MicroRNA-29b sensitizes osteosarcoma cells to doxorubicin by targeting matrix metalloproteinase 9 (MMP-9) in osteosarcoma.

OBJECTIVE: To discover the effect and mechanism of exogenous microRNA-29b (miR-29b) on proliferation, apoptosis and the sensitivity to chemotherapy of osteosarcoma (OS) cells. PATIENTS AND METHODS: We assessed the expression of microRNA-29b in osteosarcoma tissues evaluating the regulation of in on the OS cell growth and drug sensitivity in human osteosarcoma MG-63 cell model. Firstly, quantitative RT-PCR (reverse transcription-PCR, RT-PCR) was used to measure the expression of miR-29b and matrix metallopeptidase 9(MMP-9) in primary osteosarcoma samples, and to evaluate the correlation between the two molecules. Secondly, miR-29b mimics or mimics were used to modify its expression in MG-63 cells. Luciferase reporter assay, Western blotting, cell viability, colony forming assay and apoptosis examination were performed to assess the regulation by manipulated miR-29b in the osteosarcoma-derived cells. RESULTS: We found that miR-29b is down-expressed, whereas the MMP-9 level was markedly higher in primary osteosarcoma tissues and osteosarcoma-derived cells. We also found that exogenous miR-29b reduces the proliferation, promotes the apoptosis and upregulates the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the MMP-9. CONCLUSIONS: Our data suggest that the reduced miRNA-29b may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas.

Investigation of the role of VEGF gene polymorphisms in the risk of osteosarcoma.

We conducted a case-control study in a Chinese population, and assessed whether the VEGF -634G/C, +936C/T, and +1612G/A polymorphisms could affect the risk of osteosarcoma and its association with environmental factors. A total of 180 consecutive osteosarcoma patients and 360 controls were included in our study. The genotypes of VEGF -634G/C, +936C/T, and +1612G/A were determined by the polymerase chain reaction-restriction fragment length polymorphism assay. Conditional logistic regression analyses showed that subjects carrying the GG genotype and the G allele of VEGF -634G/C were significantly associated with increased risk of osteosarcoma compared to those with the CC genotype; the ORs (95%CIs) were 2.28 (1.31-3.96) and 1.51 (1.16-1.97) for the GG genotype and G allele, respectively. We found that the GG genotype of VEGF -634G/C was associated with a significantly increased risk of osteosarcoma in patients of either gender with younger age and a family history of cancer. In summary, this study found that the VEGF -634G/C gene polymorphism was associated with an increased risk of osteosarcoma.

Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer.

BACKGROUND: Studies of clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) are limited. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database. PATIENTS AND METHODS: Data for patients diagnosed with LARC who received nCRT and curative-intent surgery between 2005 and 2012 were collected from five major Canadian cancer centers. Age was analyzed as a continuous and dichotomous variable (< 70 versus ≥ 70 years) and correlated with disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression models were used to adjust for important prognostic factors. RESULTS: Of 1172 patients included, 295 (25%) were ≥ 70 years, and they were less likely to receive adjuvant chemotherapy (ACT; 60% versus 79%, P < 0.0001), oxaliplatin-based ACT (12% versus 31%, P < 0.0001), less likely to complete nCT (76% versus 86%, P < 0.001), and more likely to be anemic at initiation of nCRT (42% versus 30%, P = 0.0004). In multivariate analyses, age ≥ 70 years was associated with similar DFS [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.68-1.26, P = 0.63], similar CSS (HR 0.81, 95% CI 0.46-1.41, P = 0.45), and similar OS (HR 1.28, 95% CI 0.88-1.86, P = 0.20), compared with the younger age group. As a continuous variable, increasing age was not predictive of DFS (HR 1.00, 95% CI 0.99-1.02, P = 0.49) or CSS (HR 1.002, 95% CI 0.98-1.02, P = 0.88); however, it correlated with an inferior OS (HR 1.02, 95% CI 1.00-1.03, P = 0.04). CONCLUSIONS: Elderly patients (≥ 70 years) who receive nCRT followed by surgery appear to have similar outcomes compared with younger patients. Decisions regarding eligibility for nCRT and surgery should not be based on age alone.

PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.

Immunological study of allogeneic mesenchymal stem cells during bone formation.

Autologous mesenchymal stem cells (MSCs) are limited in their clinical application because tissue-engineered bone cannot be pre-fabricated. Allogeneic MSCs are readily available but carry the risk of transplant rejection. It is not yet clear whether allogeneic MSCs can induce a rejection response during bone formation. In this study, two strains of genetically unmatched mini-pigs were used as experimental animals to study the immunological changes in MSCs in vitro and in vivo when generating bone. Mini-pig MSCs showed low immunogenicity during osteogenesis both in vitro and in vivo, indicating that allogeneic MSCs had little or no immunogenicity in osteosis. In conclusion, allogeneic MSCs are an important source of seed cells for the tissue engineering of bone. This favours the clinical application of pre-constructed tissue-engineered bone.

Approximation of flammability region for natural gas-air-diluent mixture.

The growing implementation of exhaust gas recirculation (EGR) in reducing NO(x) emissions of engine is of paramount motivation to perform a fundamental research on the flammability characteristics of fuel-air-diluent mixtures. In this work, the influences of EGR on the flammability region of natural gas-air-diluent flames were experimentally studied in a constant volume bomb. An assumption of critical burning velocity at flammability limit is proposed to approximately determine the flammability region of these mixtures. Based on this assumption, an estimation of the flammability map for natural gas-air-diluent mixtures was obtained by using the empirical formula of burning velocity data. The flammability regions of natural gas-air mixtures with EGR are plotted versus the EGR rate. From the comparison of estimated results and experimental measurements, it is suggested that the accuracy of prediction is largely dependent upon the formula of burning velocity used. Meanwhile, the influence of pressure on the critical burning velocity at flammability limit is also investigated. On the basis of the pressure dependence criterion, the estimation was performed for the circumstance of high temperature and pressure, and the prediction results still agree well with those of experiments.

Experimental study of flammability limits of natural gas-air mixture.

Flammability limits data are essential for a quantitative risk assessment of explosion hazard associated with the use of combustible gas. The present work is to obtain the fundamental flammability data for prevention of the hazards in the practical applications. Experiments have been conducted in a constant volume combustion bomb, and the fuel considered here is natural gas (NG). The pressure histories in the combustion bomb are recorded and a criterion of 7% pressure rise has been used to judge a flammable mixture. The effects of ethane on NG-air flammability limits have been investigated. By adding diluent (carbon dioxide, nitrogen or their mixture) into NG-air mixture, the dilution effects on the flammability limits have been explored as well, and the results are plotted as functions of diluent ratio.

[Comparative study on osteogenesis of three types growth factors recombination artificial bones].

OBJECTIVE: To compare the osteogenesis of recombination artificial bones, which are bovine deproteined bone (bDPB) and bovine bone morphogenetic protein (bBMP), combined with tumor necrosis factor alpha (TNF alpha), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) respectively. METHODS: One hundred trephined skull bone defects in fifty rabbits were divided into four groups, which implanted with bDPB/bBMP/TNF alpha, bDPB/bBMP/bFGF, bDPB/bBMP/EGF, and bDPB/bBMP respectively. X-ray and histological changes were observed in the 1st, 2nd, 4th, 6th, 8th weeks after implantation. The content of 35S and 45Ca and ash weight were measured at 10 and 42 days after operation. RESULTS: The osteogenesis of bDPB/bBMP/TNF alpha group was stronger than that of bDPB/bBMP/bFGF group(P < 0.01), while bDPB/bBMP/bFGF group was stronger than that of bDPB/bBMP/EGF(P < 0.01). No significant statistical difference were found between bDPB/bBMP/EGF and bDPB/bBMP(P > 0.05). CONCLUSION: TNF alpha combined with bBMP and carrier can stimulate bone formation and increase the volume of new bone in vivo. It suggests that bDPB/bBMP/TNF alpha is a valuable biomaterial of bone graft.