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
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,with poor survival after metastasis,is considered the most common primary bone cancer in adolescents.Notwithstanding the efforts of researchers,its five-year survival rate has only shown limited improveme...Osteosarcoma,with poor survival after metastasis,is considered the most common primary bone cancer in adolescents.Notwithstanding the efforts of researchers,its five-year survival rate has only shown limited improvement,suggesting that existing therapeutic strategies are insufficient to meet clinical needs.Notably,immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis.Therefore,managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease.Additionally,given the advances in nanomedicine,there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics.Here,we review the classification,characteristics,and functions of the key components of the immune microenvironment in osteosarcoma.This review also emphasizes the application,progress,and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment.Furthermore,we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.展开更多
The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-ce...The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.展开更多
Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the...Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.展开更多
Osteosarcoma is one of the rare bone cancers that affect the individualsaged between 10 and 30 and it incurs high death rate. Early diagnosisof osteosarcoma is essential to improve the survivability rate and treatment...Osteosarcoma is one of the rare bone cancers that affect the individualsaged between 10 and 30 and it incurs high death rate. Early diagnosisof osteosarcoma is essential to improve the survivability rate and treatmentprotocols. Traditional physical examination procedure is not only a timeconsumingprocess, but it also primarily relies upon the expert’s knowledge.In this background, the recently developed Deep Learning (DL) models canbe applied to perform decision making. At the same time, hyperparameteroptimization of DL models also plays an important role in influencing overallclassification performance. The current study introduces a novel SymbioticOrganisms Search with Deep Learning-driven Osteosarcoma Detection andClassification (SOSDL-ODC) model. The presented SOSDL-ODC techniqueprimarily focuses on recognition and classification of osteosarcoma usinghistopathological images. In order to achieve this, the presented SOSDL-ODCtechnique initially applies image pre-processing approach to enhance the qualityof image. Also, MobileNetv2 model is applied to generate a suitable groupof feature vectors whereas hyperparameter tuning of MobileNetv2 modelis performed using SOS algorithm. At last, Gated Recurrent Unit (GRU)technique is applied as a classification model to determine proper class labels.In order to validate the enhanced osteosarcoma classification performance ofthe proposed SOSDL-ODC technique, a comprehensive comparative analysiswas conducted. The obtained outcomes confirmed the betterment of SOSDLODCapproach than the existing approaches as the former achieved a maximumaccuracy of 97.73%.展开更多
BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we repo...BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.展开更多
Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functi...Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular homeostasis.Contrastingly,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor cells.All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession.MET,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90.In this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug.The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase.Additionally,treatment with 17-DMAG inhibited cell proliferation and induced apoptosis.Inhibition of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with 17-DMAG.Based on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma cells.This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.展开更多
Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activiti...Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activities of cells.The aim of this study was to investigate the prognostic significance of Cuproptosis-associated lncRNAs in osteosarcoma.Methods:The Gene expression profiling of osteosarcoma samples versus normal samples and corresponding clinical data were downloaded from the public databases UCSC Xena and GTEx,and the cuproptosis gene was obtained from the published literature,the prognostic model of osteosarcoma cuproptosis-related lncRNA was constructed by using coexpression network,minimum absolute contraction and selection algorithm(LASSO)and Cox regression model.Receiver operating characteristic(ROC)curves and nomograms were used to assess the predictive power of the model.Single-sample gene set enrichment analysis(ssGSEA)was used to explore the relationship between osteosarcoma immune cells