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Osteosarcoma

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121. Clinical Significance of G Protein-Coupled Receptor 110 (GPR110) as a Novel Prognostic Biomarker in Osteosarcoma (PubMed)

Clinical Significance of G Protein-Coupled Receptor 110 (GPR110) as a Novel Prognostic Biomarker in Osteosarcoma BACKGROUND G protein-coupled receptor 110 (GPR110) belongs to the subfamily of the adhesion G protein-coupled receptors (GPCRs). The potential role of GPR110 has been correlated with cancer cell invasion in some tumors such as glioma. However, its expression and role in human osteosarcoma has not been identified. This study aimed to examine the expression level of GPR110 (...) and determine whether the expression of GPR110 was correlated with aggressive clinicopathological characteristics and prognosis of osteosarcoma. MATERIAL AND METHODS This retrospective study included 94 osteosarcoma patients. Immunohistochemistry staining and quantitative real-time polymerase chain reaction were performed to detect the expression level of GPR110 in osteosarcoma specimens. We then determined the correlation of the GPR110 expression with the clinicopathological characteristics and prognosis

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2018 Medical science monitor : international medical journal of experimental and clinical research

122. miR-141-3p is a key negative regulator of the EGFR pathway in osteosarcoma (PubMed)

miR-141-3p is a key negative regulator of the EGFR pathway in osteosarcoma Many studies have used miRNA to modulate osteosarcoma development by regulating protein expression, and these studies showed that the expression of EGFR is increased in osteosarcoma.Western blot, real-time PCR and immunohistochemical were used to detect the expression of EGFR and miR-141 in osteosarcoma tissues and cells. The correlation between miR-141 and the grading of osteosarcoma and the correlation (...) on cell migration was detected by Transwell. The regulatory effects of miR-141 on related proteins were detected by western blot and real-time PCR. Finally, we transfected EGFR and EGFR DEL (mutation with miR-141 binding site) in osteosarcoma cells, and detected the effects of miR-141 on cell proliferation, apoptosis, migration and related proteins.The expression of miR-141-3p was negatively correlated with the expression of EGFR in osteosarcoma. The overexpression of miR-141-3p was not only closely

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2018 OncoTargets and therapy

123. Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma (PubMed)

Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma Osteosarcoma accounts for roughly 60% of all malignant bone tumors in children and young adults. The five-year survival rate for localized tumors after surgery and chemotherapy is approximately 70% whilst it drastically reduces to 15-30% in metastatic cases. Metabolic modulation is known to increase sensitivity of cancers to chemotherapy. A novel treatment strategy in Osteosarcoma is needed (...) to battle this devastating malady.Electroporation-delivered metabolic modulators were more effective in halting the cell cycle of Osteosarcoma cells and this negatively affects their ability to recover and proliferate, as shown in colony formation assays. Electroporation-delivered metabolic modulators increase the sensitivity of Osteosarcoma cells to chemotherapy and this combination reduces their survivability.This novel treatment approach highlights the efficacy of electroporation in the delivery

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2018 Oncotarget

124. Micrometastatic Drug Screening Platform Shows Heterogeneous Response to MAP Chemotherapy in Osteosarcoma Cell Lines. (PubMed)

Micrometastatic Drug Screening Platform Shows Heterogeneous Response to MAP Chemotherapy in Osteosarcoma Cell Lines. Approximately 80% of patients with osteosarcoma harbor subclinical pulmonary micrometastases at diagnosis. Conventional chemotherapy includes methotrexate, doxorubicin, and cisplatin (MAP); however, this regimen and thus overall survival (60%-70%) have remained largely unchanged for 30 years. It therefore is necessary to identify novel therapeutics targeting the metastatic (...) progression of osteosarcoma.This laboratory study explored application of osteosarcoma spheroids (sarcospheres) for drug screening with the following purposes: (1) to characterize sarcosphere size; (2) to establish accurate measurement of sarcosphere growth; (3) to confirm sarcosphere uniformity; and (4) to apply the platform to evaluate MAP chemotherapy.Sarcospheres were first characterized to establish accurate measurement of sarcosphere growth and uniform production. The refined platform

2018 Clinical Orthopaedics and Related Research

125. Activation of TNF-α/NF-κB axis enhances CRL4B<sup>DCAF</sup><sup>11</sup> E3 ligase activity and regulates cell cycle progression in human osteosarcoma cells. (PubMed)

