BackgroundOsteosarcoma is the most frequent primary malignant bone tumor, notorious for its lung metastasis. Shikonin, an effective constituent extracted from Chinese medicinal herb, was demonstrated to induce necroptosis in some cancers.MethodsMTT assay was performed to detect cell survival rate in vitro. Flow cytometry was used to analyze cell cycle and cell death. Western blot was performed to determine the expression levels of RIP1, RIP3, caspase-3, caspase-6 and PARP. The tibial primary and lung metastatic osteosarcoma models were used to evaluate the anti-tumor effect of shikonin in vivo.ResultsThe cell survival rate was decreased in a dose and time dependent manner when treated with shikonin. No major change in cell cycle was observed after shikonin treatment. The cell death induced by shikonin could be mostly rescued by specific necroptosis inhibitor necrostatin-1, but not by general caspase inhibitor Z-VAD-FMK. The number of necrotic cells caused by shikonin was decreased after being pretreated with Nec-1 detected by flow cytometry in K7 cells. After 8-hour treatment of shikonin, the expression levels of RIP1 and RIP3 were increased while caspase-3, caspase-6 and PARP were not activated in K7 and U2OS cells determined by Western blot. Size of primary tumor and lung metastasis in shikonin treated group were significantly reduced. The protein levels of RIP1 and RIP3 in primary tumor tissues were increased by shikonin. The overall survival of lung metastatic models was longer compared with control group (p < 0.001).ConclusionsShikonin had prompt but profound anti-tumor effect on both primary and metastatic osteosarcoma, probably by inducing RIP1 and RIP3 dependent necroptosis. Shikonin would be a potential anti-tumor agent on the treatment of primary and metastatic osteosarcoma.

The objective of this study is to do a meta-analysis of the literature and compare the safety and efficacy of endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) for idiopathic carpal tunnel syndrome (CTS). A comprehensive literature search of the electronic databases MEDLINE, EMBASE, Google Scholar, and the Cochrane Controlled Trial Register was undertaken for randomized studies reporting carpal tunnel syndrome treated with ECTR or OCTR. The quality of randomized trials was critically assessed. Pooled relative risk (RR) and 95% confidence intervals (CIs) for safety and efficacy outcome variables were calculated by fixed-effect or random-effect methods with RevMan v.5.1 provided by the Cochrane Collaboration. A total of 13 randomized trials were included by total retrieve and riddling. The results of our meta-analysis showed no significant difference in the overall complication rate (RR = 1.34, 95% CI [0.74, 2.43], P = 0.34), subjective satisfaction (RR = 1.0, 95% CI [0.93, 1.08], P = 0.92), time to return to work (mean difference = −3.52 [−8.15, 1.10], P = 0.14), hand grip and pinch strength, and the operative time (mean difference = −1.89, 95% CI [−5.84, 2.06]) between patients in the ECTR and OCTR groups (P = 0.16, 0.70, and 0.35, respectively). The rate of hand pain (RR = 0.73, 95% CI [0.53, 0.93], P = 0.02) in the ECTR group was significantly lower than that in the OCTR group. ECTR treatment seemed to cause more reversible postoperative nerve injuries as compared with OCTR (RR = 2.38, 95% CI [0.98, 5.77], P = 0.05). Although ECTR significantly reduced postoperative hand pain, it increased the possibility of reversible postoperative nerve injury in patients with idiopathic CTS. No statistical difference in the overall complication rate, subjective satisfaction, the time to return to work, postoperative grip and pinch strength, and operative time was observed between the two groups of patients.

Bone sarcomas, which comprise less than 1% of all human malignancies, are a group of relatively rare mesenchymal-derived tumors. They are mainly composed of osteosarcoma, chondrosarcoma and Ewing's sarcoma. In spite of advances in adjuvant chemotherapy and wide surgical resection, prognosis remains poor due to the high propensity for lung metastasis, which is the leading cause of mortality in patients with bone sarcomas. Chemokines are a superfamily of small pro-inflammatory chemoattractant cytokines which can bind to specific G protein-coupled seven-span transmembrane receptors. Chemokine 12 (CXCL12), also designated as stromal cell-derived factor-1 (SDF-1), is able to bind to its cognate receptors, chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7), with high affinity. The binding of CXCL12 to CXCR4/CXCR7 stimulates the activation of several downstream signaling pathways that regulate tumor progression and metastasis. In this review, the structure and function of CXCL12 and its receptors, CXCR4 and CXCR7, as well as many factors affecting their expression are discussed. Phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are the two most important downstream pathways regulated by the CXCL12-CXCR4/CXCR7 interaction. CXCR4 expression in bone sarcomas, including tumor cells and samples and the correlation between CXCR4/CXCR7 expression and the survival of patients with bone sarcomas are also discussed. In addition, we review the involvement of the CXCL12‑CXCR4/CXCR7 axis in the growth and metastasis of bone sarcomas and the targeting of this axis in preclinical studies.