and function in different risk groups.Results:181 cuproptosis-related lncRNAs were obtained by co-expression analysis of 19 cuproptosis genes collected.Ten lncRNAs were screened out by differential analysis and single-factor Cox analysis.Three cuproptosis-related lncrnas(AC124798.1,AC090152.1,AC090559.1)were screened by Lasso and multivariate Cox regression to construct the prognostic model.Patients were divided into high and low risk groups based on the median risk score.The results of overall survival,risk score distribution and survival status in the lowrisk group were better than those in the high-risk group,and were verified in the internal data.Univariate and multivariate Cox regression analyses showed that risk score was an independent prognostic factor.Nomograms and ROC curves showed that the prognostic model had good predictive ability.The results of ssGSEA suggest that immune cells and function may be inhibited in the high-risk group.Conclusion:The 3 cuproptosis-related lncRNAs may be helpful to guide the prognosis of osteosarcoma patients and provide some theoretical basis for clinical decision.展开更多
Purpose: Development of sarcoma is a known late rare negative side effect of radiotherapy. We add two cases to emphasize the need for open-end follow-up and critical evaluation to avoid misinterpretation. Patients, Me...Purpose: Development of sarcoma is a known late rare negative side effect of radiotherapy. We add two cases to emphasize the need for open-end follow-up and critical evaluation to avoid misinterpretation. Patients, Methods, and Results: Two patients developed osteosarcoma as a second malignancy in the humerus after adjuvant radiotherapy of a primary tumor not directly involving the later affected bone. The first patient had a Ewing sarcoma of the scapula at age 13 years. Though after neoadjuvant chemotherapy the resected specimen showed only fibrotic necrotic areas within clear resection margins, the study group indicated adjuvant radiotherapy in a field including the shoulder joint. At age 24 years she developed an osteosarcoma of the humeral head, which was resected and reconstructed with a proximal humerus endoprosthesis. She is alive without disease at age 32 years. The second patient presented with an osteosarcoma of the proximal humerus 29 years after irradiation for breast cancer including the shoulder joint. The sarcoma was misinterpreted as radiation-induced necrosis and the patient was treated with a reverse shoulder endoprosthesis. Pathologic examination of the resected humeral head then showed a typical osteosarcoma. Two years later the humeral reverse shoulder implant was resected and a proximal humerus tumor prosthesis implanted leaving the original glenosphere. Conclusions: In both cases radiation-induced osteosarcoma developed in bone not affected by the primary cancer. Protecting uninvolved structures must be warranted in the planning of radiotherapy. The long latency between the primary and second cancer mandates long-term—best indefinite—follow-up, as with appropriate treatment of a radiation-induced osteosarcoma good healing rates comparable to those of primary osteosarcoma can still be achieved.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
Metastatic peritoneal sarcomatosis most commonly occurs from primary soft tissue sarcomas arising either within the abdomen or extremities. Metastatic peritoneal sarcomatosis from an osteosarcoma is extremely rare;onl...Metastatic peritoneal sarcomatosis most commonly occurs from primary soft tissue sarcomas arising either within the abdomen or extremities. Metastatic peritoneal sarcomatosis from an osteosarcoma is extremely rare;only six cases have previously been reported. We report the first case of metastatic peritoneal sarcomatosis originating from radiation-induced osteoblastic osteosarcoma in a 22-year-old woman who had previously been treated for pelvic Ewing’s sarcoma. Abdominal computed tomography, bone scintigraphy and FDG PET/CT demonstrated extensive finely nodular disseminated peritoneal lesions. Histopathologic examination of these peritoneal lesions revealed osteosarcomatosis. In summary, we describe an unusual case of metastatic peritoneal sar comatosis from secondary osteosarcoma arising in a previously irradiated pelvicEwing’s sarcoma.展开更多
Objective: To determine the expression of non-muscle myosin heavy chain 9(MYH9) in osteosarcoma and its effect on the migration and invasion abilities of tumor cell. Methods: A total of 65 cases of osteosarcoma and 20...Objective: To determine the expression of non-muscle myosin heavy chain 9(MYH9) in osteosarcoma and its effect on the migration and invasion abilities of tumor cell. Methods: A total of 65 cases of osteosarcoma and 20 cases with benign osteochondroma who underwent resection operation in the Orthopaedics Department of our hospital from January 1st 2009 to January 1st 2015 were selected. Their mR NA levels of MYH9 were tested by q rt-PCR. Immunohistochemical method was used to examine the expression of MYH9 in osteosarcoma and the correlation