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Osteosarcoma

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161. Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma (PubMed)

Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we (...) uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment

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2018 Bone research

162. Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment (PubMed)

Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment Osteosarcoma (OS) is the representative primary malignant bone tumor with the highest incidence. It is known that malignant phenotypes of OS, such as proliferation, invasion, and metastasis, are significantly influenced not only by characteristics of the tumor itself, but also by the surrounding microenvironment. In other words, OS is considered to utilize cells

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2018 Cell communication and signaling : CCS

163. Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma (PubMed)

Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma An estrogen (ES)-functionalized cationic liposomal system was developed and exploited for targeted delivery to osteosarcoma. Natural biocompatible chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal surface through a disulfate bond (-SS-) to confer reduction-responsive COS detachment, whereas estrogen was grafted via polyethylene (...) in physiological condition but rapidly release the payload in response to tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63, than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study showed that the multifunctional

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2018 Drug delivery

164. Regulatory mechanism of microRNA-128 in osteosarcoma tumorigenesis and evolution through targeting SASH1 (PubMed)

Regulatory mechanism of microRNA-128 in osteosarcoma tumorigenesis and evolution through targeting SASH1 Osteosarcoma, which commonly occurs in young individuals, is a type of malignant tumor of growing bones. MicroRNAs (miRNAs) have been found to be involved in various cancer-related processes. In the present study, it was reported that miRNA-128 (miR-128) was overexpressed in pathological tissues from patients with osteosarcoma. The present study investigated the possible regulatory mechanism (...) of miR-128 on the progression of osteosarcoma and offered a foundation for clinical therapeutics in osteosarcoma. First, the expressions levels of miR-128 and its target gene, SAM and SH3 domain-containing 1 (SASH1), were measured in tissues from patients with osteosarcoma, and their correlation with osteosarcoma in terms of the pathological level were examined. The effects of miR-128 on osteosarcoma cell proliferation and apoptosis were examined, and its regulation of the expression levels of SASH1

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2018 Oncology letters

165. Long non-coding RNA phosphatase and tensin homolog pseudogene 1 suppresses osteosarcoma cell growth via the phosphoinositide 3-kinase/protein kinase B signaling pathway (PubMed)

Long non-coding RNA phosphatase and tensin homolog pseudogene 1 suppresses osteosarcoma cell growth via the phosphoinositide 3-kinase/protein kinase B signaling pathway Osteosarcoma is a common type of human carcinoma, which exhibits a high metastasis and recurrence rate. Previous studies have indicated that long non-coding RNA phosphatase and tensin homolog pseudogene 1 (lnPTENP1) has tumor suppressive action by modulating PTEN expression in different types of tumor cells. However (...) , the potential mechanism by which lnPTENP1 has an effect in osteosarcoma cells remains elusive. In the present study, the role of lnPTENP1 in osteosarcoma cells was investigated and the possible mechanisms by which it functions were explored. It was revealed that lnPTENP1 transfection significantly inhibited osteosarcoma cell growth, proliferation, migration and invasion. LnPTENP1 transfection also significantly promoted apoptosis in Mg63 cells treated with tunicamycin. Further analysis revealed

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2018 Experimental and therapeutic medicine

166. Treatment of Saos-2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression (PubMed)

Treatment of Saos-2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression Diallyl trisulfide (DATS) is a natural organic sulfur compound that may be isolated from garlic and has strong anticancer activity. DATS has been demonstrated to upregulate the expression of calreticulin (CRT) in various types of human cancers, which is associated with the prognosis of cancer and its response to therapy. However, whether DATS has the same effect on human (...) osteosarcoma cells is not known. Therefore, in the present study, Saos-2 human osteosarcoma cells were cultured with different concentrations of DATS (0, 25, 50 and 100 µmol/l) for 24 h, or with 50 µmol/l DATS for different time periods (0, 12, 24 and 36 h). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescent staining were used to detect CRT mRNA and protein in the Saos-2 cells. Exposure to DATS changed the morphology and inhibited the growth

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2018 Experimental and therapeutic medicine

167. Activation of the complement system in an osteosarcoma cell line promotes angiogenesis through enhanced production of growth factors (PubMed)

Activation of the complement system in an osteosarcoma cell line promotes angiogenesis through enhanced production of growth factors There is increasing evidence that the complement system is activated in various cancer tissues. Besides being involved in innate immunity against pathogens, the complement system also participates in inflammation and the modulation of tumor microenvironment. Recent studies suggest that complement activation promotes tumor progression in various ways. Among some (...) cancer cell lines, we found that human bone osteosarcoma epithelial cells (U2-OS) can activate the alternative pathway of the complement system by pooled normal human serum. Interestingly, U2-OS cells showed less expression of complement regulatory proteins, compared to other cancer cell lines. Furthermore, the activated complement system enhanced the production of growth factors, which promoted angiogenesis of human endothelial cells. Our results demonstrated a direct linkage between the complement

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2018 Scientific reports

168. Cyclic Guanosine Monophosphate (cGMP)-Dependent Protein Kinase II Blocks Epidermal Growth Factor (EGF)/Epidermal Growth Factor Receptor (EGFR)-Induced Biological Effects on Osteosarcoma Cells (PubMed)

