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Dengue viruses (DENV) are herein demonstrated for the first time as being able to infect and replicate in human primary lung epithelium and various lung cancer cell lines. The detection of dengue virus particles and viral negative strand RNA synthesis in the cell, in conjunction with the release of viral progenies in culture supernatants, support the notion that lung cells are susceptible to dengue virus infection. The replication efficiency of DENV in lung cancer cells from high to low is: DEN-2 (dengue virus type-2), DEN-3, DEN-4 and DEN-1. Moreover, the susceptibility of the six lung cancer cell lines to DEN-2 infection is: SW1573>A549>H1435; H23; H520; Bes2B. DEN-2 infection significantly increased the expression levels of IL-6 and RANTES in four of the six lung cancer cell lines, which is consistent with the high expression levels of these molecules in DHF/DSS patients. IL-6 expression induced by DEN-2 infection was NF-kappaB dependent. In summary, our results indicate that lung epithelial cell is a possible target of dengue viruses and IL-6 and RANTES may play pivotal roles in lung related immuno-pathogenesis.

This paper presents the ATPG performances of verifying USB2.0 IP core. Using the USB protocol and typical properties, the ATPG-based bounded model checking mechanism is revealed. Heuristics to accelerate the ATPG search are presented and their impacts are analyzed. We feel that results from this case study are applicable to serial communication circuits of the same family and can be scaled to industrial-sized circuits.

H460 is a non-small cell lung cancer (NSCLC) cell with multidrug resistance (MDR) against a variety of anti-cancer drugs such as cisplatin and transforming growth factor-beta (TGF-beta). It has been reported that hypoxia can trigger the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and the subsequent production of P-glycoprotein (P-gp, the archetype of MDR associated proteins or MRPs) that eventually lead to chemotherapeutic resistance of various cancer cell lines as well as NSCLC patients. The primary concern of this study was to know would hypoxia promote drug resistance of H460 cells via MRPs (MRP1 and MRP3). The experimental strategies applied were to evaluate the hypoxic impacts upon: 1) the drug resistance of H460 cells against doxorubicin (DOX, a commonly used chemotherapeutic drug in many cancer treatments), using MTT assay; 2) the expression of MRP1, MRP3 and HIF-1alpha of H460 cells in the absence or presence of DOX, using Western blot analysis; 3) the intracellular accumulation of DOX in H460 cells, using flow cytometry. The current results showed that DOX triggered a dose- and time-dependent cell death of H460. A hypoxia-induced DOX resistance was observed in H460 cells. Western blot analysis further showed that DOX-decreased MRP1 was further exacerbated under hypoxic condition that precluded the possible involvement of MRP1 in hypoxia-induced drug resistance. DOX on contrary increased the expression of MRP3. The potential contribution of MRP3 to hypoxia-induced DOX resistance and its role in pumping out of DOX from H460 cells are currently investigated in our laboratory. Finally, hypoxia-induced HIF-1alpha remained still high in the presence of DOX, suggesting a potential role of HIF-1alpha in promoting the DOX resistance of H460. Results from the study can uncover the molecular mechanisms underneath hypoxia-induced DOX resistance of H460 that consequently can lead to therapeutic target(s) for treatment of NSCLC cells (H460). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3803. doi:10.1158/1538-7445.AM2011-3803

Background Clinical manifestations of enterovirus 71 (EV71) range from herpangina, hand-foot-and-mouth disease (HFMD), to severe neurological complications. Unlike the situation of switching genotypes seen in EV71 outbreaks during 1998–2008 in Taiwan, genotype B5 was responsible for two large outbreaks in 2008 and 2012, respectively. In China, by contrast, EV71 often persists as a single genotype in the population and causes frequent outbreaks. To investigate genetic changes in viral evolution, complete EV71 genome sequences were used to analyze the intra-genotypic evolution pattern in Taiwan, China, and the Netherlands. Results Genotype B5 was predominant in Taiwan’s 2008 outbreak and was re-emergent in 2012. EV71 strains from both outbreaks were phylogenetically segregated into two lineages containing fourteen non-synonymous substitutions predominantly in the non-structural protein coding region. In China, genotype C4 was first seen in 1998 and caused the latest large outbreak in 2008. Unlike shifting genotypes in Taiwan, genotype C4 persisted with progressive drift through time. A majority of non-synonymous mutations occurred in residues located in the non-structural coding region, showing annual increases. Interestingly, genotype B1/B2 in the Netherlands showed another stepwise evolution with dramatic EV71 activity increase in 1986. Phylogeny of the VP1 coding region in 1971–1986 exhibited similar lineage turnover with genotype C4 in China; however, phylogeny of the 3D-encoding region indicated separate lineage appearing after 1983, suggesting that the 3D-encoding region of genotype B2 was derived from an unidentified ancestor that contributed to intra-genotypic evolution in the Netherlands. Conclusions Unlike VP1 coding sequences long used for phylogenetic study of enteroviruses due to expected host immune escape, our study emphasizes a dominant role of non-synonymous mutations in non-structural protein regions that contribute to (re-)emergent genotypes in continuous stepwise evolution. Dozens of amino acid substitutions, especially in non-structural proteins, were identified via genetic changes driven through intra-genotypic evolution worldwide. These identified substitutions appeared to increase viral fitness in the population, affording valuable insights not only for viral evolution but also for prevention, control, and vaccine against EV71 infection.

Background We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer.