Malignant Bone Research Articles

C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter-mediated doxorubicin resistance.

Osteosarcoma is an aggressive bone malignancy with a high propensity for drug resistance and metastasis, leading to poor clinical outcomes. This study investigates the role of core 1 β1,3-galactosyltransferase 1 (C1GALT1) in osteosarcoma, focusing on its implications in chemoresistance. Our findings reveal that high expression of C1GALT1 is associated with advanced stages, adverse overall survival, and increased recurrence rates. Elevated levels of C1GALT1 were observed in doxorubicin-selected osteosarcoma cells, where its suppression significantly promoted doxorubicin-induced apoptosis and reduced drug efflux. Pharmacological inhibition of C1GALT1 using itraconazole replicated these effects, suggesting a potential therapeutic strategy to overcome chemoresistance. Additionally, we identified the involvement of the ATP-binding cassette (ABC) transporter ABCC1 in the drug-resistance phenotype mediated by C1GALT1. C1GALT1-mediated O-glycan changes were found to influence the cell-surface targeting and lysosomal degradation of ABCC1, thereby modulating its efflux capacity. In vitro and in vivo studies confirmed that C1GALT1 impacts ABCC1 expression and function, further supporting its role in osteosarcoma chemoresistance. These results highlight the clinical relevance of C1GALT1 as a biomarker for prognosis and a potential therapeutic target for osteosarcoma. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Klinefelter Syndrome: A Review.

Klinefelter syndrome (KS) is an uncommonly recognised condition typified by gynaecomastia, small testes and aspermatogenesis. It is caused by a supernumerary X chromosome, resulting in a 47 XXY karyotype. Since its first description, the phenotype of KS has evolved and there is a much greater appreciation of the subtle features of the condition. In this review, we explore the phenotype of the KS with particular consideration to patients with pre-natal and early infancy diagnosis, given that this is becoming increasingly common. The current understanding of the genetic mechanisms of KS, caused by supernumerary X chromosome are explored and the genotype-phenotype correlation are discussed. The implications of the condition both in childhood and later development are explored in detail, with particular focus on social and educational implications. Potential treatments, with emphasis on preservation of fertility are discussed. We highlight the optimal therapeutic conditions in which fertility preservation is most likely to be achieved, compared to those which can be more challenging. Finally, we discuss the other health challenges which can be associated with KS. These include poor bone health, diabetes, cardiovascular complications, and malignancy. The challenges in managing these co-morbid conditions and most up-to-date management recommendations are also explored.

Antisense mediated blockade of Dickkopf 1 attenuates tumor survival, metastases and bone damage in experimental osteosarcoma

Osteosarcoma (OS) is the most common primary bone malignancy. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has been implicated in bone destruction, tumor survival and metastases during OS. We examined the role of Dkk-1 in OS disease progression and explored strategies for targeting its activity. Dkk-1 enhances OS survival by amplifying a non-canonical Wnt pathway that upregulates aldehyde dehydrogenase 1A1. Targeting of Dkk-1 transcription with a vivo morpholino (DkkMo) reduced OS survival and enhanced osteogenic activity of OS in vitro. DkkMo as a single agent slowed tumor expansion, increased tumor necrosis, inhibited metastases and preserved bone in a PDX model of OS. DkkMo also reduced the frequency of dividing tumor cells and reinitiated a regenerative osteogenic phenotype in tumors and stroma while reducing infiltration of inflammatory cells. These findings indicate that DkkMo has the potential to safely target osteosarcoma growth, survival, metastases and bone destruction.

Aptamer-modified melittin micelles efficiently inhibit osteosarcoma deterioration by inducing immunogenic cell death.

Osteosarcoma (OS) is the most common primary bone malignancy characterized by deposition of an immature osteoid matrix. OS treatment has proven challenging because of the high risk of metastatic progression and recurrence after chemotherapy. Melittin (MLT) is recognized as a potential antitumor candidate to overcome chemotherapy resistance and provoke superior immunostimulatory effects. However, the application of MLT to OS is hampered by severe toxic side effects and a lack of tumor-targeting ability. Herein, a self-assembled nanopolymer named LC09-MLT@F127 was developed by binding MLT with F127 micelles and then modifying an aptamer (LC09) for targeted drug delivery during OS treatment. LC09-MLT@F127 exhibited significant OS-targeting ability in vitro and in vivo owing to the aptamer LC09 decoration. Moreover, LC09-MLT@F127 significantly reduced the hemolytic toxicity of MLT while maintaining its tumor-killing ability. In an orthotopic transplantation model of OS, LC09-MLT@F127 induced immunogenic cell death and facilitated the maturation of dendritic cells (DCs), thereby resulting in the activation of tumor-specific immune responses and the inhibition of OS deterioration. Taken together, these finding suggest that LC09-MLT@F127 may be an encouraging MLT-based immunotherapy option for OS.

