Search Results (1,029)

Objectives: To construct an optimal magnetic resonance imaging (MRI) texture model to evaluate histological patterns and predict prognosis in patients with osteosarcoma (OS). Methods: Thirty-four patients underwent pretreatment MRI and were diagnosed as having OS by surgical resection or biopsy between September 2008 and June 2018. Histological patterns and 3-year survival were recorded. Manual segmentation was performed in intraosseous, extraosseous, and entire lesions on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted images to extract texture features and perform principal component analysis. A support vector machine algorithm with 3-fold cross-validation was used to construct and validate the models. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate diagnostic performance in evaluating histological patterns and 3-year survival. Results: Eight patients were chondroblastic and the remaining twenty-six patients were non-chondroblastic patterns. Twenty-seven patients were 3-year survivors, and the remaining seven patients were non-survivors. In discriminating chondroblastic from non-chondroblastic patterns, the model from extraosseous lesions on the T2-weighted images showed the highest diagnostic performance (AUCs of 0.94 and 0.89 in the training and validation sets). The model from intraosseous lesions on the T1-weighted images showed the highest diagnostic performance in discriminating 3-year non-survivors from survivors (AUCs of 0.99 and 0.88 in the training and validation sets) with a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 92.6%, 75.0%, and 96.2%, respectively. Conclusions: The texture models of extraosseous lesions on T2-weighted images can discriminate the chondroblastic pattern from non-chondroblastic patterns, while the texture models of intraosseous lesions on T1-weighted images can discriminate 3-year non-survivors from survivors. Full article

Resistance to systemic therapies in sarcomas poses a significant challenge to improving clinical outcomes. Recent research has concentrated on the tumor microenvironment’s role in sarcoma progression and treatment resistance. This microenvironment comprises a variety of cell types and signaling molecules that influence tumor behavior, including proliferation, metastasis, and resistance to therapy. Adenosine, abundant in the tumor microenvironment, has been implicated in promoting immunosuppression and chemoresistance. Targeting adenosine receptors and associated pathways offers a novel approach to enhancing immune responses against tumors, potentially improving immunotherapy outcomes in cancers, including sarcomas. Manipulating adenosine signaling also shows promise in overcoming chemotherapy resistance in these tumors. Clinical trials investigating adenosine receptor antagonists in sarcomas have fueled interest in this pathway for sarcoma treatment. Ultimately, a comprehensive understanding of the tumor and vascular microenvironments, as well as the adenosine pathway, may open new avenues for improving treatment outcomes and overcoming resistance in sarcoma. Further studies and clinical trials are crucial to validate these findings and optimize therapeutic strategies, particularly for osteosarcoma. This study provides a literature review exploring the potential role of the adenosine pathway in sarcomas. Full article

Background/Objectives: Interleukin 13 receptor alpha 2 (IL-13Rα2) is a receptor with a high affinity for IL-13 and is involved in the progression of human cancers. However, studies on the role of IL-13Rα2 in osteosarcoma are limited. Therefore, this study aimed to investigate the expression and roles of IL-13Rα2 in the progression of osteosarcoma. Methods: This study evaluated the roles of IL-13Rα2 in osteosarcomas by evaluating tumor tissues from 37 human osteosarcomas and osteosarcoma cells. Results: Immunohistochemical positivity of IL-13Rα2 was an independent indicator of shorter overall survival and relapse-free survival of 37 osteosarcoma patients and 26 subpopulations of patients who received adjuvant chemotherapy with multivariate analysis. In U2OS and KHOS/NP osteosarcoma cells, overexpression of IL-13Rα2 significantly increased proliferation, migration, and invasion of cells, all of which decreased with knockdown of IL-13Rα2. Overexpression of IL-13Rα2 increased expression of TGF-β, snail, cyclin D1, and BCL2 but decreased BAX, and knockdown of IL-13Rα2 caused a decrease in expression of these molecules. In addition, both in vitro and in vivo, proliferation of osteosarcoma cells increased, and apoptosis decreased with overexpression of IL-13Rα2 under treatment with doxorubicin. Knockdown of IL-13Rα2 sensitized osteosarcoma cells to the cytotoxic effect of doxorubicin. Conclusions: The results of this study suggest that the expression of IL13Rα2 might be used as a potential prognostic indicator in osteosarcoma patients. Furthermore, it is observed that IL13Rα2 influences the resistance to the chemotherapeutic agent doxorubicin. Therefore, a therapeutic trial targeting IL13Rα2 might be a new therapeutic strategy for osteosarcoma, especially those highly expressing IL13Rα2. Full article

