Search Results (166)

Osteosarcoma is one of the most common primary bone malignancies, typically occurring around the knee. However, the forearm is a rare site, with tumors in the proximal ulna being extremely uncommon. Primary sarcoma in this location presents a surgical challenge due to the complex anatomy and limited reconstructive options. We report a rare case of a 19-year-old female with non-metastatic, high-grade giant cell-rich osteosarcoma involving the right proximal ulna. To our knowledge, this is only the second reported adult case of this histological subtype in this location. The patient was treated at a specialized oncology center with neoadjuvant and adjuvant chemotherapy, along with wide intra-articular resection for local tumor control. Reconstruction was achieved using a novel, customized 3D-printed articulating cement spacer mold with plate osteosynthesis. Artificial elbow ligamentous reconstruction was performed using FiberTape and FiberWire sutures passed through drill holes, and the triceps tendon was reattached to the cement mold using an endobutton. This cost-effective and personalized surgical approach allowed successful joint reconstruction while maintaining elbow stability and function. Our case highlights a feasible reconstructive option for rare and anatomically challenging osteosarcoma presentations, contributing to the limited literature on proximal ulna giant cell-rich osteosarcoma. Full article

Osteosarcoma (OSA) is the most common primary bone malignancy in dogs, characterized by aggressive growth and high metastatic potential. Despite advances in treatment, the prognosis for affected animals remains poor, mainly due to metastatic disease. Metastasis is a complex process that involves forming new blood vessels in the primary tumor (angiogenesis), intravasation, the transport of cancer cells to other locations, extravasation, and the growth of cancer cells in the secondary site. Gold nanoparticles (AuNPs), due to their unique physicochemical properties, are considered promising tools in cancer therapy, both as drug delivery systems and potential anti-metastatic agents. Previously, it has been demonstrated that 500 µg/mL glutathione-stabilized gold nanoparticles (Au-GSH NPs) inhibit cancer cell extravasation—one of the steps of the metastatic cascade. This study aimed to evaluate the anti-metastatic properties of Au-GSH NPs through their influence on OSA cell migration, proliferation, and colony formation in vitro, as well as their antiangiogenic properties on the chick embryo chorioallantoic (CAM) model. Additionally, we investigated whether these effects are associated with changes in alpha-2-macroglobulin (A2M) expression, as it was previously demonstrated to play an essential role in the metastatic cascade. Au-GSH NPs significantly inhibited migration and colony formation in canine osteosarcoma cells (from OSCA-8, OSCA-32, and D-17 cell lines) at 200 µg/mL concentrations. Interestingly, at 500 µg/mL, Au-GSH NPs inhibited angiogenesis on the CAM model and cancer cell migration, but fewer colonies were formed. These results may be directly related to the higher efficiency of Au-GSH NPs uptake by OSA cells at the dose of 200 μg/mL than at the dose of 500 μg/mL, as demonstrated using Microwave Plasma Atomic Emission Spectroscopy (MP-AES). Moreover, this is the first study that demonstrates a significant increase in A2M expression in cancer cells after Au-GSH NPs treatment. This study provides new insight into the potential use of Au-GSH NPs as anti-metastatic agents in canine osteosarcoma, indicating that their anti-metastatic properties may be related to A2M. However, further in vitro and in vivo studies are needed to explore the molecular mechanism underlying these effects and to evaluate the clinical relevance of AuNPs in veterinary oncology. 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

Osteosarcoma (OS), a prevalent primary malignant bone tumor in children and adolescents, has maintained consistent treatment protocols since the 1970s combining surgery, chemotherapy, and radiotherapy. While effective for localized tumors, these strategies show limited efficacy against metastatic or recurrent cases. Although emerging immunotherapies (PD-1 inhibitors, CAR-T-cell therapy) demonstrate therapeutic potential, their clinical impact remains constrained by the tumor’s low immunogenicity and immunosuppressive microenvironment, resulting in suboptimal response rates. The disease’s aggressive nature and propensity for pulmonary metastasis contribute to poor prognosis, with survival rates showing negligible improvement over five decades despite therapeutic advances, creating substantial clinical and socioeconomic challenges. Recent developments in nanomedicine offer promising solutions for OS treatment optimization. This review systematically examines nanomaterial applications in OS therapy through a materials science lens, analyzing mechanism-specific interventions and highlighting notable advancements from the past five years. We critically evaluate current strategies for enhancing therapeutic efficacy while reducing toxicity profiles, ultimately outlining translational pathways and key challenges in clinical adaptation. The analysis establishes a framework for developing next-generation nanotherapeutic platforms to address persistent limitations in OS management. Full article

