CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells and its only natural ligand, CCL25, is largely expressed in the thymus, which involutes with age. Other than the thymus, CCL25 is expressed by the small bowel. Interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for OvCa cells. The current study shows OvCa tissue and cells significantly express CCR9, which interacts with CCL25 to support carcinoma cell migration and invasion.</p> <p>Methods</p> <p>RT-PCR and flow cytometry techniques were used to quantify the expression CCR9 by OvCa cells. OvCa tissue microarrays (TMA) was used to confirm CCR9 expression in clinical samples. The Aperio ScanScope scanning system was used to quantify immunohistochemical staining. Cell invasion and migration assays were performed using cell migration and matrigel invasion chambers. Matrix metalloproteinase (MMP) mRNAs were quantified by RT-PCR and active MMPs were quantified by ELISA.</p> <p>Results</p> <p>Our results show significantly (<it>p </it>< 0.001) higher expression of CCR9 by mucinous adenocarcinoma, papillary serous carcinoma, and endometriod ovarian carcinoma cases, than compared to non-neoplastic ovarian tissue. Furthermore, CCR9 expression was significantly elevated in OvCa cell lines (OVCAR-3 and CAOV-3) in comparison to normal adult ovarian epithelial cell mRNA. OvCa cells showed higher migratory and invasive potential towards chemotactic gradients of CCL25, which was inhibited by anti-CCR9 antibodies. Expression of collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), and stromelysins (MMP-3, -10, and -11) by OvCa cells were modulated by CCL25 in a CCR9-dependent fashion.</p> <p>Conclusions</p> <p>These results demonstrate both biological significance and clinical relevance of CCL25 and CCR9 interactions in OvCa cell metastasis.</p

Open Multi-Agent Systems with Discrete States and Stochastic Interactions

We consider a multi-agent system in which agents arrive and depart from a network randomly as a Bernoulli process. Each agent that is active in the network must decide between two actions represented by 0 or 1. Each active agent then observes the action of a random neighbour and updates its preference towards a certain action. New agents that arrive into the network are activated with a random preference and action. This means that the notion of consensus in the standard sense can no longer be applied and instead, we provide conditions under which majority action preservation occurs when the number of agents is arbitrarily large. This property will imply that a large fraction of the active agent population will retain their action almost surely

Forskolin Editing via Radical Iodo- and Hydroalkylation

The modification of highly oxygenated forskolin as well as manoyl and epi-manoyl oxide, two less functionalized model substrates sharing the same polycyclic skeleton, via intermolecular carbon-centered radical addition to the vinyl moiety has been investigated. Highly regio- and reasonably stereoselective iodine atom transfer radical addition (ATRA) reactions were developed. Unprotected forskolin afforded an unexpected cyclic ether derivative. Protection of the 1,3-diol as an acetonide led the formation of the iodine ATRA product. Interestingly, by changing the mode of initiation of the radical process, in situ protection of the forskolin 1,3-diol moiety as a cyclic boronic ester took place during the iodine ATRA process without disruption of the radical chain process. This very mild radical-mediated in situ protection of 1,3-diol is expected to be of interest for a broad range of radical and non-radical transformations. Finally, by using our recently developed tert-butyl­catechol-mediated hydroalkylation procedure, highly efficient preparation of forskolin derivatives bearing an extra ester or sulfone group was achieved

Specific aspects of training IT students for modeling pulses in physics

This study presents a method for teaching fundamental aspects in mathematics and physics for students in informatics and information technology, so as these concepts to be available for modeling suddenly emerging phenomena at any moment of time during the last years of study. By teaching basic aspects using the language of their specialty and by addressing questions connected to the mathematical or physical model adequate for their projects at unexpected moment of time (using a computer connected at a local network or wireless e-mail connection of mobile phones) the students are able to improve their abilities of qualitative analysis of phenomena. Moreover, their technical judgment patterns can be established in an objective manner. Finally students in Informatics and Information Technology are able not only to understand basic phenomena in physics and electronics, but also to simulate complex phenomena as suddenly emerging pulses in a proper manner, the importance of quick and proper answers being underlined in their mind. © Springer-Verlag Berlin Heidelberg 2005

Output regulation problems in hybrid systems

This entry discusses some of the salient features of the output regulation problem for hybrid systems, especially in connection with the steady-state characterization. In order to better highlight such peculiarities, the discussion is mostly focused on the simplest class of linear time-invariant systems exhibiting such behaviors. In comparison with the usual regulation theory, the role played by the zero dynamics and by the presence of more inputs than outputs is particularly striking

Output regulation of hybrid linear systems: solvability conditions and structural implications

Hybrid output regulation aims at ensuring that the output of a hybrid system under control converges to a desired reference, despite the influence of unknown initial conditions and unmeasured disturbances, assuming that both references and disturbances are described as the output of an exosystem with a known model and unknown initial state. The main objective of this paper is to show how structural methods, based on tools from the geometric approach to control theory, allow a deep understanding of a plethora of surprising and unprecedented phenomena arising in output regulation problems for linear hybrid systems in the presence of time-driven periodic jumps, which do not possess any counterpart in classical output regulation