Primary Malignant Bone Tumor Research Articles

Endoprosthesis vs. nail-cement spacer application for reconstruction after oncologic proximal humeral resection: is there a difference in functional outcome?

The proximal humerus is a common site for primary malignant and benign aggressive bone tumors, necessitating wide resection and subsequent skeletal defect reconstruction. Various reconstruction options include osteoarticular allografts, autografts, endoprosthesis, nail-cement spacer, reverse shoulder arthroplasty, and allograft-prosthesis composites. However, there is no consensus on the optimal reconstruction method. This study aims to compare functional outcomes and complications between these two methods. A total of 40 patients with proximal humerus tumors who underwent endoprosthesis or nail-cement spacer reconstruction between March 2012 and December 2020 were included. The mean follow-up in the study was 31.37+/- 12 months. Demographic and clinical data were collected, and functional outcomes were assessed using the Musculoskeletal Tumor Society 93 scoring system and the Disabilities of the Arm, Shoulder, and Hand questionnaire. Complications and oncological outcomes were recorded. Both groups were similar in terms of demographic and clinical variables. Endoprosthesis reconstruction demonstrated significantly better active shoulder forward flexion compared to nail-cement spacer (45.8 vs. 25.2 degrees) (P=.015). Endoprosthesis group also exhibited greater active shoulder internal rotation (68.25 vs. 63.25 degrees) (P=.004). No statistically significant differences were observed in overall functional outcomes. Complications, including radial nerve palsy and infection, were comparable between groups, with one case of spacer loosening. Both endoprosthesis and nail-cement spacer reconstruction provide comparable functional outcomes and complication rates following proximal humerus tumor resection. Nail-cement spacer offers a cost-effective alternative for patients in resource-constrained settings.

Adamantinoma: About 4 Cases

Adamantinoma is a rare primary malignant bone tumor of the tibia in young adults. Histologically, it comprises malignant epithelial cells within a fibrous or osteofibrous stroma. Adamantinoma poses a problem of differential diagnosis with osteofibrous dysplasia and osteofibrodysplasia. the evolution of this low-grade sarcoma is slow. Treatment is surgical, involving resection of the tumour and reconstruction of the bone. Metastases may occur in the lungs, lymph nodes or bones. We report 4 cases of adamantinoma.

En Bloc Surgery in the Thoracic Spine: Indications, Results, and Complications in a Series of Eighty-Five Patients Affected by Primary and Secondary Malignant Bone Tumors

BackgroundEn-bloc resection remains the cornerstone treatment for malignant bone tumors affecting the spine. The thoracic spine poses unique challenges due to the proximity of crucial structures. This study assesses outcomes of patients who underwent en-bloc spondylectomy for malignant bone tumors at the thoracic level. MethodsWe retrospectively reviewed 85 cases of primary and secondary bone tumors in the thoracic spine, undergoing en-bloc spondylectomy from 1996 to 2016. Evaluation encompassed clinical presentation, tumor characteristics, surgical outcomes, complications, survival rates, and recurrence. ResultsOf 85 patients, 40 presented directly, while 45 had undergone prior intralesional surgery. Chondrosarcoma and chordoma comprised the most prevalent primary histological types; thyroid and kidney carcinomas were the most frequent secondary tumors. Pain was reported in 75 patients at diagnosis. Margins were adequate in 54 cases and intralesional in 31. Immediate postoperative deaths amounted to four. Major complications included substantial blood loss, neurological deterioration, and paraplegia. The 5-year Local Recurrence-Free Survival rate was 58.7%, significantly influenced by the surgical margin: patients with wide margins experienced a 5-year LRFS of 85.7%, while those with marginal and intralesional margins had rates of 56.7% and 45.6%, respectively; overall recurrence was 22.3% with no notable disparities between previously treated and untreated patients. The 5-year Overall Survival (OS) rates were 63.2% and 56.2% for primary and secondary tumors, respectively. The OS was not significantly influenced by surgical margins. ConclusionsManaging malignant thoracic bone tumors poses significant challenges. This study underscores the criticality of achieving adequate margins, particularly following previous intralesional approaches.

