[Research progress of Wallis dynamic stabilization system for lumbar degenerative diseases].

Wallis dynamic stabilization system is a surgical approach in the non-fusion technique of lumbar spine, consisting of interspinous blockers and dacron artificial ligaments that provide stability to the spine while maintaining a degree of motion in the affected segment. Recent studies have demonstrated the significant benefits of Wallis dynamic stabilization system in treating lumbar degenerative diseases. It not only improves clinical symptoms, but also effectively delays complications such as adjacent segmental degeneration. This paper aims to review the literature related to the Wallis dynamic stabilization system and degenerative diseases of the lumbar spine to describe the long-term prognostic effect of this system in the treatment of such diseases. This review provides a theoretical basis and reference for selecting surgical methods to treat degenerative diseases of the lumbar spine.

Melatonin and doxorubicin co-delivered via a functionalized graphene-dendrimeric system enhances apoptosis of osteosarcoma cells.

A functionalized graphene-dendrimeric system was designed via Fe3O4 nanoparticle (NP) as a magnetic nanocarrier for co-delivery of doxorubicin (DOX) and melatonin (MLT). Accordingly, ß-Cyclodextrin (ß-CD) was modified by creating amine functional groups. The modified ß-CD was grafted with Graphene oxide (GO), and the resulting platform gain many functional groups, including the hydroxyl (-OH), carboxylic acid (-COOH), and amine functional groups (-NH2). Finally, magnetic NPs were synthesized on the prepared platform to efficiently controlling and targeting drugs to tumor sites. The human osteosarcoma cell lines including Saos-2 and MG-63, as well as Human Bone Marrow Mesenchymal Stem Cells (hBM-MSC) line, were used to determine the in vitro biological effects of the functionalized graphene-dendrimeric system. The magnetic nanocarrier has encapsulation efficiency (EE) values of 99.92% for DOX and 21.5% for MLT. The biocompatibility tests of the nanocarrier revealed that the magnetic nanocarrier was appropriate as a drug carrier. Co-delivery of DOX and MLT with an efficiently anticancer performance was also was confirmed by cellular uptake, 4',6-diamidino-2-phenylindole (DAPI) staining, and apoptosis analysis in comparison with free DOX and MLT. Moreover, there was a synergy in the antitumor effect when MLT was combined with DOX, especially in the nano-formulation form, which may be due to the down-regulation of X-linked Inhibitor of Apoptosis (XIAP), survivin, and human telomerase catalytic subunit (hTERT) (p < 0.0001). Overall, the result of our study suggests that the designed carrier is a promising nanocarrier for targeted co-delivery of DOX and MLT with improved anticancer efficacy in cancer cells and thus reduced toxicity in normal cells.

Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway.

Osteosarcoma is the frequent pediatric bone cancer where pediatric osteosarcoma incidences are more than 10% within the population. Most of the patients with osteosarcoma fall within the age of 15-30 years. Therefore, in this research, we examined the anticancer effect of Rhaponticin against the human osteosarcoma (MG-63) cells. The cytotoxicity of Rhaponticin on the MC3T3-E1 and MG-63 cells was examined through the MTT assay. The intracellular ROS accumulation, cell nuclear morphological alterations, apoptotic cell death and nuclear damages, and MMP status of Rhaponticin administered MG-63 cells were inspected by fluorescent staining techniques. The cell migration was assessed through scratch assay. The mRNA expressions of PI3K-Akt-mTOR signaling proteins were studied by RT-PCR analysis. Rhaponticin showed potent cytotoxicity, substantially inhibited the MG-63 cell growth, and displayed morphological alterations. However, rhaponticin did not affect the MC3T3-E1 cell viability. Rhaponticin administered MG-63 cells demonstrated augmented intracellular ROS accretion, weakened MMP, increased nuclear damages, and increased apoptosis. Rhaponticin effectively down-regulated the PI3K-Akt-mTOR signaling cascade in the MG-63 cells. These outcomes proved that the Rhaponticin can be a hopeful chemotherapeutic agent in the future to treat human osteosarcoma.

