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Dissertations / Theses on the topic 'Fibrosarcome'
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Gourdin, Christophe. "Fibrosarcome pulmonaire néonatal." Lille 2, 1989. http://www.theses.fr/1989LIL2M018.
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LEBON, PATRICK. "Le fibrosarcome congenital : a propos d'une observation." Lille 2, 1989. http://www.theses.fr/1989LIL2M011.
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LEROY, MAGRIS ISABELLE. "Le fibrosarcome pulmonaire primitif : a propos d'un cas recueilli dans le service de chirurgie thoracique du professeur ampe de l'hopital saint-pilibert de lomme ; revue de la litterature." Lille 2, 1989. http://www.theses.fr/1989LIL2M166.
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Giessner, Caroline. "Vanin-1 et la réponse mésenchymateuse à un stress inflammatoire ou tumoral." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM4110.
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Vnn1 est une pantéthéinase participant à la gestion du stress tissulaire. L’activité pantéthéinase lyse la pantétheine, intermédiaire métabolique dans la synthèse du coenzyme A en cystéamine et pantothénate. Vnn1 est inductible sur des fibroblastes activés et participe à la réparation vasculaire en réponse à l'hypoxie. L’objectif de cette thèse est de déterminer le rôle de Vnn1 dans deux pathologies liées à des dysfonctions myofibroblastiques : la sclérodermie et le fibrosarcome. Dans le cadre d’une collaboration, nous avons montré que Vnn1 est induite sur des fibroblastes sclérodermiques chez la souris et chez l’homme. Des souris Vnn1-/- développent une forme atténuée de la pathologie, avec une réduction de la fibrose et de l’inflammation. Vnn1 pourrait être un marqueur pronostique des formes graves en pathologie humaine. En parallèle, nous avons montré que Vnn1 est exprimée au cours du développement de fibrosarcomes dans un modèle de souris Ink4a/Arf-/-, et se comporte comme un gène suppresseur de tumeur dans ce modèle. Nous avons produit des lignées fibroblastiques Ink4a/Arf-/- qui ont été transformées avec RasV12 en présence de Vnn1 active ou pas. Après greffe, ces lignées produisent des fibrosarcomes. En présence de Vnn1 active, la croissance tumorale est réduite et leur état de différenciation maintenu. De plus, la présence de Vnn1 semble réduire la transition métabolique induite par effet Warburg, amplifiant la glycolyse aérobie et limitant l’activité mitochondriale. Ces résultats montrent que Vnn1 corrèle avec un état activé du myofibroblaste, ce qui est délétère dans le cas de la sclérodermie mais limite la progression tumorale dans le cas des fibrosarcomesVanin-1 (Vnn1) is a pantetheinase which participates in the control of tissue stress. Pantetheinases hydrolyse pantetheines, metabolic intermediates in the synthesis of coenzyme A into cysteamine and pantothenate. Vnn1 is inducible in activated fibroblasts and participates in vascular repair during responses to hypoxic stress. The aim of this thesis was to determine the role of Vnn1 in two pathologies linked to myofibroblasts dysfunction : scleroderma and fibrosarcoma. A collaborative work, have shown that Vnn1 is upregulated in sclerodermic fibroblasts in mouse and in human. Mice Vnn1-/- developed less severe pathology, with a diminution of fibrosis and inflammation. Vnn1 could be a prognostic marker for the severe form of scleroderma. In parallel, we have shown that Vnn1 is expressed during fibrosarcoma development in Ink4a/Arf-/- mice and acts as a tumor suppressor gene in this model. We have generated fibroblastic Ink4a/Arf-/-cell lines which were transduced with RasV12, in presence of a Vnn1 active or not. After engraftment, these cells induced fibrosarcoma. In the presence of the active form of Vnn1, their differentiation into myofibroblasts was maintained and tumor growth was reduced. Moreover, Vnn1 appeared to diminish the metabolic transition induced by the Warburg effect which amplifies aerobic glycolysis, while limiting mitochondrial activity, beneficial for tumor growth. Together, these results show that Vnn1 expression correlates with an activated state of myofibroblasts, which is deleterious in scleroderma but susceptible to limit tumor growth and specifically the development of undifferentiated aggressive fibrosarcoma
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Brassart, Bertrand. "Influence des peptides derives de l'elastine sur les expressions des metalloproteinases matricielles par les fibroblastes dermiques humains et les cellules issues de fibrosarcome humain en culture (doctorat : biochimie et biologie moleculaire)." Reims, 2000. http://www.theses.fr/2000REIMM205.
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Poplineau, Mathilde. "Rôles des mécanismes épigénétiques dans la régulation de l’expression de gènes impliqués dans l’invasion de cellules tumorales." Thesis, Reims, 2012. http://www.theses.fr/2012REIMS033/document.
