Direct EGFR inhibition imaging in tageted treatment in neoplastic diseases

Epidermal growth factor receptor (EGFR) targeted therapy is a novel pharmacological approach to a treatment of neoplastic diseases in humans. In a clinical practice treatment results are currently monitored in vivo using indirect (not targeted to EGFR) imaging strategies, like computed tomography, ultrasound or classical magnetic resonance imaging. However, methods dedicated for direct EGFR imaging and based on positron emission tomography are already at the preclinical stage of development. In the paper, most important data related to direct EGFR expression imaging in neoplasms was reviewed. Onkol. Prak. Klin. 2010; 6, 5: 278–282Leczenie ukierunkowane na zahamowanie funkcji receptora czynnika wzrostu naskórka (EGFR) jest nowym podejściem farmakologicznym do terapii chorób nowotworowych u ludzi. Obecnie w praktyce klinicznej monitorowanie obrazowe wyników tego leczenia in vivo odbywa się w sposób pośredni (nieuwidaczniający obecności EGFR), za pomocą takich metod, jak tomografia komputerowa, ultrasonografia czy klasyczne obrazowanie rezonansu magnetycznego. Na etapie badań przedklinicznych znajdują się metody bezpośredniego obrazowania skuteczności tej terapii za pomocą pozytonowej tomografii emisyjnej. W tej publikacji uwzględniono najważniejsze dane dotyczące bezpośredniego obrazowania ekspresji EGFR w nowotworach. Onkol. Prak. Klin. 2010; 6, 5: 278–28

Does the functional polymorphism-1562C/T of MMP-9 gene influence brain disorders?

Metalloproteinase-9 (MMP-9) is one of the most strongly expressed matrix metalloproteinases (MMPs) in the brain. The MMP-9 activity in the brain is strictly regulated, and any disruptions in this regulation contribute to a development of many disorders of the nervous system including multiple sclerosis, brain strokes, neurodegenerative disorders, brain tumors, schizophrenia, or Guillain-Barré syndrome. This article discusses a relationship between development of the nervous system diseases and the functional single nucleotide polymorphism (SNP) at position -1562C/T within the MMP-9 gene. A pathogenic influence of MMP-9-1562C/T SNP was observed both in neurological and psychiatric disorders. The presence of the allele T often increases the activity of the MMP-9 gene promoter and consequently the expression of MMP-9 when compared to the allele C. This leads to a change in the likelihood of an occurrence of diseases and modifies the course of certain brain diseases in humans, as discussed below. The presented data indicates that the MMP-9-1562C/T functional polymorphism influences the course of many neuropsychiatric disorders in humans suggesting a significant pathological role of the MMP-9 metalloproteinase in pathologies of the human central nervous system

Fine-structural distribution of MMP-2 and MMP-9 activities in the rat skeletal muscle upon training: a study by high-resolution in situ zymography

Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix remodeling, but have also important intracellular targets. The purpose of this study was to examine the activity and subcellular localization of the gelatinases MMP-2 and MMP-9 in skeletal muscle of control and physically trained rats. In control hind limb muscle, the activity of the gelatinases was barely detectable. In contrast, after 5 days of intense exercise, in Soleus (Sol), but not Extensor digitorum longus (EDL) muscle, significant upregulation of gelatinolytic activity in myofibers was observed mainly in the nuclei, as assessed by high resolution in situ zymography. The nuclei of quiescent satellite cells did not contain the activity. Within the myonuclei, the gelatinolytic activity colocalized with an activated RNA Polymerase II. Also in Sol, but not in EDL, there were few foci of mononuclear cells with strongly positive cytoplasm, associated with apparent necrotic myofibers. These cells were identified as activated satellite cells/myoblasts. No extracellular gelatinase activity was observed. Gel zymography combined with subcellular fractionation revealed training-related upregulation of active MMP-2 in the nuclear fraction, and increase of active MMP-9 in the cytoplasmic fraction of Sol. Using RT-PCR, selective increase in MMP-9 mRNA was observed. We conclude that training activates nuclear MMP-2, and increases expression and activity of cytoplasmic MMP-9 in Sol, but not in EDL. Our results suggest that the gelatinases are involved in muscle adaptation to training, and that MMP-2 may play a novel role in myonuclear functions

Semi-Automatic Apparatus for Measuring Wetting Properties at High Temperatures

Determination of the physico-chemical interactions between liquid and solid substances is a key technological factor in many industrial processes in metallurgy, electronics or the aviation industry, where technological processes are based on soldering/brazing technologies. Understanding of the bonding process, reactions between materials and their dynamics enables to make research on new materials and joining technologies, as well as to optimise and compare the existing ones. The paper focuses on a wetting force measurement method and its practical implementation in a laboratory stand – an integrated platform for automatic wetting force measurement at high temperatures. As an example of using the laboratory stand, an analysis of Ag addition to Cu-based brazes, including measurement of the wetting force and the wetting angle, is presented

Studies on Wear of a Milling Chuck for a Production Line of Specialized Elements Used in Lockstitch Machines

The study aims to determine the wear intensity of selected milling chuck assembly surfaces covered with a protective DLC (Diamond Like Carbon) coating, used on the production line for elements of selected lockstitch machines, and to analyze the stress distributions in the object fixed with such a chuck for the characteristic load systems of this object during its processing. A model of the workpiece was developed using the finite element method. The boundary conditions, including the load and the method of clamping the workpiece, resulted from the parameters of the milling process and the geometric configuration of the milling chuck. Stress distributions in the workpiece for specific milling parameters and for various configurations of the milling chuck holding the workpiece are included in the article. The model experimental studies of wear were conducted in the contact zone between two surfaces covered with DLC: one on the element of the milling chuck pressing the workpiece and the other on the eccentric cams of this holder. The obtained wear values and shapes for the worn surfaces are also shown. The wear intensities for the steel plunger fins modelling swivel arm of the holder were by an order higher than those of corresponding steel shaft shoulders modelling eccentric cam of the holder. The linear wear intensities for these mating components may be expressed in terms of a function of average contact pressure and sliding speed in a corresponding contact zone. The indentation of eccentric cam into mating surface of the swivel arm of the holder increased nonlinearly with the enhancement of number of cycles of the eccentric cam

HuR (Elavl1) and HuB (Elavl2) Stabilize Matrix Metalloproteinase-9 mRNA During Seizure-Induced Mmp-9 Expression in Neurons

Matrix metalloproteinase-9 (Mmp-9) is involved in different general and cell-type–specific processes, both in neuronal and non-neuronal cells. Moreover, it is implicated in an induction or progression of various human disorders, including diseases of the central nervous system. Mechanisms regulating activity-driven Mmp-9 expression in neurons are still not fully understood. Here, we show that stabilization of Mmp-9 mRNA is one of the factors responsible for the neuronal activity-evoked upregulation of Mmp-9 mRNA expression in hippocampal neurons. Furthermore, we demonstrate that the molecular mechanism related to this stabilization is dependent on the neuronal seizure-triggered transiently increased binding of the mRNA stability-inducing protein, HuR, to ARE1 and ARE4 motifs of the 3′UTR for Mmp-9 mRNA as well as the stably augmented association of another mRNA-stabilizing protein, HuB, to the ARE1 element of the 3′UTR. Intriguingly, we demonstrate further that both HuR and HuB are crucial for an incidence of Mmp-9 mRNA stabilization after neuronal activation. This study identifies Mmp-9 mRNA as the first HuB target regulated by mRNA stabilization in neurons. Moreover, these results are the first to describe an existence of HuR-dependent mRNA stabilization in neurons of the brain