TGF-β is a central mediator of pulmonary allergic inflammation recently associated with lung metastasis of osteosarcoma. Given the controversial links between cancer and allergic diseases, this study aimed to evaluate the effects of allergic airway inflammation—particularly TGF-β—on osteosarcoma lung metastasis using a comorbidity mouse model. Osteosarcoma cells were implanted in BALB/c mice with induced allergic airway inflammation. Lung metastasis was quantified, while PCNA/TGF-β expression was assessed by immunohistochemistry and digital pathology. Bioinformatic analyses of patient datasets compared TGF-β and PCNA expression in metastatic vs. normal tissues, and their association with survival. Mice with allergic inflammation showed increased lung metastases associated with TGF-β production. In patient samples, both TGF-β and PCNA were upregulated in metastatic tissues and correlated with poor overall survival. PCNA was also linked to genes involved in cell proliferation, DNA replication, and repair. Our results show an association between allergic airway inflammation and extensive lung metastasis of osteosarcoma in a comorbidity mouse model with elevated expression of TGF-β and PCNA. Full article

Bone sarcomas, including Osteosarcoma, Ewing’s sarcoma, and Chondrosarcoma, are rare yet aggressive tumors with high metastatic potential and poor survival outcomes. Despite advances in surgical and chemotherapeutic techniques, these malignancies remain difficult to treat. They often exhibit resistance to conventional therapies and are associated with a limited prognosis for patients. MicroRNAs (miRNAs) have emerged as pivotal regulators of cancer biology, orchestrating crucial processes such as cell proliferation, apoptosis, and metastasis. Their double life as oncogenes or tumor suppressors underscores their significance in the pathogenesis of bone sarcomas. This review examines the multifaceted roles of miRNAs in these malignancies. By elucidating the complex networks affected by miRNA dysregulation, we seek to identify novel avenues for miRNA-based interventions. It is the intention of this work to stimulate future research and clinical strategies that exploit the potential of miRNAs to transform the management and outcomes of bone sarcomas. Full article

Osteosarcoma is a highly aggressive bone malignancy, particularly challenging in metastatic cases, with a 5-year survival rate remaining under 30%. Although doxorubicin (doxo) is a standard first-line chemotherapeutic agent, its clinical utility is often hindered by the development of drug resistance and associated systemic toxicity. Emerging evidence highlights the role of epigenetic alterations, particularly those involving histone deacetylases (HDACs), in promoting chemoresistance. In this context, the present study aimed to evaluate the therapeutic potential of combining doxo with the selective HDAC inhibitors, tasquinimod (Tas, targeting HDAC4) and PCI-34051 (PCI, targeting HDAC8), in SJSA-1 osteosarcoma cells. Utilizing both 2D and 3D in vitro models, the combination treatment (referred to as the T4 group) significantly reduced cell viability by 57.69% in 2D cultures and decreased spheroid volume by 35.19% in 3D models. The apoptotic response was markedly enhanced, with late apoptosis reaching 64.59% and necrosis at 32.07%, both surpassing the effects observed with doxo alone. Furthermore, wound healing assays demonstrated a 37.74% inhibition of migration, accompanied by a decreased expression of the matrix metalloproteinases MMP9 and MMP13. Mechanistically, the combination therapy led to the downregulation of protein kinase B (pAKT) and RUNX2, along with upregulation of apoptotic markers, including caspase 8, caspase 3, and cleaved caspase 3, indicating a disruption of key survival pathways. These findings suggest that dual HDAC inhibition with Tas and PCI can potentiate doxo efficacy by enhancing apoptosis, inhibiting proliferation, and reducing metastatic potential, thus offering a promising strategy to overcome chemoresistance in osteosarcoma. Further preclinical and clinical studies are required to validate these therapeutic benefits. Full article

Osteosarcoma is recognized as the most prevalent primary bone malignancy, primarily affecting children and adolescents. It is characterized by its aggressive behavior and high metastatic potential, which often leads to poor patient outcomes. Despite advancements in surgical techniques and chemotherapy regimens, the prognosis for patients with osteosarcoma remains unsatisfactory, with survival rates plateauing over the past few decades. A significant barrier to effective treatment is the development of chemotherapy resistance, which complicates the management of the disease and contributes to high rates of recurrence. This review article aims to provide a comprehensive overview of recent advancements in osteosarcoma therapy, particularly in overcoming chemotherapy resistance. We begin by discussing the current standard treatment modalities, including surgical resection and conventional chemotherapy agents such as methotrexate, doxorubicin, and cisplatin. While these approaches have been foundational in managing osteosarcoma, they are often limited by adverse effects and variability in efficacy among patients. To address these challenges, we explore novel pharmacological strategies that aim to enhance treatment outcomes. This includes targeted therapies focusing on specific molecular alterations in osteosarcoma cells and immunotherapeutic approaches designed to harness the body’s immune system against tumors. Additionally, we review innovative drug delivery systems that aim to improve the bioavailability and efficacy of existing treatments while minimizing toxicity. The review also assesses the mechanisms underlying chemotherapy resistance, such as drug efflux mechanisms, altered metabolism, and enhanced DNA repair pathways. By synthesizing current research findings, we aim to highlight the potential of new therapeutic agents and strategies for overcoming these resistance mechanisms. Ultimately, this article seeks to inform future research directions and clinical practices, underscoring the need for continued innovation in treating osteosarcoma to improve patient outcomes and survival rates. Full article