Purpose of Review: This review aims to describe the role of limbic system-associated membrane protein (LSAMP) in normal- and pathophysiology, and its potential implications in oncogenesis. We have summarized research articles reporting the role of LSAMP in the development of a variety of malignancies, such as clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. We also examine the current understanding of how defects in LSAMP gene function may contribute to oncogenesis. Finally, this review discusses the implications of future LSAMP research and clinical applications. Recent Findings: LSAMP has been originally described as a surface adhesion glycoprotein expressed on cortical and subcortical neuronal somas and dendrites during the development of the limbic system. It is categorized as part of the IgLON immunoglobulin superfamily of cell-adhesion molecules and is involved in regulating neurite outgrowth and neural synapse generation. LSAMP is both aberrantly expressed and implicated in the development of neuropsychiatric disorders due to its role in the formation of specific neuronal connections within the brain. Additionally, LSAMP has been shown to support brain plasticity via the formation of neuronal synapses and is involved in modulating the hypothalamus in anxiogenic environments. In murine studies, the loss of LSAMP expression was associated with decreased sensitivity to amphetamine, increased sensitivity to benzodiazepines, increased hyperactivity in new environments, abnormal social behavior, decreased aggressive behavior, and decreased anxiety. Findings have suggested that LSAMP plays a role in attuning serotonergic activity as well as GABA activity. Given its importance to limbic system development, LSAMP has also been studied in the context of suicide. In malignancies, LSAMP may play a significant role as a putative tumor suppressor, the loss of which leads to more aggressive phenotypes and mortality from metastatic disease. Loss of the LSAMP gene facilitates epithelial-mesenchymal transition, or EMT, where epithelial cells lose adhesion and gain the motile properties associated with mesenchymal cells. Additionally, LSAMP and the function of the RTK pathway have been implicated in tumorigenesis through the modulation of RTK expression in cell membranes and the activation of second messenger pathways and β-catenin. Summary: Beyond its many roles in the limbic system, LSAMP functions as a putative tumor suppressor protein. Loss of the LSAMP gene is thought to facilitate epithelial-mesenchymal transition, or EMT, where cells lose adhesion and migrate to distant organs. LSAMP’s role in modulating RTK activity and downstream ERK and Akt pathways adds to a large body of data investigating RTK expression in oncogenesis. The characteristics of LSAMP defects and their association with aggressive and metastatic disease are evident in reports on clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. Full article

CD47 is expressed on cell surfaces and acts as a “don’t eat me” signal by interacting with signal-regulatory protein-α on the macrophage surface. Some cancer cells express CD47 protein and can evade macrophage phagocytosis. Herein, we evaluated the feasibility of targeting CD47 for osteosarcoma by analyzing its expression patterns, clinicopathological correlations, and immunotherapeutic potential. We performed a retrospective analysis on 24 biopsy samples from patients with osteosarcoma to investigate correlations between CD47 protein positivity and clinicopathological characteristics. CD47 protein expression was detected in 20.8% of the biopsy samples. CD47 positivity correlated with metastasis at diagnosis. Patients with CD47-positive tumors were older than those with CD47-negative tumors. However, CD47 protein expression was not associated with sex, tumor size, or histologic response to preoperative chemotherapy. In vitro, CD47 antibody (B6H12) did not affect osteosarcoma cell viability or apoptosis. In a wound-healing assay, CD47 inhibited the migration of osteosarcoma cells. Differentiated macrophages exhibited higher phagocytic activity against osteosarcoma cells when pretreated with B6H12 compared with the isotype control. Our preliminary data suggest a possible interaction between CD47 protein and macrophage phagocytosis in osteosarcoma metastasis. A better understanding of the role of CD47 is necessary to develop an innovative immunotherapeutic approach against osteosarcoma. Full article

Background/Objectives: One of the most important diagnostic tools in bone tumors is X-rays. Preliminary and, in the case of some benign lesions, definitive diagnoses are formed using this basic tool. Part of the decision making in this stage is based on statistical probability using the patient’s age, as well as the incidence and predilection sites of different entities. The information used today is based on older and fragmented data. To verify the underlying principles, we retrospectively evaluated all bone tumors in children and adolescents treated by our tertiary center in the last 20 years. Methods: For this retrospective study, patients under the age of 18 years suffering from histopathologically verified bone tumors were evaluated. Data were retrieved from our local musculoskeletal tumor database. Results: We were able to include 420 children treated for bone tumors in our tertiary center. The cohort consisted of 335 benign and 85 malignant lesions. The most common lesions were 137 osteochondromas; the malignant tumors consisted mainly of osteosarcomas (53) and Ewing’s sarcomas (28). The primary predilection sites were the metaphyses of long bones. Conclusions: We were able to confirm and supplement the fragmentary data of these rare diseases using our own cohort. Full article

