Recurrent lumbar disc herniation (rLDH) is a common complication following primary discectomy. This systematic review aimed to investigate the current evidence on risk factors for rLDH.Cohort or case-control studies addressing risk factors for rLDH were identified by search in Pubmed (Medline), Embase, Web of Science, and Cochrane library from inception to June 2015. Relevant results were pooled to give overall estimates if possible. Heterogeneity among studies was examined and publication bias was also assessed.A total of 17 studies were included in this systematic review. Risk factors that had significant relation with rLDH were smoking (OR 1.99, 95% CI 1.53–2.58), disc protrusion (OR 1.79, 95% CI 1.15–2.79), and diabetes (OR 1.19, 95% CI 1.06–1.32). Gender, BMI, occupational work, level, and side of herniation did not correlate with rLDH significantly.Based on current evidence, smoking, disc protrusion, and diabetes were predictors for rLDH. Patients with these risk factors should be paid more attention for prevention of recurrence after primary surgery. More evidence provided by high-quality observational studies is still needed to further investigate risk factors for rLDH.
Rationale: Extracellular vesicles (EVs) have emerged as novel mediators of cell-to-cell communication that are capable of the stable transfer of therapeutic microRNAs (miRNAs), and thus, EVs hold immense promise as a miRNA delivery system for cancer therapy. Additionally, as miRNA-containing EVs are secreted into circulation, miRNAs contained within plasma EVs may represent ideal biomarkers for diseases. The objective of this study was to characterize a potential tumor suppressor miRNA, miR-101, and explore the potential of miR-101 delivery via EVs for in vivo therapy of metastatic osteosarcoma as well as the potential value of plasma EV-packaged miR-101 (EV-miR-101) level for predicting osteosarcoma metastasis.Methods: The relationship of miR-101 expression and osteosarcoma progression was investigated in osteosarcoma specimens by in situ hybridization (ISH), and the potential inhibitory effect of miR-101 was further investigated using in vivo models. Using prediction software analysis, the mechanism of action of miR-101 in osteosarcoma was explored using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting and dual-luciferase assay. Adipose tissue-derived mesenchymal stromal cells (AD-MSCs) were transduced with lentiviral particles to obtain miR-101-enriched EVs. A Transwell assay and lung metastasis models of osteosarcoma were used to observe the effect of miR-101-enriched EVs on osteosarcoma invasiveness and metastasis. Detection of plasma EV-miR-101 levels was carried out in osteosarcoma patients and healthy controls by qRT-PCR.Results: miR-101 expression was markedly lower in metastatic osteosarcoma specimens compared to non-metastatic specimens. Significantly fewer metastatic lung nodules were formed by Saos-2 cells overexpressing miR-101 and SOSP-9607 cells overexpressing miR-101 injected into mice. With increased miR-101 expression, B cell lymphoma 6 (BCL6) mRNA and protein expression levels were reduced, and miR-101 was found to exert its effects by directly targeting BCL6. AD-MSCs were successfully engineered to secrete miR-101-enriched EVs. Once taken up by osteosarcoma cells, these EVs showed suppressive effects on cell invasion and migration in vitro, and systemic administration of these EVs effectively suppressed metastasis in vivo with no significant side effects. Finally, the EV-miR-101 level was lower in osteosarcoma patients than in healthy controls and even lower in osteosarcoma patients with metastasis than in those without metastasis.Conclusion: Our data support the function of miR-101 as a tumor suppressor in osteosarcoma via downregulation of BCL6. AD-MSC derived miR-101-enriched EVs represent a potential innovative therapy for metastatic osteosarcoma. EV-miR-101 also represents a promising circulating biomarker of osteosarcoma metastasis.
Giant cell tumors of the bone (GCTBs) are commonly diagnosed in Asian populations, usually around the knee. Herein, we aimed to determine the clinical characteristics, local recurrence rates, and relevant risk factors of primary GCTB around the knee. Univariate and multivariate survival analyses were used to identify the risk factors for local recurrence. Four hundred ten patients with primary GCTB around the knee, treated between March 2000 and June 2014, were recruited from 7 institutions in China. The overall local recurrence rate was 23.4%, but was higher in patients aged 20–39 years (28.5%; P = 0.039). The local recurrence rate was the highest in patients treated with intralesional curettage (53.4%), and the lowest in those treated with resection (4.9%). We found a higher risk of tumor recurrence in the proximal fibula compared to the distal femur (hazard ratio: 28.52, 95% confidence interval: 5.88–138.39; P < 0.0001), and in patients treated with curettage compared to those treated with resection (hazard ratio: 12.07, 95% confidence interval: 4.99–29.18; P < 0.0001). Thus, the tumor location must be considered when selecting the optimal surgical treatment approach to reduce the risk of local recurrence and preserve joint function, especially in young patients.
The antitumor effects of curcumin have attracted widespread attention worldwide. One of its major functions is to induce the apoptosis of tumor cells, but the antitumor mechanism is currently unclear. In the present study, we found that cell mortality and curcumin concentration were dose dependent. Curcumin of low concentrations (10 μΜ) could reduce the level of reactive oxygen species (ROS) in tumor cells, while curcumin of high concentrations (80 μΜ) was able to significantly increase the content of ROS. In addition, Western blotting detection suggested that curcumin of high concentrations can induce the release of Cyto-C and the activation of Caspase-3, and that ROS scavenger NAC apparently inhibits apoptosis protein release and activation, consequently slowing the curcumin-induced apoptosis. Taken together, curcumin further activates the mitochondrial apoptotic pathway by inducing cells to generate ROS and ultimately promotes the apoptosis of tumor cells.
These findings indicate that surgical correction of adolescent idiopathic scoliosis in eligible patients can lead not only to curve correction, but also to an increase self-esteem and life satisfaction.
Giant cell tumor (GCT) of the bone is a relatively common primary bone tumor. Treatment with simple curettage often results in a high local recurrence rate. Tumor resection and reconstruction with prosthesis or an allograft has a low rate of local recurrence; however, the patient’s native joint function becomes significantly impaired. With the development and usage of aggressive curettage, it is a priority to treat GCT with a method that reduces the local recurrence rate and preserves the native joint. To evaluate the feasibility of treating GCT with aggressive curettage and cement filling using internal fixation and oral bisphosphonates, 16 patients with GCT of the bone located in the distal femur and treated in our department from January 2008 to June 2011, were followed up. The patients had received aggressive curettage, bone cement filling, internal fixation and oral administration of bisphosphonates.There were seven males and nine females in total, with a mean age of 38 years. All patients were carefully assessed prior to surgery in order to determine the integrity of the tumor cavity. Subsequently, patients were treated with aggressive curettage by high-speed burring and cementation with internal fixation, and were administered postoperative oral alendronate sodium tablets (10 mg/day) for two years. The median follow-up time was 25 months. None of the patients were lost to follow-up. No local recurrence or metastasis was observed in the last follow-up. The Enneking limb function score range of the affected limb was 24–29 (average, 26.7). At the last follow-up, all patients exhibited solid fixation without fracture of the subchondral bone in plain radiographs. Based on these data, we suggest that patients with distal femoral GCT may be treated with aggressive curettage and cement filling, with internal fixation and oral bisphosphonates. The advantages of this method are its safety and efficacy. However, the long-term outcomes require further investigation.
BackgroundThe combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma.ResultsThe resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy.ConclusionTaken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.
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