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Frontiers in Cell and Developmental... 2024Osteosarcoma, a malignant bone tumor predominantly affecting children and adolescents, presents significant therapeutic challenges, particularly in metastatic or... (Review)
Review
Osteosarcoma, a malignant bone tumor predominantly affecting children and adolescents, presents significant therapeutic challenges, particularly in metastatic or recurrent cases. Conventional surgical and chemotherapeutic approaches have achieved partial therapeutic efficacy; however, the prognosis for long-term survival remains bleak. Recent studies have highlighted the imperative for a comprehensive exploration of the osteosarcoma immune microenvironment, focusing on the integration of diverse immunotherapeutic strategies-including immune checkpoint inhibitors, tumor microenvironment modulators, cytokine therapies, tumor antigen-specific interventions, cancer vaccines, cellular therapies, and antibody-based treatments-that are directly pertinent to modulating this intricate microenvironment. By targeting tumor cells, modulating the tumor microenvironment, and activating host immune responses, these innovative approaches have demonstrated substantial potential in enhancing the effectiveness of osteosarcoma treatments. Although most of these novel strategies are still in research or clinical trial phases, they have already demonstrated significant potential for individuals with osteosarcoma, suggesting the possibility of developing new, more personalized and effective treatment options. This review aims to provide a comprehensive overview of the current advancements in osteosarcoma immunotherapy, emphasizing the significance of integrating various immunotherapeutic methods to optimize therapeutic outcomes. Additionally, it underscores the imperative for subsequent research to further investigate the intricate interactions between the tumor microenvironment and the immune system, aiming to devise more effective treatment strategies. The present review comprehensively addresses the landscape of osteosarcoma immunotherapy, delineating crucial scientific concerns and clinical challenges, thereby outlining potential research directions.
PubMed: 38915446
DOI: 10.3389/fcell.2024.1394339 -
JBJS Case Connector Apr 2024We describe 2 case studies, involving a 10-year-old girl with an aneurysmal bone cyst and a 12-year-old adolescent boy with Ewing sarcoma. The patient with Ewing sarcoma...
CASE
We describe 2 case studies, involving a 10-year-old girl with an aneurysmal bone cyst and a 12-year-old adolescent boy with Ewing sarcoma. The patient with Ewing sarcoma was previously managed with wide surgical excision and fibular graft reconstruction and subsequently experienced significant graft resorption, hardware failure, and fracture 24 months after operation. A revision limb salvage attempt was undertaken. In both cases, fibular strut grafts were harvested and fixed with intramedullary k-wires to recreate the medial and lateral columns of the distal humeral triangle.
CONCLUSION
The technique achieved complete osseous integration, structural support, and functional restoration of the elbow in both cases, with good functional outcomes.
Topics: Humans; Child; Male; Fibula; Female; Sarcoma, Ewing; Bone Neoplasms; Humerus; Bone Transplantation; Bone Cysts, Aneurysmal; Plastic Surgery Procedures
PubMed: 38913790
DOI: 10.2106/JBJS.CC.23.00539 -
Journal of Visualized Experiments : JoVE Jun 2024Decoction formula is the most commonly used dosage form in traditional Chinese medicine and applied in clinical practice for thousands of years by trans-oral...
Decoction formula is the most commonly used dosage form in traditional Chinese medicine and applied in clinical practice for thousands of years by trans-oral administration, which is characterized by quick effect, easy absorption, and individualized treatment based on the specific syndromes of patients. The quality of the decoction formula is directly responsible for the clinical efficacy of traditional Chinese medicine; therefore, the standardization process of the decoction formula is important to avoid differences in decoction quality caused by subjective factors. Meanwhile, due to the limitations of performing clinical experiments, small animals bearing human diseases, such as mice, are often used in medical research to explore the therapeutic efficacy and comprehensive mechanisms of different interventions, including the decoction formula for traditional Chinese medicine. Consequently, as an important trans-oral administration method, the skilled gavage technique is particularly important to avoid potential esophagus damage and drug spillage, which will ensure an equal amount of medicine being administered to each model animal, leading to accurate experimental results. Furthermore, the standardized method of decoction formula preparation and skilled gavage strategy are necessary to protect animal welfare and minimize the number of animals used. Here, we reported a detailed standardization process of the decoction formula and gavage technique with Yiqi Jiedu decoction in osteosarcoma mouse model as an example. The efficacy was evaluated by the tumor volume. This protocol will maximize animal protection and improve the reliability of research data, therefore providing effective strategies for future investigating therapeutic efficacy and molecular mechanisms of decoction formula for traditional Chinese medicine in vivo.
Topics: Animals; Osteosarcoma; Mice; Drugs, Chinese Herbal; Medicine, Chinese Traditional; Bone Neoplasms; Disease Models, Animal; Administration, Oral
PubMed: 38912794
DOI: 10.3791/66177 -
Heliyon Jun 2024The development of tumor vaccines has become a hot topic in immunotherapy for osteosarcoma (OS); however, more tumor antigens with stronger immunogenicity need to be...
PURPOSE
The development of tumor vaccines has become a hot topic in immunotherapy for osteosarcoma (OS); however, more tumor antigens with stronger immunogenicity need to be identified.
METHODS
We downloaded six sets of gene expression profile data from online databases. The overexpressed genes were analyzed, intersected, and used to calculate the immune infiltration abundance in the TARGET OS dataset based on their expression matrix. Potential tumor antigen genes were identified based on whether they exhibited a high correlation with the antigen-presenting cells (APCs). A total of 1330 immune-related genes (IRGs) from the ImmPort website were retrieved based on their expression, and the Consensus Cluster method was used to obtain immune subtypes of the OS samples. Prognosis, immune microenvironment, and sensitivity to drugs were compared among the immune subtypes.
RESULTS
In total, 680 genes were overexpressed in at least two datasets, of which and were positively correlated with different APCs. Based on the expression matrix of 1330 IRGs in TARGET-OS, two immune subtypes, IS1 and IS2, were identified. The prognosis of the IS1 subtype was better than that of IS2, the expression of immune checkpoint (ICP)-related genes was higher in patients with the IS1 subtype, and immune cell infiltration and sensitivity to 16 drugs were generally higher in IS1 subtype patients.
CONCLUSION
We identified three APC-correlated genes that can be considered to code for potential novel tumor antigens for OS vaccines. Two immune subtypes in patients with OS were identified to implement personalized treatments using mRNA vaccines.
PubMed: 38912457
DOI: 10.1016/j.heliyon.2024.e32231 -
Dose-response : a Publication of... 2024To investigate the biological role of miR-143 and miR-199a in mediating the progression of osteosarcoma (OS) by targeting cyclooxygenase (COX-2).
OBJECTIVE
To investigate the biological role of miR-143 and miR-199a in mediating the progression of osteosarcoma (OS) by targeting cyclooxygenase (COX-2).
INTRODUCTION
COX-2 plays a crucial role in the development and progression of OS. However, the specific regulatory mechanisms of COX-2 in OS are still not well understood.
METHODS
The expression levels of COX-2, miR-143 and miR-199a in OS tissues were detected using immunohistochemistry, qPCR, or western blot assays. The targeting relationship between miRNAs and COX-2 was determined. The effect of miRNA and COX-2 on OS cells was evaluated in vitro and in vivo.
RESULTS
COX-2 expression was upregulated while miR-143 and miR-199a were downregulated in OS tissues. miR-143 and miR-199a suppressed the proliferation, migration, and invasion of OS cells. The dual-luciferase reporter gene assay showed that COX-2 was a direct target of miR-143 and miR-199a. Genetic knockdown of COX-2 significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion of OS cells. The expression levels of COX-2 and PGE2 were decreased after the overexpression of miR-143 and miR-199a. Additionally, COX-2 silencing inhibited the tumorigenesis of OS and the synthesis of PGE2 in vivo.
CONCLUSIONS
miR-143 and miR-199a/COX-2 axis modulates the proliferation, invasion, and migration in osteosarcoma.
PubMed: 38912334
DOI: 10.1177/15593258241264947 -
Biomaterials and Biosystems Jun 2024This study evaluates the cytocompatibility of cerium-doped mesoporous bioactive glasses (Ce-MBGs) loaded with polyphenols (Ce-MBGs-Poly) for possible application in bone...
This study evaluates the cytocompatibility of cerium-doped mesoporous bioactive glasses (Ce-MBGs) loaded with polyphenols (Ce-MBGs-Poly) for possible application in bone tissue engineering after tumour resection. We tested MBGs powders and pellets on 2D and 3D models using human bone marrow-derived mesenchymal stem cells (hMSCs), osteosarcoma cells (U2OS), and endothelial cells (EA.hy926). Promisingly, at a low concentration in culture medium, Poly-loaded MBGs powders containing 1.2 mol% of cerium inhibited U2OS metabolic activity, preserved hMSCs viability, and had no adverse effects on EA.hy926 migration. Moreover, the study discussed the possible interaction between cerium and Poly, influencing anti-cancer effects. In summary, this research provides insights into the complex interactions between Ce-MBGs, Poly, and various cell types in distinct 2D and 3D models, highlighting the potential of loaded Ce-MBGs for post-resection bone tissue engineering with a balance between pro-regenerative and anti-tumorigenic activities.
PubMed: 38912165
DOI: 10.1016/j.bbiosy.2024.100095 -
Annals of Translational Medicine Jun 2024[This retracts the article DOI: 10.21037/atm-21-6123.].
[This retracts the article DOI: 10.21037/atm-21-6123.].
PubMed: 38911555
DOI: 10.21037/atm-2024-02 -
Journal of Cancer 2024T-box transcription factor 3 (TBX3) has been implicated in various malignant tumors, while its exact involvement in osteosarcoma (OS) remains unknown. Utilizing...