Diagnostic Roles of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Vertebral Fracture due to Tuberculosis and Malignancy

Background: Vertebral fracture is a serious complication that can occur due to various medical conditions, including bone tuberculosis and malignancy (eg, cancer metastasis to the vertebrae). This condition invariably causes an increase in the inflammatory process in the body, which can be identified through the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR). This study aims to investigate the differences in NLR and PLR values in patients with vertebral fractures due to TB or malignancy. Methods: A retrospective observational study was conducted on vertebral fracture patients who underwent surgery in the Orthopedic Surgery Department of Dr. Kariadi Hospital Semarang between January 1st, 2022, and December 31st, 2023. Data on demographics and laboratory test results were extracted from medical records. Statistical analysis was performed using univariate analysis and presented as percentage and frequency. T-test or Mann-Whitney test was used to determine the difference based on their normality distribution. The diagnostic value of NLR and PLR was also analyzed using the receiver operating characteristic (ROC) curve and Youden index. Results: The study included 54 vertebral fracture patients. The mean age of patients was 41.77 ± 16.00 years, and the majority were female patients (68.5%). The Neutrophil to Lymphocyte Ratio (NLR) value was significantly higher in vertebral fracture due to malignancy patients than TB (5.5 (IQR 3.92 – 13.39) vs 4.53 (IQR 2.91 – 6.96), p=0.020). In contrast, the Platelet to Lymphocyte Ratio (PLR) value was not significantly different (p>0.05). The area under the curve for the NLR (0.69, 95% confidence interval [CI], 0.54 – 0.839) was greater than that of PLR (0.408, 95% CI, 0.246 – 0.571). Conclusion: NLR showed significantly different results in determining the cause of vertebral fractures, either tuberculosis or malignancy. NLR can be used as an important diagnostic marker to help differentiate between vertebral fractures caused by malignancy and those caused by infection.

LncRNA-Associated ceRNA Network Revealing the Potential Regulatory Roles of Ferroptosis and Immune Infiltration in Osteosarcoma as well as Construction of the Prognostic Model.

Osteosarcoma (OS) is the most common primary bone malignancy in the world. Increasing studies indicate that long non-coding RNAs (lncRNAs) are involved in ferroptosis and OS progression. Therefore, this study aims to identify ferroptosis- related lncRNAs (frlncRNAs), explore potential competing endogenous RNA (ceRNA) networks, and establish a new model for predicting OS prognosis. Firstly, we downloaded data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), University of California, Santa Cruz (UCSC), and FerrDB, and screened for differentially expressed FRlncRNAs (DEFRlncRNAs) between OS patients and healthy controls. Then, we constructed the ceRNA network using the Lncbase 3.0, starBase, miRDB, miRTarBase, and TargetScan databases. Subsequently, prognosis- related DEFRlncRNAs were selected through Cox analysis, and a prognostic model was constructed. Next, the proportions of different immune cells in high and low-risk groups were quantified and evaluated using the "CIBERSORT" algorithm. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on prognosis-related DEFRlncRNAs to identify topranked biological processes and pathways. We identified 247 DEFRlncRNAs and constructed the ceRNA network comprising 37 lncRNAs, 84 microRNAs (miRNAs), and 865 messenger RNAs (mRNAs). Subsequently, we obtained 8 prognosis-related DEFRlncRNAs (AL645728.1, AL161785.1, LINC00539, AL590764.1, OLMALINC, AC110995.1, AC091180.2, and AL160006.1) and constructed a prognostic model, where metastasis and risk score were identified as important clinical factors for predicting OS prognosis. Additionally, only OLMALINC and AL160006.1 had corresponding target miRNAs in the prognosis-related ceRNA network. Lastly, we revealed the infiltration proportions of different immune cells in OS, with higher proportions of macrophages (M0 and M2 subgroups) and T cells (T cells CD4 memory resting and T cells CD8) observed. This study explored the ferroptosis-related lncRNA-miRNA-mRNA regulatory network in OS, constructed a ferroptosis-related prognostic model, and characterized its association with immune infiltration, providing new insights into the pathological mechanisms and targeted therapy development for OS.

