Cloning and pharmacological characterization of the guinea pig P2X7 receptor orthologue

BACKGROUND AND PURPOSE: The human, rat, and mouse P2X(7) receptors have been previously characterized, and in this study we report the cloning and pharmacological properties of the guinea pig orthologue. EXPERIMENTAL APPROACH: A cDNA encoding for the guinea pig P2X(7) receptor was isolated from a guinea pig brain library. The receptor was expressed in U-2 OS cells using the BacMam viral expression system. A monoclonal antibody was used to confirm high levels of cell surface expression and the functional properties were determined in ethidium bromide accumulation studies. KEY RESULTS: The predicted guinea pig protein is one amino acid shorter than the human and rat orthologues and over 70% identical to the rat and human receptors. In contrast to human and rat P2X(7) receptors, 2'-&3'-O-(4benzoylbenzoyl)ATP (BzATP) was a partial agonist of the guinea pig P2X(7) receptor when compared to ATP and acted as an antagonist in some assays. However, as at other species orthologues, BzATP was more potent than ATP. The guinea pig P2X(7) receptor possessed higher affinity for 1-[N,O-bis(5-isoquinoline sulphonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62), suramin and Coomassie Brilliant Blue than human or rat P2X(7) receptors suggesting that it is pharmacologically different to other rodent or human P2X(7) receptors. CONCLUSIONS AND IMPLICATIONS: The guinea pig recombinant P2X(7) receptor displays a number of unique properties that differentiate it from the human, rat and mouse orthologues and this structural and functional information should aid in our understanding of the interaction of agonists and antagonist with the P2X(7) receptor.     

下调lncRNA DNM3OS通过靶向miR-193a-3p增强人直肠癌细胞系SW-480的放疗敏感性

目的 探讨lncRNA DNM3OS对直肠癌SW-480细胞的增殖、凋亡以及放射敏感性的影响及分子机制.方法 选取30例直肠癌患者癌组织及癌旁组织,RT-qPCR检测DNM3OS和miR-193a-3p的表达水平;将抑制DNM3OS的表达载体、过表达miR-193a-3p载体转染至SW-480细胞,将DNM3OS与抑制...     

A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus

BackgroundA new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT.MethodsUnivariate and multivariate analysis with Wald χ² test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system.ResultsA training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2–76.9), 12.1 (11.0–13.2), 5.7 (5.1–6.2), 4.0 (3.3–4.6) and 2.5 (1.7–3.3) months for the stages 0 to IV, respectively (P<0.001) in the training cohort. The corresponding figures for the validation cohort were 6.4 (4.9–7.9), 2.8 (1.3–4.4), 10.8 (9.3–12.4), and 1.5 (1.3–1.7) months for the stages II to IV, respectively (P<0.001). The mean survival for stage 0 to 1 were 37.6 (35.9–39.2) and 30.4 (27.4–33.4), respectively (P<0.001).ConclusionsA new staging system was established which provided a good discriminatory ability to separate patients into different stages and substages after treatment. It can be used to supplement the other HCC staging systems.     

miR-363-3p Inhibits Osteosarcoma Cell Proliferation and Invasion via Targeting SOX4

miR-363-3p has been shown to suppress tumor growth and metastasis in various human cancers. However, the function of miR-363-3p in osteosarcoma (OS) has not been determined. In our study, we found that the expression of miR-363-3p was significantly downregulated in OS tissues compared with adjacent normal tissues. miR-363-3p expression was associated with the poor overall survival rate of OS patients. Moreover, we found that overexpression of miR-363-3p markedly inhibited the proliferation, migration, and invasion of U2OS and MG63 cells. Moreover, we found that SOX4 was a direct target of miR-363-3p in OS cells. Overexpression of miR-363-3p significantly inhibited the expression of SOX4. Expression levels of miR-363-3p and SOX4 were negatively correlated in OS tissues. Finally, we found that restoration of SOX4 attenuated the suppressive effects of miR-363-3p on the proliferation, migration, and invasion of U2OS and MG63 cells. Therefore, our findings demonstrated that miR-363-3p served as a tumor suppressor in OS tissues by targeting SOX4.     

Apparent diffusion coefficient histogram analysis for prediction of prognosis in glioblastoma

Background

To investigate the potential to predict prognosis of glioblastoma (GBM) patients by analysis of the broader and lower values in the lower distribution of apparent diffusion coefficient (ADC_L) (B&L-ADC_L) values in the ADC histogram.

The prognostic value of p16 and p53 expression for survival after vulvar cancer: A systematic review and meta-analysis

The tumor suppressor proteins p16 and p53 have been suggested to have prognostic value in some human papillomavirus (HPV)-associated cancers, however, this has been less well established for vulvar cancer. The aim of this review and meta-analysis was to examine the prognostic value of p16 and p53 expression status on survival after vulvar squamous cell carcinoma (VSCC). We conducted a thorough systematic literature search of multiple databases to identify studies examining survival after histolocally verified VSCC that were tested for p16 and/or p53. A total of 18 eligible studies were included. Using a fixed-effects model we calculated study-specific and pooled hazard ratios (HRs) of 5-year overall survival (OS). In the analyses of OS, we included 475 VSCC cases tested for p16 expression of which 38% were p16 positive. The pooled HR_p16 was 0.40 (95% CI: 0.29–0.55). In addition, the majority of results from studies with adjusted analyses on the prognostic value of p16 indicated that p16 expression status could be an independent prognostic marker for OS in women diagnosed with VSCC, and the same pattern was seen for disease specific survival (DSS). We also included 310 VSCC cases tested for p53 expression of which 54% were p53 positive. The pooled HR_p53 was 1.81 (95% CI: 1.22–2.68) indicating that p53 positive VSCC have a significantly lower 5-year OS compared to p53 negative. The results in relation to p53 reported from adjusted analyses OS and on DSS and disease free survival were more equivocal. This meta-analysis and review suggests that p53 and especially p16 expression status are of prognostic importance in women diagnosed with VSCC. This may be clinically important in the future design of targeted therapy and when planning the optimal follow-up strategy. Future studies should include the combined use of biomarkers such as p16, p53 and HPV status.     

Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center,Retrospective, Propensity Score–Matched Study

Purpose

To compare segmental radioembolization with segmental chemoembolization for localized, unresectable hepatocellular carcinoma (HCC) not amenable to ablation.