Human breast cancer cell metastasis is attenuated by lysyl oxidase inhibitors through down-regulation of focal adhesion kinase and the paxillin-signaling pathway

The extracellular matrix (ECM) plays a critical role in the development and invasion of primary breast tumors. Lysyl oxidase (LOX), which is an ECM remodeling enzyme, appears to play roles in promoting cancer cell motility and invasion. To ascertain whether LOX overexpression in breast tumor tissues from Asian patients is associated with decreases in metastasis-free and overall survival in breast cancer patients, the mRNA levels of LOX were examined in paired tumor/normal tissue samples using real-time RT-PCR analysis (n = 246 pair-matched samples). To test whether specifically targeting LOX by inhibiting its activity (using beta-aminopropionitrile (β-APN), a LOX inhibitor), mRNA expression (using siRNA), or protein expression (using 25 μM magnolol) attenuates the invasion of MDA-MB-231 breast cancer cells, a cancer cell migration assay was performed. Interestingly, only 78.5% (n = 193) of the breast cancer tumors displayed detectable LOX expression. Nearly 60% (n = 120) of the cases fell into Group 1 (tumor > normal, T > N); in this group, the mean LOX expression in the tumor cells was 20.2-fold greater than in normal cells. However, in Group 2 (normal > tumor, N > T), the LOX expression level in most of the normal tissues examined (80%, 59/73) was less than fivefold greater than in the tumor tissues. The increased level of active LOX in the invasive breast cancer cell line MDA-MB-231 was accompanied by the increased phosphorylation of focal adhesion kinase at Tyr-576 and of paxillin at Tyr-118. We also found that the addition of β-APN (300 μM) and magnolol (25 μM), synergistically inhibited the migration and invasion of MDA-MB-231 cells. In this article, we describe, for the first time, higher expression of a LOX protein in breast tumors compared with normal tissues from Asian patients. Moreover, the results indicate that the inhibition of LOX using magnolol may represent a more desirable strategy for breast cancer therapy than the use of β-APN.     

A TMS examination of semantic radical combinability effects in Chinese character recognition

The proposal of human foveal splitting assumes a vertical meridian split in the foveal representation and the consequent contralateral projection of information in the two hemifields to the two hemispheres and has been shown to have important implications for visual word recognition. According to this assumption, in Chinese character recognition, the two halves of a centrally fixated character may be initially projected to and processed in different hemispheres. Here, we describe a repetitive transcranial magnetic stimulation (rTMS) investigation of hemispheric processing in Chinese character recognition, through examining semantic radical combinability effects in a character semantic judgment task. The materials used were a dominant type of Chinese character which consists of a semantic radical on the left and a phonetic radical on the right. Thus, according to the split fovea assumption, the semantic and phonetic radicals are initially projected to and processed in the right hemisphere and the left hemisphere, respectively. We show that rTMS over the left occipital cortex impaired the facilitation of semantic radicals with large combinability, whereas right occipital rTMS did not. This interaction between stimulation site and radical combinability reveals a flexible division of labor between the hemispheres in Chinese character recognition, with each hemisphere responding optimally to the information in the contralateral visual hemifield to which it has direct access. The results are also consistent with the split fovea claim, suggesting functional foveal splitting as a universal processing constraint in reading.     

去糖基化改变rNav1．3门控性质：糖基化／去糖基化的动态平衡可能使电压门控钠通道的调控功能更具复杂性

目的 观察糖基化对rNav1.3电压门控性质的影响.方法 将rNav1.3在爪蟾卵母细胞中表达,衣霉素抑制其糖基化,双电极电压钳记录全细胞电流,Origin软件分析处理数据.对照组为未去糖基化的rNav1.3.结果 与糖基化的rNav1.3相比,去糖基化的rNav1.3稳态激活曲线向去极化方向偏移约10 mV,稳态失活曲线向超极化方向偏移约8 mV.结论 糖基化修饰改变rNav1.3的电压门控性质,异化其生理功能.     

