Primary Bone Tumors Research Articles

M2 macrophage exosome-derived Apoc1 promotes ferroptosis resistance in osteosarcoma by inhibiting ACSF2 deubiquitination.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. The aim of this study was to investigate the regulatory mechanisms of M2 macrophage exosomes (M2-Exos) in ferroptosis in OS. A mouse model was established to investigate the in vivo role of M2-Exos. We investigated their effects on ferroptosis in OS using erastin, a ferroptosis activator, and deferoxamine mesylate, an iron chelator. In vitro, we investigated whether the Apoc1/Acyl-CoA Synthetase Family Member 2 (ACSF2) axis mediates these effects, using shApoc1 and shACSF2. The mechanisms whereby Apoc1 regulates ACSF2 were examined using cyclohexanone, a protein synthesis inhibitor, and MG132, a proteasomal inhibitor. M2-Exos reversed the inhibitory effects of erastin on OS cells, thus enhancing their viability, migration, invasion, proliferation, and reducing ferroptosis. Apoc1 was highly expressed in M2-Exos, and interfering with this expression reversed the effects of M2-Exos on OS cells. ACSF2 mediated the effects of M2-Exos-derived Apoc1. Apoc1 interacted with ACSF2, which, in turn, interacted with USP40. Apoc1 overexpression increased ACSF2 ubiquitination, promoting its degradation, whereas USP40 overexpression inhibited ACSF2 ubiquitination and promoted its expression. Apoc1 overexpression inhibited ACSF2 binding to USP40. M2-Exos-derived Apoc1 promoted ferroptosis resistance by inhibiting USP40 binding to ACSF2 and promoting ACSF2 ubiquitination and degradation, thus enhancing OS development.

Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches

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.

Osteosarcoma with Pathological Fracture: A Rare Case Report

Introduction: Osteosarcoma is a primary malignant bone tumor originating from stem cells and is characterized by the proliferation of tumor cells that directly form immature bone or bone-like tissue. Osteosarcoma represents only 3% to 5% of all spinal malignancies. The aim of study is to discuss the importance of diagnostic investigation for a relatively rare case of spinal osteosarcoma. Case presentation: A 49 years old female came to the Emergency Unit, with a chief complaint of bilateral weakness of lower extremities for 1 year and worsening in 2 weeks. Upon examination, the initial diagnosis was mistaken for a spinal canal stenosis because metastatic bone disease from previous history of malignant melanoma. Subsequently, a decompression with stabilization fusion and biopsy is performed. Primary osteosarcoma was confirmed from histopathology results. Further chemotherapy is planned referring to confirmed primary osteosarcoma on histopathology. Discussion: Spinal osteosarcoma is very rare. Osteosarcoma occurs most frequently in the appendicular skeleton, especially the distal femur and proximal tibial metaphysis, which account for 90% of all cases. Primary osteosarcomas of the vertebral column are uncommon and occur dominantly in the vertebral body. Biopsy remains the gold standard of care for diagnosis. Conclusion: The performance of MRI and pathologic evaluation with immunohistochemistry is particularly important for the differential diagnosis of soft tissue tumors. Histopathologic analysis also plays an important role in differentiating from metastatic bone disease. An aggressive treatment plan and long-term follow-up are mandatory in managing this case. Keywords: osteosarcoma, spinal osteosarcoma, spinal canal stenosis, malignancy, pathological fracture, rare case.

Combined microscopic transoral and endoscopic endonasal approach for a clival chordoma: A case report and literature review

Background: Chordomas are primary bone tumors derived from the embryonic notochord. They represent 1–4% of all malignant bone tumors. They have a predominantly extra-axial location, arising in the clival region in 35% of reported cases. The prognosis is generally poor, and radical resection remains the first-line treatment. This study aims to describe a case of a clival chordoma that was resected through a combined microscopic transoral and endoscopic endonasal approach, with excellent clinical outcomes. Case Description: A 24-year-old woman with low cranial nerve symptomatology was admitted for a two-stage surgical approach. An occipital-cervical fixation was performed in the first stage, while a combined endonasaltransoral resection was performed later for tumor resection. Conclusion: Microscopic transoral and endoscopic endonasal approaches offer advantages for treating clival chordomas, with careful consideration of anatomical constraints and potential for postoperative recurrence being essential in approach selection.

Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy

BackgroundOsteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6. MethodsFirstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot. ResultsHKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6. ConclusionsHKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.

Impact of metadata in multimodal classification of bone tumours

The accurate classification of bone tumours is crucial for guiding clinical decisions regarding treatment and follow-up. However, differentiating between various tumour types is challenging due to the rarity of certain entities, high intra-class variability, and limited training data in clinical practice. This study proposes a multimodal deep learning model that integrates clinical metadata and X-ray imaging to improve the classification of primary bone tumours. The dataset comprises 1,785 radiographs from 804 patients collected between 2000 and 2020, including metadata such as age, affected bone site, tumour position, and gender. Ten tumour types were selected, with histopathology or tumour board decisions serving as the reference standard.MethodsOur model is based on the NesT image classification model and a multilayer perceptron with a joint fusion architecture. Descriptive statistics included incidence and percentage ratios for discrete parameters, and mean, standard deviation, median, and interquartile range for continuous parameters.ResultsThe mean age of the patients was 33.62 ± 18.60 years, with 54.73% being male. Our multimodal deep learning model achieved 69.7% accuracy in classifying primary bone tumours, outperforming the Vision Transformer model by five percentage points. SHAP values indicated that age had the most substantial influence among the considered metadata.ConclusionThe joint fusion approach developed in this study, integrating clinical metadata and imaging data, outperformed state-of-the-art models in classifying primary bone tumours. The use of SHAP values provided insights into the impact of different metadata on the model’s performance, highlighting the significant role of age. This approach has potential implications for improving diagnostic accuracy and understanding the influence of clinical factors in tumour classification.

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.

Neoadjuvant Chemotherapy for Adults with Osteogenic Sarcoma.

Osteosarcoma is the most common primary malignant bone tumor in adolescents and adults. The 5-year survival rate is 65% when localized; however, survival drops dramatically to 10-20% in cases of metastatic disease. Therapy for osteosarcoma saw its first significant advancement in the 1970-80's, with the introduction of our current standard of care, consisting of the neo/adjuvant treatment regimen methotrexate, doxorubicin (Adriamycin), and cisplatin (collectively referred to as MAP) and surgical resection. Since MAP, development of a better therapeutic approach has stalled, creating a plateau in patient outcomes that has persisted for 40 years. Despite substantial research into a variety of pathways for novel treatment options, clinical trials have not produced sizeable improvements in outcomes. In this article, we discuss our current neoadjuvant standard of care therapy, followed by a review of contemporary therapeutic options, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), monoclonal antibodies (mAbs), and chimeric antigen receptor (CAR) T cells. Lastly, we consider the challenges hindering the success of novel treatment options and future research directions.

A deep learning model to enhance the classification of primary bone tumors based on incomplete multimodal images in X-ray, CT, and MRI