T-box transcription factor 3 (TBX3) has been implicated in various malignant tumors, while its exact involvement in osteosarcoma (OS) remains unknown. Utilizing microarray data and bulk and single-cell RNA-seq data and qRT-PCR, we compared TBX3 mRNA expression levels in different stages of OS. Diagnostic ability testing and prognosis analysis were conducted to better understand the clinical importance of TBX3. Enrichment analysis was performed using gene groups with biological functions similar to TBX3 in different stages of OS to investigate the potential role of TBX3 in OS progression. In addition, we predicted medications targeted at TBX3 and identified downstream target genes to gain a comprehensive understanding of its therapeutic direction and regulatory mechanism. TBX3 expression was highly upregulated in OS and was predominantly expressed in osteoblastic OS cells, with higher expression levels in metastatic tissues. TBX3 expression appeared somewhat suitable for discriminating between OS and normal samples, as well as different stages of OS. We found that TBX3 increased the malignant development of OS by altering cell cycle and cell adhesion molecules; exisulind and tacrolimus, which are targeted small-molecule medicines, were anticipated to counteract this dysregulation. The expression of CCNA2 could potentially be regulated by TBX3, contributing to OS advancement. TBX3 emerges as a potential biomarker for OS. In-depth research into its underlying molecular processes may offer new perspectives on treating OS.
PubMed: 38911382
DOI: 10.7150/jca.96168 -
Oncology Letters Aug 2024Circular RNAs (circRNAs) are a subclass of non-coding RNAs that are important for the regulation of gene expression in eukaryotic organisms. CircRNAs exert various...
Circular RNAs (circRNAs) are a subclass of non-coding RNAs that are important for the regulation of gene expression in eukaryotic organisms. CircRNAs exert various regulatory roles in cancer progression. However, the role of hsa_circ_0064636 in osteosarcoma (OS) remains poorly understood. In the present study, the expression of hsa_circ_0064636 in OS cell lines was measured by reverse transcription-quantitative PCR (RT-qPCR). Differentially expressed mRNAs and microRNAs (miRNA or miRs) were screened using mRNA(GSE16088) and miRNA(GSE65071) expression datasets for OS. miRNAs that can potentially interact with hsa_circ_0064636 were predicted using RNAhybrid, TargetScan and miRanda. Subsequently, RNAhybrid, TargetScan, miRanda, miRWalk, miRMap and miRNAMap were used for target gene prediction based on the overlapping miRNAs to construct a circ/miRNA/mRNA interaction network. Target genes were subjected to survival analysis using PROGgeneV2, resulting in a circRNA/miRNA/mRNA interaction sub-network with prognostic significance. miRNA and circRNA in the subnetwork may also have survival significance, but relevant data are lacking and needs to be further proved. RT-qPCR demonstrated that hsa_circ_0064636 expression was significantly increased in OS cell lines. miR-326 and miR-503-5p were identified to be target miRNAs of hsa_circ_0064636. Among the target genes obtained from the miR-326 and miR-503-5p screens, ubiquitination factor E4A (UBE4A) and voltage dependent anion channel 1 (VDAC1) were respectively identified to significantly affect prognosis; only miR-326 targets UBE4A and only miR-503 targets VDAC1. To conclude, these aforementioned findings suggest that hsa_circ_0064636 may be involved in the development of OS by sponging miR-503-5p and miR-326to inhibit their effects, thereby regulating the expression of VDAC1 and UBE4A.
PubMed: 38910902
DOI: 10.3892/ol.2024.14507 -
Mechanisms of Ageing and Development Jun 2024Cellular senescence contributes to ageing and age-related diseases, and multiple therapeutic strategies are being developed to counteract it. Senolytic drugs are being...
Cellular senescence contributes to ageing and age-related diseases, and multiple therapeutic strategies are being developed to counteract it. Senolytic drugs are being tested in clinical trials to eliminate senescent cells selectively, but their effects and mechanisms are still unclear. Several studies reveal that the upregulation of senescence-associated secretory phenotype (SASP) factors in senescent cells is accompanied by increased autophagic activity to counteract the endoplasmic reticulum (ER) stress. Our study shows that Doxo-induced senescent fibroblasts yield several SASP factors and exhibit increased autophagy. Interestingly, Quercetin, a bioactive flavonoid, reduces autophagy, increases ER stress, and partially triggers senescent fibroblast death. Given the role of senescent cells in cancer progression, we tested the effect of conditioned media from untreated and quercetin-treated senescent fibroblasts on osteosarcoma cells to determine whether senolytic treatment affected tumour cell behaviour. We report that the partial senescent fibroblast clearance, achieved by quercetin, reduced osteosarcoma cell invasiveness, curbing the pro-tumour effects of senescent cells. The reduction of cell autophagic activity and increased ER stress, an undescribed effect of quercetin, emerges as a new vulnerability of Doxo-induced senescent fibroblasts and may provide a potential therapeutic target for cancer treatment, suggesting novel drug combinations as a promising strategy against the tumour.
PubMed: 38909661
DOI: 10.1016/j.mad.2024.111957