Mast cells mediate malignant pleural effusion formation.

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1 beta, which in turn induced pleural vasculature leakiness and triggered NF-kappa B activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenbcarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable

Parmenides: an opportunity for ISO TC37 SC4?

Despite the many initiatives in recent years aimed at creating Language Engineering standards, it is often the case that different projects use different approaches and often define their own standards. Even within the same project it often happens that different tools will require different ways to represent their linguistic data. In a recently started EU project focusing on the integration of Information Extraction and Data Mining techniques, we aim at avoiding the problem of incompatibility among different tools by defining a Common Annotation Scheme internal to the project. However, when the project was started (Sep 2002) we were unaware of the standardization effort of ISO TC37/SC4, and so we commenced once again trying to define our own schema. Fortunately, as this work is still at an early stage (the project will last till 2005) it is still possible to redirect it in a way that it will be compatible with the standardization work of ISO. In this paper we describe the status of the work in the project and explore possible synergies with the work in ISO TC37 SC4

Life without Geminin

The interplay of proliferation and differentiation is essential for normal development and organogenesis. Geminin is a cell cycle regulator which controls licensing of origins for DNA replication, safeguarding genomic stability. Geminin has also been shown to regulate cellular decisions of self-renewal versus commitment of neuronal progenitor cells. We discuss here our recent analysis of mice with conditional inactivation of the Geminin gene in the immune system. Our data indicate that Geminin is not indispensable for every cell division: in the absence of Geminin, development of progenitor T-cells appears largely unaffected. In contrast, rapid cell divisions, taking place in vitro upon TCR receptor activation or in vivo during homeostatic proliferation, are defective