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Les propriétés invasives des cellules cancéreuses sont liées à des modulations importantes de l’expression de gènes. Des protéases doivent être exprimées afin de permettre la dégradation de la matrice extracellulaire (MEC), l’activation protéolytique de protéines matricielles et la libération de facteurs de croissance, de cytokines, de récepteurs et de molécules d’adhérence. Parmi ces protéases, les métalloprotéinases matricielles (MMPs) jouent un rôle crucial dans la dégradation de la MEC et dans le remodelage tissulaire observéau cours de l’invasion tumorale. L’émergence de thérapeutiques anticancéreuses basées sur des stratégies épigénétiques nécessitent d’évaluer leurs effets sur les propriétés des cellules tumorales. Ce travail a pour objectif d’analyser les effets de modulateurs épigénétiques (un agent hypométhylant de l’ADN et des inhibiteurs d’histone désacétylases (inhibiteursd’HDACs ou HDIs)) sur l’expression des MMP-1, -2 et -9 dans la lignée cellulaire de fibrosarcome humain HT1080. Dans un premier temps, il apparaît que l’agenthypométhylant de l’ADN, la 5-aza-2’désoxycytidine (5-azadC), augmente l’expressiongénique et protéique des MMP-1, -2 et -9. Ces modifications de l’expression sont associées à (i) une déméthylation globale de l’ADN et (ii) des modifications de la supra-organisation chromatinienne correspondant globalement à une chromatine moins condensée. De plus, la5-azadC est capable d’accroître les propriétés invasives des cellules par l’intermédiaire,notamment, d’une augmentation de l’expression de la MMP-1 par un mécanisme transcriptionnel. Cette augmentation de la transcription implique le recrutement du facteurSp1 et un remodelage chromatinien au niveau du promoteur du gène de la MMP-1.Néanmoins, une déméthylation totale de ce promoteur n’est pas nécessaire à cette induction. De manière complémentaire, le traitement des cellules HT1080 par différents HDIs révèle le rôle potentiel d’HDACs dans la régulation de l’expression de la MMP-1. Un HDIà large spectre, la trichostatine A (TSA), est capable de moduler l’expression de la MMP-1 et la texture nucléaire, mais uniquement après déméthylation préalable de l’ADN par la 5-azadC. Par contre, l’HDI spécifique des HDACs de classe I, le MS-275, est capable d’induire, à lui seul, l’expression génique et protéique de la MMP-1. Cette expression génique requiert un remodelage de la chromatine et le recrutement de l’histone acétyltransférase p300 au niveau du promoteur du gène de la MMP-1. L’ensemble de ces résultats suggèrent que des mécanismes épigénétiques jouent un rôle crucial dans le contrôle de l’expression de laMMP-1 dans les cellules HT1080, influençant ainsi les propriétés invasives de ces cellulesInvasive properties of cancer cells require critical changes in gene expression. Proteasesmust be expressed for the degradation of the extracellular matrix (ECM), the proteolyticactivation of matrix proteins and the release of bioactive molecules such as growth factors,cytokines, receptors and adhesion molecules. Among these proteases, the matrixmetalloproteinase (MMP) family members play a crucial role in the ECM breakdown andremodeling of tissues during tumor invasion. The introduction of epigenetic strategies in thetherapeutic arsenal against cancer led to the need to evaluate the effects of suchtherapeutic approaches on cell behavior. Here we focused our attention on the effects ofepigenetic modulators, a DNA hypomethylating agent and histone deacetylase inhibitors(HDAC inhibitors or HDI), on the expressions of MMP-1,-2, and -9 in the human HT1080fibrosarcoma cell line. First, we showed that the DNA hypomethylating drug 5-aza-2’deoxycytidine (5-azadC) increases MMP-1, -2, -9 expressions both at the mRNA andprotein levels. These changes in gene expression are associated with (i) a global DNAdemethylation and with (ii) modifications in chromatin supra-organization which globally correspond to a more decondensed chromatin. Moreover, 5-azadC is able to increase theinvasive properties capability of the HT1080 cells mainly via MMP-1 transcription-dependent expression. This enhancement of transcription occurs through (i) Sp1 recruitment, (ii)chromatin remodeling and (iii) in absence of full demethylation on the MMP-1 genepromoter. Using different HDIs reveals that HDACs could potentially play a role in MMP-1expression. The pan-HDI trichostatin A (TSA) act in synergy with 5-azadC and is able tomodulate MMP-1 expression and nuclear texture, but only after DNA demethylation. Incontrast, the HDAC class I inhibitor, MS-275, which display additive effect with 5-azadC, isable to induce, alone, MMP-1 gene expression through chromatin remodeling and p300recruitment to its promoter. These data suggest that epigenetic mechanisms play a crucialrole in MMP-1 expression control in HT1080 cells thus influencing the invasive potential ofthese cells
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Harraga, Abdelhak. "Approche physiopathologique de la croissance d'un fibrosarcome androgéno-sensible chimioinduit par le 20 méthylcholanthrène chez le rat Wistar." Montpellier 2, 1991. http://www.theses.fr/1991MON20239.
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L'ensemble des travaux presentes dans cette these concerne l'etude de l'influence et du mode d'action de la restosterone sur la croissance d'un fibrosarcome chimioinduit par le 20-methylcholanthrene transplante chez le rat wistar male. Dans un premier temps, on a observe que la testosterone a doses pharmacologiques stimule la croissance tumorale tandis que l'acetate de cyproterone, antiandrogene, diminue cet effet. La castration des rats ou la greffe tumorale chez la femelle ralentissent la croissance tumorale. Dans un second temps, on a etudie le mode d'action de l'hormone en envisageant deux hypotheses: action directe par l'intermediaire de recepteurs, action indirecte, par depression du systeme immunitaire et/ou effet anabolique general. La presence de recepteurs aux androgenes a ete mise en evidence. D'autre part, l'administration de testosterone inhibe la reponse immunitaire mesuree par les tests de winn et de liberation d'interleukine 2. En outre, on observe une augmentation de la prise alimentaire et une disparition plus rapide des acides amines dans le plasma. L'effet stimulant de la testosterone sur la croissance d'un fibrosarcome est donc un processus complexe faisant intervenir les recepteurs aux androgenes, une augmentation de l'anabolisme et la depression du systeme immunitaire
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Payelle-Brogard, Béatrice. "Utilisation de cellules hybrides pour l'induction d'une immunité antitumorale chez la souris et l'étude de la suppression de cette réponse." Paris 7, 1985. http://www.theses.fr/1985PA077072.
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L'induction d'une immunité antitumorale contre un fibrosarcome chimioinduit chez la souris peut se faire par injection de cellules hybrides semi-allogeniques provenant de la fusion entre une cellule du fibrosarcome et un fibroblaste allogenique. L'immunité antitumorale ainsi induite se developpe rapidement, elle est médiée par des lymphocytes t spécifiques de la tumeur parentale, actifs in vivo et in vitro et dont l'activité peut etre amplifiée par de l'interleukine-2. Des phénomènes suppresseurs, de nature t, empêchent transitoirement l'expression de cette immunité. Ce modele d'immunisation à ete utilise pour mettre en evidence une depression de l'immunite antitumorale (immunodepression induite par de fortes doses de bcg, immunodepression liee au vieillissement) et a permis de demontrer la presence de cellules t suppressives responsables de cette immunodépression.
