Search results for "SIGNALLING"
showing 10 items of 249 documents
Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy.
2010
Drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. It is a goal of drug development programs to design selective ligands that act on single disease targets to obtain highly effective and safe drugs with low side effects. Although this strategy was successful for many new therapies, there is a marked decline in the number of new drugs introduced into clinical practice over the past decades. One reason for this failure may be due to the fact that the pathogenesis of many diseases is rather multi-factorial in nature and not due to a single cause. Phytotherapy, whose therapeutic efficacy is based on th…
Cancer: Clinical Background and Key Challenges
2011
This chapter is aimed at a wide audience ranging from biologists to medical students and cancer specialists. It provides a comprehensive overview of systems approaches to the pathology and treatment of cancer. In particular, it addresses diagnosis and therapy by interconnecting various aspects of cancer at both the molecular and clinical level, and contrasts the unifying features of malignancies with the daunting diversity of cancer types, stages, and evolutionary processes during treatment. The importance is emphasized of both prevention and innovative treatments in reducing the cancer burden, and of early detection as the link between these two major areas. It sets the stage for analysis …
Neuronal nitric oxide synthase modulates maturation of human dendritic cells.
2010
AbstractDendritic cells (DCs) are the most potent APCs of the immune system. Understanding the intercellular and intracellular signaling processes that lead to DC maturation is critical for determining how these cells initiate T cell-mediated immune processes. NO synthesized by the inducible NO synthase (iNOS) is important for the function of murine DCs. In our study, we investigated the regulation of the arginine/NO-system in human monocyte-derived DCs. Maturation of DCs induced by inflammatory cytokines (IL-1β, TNF, IL-6, and PGE2) resulted in a pronounced expression of neuronal NOS (nNOS) but only minimal levels of iNOS and endothelial NOS were detected in human mature DCs. In addition, …
A note on beliefs formation in signalling games
1994
Abstract We present a new criterion, called incentive dominance, for belief formation in signalling games, which subsumes refinements criteria such as equilibrium dominance and divinity. It captures the principle of forward induction through explicitly modelling the player's thought process when forming preliminary beliefs.
Signalling molecules and growth factors for tissue engineering of cartilage-what can we learn from the growth plate?
2009
Modern tissue engineering concepts integrate cells, scaffolds, signalling molecules and growth factors. For the purposes of regenerative medicine, fetal development is of great interest because it is widely accepted that regeneration recapitulates in part developmental processes. In tissue engineering of cartilage the growth plate of the long bone represents an interesting, well-organized developmental structure with a spatial distribution of chondrocytes in different proliferation and differentiation stages, embedded in a scaffold of extracellular matrix components. The proliferation and differentiation of these chondrocytes is regulated by various hormonal and paracrine factors. Thus, mem…
Regulation ofMUC1Expression in Human Mammary Cell Lines by the c-ErbB2 and Ras Signaling Pathways
2001
The MUC1 protein is a highly O-glycosylated transmembrane molecule that is expressed at the luminal surface of most glandular epithelial cells and is upregulated in carcinomas. Here, we report the effect of the activation of the c-ErbB2 --Ras pathway on the expression of the MUC1 gene in the nontumorigenic mammary cell lines MTSV1-7 and HB2 and in the malignant cell lines T47D and ZR75. Endogenous levels of MUC1 mRNA and protein in HB2 clones permanently overexpressing c-ErbB2 or V12-H-Ras were markedly reduced compared with levels in the parental cell lines. Furthermore, in transient transfection assays, the transcription of a CAT reporter construct driven by the MUC1 promoter was inhibite…
Transmission of Information in Neoplasia by Extracellular Vesicles.
2015
Paracrine interactions among neoplastic and nonneoplastic cells in the immediate tumor microenvironment are important for tumor growth and metastatic spreading. Most of the studies in the past decade addressing these cellular interactions have focused on tumor cell-derived soluble molecules. Recently, these studies and interest have shifted to nanosized extracellular vesicles (EVs) and especially ectosome and exosome-associated molecules [1]. They contain not only proteins, but also lipids, mRNA, and microRNA [1], which can regulate gene expression in their target cells in a much more pleiotropic manner [1]. While exosomes originate by a sequential process of inward budding of late endosome…
Indomethacin enhances endothelial NO release — evidence for a role of PGI2 in the autocrine control of calcium-dependent autacoid production
1998
Objective: We studied whether NO or prostacyclin (PGI2), which are continuously released by endothelial cells, have autocrine/paracrine effects on the calcium-dependent autacoid production by modulating the intracellular Ca2+ concentration ([Ca2+]i). Methods: Histamine(His)-induced [Ca2+]i increases (Fura 2-method) and NO-dependent cGMP increase were measured in human umbilical vein endothelial cells (HUVECs) before and after cyclooxygenase inhibition or application of cAMP- and cGMP-elevating drugs. Results: 0.3 μM His increased endothelial [Ca2+]i from 77±2 nM to 418±59 nM. The His-induced [Ca2+]i increases were significantly attenuated following treatment with PGI2 (by 23%) and forskolin…
Comparative study assessing effects of sonic hedgehog and VEGF in a human co-culture model for bone vascularisation strategies.
2011
The morphogen sonic hedgehog (Shh) seems to mediate adult repair processes in bone regeneration and vascularisation. In this study we investigated the effects of Shh on co-cultures consisting of human primary osteoblasts and outgrowth endothelial cells in terms of angiogenic activation and vessel maturation in comparison to the treatment with the commonly used proangiogenic factor, VEGF. Both, stimulation with VEGF or Shh, leads to an increase in the formation of microvessel-like structures compared to untreated controls. In contrast to VEGF, proangiogenic effects by Shh could already be observed after 24 h of treatment. Nevertheless, after 14 days the angiogenic activity of OEC was compara…
The evolution of nitric oxide signalling diverges between the animal and the green lineages
2019
AbstractNitric oxide (NO) is a ubiquitous signalling molecule with widespread distribution in prokaryotes and eukaryotes where it is involved in countless physiological processes. While the mechanisms governing nitric oxide (NO) synthesis and signalling are well established in animals, the situation is less clear in the green lineage. Recent investigations have shown that NO synthase, the major enzymatic source for NO in animals, is absent in land plants but present in a limited number of algae. The first detailed analysis highlighted that these new NO synthases are functional but display specific structural features and probably original catalytic activities. Completing this picture, analy…