MicroRNA-153 inhibits osteosarcoma cells proliferation and invasion by targeting TGF-ß2.

Increasing evidence indicates that microRNAs (miRNAs), a class of small noncoding RNAs, participate in almost every step of cellular processes. MiRNAs are aberrantly expressed in human cancers and contribute to cancer development and progression. Study of miRNAs may provide a new clue for understanding the mechanism of carcinogenesis and a new tool for cancer treatment. In the present study, miR-153 was downregulated in human osteosarcoma tissues and cell lines. Introduction of miR-153 mimics into the MG-63 cells inhibited cell proliferation and invasion. Our results further revealed that transforming growth factor beta 2 (TGF-ß2) was negatively regulated by miR-153. Furthermore, overexpression of miR-153 decreased p-SMAD2, p-SMAD3, epidermal growth factor receptor (EGFR) and insulin-like growth factor binding protein-3 (IGFBP-3) expressions, which were the downstream signaling molecules of TGF-ß. Furthermore, miRNA-153 suppressed TGF-ß-mediated MG-63 proliferation and migration. Therefore, our results suggest that miR-153 may act as a tumor suppressor in osteosarcoma through targeting TGF-ß2.

miR-454 is down-regulated in osteosarcomas and suppresses cell proliferation and invasion by directly targeting c-Met.

OBJECTIVES: Osteosarcoma is the most common primary bone malignancy of children and young adults. Increasing evidence has shown that microRNAs (miRNAs) are associated with cancer development, but, little is known concerning the role of miR-454 in osteosarcoma. MATERIALS AND METHODS: qRT-PCR was performed to detect expression of miR-454 in osteosarcoma cell lines and tissues. To understand its role in osteosarcoma, we reintroduced expression of miR-454 in the MG-63 cell line by transfection with miR-454 mimics or inhibitors. CCK-8 assay and an invasion assay were used to detect the functional role of miR-454. Luciferase assay and western blot analysis were performed to detect the target gene of miR-454. RESULTS: miR-454 was found to be down-regulated in osteosarcoma tissues and cell lines. Its over-expression inhibited tumour growth and invasion and its down-regulation promoted cell proliferation and invasion. Subsequent investigation revealed that c-Met was a direct and functional target of miR-454 in osteosarcoma. Overexpression of miR-454 impaired c-Met-induced cell proliferation and invasion. Finally, miR-454 was found to be inversely correlated to c-Met expression in human osteosarcoma tissues. CONCLUSIONS: Reduced-expression of miR-454 in osteosarcoma cells promoted tumour growth by targeting c-Met, thus miR-454 may be a potential therapy target for this tumour.

The prognostic significance of CD44V6, CDH11, and ß-catenin expression in patients with osteosarcoma.

This study aimed to examine the expression of and the relationship between CD44V6, CDH11, and ß-catenin. The expression of these cell adhesion molecules was detected in 90 osteosarcoma and 20 osteochondroma specimens using immunohistochemistry. Associations between these parameters and clinicopathological data were also examined. The expression rates of CD44V6, CDH11, and ß-catenin were 25.0% (5/20), 70.0% (14/20), and 20.0% (4/20) in osteochondroma specimens, respectively. Compared to osteochondromas, the proportions of expression of CD44V6 and ß-catenin in osteosarcoma specimens increased to 65.6% (59/90) and 60.0% (54/90), respectively. However, the expression rate of CDH11 in osteosarcomas was reduced to 40.0% (36/90). The expression of these markers was significantly associated with metastasis and overall survival (P < 0.05). Survival analysis revealed that patients with increased expression of CD44V6 and ß-catenin as well as decreased expression of CDH11 were correlated with a shorter survival time. Multivariate analysis indicated that clinical stage, metastasis status, and the expression of CD44V6, CDH11, and ß-catenin were found to be associated with overall survival. Further, the expression of ß -catenin and that of CD44V6 were positively correlated with each other. Thus, our results indicated abnormal expression of CD44V6, CDH11, and ß-catenin in osteosarcomas and osteochondromas, which may provide important indicators for further research.

