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Osteosarcoma

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121. Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma. (PubMed)

Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma. Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic (...) variant, and an additional 5.7% carry exonic variants of unknown significance in TP53.Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data.One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing

2018 Cancer

122. Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study. (PubMed)

Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study. In most countries, reference chemotherapy for osteosarcoma is MAP regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France, the standard preoperative chemotherapy for children/adolescents combines M and etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and efficacy results of patients ≤25 years treated

2018 European Journal of Cancer

123. Quantitative Primary Tumor Indocyanine Green Measurements Predict Osteosarcoma Metastatic Lung Burden in a Mouse Model. (PubMed)

Quantitative Primary Tumor Indocyanine Green Measurements Predict Osteosarcoma Metastatic Lung Burden in a Mouse Model. Current preclinical osteosarcoma (OS) models largely focus on quantifying primary tumor burden. However, most fatalities from OS are caused by metastatic disease. The quantification of metastatic OS currently relies on CT, which is limited by motion artifact, requires intravenous contrast, and can be technically demanding in the preclinical setting. We describe the ability

2018 Clinical Orthopaedics and Related Research

124. Indeterminate nodules in osteosarcoma: what's the follow-up? (PubMed)

Indeterminate nodules in osteosarcoma: what's the follow-up? Indeterminate pulmonary nodules in patients diagnosed with osteosarcoma present a challenge for accurate staging and prognosis. The aim of this study was to explore the significance of this finding.A retrospective cohort study of 120 patients with osteosarcoma was performed in the North East of England. Chest computed tomographies (CTs) at presentation were reviewed and the incidence of 'indeterminate' nodules recorded. Follow-up

2018 British Journal of Cancer

125. Postmetastasis survival in high-grade extremity osteosarcoma: A retrospective analysis of prognostic factors in 126 patients. (PubMed)

Postmetastasis survival in high-grade extremity osteosarcoma: A retrospective analysis of prognostic factors in 126 patients. Prognostic factors predictive of postmetastasis survival (PMS) in metastatic osteosarcoma are poorly understood. Our aims were to evaluate PMS in patients with high-grade osteosarcoma in extremities, and to identify prognostic factors related to PMS.A retrospective review of data for 126 patients with metastatic osteosarcoma was conducted. The study population consisted (...) any negative prognostic factor was 60.2%; with one factor, 31.6%; and with more than two factors, 3.6%.PMS in osteosarcoma patients was influenced by primary tumor-related factors such as histologic response to chemotherapy, as well as metastasis-related factors such as complete metastasectomy and metastasis site. A certain group of patients without such poor prognostic factors could be cured even after the development of metastasis.© 2018 Wiley Periodicals, Inc.

2018 Journal of Surgical Oncology

126. PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse. (PubMed)

PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse. Immune checkpoint inhibitors have led to a breakthrough in solid tumor immunotherapy, but related studies on musculoskeletal tumors are few, especially for PD-L2.We examined expression of three molecular effectors of the PD-1 axis in 234 patients with musculoskeletal tumors, including osteosarcoma, chondrosarcoma, synovial sarcoma, and giant cell tumor. Survival analyses (...) and potential mechanisms were investigated in osteosarcoma per the Gene Expression Omnibus (GEO) and immunohistochemistry analyses. In vivo, humanized mice were used to evaluate the effect of nivolumab on osteosarcoma.PD-L1, PD-L2, and PD-1 expression levels were significantly different between the histologic types of the musculoskeletal tumors. For osteosarcoma, PD-L1 was negatively correlated with prognosis, while PD-1 had a negative correlation tendency with overall survival (OS). Meanwhile, PD-L2 had

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2018 Journal of hematology & oncology

