Search

Abstract Lysophosphatidic acid (LPA) is a bioactive lipid growth factor which is present in high levels in serum and platelets. LPA binds to its specific G-protein-coupled receptors, including LPA 1 to LPA 6 , thereby regulating various physiological functions, including cancer growth, angiogenesis, and lymphangiogenesis. Our previous study showed that LPA promotes the expression of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C in prostate cancer (PCa) cells. Interestingly, LPA has been shown to regulate the expression of calreticulin (CRT), a multifunctional chaperone protein, but the roles of CRT in PCa progression remain unclear. Here we investigated the involvement of CRT in LPA-mediated VEGF-C expression and lymphangiogenesis in PCa. Knockdown of CRT significantly reduced LPA-induced VEGF-C expression in PC-3 cells. Moreover, LPA promoted CRT expression through LPA receptors LPA 1 and LPA 3 , reactive oxygen species (ROS) production, and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). Tumor-xenografted mouse experiments further showed that CRT knockdown suppressed tumor growth and lymphangiogenesis. Notably, clinical evidence indicated that the LPA-producing enzyme autotaxin (ATX) is related to CRT and that CRT level is highly associated with lymphatic vessel density and VEGF-C expression. Interestingly, the pharmacological antagonist of LPA receptors significantly reduced the lymphatic vessel density in tumor and lymph node metastasis in tumor-bearing nude mice. Together, our results demonstrated that CRT is critical in PCa progression through the mediation of LPA-induced VEGF-C expression, implying that targeting the LPA signaling axis is a potential therapeutic strategy for PCa. Highlights • LPA regulates VEGF-C expression via calreticulin and subsequently induces lymphangiogenesis in prostate cancer cells. • LPA signaling is highly correlated with CRT, VEGF-C, and lymphatic vessel density in clinical prostate cancer patients. • Blockade of LPA signaling in prostate cancer cells significantly suppresses lymphangiogenesis and lymph node metastasis. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) infection has become a public health issue of worldwide concern and is a serious health problem in Taiwan, yet there are no approved effective antiviral drugs to treat DENV. The replication of DENV requires both viral and cellular factors. Targeting host factors may provide a potential antiviral strategy. It has been known that up-regulation of PI3K/AKT signaling and GRP78 by DENV infection supports its replication. AR-12, a celecoxib derivative with no inhibiting activity on cyclooxygenase, shows potent inhibitory activities on both PI3K/AKT signaling and GRP78 expression levels, and recently has been found to block the replication of several hemorrhagic fever viruses. However the efficacy of AR-12 in treating DENV infection is still unclear. Here, we provide evidence to show that AR-12 is able to suppress DENV replication before or after virus infection in cell culture and mice. The antiviral activities of AR-12 are positive against infection of the four different DENV serotypes. AR-12 significantly down-regulates the PI3K/AKT activity and GRP78 expression in DENV infected cells whereas AKT and GRP78 rescue are able to attenuate anti-DENV effect of AR-12. Using a DENV-infected suckling mice model, we further demonstrate that treatment of AR-12 before or after DENV infection reduces virus replication and mice mortality. In conclusion, we uncover the potential efficacy of AR-12 as a novel drug for treating dengue. [ABSTRACT FROM AUTHOR]

A topic that involves communities with different competing viewpoints or stances is usually reported by a large number of documents. Knowing the association between the persons mentioned in the documents can help readers construct the background knowledge of the topic and comprehend the numerous topic documents more easily. In this paper, we investigate the stance community identification problem where the goal is to cluster important persons mentioned in a set of topic documents into stance-coherent communities. We propose a stance community identification method called SCIFNET, which constructs a friendship network of topic persons from topic documents automatically. Stance community expansion and stance community refinement techniques are designed to identify stance-coherent communities of topic persons in the friendship network and to detect persons who are stance-irrelevant about the topic. The results of experiments based on real-world datasets demonstrate the effectiveness of SCIFNET and show that it outperforms many well-known community detection approaches and clustering algorithms. [ABSTRACT FROM AUTHOR]

Online group buying involves risks and uncertainties for buyers. Because buyers may not benefit from a failed group buying auction, they usually consider several factors before deciding to join an auction. Although the factors that affect buyers’ decisions have been investigated in the literature, few studies have attempted to utilize them to predict an auction’s success. In this paper, we propose an effective method for predicting the success of a group buying auction. We model success prediction as a classification problem, and utilize five dimensions and thirteen features derived from previous research to predict the success of group buying auctions. Experiments based on a real-world group buying platform demonstrate the efficacy of the proposed method. Moreover, the method outperforms a social propagation model in terms of the prediction precision rate, recall rate, and F1 score. [ABSTRACT FROM AUTHOR]

Abstract: Business indices and indicators are used to monitor the regime shifts of business cycles. Generally, the indices and indicators are comprised of various economic variables that are compiled by different government departments. Compiling the variables involves a great deal of data processing, which delays the monitoring of business cycles. In this paper, we propose a novel business cycle surveillance system that utilizes the query logs of search engines for business cycle modeling. The system employs an effective feature selection technique to identify query terms that are representative of business cycles. The selected terms and the frequency count of queries associated with the terms are then integrated to classify the status of business cycles. We use data discretization techniques to reduce the sparseness of query frequencies. Experimental results based on a five-year dataset show that the proposed system can classify the status of business cycles accurately, and the selected query terms reveal interesting human behavior patterns in different business cycles. Unlike economic variables, query logs are readily available through online Web services, so our system can provide business cycle information in a timely manner. [Copyright &y& Elsevier]

The association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC. We retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching. Immunohistochemical studies of HER2 on all available paraffin-embedded tumour samples, either from the primary tumour, the metastasis (brain and/or extracranial sites) or both, were performed and analysed. HER2 fluorescent in situ hybridisation was applied when necessary. The expression of HER2 was compared and correlated with survival. HER2 amplifications were detected in 16 (18.4%) of 87 and 9 (3.6%) of 249 patients who had specimens available in the BM and stage IV cohorts, respectively (P <.001). After propensity score matching, HER2 amplification was significantly associated with BM (odds ratio: 5.38, P =.003). HER2 heterogeneity was frequently observed not only at the single tumour level but also in paired tumour samples. A marginally significant longer survival since BM was found in patients having HER2-amplified mCRC than in those without (P =.07). HER2 amplification was significantly associated with BM in patients having mCRC and might have prognostic value for survival since BM. Given the heterogeneity of HER2 expression, the testing of HER2 status on available tissues from both primary and metastatic tumours should be encouraged. • Propensity score matching examined HER2 amplification and brain metastases. • High frequency of HER2 amplification in patients having metastatic colorectal cancer and brain metastasis was demonstrated. • Intra-patient heterogeneities of HER2 amplification were observed. [ABSTRACT FROM AUTHOR]