CGREF1 modulates osteosarcoma proliferation by regulating the cell cycle through the Wnt/β-catenin signaling pathway

BackgroundOsteosarcoma, the most prevalent primary bone malignancy in children and adolescents, exhibits high heterogeneity. The CGREF1 gene encodes a novel 301 amino acid classical secreted protein that contains the presumed N-terminal signaling peptide and EF hand motif. However, its role in osteosarcoma remains unclear.MethodsTumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized for bioinformatics analysis. Western blot and immunohistochemistry (IHC) techniques were employed to detect the expression of relevant proteins. siRNA, lentivirus, and plasmid technologies were applied to modulate gene expression. The downstream pathway of CGREF1 was identified through RNA sequencing analysis. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were conducted for in vitro functional experiments. In vivo experiments involved subcutaneous tumor formation in nude mice.ResultsOur analysis of public databases and clinical samples revealed that CGREF1 is highly expressed in osteosarcoma and is associated with poor prognosis. Knockdown of CGREF1 impeded cell cycle progression and suppressed the proliferation of osteosarcoma cells. Conversely, upregulation of CGREF1 exhibited an opposing pattern. The RNA-seq data from 143B cells was subjected to analysis, revealing that the differentially expressed genes were predominantly enriched in the Wnt signaling pathway. Further experimental results demonstrated that CGREF1 affects activation of the Wnt pathway by regulating GSK3/β-catenin signaling, thereby affecting proliferation ability of osteosarcoma cells. Finally, experiments using subcutaneous transplanted tumor models in nude mice showed that CGREF1 knockdown inhibited tumor growth in vivo by inhibiting the Wnt/β-catenin signaling pathway.ConclusionThe expression of CGREF1 was significantly upregulated in osteosarcoma and correlated with unfavorable prognosis. CGREF1 exerted a regulatory effect on the proliferation of osteosarcoma cells both in vitro and in vivo through modulation of the wnt/β-catenin signaling pathway. In the future, targeting CGREF1 could potentially offer a novel therapeutic strategy for treating osteosarcoma.

New insights into the role of mitophagy related gene affecting the metastasis of osteosarcoma through scRNA-seq and CRISPR-Cas9 genome editing

BackgroundOsteosarcoma (OSA), the most common primary bone malignancy, poses significant challenges due to its aggressive nature and propensity for metastasis, especially in adolescents. Mitophagy analysis can help identify new therapeutic targets and combined treatment strategies.MethodsThis study integrates single-cell sequencing (scRNA-seq) data and bulk-seq to identify mitophagy-related genes (MRGs) associated with the progression of OSA metastasis and analyze their clinical significance. scRNA-seq data elucidates the relationship between mitophagy and OSA metastasis, employing “CellChat” R package to explore intercellular communications and report on hundreds of ligand-receptor interactions. Subsequently, the combination of bulk-seq and CRISPR-Cas9 gene editing identifies mitophagy-related biomarker associated with metastatic prognosis. Finally, validation of the relationship between mitophagy and OSA metastasis is achieved through cellular biology experiments and animal studies.ResultsThe distinct mitophagy activity of various mitochondria manifests in diverse spatial localization, cellular developmental trajectories, and intercellular interactions. OSA tissue exhibits notable heterogeneity in mitophagy within osteoblastic OSA cells. However, high mitophagy activity correlates consistently with high metastatic potential. Subsequently, we identified three critical genes associated with mitophagy in OSA, namely RPS27A, TOMM20 and UBB. According to the aforementioned queue of genes, we have constructed a mitophagy_score (MIP_score). We observed that it consistently predicts patient prognosis in both internal and external datasets, demonstrating strong robustness and stability. Furthermore, we have found that MIP_score can also guide chemotherapy, with varying sensitivities to chemotherapeutic agents based on different MIP_score. It is noteworthy that, through the integration of CRISPR-Cas9 genome-wide screening and validation via cellular and animal experiments, we have identified RPS27A as a potential novel biomarker for OSA.ConclusionsOur comprehensive analysis elucidated the profile of mitophagy throughout the OSA metastasis process, forming the basis for a mitophagy-related prognostic model that addresses clinical outcomes and drug sensitivity following OSA metastasis. Additionally, an online interactive platform was established to assist clinicians in decision-making (https://mip-score.shinyapps.io/labtan/). These findings lay the groundwork for developing targeted therapies aimed at improving the prognosis of OSA patients.

Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses.

Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response. Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics. The mutation spectrum was consistent with previous results for osteosarcoma. CCNE1, MCL1, MYC, and RB1 alterations were significantly associated with a younger age, while CDK4, CDKN2A, CDKN2B, H3F3A, KMT2D, MDM2, RAC1, and SETD2 alterations were significantly associated with an older age. Age, unsupervised clustering of gene alterations, and MYC amplifications were significantly associated with the response to ifosfamide. Notably, both clustered mutation signatures and MYC amplification were correlated with age. These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies.

ZFP36L2 Is a Potential Prognostic Marker of IL1β+ Osteosarcoma.

Background: Osteosarcoma stands as the predominant bone malignancy afflicting children and young adults. Despite strides in treatment, the enduring reality is that the long-term survival rates for patients grappling with recurrences and metastases linger at a mere 30%. This underscores the pressing demand for novel prognostic markers and therapeutic avenues to improve outcomes and offer hope to those battling this formidable disease. ZFP36L2, a member of the tristetraprolin family of CCCH zinc finger proteins, stands out for its pivotal role in posttranscriptional modifications and its ability to modify tumor microenvironments. Methods: We obtained RNA-seq data from TCGA and GTEx cohorts to investigate the expression of ZFP36L2 in tumor and normal tissues. We also utilized GO/KEGG analysis and immune infiltration analysis to verify the relationship between ZFP36L2 and immune cells. A Kaplan-Meier survival curve was used to study the relationship between ZFP36L2 and IL1β in osteosarcoma. Single-cell data analysis and cell-cell communication analysis were used to discover the therapeutic potential of ZFP36L2 in osteosarcoma. Results: This study elucidates the specific expression pattern of ZFP36L2 in tumors. ZFP36L2 is associated with metastasis in sarcoma, but has no statistically significant correlation with survival rate. ZFP36L2 has been shown to be associated with T cells and macrophages in the tumor microenvironment through GO/KEGG analysis and immune infiltration analysis. The survival analysis results show that ZFP36L2 can serve as a biomarker in IL1β+ osteosarcoma. Single-cell sequencing analysis shows that ZFP36L2 is present in IL1β+ macrophages. Cell-cell communication analysis indicates that ZFP36L2 targets TNF in IL1β+ osteosarcoma, thereby improving prognosis. Conclusions: ZFP36L2 has potential as a prognostic marker in IL1β+ osteosarcoma patients.

Large Language Model-Assisted Genotoxic Metal-Phenolic Nanoplatform for Osteosarcoma Therapy.

Osteosarcoma, a leading primary bone malignancy in children and adolescents, is associated with a poor prognosis and a low global fertility rate. A large language model-assisted phenolic network (LLMPN) platform is demonstrated that integrates the large language model (LLM) GPT-4 into the design of multifunctional metal-phenolic network materials. Fine-tuned GPT-4 identified gossypol as a phenolic compound with superior efficacy against osteosarcoma after evaluating across a library of 60 polyphenols based on the correlation between experimental anti-osteosarcoma activity and multiplexed chemical properties of polyphenols. Subsequently, gossypol is then self-assembled into Cu2+-gossypol nanocomplexes with a hyaluronic acid surface modification (CuGOS NPs). CuGOS NPs has demonstrated the ability to induce genetic alterations and cell death in osteosarcoma cells, offering significant therapeutic benefits for primary osteosarcoma tumors and reducing metastasis without adverse effects on major organs or the genital system. This work presents an LLM-driven approach for engineering metal-organic nanoplatform and broadening applications by harnessing the capabilities of LLMs, thereby improving the feasibility and efficiency of research activities.

Trabecular metal collars in endoprosthetic replacements: do they osseointegrate?