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Wenk, Christiane. "Chirurgie guidée par fluorescence des fibrosarcome félin et développement et caractérisation d'un vecteur bi-fonctionnel pour le ciblage du cancer." Phd thesis, Université de Grenoble, 2012. http://tel.archives-ouvertes.fr/tel-00843015.
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Actuellement, la chirurgie représente la première indication pour la thérapie du cancer. Néanmoins, la résection complète du tissu tumoral, la détection des micrométastases et la préservation des tissus sains pendant l'intervention représentent un enjeu majeur et influencent fortement le pronostic du patient. Les récents développements technologiques en imagerie pour la chirurgie guidée des cancers ont conduit à des résultats précliniques prometteurs et les premiers essais cliniques utilisant des traceurs non-spécifiques confirment déjà le potentiel de ces systèmes pour l'amélioration de la chirurgie. De plus, le diagnostic précoce des tumeurs, ainsi que le développement de thérapies ciblées sont également des axes majeurs de recherche en cancérologie. Dans ce contexte notre équipe a précédemment développé un vecteur synthétique ciblant un récepteur cellulaire l'intégrine αVβ3. Ce vecteur est constitué d'un châssis décapeptidique cyclique RAFT (Regioselectively Addressable Functionalized Template) et présentant deux domaines indépendants permettant de séparer les deux fonctions du vecteur. Sur un domaine, la fonction de ciblage est assurée par la présentation multivalente de ligands -RGD- spécifiques du récepteur. L'autre domaine du vecteur porte les molécules d'intérêt à vectoriser, agents thérapeutiques ou de détection pour l'imagerie médicale. Dans la première partie de ces travaux, nous avons évalué la combinaison de ce vecteur couplé à un fluorophore avec une sonde portative pour imager et guider le chirurgien pendant la chirurgie des fibrosarcomes spontanés chez le chat. Cette étude représente une preuve de concept pour la translation clinique chez l'homme. Les résultats ont montré que l'injection du traceur ne provoquait pas d'effets toxiques chez le chat et permettait un marquage spécifique de la tumeur avec un bon ratio tumeur/tissu sain, qui devrait améliorer la qualité de la résection tumorale en aidant le chirurgien à mieux délimiter les marges du tissu tumoral. Dans la seconde partie de ces travaux nous avons développé un nouveau vecteur bi-fonctionnel dérivé du RAFT-RGD. Au composé d'origine a été ajoutée une séquence peptidique clivable par la matrixmetalloprotease-9, une enzyme surexprimée dans la tumorigénèse. Cette molécule à fluorescence activable a montré une amélioration du ciblage tumoral in vitro et in vivo comparée au RAFT-RGD suggérant un effet additionnel lié au double ciblage. Ces résultats préliminaires encouragent la poursuite de sa caractérisation pour son potentiel de " pro-drug " mais également pour l'étude des interactions entre l'intégrine et l'environment tumoraux.
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Addadi-Rebbah, Salima. "Activité antiinvasive des anthracyclines antitumorales : effets de l'aclacinomycine sur les propriétés migratoires et invasives des cellules de fibrosarcome humain HT-1080." Reims, 2003. http://www.theses.fr/2003REIMP207.
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@Nous avons étudié les effets des anthracyclines antitumorales, en particulier l'aclacinomycine, sur les capacités migratoires et invasives de cellules à fort pouvoir invasif, la lignée de fibrosarcome humain HT-1080. Nous avons démontré que l'aclacinomycine et dans une moindre mesure la doxorubicine inhibent la migration et l'invasion des cellules HT-1080 à des concentrations n'affectant pas la croissance cellulaire. Cette inhibition des propriétés invasives n'implique pas des mécanismes de dégradation protéolytique de la matrice extracellulaire. Par contre, elle met en jeu des modifications au niveau des protéines du cytosquelette et des plaques d'adhésion focale. Nous avons observé un défaut de polarisation cellulaire, une altération des lamellipodes et de son réseau d'actine. En particulier, l'effet antiinvasif est associé à une diminution de l'expression des intégrines b1 et de leur état d'affinité. On note également une diminution de l'expression des tyrosines kinases FAK et Src et l'altération de leur état de phosphorylation. L'ensemble des résultats suggère que l'aclacinomycine pourrait être utilisée en clinique humaine à d'autres fins que son pouvoir cytotoxique@Aclacinomycin (Aclarubicinâ) is a trisaccharide anthracycline anticancer drug active against a wide variety of solid tumors and haematological malignancies. We have evaluated its antimigrative and antiinvasive properties in a Boyden chamber with or without Matrigel and in wound repair assays. Aclacinomycin was demonstrated to inhibit HT-1080 cell migration and invasion while being more potent than the classical anthracycline doxorubicin. This decrease occurred in a dose-dependent manner and without affecting cell proliferation. Importantly, the antiinvasive effect was not associated to a modification in the production of the matrix-degrading enzymes MMP-2 and MMP-9 but rather to changes in cytoskeletal and focal contact formation. Indeed, the drug reduces cell polarity, impairs the actin-mediated membrane ruffling at the leading edge and decreases b1 integrin expression and activation. Dramatic alterations in the distribution of vinculin and in the expression and phosphorylation state of both FAK and Src kinases were also detected. As a conclusion, these data suggest a novel application for this chemotherapeutic agent due to its ability to reduce tumor cell invasion. Combination of aclacinomycin with MMP inhibitors could have therapeutic potential in preventing tumor metastasis
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Dubus, Pierre. "Caractérisation de l'expression différentielle d'isoformes de la famille TRK : implication en pathologie humaine." Bordeaux 2, 1999. http://www.theses.fr/1999BOR28672.
