Inhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation status

Cataloged from PDF version of article.The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is involved in cell survival and anti-apoptotic signaling. Akt has been shown to be constitutively expressed in a variety of human tumors including hepatocellular carcinoma (HCC). In this report we analyzed the status of Akt pathway in three HCC cell lines, and tested cytotoxic effects of Akt pathway inhibitors LY294002, Wortmannin and Inhibitor VIII. In Mahlavu human hepatoma cells Akt was constitutively activated, as demonstrated by its Ser473 phosphorylation, downstream hyperphosphorylation of BAD on Ser136, and by a specific cell-free kinase assay. In contrast, Huh7 and HepG2 did not show hyperactivation when tested by the same criteria. Akt enzyme hyperactivation in Mahlavu was associated with a loss of PTEN protein expression. Akt signaling was inhibited by the upstream kinase inhibitors, LY294002, Wortmannin, as well as by the specific Akt Inhibitor VIII in all three hepatoma cell lines. Cytotoxicity assays with Akt inhibitors in the same cell lines indicated that they were all sensitive, but with different IC50 values as assayed by RT-CES. We also demonstrated that the cytotoxic effect was through apoptotic cell death. Our findings provide evidence for its constitutive activation in one HCC cell line, and that HCC cell lines, independent of their Akt activation status respond to Akt inhibitors by apoptotic cell death. Thus, Akt inhibition may be considered as an attractive therapeutic intervention in liver cancer. © Springer Science+Business Media, LLC 2010

Rivalry and uncertainty in complementary investments with dynamic market sharing

We study the effects of revenue and investment cost uncertainty, as well non- preemption duopoly competition, on the timing of investments in two complementary inputs, where either spillover-knowledge is allowed or proprietary-knowledge holds. We find that the ex-ante and ex-post revenue market shares play a very important role in firms’ behavior. When competition is considered, the leader’s behavior departs from that of the monopolist firm of Smith (Ind Corp Change 14:639–650, 2005). The leader is justified in following the conventional wisdom (i.e., synchronous investments are more likely), whereas, the follower’s behavior departs from that of the conventional wisdom (i.e., asynchronous investments are more likely)

Cloud computing in industrial SMEs: Identification of the barriers to its adoption and effects of its application

ABSTRACT: Cloud computing is a new technological paradigm that may revolutionize how organizations use IT by facilitating delivery of all technology as a service. In the literature, the Cloud is treated mainly through a technological approach focused on the concept definition, service models, infrastructures for its evelopment and security problems. However, there is an important lack of works which analyze this paradigm adoption in SMEs and its results, with a gap between the technological development and its adoption by organizations. This paper uses a qualitative technique methodology -group meetings with managers- and a quantitative one-survey- and identifies which factors act as barriers to Cloud adoption and which positive effects its application generates in 94 industrial SMEs. The conclusion is that the main barriers are of a cultural type and that the positive effects go well beyond reducing costs

Access Charges, Vertical Separation, and Lobbying

We examine how vertical separation affects the lobbying activities for the access charge of essential facilities. First, when investigating a model where the number of new entrants is fixed, we find that vertical separation either increases or decreases the access charge, and that this depends on the relative efficiency between the incumbent and the new entrants, and the number of entrants. Second, when investigating a freeentry market, we find that vertical separation always reduces the access charge in such a market. The vertically integrated firm has a stronger incentive to lobby in this market because a higher access charge reduces the number of competitors

The Law and Economics of Intermediaries of Personal Information

This paper explores a class of firms: the intermediaries of personal information. In the economics of personal information, scarcity is no longer the only, and foremost, determinant of value. The most important determinant of value becomes connection. Adapting what Gervais claims to be the first law of an information-flooded cloud-modelled economy, value is not derived from scarcity but rather from the fact that those who value it most will find it. Personal information is the raw material to create connections. Intermediaries collect personal information in exchange for goods or services, regardless of whether they actually need that information to perform their main activity, and use this information to connect other goods and services with the users who value them most, e.g. via personalisation or targeted advertising. Many firms in many different sectors are, or could become, intermediaries of personal information, from Google to supermarkets, from telecom operators to insurance companies. The descriptive analysis of this industry has consequences in terms of business model and regulatory approach. As for the former, it is worth exploring the conditions for which a firm could profitably become an intermediary of personal information and thereby exploit untapped resources for revenue generation. As for the latter, an imperfect understanding of the economics of personal information creates the risk for misaligned norms, and therefore for an uneven competition