127. Vascular endothelial growth factor polymorphisms are associated with osteosarcoma susceptibility. (PubMed)

Vascular endothelial growth factor polymorphisms are associated with osteosarcoma susceptibility. Polymorphisms in the vascular endothelial growth factor (VEGF) gene may contribute to osteosarcoma risk, but the results of previous studies have been inconsistent and inconclusive. We conducted a meta-analysis to assess this association more accurately. Relevant studies were collected systemically from three online English databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were (...) used to assess the strength of the associations of three VEGF gene polymorphisms (+936C/T, -634 G/C, +1612 G/A) with osteosarcoma risk. Seven case-control studies involving 1,350 cases and 1,706 controls were selected for the meta-analysis. The pooled OR indicated that the VEGF +936C/T polymorphism was associated with increased risk of osteosarcoma in a Chinese population (T vs. C: OR = 1.26, 95% CI = 1.12-1.42, P < 0.01; TT vs. CC: OR = 1.70, 95% CI = 1.29-2.24, P < 0.01; CT + TT vs. CC: OR = 1.23

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2018 Oncotarget

128. Targeting ABCB1 (MDR1) in multi-drug resistant osteosarcoma cells using the CRISPR-Cas9 system to reverse drug resistance. (PubMed)

Targeting ABCB1 (MDR1) in multi-drug resistant osteosarcoma cells using the CRISPR-Cas9 system to reverse drug resistance. Multi-drug resistance (MDR) remains a significant obstacle to successful chemotherapy treatment for osteosarcoma patients. One of the central causes of MDR is the overexpression of the membrane bound drug transporter protein P-glycoprotein (P-gp), which is the protein product of the MDR gene ABCB1. Though several methods have been reported to reverse MDR in vitro (...) and in vivo when combined with anticancer drugs, they have yet to be proven useful in the clinical setting.The meta-analysis demonstrated that a high level of P-gp may predict poor survival in patients with osteosarcoma. The expression of P-gp can be efficiently blocked by the clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 system (CRISPR-Cas9). Inhibition of ABCB1 was associated with reversing drug resistance in osteosarcoma MDR cell lines (KHOSR2 and U-2OSR2

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2018 Oncotarget

129. [Meta-analysis on limb salvage and amputation for patients with local Enneking II osteosarcoma].

[Meta-analysis on limb salvage and amputation for patients with local Enneking II osteosarcoma]. To explore 5-year survival rate, local recurrence and metastasis rate of limb salvage and amputation for patients with local Enneking II osteosarcoma by Meta-analysis.From January 1, 1970 to December 1, 2015, Subject term and keywords about limb salvage and amputation for local Enneking II osteosarcoma with pathological fracture were searched from Cochrane, PubMed, Ovid, Spinger Link, Embase, CNKI (...) Enneking II osteosarcoma with pathological fracture does not greatly increase risk of local recurrence or 5-year overall survival rate compared with amputation group, and has a lower risk of metastatic occurrence.

2018 Zhongguo gu shang = China journal of orthopaedics and traumatology

130. Combination of anginex gene therapy and radiation decelerates the growth and pulmonary metastasis of human osteosarcoma xenografts (PubMed)

Combination of anginex gene therapy and radiation decelerates the growth and pulmonary metastasis of human osteosarcoma xenografts Investigate whether rAAV-anginex gene therapy combined with radiotherapy could decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the mechanisms involved in this therapeutic strategy. During in vitro experiment, multiple treatment regimes (rAAV-eGFP, radiotherapy, rAAV-anginex, combination therapy) were applied to determine effects (...) on proliferation of endothelial cells (ECs) and G-292 osteosarcoma cells. During in vivo analysis, the same multiple treatment regimes were applied to osteosarcoma tumor-bearing mice. Use microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell inoculation, immunohistochemistry was used to assess the therapeutic efficacy according to microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assays

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2018 Cancer medicine

131. Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway (PubMed)

Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway The outcome of chemotherapy for osteosarcoma have improved during the past decade and more patients have access to combination chemotherapy, but there has been no significant clinical progress in the patient survival rate. Recently, forkhead-box O3 (FOXO3) was identified as a pivotal transcription factor responsible for the transcriptional regulation of genes associated with suppression of cancer (...) . The purpose of the present study was to screen small chemicals activating FOXO3 and elucidate their underlying mechanism. Using a drug discovery platform based on the phosphorylation status of FOXO3 in osteosarcoma cells, mitoxantrone (MTZ), a type of DNA-damaging agent, was selected as a possible FOXO3 activator from the food and drug administration-approved drug library. MTZ treatments significantly inhibited the phosphorylation level of Akt-pS473 and caused nuclear localization of FOXO3 in osteosarcoma

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2018 Oncology letters

132. Short Exposures to an Extremely Low-Frequency Magnetic Field (ELF MF) Enhance Protein but not mRNA Alkaline Phosphatase Expression in Human Osteosarcoma Cells (PubMed)

Short Exposures to an Extremely Low-Frequency Magnetic Field (ELF MF) Enhance Protein but not mRNA Alkaline Phosphatase Expression in Human Osteosarcoma Cells Among electromagnetic fields treatments used in orthopedics, extremely low-frequency magnetic fields (ELF MF) need more detailed information about the molecular mechanisms of their effects and exposure conditions.Evaluation of the effects of an ELF MF exposure system, recently introduced among current clinical treatments for fracture (...) healing and other bone diseases, on Alkaline Phosphatase (ALP) activity and expression in a human osteosarcoma cell line (SaOS-2), as marker typically associated to osteogenesis and bone tissue regeneration.Cells were exposed to the ELF MF physical stimulus (75 Hz, 1.5 mT) for 1h. Cell viability, enzymatic activity, protein and mRNA expression of alkaline phosphatase were then measured at different times after exposure (0, 4 and 24 h).Data demonstrate that this signal is active on an osteogenic

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2018 The Open Biochemistry Journal

133. miR-30a suppresses osteosarcoma proliferation and metastasis by downregulating MEF2D expression (PubMed)

miR-30a suppresses osteosarcoma proliferation and metastasis by downregulating MEF2D expression Many studies have revealed that microRNAs (miRNAs) play crucial roles in cancer development and progression. miRNA-30a (miR-30a), as a member of the miR-30 family, has been implicated in various cancers. However, the role of miR-30a in osteosarcoma remains unclear. In the current study, we found that miR-30a was significantly downregulated in osteosarcoma tissues and cell lines by using quantitative (...) , and invasion of osteosarcoma cell, indicating that miR-30a suppresses osteosarcoma cell proliferation and metastasis partially mediated by inhibition of MEF2D. Overall, our study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in osteosarcoma, providing a promising prognostic biomarker and a therapeutic strategy for osteosarcoma.

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2018 OncoTargets and therapy

134. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. (PubMed)

Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Regorafenib has proven activity in patients with pretreated gastrointestinal stromal tumours and colorectal and hepatocellular carcinoma. We designed REGOBONE to assess the efficacy and safety of regorafenib for patients with progressive metastatic osteosarcoma and other bone sarcomas. This trial comprised four parallel independent (...) cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. In this Article, we report the results of the osteosarcoma cohort.In this non-comparative, double-blind, placebo-controlled, phase 2 trial, patients aged 10 years or older with histologically confirmed osteosarcoma whose disease had progressed after treatment with one to two previous lines of chemotherapy for metastatic disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly

2018 Lancet Oncology

135. Identification of Key Genes and miRNAs in Osteosarcoma Patients with Chemoresistance by Bioinformatics Analysis (PubMed)

Identification of Key Genes and miRNAs in Osteosarcoma Patients with Chemoresistance by Bioinformatics Analysis Chemoresistance is a significant factor associated with poor outcomes of osteosarcoma patients. The present study aims to identify Chemoresistance-regulated gene signatures and microRNAs (miRNAs) in Gene Expression Omnibus (GEO) database. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) included positive regulation of transcription, DNA-templated (...) , tryptophan metabolism, and the like. Then differentially expressed genes (DEGs) were uploaded to Search Tool for the Retrieval of Interacting Genes (STRING) to construct protein-protein interaction (PPI) networks, and 9 hub genes were screened, such as fucosyltransferase 3 (Lewis blood group) (FUT3) whose expression in chemoresistant samples was high, but with a better prognosis in osteosarcoma patients. Furthermore, the connection between DEGs and differentially expressed miRNAs (DEMs) was explored