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Johnson, Timothy Scott. "Transglutaminase apoptosis and tumour progression." Thesis, Nottingham Trent University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283035.
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Alfaro, Alejandro. "In situ hybridization of the feline major satellite DNA FA-SAT in feline fibrosarcoma cell lines and feline fibrosarcoma tissue sections." Giessen DVG Service, 2009. http://geb.uni-giessen.de/geb/volltexte/2009/7271/index.html.
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Alfaro, Alejandro [Verfasser]. "In situ hybridization of the feline major satellite DNA FA-SAT in feline fibrosarcoma cell lines and feline fibrosarcoma tissue sections / by Alfaro, Alejandro." Gießen : DVG-Service, 2009. http://d-nb.info/1000186083/34.
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Zong, Fang. "Studies on syndecan-1 in mesenchymal tumors." Stockholm : Department of Laboratory Medicine, Karolinska Institutet, 2010. http://diss.kib.ki.se/2010/978-91-7409-749-8/.
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Devlin, Selina Jane. "Induction of fibronectin matrix and growth effects on fibrosarcoma cells." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334326.
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Gascoyne, Duncan Miles. "Regulation of apoptosis and proliferation by glucocorticoids during fibrosarcoma progression." Thesis, Institute of Cancer Research (University Of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395484.
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Andeol, Yannick. "Contribution a l'etude des oncogenes cellulaires de la famille ras : caracterisation dans trois lignees tumorales humaines." Paris 6, 1987. http://www.theses.fr/1987PA066065.
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Alkarrawi, Mohammed. "2-Hydroxybenzoate analogue mediated apoptosis in human HT-1080 fibrosarcoma cells." Thesis, Cardiff University, 2005. http://orca.cf.ac.uk/56105/.
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The antitumour activities of 18 benzoic acid and 2-hydroxybenzoic acid analogues were investigated in HT-1080 fibrosarcoma cell line. Several approaches were used to identify the most effective apoptotic agents capable of inhibiting cell population expansion of HT-1080 cells mostly at a concentration of 0.4mM. Techniques used in this study included: cell viability assays (MTT, direct count and time-lapse tracking images), morphology (DAPI, haematoxylin-eosin, methyl green-pyronin y, and SEM), immunocytochemistry (Annexin V, caspase-3) and pharmacology (2-hydroxybenzoate uptake). The results indicated that most of these compounds showed antiproliferative activities at specific concentrations (range 0.025-8mM), with an incubation time of 2-180 hours. It is evident that zinc 2-hydroxybenzoate was the most effective antiproliferative agent at 0.3 and 0.4mM. Other analogues, mainly calcium, also showed antiproliferative activities but at higher concentrations (up to 8mM). The growth inhibitory effect on HT-1080 cells population after treatment with either calcium or zinc 2-hydroxybenzoates was identified as the occurrence of apoptosis. This was confirmed by the morphological techniques as well as by immunoassay including annexin V and caspase- 3, measured by flow cytometry. Although strong evidence has been presented here for apoptosis, the genetic mechanism remains uncertain. Neither the expression of the six proteins p53, p21, Bax, Bcl-2, histones and TNF-a, nor the cell cycle analysis was able to fully elucidate the mechanism of action of calcium and zinc 2-hydroxybenzoate on HT-1080 cells. Nonetheless, calcium and zinc 2-hydroxybenzoate-induced apoptosis clearly involved caspase-3 through Bax and p53/p21, respectively, and displayed the properties of potentially therapeutic compounds.
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Aabed, Tariq Ahmad. "Radiation effects on mesenchymal stem cells in a model of fibrosarcoma." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22347/.
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Background: Radiotherapy is a mainstay of sarcoma treatment, but can cause fibrosis, characterized by production of extra-cellular matrix proteins such as collagen by cancer-associated fibroblasts (CAFs) in the cancer stroma and surrounding normal tissues, which makes tumours more aggressive and resistant to further treatment. Mesenchymal stem cells (MSCs) can be recruited to irradiated tumours and can differentiate into CAF-like cells but the mechanisms of these effects remain unclear. Aim: Determine the mechanisms of radiation effects on the recruitment of MSCs to tumours and their differentiation into CAF-like cells. Methods: Mouse MSCs were irradiated directly or exposed to irradiated mouse fibrosarcoma cells (FS120 or FS188) or their conditioned media (CM) and/or irradiated endothelial cells. Expression of CAF/fibrosis markers (collagen, fibronectin, PDGF receptor-β and α-SMA) by MSCs was assessed 3-4 days’ post radiation. Trans-well migration assays were also performed. Candidate proteins were investigated for their ability to stimulate migration and maturation of MSCs to CAF-like cells and for the ability of radiation to stimulate their production in fibrosarcoma cells. Irradiated FS120 and FS188 solid tumours were analysed for collagen, using Masson’s trichrome staining, and α-SMA using IHC and immunofluorescence. Results: Direct irradiation of MSCs had limited effects on their expression of CAF markers and migration, but exposure to irradiated tumour cells or CM and/or endothelial cells increased these effects. Candidate proteins TGF-β1, MCP-1, and SDF-1α all significantly enhanced the migration of MSCs, and radiation increased their production in fibrosarcoma cells. FS188 cells produced more MCP-1 than FS120 cells and FS188 and FS120 cells and their CM increased MSC migration in a radiation-dependent manner. Migration could be at least partially blocked by an MCP-1 blocking antibody. MSC expression of the MCP-1 receptor, CCR2, was increased after exposure to irradiated FS188 cells or their CM. In vivo, irradiated fibrosarcomas showed significant increases in collagen content, with more collagen in FS188 than in FS120 tumours. Conclusion: Results support the notion that MSCs play an important role in radiation-induced CAF activity and fibrosis in sarcoma. MCP-1 was identified as an important mediator of these effects. Moreover, endothelial cells were shown to play an important role in the recruitment of MSCs in response to radiation. In vitro results identifying FS188 cells as being more pro-fibrotic than FS120 cells were consistent with in vivo results. Further work to understand these processes should help to develop novel treatment strategies for combination with radiotherapy.