Activation of TNF-α/NF-κB axis enhances CRL4BDCAF11 E3 ligase activity and regulates cell cycle progression in human osteosarcoma cells. Cullin 4B, a member of the Cullins, which serve as scaffolds to facilitate the assembly of E3 ligase complexes, is aberrantly expressed in many cancers, including osteosarcoma. Recently, we observed that CUL4B forms the CRL4BDCAF11 E3 ligase, which specifically ubiquitinates and degrades the cyclin-dependent kinase (CDK) inhibitor p21Cip1 (...) in human osteosarcoma cells. However, the underlying mechanisms regarding the aberrant expression of CUL4B and the upstream members of this signaling pathway are mostly unknown. In this study, we demonstrate that nuclear factor kappaB (NF-κB) is a direct modulator of CUL4B expression. The CUL4B promoter is responsive to several NF-κB subunits, including RelA, RelB, and c-Rel, but not to p50 or p52. Additional studies reveal that the tumor necrosis factor alpha (TNF-α)/NF-κB axis pathway is activated

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2018 Molecular oncology

126. Prognostic Value of Metabolic and Volumetric Parameters of FDG PET in Pediatric Osteosarcoma: A Hypothesis-generating Study. (PubMed)

Prognostic Value of Metabolic and Volumetric Parameters of FDG PET in Pediatric Osteosarcoma: A Hypothesis-generating Study. Purpose To preliminarily assess the potential prognostic value of various fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters before, during, and after neoadjuvant chemotherapy (NCT). Materials and Methods Thirty-four patients with osteosarcoma were enrolled prospectively from 2008 to 2012 and underwent FDG PET/computed tomography (CT (...) at baseline, interim, or posttherapy were independently predictive of EFS and OS. In particular, baseline MTV was an independent predictor of EFS (hazard ratio, 5.0 [95% confidence interval {CI}: 1.5, 16.8]) and OS (hazard ratio, 29.4 [95% CI: 2.2, 392.2]). Conclusion SUVpeak, MTV, and TLG either at baseline, interim, or posttherapy were predictive of EFS and OS and may be useful prognostic biomarkers for osteosarcoma. © RSNA, 2018 Online supplemental material is available for this article.

2018 Radiology

127. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma.EURAMOS-1 was an open-label (...) , international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial

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2016 EvidenceUpdates

128. Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study

Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved (...) studies (100). Please remove one or more studies before adding more. Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study (Micros) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov

2018 Clinical Trials

129. Pulmonary Resectable Metastases of Osteosarcoma With Apatinib and CHemotherapy

Pulmonary Resectable Metastases of Osteosarcoma With Apatinib and CHemotherapy Pulmonary Resectable Metastases of Osteosarcoma With Apatinib and CHemotherapy - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more (...) . Pulmonary Resectable Metastases of Osteosarcoma With Apatinib and CHemotherapy (PROACH) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT03742193 Recruitment Status : Recruiting First Posted : November 15, 2018 Last Update

2018 Clinical Trials

130. Combination of gemcitabine and docetaxel: a regimen overestimated in refractory metastatic osteosarcoma? (PubMed)

Combination of gemcitabine and docetaxel: a regimen overestimated in refractory metastatic osteosarcoma? The combination of gemcitabine and docetaxel (GT) has been demonstrated to be effective against various types of solid tumors, including sarcoma. However, the regimen has not been confirmed in large, well-designed clinical trials in refractory metastatic osteosarcoma.We retrospectively reviewed the records of patients with refractory metastatic osteosarcoma at Peking University People's (...) was disappointing with an ORR of 0%, a DCR of 9.6%, and a median DOR of 3.5 months. Grade 3 or 4 toxicities were observed in 69 (39.7%) courses and in 28 (53.8%) patients, most of which were myelosuppression, especially thrombocytopenia. No fatal adverse effect (AE) was found.The combination of gemcitabine and docetaxel (GT) as a salvage regimen is well-tolerated but not as effective as expected in refractory metastatic osteosarcoma. This report highlights the need for the development of new approaches

