Osteosarcoma is the most common primary bone tumor with high malignancy.It is particularly necessary to achieve rapid and accurate diagnosis in its intraoperative examination and early diagnosis.Accordingly,the multim...Osteosarcoma is the most common primary bone tumor with high malignancy.It is particularly necessary to achieve rapid and accurate diagnosis in its intraoperative examination and early diagnosis.Accordingly,the multimodal microscopic imaging diagnosis system constructed by bright field,spontaneous fluorescence and polarized light microscopic imaging was used to study the pathological mechanism of osteosarcoma from the tissue microenvironment level and achieve rapid and accurate diagnosis.First,the multimodal microscopic images of normal and osteosarcoma tissue slices were collected to characterize the overall morphology of the tissue microenvironment of the samples,the arrangement structure of collagen fibers and the content and distribution of endogenous fluorescent substances.Second,based on the correlation and complementarity of the feature information contained in the three single-mode images,combined with convolutional neural network(CNN)and image fusion methods,a multimodal intelligent diagnosis model was constructed to effectively improve the information utilization and diagnosis accuracy.The accuracy and true positivity of the multimodal diagnostic model were significantly improved to 0.8495 and 0.9412,respectively,compared to those of the single-modal models.Besides,the difference of tissue microenvironments before and after cancerization can be used as a basis for cancer diagnosis,and the information extraction and intelligent diagnosis of osteosarcoma tissue can be achieved by using multimodal microscopic imaging technology combined with deep learning,which significantly promoted the application of tissue microenvironment in pathological examination.This diagnostic system relies on its advantages of simple operation,high efficiency and accuracy and high cost-effectiveness,and has enormous clinical application potential and research significance.展开更多
In the current settings of osteosarcoma research and drug screening,in vitro three-dimensional(3D)models,which overcome the limitations of traditional models,are favored.In in vitro 3D models,tumor microenvironment si...In the current settings of osteosarcoma research and drug screening,in vitro three-dimensional(3D)models,which overcome the limitations of traditional models,are favored.In in vitro 3D models,tumor microenvironment simulation,particularly of the mechanical microenvironment,is crucial for estimating the biological effects of a tumor.However,current in vitro osteosarcoma model construction is often limited to a single mechanical signal,which fails to simulate the diversity of osteosarcoma mechanical stimuli.In this study,we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model(IGBSTOM).We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate,methacryloylated gelatin,thrombin,and transglutaminase,which is rich in polysaccharides and proteins and exhibits self-healing properties.Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness,proliferation,and migration,and successfully reproduced the nest-like structure of tumors,providing an in vitro research platform that is more similar to the natural tumor than the existing models.This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development,drug screening,and exploration of drug resistance and metastasis mechanisms.展开更多
Osteosarcoma(OS)is the most prevalent primary malignant bone tumor affecting children and adolescents.Despite ongoing research efforts,the 5-year survival rate has remained stagnant for many years,highlighting the cri...Osteosarcoma(OS)is the most prevalent primary malignant bone tumor affecting children and adolescents.Despite ongoing research efforts,the 5-year survival rate has remained stagnant for many years,highlighting the critical need for novel drug development to enhance current treatment protocols.ZiyuglycosideⅡ(ZYGⅡ),a triterpenoid saponin extracted from S.officinalis,has recently demonstrated antitumor properties.This study evaluates the antitumor effect of ZYGⅡon osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma(ESRRG),which inhibits disease progression.The research employs in vitro experiments using multiple established osteosarcoma cell lines,as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma.Additionally,ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYGⅡexerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53.Results indicate that ZYGⅡadministration led to decreased OS cell viability and reduced tumor volumes.Furthermore,cell cycles were arrested at the G_(0)/G1 phase,while the proportion of apoptotic cells increased.Expression of p53,ESRRG,p21,Bax,Cleaved Caspase-9,and Cleaved Caspase-3 proteins increased,while expression of CDK4,Cyclin D1,and Bcl-2 proteins decreased.Multiple ZYGⅡand ESRRG docking patterns were simulated through molecular docking.Comparing the pharmacodynamic response of ZYGⅡto OS cell lines with reduced ESRRG and normal expression demonstrated that ZYGⅡinhibits osteosarcoma progression,induces cell cycle arrest,and promotes cell apoptosis through the coordination of p53 and ESRRG.In conclusion,ZYGⅡinhibits osteosarcoma progression,leads to cell cycle arrest,and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.展开更多
