Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale,Multicentre Study

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.     

An Atomic Force Microscope Study Revealed Two Mechanisms in the Effect of Anticancer Drugs on Rate-Dependent Young’s Modulus of Human Prostate Cancer Cells

Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3) are investigated using a recently developed control-based nanoindentation measurement (CNM) protocol on atomic force microscope (AFM). The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young’s modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young’s modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.     

Polyamines inhibit the assembly of stress granules in normal intestinal epithelial cells regulating apoptosis

Polyamines regulate multiple signaling pathways and are implicated in many aspects of cellular functions, but the exact molecular processes governed by polyamines remain largely unknown. In response to environmental stress, repression of translation is associated with the assembly of stress granules (SGs) that contain a fraction of arrested mRNAs and are thought to function as mRNA storage. Here we show that polyamines modulate the assembly of SGs in normal intestinal epithelial cells (IECs) and that induced SGs following polyamine depletion are implicated in the protection of IECs against apoptosis. Increasing the levels of cellular polyamines by ectopic overexpression of the ornithine decarboxylase gene decreased cytoplasmic levels of SG-signature constituent proteins eukaryotic initiation factor 3b and T-cell intracellular antigen-1 (TIA-1)-related protein and repressed the assembly of SGs induced by exposure to arsenite-induced oxidative stress. In contrast, depletion of cellular polyamines by inhibiting ornithine decarboxylase with α-difluoromethylornithine increased cytoplasmic eukaryotic initiation factor 3b and TIA-1 related protein abundance and enhanced arsenite-induced SG assembly. Polyamine-deficient cells also exhibited an increase in resistance to tumor necrosis factor-α/cycloheximide-induced apoptosis, which was prevented by inhibiting SG formation with silencing SG resident proteins Sort1 and TIA-1. These results indicate that the elevation of cellular polyamines represses the assembly of SGs in normal IECs and that increased SGs in polyamine-deficient cells are crucial for increased resistance to apoptosis.     

L1 cell adhesion molecule overexpression in hepatocellular carcinoma associates with advanced tumor progression and poor patient survival

Background

To investigate the expression of Golgi phosphoprotein-3 (GOLPH3) in prostate cancer and determine its prognostic value.

Methods

Immunohistochemical staining for GOLPH3 was performed on tissue microarrays of 342 prostate patients. The correlation between GOLPH3 expression with its clinicopathologic factors was also analyzed in order to determine its prognostic significance.

Results

GOLPH3 expression of normal prostate tissues, benign prostate hyperplasia, high-grade prostatic intraepithelial neoplasia, and hormone-dependent prostate cancer (HDPC) did not show any statistically significant difference. In contrast, statistically significant difference was reported in moderate/intense GOLPH3 expression in cases diagnosed with HDPC and castration resistant prostate cancer (CRPC) (P < 0.0005). Moderate /intense expression of GOLPH3 was associated with androgen independence (P?=?0.012), higher Gleason score (P?=?0.017), bone metastasis (P?=?0.024), higher baseline prostate-specific antigen (PSA) (P?=?0.038), and higher PSA nadir (P?=?0.032). A significantly negative correlation was found between moderate/intense GOLPH3 expression and disease-free survival (DFS) (HR?=?0.28, P?=?0.012) and overall survival (OS) (HR?=?0.42, P?=?0.027). Univariated analysis indicated that moderate/intense GOLPH3 expression created a significantly prognostic impact in patients with CRPC. On the other hand, multivariate analysis indicated that GOLPH3 was a significantly independent prognostic factor of DFS (P?=?0.027) in all prostate cancer patients.

Conclusions

In this study, it was discovered that the overexpression of GOLPH3 is associated with the transition of prostate cancer from hormone sensitive phase to hormone refractory phase. GOLPH3 might be an important prognostic factor of DFS and OS in patients with prostate cancer. In totality, GOLPH3 could be used as a novel candidate in devising a more effective therapeutic strategy to tackle CRPC.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1452541171722856.     

