriminant function analysis (DFA), and Cox proportional hazards modelling, are explored for their capacity to validate biomarker associations, adjust for demographic variability, and stratify patient risk. Further, the utility of synthetic data generation, hierarchical clustering, and dimensionality reduction techniques (e.g., t-distributed stochastic neighbour embedding) in addressing inter-individual variability and enhancing model generalisability is also examined. Collectively, this synthesis supports the integration of biomarker profiling with advanced analytical modelling to improve early OA detection, enable patient-specific classification, and inform the development of targeted therapeutic strategies. Full article

Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), cancer stemness, extracellular matrix (ECM) remodelling, and activation of key signalling pathways such as Wingless/Integrated (Wnt) Wnt/β-catenin and PI3K/Akt. Hypoxia also enhances the secretion of extracellular vesicles (EVs), enriched with pro-metastatic cargos, and upregulates bone-homing molecules including CXCR4, integrins, and PIM kinases, fostering pre-metastatic niche formation and skeletal colonisation. In this review, we analysed current evidence on how hypoxia orchestrates PCa dissemination to bone, focusing on the molecular crosstalk between HIF signalling, Wnt activation, EV-mediated communication, and cellular plasticity. We further explore therapeutic strategies targeting hypoxia-related pathways, such as HIF inhibitors, hypoxia-activated prodrugs, and Wnt antagonists, with an emphasis on overcoming therapy resistance in castration-resistant PCa (CRPC). By examining the mechanistic underpinnings of hypoxia-driven bone metastasis, we highlight promising translational avenues for improving patient outcomes in advanced PCa. Full article

Osteosarcoma (OSA) is the most prevalent bone malignancy in people and dogs. Current survival rates show the need for advances in novel therapies to help overcome the growth, survival and metastatic progression of the cancer. Canine models are often used to advance prognostic and treatment opportunities for OSA due to the similarities in the disease between species. This study focusses on the genetic and molecular similarities of OSA between human and canine specimens. Differentially expressed genes (DEGs) were compared and identified in canine and human OSA tumours, revealing 86 common genes, 36 having high and 50 having low expression. Further immunohistochemical analysis of the corresponding proteins of three identified DEGs (ASPN, STK3, BAMBI) allowed for the visualisation of protein expression in canine OSA tissues (n = 19). Overall nuclear and cytoplasmic H-scores were generated, and nuclear and cytoplasmic scores in males and females and in different anatomical locations (axial versus appendicular) were also investigated, presenting unique opportunities to understand the expression in this cancer type. This study contributes to a deeper knowledge of genetic pathways changes and identifies avenues for the diagnosis, prognosis and treatment of OSA in people and dogs, whilst encompassing the One Health concept in medicine. Full article

Odontogenic myxofibroma (OMF) is a rare, benign, and slow-growing tumour arising from odontogenic ectomesenchyme. Despite its low prevalence, accounting for approximately 0.5% to 17.7% of all odontogenic tumours worldwide and 3.1% in specific regional studies, it poses significant challenges due to its potential for local recurrence if inadequately excised. This case report presents the clinical course, surgical management, and follow-up of a 35-year-old female patient diagnosed with OMF in the mandibular body region. The patient presented with an osteolytic lesion between the first and second mandibular molars, as confirmed through CT imaging, with dimensions of 31 × 22 × 24 mm. Histopathological examination following excisional biopsy under general anaesthesia confirmed the diagnosis of OMF. The surgical procedure involved mandibular segment resection and reconstruction using an iliac crest bone graft stabilised with plates. Subsequent implantation procedures in 2021 restored dental function, and a four-year follow-up demonstrated excellent outcomes, with no signs of recurrence, periimplantitis, or bone graft compromise. This case highlights the importance of comprehensive imaging, histopathological confirmation, and long-term monitoring in managing odontogenic myxofibroma. Early detection and appropriate surgical intervention significantly improve patient outcomes and quality of life. Full article

Background/Objectives: Osteosarcoma (OSA) is the most common bone cancer, characterized by rapid progression and poor prognosis. The isothiocyanate sulforaphane (SFN), has gained scientific interest because of its potent anticancer properties. The aim of this study was to conduct a systematic review of research examining the effectiveness of SFN as a treatment for OSA. Methods: A literature search was conducted using MEDLINE, EMBASE, and Web of Science. Studies evaluating the therapeutic efficacy of SFN on OSA were included, while studies examining the effects of isothiocyanates other than SFN were excluded. The quality of the studies was evaluated using the OHAT risk of bias rating tool, and the meta-analysis was conducted using RevMan. Cancer-related outcomes evaluated included cell viability/migration/invasion, cell cycle arrest, apoptosis induction, antioxidant activity, colony formation, and tumour size. A protocol describing the review plan was registered to INPLASY (INPLASY202530001). Results: Ten articles were considered eligible for qualitative synthesis and meta-analysis. All articles included in vitro studies, with two also incorporating in vivo studies, utilizing a combination of human, canine, and murine OSA cell lines. This review indicates that SFN could be beneficial in the treatment of OSA, particularly by reducing cell viability, inducing apoptosis, arresting the cell cycle, and decreasing invasiveness and migration. It emphasizes dose-dependent effects, the need for human trials, and highlights limitations like study heterogeneity and SFN’s bioavailability challenges. Conclusions: This review explores SFN’s potential in OSA at the preclinical stage, focusing on cell apoptosis and proliferation. It highlights promising evidence but calls for more human trials. This research received no external funding. Full article

