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Osteosarcoma

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81. miR-149-5p inhibits cell growth by regulating TWEAK/Fn14/PI3K/AKT pathway and predicts favorable survival in human osteosarcoma (PubMed)

miR-149-5p inhibits cell growth by regulating TWEAK/Fn14/PI3K/AKT pathway and predicts favorable survival in human osteosarcoma MicroRNAs (miRNAs) as small non-coding RNAs act as either tumor suppressors or oncogenes in human cancers, of which miR-149-5p (miR-149) is involved in tumor growth and metastasis, but its role and molecular mechanisms underlying osteosarcoma growth are poorly understood. The correlation of miR-149 expression with clinicopathological characteristics and prognosis (...) in patients with sarcoma was analyzed by The Cancer Genome Atlas (TCGA) RNA-sequencing data. Osteosarcoma cell growth affected by miR-149 was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. As a result, we found that the expression level of miR-149 was markedly downregulated in human sarcoma samples and were negatively associated with tumor size, acting as an independent prognostic factor for overall survival of the sarcoma patients. Restoration

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2018 International journal of immunopathology and pharmacology

82. Novel lymphoid enhancer‐binding factor 1‐cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs (PubMed)

Novel lymphoid enhancer‐binding factor 1‐cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs Lung metastasis is a major cause of mortality in patients with osteosarcoma (OS). A better understanding of the molecular mechanism of OS lung metastasis may facilitate development of new therapeutic strategies to prevent the metastasis. We have established high- and low-metastatic sublines (LM8-H and LM8-L, respectively) from Dunn OS cell line LM8 by using in vivo image

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2018 Cancer science

83. Expression of Livin and PlGF in human osteosarcoma is associated with tumor progression and clinical outcome (PubMed)

Expression of Livin and PlGF in human osteosarcoma is associated with tumor progression and clinical outcome Baculoviral IAP repeat containing 7 (BIRC7/Livin/ML-IAP/KIAP; referred to as Livin throughout the present study) and placental growth factor (PlGF) are not detectable in the majority of normal differentiated tissues, but are present in a number of types of cancer, including hepatocellular carcinoma, ovarian cancer and renal cell carcinoma. The aim of the present study was to assess (...) the expression levels of Livin and PlGF in human osteosarcoma specimens and cell lines, and to analyze the functions of Livin and PIGF in the prognosis of osteosarcoma. The expression levels of Livin and PlGF in 48 osteosarcoma specimens and three osteosarcoma cells were determined using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. The positivity rates of Livin and PlGF in osteosarcoma specimens were 58.3 and 60.4%, respectively, but were 0% in normal bone tissues

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2018 Oncology letters

84. PDGF/PDGFR effects in osteosarcoma and the “add-on” strategy (PubMed)

PDGF/PDGFR effects in osteosarcoma and the “add-on” strategy New treatment options for advanced osteosarcoma have remained limited. The platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) pathway plays an important role in the development and metastasis of osteosarcoma, via either direct autocrine stimulation of tumor cells, or paracrine stimulation on tumor stromal cells. It promotes angiogenesis to overcome hypoxia in the tumor microenvironment (...) , and modulates tumor interstitial fluid pressure to control the influx and efflux of other agents. Targeting the PDGF/PDGFR pathway is a promising therapeutic method to overcome drug resistance and improve patients' outcome in osteosarcoma. Further evidence is needed to define the detailed mechanism. Results from clinical trials using PDGF/PDGFR inhibitor as a single agent were disappointing, both in osteosarcoma and soft tissue sarcoma. However, when combined with other agents, named as "add-on" strategy

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2018 Clinical sarcoma research

