Genomics and proteomics approaches to the study of cancer-stroma interactions

<p>Abstract</p> <p>Background</p> <p>The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.</p> <p>Methods</p> <p>The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.</p> <p>Results</p> <p>We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (<it>ARID4A</it>, <it>CALR</it>, <it>GNB2L1</it>, <it>RNF10</it>, <it>SQSTM1</it>, <it>USP9X</it>) were validated by real time PCR.</p> <p>Conclusions</p> <p>A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.</p

The Impact of Trade and Investment Treaties on Fiscal Resources and Taxation in Developing Countries

Developing countries need fiscal revenue to build their infrastructure, achieve energy security and environmental sustainability, and provide social services necessary for human development. While trade and investment treaties have typically been assumed to be tax revenue-neutral, economic studies demonstrate that such is not, in fact, the case. The legal literature has not given much consideration to this issue, assuming instead that the tax effects of economic globalization have been addressed by bilateral tax treaties. However, constraints on developing countries’ fiscal resources resulting from trade and investment treaties are complex and nuanced, and they go much beyond the jurisdictional overlaps addressed by tax treaties. Trade and investment treaties constrain how countries design their tax policy, how they enforce it, and how they may change it. This study offers several findings on the impact of trade treaties on the ability to raise revenue and maps issues for policymakers to consider. It analyzes direct fiscal revenue decreases, such as those resulting from lower tariff rates, and indirect constraints on fiscal policy arising from non-discrimination obligations in trade and investment treaties, as well as other investor protection clauses. It then considers whether and to what extent exceptions and carve-out clauses preserve tax policy autonomy. Lastly, it assesses how some developing countries can carve out more policy autonomy for themselves against international regulatory encroachment in current negotiation

The Return of State Remedies in Investor-State Dispute Settlement: Trends in Developing Countries

This Article explores the variety of strategies deployed by developing countries to bypass traditional investor-state arbitration and assesses the limitations and drawbacks of these efforts. From giving preeminence to domestic courts of the host state to the resurgence of diplomatic protection and other state-based processes for solving investment disputes, these tactics are reminiscent of the pre-bilateral investment treaty era, where states played a more prominent role in foreign investment dispute resolution. The main proponents of such moves are Brazil, India, UNASUR, South Africa, and Indonesia. After an overview of initiatives from these countries, this Article analyzes the hurdles and limitations of state-centric dispute resolution. It concludes that relying purely on state remedies is unlikely to fully address investor-state dispute resolution, although it may increase the pressure to critically reassess the current investor-state arbitration system. Ultimately, this Article frames the return to state-controlled dispute settlement mechanisms as part of a broader trend to reassert host states’ control of foreign investment policy

The Return of State Remedies in Investor-State Dispute Settlement: Trends in Developing Countries

This Article explores the variety of strategies deployed by developing countries to bypass traditional investor-state arbitration and assesses the limitations and drawbacks of these efforts. From giving preeminence to domestic courts of the host state to the resurgence of diplomatic protection and other state-based processes for solving investment disputes, these tactics are reminiscent of the pre-bilateral investment treaty era, where states played a more prominent role in foreign investment dispute resolution. The main proponents of such moves are Brazil, India, UNASUR, South Africa, and Indonesia. After an overview of initiatives from these countries, this Article analyzes the hurdles and limitations of state-centric dispute resolution. It concludes that relying purely on state remedies is unlikely to fully address investor-state dispute resolution, although it may increase the pressure to critically reassess the current investor-state arbitration system. Ultimately, this Article frames the return to state-controlled dispute settlement mechanisms as part of a broader trend to reassert host states’ control of foreign investment policy