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Gillingham, Helen. "Role and regulation of aminopeptidase N (CD13) in HT1080 fibrosarcoma cells." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610322.
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Nievergelt, Alexandra. "Regulation of HT1080 fibrosarcoma cell migration : role of signalling pathways and extracellular matrix proteins /." [S.l.] : [s.n.], 2004. http://www.zb.unibe.ch/download/eldiss/04nievergelt_a.pdf.
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Sjöling, Åsa. "Molecular genetic analysis of chromosomal aberrations in DMBA-induced rat fibrosarcomas /." Göteborg : Göteborg university, 2002. http://catalogue.bnf.fr/ark:/12148/cb39929313x.
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McConnell, Michael James. "Cell-surface Tumoricidal Molecules and NF-kB in the Tumor-burdened Host." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/9609.
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Tumor-distal immune suppression promotes tumor growth by preventing the recruitment of leukocytes to the tumor-proximal microenvironment. Tumor necrosis factor (TNF)-a is both secreted by and expressed on the cell-surface (mTNF-a) of macrophages. When stimulated with LPS, tumor-burdened host (TBH) macrophages secrete more TNF-a than normal host (NH) macrophages. In this study, I showed that mTNF-a is elevated both in freshly isolated and stimulated TBH macrophages. Additionally, I analyzed the expression of Fas and FasL on freshly isolated and LPS-stimulated macrophages and found no differences between TBH and NH macrophages. Fas and Fas ligand (FasL) cell-surface expression was analyzed on NH and TBH T-cells. While no difference was observed in freshly isolated cells, cell-surface expression of both proteins remained higher in TBH T-cells than NH T-cells after mitogenic stimulation. Fas and FasL analysis was also extended to the MethKDE fibrosarcoma and I found that these tumor cells express high levels of FasL. Because past observations show increased TNF-a mRNA expression in TBH macrophages relative to NH macrophages, I hypothesized that NF-kB activation may be increased as well. NF-kB is a transcription factor whose activation is required for TNF-a transcription. I observed increased NF-kB activation in both splenic and peritoneal TBH macrophages. Interestingly, electrophoretic mobility shift analysis (EMSA) suggests that different species of NF-kB were found in each distinct population of macrophages. Together, these data demonstrate that cell-surface tumoricidal molecules and NF-kB are dysregulated in the tumor-burdened host.Master of Science
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Amirkhosravi, Mohammadali. "Procoagulant activity of the MC28 fibrosarcoma in vitro and in vivo : its role in metastasis." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339478.
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Falwell, Elizabeth Paige. "Fibrosarcoma-induced Dysregulation of Interleukin (IL)-1β and IL-18 Activities and their Modulation by Paclitaxel." Thesis, Virginia Tech, 2005. http://hdl.handle.net/10919/33588.
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Cancer remains an elusive killer due, in part, to the suppression of normal immunologic antitumor responses. Normal host (NH) macrophage (Mϕ) populations have tumoricidal effects such as tumor antigen phagocytosis and presentation, and cytokine production. Tumor-infiltrating Mϕs may evade these activities by dysregulating production of immunostimulatory cytokines (including Interleukin [IL]-1β, IL-18, and tumor necrosis factor-α [TNF-α]), by production of antagonistic factors. The restoration of IL-1β, IL-18, and TNF-α production by Mϕs could re-establish antitumor host immune responses. Previous work in our laboratory suggests that tumor distal (TD) Mϕs produce
more IL-1Îβ than NH Mϕs when stimulated with IFN-γ and lipopolysaccharide (LPS). We hypothesize that the presence of immunomodulatory factors like IL-10 and TGF-γ dysregulate IL-1β production in tumor proximal (TP) Mϕs. Indeed, IL-1β production was downregulated among in situ TP Mϕs. We have proposed that IL-18, a structural homologue to IL-1β was similarly dysregulated in TD and TP Mϕs. IL-18 was enhanced in both distal and proximal Mϕs. Differences in the functions of these cytokines could account for this dissimilarity. TNF-α, another proinflammatory cytokine, followed the dysregulation pattern of IL-1β in our tumor-burdened hosts (TBH), likely because of the similar functions of these cytokines. Because it is a potential vehicle for immunotherapeutic treatment, paclitaxel's action on the immune response (TAXOL™) was investigated. Paclitaxel is a potent Mϕ activator that upregulates a variety of cytokines in an LPS-like manner. Paclitaxel enhanced TD Mϕ production of IL-1β, IL-18, and TNF-ϕ in an LPS-like manner. Production of IL-1β and TNF-ϕ was reduced in TP Mϕs when treated with paclitaxel; however, IL-18 production was enhanced. This
difference could be due to the different functions of IL-1β and IL-18. To determine whether production of these cytokines translates into downstream expression of transcription products, IL-12 and nitric oxide (NO) were assayed. NO was enhanced distally, but paclitaxel treatment failed to enhance NO production. When treated with paclitaxel, IL-12 was produced by NH and TD Mϕs. Collectively, these studies suggest that tumor-induced cytokine imbalances compromise antitumor immunity and paclitaxel may reverse this activity.Master of Science
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Mori, Akira. "Vascular endothelial growth factor-induced tumor angiogenesis and tumorigenicity in relation to metastasis in a HT1080 human fibrosarcoma cell model." Kyoto University, 1999. http://hdl.handle.net/2433/181717.
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Partridge, Juneth Ann Joaquin. "The role of MMPs in the intravasation of a highly disseminating HT-1080 fibrosarcoma cell variant a protective role for tumor-derived MMP-9 /." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3378523.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed October 22, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 119-134).
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Furuzawa, Karina Mie. "Avaliação do papel de galectina-3 no recrutamento de macrófagos e sua participação na angiogênese em modelo de fibrossarcoma." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-18012017-145414/.