Background: Brain metastases in pediatric osteosarcoma are infrequent but associated with a dire prognosis. Methods: This retrospective study examined six pediatric patients at Johns Hopkins Hospital who developed brain metastases from osteosarcoma between April 2015 and November 2023. Results: Median survival post-brain metastasis was 2.5 months. The patients underwent various treatments, including chemotherapy, surgery, and radiation. Despite these interventions, outcomes were uniformly fatal. Notably, one patient survived over 13 months post-brain metastasis with a treatment regimen of cabozantinib and nivolumab along with surgical resection and radiation, highlighting the potential efficacy of multimodal treatment regimens. This case demonstrated changes in the immune microenvironment, hinting at an anti-tumoral response, although no histologic response was observed. Conclusions: These findings emphasize the critical need for vigilant clinical monitoring, especially in patients with new neurological symptoms. The study highlights the diagnostic challenges and the rapid progression of brain metastases, underscoring the necessity for further research. Prospective studies and clinical trials focusing on novel therapeutic strategies are essential to improve outcomes. Disease biology studies examining tumor features across primary, pulmonary, and brain metastatic sites may offer insights into the mechanisms of metastasis and potential therapeutic targets, providing a foundation for better management of this devastating complication. Full article

High-grade osteosarcoma (OS) is the most common primary bone tumor mainly affecting children and young adults. First-line treatment consists of neo-adjuvant chemotherapy with doxorubicin, cisplatin, and methotrexate and surgery. The mean long-term survival rate for localized disease at diagnosis is 65–70%, dropping down to 20% when metastases are present at diagnosis. Therefore, curing OS is a clinical challenge, particularly for patients that do not respond to standard treatments. MYC has frequently been reported to be involved in the pathogenesis of OS and its high expression may be associated with drug resistance and patients’ worse prognosis. Moreover, MYC is a master regulator of ribosomal proteins (RPs) synthesis and ribosome biogenesis (RiBi), which is often up-regulated in human tumors. In recent years, RPs have been recognized not only for their traditional role in ribosome assembly but also for their extra-ribosomal functions, many of which are linked to the onset and progression of cancer. In this review we focus on the role and possible interplay of MYC and RPs expression in association with drug resistance and worse prognosis in OS and discuss therapeutic options that target de-regulated MYC, RiBi, or RPs, which are already clinically available or under evaluation in clinical trials. Full article

Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil’s biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (>90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC₅₀ 1–2 mg/mL, and in the healthy cell line (RPE1), the IC₅₀ value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries). Full article

Canine osteosarcoma (OSA) is an aggressive and highly malignant tumor of bone with a poor prognosis and it mirrors the disease in humans. Angiogenesis, the formation of new blood vessels, is driven by hypoxia-induced factors such as HIF-1α and VEGF, both of which play a crucial role in tumor growth and metastasis. However, the role of angiogenesis in OSA remains a topic of ongoing debate. This study aimed to investigate the relationship between angiogenesis, measured by intratumoral microvessel density (MVD), hypoxic markers, and clinical outcomes in 28 dogs diagnosed with appendicular OSA. Clinicopathological data such as age, breed distribution, tumor localization, histopathological subtypes, and metastatic behavior were consistent with reported epidemiologic characteristics of canine OSA, though no significant correlation was found among these variables. The results indicated a significant association between higher MVD and high-grade OSA (p = 0.029), suggesting that increased tumor vascularization is linked to more aggressive tumor behavior. Additionally, elevated VEGF expression was strongly correlated with disease-free interval DFI), with a p-value of 0.045. Although HIF-1α positivity showed a trend towards poorer survival, the results did not reach statistical significance (p = 0.07). These findings highlight the potential role of VEGF as a valuable prognostic marker in canine OSA, which could have potentially important implications for therapeutic targeting and clinical management of the disease. This study advances the understanding of angiogenesis in canine OSA, while emphasizing the need for continued research into the complex mechanisms regulating the interplay between hypoxia, angiogenesis and tumor progression. Full article

Although SeO₃²⁻ ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this study, SeO₃²⁻ ions were co-precipitated in biomimetic calcium phosphate (Se@BioCaP), and modified curcumin prodrug (mcur) was adsorbed on diverse Se@BioCaP surfaces (mcur-Se@BioCaP-Ads). Co-precipitation yielded Se@BioCaP with a significantly higher Se content and exhibited a tailorable micro-/nanostructure. The favorable pH-responsive release of Se and mcur from mcur-Se@BioCaP-Ads showed a synergistic anticancer efficiency in OS cells, enhancing OS cell inhibition more than a single dose of them, which might be associated with ROS production in OS cells. In addition, increased alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 pre-osteoblasts were also verified. These results suggest this novel mcur-Se@BioCaP-Ads has promising and widespread potential in OS treatments. Full article

