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Osteosarcoma

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41. Prognosis of osteosarcomas in the mandible: 15-year experience of 55 patients. (PubMed)

Prognosis of osteosarcomas in the mandible: 15-year experience of 55 patients. Our goal was to evaluate the prognosis of osteosarcomas (OS) in the mandible for finding out the best treatment.Patients diagnosed with OS in the mandible from January 2000 to December 2015 were retrospectively enrolled. Demographic, tumor-specific, treatment, and survival data were collected and analyzed.A total of 55 patients (35 male and 20 female) were included, all patients had first manifestation of swelling

2019 Medicine

42. A genetically engineered microRNA-34a prodrug demonstrates anti-tumor activity in a canine model of osteosarcoma. (PubMed)

A genetically engineered microRNA-34a prodrug demonstrates anti-tumor activity in a canine model of osteosarcoma. Osteosarcoma (OSA) represents the most common primary bone tumor in humans and pet dogs. Little progress has been made with regard to viable treatment options in the past three decades and patients presenting with metastatic disease continue to have a poor prognosis. Recent mouse studies have suggested that microRNA-34a (miR-34a) may have anti-tumor activities in human OSA models

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2018 PLoS ONE

43. Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition. (PubMed)

Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition. Resveratrol shows potent anti-tumor therapeutic properties in various tumors. However, the exact effect of resveratrol on osteosarcoma cells, especially cancer stem cells, remains unclear. In this study, we examined the effect of resveratrol on osteosarcoma stem cells and explored the underlying molecular mechanisms. Resveratrol inhibited cell viability, self-renewal ability and tumorigenesis of osteosarcoma (...) cells, whereas showed no significant inhibition effects to normal osteoblast cells. Mechanically, resveratrol treatment decreased cytokines synthesis and inhibited JAK2/STAT3 signaling, which was consistent with the decline of cancer stem cells marker, CD133. Exogenous STAT3 activation attenuated the cancer stem cell elimination effects of resveratrol treatment. Our results demonstrated that resveratrol inhibited osteosarcoma cell proliferation and tumorigenesis ability, which was correlated

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2018 PLoS ONE

44. MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines. (PubMed)

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines. Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well

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2018 PLoS ONE

45. Atypical "Sclerosing" Osteoblastic Neoplasm: A Tumor of Intermediate Biological Potential Between Usual Osteoblastoma and Conventional Osteosarcoma. (PubMed)

Atypical "Sclerosing" Osteoblastic Neoplasm: A Tumor of Intermediate Biological Potential Between Usual Osteoblastoma and Conventional Osteosarcoma. The existence of "aggressive" osteoblastoma (OB) or malignant transformation of OB is controversial. Over a few decades, we have encountered a group of "borderline" sclerosing osteoblastic lesions that are difficult to classify, tending toward local recurrence, especially following curettage. A search of the consultative and institutional files (...) from 3 co-authors for atypical OB, malignant transformation of OB, well-differentiated osteosarcoma (OS), and OB-like OS diagnoses revealed 8 similar cases. There were 6 males and 2 females, ages 11 to 55 years (mean, 26 y). Three arose in metatarsals, 2 in the fibula, and 1 each in the humerus, tibia, and femur. Radiologically, most were expansile, lytic to sclerotic, with circumscribed and at least partially sclerotic borders. Pathologically, all displayed a predominant, sclerosing sheet-like

2019 American Journal of Surgical Pathology

46. Tegavivint and the β-catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma. (PubMed)

Tegavivint and the β-catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma. The Wnt/β-catenin pathway is closely associated with osteosarcoma (OS) development and metastatic progression. We investigated the antitumor activity of Tegavivint, a novel β-catenin/transducing β-like protein 1 (TBL1) inhibitor, against OS employing in vitro, ex vivo and in vivo cell line and patient-derived xenograft (PDX) models that recapitulate high risk disease.The antitumor efficacy

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2019 Journal of the National Cancer Institute

47. Autocrine production of reproductive axis neuropeptides affects proliferation of canine osteosarcoma in vitro. (PubMed)

Autocrine production of reproductive axis neuropeptides affects proliferation of canine osteosarcoma in vitro. Osteosarcoma strikes hundreds of people each year, of both advanced and younger ages, and is often terminal. Like many tumor types, these bone tumors will frequently undergo a neuroendocrine transition, utilizing autocrine and/or paracrine hormones as growth factors and/or promoters of angiogenesis to facilitate progression and metastasis. While many of these factors and their actions (...) on tumor growth are characterized, some tumor-derived neuropeptides remain unexplored.Using validated canine osteosarcoma cell lines in vitro, as well as cells derived from spontaneous tumors in dogs, we explored the autocrine production of two neuropeptides typically found in the hypothalamus, and most closely associated with reproduction: gonadotropin-releasing hormone (GnRH) and kisspeptin (Kiss-1). We evaluated gene expression and protein secretion of these hormones using quantitative RT-PCR