Primary malignant bone tumours can pose significant diagnostic and therapeutic challenges due to inter-tumour heterogeneity. While traditional imaging modalities such as radiography, MRI (magnetic resonance imaging), and CT (computed tomography) remain essential for initial evaluation and staging, emerging evidence underscores the evolving role of positron emission tomography (PET), particularly PET/CT with Fluorodeoxyglucose ([18F] FDG), in the comprehensive management of bone sarcomas. This narrative review aims to critically summarise the available literature on PET imaging’s utility in the management of primary bone tumours including osteosarcoma, chondrosarcoma, and Ewing sarcoma. Despite limitations like inconsistencies in standard uptake value (SUV) cutoffs and reduced pulmonary resolution, PET/CT is valuable for staging, assessing response to neoadjuvant chemotherapy, predicting histological outcomes, detecting recurrence, and guiding biopsy in metabolically active tumour sites. Further large-scale, prospective studies are warranted to standardise protocols and establish PET’s definitive role in sarcoma management. Full article

The aim of this work was a detailed radiological and histopathological evaluation of a solid tumour that was diagnosed in a 2-year-old goose (Anser domesticus). The radiograph examination showed an osseous change involving the cervical vertebrae. The tumour measuring 15 cm × 10 cm × 9 cm was dense and had well-defined borders, suggesting the presence of calcified bone tissue. Histopathology revealed a well-defined benign neoplasm derived from bone that consisted largely of irregular, disorganized bone trabeculae surrounded by a layer of osteoblasts. The tumour has been classified as an osteoma, which originates from the body of the vertebrae. Osteoma is a benign, well-differentiated tumour with a structure that resembles bone tissue. It presents as a well-demarcated, hard, single tumour that can grow to a considerable size. The aetiology of osteomas in birds remains unclear because of the small number of cases described. Therefore, the influence of factors such as age, breed or sex, trauma, embryonic malformation, infection, developmental disorders, and genetic factors on the development of this type of tumour has not been established. Trauma seems to be the most obvious cause of growth in this case. This work provides valuable information about osteomas in birds, which is important for understanding such neoplasms. Full article

Objectives: The aim of this study was to investigate the treatment patterns and outcomes in two propensity score-matched cohorts of patients with neuroendocrine tumours (NETs) treated with first-line somatostatin analogue (SSA). Methods: Metastatic NET patients treated with first-line SSA (2009–2022) were retrospectively examined. First-line lanreotide vs. octreotide cohorts were matched 1:1 by propensity scores for demographics, tumour characteristics, and diagnosis year. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier analysis and the Cox proportional hazards model. Results: Among 441 patients, 310 were matched (155 in both the octreotide and lanreotide groups). First-line SSA was monotherapy (63.5%) or combination with other medications (36.5%). A total of 77% of second-line patients (188/244) maintained their initial SSA medication in combination with other therapies. Radioligand therapy with lanreotide (N = 72; 29.5%) or octreotide (N = 70; 28.7%) was the most common second-line treatment. First-line lanreotide and octreotide cohorts had similar median PFS (15.5; 95% CI: 13.6–19.1 vs. 14.0; 95% CI: 12.0–15.8 months), despite octreotide having a 36% higher likelihood of moving to the second line than lanreotide (95% CI: 1.05–1.76, p = 0.018). Multiple metastases (HR = 1.45; p = 0.004, 95% CI: 1.13–1.87) and Ki-67 > 20% (HR = 2.34; p < 0.001, 95% CI: 1.43–3.83) were significantly associated with the worst PFS. First-line lanreotide patients had a median OS of 10.4 years (95% CI: 7.5-NA) and octreotide 9.2 years (95% CI: 7.3-NA) (p = 0.537). Bone metastases increased death risk by 91% (p = 0.014; 95% CI: 1.14–3.20). Conclusions: SSA monotherapy is the main first-line treatment and most subsequent treatments include SSA with additional medications. Cohorts had similar PFS/OS, but octreotide demonstrated a 36% significantly higher likelihood of moving to the second-line treatment. Full article

Myeloid sarcoma (MS), or extramedullary acute myeloid leukaemia tumour (eAML), is a rare hematopoietic neoplasm. Recognised as a distinct entity within acute myeloid leukaemia (AML), MS presents significant diagnostic challenges due to its rarity, clinical heterogeneity, and variable immunophenotypic and genetic characteristics. The mechanisms by which leukaemic stem cells (LSCs) migrate to form solid tumours in extramedullary (EM) sites remain unclear. MS can occur de novo, precede AML, and manifest alongside AML relapse. It can also develop with myelodysplastic syndromes (MDSs) or myeloproliferative neoplasms (MPNs). MS frequently presents in organs such as the skin, lymph nodes, gastrointestinal (GI) tract, and central nervous system (CNS), often resulting in diverse clinical manifestations. Diagnosis relies on a comprehensive approach, including tissue biopsy, bone marrow (BM) evaluation, and advanced imaging modalities. Accurate diagnosis is crucial for risk stratification and treatment selection. Prognosis is influenced by several factors: MS’s anatomical location, timing of MS diagnosis, genetic profile, and possible treatment. This review emphasises the need for comprehensive diagnostic methods to better define individual MS characteristics and prognosis. It explores the role of novel targeted therapies in improving patient outcomes and further highlights the critical need for future multicentre data collection to optimise diagnostic and therapeutic approaches. Full article

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in different functions of cancer cells, including the regulation of their potential for metastasization, and are the main channels involved in the pathways of pain perception, through peripheral and central effects. Genetic deletion decreased pain sensitivity following tumour cell inoculation. Preclinical data suggest a potential role for modulators of some TRP channels, such as TRPV1, TRPA1, TRPM7 and TRPM8. Clinical results are still scarce; however, the physiological role in modulating bone remodelling and the involvement of TRP channels in preclinical models of bone cancer pain have garnered interest as areas of research in the last few years, as innovative analgesic strategies that may overcome the long-term side effects of opioids. Full article