Auswahl der wissenschaftlichen Literatur zum Thema „Fused and non-fused flavins“

The need for reliable and cost-effective testing procedures for Additive Manufacturing (AM) is growing. In this Dissertation, the development of a new computational-experimental method based on the realization of specific testing artifacts to address this need is presented. This research is focused on one of the widely utilized AM technologies, Fused Deposition Modeling (FDM), and can be extended to other AM technologies as well. In this method, testing artifacts are designed with simplified boundary conditions and computational domains that minimize uncertainties in the analyses. Testing artifacts are a combination of thin and thick cantilever structures, which allow measurement of natural frequencies, mode shapes, and dimensions as well as distortions and deformations. We apply Optical Non-Destructive Testing (ONDT) together with computational methods on the testing artifacts to predict their natural frequencies, thermal flow, mechanical properties, and distortions as a function of 3D printing parameters. The complementary application of experiments and simulations on 3D printed testing artifacts allows us to systematically investigate the density, porosity, moduli of elasticity, and Poisson’s ratios for both isotropic and orthotropic material properties to better understand relationships between these characteristics and the selected printing parameters. The method can also be adapted for distortions and residual stresses analyses. We optimally collect data using a design of experiments technique that is based on regression models, which yields statistically significant data with a reduced number of iterations. Analyses of variance of these data highlight the complexity and multifaceted effects of different process parameters and their influences on 3D printed part performance. We learned that the layer thickness is the most significant parameter that drives both density and elastic moduli. We also observed and defined the interactions among density, elastic moduli, and Poisson’s ratios with printing speed, extruder temperature, fan speed, bed temperature, and layer thickness quantitatively. This Dissertation also shows that by effectively combining ONDT and computational methods, it is possible to achieve greater understanding of the multiphysics that governs FDM. Such understanding can be used to estimate the physical and mechanical properties of 3D printed components, deliver part with improved quality, and minimize distortions and/or residual stresses to help realize functional components.

La fabbricazione additiva è una classe di metodi di fabbricazione in cui il componente viene costruito aggiungendo strati di materiale l’uno sull’altro, sino alla completa realizzazione dello stesso. Si tratta di un principio di fabbricazione sostanzialmente differente da quelli tradizionali attualmente utilizzati, che si avvalgono di utensili per sottrarre materiale da un semilavorato, sino a conferire all’oggetto la forma desiderata, mentre i processi additivi non richiedono l’utilizzo di utensili. Il termine più comunemente utilizzato per la fabbricazione additiva è prototipazione rapida. Il termine “prototipazione”’ viene utilizzato in quanto i processi additivi sono stati utilizzati inizialmente solo per la produzione di prototipi, tuttavia con l’evoluzione delle tecnologie additive questi processi sono sempre più in grado di realizzare componenti di elevata complessità risultando competitivi anche per volumi di produzione medio-alti. Il termine “rapida” viene invece utilizzato in quanto i processi additivi vengono eseguiti molto più velocemente rispetto ai processi di produzione convenzionali. La fabbricazione additiva offre diversi vantaggi dal punto di vista di: • velocità: questi processi “rapidi” hanno brevi tempi di fabbricazione. • realizzazione di parti complesse: con i processi additivi, la complessità del componente ha uno scarso effetto sui tempi di costruzione, contrariamente a quanto avviene nei processi tradizionali dove la realizzazione di parti complesse può richiedere anche settimane. • materiali: la fabbricazione additiva è caratterizzata dalla vasta gamma di materiali che può utilizzare per la costruzione di pezzi. Inoltre, in alcuni processi si possono costruire pezzi le cui parti sono di materiali diversi. • produzioni a basso volume: molti processi tradizionali non sono convenienti per le produzioni a basso volume a causa degli alti costi iniziali dovuti alla lavorazione con utensili e tempi di setup lunghi.