Cyclic Guanosine Monophosphate (cGMP)-Dependent Protein Kinase II Blocks Epidermal Growth Factor (EGF)/Epidermal Growth Factor Receptor (EGFR)-Induced Biological Effects on Osteosarcoma Cells BACKGROUND The present work was performed to detect the potential inhibitory effect of cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (PKG II) on epidermal growth factor (EGF) receptor-induced biological activity and related signal cascades in osteosarcoma cells. MATERIAL AND METHODS We (...) transfected the osteosarcoma MG-63 cell line with an adenoviral vector encoding PKG II cDNA (Ad-PKGII) and incubated the transfected cells with 250 μM 8-pCPT-cGMP to activate the PKG II. We stimulated the MG-63 cells with100 ng/ml EGF, and then detected their proliferation using a CCK-8 assay. Transwell assay was used to examine MG-63 cell migration; and Western blot analysis was used to detect expression of matrix metalloproteinase 9 (MMP-9) and activation of ERK and Akt. RESULTS Stimulating cells by 100

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

169. GFRA1: A Novel Molecular Target for the Prevention of Osteosarcoma Chemoresistance (PubMed)

GFRA1: A Novel Molecular Target for the Prevention of Osteosarcoma Chemoresistance The glycosylphosphatidylinositol-linked GDNF (glial cell derived neurotrophic factor) receptor alpha (GFRA), a coreceptor that recognizes the GDNF family of ligands, has a crucial role in the development and maintenance of the nervous system. Of the four identified GFRA isoforms, GFRA1 specifically recognizes GDNF and is involved in the regulation of proliferation, differentiation, and migration of neuronal cells (...) . GFRA1 has also been implicated in cancer cell progression and metastasis. Recent findings show that GFRA1 can contribute to the development of chemoresistance in osteosarcoma. GFRA1 expression was induced following treatment of osteosarcoma cells with the popular anticancer drug, cisplatin and induction of GFRA1 expression significantly suppressed apoptosis mediated by cisplatin in osteosarcoma cells. GFRA1 expression promotes autophagy by activating the SRC-AMPK signaling axis following cisplatin

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2018 International journal of molecular sciences

170. microRNA-338-3p inhibits proliferation, migration, invasion, and EMT in osteosarcoma cells by targeting activator of 90 kDa heat shock protein ATPase homolog 1 (PubMed)

microRNA-338-3p inhibits proliferation, migration, invasion, and EMT in osteosarcoma cells by targeting activator of 90 kDa heat shock protein ATPase homolog 1 Osteosarcoma (OS) is a rare, malignant bone tumor that primarily affects adolescents and has a high degree of malignancy and high incidence of recurrence and metastasis. Our study aimed to explore the role of miR-338-3p in OS cells.qRT-qPCR was performed to quantify miR-338-3p expression levels in OS tissue samples and in three common

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2018 Cancer cell international

171. miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by targeting FOSL2 (PubMed)

miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by targeting FOSL2 Osteosarcoma (OS) is the most common type of primary malignant bone tumor and mainly occurs in children and adolescent. Because of its early migration and invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs) play a crucial role in the occurrence and development of multiple tumors. In this study, we identified the aberrant-expression of miR-143-3p in osteosarcoma

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2018 Scientific reports

172. Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway (PubMed)

Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway Osteosarcoma is the most common high-grade human primary malignant bone sarcoma with lower survival in the past decades. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been proved to possess potent anti-cancer effects. However, its potential mechanism still remains not fully clear nowadays. In this study, we investigated the anticancer effect of oridonin on human (...) osteosarcoma and illuminated the underlying mechanisms. In vitro, oridonin inhibited the cell viability of various osteosarcoma cells. We demonstrated that oridonin induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (MMP), triggering reactive oxygen species (ROS) generation and activating caspase-3 and caspase-9 cleavage in MG-63 and HOS cells. Moreover, we found that oridonin triggered ROS by inhibiting NF-E2-related factor 2 (Nrf2) pathway

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2018 Cell death & disease

173. Positively selected enhancer elements endow osteosarcoma cells with metastatic competence (PubMed)

Positively selected enhancer elements endow osteosarcoma cells with metastatic competence Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung (...) metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs). Met-VELs drive coordinated waves of gene expression during metastatic colonization of the lung. Met-VELs cluster nonrandomly in the genome, indicating that activity of these enhancers and expression of their associated gene targets are positively selected. As evidence of this causal association, osteosarcoma lung metastasis is inhibited by global interruptions of Met-VEL-associated

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2018 Nature medicine

174. Sodium butyrate has anti-proliferative, pro-differentiating, and immunomodulatory effects in osteosarcoma cells and counteracts the TNFα-induced low-grade inflammation (PubMed)