Efficacy and safety of thalidomide in patients with hepatocellular carcinoma

INTRODUCTION Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer in the world. About one million people die of it each year[1,2]. Particularly in Taiwan, it poses a tremendous threat to citizens’ health and lives. HCC has been the leading c…     

Validation of structured scoring using the LA classification for esophagitis and endoscopically suspected Barrett's esophagus in a tertiary Asian endoscopy center

Aim:  To determine the inter-observer agreement and validity of the LA Classification in scoring the severity of esophagitis in Asian patients.
Methods:  Video endoscopy clips were selected from 45 consecutive patients participating in reflux studies. The videos were viewed by endoscopists who then independently scored the presence, severity and distribution of esophagitis, including endoscopically suspected Barrett's esophagus (ESBE). Each video was discussed and a consensus on findings reached. Kappa (k) correlation was calculated to describe inter-observer agreement.
Results:  Thirty-five clips were scored (no esophagitis 20%, grade-A 54%, grade-B 23%, grade-C 3%, respectively and 10 clips were excluded for poor imaging). Excellent agreement was noted on the presence of esophagitis (mean k = 0.79, range 0.77–0.82). Fifteen patients (42%) had ESBE with a mean k of 0.48 (range 0.39–0.60). Inter-observer agreement on the LA grade was good (mean k = 0.58, range 0.55–0.63), whilst in agreement between endoscopists and consensus grading, the mean kappa rose to 0.77 (range 0.73–0.81). There was a trend of increasing agreement as viewings progressed, with superior kappa correlation after 16 cases. Evaluation of the extent of esophagitis showed good k values using the alternative approach of grouping by circumferential extent (mean k = 0.64, range 0.60–0.67) at the lower categories of severity.
Conclusions:  Scoring using the LA classification for esophagitis and the concurrence on the presence of ESBE showed moderate to strong agreement amongst Asian endoscopists. Our results also suggested that an alternative method of scoring esophagitis based on proportion of circumferential involvement was reliable. A learning effect was observed and reliable scoring was achieved after 16 patients.     

Identification of Taiwan and China-like recombinant avian infectious bronchitis viruses in Taiwan

Infectious bronchitis virus (IBV) infections in poultry cause great economic losses to the poultry industry worldwide. The emergence of viral variants complicates disease control. The IBV strains in Taiwan were clustered into two groups, Taiwan group I and Taiwan group II, based on the S1 gene. A variant was previously identified and showed a distinct S1 gene homology with other local strains. This study investigated the 3′ 7.3 kb genome of eight Taiwan strains isolated from 1992 to 2007. The genes of interest were directly sequenced. Sequence analyses were performed to detect any recombination event among IBVs. The results demonstrated that all of the examined viruses maintained the typical IBV genome organization as 5′-S-3a-3b-E-M-5a-5b-N-UTR-3′. In the phylogenetic analyses, various genes from one strain were clustered into separate groups. Moreover, frequent recombination events were identified in the Simplot analyses among the Taiwan and China CK/CH/LDL/97I-type strains. Putative crossover sites were located in the S1, S2, 3b, M genes and the intergenic region between the M and 5a genes. All of the recombinants showed chimeric IBV genome arrangements originated from Taiwan and China-like parental strains. Field IBVs in Taiwan undergo genetic recombination and evolution.     

Effect of lipoprotein (a) on annexin A5 binding to cell membrane

BackgroundHigh blood lipoprotein (a) [Lp(a)] concentration is a risk factor for a thrombotic event. Annexin A5 is involved in anticoagulation on the endothelial surface. How Lp(a) affects the annexin A5 function is not clear. This study investigates annexin A5 binding on the cell membrane in the presence of Lp(a).MethodsLp(a) was isolated from human blood plasma by ultracentrifugation and annexin A5 protein was purchased commercially. The cell membrane was prepared from primary human umbilical vein endothelial cells (HUVEC) and cultured cell line HepG2 by sucrose density gradient centrifugation. Enzyme-linked immunosorbent assays (ELISA) were used to examine annexin A5 binding to the cell membrane in the presence of Lp(a). Flow cytometry was used to analyze the binding of fluorescence-labeled annexin A5 to phosphatidylserine (PS)-translocated intact cells in the presence of Lp(a).ResultsAnnexin A5 binding to the cell membrane was attenuated by a high concentration of Lp(a) in both HUVEC and HepG2 membrane surfaces. The phenomenon was also observed with annexin A5 surface labeling of HepG2 cells and flow cytometry analysis.ConclusionsThe results imply that Lp(a) interferes with annexin A5 binding to the procoagulant PS which translocates to the membrane surface under stress condition and therefore may increase the risk for thrombosis.