Bone Tumor In Children Research Articles

Pediatric Bone Tumors: Location and Age Distribution of 420 Cases

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.

METTL3/YTHDF1 stabilizes CORO6 expression promoting osteosarcoma progression through glycolysis

This study investigates the role of CORO6 (Coronin 6) in the development of osteosarcoma. Osteosarcoma is a common malignant bone tumor in children and adolescents, characterized by rapid and irregular bone growth and a high risk of distant lung metastasis. CORO6 is a member of the Coronin family, known for its conserved WD40 repeat domain. This structure allows CORO6 to inhibit actin dynamics through interactions with F-actin and Arp2/3, thereby affecting the organization of the cytoskeleton. Our research found that in osteosarcoma patients, the levels of CORO6 are significantly elevated. Experimental observations showed that reducing the expression of CORO6 significantly inhibits the growth, migration, and invasion abilities of osteosarcoma cells. Moreover, in vivo experiments demonstrated that the absence of CORO6 effectively inhibits the growth of osteosarcoma in animal models. We also discovered that CORO6 promotes the proliferation, migration and invasion capabilities of osteosarcoma cells by activating the Wnt/β-catenin signaling pathway. Moreover, CORO6 play a critical important role in glycosis of osteosarcoma cells. Mechanically, we found that METTL3/YTHDF1 induced m6A modification of CORO6 mRNA promoted the expression of CORO6 by enhancing its stability. These findings offer new directions for the treatment of osteosarcoma, suggesting that CORO6 could be a novel prognostic biomarker and an effective therapeutic target for patients.In summary, CORO6, as an oncogene, plays a key role in the development of osteosarcoma, providing a crucial theoretical basis for the development of new osteosarcoma treatment strategies.

Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition

Osteosarcoma (OS) is the most severe bone tumor in children. A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin. These drugs cause acute and chronic side effects, such as infections, thrombocytopenia, neutropenia, DNA damage, and inflammation. Therefore, to identify new therapeutic strategies, effective and with a safety profile, is necessary. The Hedgehog (Hh) signaling pathway involved in tumorigenesis is active in OS. Hh components Patched receptor 1 (PTCH1), Smoothened (SMO), and glioma-associated oncogene homolog transcription factors (GLI1 and GLI2) are overexpressed in OS cell lines and patient samples. Curcumin (CUR)—with antioxidant and anti-cancer properties—downregulates Hh components in cancer, inhibiting progression. This study investigates CUR effects on the MG-63 OS cell line, alone and combined with MTX, to propose a novel therapeutic approach. Our study suggests CUR as a novel therapeutic agent in OS, particularly when combined with MTX. Targeting the Hh signaling pathway, CUR and MTX showed significant pro-apoptotic effects, increasing the BAX/Bcl-2 ratio and total apoptotic cell percentage. They reduced the expression of Hh pathway components (PTCH1, SMO, GLI1, and GLI2), inhibiting OS cell proliferation, survival, and invasion. CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

MicroRNA signatures in osteosarcoma: diagnostic insights and therapeutic prospects.

Osteosarcoma (OSa) is the most prevalent primary malignant bone tumor in children and adolescents, characterized by complex genetic and epigenetic alterations. Traditional treatments face significant challenges due to high rates of drug resistance and lack of targeted therapies. Recent advances in microRNA (miRNA) research have opened new avenues for understanding and treating osteosarcoma. This review explores the many critical functions of miRNAs in osteosarcoma, particularly their potential for clinical use. The review highlights two key areas where miRNAs could be beneficial. Firstly, miRNAs can act as biomarkers for diagnosing osteosarcoma and predicting patient prognosis. Secondly, specific miRNAs can regulate cellular processes like proliferation, cell death, migration, and even resistance to chemotherapy drugs in osteosarcoma. This ability to target multiple pathways within cancer cells makes miRNA-based therapies highly promising. Additionally, though the interaction between miRNAs and circular RNAs (circRNAs) falls outside the scope of the paper, it has also been discussed briefly. While miRNA-based therapies offer exciting possibilities for targeting multiple pathways in osteosarcoma, challenges remain. Efficient delivery, potential off-target effects, tumor complexity, and rigorous testing are hurdles to overcome before these therapies can reach patients. Despite these challenges, continued research and collaboration among scientists, clinicians, and regulatory bodies hold the promise of overcoming them. This collaborative effort can pave the way for the development of safe and effective miRNA-based treatments for osteosarcoma.

