Bisociative knowledge discovery for microarray data analysis

Peer reviewe

SegMine workflows for semantic microarray data analysis in Orange4WS

Peer reviewe

Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours

Proteolytic enzymes are highly relevant in different processes of cancer progression. Their interplay with other signalling molecules such as cytokines represents important regulation of multicellular cross-talk. In this review, we discuss protease regulation mechanisms of cytokine signalling in various types of cancer. Additionally, we highlight the reverse whereby cytokines have an impact on protease expression in an autocrine and paracrine manner, representing complex feedback mechanisms among multiple members of these two protein families. The relevance of the protease-cytokine axis is illustrated in glioblastoma, where interactions between normal mesenchymal stem cells and cancer cells play an important role in this very malignant form of brain cancer

The Role of c-Abl Tyrosine Kinase in Brain and Its Pathologies

Differentiated status, low regenerative capacity and complex signaling make neuronal tissues highly susceptible to translating an imbalance in cell homeostasis into cell death. The high rate of neurodegenerative diseases in the elderly population confirms this. The multiple and divergent signaling cascades downstream of the various stress triggers challenge researchers to identify the central components of the stress-induced signaling pathways that cause neurodegeneration. Because of their critical role in cell homeostasis, kinases have emerged as one of the key regulators. Among kinases, non-receptor tyrosine kinase (Abelson kinase) c-Abl appears to be involved in both the normal development of neural tissue and the development of neurodegenerative pathologies when abnormally expressed or activated. However, exactly how c-Abl mediates the progression of neurodegeneration remains largely unexplored. Here, we summarize recent findings on the involvement of c-Abl in normal and abnormal processes in nervous tissue, focusing on neurons, astrocytes and microglial cells, with particular reference to molecular events at the interface between stress signaling, DNA damage, and metabolic regulation. Because inhibition of c-Abl has neuroprotective effects and can prevent neuronal death, we believe that an integrated view of c-Abl signaling in neurodegeneration could lead to significantly improved treatment of the disease

Endothelialization of Polyethylene Terephthalate Treated in SO2 Plasma Determined by the Degree of Material Cytotoxicity

Improving the biocompatibility of polyethylene terephthalate (PET) vascular grafts is an important task for avoiding thrombus formation. Therefore, SO2 plasma at various treatment periods were used to modify PET surface properties by forming sulfate functional groups. These groups were shown to act antithrombogenically, ensuring good hemocompatibility of the materials, although the biocompatibility of such materials still remains a mystery. For this reason, the adhesion and viability of HUVEC cells on SO2 plasma-modified PET surfaces were studied, and the possible toxicity of the tested material was determined using two different assays, MTT (metabolic activity assay) and SRB (in-vitro toxicology assay). Changes in chemical composition, morphology and wettability were determined as well. Improved endothelialization was observed for all plasma-treated samples, with the most optimal being the sample treated for 80 s, which can be explained by it having the best combination of surface functionalization, roughness and morphology. Furthermore, toxicity was observed to some extent on the sample treated for 160 s, indicating the lowest cell density among the plasma-treated samples. X-ray photoelectron spectroscopy showed increased oxygen and sulfur content on the surface, which was independent on treatment time. Surface roughness of the plasma-treated samples increased, reaching its maximum after 80 s of treatment, and decreased thereafter

The role of stem cells in glioma progression and therapy

The concepts of tumour origin and stochastic nature of carcinogenesis are being challenged today by hierarchical models that predict the existence of cancer stem cells (CSCs), which are postulated as unique cell population capable of infinite self renewal, multilineage differentiation and having a higher resistance to conventional cancer therapy thus facilitating malignant growth and therapy resistance. Accordingly, successful treatment of adult brain tumourglioma and its most malignant stageglioblastoma multiforme (GBM), would require the elimination of CSCs to avoid tumour relapse. Yet, with available therapy (i.e. surgery) in GBMs this cannot be achieved, due to infiltrative growth of a subpopluation of GBM cells with highly expressed migratory genes (migratome) into the normal brain tissue. Besides CSCs a proven prerequisite for tumour development and progression, tumour bulk mass also comprises haematopoietic stem cells, endothelial progenitor cells and mesenchymal stem cells (MSCs). The role of these other types of stem cell was shown to largely depend on the tumour microenvironment, where their contradictory anti-tumour action was evidenced. Yet, the exact mechanisms and MSCs role in cell-mediated modulation of tumour behaviour via paracrine and direct interactions with GBM (stem) cells still remain unknown. Nevertheless these stem cells, particularly MSCs, may represent novel therapeutic vectors for enhanced target-site delivery of chemotherapeutics, which are urgently needed to improve efficiency of current glioma treatment. So far, cell therapy using MSCs appears promising, due to MSCs selective tumour tropism and their immuno-modulatory potential regarding treatment of GBM, which will be discussed in this review