Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism ...Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism in osteosarcoma.Methods:We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments(TARGET)database and single-cell RNA sequencing.Least Absolute Shrinkage and Selection Operator(LASSO)regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma.Tumor-associated macrophages(TAMs)and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6(LPAR6)inhibitors.Results:Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3)and aldehyde dehydrogenase 7 family member A1(ALDH7A1)were identified as key prognostic genes in osteosarcoma,with high AGPAT3 expression correlating with improved survival.Single-cell analysis revealed that AGPAT3 expression is associated with tumor immune microenvironment,particularly with TAMs.Knockdown of AGPAT3 in osteosarcoma cells resulted in elevated lysophosphatidic acid(LPA)levels,which regulated the immune environment,inhibiting cytotoxic T cell function through TAMs’LPAR6 signaling.LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion,including interleukin-6(IL-6)and interleukin-10(IL-10).Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6.Conclusion:AGPAT3 is an important gene related to the prognosis of osteosarcoma.Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment,particularly in immunotherapy contexts.展开更多
The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3...The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3727/096504017X14850134190255 URL:https://www.techscience.com/or/v25n8/56908 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.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
The published article titled“MicroRNA-33b Inhibits the Proliferation andMigration of Osteosarcoma Cells via TargetingHypoxia-Inducible Factor-1α”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.397–405.
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
The published article titled“MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1”has been retracted from Oncology Research,Vol.25,No.9,2017,pp.1421–1430.
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
In the article“MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma”(Oncology Research.2024 Oct 16;32(11):1777-1789.doi:10.32604/or.2024.047704),an inadvertent error occurred during...In the article“MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma”(Oncology Research.2024 Oct 16;32(11):1777-1789.doi:10.32604/or.2024.047704),an inadvertent error occurred during the compilation of Figs.3b and 6c.This needed corrections to ensure the accuracy and integrity of the data presented.展开更多
Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewa...Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.展开更多
Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threa...Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.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
Objective： To compare the expression level of metastasis associated-1 （MTA1） in the higher and lower metastasis sublines of human osteosarcoma cells （MG63）, and to investigate the relationship between the express...Objective： To compare the expression level of metastasis associated-1 （MTA1） in the higher and lower metastasis sublines of human osteosarcoma cells （MG63）, and to investigate the relationship between the expression level of MTA1-EGFP and in vitro invasion and metastasis of human osteosarcoma cells. Methods： The expression level of MTA1 in two sublines of MG63 cells was detected by semi-quantitative RT-PCR, and cell invasion assay and cell proliferation assay were used to evaluate the invasive capacity in vitro in two sublines. The lower metastasis line of MG-63 cells were transfected with MTA1-EGFP full-length cDNA expression plasmid by lipofectamine. The changes of the MTA1-EGFP expression and in vitro invasion potential were measured after transfection. Results： M8 subline expressed significantly higher level of MTA1 than that of M6 subline by RT-PCR. The invasive potentials of low metastasis MG63 cell line were increased after MTA1 gene transfection. Conclusion： There may be a relationship between MTA1 and invasive potentials of human osteosarcoma cells, and MTA1 may play a role in the molecular mechanism of tumor metastases and be a potential target for gene therapy of osteosarcoma. Further studies of MTA1 in human ostersarcoma cell metastasis are needed.展开更多
Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, ...Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, osteochondroma and normal osseous tissue, and the expression of P-glycoprotein in osteosarcoma was detected. Results: Survivin positive expression rate was 65.71% in osteosarcoma, but no expression of Survivin was detectable in osteochondroma and normal osseous tissue. The positive expression rate of Survivin was significantly associated with Enneking clinical stages and histological typing (WHO), but no relationship was found among Survivin expression and age, sex and tumor location. The positive expression rate of P-glycoprotein was 45.71%. There was a significant correlation between Survivin and p-glycoprotein. Conclusion: Survivin overexpression was significantly associated with clinical multidrug resistance in osteosarcoma. It could be a potential target for treatment of osteosarcoma.展开更多
Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of ...Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ossification.Results: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 kD.Conclusion: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).展开更多
Objective: To investigate the p21WAF1 /CIP1gene DNA sequence change and their relationship with the phenotype of human osteosarcoma. Methods: p21WAF1 /CIP1gene DNA of 36 osteosarcoma spec- ...Objective: To investigate the p21WAF1 /CIP1gene DNA sequence change and their relationship with the phenotype of human osteosarcoma. Methods: p21WAF1 /CIP1gene DNA of 36 osteosarcoma spec- imens was examined by using polymerase chain reaction-single strand conformation polymorphism (PCR- SSCP) method. The PCR products were sequenced directly. Results: In p21WAF1 /CIP1 gene exon3 of 36 cases of human osteosarcoma, the change of C→T in the p21WAF1 /CIP1gene CDNA sequence of position 609th occurred in 17 cases with the incidence being 44.4%. In 10 normal blood samples, DNA sequence analysis showed the change of C→T in the p21WAF1 /CIP1gene CDNA sequence of position 609th occurred in 8 cases with the incidence being 80%. Conclusion: The novel location of p21WAF1 /CIP1gene polymorphism of osteosarcoma, but not mutation was de?ned, and this location might provide the meaningful reference for the further research of p21WAF1/CIP1 gene.p2lWAF1/CIP1基因DNA序列分析及其与骨肉瘤表型的关系展开更多
Biocompatible and biodegradable magnesium （Mg） based metals have attracted great interest for use in orthopedic implants and devices. Based on our previous study that Mg with and without micro-arc oxidation （MAO） ...Biocompatible and biodegradable magnesium （Mg） based metals have attracted great interest for use in orthopedic implants and devices. Based on our previous study that Mg with and without micro-arc oxidation （MAO） coating showed obvious cytotoxic effect on tumor cells due to the increase of pH value during the degradation of Mg, this study further evaluated the cytotoxic effect of Mg and MAO coated Mg on osteosarcoma （MG-63） cells by analyzing the cell adhesion, morphology and number through observation of scanning electron microscope, as well as live/dead staining, lactate dehydrogenase （LDH） activity and 4, 6- diamidino-2-phenylindole （DAPI） assay. The results indicated that, compared to titanium, Mg could strongly inhibit the cell adherence, morphology and number of MG-63 on the surface of the naked Mg, whereas the MAO coated Mg showed relative weak cytotoxic effect on MG-63 cells, expecting that magnesium based metals with suitable coating can be designed to be applied as tumor prosthesis in the clinical practice.展开更多
基金supported by the National Natural Science Foundation of China(grant number 82460425)Jiangxi Provincial Health Technology Project(grant number 202510141).
文摘Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism in osteosarcoma.Methods:We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments(TARGET)database and single-cell RNA sequencing.Least Absolute Shrinkage and Selection Operator(LASSO)regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma.Tumor-associated macrophages(TAMs)and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6(LPAR6)inhibitors.Results:Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3)and aldehyde dehydrogenase 7 family member A1(ALDH7A1)were identified as key prognostic genes in osteosarcoma,with high AGPAT3 expression correlating with improved survival.Single-cell analysis revealed that AGPAT3 expression is associated with tumor immune microenvironment,particularly with TAMs.Knockdown of AGPAT3 in osteosarcoma cells resulted in elevated lysophosphatidic acid(LPA)levels,which regulated the immune environment,inhibiting cytotoxic T cell function through TAMs’LPAR6 signaling.LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion,including interleukin-6(IL-6)and interleukin-10(IL-10).Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6.Conclusion:AGPAT3 is an important gene related to the prognosis of osteosarcoma.Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment,particularly in immunotherapy contexts.
文摘The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3727/096504017X14850134190255 URL:https://www.techscience.com/or/v25n8/56908 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
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The published article titled“MicroRNA-33b Inhibits the Proliferation andMigration of Osteosarcoma Cells via TargetingHypoxia-Inducible Factor-1α”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.397–405.
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.
文摘The published article titled“MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1”has been retracted from Oncology Research,Vol.25,No.9,2017,pp.1421–1430.
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.
文摘In the article“MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma”(Oncology Research.2024 Oct 16;32(11):1777-1789.doi:10.32604/or.2024.047704),an inadvertent error occurred during the compilation of Figs.3b and 6c.This needed corrections to ensure the accuracy and integrity of the data presented.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.
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.
基金This project was supported by 973 National Great Foundation Research Program of China (No. 2002CB513107).