Imaging of Osteosarcoma: Presenting Findings, Metastatic Patterns, and Features Related to Prognosis

Background: Osteosarcomas are rare malignancies (<1% of all cancers) that produce an osteoid matrix. Osteosarcomas are the second most frequent type of primary bone tumor after multiple myeloma and the most prevalent primary bone tumor in children. The spectrum of imaging findings of these malignancies varies significantly, reflecting different histological subtypes. For instance, conventional osteosarcoma typically presents with a mixed radiological pattern (lytic and bone mineralization) or with a completely eburneous one; aggressive periosteal reactions such as sunburst, Codman triangle, and soft-tissue components are frequently displayed. On the other hand, telangiectatic osteosarcoma usually presents as a purely lytic lesion with multiple fluid–fluid levels on MRI fluid-sensitive sequences. Other typical and atypical radiological patterns of presentation in other subtypes of osteosarcomas are described in this review. In addition to the characteristics associated with osteosarcoma subtyping, this review article also focuses on imaging features that have been associated with patient outcomes, namely response to chemotherapy and event-free and overall survivals. This includes simple semantic radiological features (such as tumor dimensions, anatomical location with difficulty of radical surgery, occurrence of pathological fractures, and presence of distant metastases), but also quantitative imaging parameters from diffusion-weighted imaging, dynamic contrast-enhanced MRI, and 18F-FDG positron emission tomography and radiomics approaches. Other particular features are described in the text. Overall, this comprehensive literature review aims to be a practical tool for oncologists, pathologists, surgeons, and radiologists involved in these patients’ care.

Clinical and Prognostic Characteristics in Childhood Osteosarcoma: A Single-Center Experience in Türkiye.

In our study, we aimed to share the clinical experiences of our center regarding osteosarcoma cases, the most common primary malignant bone tumor in children and adolescents. With approval from the Clinical Research Ethics Committee of our center, the data of 59 pediatric patients who were followed up in our center with the diagnosis of osteosarcoma between 2007 and 2021 were evaluated retrospectively. The mean time between the onset of symptoms and diagnosis was 3 months. Although not statistically significant, patients with a diagnostic delay of 3 months or less had a higher rate of recurrence and mortality. 59.3% of patients had metastatic disease, and the presence of metastases was associated with higher rates of recurrence and mortality. Significant number of patients had multiple surgical operations. Amputation as the first operation and the need for multiple surgeries were associated with higher mortality. Pathologically poor response to chemotherapy is associated with mortality. 42.4% of patients died, and the 5-year overall and disease-free survival rates were 47.5% and 30.5%, respectively. Survival rates were highest in non-metastatic and non-relapsed patients, and lowest in metastatic patients and patients with poor response to chemotherapy. Renal problems and cardiotoxicity were most frequently treatment-related complications. Significant improvements have been achieved in the survival and quality of life in osteosarcoma cases compared to previous years; however, there is still a long way to go, and more multicenter and multidisciplinary studies are needed on osteosarcoma.