Overexpression of miR-506-3p reversed doxorubicin resistance in drug-resistant osteosarcoma cells.

Background and objective: Osteosarcoma is a common primary malignant tumor of bone, and doxorubicin is one of the most widely used therapeutic drugs. While the problem of doxorubicin resistance limits the long-term treatment benefits in osteosarcoma patients. The role of miRNAs and their target genes in osteosarcoma have become increasingly prominent. Currently, there is no report on miR-506-3p reversing doxorubicin resistance by targeting STAT3 in osteosarcoma. The purpose of this study was to investigate the molecular mechanism that overexpression of miR-506-3p reverses doxorubicin resistance in drug-resistant osteosarcoma cells. Methods: Doxorubicin-resistant osteosarcoma cells (U-2OS/Dox) were constructed by intermittent stepwise increasing stoichiometry. The target genes of miR-506-3p were predicted by bioinformatics approach and the targeting relationship between miR-506-3p and STAT3 was detected using dual luciferase reporter assay. U-2OS/Dox cells were treated with miR-506-3p overexpression and STAT3 silencing respectively. Then Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of JAK2/STAT3 signaling pathway, drug-resistant and apoptotic associated molecules. The migration and invasion were assessed by cell scratch assay and transwell assay. The cell proliferative viability and apoptosis were investigated by CCK8 assay and flow cytometry assay. Results: U-2OS/Dox cells were successfully constructed with a 14.4-fold resistance. MiR-506-3p is directly bound to the 3'-UTR of STAT3 mRNA. Compared with U-2OS cells, the mRNA expression of miR-506-3p was reduced in U-2OS/Dox cells. Overexpression of miR-506-3p decreased the mRNA expression levels of JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and decreased the protein expression levels of p-JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and conversely increased Bax expression. It also inhibited the proliferation, migration and invasion of U-2OS/Dox cells and promoted cells apoptosis. The results of STAT3 silencing experiments in the above indicators were consistent with that of miR-506-3p overexpression. Conclusion: Overexpression of miR-506-3p could inhibit the JAK2/STAT3 pathway and the malignant biological behaviors, then further reverse doxorubicin resistance in drug-resistant osteosarcoma cells. The study reported a new molecular mechanism for reversing the resistance of osteosarcoma to doxorubicin chemotherapy and provided theoretical support for solving the clinical problems of doxorubicin resistance in osteosarcoma.

Revealing the pharmacological effects of Remodelin against osteosarcoma based on network pharmacology, acRIP-seq and experimental validation

Osteosarcoma (OS) is the most common primary malignant tumor of bone. Remodelin, an inhibitor of the N (4)-Acetylcytidine (ac4C) acetylation modifying enzyme N-acetyltransferase 10 (NAT10), has been shown to have therapeutic effects on cancer in several studies, and our previous studies have confirmed the inhibitory effect of Remodelin on OS cells, however, the mechanism of action has not yet been elucidated. We used network pharmacological analysis to quantify the therapeutic targets of Remodelin against OS. acRIP-seq and RNA-seq were performed to investigate the inhibitory activity of Remodelin on acetylation and its effect on the transcriptome after intervening in OS cells U2OS with Remodelin in vitro. Key target genes were deduced based on their pharmacological properties, combined with network pharmacology results and sequencing results. Finally, the deduced target genes were validated with vitro experiments. Network pharmacological analysis showed that 2291 OS-related target genes and 369 Remodelin-related target genes were obtained, and 116 overlapping genes were identified as Remodelin targets for OS treatment. Sequencing results showed that a total of 13,736 statistically significant ac4C modification peaks were detected by acRIP-seq, including 6938 hypoacetylation modifications and 6798 hyperacetylation modifications. A total of 2350 statistically significant mRNAs were detected by RNA-seq, of which 830 were up-regulated and 1520 were down-regulated. Association analyses identified a total of 382 genes that were Hypoacetylated-down, consistent with inhibition of mRNA acetylation and expression by Remodelin. Five genes, CASP3, ESR2, FGFR2, IGF1 and MAPK1, were identified as key therapeutic targets of Remodelin against OS. Finally, in vitro experiments, CCK-8 and qRT-PCR demonstrated that Remodelin indeed inhibited the proliferation of OS cells and reduced the expression of three genes: ESR2, IGF1, and MAPK1. In conclusion, ESR2, IGF1 and MAPK1 were identified as key therapeutic targets of Remodelin against OS. This reveals the target of Remodelin's pharmacological action on OS and provides new ideas for the treatment of OS.