La structuration laser femtoseconde en trois dimensions rencontre un intérêt grandissant du fait de sa facilité de mise en œuvre et des nombreuses applications qu’elle peut couvrir dans le domaine des composants photoniques. Des structures telles que des guides d’onde, des réseaux de diffraction, des mémoires optiques ou des cristaux photoniques peuvent être fabriquées grâce à cette technique. Son emploi sur des verres oxydes est prometteur car ces derniers présentent des avantages certains ; ils sont très résistants au flux et au vieillissement, leur composition chimique peut être changée facilement afin de s’adapter à un cahier des charges précis. On les retrouve déjà dans les amplificateurs Raman, les fibres optiques, les lasers à fibres, etc… Le travail de cette thèse s’articule autour de deux grands axes. Le premier axe consiste à caractériser les propriétés optiques linéaires et non-linéaires de matériaux vitreux massifs afin d’optimiser leur composition en vue d’une application particulière. Dans ce contexte, les propriétés optiques non-linéaires, leurs origines physiques (électronique et nucléaire) ainsi que leurs temps de réponse caractéristiques (de quelques femtosecondes à quelques centaines de picosecondes) sont décrits dans le cadre de l’approximation de Born-Oppenheimer. Ainsi, la silice fondue et plusieurs verres sodo-borophosphates contenant différentes concentrations en oxyde de niobium ont été étudiés. Les résultats montrent que les propriétés optiques non-linéaires dans la silice fondue sont majoritairement d’origine électronique, alors que dans les verres sodo-borophosphates, la contribution d’origine nucléaire peut devenir prépondérante lorsque la concentration en oxyde de niobium dépasse 30%. Le second axe s’articule autour de la structuration des matériaux. Trois échantillons commerciaux de silice fondue présentant des conditions de fabrication différentes (donc des taux d’impuretés distincts) et irradiés avec un laser femtoseconde proche infrarouge ont été étudiés. Les défauts induits par laser ont été identifiés au moyen de plusieurs techniques de spectroscopie. Elles ont montré la formation de centres colorés ainsi qu’une densification au niveau de la zone irradiée. Leurs propriétés optiques linéaire (indice de réfraction) et non-linéaire (susceptibilité du troisième ordre) ont été mesurées. De plus, la structuration de la silice fondue à l’échelle sub-micrométrique sous forme de « nano-réseaux » est observée et la biréfringence de forme induite par ces structures est discutée. En plus des échantillons de silice fondue, plusieurs verres oxydes présentant des compositions chimiques très distinctes ont été étudiés. Un verre sodo-borophosphate contenant de l’oxyde de niobium exhibe des micro-craquelures et des nano-crystallites après irradiation. Un verre silicate contenant ou non de l’argent dévoile des structures en anneau fluorescentes ou en « nano-réseaux ». Un verre zinc phosphate contenant de l’argent présente lui aussi des structures en anneau fluorescentes, d’une taille de l’ordre de 80 nm, bien inférieure à la limite de diffraction. Des techniques pompe-sonde sous microscope ont été mises en œuvre sur ce dernier verre pour étudier l’interaction laser-verre. Le mécanisme d’absorption de l’énergie lumineuse pour ce verre est l’absorption à quatre photons. La densité d’électrons libres générée est de l’ordre de 1017 cm-3, ce qui permet de conclure qu’un gaz d’électrons plutôt qu’un plasma se forme pendant l’irradiation laser<br>Three-dimensional femtosecond laser structuring has a growing interest because of its ease of implementation and the numerous possible applications in the domain of photonic components. Structures such as waveguides, diffraction gratings, optical memories or photonic crystals can be fabricated thanks to this technique. Its use with oxide glasses is promising because of several advantages; they are resistant to flux and ageing, their chemical composition can easily be changed to fit the well-defined requirements of an application. They can already be found in Raman amplifiers, optical fibers, fiber lasers, and other devices. This thesis is based on two axes. The first axis consists in characterizing the linear and nonlinear optical properties of bulk vitreous materials in order to optimize their composition with a particular application in view. Within this context, the nonlinear optical properties, their physical origins (electronic and nuclear) as well as their characteristic response times (from a few femtoseconds to a few hundreds of picoseconds) are described within the Born-Oppenheimer approximation. Fused silica and several sodium-borophosphate glasses containing different concentrations in niobium oxide have been studied. Results show that the nonlinear optical properties of fused silica are mainly from electronic origin, whereas in the sodium-borophosphate glasses, the contribution from nuclear origin becomes predominant when the concentration of niobium oxide exceeds 30%. The second axis is based on the structuring of materials. Three commercially available fused silica samples presenting different fabrication conditions (therefore distinct impurity levels) and irradiated