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2018 BMC Cancer

131. Platelet-derived TGF-β induces tissue factor expression via the Smad3 pathway in osteosarcoma cells. (PubMed)

Platelet-derived TGF-β induces tissue factor expression via the Smad3 pathway in osteosarcoma cells. Over the last three decades, the prognosis of osteosarcoma has remained unchanged; the prognosis for patients with lung metastasis is still poor, and the development of new treatments is urgently required. We previously showed that aggressive osteosarcoma cells express more tissue factor (TF) and demonstrate enhanced extrinsic pathway capacity. Furthermore, tumor growth can be suppressed (...) with the anticoagulant low molecular weight heparin. However, the molecular mechanisms underlying TF regulation are still unclear. Here, we report that transforming growth factor-β (TGF-β) upregulates TF, which can occur via activated platelets. TF was found to be expressed on osteosarcoma cell surfaces, which mediated the production of Xa and thrombin. TF induction by TGF-β was observed in several osteosarcoma cells, and especially in MG 63 cells. Both TF expression by TGF-β and extrinsic pathway activity through

2018 Journal of Bone and Mineral Research

132. Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis. (PubMed)

Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis. Low-grade osteosarcoma (LGOS) encompasses low-grade central osteosarcoma (LGCOS) and parosteal osteosarcoma (POS). LGOSs are characterized by a supernumerary ring and giant rod chromosomes containing the 12q13-15 amplicon. The fibroblast growth factor receptor substrate 2 (FRS2) gene is located close to MDM2 and CDK4. Recent studies identified consistent (...) of the 22 LGOSs were described. Amplification of FRS2 was detected in 21/22 (95%) of the LGOSs, including 3 (100%) LGCOSs and 18 (95%) POSs. All 22 LGOSs showed MDM2 amplification (100%). The only MDM2/FRS2 LGOS was dedifferentiated POS (the dedifferentiated component was conventional osteosarcoma). In the control group, all of the atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcomas (DDLs) (10/10, 100%) were FRS2-amplified, whereas the remaining 75 control cases were

2018 American Journal of Surgical Pathology

133. Extracellular Vesicle RNA Sequencing Reveals Dramatic Transcriptomic Alterations Between Metastatic and Primary Osteosarcoma in a Liquid Biopsy Approach. (PubMed)

Extracellular Vesicle RNA Sequencing Reveals Dramatic Transcriptomic Alterations Between Metastatic and Primary Osteosarcoma in a Liquid Biopsy Approach. Osteosarcoma (OS) is a highly metastasizing bone malignancy despite wide surgical resection of the primary lesion. A liquid biopsy approach to detect residual disease and identify therapeutic targets is still lacking. In this report, we aimed to track the metastasis of OS via extracellular vesicle (EV) RNA profiling in a non-invasive manner.We

2018 Annals of Surgical Oncology

134. The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients. (PubMed)

The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients. Cisplatin is one of the major drugs that used in the treatment of osteosarcoma. Cisplatin exerts its function by making cisplatin-DNA adducts culminating in cellular death. These adducts found to be repaired by nucleotide excision repair (NER) pathway. This study aimed to evaluate if polymorphisms in two main genes in the NER pathway, excision repair cross-complementing group 1 (...) and 2 (ERCC1 and ERCC2) could affect the histological response to cisplatin based chemotherapy or clinical outcomes, particularly, event free survival (EFS) and overall survival (OS) rates.ERCC1 (C118T (rs11615) and C8092A (rs3212986)) and ERCC2 (A751C (rs171140) and G312A (rs1799793)) polymorphisms were analysed in 44 patients with osteosarcoma, who were treated with cisplatin based neoadjuvant chemotherapy. DNA was extracted from patient's formalin-fixed paraffin-embedded (FFPE) samples, patient's

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2018 BMC Medical Genetics

135. Possible roles of genetic variations in chemotherapy related cardiotoxicity in pediatric acute lymphoblastic leukemia and osteosarcoma. (PubMed)

Possible roles of genetic variations in chemotherapy related cardiotoxicity in pediatric acute lymphoblastic leukemia and osteosarcoma. The treatment of acute lymphoblastic leukemia (ALL) and osteosarcoma (OSC) is very effective: the vast majority of patients recover and survive for decades. However, they still need to face serious adverse effects of chemotherapy. One of these is cardiotoxicity which may lead to progressive heart failure in the long term. Cardiotoxicity is contributed mainly