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Assim como tecidos normais, tumores possuem uma demanda de nutrientes e oxigênio, suprida através da vasculatura a eles associada que resulta do processo de angiogênese. Fatores pró-angiogênicos são capazes de atrair monócitos, os quais se diferenciam em macrófagos associados a tumores (TAMs). TAMs comumente apresentam fenótipo M2, cujas características são consideradas pró-tumorais, como a promoção da angiogênese e a degradação de matriz extracelular. Estudos indicam que galectina-3 (gal-3), uma proteína pleiotrópica que se liga a ?-galactosídeos, participa do controle da angiogênese e da infiltração de macrófagos M2 na massa tumoral, mas pouco se sabe sobre os mecanismos envolvidos. No presente estudo, utilizamos um modelo de sarcoma induzido por carcinógeno em camundongos selvagens (WT) e knockout para gal-3 (Gal- 3 KO). Comparando os tumores de animais WT e Gal-3 KO, não observamos diferenças no padrão de crescimento tumoral, na área necrótica relativa, na proliferação celular e na quantificação de fibras de colágeno. Demonstramos que, embora ambos os grupos desenvolvam tumores, a angiogênese foi inibida em um microambiente desprovido de gal-3. Entretanto, não houve diferença na produção do fator de crescimento endotelial vascular (VEGF). As imagens obtidas in vivo indicaram que gal- 3 também influencia na formação estrutural de vasos adjacentes ao tumor. Além de mediar aspectos morfológicos relacionados à angiogênese, demonstramos que gal-3 também contribuiu para a funcionalidade vascular, pois houve uma redução na velocidade de fluxo sanguíneo nos vasos intratumorais de animais Gal-3 KO. Nossos dados sugeriram que há menos macrófagos no tumor que não expressa gal-3 e, dentre os TAMs, há mais M2 em comparação ao tumor gal-3-positivo. A análise do tecido onde o tumor se desenvolve, na fase inicial da tumorigênese, indicou que a ausência de gal-3 está relacionada a uma maior densidade de macrófagos M2. Considerando que a presença maior de macrófagos M2 nos sarcomas gal-3-negativos não resultou em maior produção de VEGF, mas sim na inibição da angiogênese, nossos resultados apontam para uma participação significativa de gal-3 na mediação da angiogênese pelos macrófagosAs well as normal tissues, tumors require nutrients and oxygen, which are supplied by the associated vasculature that results from the process of angiogenesis. Pro-angiogenic factors are able to attract monocytes and they differentiate into tumor-associated macrophages (TAMs). TAMs commonly exhibit M2 phenotype, which has characteristics considered pro-tumoral, such as angiogenesis promotion and degradation of extracellular matrix. Studies show that galectin-3 (gal-3), a pleiotropic ?-galactosidebinding protein, participates in angiogenesis control and M2 macrophage infiltration into the tumor mass, but little is known about the mechanisms involved. In this work, we established a model of carcinogen-induced sarcoma in wild-type (WT) and gal-3 knockout (Gal-3 KO) mice. Comparing tumors from WT and Gal-3 KO animals, there were no differences in the pattern of tumor growth, relative necrotic area, cell proliferation and collagenous fibers. We demonstrated that, although both groups develop tumors, angiogenesis was inhibited in a microenvironment devoid of gal-3. However, there was no difference in the production of vascular endothelial growth factor (VEGF). The images obtained in vivo indicated that gal-3 also influenced the structural formation of vessels adjacent to the tumor. In addition to mediating morphological aspects related to angiogenesis, we demonstrated that gal-3 also contributes to vascular functionality, since there was a reduction in blood flow velocity in intratumoral vessels from Gal-3 KO animals. Our data suggested that there are fewer macrophages in tumors without gal-3 and, among TAMs, there are more M2 compared to gal-3-positive tumors. Analysis of the tissue where the tumor develops, in early stages of tumorigenesis, indicated that the lack of gal-3 is related to an increased density of M2 macrophages. Since the greater number of M2 macrophages in gal-3-negative fibrosarcomas did not result in increased VEGF production, but inhibited angiogenesis, our results suggest a significant role of gal-3 in regulation of angiogenesis by macrophages
30
Valverde, Sara Mesquita de Sousa Ferreira. "Clínica de pequenos animais: megaesófago adquirido: abordagem diagnóstica e tratamento." Master's thesis, Universidade de Évora, 2014. http://hdl.handle.net/10174/13549.
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O presente relatório de estágio integra o curso de Medicina Veterinária e resulta de um culminar de seis meses de estágio no Hospital Veterinário Montenegro na área de clínica e cirurgia de pequenos animais. Encontra-se dividido em duas partes: a primeira refere-se à casuística observada durante o estágio e a segunda engloba uma monografia subordinada ao tema “Megaesófago adquirido – abordagem diagnóstica e tratamento”, incluindo o relato de um caso clínico de fibrossarcoma num gato. O megaesófago é uma doença esofágica caraterizada por dilatação difusa e hipomotilidade esofágica. Classifica-se em idiopático (congénito e adquirido) e adquirido secundário. Doenças neuromusculares, gastrointestinais, endócrinas, imunomediadas, neoplásicas e tóxicas podem estar associadas a megaesófago adquirido. Sinais clínicos comuns são regurgitação, perda de peso, tosse e halitose. O diagnóstico baseia-se na história clínica e radiografias torácicas, podendo ser necessário métodos de diagnóstico adicionais. O tratamento, maneio e prognóstico de megaesófago variam consoante a causa subjacente; Abstract:
Small animal practice
This work is a compilation of both the integrated Master in Veterinary Medicine and a six months internship at the Veterinary Hospital Montenegro, in small animal practice. It is divided in two main parts: the first one presents the activities carried out, the second part encompasses the subject "Acquired megaesophagus - diagnostic and treatment" including a case report of fibrosarcoma in a cat. Megaesophagus is a disorder of the esophagus characterized by diffuse dilation and decreased peristalsis. It is classified into idiopathic (congenital and acquired forms) and acquired secondary. Neuromuscular, gastrointestinal, endocrine, imune-mediated, neoplasic and toxic disorders have been associated with acquired megaesophagus. Common clinical signs are regurgitation, weight loss, coughing and halitosis. The diagnosis is based on clinical history and chest radiographs, but additional methods of diagnosis may be necessary. The treatment, management and prognosis of megaesophagus vary greatly depending on the underlying cause.