Osteosarcoma(OS)is a prevalent primary bone malignancy with limited treatment options.Therefore,it is imperative to investigate and understand the mechanisms underlying OS pathogenesis.Cancer-associated fibroblasts(CA...Osteosarcoma(OS)is a prevalent primary bone malignancy with limited treatment options.Therefore,it is imperative to investigate and understand the mechanisms underlying OS pathogenesis.Cancer-associated fibroblasts(CAFs)are markedly abundant in tumor stromal cells and are essentially involved in the modulation of tumor occurrence and development.In recent years,CAFs have become a hotspot as researchers aim to elucidate CAF mechanisms that regulate tumor progression.However,most studies on CAFs are limited to a few common cancers,and their association with OS remains elusive.This review describes the role and current knowledge of CAFs in OS,focusing on their potential cellular origin,classification,and diverse functionality.It was found that CAFs influenced OS tumor cell signaling,proliferation,invasion,metastasis,epithelial-mesenchymal transition,stemness maintenance,angiogenesis,and the ability to modify immune system components.Furthermore,findings on other common cancers indicated that effective therapeutic strategies included the manipulation of CAF activation,targeting CAF-derived components,and depletion of CAFs by biomarkers.This review provides new insights and a theoretical basis for OS research.展开更多
Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation wa...Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were utilized.Microarray experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were performed.In MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity levels.HYSA reduced the Warburg effect and induced ferroptosis(FPT)in MG63 cells.Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells.The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells.HIF-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°C.HYSA significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand HYSA.Conclusively,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway.HYSA is a possible therapeutic option for OC or other cancers.展开更多
OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-...OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in ...Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.展开更多
In the article‘MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1’(Oncology Research,2024,Vol.32,No.3,pp.463−476.doi:10.32604/or.20...In the article‘MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1’(Oncology Research,2024,Vol.32,No.3,pp.463−476.doi:10.32604/or.2023.044085),there was an error in the compilation of Fig.8D.We have revised Fig.8D to correct this error.A corrected version of Fig.8 is provided.This correction does not change any results or conclusions of the article.We apologize for any inconvenience caused.展开更多
An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(...An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.展开更多
Patients diagnosed with advanced osteosarcoma,often in the form of lung metastases,have abysmal five-year overall survival rates.The complexity of the osteosarcoma immune tumor microenvironment has been implicated in ...Patients diagnosed with advanced osteosarcoma,often in the form of lung metastases,have abysmal five-year overall survival rates.The complexity of the osteosarcoma immune tumor microenvironment has been implicated in clinical trial failures of various immunotherapies.The purpose of this exploratory study was to spatially characterize the immune tumor microenvironment of metastatic osteosarcoma lung specimens.Knowledge of the coordinating cellular networks within these tissues could then lead to improved outcomes when utilizing immunotherapy for treatment of this disease.Importantly,various cell types,interactions,and cellular neighborhoods were associated with five-year survival status.Of note,increases in cellular interactions between T lymphocytes,positive for programmed cell death protein 1,and myeloid-derived suppressor cells were observed in the 5-year deceased cohort.Additionally,cellular neighborhood analysis identified an Immune-Cold Parenchyma cellular neighborhood,also associated with worse 5-year survival.Finally,the Osteosarcoma Spatial Score,which approximates effector immune activity in the immune tumor microenvironment through the spatial proximity of immune and tumor cells,was increased within 5-year survivors,suggesting improved effector signaling in this patient cohort.Ultimately,these data represent a robust spatial multiplexed immunofluorescence analysis of the metastatic osteosarcoma immune tumor microenvironment.Various communication networks,and their association with survival,were described.In the future,identification of these networks may suggest the use of specific,combinatory immunotherapeutic strategies for improved anti-tumor immune responses and outcomes in osteosarcoma.展开更多
Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including color...Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.展开更多
Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment reg...Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.展开更多
Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patient...Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patients between January 2007 and July 2020,50 patients aged 13 to 39 years with Enneking stage II disease were included in the study.Serum lipid levels,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lipoprotein-α[Lp(a)],and apolipoprotein A1,B,and E(ApoA1,ApoB,and ApoE),and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.Results The mean levels of TC,TG,and ApoB were significantly increased following neoadjuvant chemotherapy(16%,38%,and 20%,respectively,vs.pretreatment values;P<0.01).The mean levels of LDL-C and ApoE were also 19%and 16%higher,respectively(P<0.05).No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy.An increase in Lp(a)was strongly correlated with the Ki-67 index(R=0.31,P=0.023).Moreover,a trend toward longer disease-free survival(DFS)was observed in patients with decreased TG and increased LDL-C following chemotherapy,although this difference was not statistically significant(P=0.23 and P=0.24,respectively).Conclusion Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma.There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy.The scale of increase in serum Lp(a)might have a potential prognostic role in osteosarcoma.Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.展开更多