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2018 BMC Cancer

136. Lumbar spinal canal osteosarcoma: A case report. (PubMed)

Lumbar spinal canal osteosarcoma: A case report. Osteosarcoma is a rare neoplasm in the lumbar spine. Although osteosarcoma can arise in any portion of the skeleton, it very rarely arises in the spinal canal, which accounts for <0.1% of all cases of adult sarcomas. Here, we describe a case of osteosarcoma arising in the L4-5 spinal canal.The present report describes the case of a 55-year-old female patient with osteosarcoma of the L4-5 spinal canal.The patient was initially diagnosed (...) findings, the diagnosis of osteosarcoma was confirmed by an expert pathology consultant. The patient then received chemotherapy. Postoperative follow-up at 6 months revealed no evidence of recurrent disease or residual side effects from therapy.Osteosarcoma in the L4-5 spinal canal is extremely rare and very difficult to distinguish histologically from benign nervous and fibrous tissue. This is a very valuable case, which highlights the need for orthopedic surgeons to consider this when diagnosing

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2018 Medicine

137. Predictive value of dynamic change of haemoglobin levels during therapy on treatment outcomes in patients with Enneking stage IIB extremity osteosarcoma. (PubMed)

Predictive value of dynamic change of haemoglobin levels during therapy on treatment outcomes in patients with Enneking stage IIB extremity osteosarcoma. We aimed to investigate the roles of hemoglobin (Hb) concentrations and dynamic change during treatment on outcomes of patients with extremity osteosarcoma.We retrospectively analysed 133 patients with Enneking stage IIB extremity osteosarcoma who underwent standard treatments, including univariate and multivariate analyses of patient (...) ). Patients with ΔHb > 7.6 g/L had lower 5-year OS (57.5%) than those with ΔHb ≤7.6 g/L (75.8%, P = 0.04). However, continuous Hb decrease had no prognostic effect on 5-year LMFS. Subgroup analyses showed that patients who were anaemic during pretreatment, neoadjuvant, or adjuvant chemotherapy with ΔHb ≤7.6 g/L had better outcomes than those with ΔHb > 7.6 g/L (P < 0.05, for both).Dynamic Hb decrease and ΔHb > 7.6 predicted poor5-year OS in patients with Enneking stage IIB extremity osteosarcoma. Attempts

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2018 BMC Cancer

138. Metastatic Tumor Cells Detection and Anti-Metastatic Potential with Vesicular Stomatitis Virus in Immunocompetent Murine Model of Osteosarcoma. (PubMed)

Metastatic Tumor Cells Detection and Anti-Metastatic Potential with Vesicular Stomatitis Virus in Immunocompetent Murine Model of Osteosarcoma. Sarcomas are associated with a high incidence of lung metastasis, which leads to a high-risk of cancer death. This study was performed to explore the pre-clinical theranostic potential of a novel fully functional recombinant vesicular stomatitis virus carrying imaging gene Katushka (rVSV-K), as virotherapy and circulating tumor cells (CTCs) detection (...) in the syngeneic mouse model of osteosarcoma with spontaneous pulmonary metastases. Recombinant VSV-K was generated and evaluated in vitro on human and murine osteosarcoma cells. Spontaneous osteosarcoma metastases were established in immune-competent mice by implanting subcutaneously syngeneic osteosarcoma LM8 cells. The vector was injected into the tumor-bearing mice via jugular vein either once or repeatedly. To assess effectiveness, primary tumor growth and development of lung metastasis as well

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2018 Journal of Orthopaedic Research

139. Neoadjuvant Chemotherapy Followed by Delayed Surgery: Is it Necessary for All Patients With Nonmetastatic High-Grade Pelvic Osteosarcoma? (PubMed)

Neoadjuvant Chemotherapy Followed by Delayed Surgery: Is it Necessary for All Patients With Nonmetastatic High-Grade Pelvic Osteosarcoma? Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy is the most-frequently employed strategy for patients with high-grade osteosarcoma. However, the contribution of neoadjuvant chemotherapy compared with postoperative adjuvant chemotherapy has not been tested rigorously in patients with nonmetastatic high-grade pelvic osteosarcoma.(1) Does (...) neoadjuvant chemotherapy followed by delayed surgery offer a survival benefit to patients with nonmetastatic high-grade pelvic osteosarcoma compared with immediate surgery and adjuvant chemotherapy? (2) Is the timing of chemotherapy and surgery associated with a difference in the survivorship free from local recurrence and the risk of complications? (3) Is the threshold of 90% necrosis after neoadjuvant chemotherapy appropriate to distinguish responders from nonresponders in patients with pelvic

2018 Clinical Orthopaedics and Related Research

140. MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4. (PubMed)

MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4. MicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer.We performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug

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2018 BMC Cancer

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