Sarcomas are a heterogeneous group of malignancies with a high mortality rate. Detection of circulating tumor-derived material, such as circulating RNA in the peripheral blood of patients, has shown to be useful in diagnosis, prediction of prognosis and disease monitoring in several malignancies. This systematic review aims to probe the existing methods for detecting circulating tumor-derived RNAs from patients affected by sarcoma and their possible clinical application. A systematic review of the literature indexed in PubMed was performed. Each article had to analyze circulating RNA in human specimens obtained from liquid biopsies of patients affected by sarcoma. A total of 26 articles were included. We evaluated 1381 patients; 72% were affected by bone sarcoma and 28% by soft tissue sarcoma. By PCR-based methods, all the studies investigated circulating tumor RNA, mostly in the peripheral blood. Nearly half of the authors investigated the tumor expression and/or release of miRNA (42%). Several authors pointed out that circulating tumor-derived RNA has proven to have potential application in a clinical setting for sarcomas. To the best of our knowledge, this is the first review in the literature to attempt to put together data specifically on ctRNA in patients affected by sarcoma. Full article

Human osteosarcoma (OS) is a rare tumor predominantly affecting long bones and characterized by a poor prognosis. Currently, the first line of intervention consists of the surgical resection of primary tumors combined with radiotherapy and chemotherapy, with a profound impact on the patient’s life. Since the surgical removal of OS frequently results in a large resection of bones, the use of biomaterials to sustain the stability of the remaining tissue and to stimulate bone regeneration is challenging. Moreover, residual neoplastic cells might be responsible for tumor recurrence. Here, we explored the potential of tellurium-ion-doped bioactive glass as a novel therapeutic intervention to both eradicate residual malignant cells and promote bone regeneration. Bioactive glass (BAG) has been extensively studied and employed in the field of regenerative medicine due to its osseointegration properties and ability to improve bone tissue regeneration. We found that the incorporation of tellurium (Te) in BAG selectively kills OS cells through ferroptosis while preserving the viability of hBMSCs and stimulating their osteodifferentiation. However, the mechanism of Te toxicity is still unclear: (i) Te-BAG generates lipid-ROS through LOXs activity but not iron overload; (ii) Te-dependent ferroptosis is mediated by GPX4 down-regulation; and (iii) the anti-ferroptotic activity of FSP1 is abrogated, whose expression confers the resistance of OS to the canonical induction of ferroptosis. Overall, our data show that Te-doped bioglass could represent an interesting biomaterial with both pro-ferroptotic activity towards residual cancer cells and pro-osteoregenerative activity. Full article

Bone is the preferential site of metastasis for the most common tumors, including breast cancer. On the other hand, osteosarcoma is the primary bone cancer that most commonly occurs and causes bone cancer-related deaths in children. Several treatment strategies have been developed so far, with little or no efficacy for patient survival and with the development of side effects. Therefore, there is an urgent need to develop more effective therapies for bone primary tumors and bone metastatic disease. This almost necessarily requires the use of in vivo animal models that better mimic human pathology and at the same time follow the ethical principles for the humane use of animal testing. In this review we aim to illustrate the main and more suitable in vivo strategies employed to model bone metastases and osteosarcoma. We will also take a look at the recent technologies implemented for a partial replacement of animal testing. Full article

Hypertension has always posed a severe threat to people’s health. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have the potential to both prevent and treat hypertension. In the current investigation, two ACE-inhibitory peptides (SLPQ and PYVRYL) from goat milk were studied for their endothelial effects using EA.hy926 cells. PYVRYL outperformed SLPQ, yet neither impacted cell survival below 200 μg/mL. Investigation of SLPQ’s impact on EA.hy926 cell expression revealed 114 differentially expressed genes, with 65 downregulated and 49 upregulated. The genes were enriched in cytokine interactions, coagulation cascades, Hippo signaling, and ECM–receptor interaction. Decreased c-x-c motif chemokine ligand 2 (CXCL2), integrin subunit beta 2 (ITGB2), and fbj murine osteosarcoma viral oncogene homologue (FOS) expression and increased secreted phosphoprotein 1 (SPP1) expression may protect endothelial cells from inflammation. Our findings suggest that beyond ACE inhibition, SLPQ aids blood pressure control by influencing endothelial function, paving the way for its use as an antihypertensive food ingredient. Full article