Correction to: microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

An amendment to this paper has been published and can be accessed via the original article.

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications.

BACKGROUND: The present study was designed to explore the underlying role of hypoxia-inducible factor 1α (HIF-1α) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. METHODS: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1α expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information's Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1α and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1α. We inhibited HIF-1α via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As2O3 treatment. RESULTS: Ad interim knockdown of HIF-1α also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1α silencing via siRNA. CONCLUSIONS: Our data reveal that HIF-1α inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1α inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As2O3) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

BACKGROUND: Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer. METHODS: In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis. CONCLUSIONS: Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.

En Bloc Resection of Primary Malignant Bone Tumor in the Cervical Spine Based on 3-Dimensional Printing Technology.

OBJECTIVE: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model. METHODS: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed. RESULTS: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up. CONCLUSION: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3-D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure.

Development of innovative techniques for the endoscopic implantation and securing of a novel, wireless, miniature gastrostimulator (with videos).

BACKGROUND: Gastric stimulation via high-frequency, low-energy pulses can provide an effective treatment for gastric dysmotility; however, the current commercially available device requires surgical implantation for long-term stimulation and is powered by a nonrechargeable battery. OBJECTIVE: To test and describe endoscopic implantation techniques and testing of stimulation of a novel, wireless, batteryless, gastric electrical stimulation (GES) device. DESIGN: Endoscopic gastric implantation techniques were implemented, and in vivo gastric signals were recorded and measured in a non-survival swine model (n = 2; 50-kg animals). INTERVENTION: Five novel endoscopic gastric implantation techniques and stimulation of a novel, wireless, batteryless, GES device were tested on a non-survival swine model. MAIN OUTCOME MEASUREMENTS: Feasibility of 5 new endoscopic gastric implantation techniques of the novel, miniature, batteryless, wireless GES device while recording and measurement of in vivo gastric signals. RESULTS: All 5 of the novel endoscopic techniques permitted insertion and securing of the miniaturized gastrostimulator. By the help of these methods and miniaturization of the gastrostimulator, successful GES could be provided without any surgery. The metallic clip attachment was restricted to the mucosal surface, whereas the prototype tacks, prototype spring coils, percutaneous endoscopic gastrostomy wires/T-tag fasteners, and submucosal pocket endoscopic implantation methods attach the stimulator near transmurally or transmurally to the stomach. They allow more secure device attachment with optimal stimulation depth. LIMITATIONS: Non-survival pig studies. CONCLUSION: These 5 techniques have the potential to augment the utility of GES as a treatment alternative, to provide an important prototype for other dysmotility treatment paradigms, and to yield insights for new technological interfaces between non-invasiveness and surgery.

An endoscopic wireless gastrostimulator (with video).

BACKGROUND: Gastric electric stimulation (GES) at a high-frequency, low-energy setting is an option for treating refractory gastroparesis. The currently available commercial stimulator, the Enterra neurostimulator (Medtronic Inc, Minneapolis, MN), however, requires surgical implantation and is powered by a nonrechargeable battery. OBJECTIVE: To develop and test a miniature wireless GES device for endoscopic implantation in an experimental model. DESIGN: In-vivo gastric signals were recorded and measured in a nonsurvival swine model (n = 2; 110-lb animals). INTERVENTION: An endoscopically placed, wireless GES device was inserted into the stomach through an overtube; the two GES electrodes were endoscopically attached to the gastric mucosa and secured with endoclips to permit stimulation. MAIN OUTCOME MEASUREMENTS: Stable electrogastrogram measures were observed during GES stimulation. RESULTS: Electrogastrogram recordings demonstrated that gastric slow waves became more regular and of constant amplitudes when stomach tissues were stimulated, in comparison with no stimulation. The frequency-to-amplitude ratio also changed significantly with stimulation. LIMITATION: Nonsurvival pig studies. CONCLUSION: Gastric electric stimulation is feasible by our endoscopically implanted, wireless GES device.

[Surgical intervention and radiotherapy outcome of solitary plasmacytoma of cervical spine].

OBJECTIVE: To study the clinical features, treatment methods and outcome of solitary plasmacytoma of cervical spine. METHODS: From January 1995 to December 2007, the data of 23 cases with solitary plasmacytoma of cervical spine was analyzed. There were 16 males and 7 females (mean age 56 years, range: 32 - 76 years). Two cases underwent radiotherapy alone and 21 patients received surgery. According to WBB staging system, surgical procedures were defined as total or subtotal resection (6 cases), appendix resection (4 cases), sagittal resection (3 cases) and total spondylectomy (8 cases). All surgical cases were managed using an anterior approach, posterior approach or combined anterior and posterior approach. The cervical spinal reconstruction was achieved through anterior cervical titanium plate and titanium mesh cage filled with auto iliac graft or bone cement, or anterior and posterior combined instrumented fusion. All patients received radiotherapy as adjunctive therapy. RESULTS: Follow-up of the 23 cases lasted 24.0 - 143.0 months (mean: 64.7 months). Neck pains obviously improved, and nerve compression symptoms disappeared or improved after surgery. Neurological function improved by 1 - 2 grades based on Frankel grading system. All the internal fixations were fused well and stability of the cervical spine was fine and no spine instability could be seen in our series. The bone graft fusion rate was 100%. During the follow-up period, 6 surgical cases had local recurrence and finally progressed to multiple myeloma (MM) and 3 died. Two cases without surgical treatment progressed to MM in 1 year and 1.5 years after confirmed diagnosis. They were given systemic chemotherapy. The other 15 patients had disease-free survival and after surgery and adjunctive radiotherapy. Obvious abnormity were not found in such examinations as M protein, bone marrow aspiration and emission computed tomography or PET-CT examinations. CONCLUSIONS: Solitary plasmacytoma of cervical spine is rarely seen clinically. Surgery is recommended as the primary management for patients with overt bone destruction and spinal instability or neurological dysfunction. Tumor excision with adjunctive radiotherapy can obviously reduce local recurrences and lower the possibility of progression to MM. The patients with progression to MM should receive chemotherapy according to chemotherapy protocol while the prognosis is comparatively worse.