骨关节炎患者线粒体转录因子A表达与线粒体DNA拷贝数关系的研究

目的研究膝关节骨关节炎患者与正常人外周血及关节软骨细胞中的线粒体转录因子A(TFAM)表达和线粒体DNA拷贝数的关系,探讨其相关性。方法选择20例的膝关节骨关节炎患者为骨关节炎组,以正常关节软骨患者20例为对照组。各收集其外周血及关节软骨细胞,逆转录-聚合酶链反应(RT-PCR)及实时荧光PCR(SYBR GREEN I染料法)检测外周血及软骨组织中TFAM mRNA的表达水平和软骨细胞线粒体DNA拷贝数。结果骨关节炎组外周血和软骨细胞TFAM mRNA的表达量均低于正常组患者(P0.05),且二者表达量呈正相关(P0.01);骨关节炎组线粒体DNA的平均拷贝数均于正常组患者软骨细胞(P0.01),且与软骨细胞TFAM mRNA的表达量呈正相关(P0.01)。结论 TFAM通过增加其线粒体DNA拷贝数,这将可以对骨关节炎的病因提出新的解释和补充,可能为骨关节炎的检测和治疗提供新的途径。     

血细胞线粒体DNA拷贝数变化与高原红细胞增多症易感性的关联研究

目的探讨血细胞线粒体DNA(mtDNA)拷贝数的变化与高原红细胞增多症易感性的关联性。方法分别采集年龄、职业等相匹配的高原红细胞增多症患者37例及对照组42例的静脉血2 mL,提取总DNA,通过定量PCR法(染料法)检测白细胞的mtDNA相对拷贝数。结果高原红细胞增多症患者中,mtDNA拷贝数显著低于对照组(P<0.05)。通过线性回归分析显示,在对照组中,随血红蛋白浓度的增加mtDNA拷贝数增加(P<0.05);然而在高原红细胞增多症病例组中,随着血红蛋白浓度的增加,mtDNA拷贝数降低(P<0.05)。结论高原红细胞增多症患者中,mtDNA拷贝数较低,可能作为该病的分子标记。     

尤文氏肉瘤的影像学分析

目的：探讨尤文氏肉瘤的影像学表现及其意义,提高其影像学诊断水平。资料与方法：回顾性分析17例经病理证实的尤文氏肉瘤的X线、CT及MRI表现。结果：17例尤文氏肉瘤中,骨尤文氏肉瘤14例,骨外尤文氏肉瘤3例。①长管骨：病变范围广,易沿骨长轴扩展,常呈筛孔样、虫蚀样溶骨性骨质破坏,并见层状、葱皮样骨膜反应,常见骨旁长条形软组织肿块, MRI横断位扫描见“同心圆征”,具有一定的特征性。②扁骨及不规则骨：骨质破坏表现多样,骨膜反应不明显,骨外软组织肿块常较大。③骨外尤文氏肉瘤：骨旁软组织内肿块,大部分边界清晰,内可见片状低密度坏死,增强扫描肿瘤实质明显不均匀强化,未见明确骨质破坏。结论：尤文氏肉瘤在不同部位有不同的影像表现;发生于长管骨的尤文氏肉瘤具有相对的特征性表现,正确诊断率高,X线平片和MRI结合诊断,能提高其正确诊断率;骨外尤文氏肉瘤影像表现缺乏特征性,误诊率高,确诊依赖病理及免疫组化检查。     

Present trends in treatment of Ewing's sarcoma

The prognosis of Ewing's sarcoma, the first malignant tumor in children under 10, has improved dramatically in the last 10 yrs. The authors review the signs and symptoms that permit diagnosis and analyse the improvement in treatment, based on multidrug's combination, neoadjuvant chemotherapy and surgical treatment of the primary. They point out the necessity of closed multidisciplinary co-operation to treat these patients. Under these conditions, disease free survival now reaches more than 90% at 3 years 1/2.     

DNA copy number analysis by MAPH: molecular diagnostic applications

DNA copy number variation is an important cause of genetic disease. There are several techniques available to detect copy number changes of various sizes, each with their limitations in resolution and cost. Here we outline the development of multiplex amplifiable probe hybridization (MAPH) into a high-throughput diagnostic technique for detecting copy number variation of almost any size. Its application in testing for genetic mutations causing diseases, such as familial breast cancer, Charcot-Marie-Tooth disease Type 1A, Duchenne/Becker muscular dystrophy and familial colorectal cancer is described, as well as its use in identifying chromosomal changes in some individuals with mental retardation. The analysis of the data produced by MAPH is also considered, along with its potential for automation and development of microarray-based MAPH.     

Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines

A common aim of pharmacogenomic studies that use genome-wide assays on panels of cancers is the unbiased discovery of genomic alterations that are associated with clinical outcome and drug response. Previous studies of lapatinib, a selective dual-kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2 tyrosine kinases, have shown predictable relationships between the activity of these target genes and response. Under the hypothesis that additional genes may play a role in drug sensitivity, a predictive model for lapatinib response was constructed from genome-wide DNA copy number data from 24 cancer cell lines. An optimal predictive model which consists of aberrations at nine distinct genetic loci, includes gains of HER2, EGFR, and loss of CDKN2A. This model achieved an area under the receiver operating characteristic curve of approximately 0.85 (80% confidence interval, 0.70-0.98; P < 0.01), and correctly classified the sensitivity status of 8 of 10 head and neck cancer cell lines. This study shows that biomarkers predictive for lapatinib sensitivity, including the previously described copy number gains of EGFR and HER2, can be discovered using novel genomic assays in an unbiased manner. Furthermore, these results show the utility of DNA copy number profiles in pharmacogenomic studies.     

Ewing's sarcoma: transplantation in nude rat

Eight Ewing's sarcoma, primary tumor or metastasis, have been transplanted in Nude Rats. These tumors grow slowly and only in female rats. One of them has been maintained for 13 months with 5 passages. It has conserved all the characteristics of the primary tumor, histologic and ultramicroscopic morphology, glycogen secretion and cytogenetic modification (11.22 translocation). The graft of Ewing's sarcoma to Nu/Nu rats is a valuable system to get more material in good condition to study the nature and the origin of Ewing's cells, to test the new chemotherapy trials and to prepare and test the monoclonal antibodies.     

增生性瘢痕与瘢痕疙瘩DNA拷贝数变化的差异分析

背景:近年来临床遗传学和分子生物学研究均表明,瘢痕疙瘩的形成与遗传具有密切的关系.但增生性瘢痕与遗传是否有关,目前尚未明确.目的:了解增生性瘢痕与瘢痕疙瘩在遗传学改变上的异同.设计、时间及地点;对比观察,实验于2007-03/2008-12在广东医学院完成.材料:瘢痕标本均来自2003-01/2008-12广东医学院附属医院整形外科门诊及住院患者16例,其中增生性瘢痕10例,男3例,女7例,年龄20～50岁;瘢痕疙瘩6例,男1例,女5例,年龄19～46岁.方法:提取瘢痕疙瘩及增生性瘢痕组织DNA,应用比较基因组杂交技术观察增生性瘢痕及瘢痕疙瘩基因组的不平衡即遗传物质的丢失或扩增情况,比较两者间DNA拷贝数变化的差异.主要观察指标:①两组DNA拷贝数的缺失率的比较.②两组DNA拷贝数的扩增率的比较.结果:增生性瘢痕组未发现特异区域的DNA拷贝数的高频率缺失或扩增;瘢痕疙瘩组出现高频率的DNA拷贝数缺失的染色体是1,16,20号及22号染色体,未发现特异区域的DNA拷贝数的高频率扩增.两组1,16,20,22染色体DNA拷贝数的缺失率相比较,瘢痕疙瘩组明显高于增生性瘢痕组(P<0.05).结论:与瘢痕疙瘩相比,增生性瘢痕不存在明显的DNA拷贝数缺失或扩增,增生性瘢痕的形成与发展可能与遗传没有直接的关系.     

Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin

Statins are generally well tolerated, but can cause myopathy and have been associated with mitochondrial abnormalities. The aim of this study was to determine whether muscle mitochondrial DNA (mtDNA) levels are altered during statin therapy. We retrospectively quantified mtDNA in 86 skeletal muscle biopsy specimens collected as part of a previously published clinical trial of high-dose simvastatin or atorvastatin versus placebo.     