CircZMYM2 plays a pivotal role in osteosarcoma by regulating the translation of NACA and ARPC1B

Osteosarcoma (OS) is a primary malignant bone tumor in children and young adults because of its intertumoral heterogeneity and absence of molecular targets. This study aimed to elucidate the role of circular RNA in the pathogenesis of OS. Using bioinformatics analysis and OS clinical samples, we found that hsa_circ_0029634 formed during the splicing process of Zinc finger MYM-type containing 2 (circZMYM2) was highly expressed in OS tissues. Nuclear cap-binding protein subunit 2 regulated circZMYM2 bio-generation by binding to flanking sequences of ZMYM2 transcripts. In addition, knockdown circZMYM2 inhibited cell growth and metastasis in OS cell lines in vitro and inhibited tumor growth in vivo. Mechanistically, circZMYM2 competitively bound to FXR1 to regulate the translation of NACA and ARPC1B. CircZMYM2 may be a crucial regulator of OS tumorigenesis and a potential diagnostic and therapeutic biomarker for OS patients.

Prognostic signature and immunotherapeutic relevance of Focal adhesion signaling pathway-related genes in osteosarcoma

BackgroundAs the most common primary malignant bone tumor in children and adolescents, osteosarcoma currently lacks an effective clinical cure. Focal adhesion plays a crucial role in tumor invasion, migration, and drug resistance by mediating communication between the extracellular matrix and tumor cells. This study investigated the prognostic features and immunotherapeutic relevance of focal adhesion pathway-related genes in osteosarcoma to aid in the development of new therapeutic options. MethodsWe obtained mutational, transcriptomic, gene expression, and clinical data of osteosarcoma patients from the Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective (TARGET) databases. Differentially expressed genes were screened, followed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Kaplan-Meier survival analysis was performed for genes related to the focal adhesion pathway, and multivariate Cox regression analysis was employed to construct a prognostic signature model. Genes such as SIGLEC15, TIGIT, CD274, HAVCR2, PDCD1, CTLA4, and LAG3 were extracted from the TARGET and CCLE databases for osteosarcoma patients and osteosarcoma cell lines, respectively，to observe the expression of immune checkpoint-related genes. Finally, qRT-PCR was used to verify the expression of these immune checkpoint-related genes in osteosarcoma cell lines. ResultsIn our study, 376 samples were analyzed, including 369 osteosarcoma samples and 7 normal tissue samples. We identified 50 up-regulated and 28 down-regulated differentially expressed genes. Among these, 10 Candidate genes relative to focal Adhesion were selected， and CAV1, ZYX, and ITGA5 were found to have a significant prognostic role based on survival analysis of osteosarcoma samples from the TARGET database. A predictive signature model related to the focal adhesion signaling pathway was constructed using these genes, and the AUCs of the 1-year, 3-year, and 5-year ROC curves were 0. 647, 0. 712, and 0. 717, respectively. The overall survival (OS) rate of osteosarcoma patients with high-risk scores was poorer than those with low-risk scores. Then, samples were divided into two subgroups based on the expression of the three genes, revealing significant differences in the expression of certain immune checkpoint-related genes between the subgroups. Additionally, above three genes and immune checkpoint-related genes in osteosarcoma cell lines were extracted from the CCLE database, showing high expression levels in eight osteosarcoma cell lines. We observed that CD274 and PDCD1LG2 were highly expressed in some osteosarcoma cell lines. Finally, the expression of CAV1, ZYX, ITGA5, CD80, CD274, and PDCD1LG2 in osteosarcoma cell lines was verified by qRT-PCR. ConclusionsOur study validated the prognostic role of three focal adhesion pathway-related genes (ZYX, CAV1, and ITGA5) in patients with osteosarcoma and constructed a prognostic signature model associated with the focal adhesion signaling pathway. We identified significant differences in the expression of multiple immune checkpoint-related genes among subgroups defined by the three genes. Additionally, CD274 and PDCD1LG2 showed higher expression in osteosarcoma cell lines characterized by these genes. These findings may aid in the selection of effective immunotherapy for specific osteosarcoma patients.