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2018 BioMed research international

136. Gene expression profiles and pathway enrichment analysis of human osteosarcoma cells exposed to sorafenib (PubMed)

Gene expression profiles and pathway enrichment analysis of human osteosarcoma cells exposed to sorafenib Sorafenib is an inhibitor of a variety of tyrosine kinase receptors used to treat various cancers including hepatocellular, renal cell and thyroid carcinoma. It has been shown to change various targets associated with osteosarcoma, but the detailed mechanism remains unclear. In order to identify key genes, enriched pathways and important modules during the exposure of human osteosarcoma (...) interaction network was constructed by string and visualized in cytoscape, and eight genes were selected as hubs: IL8,CXCL2,PTGS2,FOS,CXCL1, C3,EHMT2 and PGF. Subsequently, only one cluster was identified by mcode, which consisted of six nodes (CXCL1,CXCL2,PTGS2,FOS, C3 and PGF) and nine edges. PGF was the seed gene in this cluster. In conclusion, the results of this data mining and integration should help in revealing new mechanisms and targets of sorafenib in inhibiting osteosarcoma.

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2018 FEBS open bio

137. Carbon ion radiotherapy for inoperable pediatric osteosarcoma (PubMed)

Carbon ion radiotherapy for inoperable pediatric osteosarcoma Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments.Twenty-six patients aged 11-20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions (...) patients (except 1) were able to ambulate after CIRT.CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments.We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014.

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2018 Oncotarget

138. TIMP3 Overexpression Improves the Sensitivity of Osteosarcoma to Cisplatin by Reducing IL-6 Production (PubMed)

TIMP3 Overexpression Improves the Sensitivity of Osteosarcoma to Cisplatin by Reducing IL-6 Production Osteosarcoma is the most common bone cancer in children and adolescents. Tissue inhibitors of metalloproteinases (TIMPs)-3 inhibit matrix metalloproteinases to limit extracellular matrix degradation. Cisplatin is a widely used chemotherapeutic drug used to cure osteosarcoma. Interleukin (IL)-6 and TIMP3 play important roles in the drug resistance of osteosarcoma; however, their relationship (...) in this process remains unclear. This study aimed to explore the role of TIMP3 in the cisplatin sensitivity of osteosarcoma and its underlying molecular mechanisms in vitro and in vivo. We compared TIMP3 expression levels between patients with cisplatin-sensitive and -insensitive osteosarcoma. TIMP3 was overexpressed or knocked down in the Saos2-lung cell line, which is a Saos2 subtype isolated from pulmonary metastases that has higher cisplatin chemoresistance than Saos2 cells. IL-6 expression, cell

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2018 Frontiers in genetics

139. MicroRNA-183 suppresses the vitality, invasion and migration of human osteosarcoma cells by targeting metastasis-associated protein 1 (PubMed)

MicroRNA-183 suppresses the vitality, invasion and migration of human osteosarcoma cells by targeting metastasis-associated protein 1 The aim of the present study was to investigate the effects of microRNA (miR)-183 on vitality, invasion, metastasis and apoptosis in osteosarcoma (OS) cells, mediated by its binding to metastasis-associated protein 1 (MTA1). A dual luciferase reporter assay was performed to determine whether MTA1 was a direct target of miR-183. Cell Counting Kit-8, Transwell

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2018 Experimental and therapeutic medicine

140. Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma (PubMed)

Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma Circular RNA (circRNA) is associated with human cancers, however, few studies have reported its value in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we investigated the expression level of eight selected cancer-related circRNAs including circ-Cdr1as, circ_HIPK3 and circ-ITCH in OS cell lines, tissues and plasmas by quantitative real-time polymerase

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2018 Journal of Cancer

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