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2019 BMC Cancer

48. Novel near-infrared fluorescence-guided surgery with vesicular stomatitis virus for complete surgical resection of osteosarcomas in mice. (PubMed)

Novel near-infrared fluorescence-guided surgery with vesicular stomatitis virus for complete surgical resection of osteosarcomas in mice. Attempts have been made to visualize tumor cells intraoperatively with fluorescence guidance. However, the clear demarcation and complete tumor resection have always been a challenging task. To address this, we have developed a novel fluorescence bioimaging system with vesicular stomatitis virus (VSV) incorporating Katushka, near-infrared fluorescent protein (...) . VSV is tumor-specific owing to the deficiency of antiviral interferon signaling pathways in tumor cells. We aimed to evaluate the tumor specificity of the recombinant VSV-Katushka (rVSV-K) in osteosarcoma cells and to assess the feasibility of complete tumor resection by the rVSV-K fluorescence guidance. In in vitro experiments, mouse and human osteosarcoma cell lines and normal human mesenchymal stem cells were infected with rVSV-K and observed by fluorescence microscopy. Near-infrared

2019 Journal of Orthopaedic Research

49. Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma. (PubMed)

Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma. Osteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Many circRNAs have been proved to play important roles in the pathogenesis of some diseases. However, the occurrence of circRNAs in OS remains little known.The circular RNA (circRNA) expression file GSE96964 dataset, which included seven osteosarcoma cell (...) lines and one control sample (osteoblast cell line), was downloaded from the Gene Expression Omnibus (GEO) database to explore the potential function of circRNAs in osteosarcoma by competing endogenous RNA (ceRNA) analysis. Three gene expression profiles of OS were downloaded from GEO database and then used for the pathway enrichment analysis, Venn analysis and protein-protein interaction (PPI) network analysis. Real-time qPCR validation and RNA interference were conducted to verify our

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2018 PLoS ONE

50. Alpha particle Radium 223 dichloride in high-risk osteosarcoma: a phase I dose escalation trial. (PubMed)

Alpha particle Radium 223 dichloride in high-risk osteosarcoma: a phase I dose escalation trial. The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (223RaCl2) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers.A 3+3 phase I, dose-escalation trial of 223RaCl2 (50, 75 (...) , and 100 kBq/kg) was designed in recurrent/metastatic osteosarcoma patients aged ≥15 years. Objective measurements included changes in SUV of PET (18FDG and/or NaF-18) and single-photon-emission-computed-tomography-computed tomography (99mTc-MDP) as well as alkaline phosphatase and bone turnover markers at baseline, mid-study, and the end of the study.Among 18 patients enrolled (including 15 males) aged 15-71 years, tumor locations included spine (n=12, 67%), pelvis (n=10, 56%), ribs (n=9, 50

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2019 Clinical Cancer Research

51. Integrative analysis reveals driver long non-coding RNAs in osteosarcoma. (PubMed)

Integrative analysis reveals driver long non-coding RNAs in osteosarcoma. Transcriptome profiling of osteosarcoma (OS) by next generation sequencing technology (NGS) has been broadly performed by previous researches, which uncovers a large number protein-coding driver genes, facilitates our understanding of the molecular mechanisms of OS formation, progression and metastasis. Recently, more and more researchers realize the importance of long non-coding RNAs (lncRNAs) on the development of OS

2019 Medicine

52. Efficacy of methotrexate, doxorubicin, and cisplatin for osteosarcoma: Study protocol for a systematic review of randomized controlled trial. (PubMed)

Efficacy of methotrexate, doxorubicin, and cisplatin for osteosarcoma: Study protocol for a systematic review of randomized controlled trial. This systematic review will address the efficacy and safety of methotrexate, doxorubicin, and cisplatin (MAP) for the treatment of patients with osteosarcoma.We will retrieve the studies from the following 9 electronic databases: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (...) of patients with osteosarcoma. The primary outcome includes event-free survival. The secondary outcomes consist of overall survival, quality of life, and toxicity. In addition, 2 independent researchers will extract data, and will assess the quality of included studies by using Cochrane risk of bias tool. Results data will be pooled and meta-analysis will be conducted if >2 eligible studies will be included.This systematic review will evaluate the efficacy and safety of MAP for the treatment of patients

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2019 Medicine

53. Targeting mutant TP53 as a potential therapeutic strategy for the treatment of osteosarcoma. (PubMed)

Targeting mutant TP53 as a potential therapeutic strategy for the treatment of osteosarcoma. Mutant TP53 is a promising therapeutic target in cancers. Considering the current challenges facing the clinical treatment of cancer, as well as the urgent need to identify novel therapeutic targets in osteosarcomas, we aimed to evaluate the clinical significance of mutant TP53 in osteosarcoma patients and to explore the therapeutic effect of targeting mutant TP53 in osteosarcomas. We performed a meta (...) -analysis to investigate the relationship between mutant TP53 and the overall survival of patients with osteosarcoma. A CRISPR-Cas9 system and a TP53 inhibitor, NSC59984, were also used to specifically knock-out and inhibit mutant TP53 in the human osteosarcoma cell lines, KHOS, and KHOSR2. The meta-analysis demonstrated that mutations in the TP53 gene could be used to predict a poor 2-year survival in osteosarcoma patients. We also demonstrated that the expression of mutant TP53 in human osteosarcoma

