Time filter

Source Type

Sebens S.,Institute of Experimental Medicine | Schafer H.,Laboratory of Molecular Gastroenterology and Hepatology
Current Pharmaceutical Biotechnology | Year: 2012

Tumors irrespective of their origin are heterogenous cellular entities whose growth and progression greatly depend on reciprocal interactions between genetically altered (neoplastic) cells and their non-neoplastic microenvironment. Thus, microenvironmental factors promote many steps in carcinogenesis, e.g. proliferation, invasion, angiogenesis, metastasis and chemoresistance. Drug resistance, either intrinsic or acquired, essentially limits the efficacy of chemotherapy in many cancer patients. To some extent, this resistance is maintained by reduced drug accumulation, alterations in drug targets and increased repair of drug-induced DNA damage. However, the pivotal mechanism by which tumor cells elude the cytotoxic effect of chemotherapeutic drugs is their efficient protection from induction and excecution of apoptosis. It is meanwhile well established that cellular and non-cellular components of the tumoral microenvironment, e.g. myofibroblasts and extracellular matrix (ECM) proteins, respectively, contribute to the anti-apoptotic protection of tumor cells. Cellular adhesion molecules (e.g. L1CAM or CD44), chemokines (e.g. CXCL12), integrins and other ECM receptors which are involved in direct and indirect interactions between tumor cells and their microenvironment have been identified as suitable molecular targets to overcome chemoresistance. Accordingly, several therapeutic strategies based on these targets have been already elaborated and tested in preclinical and clinical studies, including inhibitors and blocking antibodies for CD44/hyaluronan, integrins, L1CAM and CXCL12. Even though these approaches turned out to be promising, the upcoming challenge will be to prove the efficacy of these strategies in improving treatment and prognosis of cancer patients. © 2012 Bentham Science Publishers. Source

Haller J.,Institute of Experimental Medicine | Harold G.,University of Sussex | Sandi C.,Ecole Polytechnique Federale de Lausanne | Neumann I.D.,University of Regensburg
Journal of Neuroendocrinology | Year: 2014

We review the impact of early adversities on the development of violence and antisocial behaviour in humans, and present three aetiological animal models of escalated rodent aggression, each disentangling the consequences of one particular adverse early-life factor. A review of the human data, as well as those obtained with the animal models of repeated maternal separation, post-weaning social isolation and peripubertal stress, clearly shows that adverse developmental conditions strongly affect aggressive behaviour displayed in adulthood, the emotional responses to social challenges and the neuronal mechanisms activated by conflict. Although similarities between models are evident, important differences were also noted, demonstrating that the behavioural, emotional and neuronal consequences of early adversities are to a large extent dependent on aetiological factors. These findings support recent theories on human aggression, which suggest that particular developmental trajectories lead to specific forms of aggressive behaviour and brain dysfunctions. However, dissecting the roles of particular aetiological factors in humans is difficult because these occur in various combinations; in addition, the neuroscientific tools employed in humans still lack the depth of analysis of those used in animal research. We suggest that the analytical approach of the rodent models presented here may be successfully used to complement human findings and to develop integrative models of the complex relationship between early adversity, brain development and aggressive behaviour. © 2014 British Society for Neuroendocrinology. Source

Vasilyev V.B.,Institute of Experimental Medicine
Biochemical Society Transactions | Year: 2010

The first detailed report of a specific interaction of CP (caeruloplasmin) with another protein described its complex with LF (lactoferrin) in 2000. Since then, several protein-protein interactions involving CP have been reported, mostly concerning iron-containing proteins. The CP-LF complex was studied thoroughly, and evidence of reciprocal effects of CP and LF was obtained. Another specific interaction investigated in detail occurs between CP and MPO (myeloperoxidase). CP-LF, CP-MPO and CP-LF-MPO complexeswere found in sera of patients with inflammation. Modelling in vitro allowed understanding of which structural peculiarities of CP and partners allow the modification of their functions in a complex. The present paper reviews the latest data on complexes of CP with LF and MPO, and advances some suggestions about their role in health and disease. ©The Authors. Source

Milman B.L.,Institute of Experimental Medicine
TrAC - Trends in Analytical Chemistry | Year: 2015

The review is devoted to chemical identification using mass spectrometry as the most powerful technique of qualitative analysis. The review begins with consideration of basic principles and means of chemical identification. Following are sections covering techniques and instruments and metrological issues. Procedures for identification outlined next are divided into target identification by methods and unknown/non-target analysis. For the latter, information support, such as mass spectral libraries and chemical databases, programs of formula generation and spectral prediction/interpretation, are reviewed. Finally, identification of samples and some general trends are briefly noted. © 2014 Elsevier B.V. Source

Golubev A.,Institute of Experimental Medicine
Journal of Theoretical Biology | Year: 2010

Positively skewed distributions common in biology are often approximated with lognormal or gamma functions. It is shown here that for some classes of phenomena, including intermitotic time and protein expression variabilities, exponentially modified Gaussian (EMG) may provide better fit. EMG is generated by processes involving normally distributed entry rates and exponentially distributed exit rates; therefore, its parameters may be straightforwardly interpreted in biologically meaningful terms and thus may help to choose between theoretical models of the respective phenomena. In particular, EMG is consistent with the transition probability model of cell cycle and may be used to estimate its deterministic and probabilistic parts. EMG is also consistent with the assumption that the probabilistic part is determined by competing stochastic transcriptional events committing cells to proliferative mitoses, differentiation, or apoptosis. Discrete event simulation modelling of this situation suggests that cell differentiation rate is primarily increased by decreasing the frequencies of the events that result in the realisation of the competing options, including proliferation, rather than by the direct changes in the differentiation-inducing events. © 2009 Elsevier Ltd. All rights reserved. Source

Discover hidden collaborations