with a near infrared femtosecond laser have been studied. The laser induced defects have been identified by means of several spectroscopic techniques. They show the formation of color centers as well as a densification inside the irradiated area. Their linear refractive index and nonlinear third-order susceptibility properties have been measured. Moreover, the structuring of fused silica at the subwavelength scale into “nanogratings” is observed and the form of birefringence induced by these structures is discussed. In addition to the fused silica samples, several oxide glasses presenting very distinct chemical compositions have been studied. A sodium-borophosphate glass containing niobium oxide exhibits micro-cracks and nano-crystallites following irradiation. A silicate glass with or without a silver component reveals fluorescent rings or “nanograting” structures. A zinc phosphate glass containing silver also presents fluorescent ring structures, with a size of the order of 80 nm, well below the diffraction limit. Pump-probe microscope techniques have been performed on this glass to investigate the laser-glass interaction. The absorption mechanism is determined to be four-photon absorption. The generated free electron density is ~ 1017 cm-3, which suggests the conclusion that an electron gas rather than a plasma is formed during the laser irradiation

Chacun des 176 faisceaux du Laser MégaJoule (LMJ) délivrera une énergie de 8 kJ à 351 nm, dans le régime nanoseconde, sur une cible millimétrique. Ce flux laser est susceptible d’être absorbé par des défauts présents sous la surface des optiques et d’endommager le composant. L’optique étant affaiblie dans les zones endommagées, tir après tir, les dommages absorbent le flux laser, et leurs surfaces augmentent. Le composant optique le plus sensible de l’installation est le hublot de chambre, composant épais (34mm) exposé à de fortes valeurs de flux laser à 351 nm. Le but de cette thèse est d’étudier l’initiation et la croissance des dommages sur ce composant avec un faisceau laser dont les propriétés sont proches de celles du LMJ. Un tel faisceau est délivré par le banc d’endommagement laser MELBA, permettant d’atteindre des valeurs de flux similaires à celles du LMJ sur un profil spatial homogène circulaire dont le diamètre est de l’ordre du centimètre et avec un profil temporel accordable. Cette étude est organisée en trois axes. Premièrement, la mesure de l’amorçage des dommages sur des composants épais, en tenant compte de l’impact de l’effet Kerr. Deuxièmement, l’étude de la croissance d’une population de dommages en fonction de la fluence et de la durée d’impulsion. Troisièmement, l’étude de la croissance de très gros dommages, de tailles millimétriques<br>Each of the 176 beams of the Laser MégaJoule (LMJ) facility will deliver an energy of 8 kJ at 351 nm, in the nanosecond regime, on a millimeter scale target. This energy density is likely to be absorbed by sub-surface defects induced by the polishing processes. This absorption eventually leads to laser-induced damage sites. These initiated damage sites absorb the laser energy during the subsequent shots and are likely to grow in size. The thick (34mm) optical windows situated after the frequency conversion module are exposed to the highest laser energies at 351nm and are the most sensitive to these phenomena. The goal of this thesis is to study the initiation and growth of damage sites on thick optical components with a laser beam that have similar properties to those of a LMJ beam. Such a beam can be delivered by the MELBA facility which can reach similar energy densities to those that can be found on the LMJ. The beam energy is evenly distributed on a centimeter scale circular aperture and the pulse shape and duration can be defined by the user. Three main axes have been explored in this work. The measurement of damage initiation on thick fused silica optical components have firstly been studied with an accurate metrology of the energy density after the propagation through the optical component, thus taking Kerr small scale self focusing into account. The growth of a population of damage sites have secondly been studied as a function of the laser fluence and pulse duration. Finally, the growth of damage sites up to millimeter scales have been studied

La fatigue du seuil d’endommagement laser dans la silice fondue a été largement étudiée au cours des dernières années, car ce phénomène est directement lié à la durée de vie des matériaux optiques utilisés dans des applications laser, le plus souvent à forte puissance. En effet, dans l’UV, on observe une décroissance du seuil d’endommagement laser quand le nombre de tirs laser augmente. Ce phénomène a été attribué pour ce couple longueur d’onde-matériau à des modifications laser-induites dans le matériau. Sous irradiation laser multiple à 266 nm, en utilisant des impulsions nanosecondes de densité d’énergie constante, nous avons observé que le signal de photoluminescence est modifié jusqu’à l’endommagement. A partir de cela, nous proposons une nouvelle représentation des données expérimentales qui permet de prédire l’apparition d’un endommagement dans le matériau. Cette prédiction