between the positive expression of MYH9 and the clinicopathological features of patients was illustrated by statistical analysis. MYH9 was compounded artificially. The expression of MYH9 in SAOS2 osteosarcoma cells was decreased by si RNA. Scratch test was used to determine the change of SAOS2 cell migration ability after MYH9 silence. Transwell assay was employed to detect the change of cell invasion ability after MYH9 silence.Results: The expression levels of m RNA of MYH9 and protein in osteosarcoma tissues were significant higher than those in benign osteochondroma tissues. The high expression of MYH9 in osteosarcoma tissues was apparently related to the high Enneking classification(III classification) and lung metastasis. SiR NA of MYH9 could evidently decrease the expression level of MYH9 in SAOS2. The down-regulated expression of MYH9 could inhibit the migration and invasion abilities of SAOS2 cells. Conclusions: MYH9 shows a trend of high expression in osteosarcoma tissues, and its high expression is associated with features such as tumor invasion and metastasis. The down-regulated MYH9 can realize an anti-tumor effect by inhibiting the migration and invasion of osteosarcoma cells.展开更多
Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the ...Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the probability of distant metastasis-free survival(DMFS) and overall survival(OS) in patients newly diagnosed with non-metastatic conventional osteosarcoma.Methods: This was a controlled non-randomized clinical study that included 388 patients without clinically detectable metastatic disease enrolled from January 2008 to April 2012. The control treatment group had 272 patients; 180 were male and 92, female,with a median age of 17 years. The treatment group had 58 patients; 36 were male and 22, female, with a median age of 16 years.The control group received preoperative chemotherapy followed by surgery and postoperative chemotherapy. The treatment group received 4 cycles of rh-endostatin perioperatively in addition to chemotherapy as per the control group. Patients were followed up from 6-101 months with a median follow-up period of 50.2 months.Results: The 5-year DMFS of the control group(61%) was significantly lower than that of the rh-endostatin group(79%)(P = 0.013). The 5-year OS of the control group(74%) was significantly lower than that of the rh-endostatin treatment group(87%)(P = 0.029). No difference in adverse drug reactions was found between these 2 groups.Conclusions: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.展开更多
Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the ...Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma(NPC).Methods:We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012.Of these patients,47 who developed RISOM and met inclusion criteria were included in this study.Two of these 47 patients refused treatment and were then excluded.Results:For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period,the total incidence of RIOSM after radiotherapy was 0.084%(47/53,760).Two patients(4.4%) had metastases at the diagnosis of RIOSM.Thirty-nine of the 45(86.7%) patients underwent surgery for RIOSM;most patients(24/39;61.5%) who underwent resection had gross clear margins,with 15 patients(38.5%) having either a gross or microscopic positive margin.All patients died.The 1-,2-,and 3-year overall survival(OS) rates for the entire cohort of 45 patients were 53.3%,35.6%and 13.5%,respectively.The independent prognostic factors associated with high OS rate were tumor size and treatment type.Conclusions:RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention.Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.展开更多
Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.Wh...Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.展开更多
The inhibitory effects of diallyl sulfide(DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism,and the influence of DAS on invasive capability of M...The inhibitory effects of diallyl sulfide(DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism,and the influence of DAS on invasive capability of MG-63 cells were investigated in order to search for the novel medicines for osteosarcoma.In the in vitro experiment,MG-63 cells were treated with different concentrations of DSA,and the morphological changes of MG-63 cells were observed under an inverted phase microscope.MTT method was used to assay the proliferation of MG-63 cells.