Limb salvage surgery (LSS) is the primary treatment option for primary bone malignancy. It involves the removal of bone and tissue, followed by reconstruction with endoprosthetic replacements (EPRs) to prevent amputation. Trabecular metal (TM) collars have been developed to encourage bone ingrowth (osseointegration (OI)) into EPRs. The primary aim of this study was to assess whether OI occurs when TM collars are used in EPRs for tumour. A total of 124 patients from July 2010 to August 2021 who underwent an EPR for tumour under the West of Scotland orthopaedic oncology team were identified. Overall, 81 patients (65%) met the inclusion criteria, and two consultants independently analyzed radiographs at three and 12 months, as well as the last radiograph, using a modified version of the Stanford Radiological Assessment System. OI of the TM collar occurred in approximately 65% of patients at last radiograph. The percentage of patients with OI at three months (65.4%) reflected the 12-month (65%) and long-term (64.4%) follow-up. The median amount of OI across all radiographs was one at all three timepoints, with only five cases (11.1%) showing OI in all four zones at last radiograph. Radiolucency at the bone:collar junction was present in 23 cases (28.4%) at three months, but only four (6.7%) showed progression of this at 12 months. The interobserver reliability was found to be highly reliable in all parameters (p < 0.001). OI occurs in approximately 65% of TM collars, and is similar at three months, 12 months, and last radiograph. The extent of OI at the bone:collar junction was found to have decreased at longer-term follow-up. Furthermore, radiolucency at the bone-collar impact junction does occur in some patients but only a low number will show radiolucency progression at longer-term follow-up.

Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling

Osteosarcoma is the most common bone malignancy in children and adolescents with a less than 30% overall survival rate for those with metastatic disease, particularly pulmonary metastases. Drug resistance hinders the effectiveness of current chemotherapies, making osteosarcoma a leading cause of mortality and an urgent requirement of new therapeutics in this population. Here, we developed a triptolide (TP)-loaded, pH-responsive and near-infrared light-activated nanoplatform (TP-TPBC-PEG) with photodynamic therapy (PDT) to target osteosarcoma cells both in vitro and in vivo. Our results demonstrated that PDT and chemotherapy of TP-TPBC-PEG synergistically reduced cell viability, colony proliferation, migration, and invasion in vitro, and inhibited osteosarcoma growth and pulmonary metastasis in vivo which the nano-micelles were intravenously injected to intratibia injection induced osteosarcoma mouse models, showing enhanced osteosarcoma cell killing by nanoparticle inflating in response to acidic endosomal pH and sensitized osteosarcoma cells to TP chemotherapy. Importantly, the nano-micelles did not exhibit organ toxicity in vivo. Dual-luciferase reporter gene and nuclear/ cytoplasm protein expression assays identified the involvement of HIPPO signaling pathway in mediating these effects. Overall, our study provides a promising therapeutic approach for treating primary osteosarcoma and preventing pulmonary metastases by activating the HIPPO signaling pathway.

Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma

Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic strategies. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the cellular heterogeneity and transcriptional dynamics of OSA tumors. Our study identified eleven distinct tumor cell subpopulations, including osteoblastic, chondroblastic, and myeloid lineages, each exhibiting unique transcriptional profiles associated with disease progression and metastasis. Epithelial-mesenchymal transition (EMT) emerged as a critical process driving aggressive phenotypes, supported by gene set enrichment analyses (GSVA) and transcription factor regulatory network analyses. Integration of copy number variation (CNV) data highlighted genomic alterations in osteoblastic and chondroblastic cells, implicating potential therapeutic targets. Furthermore, immune cell infiltration analyses revealed distinct immune profiles across OSA subtypes, correlating with tumor mutational burden (TMB) and clinical outcomes. Our findings underscore the complexity of OSA biology and provide a foundation for developing personalized treatment strategies targeting tumor heterogeneity and immune interactions.

Significance of exosomes in osteosarcoma research: a systematic review and meta-analysis of a singular clinical investigation.

