Association between CTLA-4 genetic polymorphisms and susceptibility to osteosarcoma in Chinese Han population.

Osteosarcoma (OS) is the most common malignant primary bone tumor in the world. The cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) is an important candidate gene for influencing the development of OS. This study aimed to investigate the potential association of CTLA-4 genetic polymorphisms with OS risk in Chinese Han population. A total of 415 OS patients and 431 healthy controls were enrolled in this study. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were used to detect the genotyping of CTLA-4 c.75G[C and c.326G[A genetic polymorphisms. We observed that the genotypes/alleles of c.75G[C and c.326G[A genetic polymorphisms were statistically associated with the increased risk of OS (for c.75G[C, CC versus (vs.) GG: OR 1.72, 95% CI 1.09­2.74; C vs. G: OR 1.30, 95% CI 1.06­1.60; for c.326G[A, AA vs. GG: OR 2.12, 95% CI 1.31­3.42; A vs. G: OR 1.31, 95% CI 1.07­1.61). The allele-C/genotype-CC of c.75G[C and allele-A/genotype-AA of c.326G[A may contribute to OS susceptibility. These data indicate that CTLA-4 genetic polymorphisms are potentially related to OS risk in Chinese Han population, and might be used as molecular markers for evaluating the risk of OS.

Association analysis between genetic variants of MDM2 gene and osteosarcoma susceptibility in Chinese.

Osteosarcoma (OS) is the most common pediatric bone malignancy worldwide. The MDM2 gene is an important candidate gene for influencing the susceptibility to OS. The objective of this study aimed to detect the potential association between MDM2 genetic variants and OS susceptibility in Chinese Han population. We recruited 415 OS patients and 431 cancer-free controls in this case-control study. The c.44C>T and c.1002T>C genetic variants in MDM2 gene were investigated using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. We found that the genotypes/alleles of c.44C>T and c.1002T>C were statistically associated with the increased risk of OS (for c.44C>T, TT versus (vs.) CC: OR = 2.43, 95% CI 1.49-3.95, p < 0.001; T vs. C: OR = 1.36, 95% CI 1.11-1.67, p = 0.003; for c.1002T>C, CC vs. TT: OR = 2.38, 95% CI 1.37-4.13, p = 0.002; C vs. T: OR = 1.27, 95% CI 1.02-1.56, p = 0.030). The T allele and TT genotype of c.44C>T and C allele and CC genotype of c.1002T>C could be increased risk factors for the susceptibility to OS. Results from this study suggest that MDM2 genetic variants are potentially related to OS susceptibility in Chinese Han population, and might be used as molecular markers for assessing OS susceptibility.

A comparative study of the preventive effects of mitomycin C and chitosan on intraarticular adhesion after knee surgery in rabbits.

We sought to compare the preventive effects of mitomycin-C(MMC) and chitosan on intraarticular adhesion after knee surgery in rabbits. For this purpose, 48 New-Zealand rabbits were randomly and equally divided into MMC, chitosan, and control groups. Approximately 10 × 10 mm(2) of the cortical bone was removed from both sides of left femoral condyle and the cancellous bone underneath was exposed. The decorticated areas were topically treated with MMC and chitosan while control group was treated with physiological saline. The lower left limb was fixed in flexed position with Kirschner-wire for 4 weeks postoperatively. After 4 weeks, gross and histopathological examination, biochemical analysis, and fibroblast counts were performed on knee intraarticular adhesion in each group. The data show mild membrane-like fibrous intraarticular adhesion, presented in loose, in MMC group. There was moderate intraarticular adhesion in chitosan group while in controls; there was large-size compact fibrous tissue adhesion. Hydroxyproline contents and fibroblast quantity of MMC and chitosan groups were lower (P < 0.05) than that of control group. We, therefore, concluded that MMC and chitosan could prevent intraarticular adhesion of the knee in rabbits by inhibiting fibroblast proliferation and reducing collagenous fiber formation while MMC had a better preventive effect than that of chitosan.

The effect of mitomycin C in reducing intraarticular adhesion after knee surgery in rabbits.

Mitomycin C (MMC) is known to inhibit fibroblast proliferation through suppressing DNA dependent RNA synthesis. Based on this knowledge, we illustrated the effect of MMC on inhibiting fibroblast collagen synthesis and reducing intraarticular fibrous adhesion in a rabbit model. Forty-eight New Zealand white rabbits were randomly divided into four groups. Approximately 10 x 10 mm squares of the cortical bone was removed from both sides of the femoral condyle, and the underneath cancellous bone was exposed. MMC in various concentrations or saline were then applied to the decorticated areas. The intraarticular adhesions were evaluated after four weeks by macroscopic evaluation, histological evaluation and biochemical analysis of hydroxyproline content. The results demonstrated that MMC could suppress the formation of intraarticular fibrous adhesion in a dose-dependent manner. The intraarticular adhesion score, the hydroxyproline content and the fibroblast number in 0.1mg/ml MMC group were significantly less than those in 0.05 mg/ml MMC group, 0.01 mg/ml MMC group and control group. However, dense adhesions were found in 0.01 mg/ml MMC group and control group. These results indicated that topical application of 0.1mg/ml MMC could reduce intraarticular adhesion through inhibiting fibroblast proliferation in rabbits.