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) was used to detect the VEGF mRNA expression level in MG-63 cells.By using Transwell invasion assay,the influence of DAS on invasive ability of MG-63 cells was tested.In the in vivo experiment,the nude mice MG-63 cells tumor-bearing model was established,and different concentrations of DAS were injected beside the tumor.Twenty-one days after treatment,the mice were killed,the tumor size and tumor inhibition rate were calculated.The microvessel density(MVD) was determined by using immunohistochemistry.In the in vitro experiment,different concentrations of DAS could obviously inhibit proliferation of MG-63 cells in a time-and concentration-dependent manner.RT-PCR revealed that the expression levels of VEGF mRNA in DSA groups(different concentrations) were significant reduced as compared with those in control group(all P<0.05).Transwell invasion assay indicated that in 20 and 40 μg/mL DAS groups,the number of migratory cells was 91.4±8.3 and 81.8±7.4 respectively,which was significantly declined as compared with that in control group(150.4±14.7,both P<0.05).In the in vivo experiment,DAS could significantly suppress the growth of MG-63 tumor-bearing tissue.Immunohistochemistry demonstrated that different concentrations(20 and 40 μg/mL) of DAS could significantly decrease MVD of MG-63 tumor-bearing tissue(all P<0.05).It was suggested that DAS could inhibit the growth of MG-63 cells probably by suppressing the expression of VEGF mRNA.展开更多
Objective: To investigate clinical signii cance of microRNA-130b(mi R-130b) in osteosarcoma and its role in cell growth and invasion. Methods: miR-130b expression was detected in 68 samples of surgically resected oste...Objective: To investigate clinical signii cance of microRNA-130b(mi R-130b) in osteosarcoma and its role in cell growth and invasion. Methods: miR-130b expression was detected in 68 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues by q RT-PCR. The expression of miR-130b was altered by corresponding vectors in osteosarcoma cells, and then Western blot was used to detect the expression of PPAR毭. Brd U cell proliferation and Transwell assays were performed to determine cell proliferation and invasion. Results: The expression of miR-130b in osteosarcoma tissues was signii cantly higher than that in normal tumor-adjacent tissues. Its expression in patients with metastasis was signii cantly higher than that in those without metastases. miR-130b expression in tumor tissues was signii cantly associated with tumor size, clinical stage and distant metastasis. And its expression was signii cantly correlated with overall survival and disease free survival. miR-130b overexpression obviously repressed the expression of PPAR毭, and resulted in signii cant increase of Saos-2 cell proliferation and invasion. On the contrast, repressing miR-130b expression with its inhibitor signii cantly increased PPAR毭 expression, and inhibited MG-63 cell proliferation and invasion. Conclusions: The high-expression of miR-130b is correlated with the adverse clinicopathological features and poor prognosis in osteosarcoma. miR-130b may regulate proliferation and invasion of osteosarcoma cells by targeting PPAR毭, suggesting miR-130b may play a key role in the progression of osteosarcoma.展开更多
Pancreatic metastases are uncommon. They have been reported in lung cancer, gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma, lymphoma and sarcoma, and usually have solid morphology. Cystic...Pancreatic metastases are uncommon. They have been reported in lung cancer, gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma, lymphoma and sarcoma, and usually have solid morphology. Cystic metastasis to the pancreas is even more rare with few case reports in the literature. However, with the increasing use of computed tomography and magnetic resonance imaging as well as endoscopic ultrasound, more such lesions may be detected. Metastasis to the pancreas from osteosarcoma is highly unusual, but can be seen with the increasing survival of patients with osteosarcoma. We present an extremely rare case of a predominantly cystic lesion of the pancreas, which was diagnosed as metastasis from osteosarcoma. The pathophysiology of the cystic component of the metastasis of osteosarcoma is unknown. Cystic necrotic degeneration of the solid metastasis or pancreatitis secondary to the metastasis with development of associated fluid collection can be considered. Metastasis should remain a differential consideration even for primarily cystic lesions of the pancreas.展开更多
Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site....Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site.In this work,we report a rational integration of photonic-responsive two-dimensional(2D)ultrathin niobium carbide(Nb2C)MXene nanosheets(NSs)into the 3D-printed bone-mimetic scaffolds(NBGS)for osteosarcoma treatment.The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared(NIR-II)biowindow with high tissue-penetrating depth,making it highly efficient in killing bone cancer cells.Importantly,Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site,which can transport more oxygen,vitamins and energy around the bone defect for the reparative process,and gather more immune cells around the defect site to accelerate the degradation of NBGS.The degradation of NBGS provides sufficient space for the bone remodeling.Besides,calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue.The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXeneintegrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.展开更多
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.