Introduction: Osteosarcoma is the most common primary malignant bone tumor in children. It is highly aggressive and has a poor prognosis. A late presentation modifies and makes difficult the management affecting the s...Introduction: Osteosarcoma is the most common primary malignant bone tumor in children. It is highly aggressive and has a poor prognosis. A late presentation modifies and makes difficult the management affecting the survival of children. We report the case of a large conventional osteosarcoma in a 13-year-old girl. Case Presentation: Adolescent girl admitted for painful swelling of the left shoulder with absolute functional impotence of the thoracic limb and severe anemia. The painful swelling was thought to have been caused by a minor trauma that had occurred six months previously. The patient’s general condition was poor, and she presented with a large, shiny, painful mass over the shoulder and upper 2/3 of the left arm, measuring 28 cm long by 28 cm wide and 57 cm in circumference, and a large fistulous axillary adenopathy. CT scan showed a tumour lesion of the left humerus with liver and lung metastases, raising suspicion of osteogenic osteosarcoma. The tumor was classified according to TNM staging: T2N1M1(a + b). Management was modified when uncontrolled bleeding developed. It consisted of an extended amputation of the left thoracic limb. Pathological analysis showed a high-grade conventional osteosarcoma. Quality improvement was obtained for thirty days, followed by the onset of dyspnea. The evolution was towards death at forty days post-operatively. Conclusion: Osteosarcoma is a highly aggressive cancer. Delayed treatment leads to a fatal outcome. Early diagnosis is one of the challenges to be met in order to improve survival.展开更多
Osteosarcoma is the most prevalent primarymalignant bone tumor,primarily affecting adolescents aged 15–25 years.It is characterized by a high recurrence rate,poor prognosis,and lack of important biomarkers.Significan...Osteosarcoma is the most prevalent primarymalignant bone tumor,primarily affecting adolescents aged 15–25 years.It is characterized by a high recurrence rate,poor prognosis,and lack of important biomarkers.Significant mitochondrial dysfunction in osteosarcoma cells has been widely reported by recent studies.Dysfunctional mitochondria occupy an important position in cellularmetabolic reprogramming,immune microenvironment regulation,and programmed cell death.Therefore,targeting mitochondrial dysfunction may represent a new mechanism to overcome therapeutic barriers in the treatment of osteosarcoma and provides crucial target molecules for further development of targeted therapies and immunotherapies.The present article summarizes the recent reports of mitochondrial dysfunction in osteosarcoma and links it to various programmed cell death mechanisms,aiming to provide the basis for further clinical practice.展开更多
Background:Osteosarcoma is the most common primary bone malignancy,with a strong tendency towards local invasion and metastasis.The SRY-Box Transcription Factor 1(SOX1)gene,a member of the HMG-box family of DNA-bindin...Background:Osteosarcoma is the most common primary bone malignancy,with a strong tendency towards local invasion and metastasis.The SRY-Box Transcription Factor 1(SOX1)gene,a member of the HMG-box family of DNA-binding transcription factors,plays a crucial role in embryogenesis and tumorigenesis.However,its role in osteosarcoma,particularly in relation to metastatic potential,is not well understood.Methods:The GSE14359 dataset containing five samples of conventional osteosarcoma and four samples of lung metastatic osteosarcoma was obtained from the Gene Expression Omnibus(GEO)database and analyzed for differential gene expression using the R language.Gene expression was detected using qPCR and Western blotting.Transcriptional activity was assessed by Luciferase reporter gene assays,and cell metastatic ability was assessed by migration and invasion assays.Results:The study demonstrated that SOX1 binds to a specific response element within the Transmembrane 4 Superfamily Member 12(TSPAN12)promoter,upregulating TSPAN12 and its associated inflammatory pathways.Silencing TSPAN12 markedly reduces SOX1-mediated osteosarcoma cell invasion and inflammatory response,while TSPAN12 overexpression reverses these effects in SOX1-suppressed cells.Conclusion:In this study,our findings elucidate SOX1’s role in enhancing osteosarcoma metastasis via TSPAN12 upregulation,offering new insights into the molecular mechanisms of osteosarcoma progression.展开更多
BACKGROUND Giant cell-rich osteosarcoma(GCRO) is a rare histological variant of osteosarcoma. Spinal GCROs are extremely rare, with challenging diagnosis and management. Herein, we present a case of spinal GCRO at T2,...BACKGROUND Giant cell-rich osteosarcoma(GCRO) is a rare histological variant of osteosarcoma. Spinal GCROs are extremely rare, with challenging diagnosis and management. Herein, we present a case of spinal GCRO at T2, which was not diagnosed in initial biopsy but after T2 corpectomy. We detailed the clinical course, management strategy, and outcome after a 4-year follow-up.CASE SUMMARY A 17-year-old female patient presented with back pain followed by ascending paresthesia. Spinal computed tomography(CT) and magnetic resonance imaging(MRI) revealed a collapsed T2 vertebra with an enhancing osteolytic mass. CTguided biopsy showed inconclusive morphology. Pathology from T2 corpectomy revealed GCRO. The patient subsequently received neoadjuvant chemotherapy followed by salvage operation of T2 costotransversectomy with grossly-total resection adjuvant chemoradiation. Upon treatment completion, she had complete GCRO remission. The 4-year follow-up spinal MRI showed no tumor recurrence.CONCLUSION Spinal GCRO poses unique challenges in obtaining sufficient tissue diagnosis and complete surgical removal. However, long-term local control of spinal GCRO is possible following complete resection and adjuvant chemoradiation.展开更多