基于FPGA的随机字符发生器在ERP中的应用

脑电领域的众多探索一直以来都是各国科学家研究的热点。刺激源是脑电实验中不可或缺的一部分。刺激序列正确编排和稳定发生是诱发脑电信号被正确提取的先决条件。利用可编程逻辑器件作为随机字符信号发生器,使之同时具有计数和VGA显示功能,由此产生的视觉ERP刺激序列,可以作为脑区功能存在病变的病人的理想刺激源。     

CDK phosphorylates the polarisome scaffold Spa2 to maintain its localization at the site of cell growth

Polarisome is a protein complex that plays an important role in polarized growth in fungi by assembling actin cables towards the site of cell growth. For proper morphogenesis, the polarisome must localize to the right place at the right time. However, the mechanisms that control polarisome localization remain poorly understood. In this study, using the polymorphic fungus Candida albicans as a model, we have discovered that the cyclin‐dependent kinase (CDK) Cdc28 phosphorylates the polarisome scaffold protein Spa2 to govern polarisome localization during both yeast and hyphal growth. In a yeast cell cycle, Cdc28‐Clb2 phosphorylates Spa2 and controls the timing of polarisome translocation from the bud tip to the bud neck. And during hyphal development, Cdc28‐Clb2 and the hyphal‐specific Cdc28‐Hgc1 cooperate to enhance Spa2 phosphorylation to maintain the polarisome at the hyphal tip. Blocking the CDK phosphorylation causes premature tip‐to‐neck translocation of Spa2 during yeast growth and inappropriate septal localization of Spa2 in hyphae and abnormal hyphal morphology under certain inducing conditions. Together, our results generate new insights into the mechanisms by which fungi regulate polarisome localization in the control of polarized growth.     

肉鸭发酵床抗生素、重金属累积及细菌耐药性的演变特性

【目的】了解肉鸭发酵床使用过程中抗生素、各类金属元素累积特性,细菌抗生素耐受性演变特性。【方法】2011年11月至2013年7月,江苏某肉鸭发酵床养殖场饲养肉鸭期间,选取刚制作完成发酵床的鸭舍,和饲养4批次、8批次肉鸭时的鸭舍,检测发酵床中抗生素、金属元素含量,及发酵床中细菌的抗生素耐受水平。【结果】肉鸭发酵床垫料内强力霉素残留量因每批次肉鸭饲料中的使用而显著上升,氧氟沙星未现在垫料内累积。发酵床垫料饲养至8批次肉鸭时,垫料内耐受16、100μg/m L强力霉素三种可培养细菌的平均菌落数与比例为最高,而耐受8、50μg/m L氧氟沙星的平均菌落数、菌落数比例未现明显的增长趋势。发酵床使用过程中,垫料内As、Pb、Hg元素含量未显著增加,Cd元素检测量极低,Zn、Mn元素含量增加趋势明显,Cu、Cr元素累积速度缓慢。【结论】每批次使用强力霉素可在多批次肉鸭饲养后显著增加发酵床垫料中强力霉素含量,显著增强垫料中肠道菌群耐受强力霉素能力,Zn、Mn元素含量总体呈上升趋势。     

不同寄主来源的马铃薯Y病毒群体遗传结构的比较分析

文章以马铃薯Y病毒(Potato virus Y, PVY) P3和pipo基因为分子标记,比较分析烟草和马铃薯两个寄主的PVY遗传多样性和群体分化,并评估突变、选择、基因流等遗传力所起的作用。通过P3和pipo基因计算获得的烟草和马铃薯群体分化指数F_ST分别为0.116和0.120,且统计检验差异显著,表明烟草和马铃薯寄主的PVY之间中度分化。变异分析结果显示,烟草分离物P3和pipo基因的核苷酸序列一致性分别为85.2%~100%和76.5%~100%,而马铃薯分离物的P3和pipo基因的核苷酸序列一致性分别为95.7%~100%和93.0%~100%,表明烟草PVY变异程度高于马铃薯。同时,P3基因内检测到大量的净化选择位点,表明该基因大部分位点的变异为有害突变,在进化过程中被剔除。此外,P3基因内还检测到两个显著正向选择位点,表明这两个位点的变异为有益突变,有利于病毒的生存竞争。在pipo基因中未检测到显著的选择位点,表明该基因上的变异基本不受自然选择影响。通过P3和pipo基因计算烟草和马铃薯群体间的基因流Nm值分别为1.91和1.83,表明这两个群体间存在较强的基因交流。以上结果表明,来源于烟草和马铃薯寄主的PVY遗传差异显著,突变、自然选择以及基因流都影响两者的遗传多样性及遗传分化程度。