甲状腺肿瘤组织中VEGF、p73蛋白表达情况及相互关系研究

目的 探析甲状腺肿瘤组织中血管内皮生长因子(VEGF)、肿瘤抑制因子(p73)的表达及其相关性.方法 选取某院2013年1月至2014年1月收治的60例甲状腺癌和60例甲状腺腺瘤患者作为观察对象,并将同期60例健康人群作为对照,采用免疫组化(SP)法检测组织中VEGF和p73的表达,并采用Pearson相关分析研究组织中VEGF和p73的相关性.结果 甲状腺癌组组织中VEGF阳性表达率86.7％(52/60)显著高于甲状腺腺瘤组71.7％(43/60),高于正常对照组0％,差异均有统计学意义(P＜0.05);甲状腺癌组组织中p73阳性表达率93.3％(56/60)显著高于甲状腺腺瘤组80.0％(48/60),高于正常对照组0％,差异均有统计学意义(P＜0.05).甲状腺组织中VEGF和p73呈正相关,在甲状腺癌组织中相关系数r=0.723,P＜0.05,在甲状腺腺瘤组织中相关系数r=0.542,P＜0.05.结论 甲状腺肿瘤患者组织中VEGF和p73蛋白表达均显著升高,且二者呈正相关.     

Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET

Background: High expression of glucagon-like peptide-1 receptor (GLP-1R) in insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can specifically bind to GLP-1R as an agonist and its analogs are extensively used in receptor imaging studies.

Purpose: A new GLP-1R imaging agent, [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4, was designed and prepared for insulinoma imaging.

Methods: Cys³⁹-exendin-4 was conjugated with NOTA-MAL, then the compound was radiolabeled with [¹⁸F]AlF complex to obtained [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1 cells and BALB/c nude mice models.

Results: [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 can be efficiently produced with a yield of 17.5?±?3.2% (non-decay corrected) and radiochemical purity of >95%. The IC₅₀ value of displacement [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 with Cys³⁹-exendin-4 was 13.52?±?1.36?nM. PET images showed excellent tumor visualization with high uptake (9.15?±?1.6%ID/g at 30?min and 7.74?±?0.87%ID/g at 60?min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60?min after injection. GLP-1R binding specificity was demonstrated by co-injection with an excess of unlabeled Cys³⁹-exendin-4 and the tumor uptake was found to be reduced significantly.

Conclusion: [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.     

m6A regulators are associated with osteosarcoma metastasis and have prognostic significance: A study based on public databases

Background:Osteosarcoma represents the most common malignant bone tumor with high metastatic potential and inferior prognosis. RNA methylation (N6-methyladenosine [m6A]) is a prevalent RNA modification that epigenetically influences numerous biological processes including tumorigenesis. This study aims to determine that m6A regulators are significant biomarkers for osteosarcoma, and establish a prognostic model to predict the survival of patients.Methods:In this study, we comprehensively analyzed the underlying associations between m6A regulators’ mRNA expressions and metastasis as well as prognosis of osteosarcoma patients in the Cancer Genome Atlas. Multivariate Cox-regression analysis was used to screen regulators that were significantly associated with overall survival of osteosarcoma patients. Least absolute shrinkage and selection operator (LASSO) Cox-regression analysis was used for constructing m6A regulator-based osteosarcoma prognostic signature.Results:Some of the regulators exhibited aberrant mRNA levels between osteosarcoma samples with and without metastasis. Multivariate Cox-regression analysis identified several regulators with potential prognostic significance. A risk score formula consisted of methyltransferase-like 3, YTH domains of Homo sapiens, and fat mass and obesity-associated protein was obtained through which patients could be prognostically stratified independently of potential confounding factors. The signature was also significantly associated with the metastatic potential of osteosarcoma. All the analyses could be well reproduced in another independent osteosarcoma cohort from the Gene Expression Omnibus.Conclusions:In conclusion, this study first revealed potential roles of m6A regulators in osteosarcoma metastasis and prognosis, which should be helpful for its clinical decision-making.     

Urinary Nucleic Acid TSPAN13-to-S100A9 Ratio as a Diagnostic Marker in Prostate Cancer

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.     