Objective: To observe whether there is evidence for vascular channel formation by osteosarcoma cellsin vitro and to illustrate mechanism of vasculogenic mimicry in osteosarcoma.Methods: Osteosarcoma cell lines (U-2OS)...Objective: To observe whether there is evidence for vascular channel formation by osteosarcoma cellsin vitro and to illustrate mechanism of vasculogenic mimicry in osteosarcoma.Methods: Osteosarcoma cell lines (U-2OS) were tested for their ability to form tubular networks in three-dimensional culture containing type I collagen. The structures of the tubular networks were observed under a phase contrast microscope and an electron microscope.Results: Observation under light microscopy and electron microscopy showed that high aggressive osteosarcoma cells line (U-2OS) formed networks containing channels when grown in three-dimensional culture containing type I collagen in the absence of endothelial cells or fibroblasts.Conclusion: These observations strongly suggest that aggressive osteosarcoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis and have the ability of vasculogenic mimicry. Key words osteosarcoma cells line - vasculogenesis mimicry - angiogenesis - 3-dimensional cultures This study was supported in part by the National Natural Sciences Foundation of China (No. 30271314).展开更多
Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with ost...Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with osteosarcoma. Methods: Two children (aged 5 and 10 years, 1 male and 1 female) with osteosarcoma underwent inactivated bone replantation with preserving epiphysis following chemotherapy (MMIA protocol, including high-dose methotrexate, adriamycin and ifosfamide). After two cycles of preop-erative chemotherapy, pain vanished, the local mass shrank and there was no pain on pressing the affected parts. Sera AKP and LDH were reduced to normal levels; marked shrinkage and sclerotic changes and good margin of lesions were seen on plain radiographs and MR images. Two courses of the same protocol as preoperative chemotherapy were administered postoperatively. Results: Postoperative histological examination of the specimens demonstrated absence of vital tumor cells. Incisions healed well and no complications occurred. The replanted inactivated bone healed with host at 6 months after operation. In the two patients, no evidence was seen of metastasis and recurrence and discrepancy of the affected limbs in postoperative 36 and 48 months. Functions of the affected limbs were satisfactory. Conclusion: Inactivated bone replantation with preserving epiphysis was a viable option for osteosarcoma in children. The long-term outcomes remain to be further proven.展开更多
基金the National Natural Science Foundation of China(62375127,82272664)Hunan Provincial Natural Science Foundation of China(2022JJ30843)+5 种基金the Science and Technology Development Fund Guided by Central Govern-ment(2021Szvup169)the Scientic Research Program of Hunan Provincial Health Commission(B202304077077)the Fundamental Research Funds for the Central Universities(NS2022035)Prospective Layout Special Fund of Nanjing University of Aero-nautics and Astronautics(ILA-22022)Graduate Research and Innovation Program of Nanjing University of Aeronautics and Astronautics(xcxjh20220328)Experimental Technology Research and Development Project of NUAA(No.SYJS202303Z)for the grant。
文摘Osteosarcoma is the most common primary bone tumor with high malignancy.It is particularly necessary to achieve rapid and accurate diagnosis in its intraoperative examination and early diagnosis.Accordingly,the multimodal microscopic imaging diagnosis system constructed by bright field,spontaneous fluorescence and polarized light microscopic imaging was used to study the pathological mechanism of osteosarcoma from the tissue microenvironment level and achieve rapid and accurate diagnosis.First,the multimodal microscopic images of normal and osteosarcoma tissue slices were collected to characterize the overall morphology of the tissue microenvironment of the samples,the arrangement structure of collagen fibers and the content and distribution of endogenous fluorescent substances.Second,based on the correlation and complementarity of the feature information contained in the three single-mode images,combined with convolutional neural network(CNN)and image fusion methods,a multimodal intelligent diagnosis model was constructed to effectively improve the information utilization and diagnosis accuracy.The accuracy and true positivity of the multimodal diagnostic model were significantly improved to 0.8495 and 0.9412,respectively,compared to those of the single-modal models.Besides,the difference of tissue microenvironments before and after cancerization can be used as a basis for cancer diagnosis,and the information extraction and intelligent diagnosis of osteosarcoma tissue can be achieved by using multimodal microscopic imaging technology combined with deep learning,which significantly promoted the application of tissue microenvironment in pathological examination.This diagnostic system relies on its advantages of simple operation,high efficiency and accuracy and high cost-effectiveness,and has enormous clinical application potential and research significance.