BackgroundAccurately classifying primary bone tumors is crucial for guiding therapeutic decisions. The National Comprehensive Cancer Network guidelines recommend multimodal images to provide different perspectives for the comprehensive evaluation of primary bone tumors. However, in clinical practice, most patients’ medical multimodal images are often incomplete. This study aimed to build a deep learning model using patients’ incomplete multimodal images from X-ray, CT, and MRI alongside clinical characteristics to classify primary bone tumors as benign, intermediate, or malignant.MethodsIn this retrospective study, a total of 1305 patients with histopathologically confirmed primary bone tumors (internal dataset, n = 1043; external dataset, n = 262) were included from two centers between January 2010 and December 2022. We proposed a Primary Bone Tumor Classification Transformer Network (PBTC-TransNet) fusion model to classify primary bone tumors. Areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the model’s classification performance.ResultsThe PBTC-TransNet fusion model achieved satisfactory micro-average AUCs of 0.847 (95% CI: 0.832, 0.862) and 0.782 (95% CI: 0.749, 0.817) on the internal and external test sets. For the classification of benign, intermediate, and malignant primary bone tumors, the model respectively achieved AUCs of 0.827/0.727, 0.740/0.662, and 0.815/0.745 on the internal/external test sets. Furthermore, across all patient subgroups stratified by the distribution of imaging modalities, the PBTC-TransNet fusion model gained micro-average AUCs ranging from 0.700 to 0.909 and 0.640 to 0.847 on the internal and external test sets, respectively. The model showed the highest micro-average AUC of 0.909, accuracy of 84.3%, micro-average sensitivity of 84.3%, and micro-average specificity of 92.1% in those with only X-rays on the internal test set. On the external test set, the PBTC-TransNet fusion model gained the highest micro-average AUC of 0.847 for patients with X-ray + CT.ConclusionsWe successfully developed and externally validated the transformer-based PBTC-Transnet fusion model for the effective classification of primary bone tumors. This model, rooted in incomplete multimodal images and clinical characteristics, effectively mirrors real-life clinical scenarios, thus enhancing its strong clinical practicability.

Postoperative challenges addressed through nursing care of patients receiving lower extremity tumor prosthesis

BackgroundPatients with primary Bone Sarcoma and Giant Cell Tumors in the lower extremities often require major surgery involving tumor prostheses. The postoperative course for this patient group can be complex and influenced by various factors and challenges that demand careful nursing care. This study aims to identify challenges related to the nursing care of individuals with primary bone tumors following surgery for tumor prostheses in the lower extremities.MethodsA retrospective cohort study of 15 patients treated at Rigshospitalet, Copenhagen, Denmark, between November 5. 2016, and April 1. 2020 was conducted by medical record review, focusing on challenges related to postoperative nursing care. All patients with the surgery code “Bone Excision” were identified within the surgery booking system and screened for eligibility.ResultsPatients experienced postoperative challenges such as severe pain, prolonged time to mobilization (mean: 4 days), and defecation (mean: 5 days). The mean length of stay at the Rigshospitalet was 13 days. Furthermore, eleven patients (73%) reported disrupted sleep and nausea.ConclusionPatients undergoing tumor prosthesis surgery in the lower extremities face considerable postoperative challenges that contribute to a prolonged hospital stay. These challenges, including severe pain, delayed mobilization, and gastrointestinal issues, significantly impact recovery. The findings highlight the urgent need for targeted nursing interventions to address these issues effectively. Enhanced pain management protocols, early mobilization strategies, and comprehensive postoperative care plans are essential to improve patient outcomes and reduce the length of hospital stays. Addressing these challenges through dedicated nursing care is crucial for optimizing the recovery process for patients receiving lower extremity tumor prostheses.

Enzymatic TET-1 inhibition highlights different epigenetic behaviours of IL-1β and TNFα in tumour progression of OS cell lines

Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial–mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review

BackgroundXanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported.Case presentationWe present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed.ConclusionsAlthough rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.

IGFBP5 in osteosarcoma tumorigenesis: Gene expression profile among metastatic and non-metastatic patients

Osteosarcoma (OS) is the most frequent primary malignant bone tumor among children and adolescents, with a peak of incidence in the second decade of life. The presence of metastasis at diagnosis in OS patients significantly decreases the chances of survival and new therapy approaches are needed. The IGFBP5 gene is related to osteoblasts metabolism and some studies have pointed out a role of its low expressions in OS development and metastasis. In this study, we aimed to establish an IGFBP5 gene expression profile among metastatic and non-metastatic OS patients throughout the treatment and development of the disease. Fresh-frozen tumor samples were obtained from 40 patients admitted to treatment at the Pediatric Oncology Institute (IOP/GRAACC/UNIFESP) and divided by clinical status: metastatic or non-metastatic disease. For each patient, samples before and after chemotherapy treatment were obtained, as well as metastasis and lung tissue surrounding metastasis samples from the metastatic patients. A quantitative real-time PCR was used to investigate IGFBP5 expression. Our analyses demonstrate that non-metastatic patients presented lower IGFBP5 expression in their pre-chemotherapy samples compared with metastatic patients, suggesting that low expressions of this gene could help triggering the OS tumorigenesis but that its action alone is not sufficient to activate the metastatic process. Heterogeneity in IGFBP5 expressions within groups was also seen. We observed that IGFBP5 and two MAPK genes, a downstream pathway in the IGFBP5 axis, are differentially expressed in OS samples of non-metastatic patients. Further investigation about these genes’ modulations might lead to a better understanding of metastasis development in OS.

