Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Extracellular vesicles in gastrointestinal cancer in conjunction with microbiota: On the border of Kingdoms

Abstract Extracellular vesicle (EV) production is a universal feature of metazoan cells as well as prokaryotes (bMVs - bacterial microvesicles). They are small vesicles with phospholipid membrane carrying proteins, DNA and different classes of RNAs and are heavily involved in intercellular communication acting as vectors of information to target cells. For the last decade, the interest in EV research has exponentially increased though thorough studies of their roles in various pathologies that was not previously possible due to technical limitations. This review focuses on research evaluating the role of EV production in gastrointestinal (GI) cancer development in conjunction with GI microbiota and inflammatory diseases. We also discuss recent studies on the promising role of EVs and their content as biomarkers for early diagnosis of GI cancers.The bMVs have also been implicated in the pathogenesis of GI chronic inflammatory diseases, however, possible role of bMVs in tumorigenesis remains underestimated. We propose that EVs from eukaryotic cells as well as from different microbial, fungi, parasitic species and edible plants in GI tract act as mediators of intracellular and inter-species communication, particularly facilitating tumor cell survival and multi-drug resistance.In conclusion, we suggest that matching sequences from EV proteomes (available from public databases) with known protein sequences of microbiome gut bacteria will be useful in identification of antigen mimicry between evolutionary conservative protein sequences. Using this approach we identified Bacteroides spp. pseudokinase with activation loop and homology to PDGFRα, providing a proof-of-concept strategy. We speculate that existence of microbial pseudokinase that ‘mimics’ PDGFRα may be related to PDGFRα and Bacteroides spp. roles in colorectal carcinogenesis that require further investigation

Personalized diagnosis and therapy.

Personalized medicine, i.e., the use of information about a person’s genes, proteins, metabolites, and environment to prevent, diagnose, and treat disease, has been much talked about in recent years. So some observers are wondering what the excitement is all about cumulating in the following statement: “Personalized health care is nothing new. Doctors have always tried to fit the therapy to the patient’s need if possible.” But what has happened more recently is that one has now begun to go a level deeper, i.e., to explore the biology of the disease and its treatment at the molecular level. However, molecular medicine does not per se define personalized medicine, but the molecular tools are important as they should enable greater relevance in the information provided by corresponding diagnostic tests (see below) (Edwards et al. 2008; Weedon et al. 2006; Romeo et al. 2007; Hegel et al. 1999; Wildin et al. 2001; Grant et al. 2006; Rothman and Greenland 2005; Raeder et al. 2006; Hegele et al. 2000; Capell and Collins 2006; Delepine et al. 2000; Janssens et al. 2006; Xiayan and Legido-Quigley 2008; Figeys and Pinto 2001; Müller 2002, 2010; Pearson et al. 2007; Janssens et al. 2008; Risch and Merikangas 1996; Janssens and van Duijn 2008; McCarthy 2003; McCarthy et al. 2003; Stumvoll et al. 2005; Lyssenko et al. 2005; Florez et al. 2003)