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Dinis, Rúben Miguel de Sousa. "Avaliação de fatores de prognóstico associados ao fibrossarcoma no gato : estudo retrospetivo." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2017. http://hdl.handle.net/10400.5/13139.
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Dissertação de Mestrado Integrado em Medicina VeterináriaOs fibrossarcomas são neoplasias mesenquimatosas que ocorrem sobretudo na pele e tecido subcutâneo, sendo comuns na espécie felina. A excisão cirúrgica agressiva com amplas margens é o tratamento de eleição que pode ser associado a radioterapia, quimioterapia ou imunoterapia adjuvantes ou neoadjuvantes. Devido às características invasivas destes tumores, o prognóstico é reservado em relação ao controlo local, no entanto mesmo perante múltiplas recidivas a sobrevivência tende a ser prolongada. Torna-se por isso imperativo avaliar variáveis que possam ajudar o clínico e o dono a prever o sucesso terapêutico ou o curso da doença, e determinar que tratamentos complementares possam beneficiar o animal. O presente estudo retrospetivo teve como objetivo a avaliação de fatores de prognóstico, em 38 casos clínicos submetidos a cirurgia associado ou não a tratamento quimioterápico. A idade mediana foi de 10,3 anos, não houve predisposição de género, os gatos eram maioritariamente de raça Europeu Comum e a localização anatómica mais frequente foi a interescapular (32,4%). A recidiva ocorreu em 31,6% dos casos e a metastização em 7,9%. A mediana do intervalo livre de doença não foi atingida e a mediana do tempo de sobrevida foi de 761 dias. Não foi identificada uma associação entre o intervalo livre de doença e as variáveis: idade no momento do diagnóstico, género, localização tumoral, avaliação pré-cirúrgica com tomografia computorizada, ocorrência de deiscência de sutura cirúrgica, realização de quimioterapia e estatuto das margens histológicas. O estadiamento clínico foi o único fator de prognóstico identificado com influência no intervalo livre de doença. Os casos com tumores de menores dimensões (menores ou iguais a 5 cm; T1 e T2) apresentaram intervalos livres de doença mais longos que casos com tumores de maiores dimensões (maiores que 5 cm; T3). Os resultados obtidos sugerem que o tamanho tumoral está associado ao intervalo livre de doença, no entanto, outros estudos, com amostras e acompanhamento maiores, são necessários para apoiar estes resultados.
ABSTRACT - EVALUATION OF PROGNOSTIC FACTORS ASSOCIATED WITH FIBROSSARCOMA IN CAT - RETROSPECTIVE STUDY - Fibrosarcomas are mesenchymal neoplasms occurring mainly in the skin and subcutaneous tissue, being common in the feline species. Aggressive surgical excision with wide margins is the treatment of choice that may be associated with adjuvant or neoadjuvant radiotherapy, chemotherapy or immunotherapy. Due to the invasive characteristics of these tumors, the prognosis is reserved in relation to the local control, however even in the case of multiple relapses the survival tends to be long. It is therefore imperative to evaluate variables that may help the clinician and the owner to predict the therapeutic success or course of the disease and determine which complementary treatments may benefit the animal. The present retrospective study had as objective the evaluation of prognostic factors, in 38 clinical cases submitted to surgery associated or not to chemotherapeutic treatment. The median age was 10.3 years, there was no gender predisposition, the cats were mostly of European Common breed and the most frequent anatomic location was the interscapular (32.4%). Recurrence occurred in 31.6% of cases and metastasis in 7.9%. The median disease free interval was not reached and the median survival time was 761 days. No association was identified between the disease free interval and the variables: age at diagnosis, gender, tumor location, pre-surgical evaluation with computed tomography, surgical suture dehiscence, use of chemotherapy and histological margins status. Clinical staging was the only prognostic factor identified with influence on the disease free interval. Cases with smaller tumors (less than or equal to 5 cm, T1 and T2) had longer disease-free intervals than cases with larger tumors (greater than 5 cm, T3). The results suggest that tumor size is associated with the disease free interval, however, other studies, with larger samples and follow-up, are necessary to back up these results.
N/A
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Siqueira, Adriane Sousa de. "Peptídeo C16, derivado da laminina, regula invasão, dinâmica de formação e atividade de invadopódios em linhagens celulares de carcinoma epidermóide e fibrossarcoma." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-24092014-154312/.
Full textAbstract:
A laminina contém peptídeos que podem ser liberados por proteólise. Nosso laboratório estuda os efeitos de peptídeos da laminina em biologia tumoral. Neste trabalho, verificamos se C16 (cadeia g1) estimularia invasão e atividade de invadopódios em células de carcinoma epidermóide (CAL27) e fibrossarcoma (HT1080). C16 promoveu aumento na taxa de invasão e atividade de invadopódios em ambas às linhagens celulares, comparado ao peptídeo controle C16SX. Microscopia em time-lapse demonstrou que C16 induz aumento na atividade de invadopódios em função do tempo. C16 estimula fosforilação de Src e ERK 1/2, e inibição da via ERK reduz invasão e atividade de invadopódios relacionados ao peptídeo. C16 conjugado à rodamina foi encontrando decorando a membrana de células CAL27, sugerindo possível interação com receptores. Diminuição dos níveis de integrina b1 reduzem atividade de invadopódios em amostras tratadas com C16. Nossos dados sugerem que C16 regula invasão e atividade de invadopódios em células CAL27 e HT1080, provavelmente por meio de Src, ERK e integrina b1.Laminin harbors bioactive peptides released upon tumor-induced proteolysis. Our Laboratory has been studying laminin peptides effects in tumor biology. Here we addressed whether C16 (g1 chain) would regulate invasion and invadopodia activity in cell lines from squamous cell carcinoma (CAL27) and fibrosarcoma (HT1080). C16 increased invasion rate and invadopodia activity compared to control peptide (C16SX). Through time-lapse microscopy, we observed that C16 stimulated invadopodia activity overtime. We searched for signaling pathways related to peptide effects. C16 stimulated Src and ERK 1/2 phosphorylation, and ERK signaling cascade inhibition decreased C16-induced invasion and invadopodia. Next, we addressed how C16 would interact with tumor cells. Rhodamine-conjugated C16 was found decorating CAL27 cell membrane, suggesting an interaction with receptors. Knockdown of b1 integrin reduced invadopodia activity of C16-treated cells. We propose that C16 regulates invasion and invadopodia activity of CAL27 and HT1080 cells through Src, ERK and b1 integrin.
