Evaluation of Quality of Life Using EORTC QLQ-BM22 in Patients with Bone Metastases after Treatment with Magnetic Resonance Guided Focused Ultrasound.

OBJECTIVE: To reveal the alterations in quality of life (QOL) in bone metastases patients after magnetic resonance guided focused ultrasound (MRgFUS). METHODS: This retrospective study enrolled 26 patients diagnosed with bone metastases. Patients had various primary malignant tumors and tumor lesions in different locations. All patients received MRgFUS for bone metastasis. Each focal spot sonication pulse that was applied to create energy deposition lasted 20 s and was performed at a frequency of 1.05 MHz. The visual analog scale (VAS) was used to measure pain level and the EORTC QLQ-BM22 was applied to evaluate QOL for 12 months. The lower the QLQ-BM22 score, the better the QOL of patients. RESULTS: The painful site subscale of the EORTC QLQ-BM22 was observed without significant change. Significant reductions in the functional subscales were observed after therapy compared with the baseline. The functional interference was reduced significantly during the first 12 months. From the 2-month time point onwards, the pain characteristics subscale also decreased significantly. VAS scores had decreased by 40.8% 1 month after the operation and had decreased 10.9% compared with VAS scores preoperation. Scores for pain characteristics decreased by 28.8% after the operation and the scores were still down by 10.8% 1 year after the treatment. VAS scores indicated a significant reduction in pain over the course of the research until the 12-month time point follow-up compared with the baseline. CONCLUSION: MRgFUS therapy improved the QOL of patients with bone metastasis by relieving bone pain.

Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation.

Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.

AMD3100 reduces CXCR4-mediated survival and metastasis of osteosarcoma by inhibiting JNK and Akt, but not p38 or Erk1/2, pathways in in vitro and mouse experiments.

Osteosarcoma (OS) has an unfavorable prognosis and tends to metastasize to lung tissue. Although the CXCL12-CXCR4 axis appears to affect progression and metastasis in numerous tumors, its mechanism and downstream pathways in OS remain unclear. We used western blotting and flow cytometry to detect CXCR4 and CXCR7 expression in two OS cell lines (LM8 and Dunn). An MTT assay was used to evaluate the effects of CXCL12 and AMD3100, a specific CXCR4 antagonist, on cell viability. Flow cytometry was utilized to analyze changes in apoptosis induced by serum deprivation following treatment with CXCL12 and AMD3100. A Transwell assay was used to assess cell migration in response to CXCL12 and AMD3100. Western blotting was performed to identify the phosphorylation of signaling molecules (JNK, c-Jun, Akt, p38 and Erk1/2) and expression of caspase-3 and -8, and PARP. Mouse models were employed to evaluate AMD3100 inhibition of primary OS growth and lung metastasis in vivo. CXCR4 expression was detected in LM8 but not Dunn cells, and neither cell line expressed CXCR7. The addition of CXCL12 induced the survival and migration of serum-starved CXCR4+ LM8 cells activating JNK and Akt pathways, which were abrogated by adding AMD3100. However, similar results were not observed in CXCR4- Dunn cells. CXCL12 protected LM8, but not Dunn cells, from apoptosis induced by serum deprivation by suppressing PARP cleavage, which was partly reversed by AMD3100. In a mouse model, AMD3100 reduced primary tumor growth and lung metastasis compared with the controls. Thus, the CXCL12-CXCR4 axis regulated OS survival and metastasis through the JNK and Akt pathways, and blocking them with AMD3100 was found to be a potential OS treatment.

Prognostic significance of serum lactate dehydrogenase level in osteosarcoma: a meta-analysis.

BACKGROUND: A number of studies have investigated the role of serum lactate dehydrogenase (LDH) level in patients with osteosarcoma but have yielded inconsistent and inconclusive results. Thus, we conducted a meta-analysis to assess its prognostic value more precisely. METHODS: Systematic computerized searches of PubMed, Embase and Web of Science databases were performed. The pooled hazard ratio (HR) with 95 % confidence intervals (95 % CI) of overall survival was used to assess the prognostic role of serum LDH level. RESULTS: Ten studies published between 1997 and 2013 with a total of 943 osteosarcoma patients were included. Overall, the pooled HR for all ten eligible studies evaluating high LDH level on overall survival was 1.92(95 % CI 1.53-2.40). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was some possibility of publication bias risk in the meta-analysis. CONCLUSION: This meta-analysis shows that high serum LDH level is obviously associated with lower overall survival rate in patients with osteosarcoma, and it is an effective biomarker of prognosis.