Osteosarcoma is the most prevalent among primary bone malignancies, and its standard intervention involves neoadjuvant chemotherapy - surgical adjuvant chemotherapy (MAP regimen) with adriamycin, cisplatin, and high-dose methotrexate. Early-stage osteosarcoma can be effectively treated with surgical resection along with chemotherapy or radiotherapy. However, as the cancer progresses, the efficacy of chemo- and radiotherapy decreases, and the associated problems increase. The current understanding of osteosarcoma development, diagnosis, and treatment does not meet clinical demands. More recently, there has been a significant increase in exosome-associated osteosarcoma research, potentially opening up novel possibilities for osteosarcoma research. We comprehensively evaluated and analyzed the advancement of preclinical research related to exosome-osteosarcoma. We aimed to establish a practical, theoretical foundation for future research initiatives. The selected design was a systematic review and meta-analysis. Scientific databases, such as PubMed, Embase, The Cochrane Library, and Web of Science, were extensively screened for exosome and osteosarcoma articles. Two highly trained investigators separately reviewed the literature, extracted relevant information, and assessed study quality. Subsequently, we conducted a meta-analysis using Review Manager 5.4. In total, 25 animal-based randomized controlled trials (RCTs) were selected for analysis. Among them, 13 studies provided strong evidence of cellular exosomes regulating osteosarcoma development from bone marrow mesenchymal stem cells, osteosarcoma cells, and macrophages. In addition, 12 studies demonstrated the therapeutic potential of exosomes in managing osteosarcoma, among which 7 studies transplanted transfected exosomes directly into animals as drugs, and five studies employed exosomes as drug carriers, which were next transplanted into animals. Based on our meta-analysis, macrophages strongly modulate osteosarcoma development, and engineered exosomes provide the most effective exosome-based osteosarcoma treatment.

Hsa_circ_0078767 Enhances Osteosarcoma Chemoresistance to Doxorubicin Through the Regulation of the miR-188-3p/GPX4 Axis.

Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS. Levels of hsa_circ_0078767, miR-188-3p, and glutathione peroxidase 4 (GPX4) in OS clinical tissue samples and cell lines were evaluated by quantitative polymerase chain reaction (qPCR) and Western blotting. Associations between hsa_circ_0078767 levels in clinical samples and patient overall survival were assessed with Kaplan-Meier curves. CCK-8 assays were utilized as a means of examining DOX half-inhibitory concentration (IC50) values. RNA immunoprecipitation and pull-down, as well as reporter assays, investigated interactions between hsa_circ_0078767, miR-188-3p, and GPX4 within OS cells exhibiting DOX resistance. OS patient tissues and cell lines resistant to DOX exhibited elevated hsa_circ_0078767 and GPX4 expression together with a reduction in miR-188-3p levels. Inhibiting hsa_circ_0078767 expression contributed to a profound decrease in the ability of OS tumors to resist DOX. Mechanistically, it was determined that hsa_circ_0078767 can enhance DOX chemoresistance through its ability to bind and sequester miR-188-3p, which otherwise negatively modulates GPX4 to enhance chemosensitivity. Accordingly, the sequestration of miR-188-3p by hsa_circ_0078767 led to the derepression and upregulation of GPX4. Hsa_circ_0078767 was found to modulate miR-188-3p/GPX4 signaling to enhance OS cell resistance to DOX treatment and facilitate disease progression. As such, hsa_circ_0078767 may represent a valuable biomarker or target for use in the context of OS patient management.

The Landscape of microRNAs in Bone Tumor: A Comprehensive Review in Recent Studies.

Cancer, the second greatest cause of mortality worldwide, frequently causes bone metastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord compression. These injurious incidents leave uncomfortably in each of the cancer patient's life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and exhibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various biological processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.

Amputation and limb-sparing surgery in childhood sarcoma: Post-operative imaging appearances and complications.

Limb-sparing surgery and amputation are common surgical techniques used to achieve local tumour control in childhood primary bone and soft tissue malignancy of the limbs. The interpretation of post-operative limb imaging in these frequently complex cases is assisted by knowledge of the surgical techniques employed. This review discusses the rationale underpinning the most common surgical techniques used for these patients as well as their expected post-operative imaging appearance and complications. Amputation, long bone resection, endoprosthetic reconstruction, allograft reconstruction, the use of fibular autografts, allograft-prosthetic composite reconstruction and arthrodesis are discussed.

Superscan Pattern on Bone Scintigraphy: A Comprehensive Review

Background/Objectives: The superscan pattern is a characteristic finding on bone scintigraphy, associated with a variety of metabolic bone diseases, malignancies, and other conditions. This pattern is characterized by a diffuse and intense uptake of radiotracer throughout the entire skeleton. Despite being a relatively rare finding, the superscan pattern can have significant clinical implications. Methods: This comprehensive review summarizes the available literature on the superscan pattern, focusing on its pathophysiology, clinical significance, and differential diagnoses. Relevant studies and case reports were analyzed to outline the diagnostic challenges associated with the interpretation of bone scintigraphy featuring the superscan pattern. Results: The literature highlights the clinical significance of the superscan pattern in various metabolic and oncologic conditions. Misinterpretation of this pattern can lead to diagnostic challenges, especially in distinguishing it from other pathologic conditions. Differential diagnosis remains crucial in the accurate interpretation and subsequent management of patients with this finding. Conclusions: This review provides a comprehensive overview of the superscan pattern on bone scintigraphy, aiming to assist clinicians in recognizing and managing this rare yet clinically important finding.