85. miRNA-21 inhibition inhibits osteosarcoma cell proliferation by targeting PTEN and regulating the TGF-β1 signaling pathway (PubMed)

miRNA-21 inhibition inhibits osteosarcoma cell proliferation by targeting PTEN and regulating the TGF-β1 signaling pathway The present study aimed to investigate the role of microRNA (miRNA)-21 in the growth of osteosarcoma. A total of 46 patients with osteosarcoma and 20 healthy controls were included in the study. The expression of miRNA-21 was detected by reverse transcription-quantitative polymerase chain reaction in tumor tissues and adjacent healthy tissues from patients (...) with osteosarcoma, as well as the serum of patients with osteosarcoma and the healthy controls was. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic values of serum miRNA-21 for osteosarcoma at different T stages. Survival curves plotted using the Kaplan-Meier method were used to evaluate the prognostic value. miRNA-21 knockdown osteosarcoma cell lines were established and their effects on cell proliferation were explored using a Cell Counting Kit-8 assay. The effect

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2018 Oncology letters

86. Long non-coding RNA NEAT1 promotes proliferation, migration and invasion of human osteosarcoma cells (PubMed)

Long non-coding RNA NEAT1 promotes proliferation, migration and invasion of human osteosarcoma cells Aim: Long non-coding RNAs (LncRNAs) have been identified to play a crucial role in tumorigenesis and the progression of many types of tumors. However, the clinical significance and biological function of lncRNA nuclear-enriched abundant transcript 1(NEAT1) in human osteosarcoma remains unknown. Here, we investigated the role of NEAT1 in human osteosarcoma cell lines and clinical tumor samples (...) . Methods: In this study, expression of NEAT1 was analyzed in 19 osteosarcoma tissues and paired adjacent non-tumor tissues by using quantitative real-time PCR. Additionally, knockdown of NEAT1 expression using Lentivirus-mediated siRNA was performed in order to explore the biological function of NEAT1 on osteosarcoma cell proliferation and metastasis through MTT, colony formation assay and transwell assay. Results: NEAT1 was over-expressed in osteosarcoma tissues compared with adjacent non-tumor

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2018 International journal of medical sciences

87. CSCs: regenerating optimism for osteosarcoma treatment (PubMed)

CSCs: regenerating optimism for osteosarcoma treatment 30167075 2018 11 14 1949-2553 9 60 2018 Aug 03 Oncotarget Oncotarget CSCs: regenerating optimism for osteosarcoma treatment. 31562-31563 10.18632/oncotarget.25820 Levin Adam S AS Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA. eng News Comment 2018 08 03 United States Oncotarget 101532965 1949-2553 Oncotarget. 2018 Jul 10;9(53):30163-30172 30046395 cancer stem cells osteosarcoma 2018 06 25 2018 07 16

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2018 Oncotarget

88. The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma (PubMed)

The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor; the survival is related to the response to chemotherapy and development of metastases. KMT2C is a chromatin-modifying and remodelling protein and its expression has never been studied in osteosarcoma. The aim of this study was to understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic (...) progression to identify a new molecular target and to provide new therapeutic approach. We performed the immunohistochemical and gene expression analysis of KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic-pathological data and we analysed the expression of genes involved in the metastatic pathway in four osteosarcoma cell lines by blocking the KMT2C expression using siRNA. We found a nuclear-cytoplamic trafficking of KMT2C and the cytoplasmic localization was higher than

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2018 Oncotarget

89. Analyzing the disease module associated with osteosarcoma via a network- and pathway-based approach (PubMed)

Analyzing the disease module associated with osteosarcoma via a network- and pathway-based approach Osteosarcoma is the most common type of primary malignant bone tumor observed in children and adolescents. The aim of the present study was to identify an osteosarcoma-related gene module (OSM) by looking for a dense module following the integration of signals from genome-wide association studies (GWAS) into the human protein-protein interaction (PPI) network. A dataset of somatic mutations (...) in osteosarcoma was obtained from the dbGaP database and their testing P-values were incorporated into the PPI network from a recent study using the dmGWAS bioconductor package. An OSM containing 201 genes (OS genes) and 268 interactions, which were closely associated with immune response, intracellular signal transduction and cell activity was identified. Topological analysis of the OSM identified 11 genes, including APP, APPBP2, ATXN1, HSP90B1, IKZF1, KRTAP10-1, PAK1, PDPK1, SMAD4, SUZ12 and TP53