Background/Objectives: Osteosarcoma is an aggressive bone malignancy with high metastatic potential to the lungs. CTCs, as seeds of metastasis, play an important role in the spread of this cancer, and, therefore, their isolation, culture, and gene expression analysis promises valuable insights into the progression and metastatic cascade of osteosarcoma. The aim of this study was to isolate and culture CTCs from osteosarcoma-bearing mice and compare their migration, radioresistance, and gene expression with their parental cell line. Methods: CTCs from LM8-inoculated mice were isolated and cultured. The gene expression of the CTC-derived cell lines was then compared to the parental cell line. Furthermore, a Transwell assay, a clonogenic assay after irradiation, and immunohistochemical stainings were used to compare the CTC-derived cell lines with the parental cell line. Results: The CTC-derived cell lines differed significantly in gene expression from their parental cell line. 361 differentially expressed genes were identified, among which GO and KEGG analysis revealed major differences in the expression of genes related to antigen processing and presentation and extracellular matrix constituents. In addition, the CTC-derived cell lines were observed to have a higher migratory capacity and comparable radioresistance compared to the parental cell line. CD44 expression was found to be conserved in CTC-derived cell lines. Conclusions: This study provides a comparison between CTC-derived and their parental cell lines in terms of gene expression, migration, and radioresistance. Our findings allow for further research in the field of osteosarcoma CTCs and their generation. Furthermore, the identified DEGs between CTCs and their parental cell line can serve as a reference point for targeted therapies against osteosarcoma CTCs. Full article

Osteosarcoma is the most common primary malignancy of bone. Previous studies have demonstrated rural-urban disparities in metastatic disease incidence and overall survival in high-grade osteosarcoma patients. However, there is a paucity of literature investigating disease-specific survival (DSS) disparities between rural and urban patients, which is explored herein using the SEER database. Patients with biopsy-proven cases of osteosarcoma were identified from 2000–2021. Statistical analysis was completed using SPSS version 29.0.2 and included chi-squared, Kaplan–Meier and log-rank, and stepwise Cox regressions. Statistical significance was considered at p < 0.05. Kaplan–Meier analysis revealed no significant differences in 5- and 10-year DSS between rural (55.0% and 47.0%) and urban patients (56.0% and 51.0%) (p = 0.107). Multivariable analysis further revealed no significant DSS difference between rural and urban patients (aHR: 1.03; 95% CI: 0.86–1.24; p = 0.757). This study expands upon prior research by investigating DSS between rural and urban osteosarcoma patients and finding no significant differences. While rural living is often associated with worse outcomes, important prognostic factors for osteosarcoma, including metastatic disease at presentation and tumor grade, were not significantly different between rural and urban patients in our study, possibly explaining our DSS-related findings. Factors other than geographical location likely impact outcomes, and future research should examine other ways that rural living may influence cancer care. Full article

Background: Osteosarcoma is a rare but aggressive bone malignancy. Despite advances in multimodal therapy, survival remains suboptimal, highlighting the need for prognostic markers to guide treatment. Methods: This study included 162 osteosarcoma patients who received neoadjuvant chemotherapy followed by surgery between January 2009 and March 2024. Patients received either double (cisplatin + doxorubicin) or triple (MAP or PEI) chemotherapy. Survival analyses were conducted using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models. Results: The median age was 20 years (IQR: 18–29), and 53.1% were male. Patients who received triple chemotherapy regimens demonstrated significantly longer overall survival (OS) compared to those on doublet regimens. High tumor necrosis rates (>90%) and negative surgical margins were strongly associated with improved OS, while metastatic disease at diagnosis, elevated alkaline phosphatase (ALP), and male gender were linked to poorer survival. Multivariate analysis identified adjuvant therapy, age under 18, high necrosis rate, negative margins, and normal ALP as significant OS predictors. Conclusions: Triple-agent chemotherapy, necrosis rate ≥90 and negative surgical margins are strongly associated with prolonged survival in osteosarcoma. The key prognostic indicators such as ALP levels, surgical margins and age at diagnosis should guide personalized treatment strategies to improve outcomes in curable patients. Full article