Establishing an osteosarcoma associated protein-protein interaction network to explore the pathogenesis of osteosarcoma.

BACKGROUND: The aim of this study was to establish an osteosarcoma (OS) associated protein-protein interaction network and explore the pathogenesis of osteosarcoma. METHODS: The gene expression profile GSE9508 was downloaded from the Gene Expression Omnibus database, including five samples of non-malignant bone (the control), seven samples for non-metastatic patients (six of which were analyzed in duplicate), and 11 samples for metastatic patients (10 of which were analyzed in duplicate). Differentially expressed genes (DEGs) between osteosarcoma and control samples were identified by packages in R with the threshold of |logFC (fold change)| > 1 and false discovery rate < 0.05. Osprey software was used to construct the interaction network of DEGs, and genes at protein-protein interaction (PPI) nodes with high degrees were identified. The Database for Annotation, Visualization and Integrated Discovery and WebGestalt software were then used to perform functional annotation and pathway enrichment analyses for PPI networks, in which P < 0.05 was considered statistically significant. RESULTS: Compared to the control samples, the expressions of 42 and 341 genes were altered in non-metastatic OS and metastatic OS samples, respectively. A total of 15 significantly enriched functions were obtained with Gene Ontology analysis (P < 0.05). The DEGs were classified and significantly enriched in three pathways, including the tricarboxylic acid cycle, lysosome and axon guidance. Genes such as HRAS, IDH3A, ATP6ap1, ATP6V0D2, SEMA3F and SEMA3A were involved in the enriched pathways. CONCLUSIONS: The hub genes from metastatic OS samples are not only bio-markers of OS, but also help to improve therapies for OS.

Telangiectatic osteosarcoma: a review of literature.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma and hence its occurrence, presentation, and prognosis are poorly understood. With advancements in technology and available treatment options, the scenario of its diagnosis, management, and outcome has changed. Chemotherapy with surgery was challenged previously, but has now been proved to be beneficial. We reviewed the available literature and compared results to define the characteristics of the disease, its presentation, radiographic and pathologic features, optimal treatment, and prognosis.

Current advances in animal model of chondrosarcoma and related research.

Chondrosarcoma is a type of malignant cartilage tumor with a high local recurrence. Due to its resistance to chemo- and radiotherapy, current treatment is limited to surgical resection. Animal model is one of the most important approaches to studying this disease, although systematic reporting on its development is rare. In this review, we summarized the elements involving animal model establishment. On the basis of these elements, we further classified chondrosarcoma animal models into various types. In addition, we compared various measurements for evaluating the animal model. Finally, its specific applications were discussed.

[Screening of serum marker proteins in osteosarcoma and preliminary bioinformatic analysis on POLR3F].

OBJECTIVE: To screen potential serum marker proteins of osteosarcoma, and to make a preliminary bioinformatics analysis of RNA polymerase III polypeptide F (POLR3F). METHODS: Gene chip and SELDI-TOF MS was used to screen genes differentially expressed in osteosarcoma. The associations of potential biomarkers from SELDI data and microarray analysis were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. MATLAB was used to search transcription factors binding site in the promoter region and miRNAs binding site in 3'-UTR of POLR3F, respectively. RESULTS: 653 differentially expressed genes were found in osteosarcoma cells, while six differentially expressed protein peaks with significant statistical significances were detected by SELDI-TOF MS in patient's serum. 13 potential biomarkers for early diagnosis of osteosarcoma were screened by link-test. A conserved STAT3 binding site and a miRNA target site were found in proximal promoter regions and 3'-UTR region of POLR3F, respectively. CONCLUSIONS: Link-test is a effective method to identify osteosarcoma biomarkers from both microarray and SELDI-TOF MS database. The results confirmed that POLR3F may be a promising biomarker for early diagnosis and a therapy target of osteosarcoma.