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2018 Experimental and therapeutic medicine

90. Survival Prediction in High-grade Osteosarcoma Using Radiomics of Diagnostic Computed Tomography (PubMed)

Survival Prediction in High-grade Osteosarcoma Using Radiomics of Diagnostic Computed Tomography The poor 5-year survival rate in high-grade osteosarcoma (HOS) has not been increased significantly over the past 30 years. This work aimed to develop a radiomics nomogram for survival prediction at the time of diagnosis in HOS. In this retrospective study, an initial cohort of 102 HOS patients, diagnosed from January 2008 to March 2011, was used as the training cohort. Radiomics features were

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2018 EBioMedicine

91. A Preliminary Proteomic Investigation of Circulating Exosomes and Discovery of Biomarkers Associated with the Progression of Osteosarcoma in a Clinical Model of Spontaneous Disease (PubMed)

A Preliminary Proteomic Investigation of Circulating Exosomes and Discovery of Biomarkers Associated with the Progression of Osteosarcoma in a Clinical Model of Spontaneous Disease Circulating cancer exosomes are microvesicles which originate from malignant cells and other organs influenced by the disease and can be found in blood. The exosomal proteomic cargo can often be traced to the cells from which they originated, reflecting the physiological status of these cells. The similarities (...) between cancer exosomes and the tumor cells they originate from exhibit the potential of these vesicles as an invaluable target for liquid biopsies. Exosomes were isolated from the serum of eight osteosarcoma-bearing dogs, five healthy dogs, and five dogs with traumatic fractures. We also characterized exosomes which were collected longitudinally from patients with osteosarcoma prior and 2 weeks after amputation, and eventually upon detection of lung metastasis. Exosomal proteins fraction were

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2018 Translational oncology

92. Synergistic antitumor effect of suberoylanilide hydroxamic acid and cisplatin in osteosarcoma cells (PubMed)

Synergistic antitumor effect of suberoylanilide hydroxamic acid and cisplatin in osteosarcoma cells Cisplatin, as a first-line chemotherapy drug, has been widely applied for therapy of osteosarcoma. However, its application is limited by drug resistance and serious side effects, including nephrotoxicity and ototoxicity. Suberoylanilide hydroxamic acid (SAHA) is a newly developed histone deacetylase (HDAC) inhibitor, which is the first Food and Drug Administration-approved HDAC inhibitor (...) for the treatment of cutaneous manifestations of T-cell lymphoma. However, SAHA as a monotherapy was revealed to be limited, particularly in solid tumors. In the present study, 143B osteosarcoma cells were treated with multiple concentrations of SAHA or cisplatin, either alone or combined. The morphological characteristics of the treated cells were observed using an inverted microscope. The cytotoxicity effects of the combination of SAHA and cisplatin on 143B cells were analyzed by MTT assay, colony formation

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2018 Oncology letters

93. Isolation of circulating tumor cells in a preclinical model of osteosarcoma: Effect of chemotherapy (PubMed)

Isolation of circulating tumor cells in a preclinical model of osteosarcoma: Effect of chemotherapy Osteosarcoma is a rare primary bone tumor, which mainly affects children and adolescents and has a poor prognosis, especially for patients with metastatic disease. A poor therapeutic response to the conventional chemotherapy is observed with the development of lung metastases, highlighting the need for improving the current regimens and the identification of early markers of the recurrent (...) and metastatic disease. Circulating Tumour Cells (CTCs) play a key role in the metastatic process and could be powerful biomarkers of the progressive disease. The present study aimed to isolate CTCs by using a pre-clinical model of human osteosarcoma and to monitor their kinetic of release and their modulation by ifosfamide. CTCs were detectable into the bloodstream before any palpable primary tumors. Ifosfamide increased CTCs count and in contrast decreased the number of lung tumor nodules. On established

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2018 Journal of bone oncology

94. 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

95. 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

96. 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

97. 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

98. 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

99. 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

100. 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

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