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Guangdong Basic and Applied Basic Research Foundation(No.2019B030302012)National Key Research and Development Project(No.2020YFA0509400)+3 种基金National Natural Science Foundation of China(No.81821002,82130082)Excellent Young Scientists Fund of Natural Science Foundation of Henan Province(222300420072)Distinguished Young Scientists Fund of Henan Provincial Health Commission(YXKC2020025)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC21004 and ZYGD22007)。
文摘Osteosarcoma,with poor survival after metastasis,is considered the most common primary bone cancer in adolescents.Notwithstanding the efforts of researchers,its five-year survival rate has only shown limited improvement,suggesting that existing therapeutic strategies are insufficient to meet clinical needs.Notably,immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis.Therefore,managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease.Additionally,given the advances in nanomedicine,there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics.Here,we review the classification,characteristics,and functions of the key components of the immune microenvironment in osteosarcoma.This review also emphasizes the application,progress,and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment.Furthermore,we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.
基金National Natural Sciences Foundation of China(grant91949203,grant 82072979 and grant 81673456)Nonprofit Central ResearchInstitute Fund of the Chinese Academy of Medical Sciences(2019PT320001)Natural Sciences Foundation of Hubei Province(2020CFB778)。
文摘The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.
基金National Natural Science Foundation of China(Nos.31970663 and 82173028 to J.X.,No.81874180 to T.W.,No.81201556 to W.Z.,No.82072971 to H.W.and No.81972505 to Z.W.)。
文摘Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.
基金The Deanship of Scientific Research (DSR)at King Abdulaziz University (KAU),Jeddah,Saudi Arabia has funded this project,under grant no KEP-1-120-42.
文摘Osteosarcoma is one of the rare bone cancers that affect the individualsaged between 10 and 30 and it incurs high death rate. Early diagnosisof osteosarcoma is essential to improve the survivability rate and treatmentprotocols. Traditional physical examination procedure is not only a timeconsumingprocess, but it also primarily relies upon the expert’s knowledge.In this background, the recently developed Deep Learning (DL) models canbe applied to perform decision making. At the same time, hyperparameteroptimization of DL models also plays an important role in influencing overallclassification performance. The current study introduces a novel SymbioticOrganisms Search with Deep Learning-driven Osteosarcoma Detection andClassification (SOSDL-ODC) model. The presented SOSDL-ODC techniqueprimarily focuses on recognition and classification of osteosarcoma usinghistopathological images. In order to achieve this, the presented SOSDL-ODCtechnique initially applies image pre-processing approach to enhance the qualityof image. Also, MobileNetv2 model is applied to generate a suitable groupof feature vectors whereas hyperparameter tuning of MobileNetv2 modelis performed using SOS algorithm. At last, Gated Recurrent Unit (GRU)technique is applied as a classification model to determine proper class labels.In order to validate the enhanced osteosarcoma classification performance ofthe proposed SOSDL-ODC technique, a comprehensive comparative analysiswas conducted. The obtained outcomes confirmed the betterment of SOSDLODCapproach than the existing approaches as the former achieved a maximumaccuracy of 97.73%.
文摘BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.
基金supported in part by the fund of National Cancer Center Research and Development(26-A-4)the Grants-in-Aid for Scientific Research(Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper conformations.HSP90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular homeostasis.Contrastingly,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor cells.All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession.MET,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90.In this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug.The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase.Additionally,treatment with 17-DMAG inhibited cell proliferation and induced apoptosis.Inhibition of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with 17-DMAG.Based on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma cells.This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.
基金National Natural Science Foundation Project of China (No.81860793)Natural Science Foundation Project of Guangxi Province (No.2020JJA140375)Guangxi Graduate Education Innovation Program (No.YCSY2022027)。
文摘Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activities of cells.The aim of this study was to investigate the prognostic significance of Cuproptosis-associated lncRNAs in osteosarcoma.Methods:The Gene expression profiling of osteosarcoma samples versus normal samples and corresponding clinical data were downloaded from the public databases UCSC Xena and GTEx,and the cuproptosis gene was obtained from the published literature,the prognostic model of osteosarcoma cuproptosis-related lncRNA was constructed by using coexpression network,minimum absolute contraction and selection algorithm(LASSO)and Cox regression model.Receiver operating characteristic(ROC)curves and nomograms were used to assess the predictive power of the model.Single-sample gene set enrichment analysis(ssGSEA)was used to explore the relationship between osteosarcoma immune cells and function in different risk groups.Results:181 cuproptosis-related lncRNAs were obtained by co-expression analysis of 19 cuproptosis genes collected.Ten lncRNAs were screened out by differential analysis and single-factor Cox analysis.Three cuproptosis-related lncrnas(AC124798.1,AC090152.1,AC090559.1)were screened by Lasso and multivariate Cox regression to construct the prognostic model.Patients were divided into high and low risk groups based on the median risk score.The results of overall survival,risk score distribution and survival status in the lowrisk group were better than those in the high-risk group,and were verified in the internal data.Univariate and multivariate Cox regression analyses showed that risk score was an independent prognostic factor.Nomograms and ROC curves showed that the prognostic model had good predictive ability.The results of ssGSEA suggest that immune cells and function may be inhibited in the high-risk group.Conclusion:The 3 cuproptosis-related lncRNAs may be helpful to guide the prognosis of osteosarcoma patients and provide some theoretical basis for clinical decision.