Proliferation inhibition effect of docetaxel combined with cisplatin on osteosarcoma cells.

This research, studies the proliferation inhibition effect of combined use of docetaxel and cisplatin on osteosarcoma cells. The effects of docetaxel and cisplatin used alone and combined on osteosarcoma cell line HOS8603 were examined by means of cell count, morphologic observation, and flow cytometry (FCM). It was found that docetaxel and cisplatin either used alone or in combination, significantly inhibited the proliferation of osteosarcoma cells and apparently induced the apoptosis, and the effect of the combined drugs was better than that of the drugs used alone (growth inhibition ratio >or=59.34%, P < 0.05; apoptosis ratio = 18.31%, P < 0.01). Therefore, the combined use of docetaxel and cisplatin is more effective than either of the drugs used alone in inhibiting the proliferation of osteosarcoma cells.

Polybutylcyanoacrylate magnetic nanoparticles as carriers of adriamycin.

OBJECTIVE: The present study was designed to prepare and evaluate adriamycin-polybutylcyanoacrylate magnetic nanoparticles (ADR-PBCA-MNPs) as novel carriers of adriamycin. METHODS: ADR-PBCA-MNPs was prepared by the emulsion polymerization technique. Entrapment efficiency (ER) and drug load (DL) of nanoparticles, along with in vitro release were studied. Pharmacokinetic analysis was carried out in Kunming mice, with blood obtained at determined time points post administration. Biodistribution and recovery rate of ADR was measured and determined. RESULTS: Nanoparticles were visible as approximate spherical particles with good disparity, with an average diameter of 184.6 nm, a minimum diameter of 59.07 nm, and a maximum diameter of 291.66 nm as demonstrated by transmission electron microscopy. The ER and quantity of DL of ADR-PBCA-MNPs were 90.73 and 10.68%, respectively, measured by an ultraviolet-visible light spectrophotometer. In vitro study demonstrated that the release reached a balance after 72 h, with a total release rate of approximately 80%. As shown in pharmacokinetic studies in rats,the ADR-PBCA-MNPs group displayed a slowed doxorubicin release associated with better bioavailability. ADR-PBCA-MNPs reduced ADR accumulation at nontarget sites in the magnetic field, contributing to the reduced toxicity and side effects of ADR. CONCLUSION: ADR-PBCA-MNPs was successfully prepared and had a satisfactory targeted effect under the magnetic field, which can increase ADR concentration at target sites but not at non-target sites. As a result, the therapeutic effect of ADR may be greatly enhanced with minimized drug toxicity and side effects.

The combined effects of celecoxib and minocycline hydrochloride on inhibiting the osseous metastasis of breast cancer in nude mice.

Breast carcinomas show a trend toward bone metastasis that is prevalent worldwide. Celecoxib (CX) and minocycline hydrochloride (MH) have both been widely used in treating breast cancer; however, their combined effects on the osseous metastasis of breast cancer have not yet been studied. In the present study, breast cancer cells were injected into the back of the femoral bone of nude mice, and CX and MH were intraperitoneally administered every other day at doses of 30 and 40 mg/kg/day, respectively, for 30 days. Tumor weights and volumes were significantly lower and the tumor inhibition rate was significantly higher in the CX + MH group than those of the control and CX or MH alone groups (p < 0.05). The cell density in the tumor tissue was significantly decreased and apoptotic and necrotic cell death was significantly increased in the CX + MH group, as compared with those of the control and CX or MH alone groups. Microvessel density and expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 in the tumor tissues of the CX + MH group were significantly lower than those of the CX, MH, and control groups. The serum alkaline phosphatase level of the CX + MH group was significantly lower than those of the other groups (p < 0.01). These results suggest that a combined use of CX and MH has better inhibitory effects on the osseous metastasis of breast cancer, as compared to CX or MH alone. They exerted their combined effects by increasing tumor-cell death and decreasing the tumor expression of MMP-9 and VEGF systems.