SNHG9/miR-214-5p/SOX4 feedback loop regulates osteosarcoma progression.

Osteosarcoma (OS) is a high-grade, aggressive bone sarcoma. LncRNAs play a key regulatory role in controlling biological and pathological processes. The expression of lncRNA SNHG9 varies among different cancer tissues, and the role of SNHG9 in OS progression is unclear. In this study, we found SNHG9 overexpression in OS tissues and cells. In addition, downregulated SNHG9 expression impaired the proliferation, migration, and invasion abilities of OS cells. SNHG9 expression was positively regulated by the transcription factor SOX4. SNHG9 interacted with miR-214-5p as a molecular sponge and SOX4 was identified as the target of miR-214-5p. The interaction affected the expression of SNHG9, miR-214-5p, and SOX4, and regulated OS cell proliferation, migration, and invasion. Therefore, the SNHG9/miR-214-5p/SOX4 feedback loop performs an important role in OS progression and might be used as a new potential therapeutic target for the treatment of OS.

The efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis. METHODS: Designed as a retrospective study, a total of 105 metastatic osteosarcoma patients who progressed after standard therapy were included in this study. The metastatic osteosarcoma patients received 500-750 mg Apatinib mesylate according to body surface area until disease progression or unacceptable toxicity with 28 days one cycle. Overall response was evaluated after two cycles Apatinib treatment, then progression-free survival (PFS) and overall survival (OS) were evaluated, and safety data were recorded. Additionally. peripheral blood and peripheral blood mononuclear cell (PBMC) specimens in the osteosarcoma patients were collected for the genotyping of VEGFR2 genetic variation and mRNA expression, respectively. Analysis on the association between genotype and baseline characteristics and VEGFR2 gene mRNA expression was analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis. RESULTS: The objective response rate (ORR) of the 105 metastatic osteosarcoma patients was 37.14%, disease control rate (DCR) was 77.14%, median PFS was 4.1 months, and median OS was 9.0 months. Regarding the VEGFR2 gene polymorphisms analysis, only - 906 T > C was of clinical significance. The prevalence of - 906 T > C in VEGFR2 among the study population was as follows: TT genotype 62 cases (59.05%), TC genotype 36 cases (34.29%) and CC genotype 7 cases (6.66%), minor allele frequency of - 906 T > C was 0.24. Compared with patients with TC/CC genotype, patients with TT genotype showed longer median PFS (5.0 versus 3.1 months, P = 0.011) and median OS (9.8 versus 7.6 months, P = 0.032). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression in 69 randomly selected sample indicated that the mRNA expression of VEGFR2 of the patients with CC/TC genotypes were significantly higher than those of the TT genotype patients (P < 0.001). CONCLUSION: Apatinib was safe and effective in the treatment of metastatic osteosarcoma patients who progressed after standard therapy. The clinical outcomes of Apatinib may be influenced by the polymorphism - 906 T > C of VEGFR2 through mediating the mRNA expression of VEGFR2.

A type of block withholding delay attack and the countermeasure based on type-2 fuzzy inference.

We proposed a new type of bitcoin withholding attack named block withholding delay (BWD). It is different from the traditional withholding attacks which always drop valid blocks. BWD attackers never discard blocks but they delay the submissions of blocks to the pool managers, resulting the pool failed in the mining competitions and loss of rewards. We analyzed the optimum strategy of a BWD attacker who split its computing power into two parts, one was utilized to launch BWD attacks on the victim pools, while the other part was used for solo mining. We present detailed quantitative analysis of the maximum incentive that an attacker can earn by carefully splitting its computing power, and demonstrated that the attacker can obtain higher incentives than its contribution to the network in different conditions. Furthermore, we proposed a countermeasure against BWD based on the interval type-2 Takagi-Sugeno-Kang fuzzy inference system (IT2-TSK-FIS). The principle is to modify the private payoff scheme of pools to increase the risk of losing revenues of the rogue miners who deliberately delay block submissions. The scheme dealing the uncertain cause of block delay using fuzzy inference, and it is so designed that it does not require modifications of public mining protocols or data structures of the bitcoin network, which makes it applicable in practical pools.

Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in sacral chordoma.

Sacral chordoma is a vessel-rich and infiltrative tumor, but the fundamental knowledge of its biological behavior remains unknown. This study was designed to investigate the expression levels and contributions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the angiogenesis and recurrence of sacral chordoma and their correlations. An immunohistochemical method was used to investigate the expression of VEGF, MMP-9, and microvascular density (MVD) in 36 patients with sacral chordoma. Their differences in expressions were statistically analyzed and their correlations with angiogenesis and recurrence were evaluated. The mean MVD of sacral chordomas was significantly higher than that of the adjacent normal tissues (P = 0.033). Immunoreactivity for VEGF and MMP-9 was significantly higher in sacral chordoma tissues than in adjacent normal tissues (P = 0.008, P = 0.005). The mean MVD of VEGF and MMP-9 were statistically higher in positive group than in negative group (P = 0.015, P = 0.004), respectively . Moreover, a significant correlation was found between the VEGF and MMP-9 (P = 0.002). The log-rank test revealed that continuous disease-free survival time (CDFS) was significantly shorter in the MMP-9-positive group than in the MMP-9-negative group (P = 0.019), but the difference in the VEGF-positive group and the VEGF-negative group was not statistically significant (P = 0.938). Our data suggest that VEGF and MMP-9 might act with a synergistic effect and can positively regulate the angiogenesis in sacral chordoma. Positive expression of MMP-9 might indicate the local recurrence of sacral chordoma. The result suggests that some specific drugs which inhibit VEGF, MMP-9, or their receptors may have a good therapeutic effect for sacral chordoma.

Pre-operative transarterial embolization for treatment of primary sacral tumors.

Pre-operative embolization of hypervascular spinal tumors can be helpful in tumour resection; however, few studies have been reported on its effectiveness in sacral tumors. We aimed to investigate the value of surgical excision with pre-operative transarterial embolization for primary sacral tumors and evaluate the long-term follow-up outcomes. Data were obtained from a consecutive series of 60 patients (33 female, 27 male) who had sacral tumors and who, between 1992 and 2007, underwent surgical excision in conjunction with arterial embolization. The evaluation parameters included intraoperative blood loss, transfusion, treatment, local recurrence and complications associated with surgery. All tumor masses were resected without intraoperative shock or death. The mean intraoperative blood loss was 1168.3mL (range: 200-5700mL) and the mean transfusion amount was 5.2 units (range: 0-35 units). Radical wide excision was performed on eight patients, marginal excision was conducted for 34 patients and intralesional excision was undertaken for the remaining 18 patients. The mean follow-up period was 75.2months (range: 15-180months). Nineteen (31.7%) patients developed local recurrences. Of the patients who had at least the second sacral roots and the unilateral S3 preserved, 33 (84.6%) had normal bladder function and 34 (87.2%) had normal bowel control. Pre-operative arterial embolization may significantly reduce the likelihood of intraoperative hemorrhage, and has the potential to assist surgeons in completing tumor resection and improving the outcomes for these patients.

Review of current treatment of sacral chordoma.

Chordoma is a relatively rare, locally aggressive tumor which is known to arise from embryonic remnants of the notochord and to occur exclusively along the spinal axis, with a predilection for the sacrum. Although chordoma typically presents as a single lesion, a few cases of metastasis have been reported and the prognosis of such patients may be poor. Chordomas are slowly growing tumors with insidious onset of symptoms, making early diagnosis difficult. Recent improvements in imaging have provided valuable information for early diagnosis. The optimal treatment for sacral chordoma is en bloc sacral resection with wide surgical margins. Improvement in surgical techniques has widened the opportunities to provide effective treatment. However, the effects of adjuvant treatment options are still both unclear and controversial. Substantial progress has been made in the study of molecular-targeted therapy. The authors review the current surgical and adjuvant treatment modalities, including molecular-targeted therapy, available for management of sacral chordoma.