An Analysis of The Pattern and Frequency of Primary Malignant Bone Tumors in Nassyriah

Bone tumors are uncommon lesions and account for only 0.2% of all malignant tumors. Primary malignant bone tumors develop from bony tissue and are categorized according to their location of origin and the cell type that makes up the tumor. This research aims to report on the prevalence, geographic distribution, and comparison of malignant bone tumors in Nassyriha province. Malignant bone tumors were studied in 182 people (119 men and 63 females) between February 2021 and February 2023. Their ages varied widely (from 5 to 70), with the second decade being the most prevalent. The most common cancer was osteosarcoma, which accounted for 34.62 percent, followed by Ewing's sarcoma (24.73), chondrosarcoma (13.74), multiple myeloma (11.53), malignant giant cell tumors (8.14%), fibrosarcoma (2.74%), and 2 instances of chordoma (1.10%). None of the six instances (3.30%) could be definitively diagnosed. Primary malignant bone tumors are rising, with men being disproportionately impacted. Information gleaned from this study will be useful for both researchers and clinicians.

A Rare Case of Primary Bone Follicular Lymphoma with Multiple Osteolytic Lesions: A Case Report and Review of the Literature

Introduction: Primary bone lymphoma (PBL) is a rare clinical entity, accounting for less than 5% of all extranodal non-Hodgkin lymphomas and approximately 5% of primary bone tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common histotype, accounting for about 80% of all PBL cases. Conversely, the incidence of indolent primary bone lymphomas (iPBL) represents less than 1% of all reported PBL cases, and data on these rarer lymphomas are scarce. Drawing on diagnostic criteria developed by the World Health Organization (WHO) and the International Extranodal Lymphoma Study Group (IELSG), we report a rare case of primary bone follicular lymphoma, focusing specifically on the clinical presentation and treatment. Discussion: Additionally, we provide a systematic review of the literature data on this very rare lymphoproliferative entity.

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.

From Pelvic Bone to Pleura: A Rare Metastatic Pathway in Osteosarcoma

ABSTRACT Osteosarcoma stands out as the predominant primary malignant bone tumor originating from primitive mesenchymal bone-forming cells. Its usual onset occurs in individuals aged 10–20 years, with occurrences beyond 40 years being rare, particularly in the absence of conditions such as Paget’s disease or osteogenesis imperfecta. Where lungs are the most common site for metastasis, the involvement of the pleura presents as an unusual aspect, given that pleural effusion and calcified thickening are not typical manifestations of osteosarcoma. This case involves a 61-year-old male who presented with osteosarcoma localized in the right pelvic bone, accompanied by concurrent right pleural effusion and calcified pleural thickening.

Outcome of recycle bone reconstruction using liquid nitrogen in primary malignant bone tumor

Primary malignant bone tumors constitute a small but significant portion, accounting for 3–5% of childhood cancers. Cryosurgery, utilizing liquid nitrogen to induce tumor necrosis through extreme cold, emerges as a favorable surgical technique for bone tumor. This study delves into the clinical and radiological outcomes of individuals underwent cryosurgery. This descriptive study focused on patients with primary malignant bone tumors subjected to wide resection and cryosurgery with follow-up period from 6 up to 48 months from year 2018 - 2023. The data was collected from medical records and database, we evaluated the demographic data, clinical with Musculoskeletal Tumor Society (MSTS), radiological outcome with International Society of Limb Salvage (ISOLS) score, and the complications of cryosurgery observed. Among the 37 patients examined, 20 males and 17 females were averaging 21.7 years of age. 29 of 37 (78%) cases identified as osteosarcoma most common location in the epimetaphyseal of the long bone with Grade Enneking IIB. MSTS score averaged 25.35 ± 5.54, with more than 68% achieving excellent and good score. ISOLS for radiological score revealed 37.8% with an excellent score, 48.6% with a good score. The most common complication, reccurence, occurs in 6 cases (16.2%). Patients with primary malignant bone tumors who underwent cryosurgery showed successful clinical and radiological outcomes, as measured by MSTS and ISOLS scores. This underscores the significance of cryosurgery in primary malignant bone tumor as favorable and cost-effective treatment, showcasing improved functionality and positive radiological results.

Allograft-prosthesis composite after proximal femur bone tumor resection in pediatric age: Is it effective in preserving bone stock?

The purpose of the study was to answer the following questions. What was functional results of pediatric patients receiving a short stem allograft-prosthesis composite of the proximal femur? What was complication rate and revision-free implant survival? Was it possible to preserve the bone stock of the proximal femur in pediatric patients? We reviewed 10 pediatric patients treated with proximal femur resection for a primary bone tumor and reconstruction with short stem allograft-prosthesis composite, with at least 24 months follow-up. The median age was 9 years (4-13) at surgery. The mean resection length was 15 cm (6-29). In six cases, fixation was performed with a short plate positioned under the great trochanter while in four cases a long plate extended over the great trochanter was employed. Nine complications that required surgical revision were assessed in six patients (one wound dehiscence, two nonunions, two fractures, one acetabular wear, three hypometria), while allograft-prosthesis composite removal was required in three patients. The revision-free survival was 57% (95% confidence interval 33%-100%) at 5 and 10 years. The graft removal-free survival was 75% (95% confidence interval 50%-100%) at 5 and 10 years. The mean Musculo-Skeletal Tumor Society Score was 28 (20-30). Allograft-prosthesis composites with short stem and compression plate represents an effective reconstructive option after proximal femur resection for primary bone tumors in growing patients, preserving bone stock. The use of a compression plate extended over the greater trochanter seemed to reduce failure rate.

GNAS, not a Highly Mutated Gene, Has Prognostic Significance and Carcinogenic Effects in Osteosarcoma.

Osteosarcoma is a prevalent and aggressive primary malignant bone tumor affecting children and adolescents. Despite advancements in sequencing technologies, there remains a lack of reliable prognostic biomarkers and effective targeted therapies for osteosarcoma. This study focuses on identifying key prognostic genes, particularly the role of GNAS, in osteosarcoma progression. Bioinformatics analyses were performed on osteosarcoma datasets from the Gene Expression Omnibus (GEO). Differential gene expression analysis, weighted correlation network analysis (WGCNA), and survival analysis identified potential prognostic hub genes. The expression and function of these genes were validated through immunohistochemistry and animal experiments. Specifically, the role of GNAS was investigated through siRNA-mediated knockdown in osteosarcoma cell lines and nude mice models. Five hub genes (PROP1, GNAS, CYP4F2, LHX3, CNGB1) were identified as significantly related to osteosarcoma prognosis. Among these, GNAS was found to be highly expressed in osteosarcoma tissues compared to normal tissues. Immunohistochemical analysis confirmed the elevated expression of GNAS in osteosarcoma samples. GNAS mutation analysis revealed a low mutation rate in osteosarcoma, suggesting its oncogenic role is independent of mutational status. Animal experiments demonstrated that knocking down GNAS significantly inhibited tumor growth and induced apoptosis in osteosarcoma cells. GNAS is highly expressed in osteosarcoma and associated with poor prognosis, acting as an oncogene in osteosarcoma progression. Targeting GNAS could be a potential therapeutic strategy for osteosarcoma. Further studies on GNAS-related signaling pathways may provide deeper insights into the molecular mechanisms driving osteosarcoma malignancy.