Sodium butyrate has anti-proliferative, pro-differentiating, and immunomodulatory effects in osteosarcoma cells and counteracts the TNFα-induced low-grade inflammation Butyrate, an essential factor for colonocytes and regulator in the development of colon cancer, is partially absorbed by the gut. It influences the proliferation and differentiation of several cell types including osteoblasts. We evaluated the effects of different doses of butyrate on differentiation and functionality (...) of osteosarcoma cells in vitro and the expression of a pro-inflammatory phenotype in a normal or inflammatory environment. SaOS-2 osteosarcoma cells were induced to differentiate and contemporarily treated for 24 h, 48 h, or 7 days with sodium butyrate 10-4, 5 × 10-4, or 10-3 M in the presence or absence of tumor necrosis factor alpha (TNFα) 1 ng/mL, a pro-inflammatory stimulus. Despite the mild effects on proliferation and alkaline phosphatase activity, butyrate dose- and time-dependently induced

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2018 International journal of immunopathology and pharmacology

175. Long non-coding RNA RAB11B-AS1 prevents osteosarcoma development and progression via its natural antisense transcript RAB11B (PubMed)

Long non-coding RNA RAB11B-AS1 prevents osteosarcoma development and progression via its natural antisense transcript RAB11B Long non-coding RNAs (lncRNAs) have been shown to exert essential roles in development and progression of tumors. Here we discovered a novel lncRNA, RAB11B antisense RNA (RAB11B-AS1), which is markedly down-regulated in human osteosarcoma (OS) and associated with OS metastasis and poor prognosis. We find that reduction of RAB11B-AS1 significantly facilitates proliferation (...) through antisense pairing. Most importantly, all the effects of RAB11B-AS1 were abrogated by RAB11B down-regulation. Thus our findings revealed that lnc-RAB11B-AS1 prevents osteosarcoma development and progression via inhibiting RAB11B expression, indicating lnc-RAB11B-AS1 as a potential therapeutic target for osteosarcoma.

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2018 Oncotarget

176. To Explore the Mechanism of the GRM4 Gene in Osteosarcoma by RNA Sequencing and Bioinformatics Approach (PubMed)

To Explore the Mechanism of the GRM4 Gene in Osteosarcoma by RNA Sequencing and Bioinformatics Approach BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells (...) in the four significant enrichment pathways might participate in the development and progression of osteosarcoma through GRM4. The results revealed that EGR1 and CTCF are probably involved in the transcriptional regulation of GRM4, which participates in the progress of osteosarcoma by interacting with chemokines and their receptors.

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2018 Medical science monitor basic research

177. Aerosol Gemcitabine after Amputation Inhibits Osteosarcoma Lung Metastases but Not Wound Healing (PubMed)

Aerosol Gemcitabine after Amputation Inhibits Osteosarcoma Lung Metastases but Not Wound Healing In newly diagnosed osteosarcoma (OS) patients, the time between surgery and resumption of chemotherapy is 2-7 weeks. Delays > 16 days are associated with increased risk of relapse and decreased overall survival. Identifying an effective therapy that can be used postoperatively may prevent relapse. We investigated whether aerosol gemcitabine (GCB) initiated after tumor resection inhibited the growth

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2018 Sarcoma

178. Homeobox C10 knockdown suppresses cell proliferation and promotes cell apoptosis in osteosarcoma cells through regulating caspase 3 (PubMed)

Homeobox C10 knockdown suppresses cell proliferation and promotes cell apoptosis in osteosarcoma cells through regulating caspase 3 Homeobox (HOX) genes and their protein products have been found to function as oncogenes in the progression of many cancers. But the role of Homeobox C10 (HOXC10) in osteosarcoma (OS) still remains less understood. In this study, we firstly determine the biologic functions of HOXC10 in OS.We examined the expression of HOXC10 in OS tissues by quantitative real-time

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2018 OncoTargets and therapy

179. Osteosarcoma: Accelerating Progress Makes for a Hopeful Future (PubMed)

Osteosarcoma: Accelerating Progress Makes for a Hopeful Future Patients who develop osteosarcoma in 2017 receive treatment that remains essentially unchanged since the 1970s. Outcomes likewise remain largely unimproved. Large, collaborative, multinational efforts to improve therapy have evaluated strategies leveraging both cytotoxic intensification and immunomodulatory agents. While these have confirmed our capacity to conduct such trials, results have proved largely disappointing. This has (...) motivated efforts to focus on the basic biology of osteosarcoma, where understanding remains poor but has improved significantly. Recent advances have identified characteristic genetic features of osteosarcoma, including profound chromosomal disruption, marked patient-patient heterogeneity, and a paucity of recurrent mutations. Analyses suggest genesis in early catastrophic genetic events, although the nature of the inciting events remains unclear. While p53 and Rb inactivation occurs in most

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2018 Frontiers in oncology

180. Iatrogenic seeding of osteosarcoma in a tracheotomy tract – a case report (PubMed)

Iatrogenic seeding of osteosarcoma in a tracheotomy tract – a case report Here, we describe the first reported case of osteosarcoma occurring postsurgically in a tracheotomy tract, highlighting the possibility of osteosarcoma seeding during head and neck surgery. Preventative measures such as performing the tracheostomy after the tumor resection while walling off the tracheostomy site from the operative field should be considered.

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2018 Clinical Case Reports

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