Systemic Cisplatin Does Not Affect the Bone Regeneration Process in a Critical Size Defect Murine Model.

Osteosarcoma (OS) is the most common primary malignant bone tumor, and the current standard of care for OS includes neoadjuvant chemotherapy, followed by an R0 surgical resection of the primary tumor, and then postsurgical adjuvant chemotherapy. Bone reconstruction following OS resection is particularly challenging due to the size of the bone voids and because patients are treated with adjuvant and neoadjuvant systemic chemotherapy, which theoretically could impact bone formation. We hypothesized that an osteogenic material could be used in order to induce bone regeneration when adjuvant or neoadjuvant chemotherapy is given. We utilized a biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of systemic chemotherapy in a murine critical size defect model. We found that in the presence of neoadjuvant or adjuvant chemotherapy, MHA/Coll is able to enhance and increase bone formation in a murine critical size defect model (11.16 ± 2.55 or 13.80 ± 3.18 versus 8.70 ± 0.81 mm3) for pre-op cisplatin + MHA/Coll (p-value = 0.1639) and MHA/Coll + post-op cisplatin (p-value = 0.1538), respectively, at 12 weeks. These findings indicate that neoadjuvant and adjuvant chemotherapy will not affect the ability of a biomimetic scaffold to regenerate bone to repair bone voids in OS patients. This preliminary data demonstrates that bone regeneration can occur in the presence of chemotherapy, suggesting that there may not be a necessity to modify the current standard of care concerning neoadjuvant and adjuvant chemotherapy for the treatment of metastatic sites or micrometastases.

"Intercalary Allograft Reconstruction using 3D Designed, Patient-Specific Surgical Guides and Plate during Resection of Primary Malignant Bone Tumors: Workflow and Surgical Technique"

"Intercalary Allograft Reconstruction using 3D Designed, Patient-Specific Surgical Guides and Plate during Resection of Primary Malignant Bone Tumors: Workflow and Surgical Technique"

Dipsacus Asperoides-Derived Exosomes-Like Nanoparticles Inhibit the Progression of Osteosarcoma via Activating P38/JNK Signaling Pathway.

Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo. DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry. Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis. Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.

Doxorubicin-Loaded Microalgal Delivery System for Combined Chemotherapy and Enhanced Photodynamic Therapy of Osteosarcoma.

Osteosarcoma (OS) is considered the most frequent type of primary malignant bone tumor. Currently, radiotherapy, photodynamic (PDT), and other therapies for osteosarcoma are limited by tumor hypoxia and single efficacy and serve side-effects. Herein, we reported a microalgal drug delivery system (SpiD), doxorubicin (DOX)-loaded Spirulina platensis (Spi) for OS therapy. The specific surface of Spirulina platensis allowed for effective loading of DOX via surface channels and electrostatic interactions. Under 650 nm laser irradiation, SpiD enabled high oxygen production by photosynthesis and enhanced reactive oxygen species (ROS) generation via chlorophyll-assisted photosensitization, synergistically killing tumor cells with the released DOX. Combined chemotherapy and enhanced PDT mediated by SpiD exerted synergic antitumor effects and resulted in potent therapeutic efficacy in orthotopic osteosarcoma mice. Furthermore, SpiD could reduce the side-effects of chemotherapy, showing excellent blood and tissue safety. Taken together, this microalgal drug delivery system provided a natural, efficient, safe, and inexpensive strategy for OS treatment.