2019 Journal of Orthopaedic Research

54. Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome. (PubMed)

Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome. Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains unknown. In the present study, we evaluated the prognostic value and biological relevance

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2019 BMC Cancer

55. Mitochondrial genome and functional defects in osteosarcoma are associated with their aggressive phenotype. (PubMed)

Mitochondrial genome and functional defects in osteosarcoma are associated with their aggressive phenotype. Osteosarcoma (OSA) is an aggressive mesenchymal tumor of the bone that affects children and occurs spontaneously in dogs. Human and canine OSA share similar clinical, biological and genetic features, which make dogs an excellent comparative model to investigate the etiology and pathogenesis of OSA. Mitochondrial (mt) defects have been reported in many different cancers including OSA

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2018 PLoS ONE

56. Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. (PubMed)

Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort.This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who (...) survival. Fourteen (64%) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation.The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.

2019 Journal of Clinical Oncology

57. Osteosarcoma after the age of fifty: A clinicopathological study. (PubMed)

Osteosarcoma after the age of fifty: A clinicopathological study. Osteosarcoma, a primary malignant bone tumor, has a well-recognised double peak of incidence in early adolescence and after 50 years. This study investigates the clinical features and prognostic factors of patients older than 50 years with osteosarcoma.From January 2000 to December 2012, in one bone tumor reference center, 32 patients aged more than 50 years at the diagnosis (mean age: 62.4 years (50-85), sex ratio: 13 males, 19 (...) females) diagnosed with osteosarcoma were included. Patients younger than 50 years at diagnosis or with a non-histologically proved osteosarcoma were excluded. For each patient, we registered medical history, tumor location, systemic and local extension, treatment, and survival.62% were located in the extremities and 28% in the axial skeleton. 6 were secondary sarcomas. Mean delay between first symptoms and biopsy was 7.4 months (range from 0 to 28 months). Ten patients had a systemic osteosarcoma

2019 European Journal of Surgical Oncology

58. Surgery and proton beam therapy for mediastinal extraskeletal osteosarcoma. (PubMed)

Surgery and proton beam therapy for mediastinal extraskeletal osteosarcoma. Extraskeletal osteosarcoma (ESOS) arising from the mediastinum is a rare malignant tumor and associated with a poor prognosis. We present the case of a 73-year-old man with a hoarseness. Imaging studies revealed a large calcified tumor of the median mediastinum. Surgery was performed, but complete resection was impossible and about two-thirds of the tumor was excised. The tumor was pathologically diagnosed as ESOS

2019 Annals of Thoracic Surgery

59. Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients. (PubMed)

Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients. Osteosarcoma is the most common malignant bone tumor in children. Survival remains poor among histologically poor responders, and there is a need to identify them at diagnosis to avoid delivering ineffective therapy. Genetic variation contributes to a wide range of response and toxicity related to chemotherapy. The aim of this study is to use sequencing (...) of blood cells to identify germline haplotypes strongly associated with drug resistance in osteosarcoma patients.We used sequencing data from two patient datasets, from Inova Hospital and the NCI TARGET. We explored the effect of mutation hotspots, in the form of haplotypes, associated with relapse outcome. We then mapped the single nucleotide polymorphisms (SNPs) in these haplotypes to genes and pathways. We also performed a targeted analysis of mutations in Drug Metabolizing Enzymes and Transporter

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2019 BMC Cancer

60. Interaction between the BAG1S isoform and HSP70 mediates the stability of anti-apoptotic proteins and the survival of osteosarcoma cells expressing oncogenic MYC. (PubMed)

Interaction between the BAG1S isoform and HSP70 mediates the stability of anti-apoptotic proteins and the survival of osteosarcoma cells expressing oncogenic MYC. The oncoprotein MYC has the dual capacity to drive cell cycle progression or induce apoptosis, depending on the cellular context. BAG1 was previously identified as a transcriptional target of MYC that functions as a critical determinant of this cell fate decision. The BAG1 protein is expressed as multiple isoforms, each having (...) an array of distinct biochemical functions; however, the specific effector function of BAG1 that directs MYC-dependent cell survival has not been defined.In our studies the human osteosarcoma line U2OS expressing a conditional MYC-ER allele was used to induce oncogenic levels of MYC. We interrogated MYC-driven survival processes by modifying BAG1 protein expression. The function of the separate BAG1 isoforms was investigated by depleting cells of endogenous BAG1 and reintroducing the distinct isoforms

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2019 BMC Cancer

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