7901 Clinical Challenges Of Paraneoplastic Endocrine Metabolic Syndromes: An Illustrative Example

Abstract Disclosure: S. Shankar: None. S.S. Sundar: None. M.S. Vaishnav: None. K. Thummala: None. L. Lekkala: None. S. Srikanta: None. K. Muniraj: None. T. Deepak: None. R.B. Vijay: None. V. Nath: None. C. Siddlingappa: None. P. Ravikumar: None. M.D. Chitra: None. Introduction: Paraneoplastic endocrine syndromes result from aberrant production by tumors of protein hormones, hormone precursors, or hormone like substances. In patients who are already receiving treatment for cancer, the onset of a paraneoplastic syndrome may be an indication of progression or relapse. Clinical Case: 2021: Age 81 female (hypertension). Carcinoma rectum; S/P surgery, colostomy, chemotherapy and radiotherapy. 2023: Palliative care, due to progressive metastatic (hepatic, pulmonary, bone) malignancy. 2023 Aug: Hospital admission for generalized weakness, not able to walk, severe pain and low-grade fever 10 days. A: Paraneoplastic Hyponatremia: Evaluation: S Sodium= 127, 129, 129, 137, 134 mmol/L (134-145); Spot urine sodium= 65 mmol; S Uric acid= 3.5 mg/dL (4.4-7.6); S Cortisol 8 am= 15.5 (6.7-22.6); T3 total= 0.34 ng/mL (0.97-1.69), T4 total= 6.87 mcg/dL (5.5-11), TSH= 1.87 mIU/mL (0.46-4.68); LH= 0.35 mIU/mL (16-54); FSH= 1.9 mIU/mL (23-116); S calcium= 8.9 mg/dL (8.4-10.2); S Phosphorus= 2.31mg/dL (2.5-4.5) Diagnosis: Possible paraneoplastic ADH secretion/ SIADH; pain/ narcotics-induced hypothalamic ADH secretion. Treatment: Fluid restriction, liberal salt intake, 3% saline; oral sodium bicarbonate and tolvaptan; tapentadol. B: Paraneoplastic Leukemoid reaction: Evaluation: Total leucocyte count= 29960, 36670, 44130, 58450 cells/mm3 (4000-11,000); Differential count: Neutrophils= 85-94%; Lymphocytes= 10-4%; CRP= 93.7, 24.0 mg/dL (&amp;lt;0.3); Procalcitonin= 0.097, 0.083 ng/mL (&amp;lt;0.1); Ruled out significant sepsis; no obvious laboratory or imaging evidence of any infectious or leukemic etiology. Diagnosis: Progressive leucocytosis due to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) secretion from various neoplasms has been reported in literature. Treatment: Empirical antibiotic coverage. C: Paraneoplastic Hypokalemia: Evaluation: S Potassium= 3.3, 3.4, 3.7, 2.9, 3.0 mmol/L (3.5-5.1). Diagnosis: Hypokalemia likely due to (in vivo and in vitro) intracellular potassium uptake by rapidly proliferating leukocytes (and neoplasm- primary and metastatic). (Ectopic ACTH secretion / ruled out). Therapy: IV and oral potassium supplements. D: Paraneoplastic Fever: Cytokines (e.g., tumor necrosis factor and interleukin-1) release from tumor cells or infiltrating mononuclear cells. Clinical Lessons: Endocrine paraneoplastic syndromes can complicate patient’s clinical course, response to treatment, impact prognosis and even be confused as metastatic spread or another “non-existent” clinical entity. They can precede, occur concomitantly or present at later stage of tumour development. Recognition of the diverse clinical manifestations improves clinical outcomes (earlier cancer diagnosis, better quality of life, optimal tumour-directed therapy or decision towards non-aggressive focussed palliative care). Presentation: 6/2/2024