文摘Purpose: Development of sarcoma is a known late rare negative side effect of radiotherapy. We add two cases to emphasize the need for open-end follow-up and critical evaluation to avoid misinterpretation. Patients, Methods, and Results: Two patients developed osteosarcoma as a second malignancy in the humerus after adjuvant radiotherapy of a primary tumor not directly involving the later affected bone. The first patient had a Ewing sarcoma of the scapula at age 13 years. Though after neoadjuvant chemotherapy the resected specimen showed only fibrotic necrotic areas within clear resection margins, the study group indicated adjuvant radiotherapy in a field including the shoulder joint. At age 24 years she developed an osteosarcoma of the humeral head, which was resected and reconstructed with a proximal humerus endoprosthesis. She is alive without disease at age 32 years. The second patient presented with an osteosarcoma of the proximal humerus 29 years after irradiation for breast cancer including the shoulder joint. The sarcoma was misinterpreted as radiation-induced necrosis and the patient was treated with a reverse shoulder endoprosthesis. Pathologic examination of the resected humeral head then showed a typical osteosarcoma. Two years later the humeral reverse shoulder implant was resected and a proximal humerus tumor prosthesis implanted leaving the original glenosphere. Conclusions: In both cases radiation-induced osteosarcoma developed in bone not affected by the primary cancer. Protecting uninvolved structures must be warranted in the planning of radiotherapy. The long latency between the primary and second cancer mandates long-term—best indefinite—follow-up, as with appropriate treatment of a radiation-induced osteosarcoma good healing rates comparable to those of primary osteosarcoma can still be achieved.
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.
文摘Metastatic peritoneal sarcomatosis most commonly occurs from primary soft tissue sarcomas arising either within the abdomen or extremities. Metastatic peritoneal sarcomatosis from an osteosarcoma is extremely rare;only six cases have previously been reported. We report the first case of metastatic peritoneal sarcomatosis originating from radiation-induced osteoblastic osteosarcoma in a 22-year-old woman who had previously been treated for pelvic Ewing’s sarcoma. Abdominal computed tomography, bone scintigraphy and FDG PET/CT demonstrated extensive finely nodular disseminated peritoneal lesions. Histopathologic examination of these peritoneal lesions revealed osteosarcomatosis. In summary, we describe an unusual case of metastatic peritoneal sar comatosis from secondary osteosarcoma arising in a previously irradiated pelvicEwing’s sarcoma.