骨桥蛋白在卵巢癌中的表达及其与不同临床病理特征关系的Meta分析

目的:评价有关骨桥蛋白(OPN)在卵巢癌组织中表达的情况及与卵巢癌不同临床病理特征的关系。方法:系统检索NCBI PubMed、EMBASE、维普、万方数据库中截止2013年11月符合纳入标准的国内外公开发表的有关OPN在卵巢癌组织中表达的文献7篇,通过固定效应模型综合分析合并效应量,采用RevMan 5.1统计软件进行分析。结果:Meta分析显示,OPN在卵巢癌组和正常卵巢组表达差异有统计学意义[OR=20.24,95%CI(9.66,42.43),P<0.000 01]。OPN在卵巢癌组和良性卵巢组表达差异有统计学意义[OR=16.58,95%CI(9.60,28.64),P<0.000 01]。OPN在卵巢癌高分化组和中低分化组表达的差异有统计学意义[OR=0.16,95%CI(0.08,0.32),P<0.000 01]。OPN在卵巢癌临床Ⅰ-Ⅱ期组和临床Ⅲ-Ⅳ期组表达的差异有统计学意义[OR=0.16,95%CI(0.09,0.29),P<0.000 01]。OPN在卵巢癌淋巴结转移组和淋巴结未转移组表达的差异有统计学意义[OR=4.20,95%CI(2.24,7.88),P<0.000 01]。结论:OPN高表达与卵巢癌及其不同临床病理特征有显著相关性。但受纳入文献质量影响,还需进一步用国内外高质量的研究来证实。     

Alterations in central preproenkephalin mRNA expression after chronic free-choice ethanol consumption by fawn-hooded rats

BACKGROUND: Neurotransmission mediated via opioid and dopamine receptors is believed to be involved in the reinforcing and/or rewarding effects of ethanol consumption. We previously examined the effect of ethanol consumption (and naltrexone treatment, used clinically to treat alcoholism) on micro-opioid receptor density. We describe here the effect of free-choice ethanol consumption and naltrexone treatment on preproenkephalin, preprodynorphin, and dopamine D1 and D2 receptor mRNA expression in the central nervous system. METHODS: Fawn-hooded rats were given continual free-choice access to a 5% ethanol solution or water (4 weeks) followed by 2 weeks of water alone. At the end of this abstinence period, osmotic minipumps were implanted subcutaneously to deliver saline (n = 4) or naltrexone (n = 4; 8.4 mg/kg/day for 4 weeks). After recovery from surgery, the rats again were given access to 5% ethanol under the same free-choice conditions (4 weeks). A third group of age-matched controls drank only water during the behavioral trial. At the end of the behavioral trial, the rats were decapitated, and a quantitative examination of peptide precursor mRNAs was made by using in situ hybridization histochemistry. RESULTS: Naltrexone treatment significantly decreased preprodynorphin expression in the nucleus accumbens, but neither naltrexone treatment nor ethanol consumption significantly affected dopamine D1 and D2 receptor mRNA expression. In contrast, ethanol consumption increased preproenkephalin mRNA in the central and intercalated nuclei of the amygdala but decreased preproenkephalin mRNA in the nucleus accumbens and olfactory tubercle. The decreased level of preproenkephalin mRNA in the nucleus accumbens may reflect a neuroadaptive response to increased release of dopamine, whereas the increased level of preproenkephalin mRNA in the central nucleus of the amygdala may be associated with an anxiolytic effect of ethanol consumption. CONCLUSIONS: The data support the putative role of opioid peptides in the effects of ethanol and suggest that the nucleus accumbens and central nucleus of the amygdala are loci for the reinforcing effects of ethanol.     

靶向表达的逆转录病毒载体LN.ALBTRS.TK的构建

目的:构建出在肝细胞中具靶向表达潜能的逆转录 TK 基因载体。方法:用 p2335A-1中的一段2.0Kb的人白蛋白组织特异性转录调节序列(ALBTRS)取代 pSTK 中的 SV40启动子,所构建的载体命名为 LN.ALB-TRS.TK。结果:载体 LN.ALBTRS.TK 的结构中,含有 ALBTRS 启动子,具有在肝细胞中特异表达白蛋白的潜能,载体经酶切鉴定表明结构符合要求。结论:成功地构建出具靶向表达潜能的逆转录载体 LN.ALBTRS.TK。