基金appreciate financial support from the National Key R&D Program of China(No.2022YFA1104600)2022 Lingang Laboratory“Seeking Outstanding Youth Program”Open Project(No.LGQS-202206-04)+3 种基金Shanghai Ninth People’s Hospital–Shanghai Jiao Tong University School of Medicine–Shanghai University of Science and Technology Cross-funded Collaborative Program(No.JYJC202233)the National Natural Science Foundation of China(No.82372377)Biomaterials and Regenerative Medicine Institute Cooperative Research Project by Shanghai Jiao Tong University School of Medicine(No.2022LHBO8),Shanghai Key Laboratory of Orthopaedic Implants,Department of Orthopaedics by Shanghai Ninth People’s Hospital–Shanghai Jiao Tong University School of Medicine(No.KFKT202206),the Key R&D Program of Jiangsu Province Social Development Project(No.BE2022708)the Project of Shanghai Science and Technology Commission(No.22015820100).
文摘In the current settings of osteosarcoma research and drug screening,in vitro three-dimensional(3D)models,which overcome the limitations of traditional models,are favored.In in vitro 3D models,tumor microenvironment simulation,particularly of the mechanical microenvironment,is crucial for estimating the biological effects of a tumor.However,current in vitro osteosarcoma model construction is often limited to a single mechanical signal,which fails to simulate the diversity of osteosarcoma mechanical stimuli.In this study,we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model(IGBSTOM).We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate,methacryloylated gelatin,thrombin,and transglutaminase,which is rich in polysaccharides and proteins and exhibits self-healing properties.Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness,proliferation,and migration,and successfully reproduced the nest-like structure of tumors,providing an in vitro research platform that is more similar to the natural tumor than the existing models.This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development,drug screening,and exploration of drug resistance and metastasis mechanisms.
基金supported by the National Key Research and Development Program of China(No.2022YFC3502100)the National Natural Science Foundation of China(No.82274197)+1 种基金the Cutting Edge Development Fund of Advanced Medical Research Institute Municipal Science and(No.GYY2023QY01)the Technology Project of Jinan City(No.202228099).
文摘Osteosarcoma(OS)is the most prevalent primary malignant bone tumor affecting children and adolescents.Despite ongoing research efforts,the 5-year survival rate has remained stagnant for many years,highlighting the critical need for novel drug development to enhance current treatment protocols.ZiyuglycosideⅡ(ZYGⅡ),a triterpenoid saponin extracted from S.officinalis,has recently demonstrated antitumor properties.This study evaluates the antitumor effect of ZYGⅡon osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma(ESRRG),which inhibits disease progression.The research employs in vitro experiments using multiple established osteosarcoma cell lines,as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma.Additionally,ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYGⅡexerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53.Results indicate that ZYGⅡadministration led to decreased OS cell viability and reduced tumor volumes.Furthermore,cell cycles were arrested at the G_(0)/G1 phase,while the proportion of apoptotic cells increased.Expression of p53,ESRRG,p21,Bax,Cleaved Caspase-9,and Cleaved Caspase-3 proteins increased,while expression of CDK4,Cyclin D1,and Bcl-2 proteins decreased.Multiple ZYGⅡand ESRRG docking patterns were simulated through molecular docking.Comparing the pharmacodynamic response of ZYGⅡto OS cell lines with reduced ESRRG and normal expression demonstrated that ZYGⅡinhibits osteosarcoma progression,induces cell cycle arrest,and promotes cell apoptosis through the coordination of p53 and ESRRG.In conclusion,ZYGⅡinhibits osteosarcoma progression,leads to cell cycle arrest,and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
基金supported by the National Natural Science Foundation of China(grant number 81773285)Beijing Chao-Yang Hospital Golden Seeds Foundation(grant number CYJZ202341).