基金supported by Hubei Natural Science Foundation Project(Grant No.2014CFB199)
文摘Objective: To determine the expression of non-muscle myosin heavy chain 9(MYH9) in osteosarcoma and its effect on the migration and invasion abilities of tumor cell. Methods: A total of 65 cases of osteosarcoma and 20 cases with benign osteochondroma who underwent resection operation in the Orthopaedics Department of our hospital from January 1st 2009 to January 1st 2015 were selected. Their mR NA levels of MYH9 were tested by q rt-PCR. Immunohistochemical method was used to examine the expression of MYH9 in osteosarcoma and the correlation between the positive expression of MYH9 and the clinicopathological features of patients was illustrated by statistical analysis. MYH9 was compounded artificially. The expression of MYH9 in SAOS2 osteosarcoma cells was decreased by si RNA. Scratch test was used to determine the change of SAOS2 cell migration ability after MYH9 silence. Transwell assay was employed to detect the change of cell invasion ability after MYH9 silence.Results: The expression levels of m RNA of MYH9 and protein in osteosarcoma tissues were significant higher than those in benign osteochondroma tissues. The high expression of MYH9 in osteosarcoma tissues was apparently related to the high Enneking classification(III classification) and lung metastasis. SiR NA of MYH9 could evidently decrease the expression level of MYH9 in SAOS2. The down-regulated expression of MYH9 could inhibit the migration and invasion abilities of SAOS2 cells. Conclusions: MYH9 shows a trend of high expression in osteosarcoma tissues, and its high expression is associated with features such as tumor invasion and metastasis. The down-regulated MYH9 can realize an anti-tumor effect by inhibiting the migration and invasion of osteosarcoma cells.
基金Ministry of Human Resources and Social Security of the People's Republic of China (MOHRSS) (Grant No. 2017199)
文摘Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the probability of distant metastasis-free survival(DMFS) and overall survival(OS) in patients newly diagnosed with non-metastatic conventional osteosarcoma.Methods: This was a controlled non-randomized clinical study that included 388 patients without clinically detectable metastatic disease enrolled from January 2008 to April 2012. The control treatment group had 272 patients; 180 were male and 92, female,with a median age of 17 years. The treatment group had 58 patients; 36 were male and 22, female, with a median age of 16 years.The control group received preoperative chemotherapy followed by surgery and postoperative chemotherapy. The treatment group received 4 cycles of rh-endostatin perioperatively in addition to chemotherapy as per the control group. Patients were followed up from 6-101 months with a median follow-up period of 50.2 months.Results: The 5-year DMFS of the control group(61%) was significantly lower than that of the rh-endostatin group(79%)(P = 0.013). The 5-year OS of the control group(74%) was significantly lower than that of the rh-endostatin treatment group(87%)(P = 0.029). No difference in adverse drug reactions was found between these 2 groups.Conclusions: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.
文摘Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma(NPC).Methods:We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012.Of these patients,47 who developed RISOM and met inclusion criteria were included in this study.Two of these 47 patients refused treatment and were then excluded.Results:For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period,the total incidence of RIOSM after radiotherapy was 0.084%(47/53,760).Two patients(4.4%) had metastases at the diagnosis of RIOSM.Thirty-nine of the 45(86.7%) patients underwent surgery for RIOSM;most patients(24/39;61.5%) who underwent resection had gross clear margins,with 15 patients(38.5%) having either a gross or microscopic positive margin.All patients died.The 1-,2-,and 3-year overall survival(OS) rates for the entire cohort of 45 patients were 53.3%,35.6%and 13.5%,respectively.The independent prognostic factors associated with high OS rate were tumor size and treatment type.Conclusions:RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention.Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.
基金grants from the National Natural Science Foundation of China(Grant No.81802689)China International Medical Foundation(Grant No.Z-2014-06-15331)Conflict of interest。
文摘Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.
基金supported by a grant from Natural Science Foundation of Hubei Province of China (No. 2008CBD112)
文摘The inhibitory effects of diallyl sulfide(DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism,and the influence of DAS on invasive capability of MG-63 cells were investigated in order to search for the novel medicines for osteosarcoma.In the in vitro experiment,MG-63 cells were treated with different concentrations of DSA,and the morphological changes of MG-63 cells were observed under an inverted phase microscope.MTT method was used to assay the proliferation of MG-63 cells.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) was used to detect the VEGF mRNA expression level in MG-63 cells.By using Transwell invasion assay,the influence of DAS on invasive ability of MG-63 cells was tested.In the in vivo experiment,the nude mice MG-63 cells tumor-bearing model was established,and different concentrations of DAS were injected beside the tumor.Twenty-one days after treatment,the mice were killed,the tumor size and tumor inhibition rate were calculated.The microvessel density(MVD) was determined by using immunohistochemistry.In the in vitro experiment,different concentrations of DAS could obviously inhibit proliferation of MG-63 cells in a time-and concentration-dependent manner.RT-PCR revealed that the expression levels of VEGF mRNA in DSA groups(different concentrations) were significant reduced as compared with those in control group(all P<0.05).Transwell invasion assay indicated that in 20 and 40 μg/mL DAS groups,the number of migratory cells was 91.4±8.3 and 81.8±7.4 respectively,which was significantly declined as compared with that in control group(150.4±14.7,both P<0.05).In the in vivo experiment,DAS could significantly suppress the growth of MG-63 tumor-bearing tissue.Immunohistochemistry demonstrated that different concentrations(20 and 40 μg/mL) of DAS could significantly decrease MVD of MG-63 tumor-bearing tissue(all P<0.05).It was suggested that DAS could inhibit the growth of MG-63 cells probably by suppressing the expression of VEGF mRNA.