Background: Angiogenesis, the process of new blood vessel formation, is critically regulated by a balance of pro- and anti-angiogenic factors. This process plays a central role in tumor progression and is modulated by tumor cells. Sphingosine-1-phosphate (S1P), a bioactive lipid signaling molecule acting via G-protein-coupled receptors (S1PR1–5), has emerged as a key mediator of vascular development and pathological angiogenesis in cancer. Consequently, targeting the S1P-S1PRs axis represents a promising strategy for antiangiogenic therapies. This study explores S1PR3 as a potential therapeutic target in osteosarcoma, the most common primary bone malignancy, which we have previously demonstrated to secrete S1P within the acidic tumor microenvironment. Methods: The effects of KRX-725-II and its derivatives, Tic-4-KRX-725-II and [D-Tic]4-KRX-725-II—pepducins acting as S1PR3 antagonists as allosteric modulators of GPCR activity—were tested on metastatic osteosarcoma cells (143B) for proliferation and migration inhibition. Anti-angiogenic activity was assessed using endothelial cells (HUVEC) through proliferation and tubulogenesis assays in 2D, alongside sprouting and migration analyses in a 3D passively perfused microfluidic chip. Results: S1PR3 inhibition did not alter osteosarcoma cell growth or migration. However, it impaired endothelial cell tubulogenesis up to 75% and sprouting up to 30% in respect to controls. Conventional 2D assays revealed reduced tubule nodes and length, while 3D microfluidic models demonstrated diminished sprouting area and maximum migration distance, indicating S1PR3’s role in driving endothelial cell differentiation. Conclusions: These findings highlight S1PR3 as a critical regulator of angiogenesis and posit its targeting as a novel anti-angiogenic strategy, particularly for aggressive, S1P-secreting tumors with pronounced metastatic potential and an acidic microenvironment. Full article

Chondrosarcoma (CS), the second most common malignant bone tumor after osteosarcoma, accounts for 20–30% of all malignant bone tumors. It mainly affects adults, middle-aged, and elderly people. The CS family includes various entities displaying peculiar biological, genetic, and epigenetic characteristics and clinical behaviors. Conventional CS is the most common subtype. High-grade, dedifferentiated, and mesenchymal CS, as well as unresectable and metastatic CS, exhibit poor prognoses due to their intrinsic resistance to radiotherapy and chemotherapy, underscoring the urgent need for novel therapeutic strategies. CS research is dealing with several challenges. Experimental studies can rely on animal and patient-derived models, but the paucity of representative near-patient preclinical models has hampered predictive drug screening research. This review describes the main clinical and molecular features of CS subtypes, discussing recent data on the genetic alterations and molecular mechanisms involved in CS pathogenesis and progression. The review provides an overview of the current in vitro and in vivo CS models, discusses their advantages and limitations, and highlights the recent efforts in the development of new targeted therapies against CS dependencies, including IDH1/2 mutations, NAD⁺ dependency, and SIRT1-HIF-2α axis, or exploring DR5 targeting, antiangiogenic therapies, epigenetic drugs, and immunological approaches. All such strategies, in combination with advanced preclinical modeling and personalized multi-omic profiling, hold promise for improving the survival of patients with advanced CS. Full article

There are numerous ways of portraying cancer complexity based on combining multiple types of data. A common approach involves developing signatures from gene expression profiles to highlight a few key reproducible features that provide insight into cancer risk, progression, or recurrence. Normally, a selection of such features is made through relevance or significance, given a reference context. In the case of highly metastatic cancers, numerous gene signatures have been published with varying levels of validation. Then, integrating the signatures could potentially lead to a more comprehensive view of the connection between cancer and its phenotypes by covering annotations not fully explored in individual studies. This broader understanding of disease phenotypes would improve the predictive accuracy of statistical models used to identify meaningful associations. We present an example of this approach by reconciling a great number of published signatures into meta-signatures relevant to Osteosarcoma (OS) metastasis. We generate a well-annotated and interpretable interactome network from integrated OS gene expression signatures and identify key nodes that regulate essential aspects of metastasis. While the connected signatures link diverse prognostic measurements for OS, the proposed approach is applicable to any type of cancer. Full article

Osteosarcoma (OS) is the most prevalent malignant bone tumor in adolescents and young adults. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, and drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb and p53), the molecular mechanism of development of OS remains unclear, and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects, along with side effects at high doses. For these reasons, many efforts have been made to characterize the complex genome of OS thanks to the whole-exome analysis, with the aim of identifying predictive biomarkers to give these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine. Full article