文摘Osteosarcoma(OS)is a prevalent primary bone malignancy with limited treatment options.Therefore,it is imperative to investigate and understand the mechanisms underlying OS pathogenesis.Cancer-associated fibroblasts(CAFs)are markedly abundant in tumor stromal cells and are essentially involved in the modulation of tumor occurrence and development.In recent years,CAFs have become a hotspot as researchers aim to elucidate CAF mechanisms that regulate tumor progression.However,most studies on CAFs are limited to a few common cancers,and their association with OS remains elusive.This review describes the role and current knowledge of CAFs in OS,focusing on their potential cellular origin,classification,and diverse functionality.It was found that CAFs influenced OS tumor cell signaling,proliferation,invasion,metastasis,epithelial-mesenchymal transition,stemness maintenance,angiogenesis,and the ability to modify immune system components.Furthermore,findings on other common cancers indicated that effective therapeutic strategies included the manipulation of CAF activation,targeting CAF-derived components,and depletion of CAFs by biomarkers.This review provides new insights and a theoretical basis for OS research.
文摘Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were utilized.Microarray experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were performed.In MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity levels.HYSA reduced the Warburg effect and induced ferroptosis(FPT)in MG63 cells.Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells.The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells.HIF-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°C.HYSA significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand HYSA.Conclusively,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway.HYSA is a possible therapeutic option for OC or other cancers.
基金National Key R&D Program of China:Cooperating Studies on Measurement Technologies of Human Phenome and Crossscale Correlation of Phenotypic Data(No.2020YFE0201600)National Nature Science Foundation:Study on LncRNA-CCDC18-AS1 Mediated Osteosarcoma Occurrence by Activating YAP/TAZ and Tumor Microenvironment M2 TAM-dependent Lung Metastasis,and Efficacy/mechanism of Removing Blood Stasis/clearing heat/eliminating Toxic Material Principle(No.81973877)+2 种基金Mechanism Study on m6A Methyltransferase RBM15 Mediated YAP Epigenetic Modification to Promote Osteosarcoma Lung Metastasis through Lymphatic System and Management with Qichong Powder(No.82174408)Shanghai Collaborative Innovation Center of Industrial Transformation of Hospital TCM Preparation:Preclinical Study on the Treatment of Osteosarcoma with Qingre Jiedu GranulesResearch Projects within Budget of Shanghai University of Traditional Chinese Medicine:the Research on the Mechanism of the HIPK3 Activation of Wnt/β-catenin Induction the Osteosarcoma and the Intervention of Banmao Decoction(No.2021LK047)。
文摘OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
基金This work was supported by the National Natural Science Foundation(82172594 and 82373046)the Hunan Graduate Research Innovation Project(CX20230318),China.
文摘Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.
文摘In the article‘MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1’(Oncology Research,2024,Vol.32,No.3,pp.463−476.doi:10.32604/or.2023.044085),there was an error in the compilation of Fig.8D.We have revised Fig.8D to correct this error.A corrected version of Fig.8 is provided.This correction does not change any results or conclusions of the article.We apologize for any inconvenience caused.
基金The Fund of National Cancer Center Research and Development(26-A-4),The Grants-in-Aid for Scientific Research(Grant Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.
基金This project used the UPMC Hillman Cancer Center and Tissue and Research Pathology/Pitt Biospecimen Core shared resource,which is supported,in part,by award P30CA047904supported through grant funding by the Pittsburgh Cure Sarcoma Foundationinternal funding by the West Virginia University School of Medicine,Department of Orthopaedics。
文摘Patients diagnosed with advanced osteosarcoma,often in the form of lung metastases,have abysmal five-year overall survival rates.The complexity of the osteosarcoma immune tumor microenvironment has been implicated in clinical trial failures of various immunotherapies.The purpose of this exploratory study was to spatially characterize the immune tumor microenvironment of metastatic osteosarcoma lung specimens.Knowledge of the coordinating cellular networks within these tissues could then lead to improved outcomes when utilizing immunotherapy for treatment of this disease.Importantly,various cell types,interactions,and cellular neighborhoods were associated with five-year survival status.Of note,increases in cellular interactions between T lymphocytes,positive for programmed cell death protein 1,and myeloid-derived suppressor cells were observed in the 5-year deceased cohort.Additionally,cellular neighborhood analysis identified an Immune-Cold Parenchyma cellular neighborhood,also associated with worse 5-year survival.Finally,the Osteosarcoma Spatial Score,which approximates effector immune activity in the immune tumor microenvironment through the spatial proximity of immune and tumor cells,was increased within 5-year survivors,suggesting improved effector signaling in this patient cohort.Ultimately,these data represent a robust spatial multiplexed immunofluorescence analysis of the metastatic osteosarcoma immune tumor microenvironment.Various communication networks,and their association with survival,were described.In the future,identification of these networks may suggest the use of specific,combinatory immunotherapeutic strategies for improved anti-tumor immune responses and outcomes in osteosarcoma.