réalisée à partir du signal de fluorescence et non de la statistique d’endommagement utilisée jusque-là, permet une économie significative de surface de composant et du temps d’expérience. Afin d’étendre l’intérêt de l’étude à un plus grand nombre d’applications, une extension des résultats à la longueur d’onde de 355 nm est proposée. Nous proposons un modèle où l’endommagement dans la silice fondue sous irradiation multiple à 266 nm est causé par une accumulation de modifications laser-induites induisant de l’autofocalisation non-linéaire. Afin d’essayer de généraliser la méthode de diagnostic de la fatigue par fluorescence, nous avons aussi réalisé des tests préliminaires sur des cristaux optiques non-linéaires bien connus comme le LBO ou le KDP<br>Fatigue effects in fused silica have been largely studied in the past years, as this phenomenon is directly linked to the lifetime of high power photonic materials. Indeed, in the UV regime, we observe a decrease of the LIDT (Laser-Induced Damage Threshold) when the number of laser shots increases and this has been attributed for this couple wavelength/material to laser-induced material modifications. Under 266 nm laser irradiation, with nanosecond pulses of constant fluence, we observed that the photoluminescence is modified until damage occurs. Based on this observation, we propose a new representation of the experimental S-on-1 breakdown data which allows predicting the occurrence of material breakdown. This prediction, based on fluorescence signal and not damage statistics (presently widely used) allows consuming fewer sample surface and saving time. To extend the interest of the study to many more applications, we propose an extension of the results at 355 nm. We suppose that damage is caused in our fused silica samples by accumulation of laser-induced modifications under multiple-pulse UV irradiation inducing catastrophic non-linear self-focusing. In order to try to extend the fatigue diagnostic method by fluorescence, we have also realized preliminary tests in well-known non-linear crystals like LBO and KDP

Le lymphome à cellules du manteau (LCM) est une hémopathie maligne B mature, appartenant à la famille des lymphomes non hodgkiniens. Le LCM est caractérisé par la translocation t(11;14)(q13;q32) qui provoque une expression aberrante de cycline D1. C’est une pathologie rare mais à haut risque de rechute, et qui reste le plus souvent incurable suite à l’apparition de clones chimiorésistants. L’acquisition de résistance est intimement liée aux interactions entre les cellules tumorales et leur microenvironnement. Afin de mimer de la manière la plus pertinente possible ces interactions, nous avons mis en place un modèle murin de xénogreffe en utilisant les lignées cellulaires de LCM JeKo1, REC1, Z138 et Granta-519 que nous avons modifiées afin qu’elles expriment un fluorophore (GFP ou m-cherry) et/ou le gène codant pour la luciférase. Après injection aux souris du substrat de la luciférase, la luciférine, nous sommes en mesure de suivre au cours du temps la progression tumorale. Nous pouvons également évaluer le degré d’infiltration tumorale dans la moelle osseuse, la rate, le cerveau et le sang après euthanasie des animaux, par des techniques de cytométrie en flux et d’immunocytochimie. Ce modèle nous a permis de montrer l’intérêt thérapeutique d’un inhibiteur de l’exportine 1 (XPO1) : le KPT 330 (ou selinexor) qui est capable de contenir cycline D1 uniquement au niveau nucléaire. Nous avons montré que la localisation subcellulaire de cycline D1, est retrouvée majoritairement cytoplasmique dans certaines lignées cellulaires de LCM (2/7) et chez un certain nombre de patients (6/42, 14%), et est associée à un fort potentiel d’invasion, de migration et à un phénotype agressif. Par ailleurs, grâce à ce modèle, nous avons pu objectiver le manque d’efficacité in vivo d’agonistes aux récepteurs aux œstrogènes de type β (ER β). Ces récepteurs, présents sur les lymphocytes B étaient supposés inhiber la prolifération cellulaire et provoquer la mort des cellules par apoptose. L’utilisation de deux agonistes des ER β, le diarylpropionitrile (DPN) et l’ERB-041 a montré une absence d’effet de ces molécules, lorsque les cellules tumorales sont au contact de leur microenvironnement. D’autre part, afin de mieux comprendre les mécanismes de résistance aux chimiothérapies, nous avons étudié la résistance de la lignée cellulaire REC-1 traitée par des agents génotoxiques. Nous avons montré que cette lignée présentait une anomalie de dégradation de cycline D1 associée à une activité diminuée du protéasome 26S. Enfin, nous avons montré dans des travaux préliminaires que la protéine fused in sarcoma (FUS) pourrait, lorsqu’elle est associée à cycline D1, être capable de réguler les voies de réparation des dommages à l’ADN. Des anomalies de ces voies induisent une grande instabilité génétique responsable de l’échappement des tumeurs aux traitements, le ciblage de FUS pourrait par conséquent présenter un intérêt thérapeutique.Pris dans leur ensemble, ces résultats permettent de renforcer ou d’infirmer l’intérêt de certaines cibles thérapeutiques dans l’espoir de pouvoir continuer à améliorer la prise en charge