Solitary bone plasmacytoma of spine with involvement of intervertebral disk: a case report and literature review.

Primary malignant bone tumors of the spine are exceedingly rare, with solitary bone plasmacytoma (SBP) representing approximately 30% of all cases. Radiological assessments are crucial for localizing SBP and for ruling out a diagnosis of multiple myeloma (MM). Imaging features resembling a "mini-brain" appear to be distinctive for SBP. Vertebral lesions accompanied by adjacent disc space involvement typically suggest spinal infections, while the potential for SBP involvement is often overlooked. We present a case of a 61-year-old female with SBP who exhibited thoraco-lumbar spine destruction and adjacent disc space involvement. The patient sought treatment at our medical center due to lumbodorsal pain radiating bilaterally to the inguinal regions. Radiological findings revealed an osteolytic lesion involving the intervertebral disc, making it challenging to distinguish between tumor and inflammation. A biopsy of the vertebral lesion confirmed the diagnosis of SBP, which was further supported by laboratory results. Post-diagnosis, the patient underwent radiotherapy, receiving a total dose of 4000Gy, which alleviated her symptoms. We also provide a comprehensive literature review on SBP with disc involvement to aid both clinical and radiological diagnoses.

Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma

BackgroundOsteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown.MethodsIn this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The “ESTIMATE” package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug.ResultsFive genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments.ConclusionThe ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.

Diagnostic Performance of Artificial Intelligence in Detection of Primary Malignant Bone Tumors: a Meta-Analysis.

We aim to conduct a meta-analysis on studies that evaluated the diagnostic performance of artificial intelligence (AI) algorithms in the detection of primary bone tumors, distinguishing them from other bone lesions, and comparing them with clinician assessment. A systematic search was conducted using a combination of keywords related to bone tumors and AI. After extracting contingency tables from all included studies, we performed a meta-analysis using random-effects model to determine the pooled sensitivity and specificity, accompanied by their respective 95% confidence intervals (CI). Quality assessment was evaluated using a modified version of Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Study Risk of Bias Assessment Tool (PROBAST). The pooled sensitivities for AI algorithms and clinicians on internal validation test sets for detecting bone neoplasms were 84% (95% CI: 79.88) and 76% (95% CI: 64.85), and pooled specificities were 86% (95% CI: 81.90) and 64% (95% CI: 55.72), respectively. At external validation, the pooled sensitivity and specificity for AI algorithms were 84% (95% CI: 75.90) and 91% (95% CI: 83.96), respectively. The same numbers for clinicians were 85% (95% CI: 73.92) and 94% (95% CI: 89.97), respectively. The sensitivity and specificity for clinicians with AI assistance were 95% (95% CI: 86.98) and 57% (95% CI: 48.66). Caution is needed when interpreting findings due to potential limitations. Further research is needed to bridge this gap in scientific understanding and promote effective implementation for medical practice advancement.

Coverage of lateral soft tissue defects with sartorius muscle flap after distal femoral replacement for malignant bone tumors.

To prevent infection after limb-sparing surgery for primary malignant bone tumors, it is important to cover the megaprosthesis with muscle tissue that has sufficient blood flow. Coverage with a lateral gastrocnemius flap has been reported in cases of distal femoral replacement in which the vastus lateralis and vastus intermedius muscles have been resected; however, the risk of peroneal nerve palsy is reportedly high because the muscle flap passes near the peroneal head. This study was performed to examine the postoperative outcomes of patients with primary malignant bone tumors of the distal femur who underwent wide resection (including the vastus lateralis and vastus intermedius muscles) followed by reconstruction with a megaprosthesis and coverage of the lateral side of the prosthesis with a sartorius muscle flap. We retrospectively analyzed three patients who underwent reconstruction with a megaprosthesis after wide resection of a primary malignant bone tumor of the distal femur involving the vastus lateralis and vastus intermedius muscles and reconstruction of the soft tissue defect on the lateral side of the prosthesis with a sartorius muscle flap. The average defect size was 6×13cm, the average time required for a sartorius muscle flap was 100min, and the average implant coverage was 93%. The average postoperative follow-up period was 35 months, during which no postoperative complications such as infection, skin necrosis, or nerve palsy occurred. The distally based sartorius muscle flap is easy to elevate in the supine position, has minimal functional loss after harvesting, and has minimal risk of nerve palsy. It can be advocated as the first option for coverage of soft tissue defects lateral to distal femoral replacement.

