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
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
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
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
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
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 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
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
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
[目的]本文旨在解决在自然环境下不同成熟度苹果目标检测精度较低的问题。[方法]提出了一种改进的YOLOv5s模型SODSTR-YOLOv5s(YOLOv5s with small detection layer and omni-dimensional dynamic convolution and swin transformer bloc...[目的]本文旨在解决在自然环境下不同成熟度苹果目标检测精度较低的问题。[方法]提出了一种改进的YOLOv5s模型SODSTR-YOLOv5s(YOLOv5s with small detection layer and omni-dimensional dynamic convolution and swin transformer block),用于不同成熟度苹果检测。首先改进YOLOv5s的多尺度目标检测层,在Prediction中构建检测160×160特征图的检测头,提高小尺寸的不同成熟度苹果的检测精度;其次在Backbone结构中融合Swin Transformer Block,加强同级成熟度的苹果纹理特征融合,弱化纹理特征分布差异带来的消极影响,提高模型泛化能力;最后将Neck结构的Conv模块替换为动态卷积模块ODConv,细化局部特征映射,实现局部苹果细粒度特征的充分提取。基于不同成熟度苹果数据集进行试验,验证改进模型的性能。[结果]改进模型SODSTR-YOLOv5s检测的精确率、召回率、平均精度均值分别为89.1%、95.5%、93.6%,高、中、低成熟度苹果平均精度均值分别为94.1%、93.1%、93.7%,平均检测时间为16 ms,参数量为7.34 M。相比于YOLOv5s模型,改进模型SODSTR-YOLOv5s精确率、召回率、平均精度均值分别提高了3.8%、5.0%、2.9%,参数量和平均检测时间分别增加了0.32 M和5 ms。[结论]改进模型SODSTR-YOLOv5s提升了在自然环境下对不同成熟度苹果的检测能力,能较好地满足实际采摘苹果的检测要求。展开更多
针对煤矿高噪声、低照度、运动模糊与大批量煤矸混杂等复杂工况环境因素导致煤矸识别存在误检、漏检以及检测精度低的问题,提出一种基于CFS-YOLO算法的煤矸智能识别模型。采用ConvNeXt V2(Convolutional Neural Network with NeXt Units...针对煤矿高噪声、低照度、运动模糊与大批量煤矸混杂等复杂工况环境因素导致煤矸识别存在误检、漏检以及检测精度低的问题,提出一种基于CFS-YOLO算法的煤矸智能识别模型。采用ConvNeXt V2(Convolutional Neural Network with NeXt Units Version 2)特征提取模块替换主干网络末端的2个C3(Cross Stage Partial Bottle Neck Mudule)模块,通过将掩码自动编码器(Masked Autoencoders,MAE)和全局响应归一化(Global Response Normalization,GRN)层添加到ConvNeXt架构中,有效缓解特征崩溃问题以及保持特征在网络传递过程中的多样性;采用Focal-EIOU(Focal and Efficient Intersection Over Union)损失函数替换原CIOU(Computer Intersection Over Union)损失函数,通过其Focal-Loss机制和调整样本权重的方式优化边界框回归任务中的样本不平衡问题,提高模型的收敛速度和定位精度;添加无参注意力机制(Simple Attention Mechanism,SimAM)于主干网络每个C3模块的后端,凭借其注意力权重自适应调整策略,提升模型对尺度变化较大或低分辨率煤矸目标关键特征的提取能力。通过消融试验和对比试验验证所提CFS-YOLO模型的有效性与优越性。试验结果表明:CFS-YOLO模型对于煤矸在煤矿高噪声、低照度、运动模糊与大批量煤矸混杂等复杂环境下的检测效果均得到有效提高,模型的平均精度均值达到90.2%,相较于原YOLOv5s模型的平均精度均值提高了3.7%,平均检测速度达到90.09 FPS,可充分满足煤矸实时检测的需求。同时与YOLOv5s、YOLOv7-tiny与YOLOv8n等6种YOLO系列算法相比,CFS-YOLO模型对煤矿复杂环境的适应性最强且综合检测性能最佳,可为煤矸的智能高效分选提供技术支持。展开更多
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.
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.
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.
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.
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[目的]本文旨在解决在自然环境下不同成熟度苹果目标检测精度较低的问题。[方法]提出了一种改进的YOLOv5s模型SODSTR-YOLOv5s(YOLOv5s with small detection layer and omni-dimensional dynamic convolution and swin transformer block),用于不同成熟度苹果检测。首先改进YOLOv5s的多尺度目标检测层,在Prediction中构建检测160×160特征图的检测头,提高小尺寸的不同成熟度苹果的检测精度;其次在Backbone结构中融合Swin Transformer Block,加强同级成熟度的苹果纹理特征融合,弱化纹理特征分布差异带来的消极影响,提高模型泛化能力;最后将Neck结构的Conv模块替换为动态卷积模块ODConv,细化局部特征映射,实现局部苹果细粒度特征的充分提取。基于不同成熟度苹果数据集进行试验,验证改进模型的性能。[结果]改进模型SODSTR-YOLOv5s检测的精确率、召回率、平均精度均值分别为89.1%、95.5%、93.6%,高、中、低成熟度苹果平均精度均值分别为94.1%、93.1%、93.7%,平均检测时间为16 ms,参数量为7.34 M。相比于YOLOv5s模型,改进模型SODSTR-YOLOv5s精确率、召回率、平均精度均值分别提高了3.8%、5.0%、2.9%,参数量和平均检测时间分别增加了0.32 M和5 ms。[结论]改进模型SODSTR-YOLOv5s提升了在自然环境下对不同成熟度苹果的检测能力,能较好地满足实际采摘苹果的检测要求。
文摘针对煤矿高噪声、低照度、运动模糊与大批量煤矸混杂等复杂工况环境因素导致煤矸识别存在误检、漏检以及检测精度低的问题,提出一种基于CFS-YOLO算法的煤矸智能识别模型。采用ConvNeXt V2(Convolutional Neural Network with NeXt Units Version 2)特征提取模块替换主干网络末端的2个C3(Cross Stage Partial Bottle Neck Mudule)模块,通过将掩码自动编码器(Masked Autoencoders,MAE)和全局响应归一化(Global Response Normalization,GRN)层添加到ConvNeXt架构中,有效缓解特征崩溃问题以及保持特征在网络传递过程中的多样性;采用Focal-EIOU(Focal and Efficient Intersection Over Union)损失函数替换原CIOU(Computer Intersection Over Union)损失函数,通过其Focal-Loss机制和调整样本权重的方式优化边界框回归任务中的样本不平衡问题,提高模型的收敛速度和定位精度;添加无参注意力机制(Simple Attention Mechanism,SimAM)于主干网络每个C3模块的后端,凭借其注意力权重自适应调整策略,提升模型对尺度变化较大或低分辨率煤矸目标关键特征的提取能力。通过消融试验和对比试验验证所提CFS-YOLO模型的有效性与优越性。试验结果表明:CFS-YOLO模型对于煤矸在煤矿高噪声、低照度、运动模糊与大批量煤矸混杂等复杂环境下的检测效果均得到有效提高,模型的平均精度均值达到90.2%,相较于原YOLOv5s模型的平均精度均值提高了3.7%,平均检测速度达到90.09 FPS,可充分满足煤矸实时检测的需求。同时与YOLOv5s、YOLOv7-tiny与YOLOv8n等6种YOLO系列算法相比,CFS-YOLO模型对煤矿复杂环境的适应性最强且综合检测性能最佳,可为煤矸的智能高效分选提供技术支持。