基金the Sichuan Provincial Central Leading Local Science and Technology Development Special Project(Grant No.2023ZYD0072)the National Natural Science Foundation of China(Grant No.82301785)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2019A1515111078).
文摘Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.
文摘Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
基金supported by China Medicine Education Association(CMEA)(No.2020KTS012)the National Natural Science Foundation of China(NSFC)(No.82002962 and No.81900189).
文摘Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patients between January 2007 and July 2020,50 patients aged 13 to 39 years with Enneking stage II disease were included in the study.Serum lipid levels,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lipoprotein-α[Lp(a)],and apolipoprotein A1,B,and E(ApoA1,ApoB,and ApoE),and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.Results The mean levels of TC,TG,and ApoB were significantly increased following neoadjuvant chemotherapy(16%,38%,and 20%,respectively,vs.pretreatment values;P<0.01).The mean levels of LDL-C and ApoE were also 19%and 16%higher,respectively(P<0.05).No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy.An increase in Lp(a)was strongly correlated with the Ki-67 index(R=0.31,P=0.023).Moreover,a trend toward longer disease-free survival(DFS)was observed in patients with decreased TG and increased LDL-C following chemotherapy,although this difference was not statistically significant(P=0.23 and P=0.24,respectively).Conclusion Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma.There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy.The scale of increase in serum Lp(a)might have a potential prognostic role in osteosarcoma.Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.
文摘Introduction: Osteosarcoma is the most common primary malignant bone tumor in children. It is highly aggressive and has a poor prognosis. A late presentation modifies and makes difficult the management affecting the survival of children. We report the case of a large conventional osteosarcoma in a 13-year-old girl. Case Presentation: Adolescent girl admitted for painful swelling of the left shoulder with absolute functional impotence of the thoracic limb and severe anemia. The painful swelling was thought to have been caused by a minor trauma that had occurred six months previously. The patient’s general condition was poor, and she presented with a large, shiny, painful mass over the shoulder and upper 2/3 of the left arm, measuring 28 cm long by 28 cm wide and 57 cm in circumference, and a large fistulous axillary adenopathy. CT scan showed a tumour lesion of the left humerus with liver and lung metastases, raising suspicion of osteogenic osteosarcoma. The tumor was classified according to TNM staging: T2N1M1(a + b). Management was modified when uncontrolled bleeding developed. It consisted of an extended amputation of the left thoracic limb. Pathological analysis showed a high-grade conventional osteosarcoma. Quality improvement was obtained for thirty days, followed by the onset of dyspnea. The evolution was towards death at forty days post-operatively. Conclusion: Osteosarcoma is a highly aggressive cancer. Delayed treatment leads to a fatal outcome. Early diagnosis is one of the challenges to be met in order to improve survival.
基金supported by the Guangxi Natural Science Foundation(No.2023JJA140880).
文摘Osteosarcoma is the most prevalent primarymalignant bone tumor,primarily affecting adolescents aged 15–25 years.It is characterized by a high recurrence rate,poor prognosis,and lack of important biomarkers.Significant mitochondrial dysfunction in osteosarcoma cells has been widely reported by recent studies.Dysfunctional mitochondria occupy an important position in cellularmetabolic reprogramming,immune microenvironment regulation,and programmed cell death.Therefore,targeting mitochondrial dysfunction may represent a new mechanism to overcome therapeutic barriers in the treatment of osteosarcoma and provides crucial target molecules for further development of targeted therapies and immunotherapies.The present article summarizes the recent reports of mitochondrial dysfunction in osteosarcoma and links it to various programmed cell death mechanisms,aiming to provide the basis for further clinical practice.
