Prognostic significance of TP53 expression for patients with hepatocellular carcinoma: a meta-analysis

Background

Various studies evaluated the relationship between p53 expression and the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded conflicting results.

Methods

Electronic databases updated to Dec 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between p53 expression and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed.

Results

We performed a meta-analysis of 24 studies that evaluated the correlation between p53 expression and survival in patients with HCC. Combined hazard ratios (HRs) suggested that p53 expression had an unfavorable impact on overall survival (OS) [HR =1.64, 95% confidence interval (CI): 1.40-1.85], and disease free survival (DFS) (HR =1.57, 95% CI: 1.26-1.87) in patients with HCC.

Conclusions

p53 expression indicates a poor prognosis for patients with HCC.     

The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis)

BACKGROUND: The membrane bound receptor OX40 (CD134) - a member of the TNF-R/NGF-R superfamily - is expressed on activated CD4+-T cells in humans and rodents. The interaction of OX40 with its ligand (OX40L) has been shown to be important in T-cell dependent B cell-stimulation and T-cell costimulation in vitro and in vivo. Several studies in experimental animal models for immunologically mediated GI-diseases have stressed the important role of the OX40-OX40L interaction for their manifestations. To assess if the OX40-OX40L interaction is also crucial in the pathogenesis of immunologically mediated diseases of the human gastrointestinal tract (e.g. celiac disease, Crohn's disease, ulcerative colitis) we investigated, in a first line of experiments, the expression of OX40 in biopsy specimens of patients suffering from these diseases. METHODS: The biopsies were formalin fixed and paraffin-embedded and cut into 5 microm slides. To demask the antigen, the slides were consecutively cooked in citrate buffer for 20 min. Binding of anti-OX40 antibody was detected using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. RESULTS: Nine of 11 biopsy specimens of patients with celiac disease were OX40-positive; none of the 20 control duodenal biopsies demonstrated OX40-positivity; and all biopsies of patients with ulcerative colitis (n = 11) or Crohn's disease (n = 11), respectively, stained positively for OX40. One of the 20 control biopsies showed OX40 staining. DISCUSSION: OX40 is highly expressed in the gastrointestinal tissue of patients with immunologically mediated bowel diseases. Together with previous studies in animal models for these diseases, the present results point to a potential role of OX40 in their pathogenesis.     

妊娠相关血浆蛋白A的原核表达及蛋白纯化

目的构建原核表达PAPP-A重组蛋白,并对蛋白质进行纯化。方法根据DNAstar软件分析获得的编码PAPP-A特异抗原表位,利用Primer Premier 5.0软件设计引物,以PAPP-A c DNA-质粒转化菌液为模板,进行PCR扩增。PAPP-A的DNA和p ET42a质粒分别双酶切,经琼脂糖凝胶电泳及胶回收后进行连接反应,转化至大肠埃希菌Top10,筛选阳性克隆经测序鉴定正确后,转化至大肠埃希菌BL21,诱导产生PAPP-A重组蛋白,利用镍柱初步纯化及离子交换层析柱进一步纯化,用SDS-PAGE及DEAE层析鉴定重组抗原蛋白。结果筛选出抗原表位集中区,在大肠埃希菌BL21中高效表达了重组的PAPP-A蛋白,经过镍柱及离子交换层析纯化后,PAPP-A浓度为0.22 g/L,DEAE层析分析证实其纯度较高。结论成功筛选出PAPP-A的抗原表位集中区,并制备了重组抗原蛋白,为PAPP-A的后续临床研究提供依据。     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.     

Mechanisms and biomarkers of immune quiescence in kidney transplantation

This review discusses the current understanding of biomarkers of immune quiescence based on reviews of published literature in kidney transplant operational tolerance and mechanistic studies based on a better characterization of the stable, well-functioning renal allograft.     

Generation and characterization of a novel shoulder contracture mouse model

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self‐limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1732–1738, 2015.