Exploring the Impact of Exosomal Cargos on Osteosarcoma Progression: Insights into Therapeutic Potential.

Osteosarcoma (OS) is a primary malignant bone tumor with high metastasis. Poor prognosis highlights a clinical need for novel therapeutic strategies. Exosomes, also known as extracellular vesicles, have been identified as essential players in the modulation of cancer. Recent studies have suggested that OS-derived exosomes can drive pro-tumorigenic or anti-tumorigenic phenotypes by transferring specific cargos, including proteins, nucleic acids, and metabolites, to neighboring cells, significantly impacting the regulation of cellular processes. This review discusses the advancement of exosomes and their cargos in OS. We examine how these exosomes contribute to the modulation of cellular phenotypes associated with tumor progression and metastasis. Furthermore, we explore the potential of exosomes as valuable biomarkers for diagnostics and prognostic purposes and their role in shaping innovative therapeutic strategies in OS treatment development.

Chronic Pain and Bone-Related Pathologies: A Narrative Review.

Pain related to bone may occur as a result of trauma, bone fracture, genetic disease, arthritis, benign or malignant primary bone tumors and bone cancer metastases. We discuss the pathophysiology of chronic bone-related pain, treatment options and therapeutic perspectives. Using predefined terms, we searched PubMed, MEDLINE, and Google Scholar for meta-analyses, evidence-based reviews, and clinical practice guidelines. This narrative article reviews pathologies linked to chronic bone pain and discusses the preventive and therapeutic strategies for better bone pain management. Pathophysiology of bone-related pain is complex, especially in cancer conditions and missing gaps are underlined. Treatment of pain, after adequate evaluation, includes classical analgesics, adjuvants for neuropathic and refractory pain, specific bone drugs, surgery and non-pharmacological approaches. Prevention of chronic bone pain encompasses prevention of central sensitization and of causal diseases. Translational research, drug repurposing, an interdisciplinary approach and a person-centered assessment to evaluate, beyond pain, physical, social and functional abilities, are proposed future directions to improve chronic bone pain management and optimize independence and quality of life. Chronic bone-related pain is frequent and is associated with an impairment of quality of life. In this review, we summarize the pathophysiology of chronic bone pain, describe treatment approaches and envisage new avenues for pain alleviation. Our article will help doctors manage chronic bone pain and address unmet needs for future research to alleviate bone-related pain.

A Systematic Review and Meta-Analysis of the Outcomes of Reconstruction with Vascularised vs Non-Vascularised Bone Graft after Surgical Resection of Primary Malignant and Non-Malignant Bone Tumors.