文摘Background:Osteosarcoma is the most common primary bone malignancy,with a strong tendency towards local invasion and metastasis.The SRY-Box Transcription Factor 1(SOX1)gene,a member of the HMG-box family of DNA-binding transcription factors,plays a crucial role in embryogenesis and tumorigenesis.However,its role in osteosarcoma,particularly in relation to metastatic potential,is not well understood.Methods:The GSE14359 dataset containing five samples of conventional osteosarcoma and four samples of lung metastatic osteosarcoma was obtained from the Gene Expression Omnibus(GEO)database and analyzed for differential gene expression using the R language.Gene expression was detected using qPCR and Western blotting.Transcriptional activity was assessed by Luciferase reporter gene assays,and cell metastatic ability was assessed by migration and invasion assays.Results:The study demonstrated that SOX1 binds to a specific response element within the Transmembrane 4 Superfamily Member 12(TSPAN12)promoter,upregulating TSPAN12 and its associated inflammatory pathways.Silencing TSPAN12 markedly reduces SOX1-mediated osteosarcoma cell invasion and inflammatory response,while TSPAN12 overexpression reverses these effects in SOX1-suppressed cells.Conclusion:In this study,our findings elucidate SOX1’s role in enhancing osteosarcoma metastasis via TSPAN12 upregulation,offering new insights into the molecular mechanisms of osteosarcoma progression.
文摘BACKGROUND Giant cell-rich osteosarcoma(GCRO) is a rare histological variant of osteosarcoma. Spinal GCROs are extremely rare, with challenging diagnosis and management. Herein, we present a case of spinal GCRO at T2, which was not diagnosed in initial biopsy but after T2 corpectomy. We detailed the clinical course, management strategy, and outcome after a 4-year follow-up.CASE SUMMARY A 17-year-old female patient presented with back pain followed by ascending paresthesia. Spinal computed tomography(CT) and magnetic resonance imaging(MRI) revealed a collapsed T2 vertebra with an enhancing osteolytic mass. CTguided biopsy showed inconclusive morphology. Pathology from T2 corpectomy revealed GCRO. The patient subsequently received neoadjuvant chemotherapy followed by salvage operation of T2 costotransversectomy with grossly-total resection adjuvant chemoradiation. Upon treatment completion, she had complete GCRO remission. The 4-year follow-up spinal MRI showed no tumor recurrence.CONCLUSION Spinal GCRO poses unique challenges in obtaining sufficient tissue diagnosis and complete surgical removal. However, long-term local control of spinal GCRO is possible following complete resection and adjuvant chemoradiation.
基金This study was supported in part by the National Natural Sciences Foundation of China(No.30271314).
文摘Objective: To observe whether there is evidence for vascular channel formation by osteosarcoma cellsin vitro and to illustrate mechanism of vasculogenic mimicry in osteosarcoma.Methods: Osteosarcoma cell lines (U-2OS) were tested for their ability to form tubular networks in three-dimensional culture containing type I collagen. The structures of the tubular networks were observed under a phase contrast microscope and an electron microscope.Results: Observation under light microscopy and electron microscopy showed that high aggressive osteosarcoma cells line (U-2OS) formed networks containing channels when grown in three-dimensional culture containing type I collagen in the absence of endothelial cells or fibroblasts.Conclusion: These observations strongly suggest that aggressive osteosarcoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis and have the ability of vasculogenic mimicry. Key words osteosarcoma cells line - vasculogenesis mimicry - angiogenesis - 3-dimensional cultures This study was supported in part by the National Natural Sciences Foundation of China (No. 30271314).
文摘Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with osteosarcoma. Methods: Two children (aged 5 and 10 years, 1 male and 1 female) with osteosarcoma underwent inactivated bone replantation with preserving epiphysis following chemotherapy (MMIA protocol, including high-dose methotrexate, adriamycin and ifosfamide). After two cycles of preop-erative chemotherapy, pain vanished, the local mass shrank and there was no pain on pressing the affected parts. Sera AKP and LDH were reduced to normal levels; marked shrinkage and sclerotic changes and good margin of lesions were seen on plain radiographs and MR images. Two courses of the same protocol as preoperative chemotherapy were administered postoperatively. Results: Postoperative histological examination of the specimens demonstrated absence of vital tumor cells. Incisions healed well and no complications occurred. The replanted inactivated bone healed with host at 6 months after operation. In the two patients, no evidence was seen of metastasis and recurrence and discrepancy of the affected limbs in postoperative 36 and 48 months. Functions of the affected limbs were satisfactory. Conclusion: Inactivated bone replantation with preserving epiphysis was a viable option for osteosarcoma in children. The long-term outcomes remain to be further proven.