des patients. Ils fournissent également un outil pour l’évaluation de nouvelles molécules dans un modèle murin prenant en compte les interactions entre la cellule tumorale et son microenvironnement<br>Mantle cell lymphoma (MCL) is a mature malignant hemopathy, belonging to the non-Hodgkin's lymphoma family. The MCL is characterized by the translocation t(11;14)(q13;q32) which causes an aberrant expression of cyclin D1. It is a rare disease but at high risk of relapse, and it is most often incurable due to the appearance of chemoresistant clones. The acquisition of resistance is intimately linked to the interactions between the tumor cells and their microenvironment. In order to mimic, in the most relevant way, these interactions, we have implemented a mouse xenograft model using the MCL cell lines JeKo1, REC1, Z138 and Granta-519 which we have modified so that they express a fluorophore (GFP or m-cherry) and / or the gene encoding the luciferase. After injection to the mice of the luciferase substrate, luciferin, we are able to follow over time the tumor progression. We can also assess the degree of tumor infiltration in bone marrow, spleen, brain and blood after euthanasia of animals, by flow cytometry and immunocytochemistry. This model allowed us to show the therapeutic interest of an inhibitor of exportin 1 (XPO1): the KPT 330 (or selinexor) which is able to contain cyclin D1 only on the nuclear level. We have shown that the subcellular localization of cyclin D1 is mainly cytoplasmic in some LCM (2/7) cell lines and in a number of patients (6/42, 14%), and is associated with a high potential Invasion, migration and an aggressive phenotype. Moreover, thanks to this model, we have been able to objectify the in vivo lack of efficacy of agonists to β-type estrogen receptors (ER β). These receptors, present on B lymphocytes, were thought to inhibit cell proliferation and cause cell death by apoptosis. The use of two ER β agonists, diarylpropionitrile (DPN) and ERB-041 showed an absence of effect of these molecules, when the tumor cells are in contact with their microenvironment. On the other hand, in order to better understand the mechanisms of resistance to chemotherapies, we studied the resistance of the REC-1 cell line treated with genotoxic agents. We have shown that this line has an abnormality of cyclin D1 degradation associated with decreased activity of the 26S proteasome. Finally, we have shown in preliminary work that the fused in sarcoma protein (FUS) could, when associated with cyclin D1, be able to regulate the repair pathways of DNA damage. Abnormalities of these pathways induce a great genetic instability responsible for the escape of tumors to treatments, the targeting of FUS could therefore be of therapeutic interest.Taken as a whole, these results reinforce or invalidate the interest of certain therapeutic targets in the hope of continuing to improve the management of patients. They also provide a tool for evaluating new molecules in a murine model that takes into account the interactions between the tumor cell and its microenvironment

Today, the main research field for the automotive industry is to find solutions for active safety. In order to perceive the surrounding environment, tracking nearby traffic objects plays an important role. Validation of the tracking performance is often done in staged traffic scenarios, where additional sensors, mounted on the vehicles, are used to obtain their true positions and velocities. The difficulty of evaluating the tracking performance complicates its development. An alternative approach studied in this thesis, is to record sequences and use non-causal algorithms, such as smoothing, instead of filtering to estimate the true target states. With this method, validation data for online, causal, target tracking algorithms can be obtained for all traffic scenarios without the need of extra sensors. We investigate how non-causal algorithms affects the target tracking performance using multiple sensors and dynamic models of different complexity. This is done to evaluate real-time methods against estimates obtained from non-causal filtering. Two different measurement units, a monocular camera and a LIDAR sensor, and two dynamic models are evaluated and compared using both causal and non-causal methods. The system is tested in two single object scenarios where ground truth is available and in three multi object scenarios without ground truth. Results from the two single object scenarios shows that tracking using only a monocular camera performs poorly since it is unable to measure the distance to objects. Here, a complementary LIDAR sensor improves the tracking performance significantly. The dynamic models are shown to have a small impact on the tracking performance, while the non-causal application gives a distinct improvement when tracking objects at large distances. Since the sequence can be reversed, the non-causal estimates are propagated from more certain states when the target is closer to the ego vehicle. For multiple object tracking, we find that correct associations between measurements and tracks are crucial for improving the tracking performance with non-causal algorithms.

