ObjectiveTo analyze the efficacy of gemcitabine with or without erlotinib for pancreatic cancer, and to determine the predictive role of epidermal growth factor receptor (EGFR) and KRAS mutations in these patients.MethodsThis was a single-center, randomized, open-label, prospective trial. Eighty-eight chemotherapy-naïve metastatic pancreatic cancer patients were randomized for treatment with gemcitabine or gemcitabine plus erlotinib. EGFR and KRAS mutations were analyzed, respectively. The primary endpoint was the disease control rate.ResultsDisease control rate (64% vs. 25%; P < 0.001), progression-free survival (median 3.8 vs. 2.4 months; P < 0.001), and overall survival (median 7.2 vs. 4.4 months; P < 0.001) were better in the gemcitabine plus erlotinib group than in the gemcitabine alone group. In the gemcitabine plus erlotinib group, disease control (85% vs. 33%; P = 0.001), progression-free survival (median 5.9 vs. 2.4 months; P = 0.004), and overall survival (median 8.7 vs. 6.0 months; P = 0.044) were better in patients with EGFR mutations than in those without EGFR mutations. KRAS mutation was not associated with treatment response or survival.ConclusionsGemcitabine plus erlotinib is more effective than gemcitabine alone for treating metastatic pancreatic cancer patients, especially those with EGFR mutations. ClinicalTrials.gov number, NCT01608841.

Background: Mevastatin (MVS), a 3-hydroxy-3-methylglutaryl coenzyme, a reductase (HMG-CoA) inhibitor, has anti-inflammatory effects potentially via up-regulation of heme oxygenase-1 (HO-1). However, the mechanisms underlying MVS-induced HO-1 expression remain largely unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). Methods: HO-1 and intercellular adhesion molecule (ICAM)-1 expression were determined using real-time PCR, Western blotting, and promoter reporter analyses. The signaling components were investigated using pharmacological inhibitors or specific small interfering RNA (siRNA)s. Interaction between Nrf2 and the antioxidant response element (ARE) binding site for the HO-1 promoter was determined by chromatin immunoprecipitation (ChIP) assay. Results: Upregulation of HO-1 by MVS attenuated the tumor necrosis factor (TNF)-α-stimulated ICAM-1 expression associated with THP-1 adhesion to HPAEpiCs. These inhibitory effects of HO-1 were reversed by tin protoporphyrin (SnPP)IX or by transfection with HO-1 siRNA. MVS-induced HO-1 expression was mediated via NADPH oxidase (Nox)-derived reactive oxygen species (ROS) generation. Activation of Nox2/ROS further stimulated the phosphorylation of p47phox, proto-oncogene tyrosine-protein kinase (c-Src), platelet-derived growth factor receptor (PDFGR)α, protein kinase B (Akt), and Nrf2, which were inhibited by siRNAs. Pretreatment with pharmacological inhibitors, including diphenyleneiodonium (DPI), apocynin (APO), N-acetyl-L-cysteine (NAC), PP1, AG1296, or LY294002, reduced the MVS-activated Nrf2 nuclear-translocation binding to the ARE on the HO-1 promoter. Conclusions: MVS-induced HO-1 is, at least in part, mediated through a p47phox/Nox2/ROS-dependent activation of c-Src/PDGFRα/PI3K/Akt-regulated Nrf2/ARE axis and suppresses the TNF-α-mediated inflammatory responses in HPAEpiCs.

The purpose of this study was focused on exploring the relationship among the fans’ preferences, fans’ para-social interaction, and fans’ word-of-mouth. A survey consisted of 21 items based on the literature review and developed by this study. An online survey was distributed to the users of YouTube in Taiwan. A total of 606 valid samples was collected by survey. The instrument passed the reliability and validity test. Further, the data process applied the PLS (partial least squares) regression analysis methodology. The result shows that the ‘attractive’ impacted ‘para-social interaction’, ‘e-word-of-mouth’, and ‘preferences of fans’ positively. In addition, the para-social interaction plays an important role as a mediator between influencer’s attractiveness, w-word-of-mouth, and preferences of fans. Some suggestions were provided for social media influence’ related studies as reference.

Nowadays, enterprises are trying hard to reach sustainability when the industry faces the challenge of high cost in the era of meager profit. Companies with corporate sustainable approaches based on cost leadership are trying to reduce operational expenses, increase business efficiency, and implement comprehensive cost reductions within their organisations. Cost is a strategic issue for businesses to survive and stand out. The deployment of profit costs is becoming strategically important to be sustainable and competitive in the market. The research design of this study integrates both qualitative and quantitative methods. 143 valid responses to snowball sampling in Taiwan (108 responses) and mainland China (35 responses) and 24 interviews with executive-level employees in Taiwan were conducted. In addition, a total of 51 companies’ financial statements were reviewed to triangulate the foundation of research findings. Reducing costs strategically should be considered as a principal concern of a firm that wants to make its efforts for business sustainability. The result shows that nonstrategic costs are between 10 and 30 percent of the sales turnover (revenue) in a firm, and strategic costs normally account for 70 to 90 percent of its all costs. Furthermore, only 20% really makes a difference to stand out from other market players. This provides a new orientation of cost management opinion that there is a need for paying more attention and extending the concept of strategic cost management to the management of nonstrategic costs. It is also supported that the dichotomy of nonstrategic and strategic is a viable and practical way for managing all costs across sectors, industries, and business scales from a strategic and sustainable perspective.

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