Vascularised bone grafting (VBG) and non-vascularised bone grafting (NVBG) are crucial biological reconstructive procedures extensively employed in the management of bone tumours. The principal aim of this study is to conduct a comparative analysis of the post-resection outcomes associated with the utilisation of vascularised and non-vascularised bone grafts. A comprehensive and systematic literature review spanning the years 2013 to 2023 was meticulously executed, utilising prominent online databases including PubMed/Medline, Google Scholar, and Cochrane Library. Inclusion criteria were restricted to comparative articles that specifically addressed outcomes pertaining to defect restoration following bone tumour resection via vascularised and non-vascularised bone grafting techniques. The quality of research methodologies was assessed using the Oxford Quality Scoring System for randomised trials and the Newcastle Ottawa Scale for non-randomised comparative studies. Data analysis was conducted using SPSS version 24. Key outcome measures encompassed the Musculoskeletal Tumour Society Score (MSTS), bone union duration, and the incidence of post-operative complications. This analysis incorporated four clinical publications, enrolling a total of 178 participants (comprising 92 males and 86 females), with 90 patients subjected to VBG and 88 to NVBG procedures. The primary endpoints of interest encompassed MSTS scores and bone union durations. Although no statistically significant distinction was observed in the complication rates between the two cohorts, it is noteworthy that VBG exhibited a markedly superior bone union rate (P<0.001). Our systematic evaluation revealed that VBG facilitates expedited bone union, thereby contributing to accelerated patient recovery. Notably, complication rates and functional outcomes were comparable between the VBG and NVBG groups. Moreover, the correlation between bone union duration and functional scores following VBG and NVBG merits further investigation. reconstruction techniques, vascularised bone grafting, non-vascularised bone grafting, bone tumor, resection.

A Systemic Review of Primary Malignant Long Bone Tumors in Children and Adolescents.

Managing bone tumours is complex, relying on limited evidence, expert opinions, and retrospective reviews. Multidisciplinary approaches and early diagnosis are crucial for better outcomes, especially in young patients with growing skeletons. The aim of this systemic review and meta-analysis is to give a comprehensive review of common malignant tumors affecting long bones in children and adolescents. A PubMed/Medline search for "primary malignant long bone tumours in children" initially retrieved 1120 papers, which were subsequently narrowed down to 110 articles based on inclusion and exclusion criteria. These articles were reviewed, focusing on clinical presentation, diagnostic workup, treatment options, surgical planning, and variations in presentation, including rare tumours. The two most commonly reported tumours were osteosarcoma and Ewing sarcoma, leading to the division of studies into five groups. The inclusion criteria encompassed malignancies in patients aged 2-25 years, work-up, imaging, surgical treatment, rare tumour case reports, and surgical management principles, resulting in a heterogeneous group of articles. To enhance categorisation, it was clarified that studies with 10 or more cases were considered retrospective reviews. Reviewing of results thus demonstrate that the two likely tumours in children under consideration were osteosarcoma and Ewing sarcoma. Their presentation findings and clinical features were discussed in detail in the review. It is worth noting here that in case of differential diagnosis this should be the first on the list. Although focus of literature is more on the two most common tumours. However, rare tumours should be considered as they can mimic these common tumors. primary, malignant, bone tumors, children, adolescent.

Nerve growth factor promote VCAM-1-dependent monocyte adhesion and M2 polarization in osteosarcoma microenvironment: Implications for larotrectinib therapy.

Osteosarcoma is the most prevalent form of primary malignant bone tumor, primarily affecting children and adolescents. The nerve growth factors (NGF) referred to as neurotrophins have been associated with cancer-induced bone pain; however, the role of NGF in osteosarcoma has yet to be elucidated. In osteosarcoma samples from the Genomic Data Commons data portal, we detected higher levels of NGF and M2 macrophage markers, but not M1 macrophage markers. In cellular experiments, NGF-stimulated osteosarcoma conditional medium was shown to facilitate macrophage polarization from the M0 to the M2 phenotype. NGF also enhanced VCAM-1-dependent monocyte adhesion within the osteosarcoma microenvironment by down-regulating miR-513c-5p levels through the FAK and c-Src cascades. In in vivo xenograft models, the overexpression of NGF was shown to enhance tumor growth, while the oral administration of the TrK inhibitor larotrectinib markedly antagonized NGF-promoted M2 macrophage expression and tumor progression. These results suggest that larotrectinib could potentially be used as a therapeutic agent aimed at mitigating NGF-mediated osteosarcoma progression.

Results of invasive diagnosis of primary malignant bone tumors of the pelvis

Results of invasive diagnosis of primary malignant bone tumors of the pelvis

A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble.

Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls' Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. SPIO/TP53/PLGA NBs with a particle size of approximately 200nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.