The purpose of this master’s thesis is foremost to provide a simple guide how to build elements of optical metropolitan area network. The basic model consists to sequence of construction, network topology, passive and active parts. The collection contains examples of alternative technology such as Wireless LAN with different frequency. The optical network construction based on optical cable, fibres, splices, trays, adapters, connectors and active parts for example a lot of media convertor models. After that there are demonstrating type of wavelength division multiplexer used in metropolitan area network – passive planar PCL splitter. One of the passive planar splitter are used to increase optical fibre channel. At the end of the collection a simplified examples of used measurements – optical time domain reflectometry and optical fibre transmission. Contains standard protocols or reflectogram. The conclusion of this thesis summarizes costs of FTTb (Fibre To The Building) model of optical metropolitan area network in Czech republic and future contribution for society.

碩士<br>國立中山大學<br>生物科學系研究所<br>90<br>Endostatin, an angiogensis inhibitor, was discovered by Dr. Judah Folkman’s group in 1997. From their series studies, they demonstrated that the angiogenesis inhibition approach, which abolished the formation of new blood vessels and led to starvation of cancer cells, is a safe, effective anticancer method without side effect and drug resistance. Phase clinical trial on endostatin was carried out in 1999 and completed in 2001, heralding the approaching of a new arsenal of cancer therapy drugs. Endostatin is also a proteolytic fragment (~20 kDa) from an extracellular protein, collagen XVIII. It potently inhibits endothelial cell proliferation and angiogenesis, but has no cytotoxic effects on other cells. Above all, cycled therapy of experimental cancer in rodents with endostatin led to tumor dormancy without drug resistance. However, the exact mechanism on how endostatin inhibited endothelial cells proliferation remains largely unknown. We have cloned mouse endostatin cDNA from mice liver by RT-PCR. After verification by DNA sequencing, endostatin cDNA was subcloned in to E. coli expression vector to express and generate large quantities of recombinant GST-fused endostatin. Unlike His-tagged endostatin, GST-endostatin is soluble and capable of inhibiting endothelial cell lines EA.hy926 with a half-maximal inhibition concentration (IC50) of 20 nM. In present study, we investigated whether GST-endostatin caused alterations in cytoskeleton in endothelial cells. By using a fluorescence dye to visualize the actin filament under confocal microscope, it was found that endostatin induced the corruption of actin network in endothelial cells. Western blot analysis revealed that GST-endostatin treatment caused downregulation of cytoskeleton proteins such as tubulin, vimentin and ECM-related signaling molecules such as focal adhesion kinase (FAK), mitogen activated protein kinse (MAPK), Erk in a dose-dependent manner. Moreover, GST-endostatin decreased the levels of cell survival factor such as AKT and NF-κB. Since GST-endostatin induced sustained calcium rise, the effect of endostatin on protein kinase Cs (PKCs) were studied and revealed that endostatin reduced the levels of PKCK1、PKC eta、PKC iota and PKC lamda. Other than endothelial cell, the cytotoxicity of GST-endostatin in hepatoma cells were investigated since liver the primary expression site of collagen XVIII, precursor of endostatin. Unexpectedly, endostatin also inhibited the proliferation of hepatoma cells. Flow cytometry and nucleus staining indicated that GST-endostatin also induced apoptosis in hepatoma cells. Moreover, GST-endostatin exhibited differential cytotoxic effect against well-differentiated (such as HepG2, Hep3B) and poor differentiated (such as Mahlavu, Sk-hep-1) hepatoma cells that the IC50 for well differentiated hepatoma cells were 8-10 folds lower than for poor-differentiated cells. Above all, GST-endostatin inhibited the migration of SK-hep-1 and modulated the secretion of matrix-metalloproteinases (MMPs) by Mahlavu and SK-hep-1 cells. In summary, present study explored the role of alterations in cytoskeleon network in the cytotoxic mechanism of GST-endostatin. Moreover, the inhibitory effects of GST-endostatin on proliferation of hepatoma cells were reported for the first time.