文摘Objective: To investigate clinical signii cance of microRNA-130b(mi R-130b) in osteosarcoma and its role in cell growth and invasion. Methods: miR-130b expression was detected in 68 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues by q RT-PCR. The expression of miR-130b was altered by corresponding vectors in osteosarcoma cells, and then Western blot was used to detect the expression of PPAR毭. Brd U cell proliferation and Transwell assays were performed to determine cell proliferation and invasion. Results: The expression of miR-130b in osteosarcoma tissues was signii cantly higher than that in normal tumor-adjacent tissues. Its expression in patients with metastasis was signii cantly higher than that in those without metastases. miR-130b expression in tumor tissues was signii cantly associated with tumor size, clinical stage and distant metastasis. And its expression was signii cantly correlated with overall survival and disease free survival. miR-130b overexpression obviously repressed the expression of PPAR毭, and resulted in signii cant increase of Saos-2 cell proliferation and invasion. On the contrast, repressing miR-130b expression with its inhibitor signii cantly increased PPAR毭 expression, and inhibited MG-63 cell proliferation and invasion. Conclusions: The high-expression of miR-130b is correlated with the adverse clinicopathological features and poor prognosis in osteosarcoma. miR-130b may regulate proliferation and invasion of osteosarcoma cells by targeting PPAR毭, suggesting miR-130b may play a key role in the progression of osteosarcoma.
文摘Pancreatic metastases are uncommon. They have been reported in lung cancer, gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma, lymphoma and sarcoma, and usually have solid morphology. Cystic metastasis to the pancreas is even more rare with few case reports in the literature. However, with the increasing use of computed tomography and magnetic resonance imaging as well as endoscopic ultrasound, more such lesions may be detected. Metastasis to the pancreas from osteosarcoma is highly unusual, but can be seen with the increasing survival of patients with osteosarcoma. We present an extremely rare case of a predominantly cystic lesion of the pancreas, which was diagnosed as metastasis from osteosarcoma. The pathophysiology of the cystic component of the metastasis of osteosarcoma is unknown. Cystic necrotic degeneration of the solid metastasis or pancreatitis secondary to the metastasis with development of associated fluid collection can be considered. Metastasis should remain a differential consideration even for primarily cystic lesions of the pancreas.
基金the financial support from the National Key R&D Program of China(Grant No.2016YFA0203700)the National Natural Science Foundation of China(Grant Nos.51872185,51722211,51672303,81672131,81672143,82072417 and 81802247)+2 种基金the Program of Shanghai Academic Research Leader(Grant No.18XD1404300)the National Key Research and Development Project of China(Grant No.2018YFC1106303)the Science and Technology Commission of Shanghai Municipality(Grant No.17060502400).
文摘Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site.In this work,we report a rational integration of photonic-responsive two-dimensional(2D)ultrathin niobium carbide(Nb2C)MXene nanosheets(NSs)into the 3D-printed bone-mimetic scaffolds(NBGS)for osteosarcoma treatment.The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared(NIR-II)biowindow with high tissue-penetrating depth,making it highly efficient in killing bone cancer cells.Importantly,Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site,which can transport more oxygen,vitamins and energy around the bone defect for the reparative process,and gather more immune cells around the defect site to accelerate the degradation of NBGS.The degradation of NBGS provides sufficient space for the bone remodeling.Besides,calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue.The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXeneintegrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.