Prognostic factors and outcome of relapsed/progressive pediatric Ewing sarcoma: single-center 10-year experience

BackgroundEwing sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Despite more intensive chemotherapy regimens and improved local control therapy, there is still a considerable rate of recurrent/progressive disease.MethodsA retrospective study of 50 relapsed/progressive ES patients who were treated at the National Cancer Institute (NCI), Cairo University, during the period from 1st of January 2008 to the end of December 2018, to assess different prognostic variables and disease outcomes.ResultsOut of fifty eligible cases, 32 patients (64%) had disease recurrence, and 18 (36%) developed disease progression on treatment. The median follow-up period was 7.4 months. The median overall survival (OS) was 7.5 months, and the cumulative OS was 64% at 6 months and 32.6% at 1 year. The cumulative event-free survival (EFS) was 41.3% at 6 months and 22.3% at 1 year. Patients with disease recurrence had better OS and EFS than patients with disease progression (p = 0.019). Patients who underwent local control at relapse/progression had a significantly better outcome than patients who received chemotherapy only (p < 0.001). Recurrence > 2 years from initial diagnosis was the only independent predictor of better survival outcome.ConclusionsPatients with relapsing/progressive ES portended a poor outcome, with disease progression on treatment faring worse than relapse. Better outcome was observed in patients who experienced recurrence > 2 years after diagnosis, patients with disease recurrence rather than disease progression on treatment, and patients who underwent local control along with intensive chemotherapy.

Effect of ac4C acetyltransferase NAT10 on tumor progression via ATF4/ASNS mediated asparagine biosynthesis in osteosarcoma.

234 Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, characterized by high malignancy, high mortality, and high disability rates. Investigating the mechanism of osteosarcoma progression, identifying new targets, and developing effective therapy are of great significance for improving patient clinical outcomes. NAT10-mediated ac4C modification is widely present in mRNA and plays important roles in multiple biological processes of mRNA. NAT10 and ac4C modification also play a crucial role in the occurrence and development of malignant tumors such as bladder cancer, esophageal cancer, and breast cancer. Methods: Through RNA-seq and functional screening, NAT10 was identified as the potential therapeutic target. The biological functions of NAT10 and ac4C modification in osteosarcoma were explored in vivo and in vitro. Downstream target of NAT10 was identified through acRIP-seq combined with RNA-seq. The ac4C modification of downstream target gene were detected using RIP-qPCR and its regulatory effect on mRNA stability was explored using RNA half-life analysis. Drug screening was performed using FDA-approved drugs and a small molecule compound library to identify NAT10 inhibitors. The efficacy of inhibitors in osteosarcoma treatment is validated through in vivo, in vitro experiments and patient-derived tumor xenograft (PDX) models. Results: Functional screening targeting RNA modification regulatory factors demonstrated that inhibiting NAT10 significantly reduced the proliferation, migration and invasion of osteosarcoma cells. NAT10 knockout significantly inhibited the proliferation and metastasis of osteosarcoma cells, as well as the malignant progression in vivo. The acRIP-seq and RNA-seq revealed that ATF4 is a downstream target gene regulated by NAT10 in osteosarcoma. NAT10 promoted ac4C modification of ATF4 mRNA, enhanced the stability of ATF4 mRNA, and ATF4 promoted the transcription and expression of ASNS. ASNS catalyzes the synthesis of asparagine (Asn), thereby promoting the malignant progression of osteosarcoma. Drug screening identified Paliperidone and AG-401 as potential inhibitors of NAT10. Through cell functional experiments, orthotopic osteosarcoma models, organoids model, and PDX models, it was demonstrated that Paliperidone and AG-401 can inhibit the malignant progression of osteosarcoma. Conclusions: NAT10 was highly expressed in osteosarcoma and associated with patient prognosis. Through ac4C modification, NAT10 regulated the synthesis of asparagine mediated by ATF4/ASNS, providing materials for protein and nucleotide synthesis in tumor cells, thus promoting the malignant progression of osteosarcoma. Paliperidone and AG-401 were identified as potential NAT10 inhibitors and targeting NAT10 could be a promosing strategy in osteosarcoma treatment.

Surface Markers and Chemokines/Cytokines of Tumor-Associated Macrophages in Osteosarcoma and Other Carcinoma Microenviornments-Contradictions and Comparisons.

Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Prognosis is improving with advances in multidisciplinary treatment strategies, but the development of new anticancer agents has not, and improvement in prognosis for patients with pulmonary metastases has stalled. In recent years, the tumor microenvironment (TME) has gained attention as a therapeutic target for cancer. The immune component of OS TME consists mainly of tumor-associated macrophages (TAMs). They exhibit remarkable plasticity, and their phenotype is influenced by the TME. In general, surface markers such as CD68 and CD80 show anti-tumor effects, while CD163 and CD204 show tumor-promoting effects. Surface markers have potential value as diagnostic and prognostic biomarkers. The cytokines and chemokines produced by TAMs promote tumor growth and metastasis. However, the role of TAMs in OS remains unclear to date. In this review, we describe the role of TAMs in OS by focusing on TAM surface markers and the TAM-produced cytokines and chemokines in the TME, and by comparing their behaviors in other carcinomas. We found contrary results from different studies. These findings highlight the urgency for further research in this field to improve the stalled OS prognosis percentages.

Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.

Bromelain-facilitated GNPs: A strategic innate anticancer delivery system for methotrexate into osteosarcoma cells

Osteosarcoma is the most common malignant bone tumor in children and adolescents during rapid bone growth. Traditional chemotherapy has markedly improved patient outcomes but suffers from nonspecific side effects due to nonspecific drug distribution, highlighting the need for targeted therapies. Methotrexate, although effective, poses toxicity concerns and prompts exploration into advanced drug delivery systems like nanoparticles. Here, we developed a novel method of synthesizing gold nanoparticles using bromelain (G-BNPs) as a reducing and capping agent, and we conjugated G-BNPs with methotrexate (G-B-MNPs) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) as crosslinker. Our meticulous characterization, which included UV–visible spectroscopy, Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Zeta potential, and Fourier-transform infrared spectroscopy (FTIR) analyses confirmed the successful fabrication and drug conjugation of the G-BNPs. We then evaluated the cytotoxicity of the G-BNPs (sized ∼ 21 nm) and G-B-MNPs (sized ∼ 24 nm) on the osteosarcoma cell lines, Saos-2 and MG-63, as well as the non-cancerous primary osteoblast cells. Our findings revealed that G-B-MNPs significantly increased the cytotoxic impact on osteosarcoma cells compared to methotrexate alone while showing minimal toxicity toward primary osteoblast cells. Importantly, using 4`,6-diamidino-2-phenylindole(DAPI), we demonstrated that G-B-MNPs were delivered directly into the nucleus of the cells without encountering lysosomes. G-B-MNPs can be considered a potential drug delivery method for osteosarcoma treatment by improving effectiveness and reducing adverse effects, thereby enhancing patient prognosis.

P53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

Downregulation of B4GALNT1 inhibits proliferation and metastasis of osteosarcoma cells.

Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by a high potential for proliferation and metastasis. Patients with osteosarcoma who have distant metastases generally have a poor prognosis. Challenges in treatment include incomplete resection of tumor and chemotherapy resistance, with no effective cure currently available. Recent studies suggest that β-1,4-N-acetyl-galactosaminyltransferase 1 (B4GALNT1) plays a role in the progression of various malignant tumors. However, the function of B4GALNT1 in osteosarcoma cells has not been reported. This study aims to investigate the expression of B4GALNT1 in osteosarcoma tissues compared to normal tissues and to explore its effects on the proliferation, migration, and invasion of osteosarcoma cells, thereby providing new theoretical foundations and directions for the treatment of osteosarcoma patients. Tumor tissues and corresponding normal tissue samples were collected from 16 osteosarcoma patients who underwent tumor resection at the Second Xiangya Hospital of Central South University. The patients' ages ranged from 8 to 17 years (median age 12 years). The expression of B4GALNT1 mRNA in osteosarcoma tissues, corresponding normal tissues, 3 osteosarcoma cell lines (MG63, Saos-2, and U2OS), and human fetal osteoblastic cells (hFOB) was detected using real-time reverse transcription PCR (real-time RT-PCR). The effects of B4GALNT1 knockdown on the proliferation of osteosarcoma cells Saos-2 and U2OS were analyzed using cell counting kit-8 (CCK-8) assays and colony formation assays. The effects of B4GALNT1 knockdown on the migration and invasion abilities of Saos-2 and U2OS cells were evaluated using Transwell migration and invasion assays. Western blotting analysis was performed to assess the impact of B4GALNT1 knockdown on the expression of epithelial-mesenchymal transition (EMT) and invasion-related proteins in Saos-2 and U2OS cells. Real-time RT-PCR results showed that B4GALNT1 mRNA expression levels were significantly higher in osteosarcoma tissues and the 3 osteosarcoma cell lines compared to normal tissues and hFOB cells (all P<0.01). CCK-8 and colony formation assays indicated that B4GALNT1 knockdown significantly reduced the proliferation rate of osteosarcoma cells compared to the control group (all P<0.05). Transwell migration and invasion assays demonstrated that B4GALNT1 knockdown significantly decreased the number of migrating and invading osteosarcoma cells (all P<0.01). Western blotting analysis revealed that B4GALNT1 knockdown inhibited the expression of N-cadherin, Snail, Vimentin, and matrix metalloproteinase 9 (MMP9) compared to the control group (all P<0.01). B4GALNT1 is upregulated in osteosarcoma tissues and cell lines, and its knockdown suppresses the malignant phenotype of osteosarcoma cells. B4GALNT1 may function as an oncogene in the proliferation and metastasis of osteosarcoma cells.

Predictors of pulmonary metastases on chest computed tomography in children and adolescents with osteosarcoma—tips for qualifying patients for thoracotomy

BackgroundOsteosarcoma is the most common primary malignant bone tumour in children and adolescents. Lungs are the most frequent and often the only site of metastatic disease. The presence of pulmonary metastases is a significant unfavourable prognostic factor. Thoracotomy is strongly recommended in these patients, while computed tomography (CT) remains the gold imaging standard. The purpose of our study was to create tools for the CT-based qualification for thoracotomy in osteosarcoma patients in order to reduce the rate of useless thoracotomies.MethodsSixty-four osteosarcoma paediatric patients suspected of lung metastases on CT and their first-time thoracotomies (n = 100) were included in this retrospective analysis. All CT scans were analysed using a compartmental evaluation method based on the number and size of nodules. Calcification and location of lung lesions were also analysed. Inter-observer reliability between two experienced radiologists was assessed. The CT findings were then correlated with the histopathological results of thoracotomies. Various multivariate predictive models (logistic regression, classification tree and random forest) were built and predictors of lung metastases were identified.ResultsAll applied models proved that calcified nodules on the preoperative CT scan best predict the presence of pulmonary metastases. The rating of the operated lung on the preoperative CT scan, dependent on the number and size of nodules, and the total number of nodules on this scan were also found to be important predictors. All three models achieved a relatively high sensitivity (72–92%), positive predictive value (81–90%) and accuracy (74–79%). The positive predictive value of each model was higher than of the qualification for thoracotomy performed at the time of treatment. Inter-observer reliability was at least substantial for qualitative variables and excellent for quantitative variables.ConclusionsThe multivariate models built and tested in our study may be useful in the qualification of osteosarcoma patients for metastasectomy through thoracotomy and may contribute to reducing the rate of unnecessary invasive procedures in the future.

Epidemiology of bone tumors in children and adolescents: a retrospective study of 266 patients in the south of Tunisia.