文摘Objective： To compare the expression level of metastasis associated-1 （MTA1） in the higher and lower metastasis sublines of human osteosarcoma cells （MG63）, and to investigate the relationship between the expression level of MTA1-EGFP and in vitro invasion and metastasis of human osteosarcoma cells. Methods： The expression level of MTA1 in two sublines of MG63 cells was detected by semi-quantitative RT-PCR, and cell invasion assay and cell proliferation assay were used to evaluate the invasive capacity in vitro in two sublines. The lower metastasis line of MG-63 cells were transfected with MTA1-EGFP full-length cDNA expression plasmid by lipofectamine. The changes of the MTA1-EGFP expression and in vitro invasion potential were measured after transfection. Results： M8 subline expressed significantly higher level of MTA1 than that of M6 subline by RT-PCR. The invasive potentials of low metastasis MG63 cell line were increased after MTA1 gene transfection. Conclusion： There may be a relationship between MTA1 and invasive potentials of human osteosarcoma cells, and MTA1 may play a role in the molecular mechanism of tumor metastases and be a potential target for gene therapy of osteosarcoma. Further studies of MTA1 in human ostersarcoma cell metastasis are needed.
基金The project was supported by the reasearch of Education Institution in Jiangxi (No. E040506).
文摘Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, osteochondroma and normal osseous tissue, and the expression of P-glycoprotein in osteosarcoma was detected. Results: Survivin positive expression rate was 65.71% in osteosarcoma, but no expression of Survivin was detectable in osteochondroma and normal osseous tissue. The positive expression rate of Survivin was significantly associated with Enneking clinical stages and histological typing (WHO), but no relationship was found among Survivin expression and age, sex and tumor location. The positive expression rate of P-glycoprotein was 45.71%. There was a significant correlation between Survivin and p-glycoprotein. Conclusion: Survivin overexpression was significantly associated with clinical multidrug resistance in osteosarcoma. It could be a potential target for treatment of osteosarcoma.
基金This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No.002p1503).
文摘Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ossification.Results: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 kD.Conclusion: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).
文摘Objective: To investigate the p21WAF1 /CIP1gene DNA sequence change and their relationship with the phenotype of human osteosarcoma. Methods: p21WAF1 /CIP1gene DNA of 36 osteosarcoma spec- imens was examined by using polymerase chain reaction-single strand conformation polymorphism (PCR- SSCP) method. The PCR products were sequenced directly. Results: In p21WAF1 /CIP1 gene exon3 of 36 cases of human osteosarcoma, the change of C→T in the p21WAF1 /CIP1gene CDNA sequence of position 609th occurred in 17 cases with the incidence being 44.4%. In 10 normal blood samples, DNA sequence analysis showed the change of C→T in the p21WAF1 /CIP1gene CDNA sequence of position 609th occurred in 8 cases with the incidence being 80%. Conclusion: The novel location of p21WAF1 /CIP1gene polymorphism of osteosarcoma, but not mutation was de?ned, and this location might provide the meaningful reference for the further research of p21WAF1/CIP1 gene.p2lWAF1/CIP1基因DNA序列分析及其与骨肉瘤表型的关系
基金financially supported by the National Basic Research Program of China(Grant No.2012CB619100)the Military Medical Research fund of "12th Five-Year Plan"(Grant No.cws11c268)
文摘Biocompatible and biodegradable magnesium （Mg） based metals have attracted great interest for use in orthopedic implants and devices. Based on our previous study that Mg with and without micro-arc oxidation （MAO） coating showed obvious cytotoxic effect on tumor cells due to the increase of pH value during the degradation of Mg, this study further evaluated the cytotoxic effect of Mg and MAO coated Mg on osteosarcoma （MG-63） cells by analyzing the cell adhesion, morphology and number through observation of scanning electron microscope, as well as live/dead staining, lactate dehydrogenase （LDH） activity and 4, 6- diamidino-2-phenylindole （DAPI） assay. The results indicated that, compared to titanium, Mg could strongly inhibit the cell adherence, morphology and number of MG-63 on the surface of the naked Mg, whereas the MAO coated Mg showed relative weak cytotoxic effect on MG-63 cells, expecting that magnesium based metals with suitable coating can be designed to be applied as tumor prosthesis in the clinical practice.