Effects of ginseng on peripheral blood mitochondrial DNA copy number and hormones in men with metabolic syndrome: A randomized clinical and pilot study

BackgroundIt has been observed that mitochondrial dysfunction is associated with an increased risk of metabolic syndrome. There is growing evidence that hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and hormone (testosterone and growth hormone) deficiency may lead to metabolic syndrome. Recent studies have reported that ginseng treatment improves mitochondrial and HPA-axis function and increases anabolic hormone secretion.ObjectivesThe objective of this study was to investigate the effect of red ginseng (RG) on metabolic syndrome, hormones, and mitochondrial function using leukocyte mitochondrial DNA copy number in men with metabolic syndrome.MethodsWe performed a randomized, double-blind, placebo-controlled study in 62 subjects who were not taking drugs that could affect their metabolic function. A total of 62 men with metabolic syndrome were randomly assigned to either an RG group (3.0 g/day) or a placebo group for 4 weeks. We analyzed changes in metabolic syndrome components, leukocyte mitochondrial DNA copy number, hormones (total testosterone, IGF-1, cortisol, and DHEAS) and inflammatory markers (C-reactive protein, ferritin) from baseline to 4 weeks.ResultsSignificant improvement in mitochondrial function (95% CI −44.9 to −1.3) and an increase in total testosterone (95% CI −70.1 to −1.0) and IGF-1(P = 0.01) levels were observed in the RG group when compared with the placebo group. Diastolic blood pressure (95% CI 2.0–9.4) and serum cortisol (95% CI 1.1–5.5) significantly decreased in the RG group.ConclusionsWe found evidence that RG had a favorable effect on mitochondrial function and hormones in men with metabolic syndrome.     

额骨尤文肉瘤1例

患者男,20岁.1年前无明显诱因额部出现蚕豆样大小的包块,未引起重视,后逐渐增大.查体:额部包块约4 cm×5 cm,无压痛,质地较硬,与周围组织无粘连,未闻及血管杂音,局部皮肤无红肿.     

髂骨原发骨肉瘤和尤文肉瘤的影像学分析

目的 对比分析髂骨原发骨肉瘤和尤文肉瘤的X线、CT和MRI特征,探讨其临床特点。方法 回顾性分析13例髂骨骨肉瘤患者及10例尤文肉瘤患者的临床和影像学资料。结果 骨肉瘤患者发病年龄12～51岁,平均（26.6±13.5）岁,尤文肉瘤患者发病年龄4～22岁,平均（16.2±8.2）岁。骨肉瘤患者混合型骨质破坏7例、成骨型骨质破坏3例;瘤骨形态多为棉絮状、针状、不规则形,体积较大。2例骨肉瘤内见多囊性灶并液-液平面。尤文肉瘤患者混合性骨质破坏8例,溶骨性骨质破坏2例;层状骨膜反应7例;尤文肉瘤内可见反应性新生骨,多为淡片状。骨盆内尤文肉瘤最大层面面积为（38.55±28.74）cm²,盆外为（22.85±15.70）cm²。结论 髂骨骨肉瘤的发病年龄较尤文肉瘤偏大;大面积瘤骨、单纯成骨性骨质破坏和软组织肿块内出现液-液平面提示骨肉瘤;层状骨膜反应和倾向于向骨盆内生长的软组织肿块多见于尤文肉瘤。     

Targeting Lyn inhibits tumor growth and metastasis in Ewing's sarcoma

Src family tyrosine kinases (SFK) play an important role in growth and metastasis of many types of human malignancies. However, their significance in Ewing's sarcoma remains to be elucidated. The purpose of this study was to evaluate the role of Lyn, one member of the SFK, in Ewing's sarcoma growth and metastasis and to determine whether a SFK inhibitor can induce Ewing's tumor regression. Lyn was expressed and activated in TC71, A4573, and SK-ES human Ewing's sarcoma cells. Lyn expression was seen in 13 of 15 patient tumor samples, 6 of which showed Lyn activation. Specific inhibition of Lyn using small interfering RNA significantly decreased primary tumor growth and lytic activity, and also reduced lung metastases in vivo. Down-regulation of Lyn resulted in decreased invasive capacity of tumor cells in vitro. AP23994, a small-molecule SFK inhibitor, decreased Lyn kinase activity and suppressed TC71 cell growth in vitro in a dose-dependent manner. Furthermore, treatment of mice bearing s.c. TC71 tumors with AP23994 or with polyethylenimine/Lyn-small interfering RNA gene therapy resulted in reduced Lyn kinase activity and significant tumor growth suppression. EWS/FLI-1, which is translocation fusion protein associated with Ewing's sarcoma, regulated Lyn gene expression and kinase activity. These data suggest that targeting Lyn may be a new therapeutic approach in treatment of Ewing's sarcoma.