Although bone tumors (BT) are relatively uncommon among the human neoplasm, they constitute the most frequent tumors in children and adolescents (CAA). Little information is available about the epidemiologic features of BT in CAA. We aimed to present and discuss epidemiological characteristics of BT in CAA in southern Tunisia, regarding the different histological types. This is a retrospective study including cases of BT in CAA collected in the pathology department at the Habib Bourguiba university hospital over a period of 15 years (2006- 2020). A total of 266 BT was diagnosed in our institution (42,7% among all BT in Southern Tunisia) divided into 200 benign bone tumors (BBT) (75,2%) and 66 malignant bone tumors (MBT) (24,8%). The mean age for all BT was 14,2 years (3-20 years) with male predominance (sex ratio: 1,48). The most common tumor was osteochondroma (42.2%) followed by osteosarcoma (14.6%) and Ewing sarcoma (6.4%). For BBT, the most affected age group was the 16 to 20 year - old - group (50,7%) with a male predominance (59.8%) and a predilection for lower limb (66.8%) then the upper limb (16,8%). Osteochondroma was the most common histological type (56.5%) followed by aneuvrysmal cyst (8,5%) and osteoid osteoma (6,5%). For MBT, the mean age was 12,5 years (5-20 years) and the most affected age group was the 11 to 15 year -old -group (59%). Boys were more affected (60.6%), with a preference for the lower limb (57%) followed by the pelvis (15,6%). Osteosarcoma was the most common MBT (60%) followed by Ewing sarcoma (24%). Given their rarity and heterogeneity, the diagnosis of BT is particular in CAA and requires a multidisciplinary approach. The reporting of epidemiological studies remains essential in order to expand our knowledge regarding these uncommon tumors.

High expression of DEC2 distinguishes chondroblastic osteosarcoma and promotes tumour growth by activating the VEGFC/VEGFR2 signalling pathway.

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and young adults. Account for 80% of all OS cases, conventional OS are characterized by the presence of osteoblastic, chondroblastic and fibroblastic cell types. Despite this heterogeneity, therapeutic treatment and prognosis of OS are essentially the same for all OS subtypes. Here, we report that DEC2, a transcriptional repressor, is expressed at higher levels in chondroblastic OS compared with osteoblastic OS. This difference suggests that DEC2 is disproportionately involved in the progression of chondroblastic OS, and thus, DEC2 may represent a possible molecular target for treating this type of OS. In the human chondroblastic-like OS cell line MNNG/HOS, we found that overexpression of DEC2 affects the proliferation of the cells by activating the VEGFC/VEGFR2 signalling pathway. Enhanced expression of DEC2 increased VEGFR2 expression, as well as increased the phosphorylation levels at sites Y951 and Y1175 of VEGFR2. On the one hand, activation of VEGFR2Y1175 enhanced cell proliferation through VEGFR2Y1175-PLCγ1-PKC-SPHK-MEK-ERK signalling. On the other hand, activation of VEGFR2Y951 decreased mitochondria-dependent apoptosis rate through VEGFR2Y951-VARP-PI3K-AKT signalling. Activation of these two signalling pathways resulted in enhanced progression of chondroblastic OS. In conclusion, DEC2 plays a pivotal role in cell proliferation and apoptosis-resistance in chondroblastic OS via the VEGFC/VEGFR2 signalling pathway. These findings lay the groundwork for developing focused treatments that target specific types of OS.

KAT7 serves as an oncogenic gene and regulates CCL3 expression via STAT1 signaling in osteosarcoma

Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment.

Ewing's Sarcoma of the Scapula in an Infant: About a Case

Ewing sarcoma (ES)/primary neuroectodermal tumor (PNET) is the second most common malignant bone tumor of childhood and adolescence. It can occur at central or peripheral sites, at skeletal or extraskeletal sites, and is more common at the femurs, ilium, and tibia. We report a rare case of Ewing's sarcoma of the scapula in a 2-year-old infant diagnosed with pain and swelling of the left shoulder. Histopathological confirmation of Ewing's sarcoma was possible following ultrasound-guided biopsy. Treatment consisted of initial chemotherapy, followed by surgical tumor resection after good initial response, followed by adjuvant therapy. The current post-treatment follow-up is 2 years without incident. This case is reported to highlight the rarity of localization and therapeutic modalities, particularly surgical.