33
Gaggioli, Cédric. "Etude de l'expression de la fibronectine dans les cellules de mélanome : rôle de la voie de signalisation des MAP kinases ERK et du facteur de transcription Egr-1." Paris 7, 2005. http://www.theses.fr/2005PA077021.
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Sii, Felice Karine. "Régulation par phosphorylation du facteur de transcription MafA." Paris 7, 2005. http://www.theses.fr/2005PA077081.
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Pecoraro, Matteo 1984. "The Role of p63 and the chromatin remodeler Lsh in senescence, tumor development and lymphangiogenesis." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/326749.
Full textAbstract:
La senescencia celular es una detención irreversible del ciclo celular que tiene lugar en respuesta a diversos estímulos de estrés, actuando como un mecanismo supresor de tumores para impedir la proliferación de células con riesgo de transformación maligna. Así, mutaciones que interfieren con el proceso de la senescencia pueden favorecer la formación tumoral. De todas formas, cada vez hay más pruebas que sugieren que las células senescentes también pueden ejercer efectos pro-tumorigénicos en el tejido circundante mediante el fenotipo secretor asociado a senescencia (SASP). Así, descifrar los mediadores moleculares de la senescencia y el SASP es crítico para entender los estadios tempranos de la formación y progresión tumoral. Aquí mostramos que la isoforma ΔNα de p63, un factor de transcripción relacionado con p53, es un oncogén que promueve la iniciación tumoral en colaboración con Ras mediante la inhibición de la senescencia inducida por oncogenes (OIS). Efectivamente, el incremento en la expresión de ΔNp63α en queratinocitos primarios de ratón bloquea la OIS y directamente conduce a la formación de un carcinoma de células escamosas (SCC). También identificamos la Helicasa Específica Linfoide (Lsh), un miembro de la familia SNF2 de remodeladores de la cromatina, como nueva diana de p63 necesaria para la inhibición de la senescencia. Posteriormente, demostramos que Lsh es suficiente para iniciar la formación tumoral independientemente de p63, y que el aumento en su expresión conduce a un desarrollo tumoral más agresivo. Sorprendentemente, mostramos que Lsh tiene un papel en la inducción de la linfangiogénesis, un proceso característico de la progresión maligna y la metástasis. Es interesante notar que las pruebas apuntan hacia Lsh actuando sobre el SASP para dirigir la formación y la progresión tumoral. En conjunto, en este trabajo se identifican nuevos mediadores críticos de la senescencia y funciones de la desregulación de la senescencia durante la formación y la progresión tumoral.Cellular senescence is an irreversible cell cycle arrest that occurs in response to various stresses, acting as a tumor-suppressive mechanism to impede the proliferation of cells at risk for malignant transformation. As such, mutations that interfere with the senescence process can favor tumor formation. However, increasing evidence suggests that senescent cells can also exert pro-tumorigenic effects on the surrounding tissue, through the senescence-associated secretory phenotype (SASP). As such, understanding the molecular mediators of senescence and the SASP is critical to unravel the early stages of tumor formation and progression. Here we show that the ΔNα isoform of p63, a p53-related transcription factor, is an oncogene that promotes tumor initiation in cooperation with Ras, through the inhibition of oncogene-induced senescence (OIS). Indeed, increased expression of Np63 in primary mouse keratinocytes blocks OIS and directly leads to the formation of squamous cell carcinoma (SCC). We also identify Lymphoid Specific Helicase (Lsh), a member of the SNF2 family of chromatin remodelers, as a novel target of p63, required for senescence bypass. Subsequently, we demonstrate that Lsh is sufficient to initiate tumor formation independently of p63, and that its increased expression leads to aggressive tumor development. Surprisingly, we show a role for Lsh in the induction of lymphangiogenesis, a hallmark of malignant progression and metastasis. Interestingly, the evidence points towards Lsh acting on the SASP to instruct tumor formation and progression. Together, this work identifies critical new mediators of senescence, and functional roles for senescence deregulation during tumor formation and progression.
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En-Shing, Hong, and 洪恩馨. "Mob2 Regulates Rab11 Recycling in fibrosarcoma Cell Migration." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/91020872957597153679.
Full textAbstract:
碩士東海大學
生命科學系
103
Cell migration is an important process which is involved in many biological functions. Focal adhesion, an integrin containing protein complex connected with extracellular matrix and cytoskeleton, plays the major role during cell migration. It has been reported that integrin is transported to cell membrane through vesicular trafficking and been regulated by Rab11, the endosome traffic protein. But how Rab11 been regulated is still unknown. Mob2, which has been first found in Saccharomyces cerevisiae, conserved from yeast, drosophila and mammals to human and is reported to regulate vesicular trafficking through Rab GTPase. Therefore, in this study, we investigated whether Mob2 could regulate sarcoma cell migration through Rab11 mediated integrin recycling. Results showed that Mob2 knockdown inhibited fibrosarcoma cell (HT1080) migration, and Mob2 regulated integrin recycling during the cell polarization. We further demonstrated Rab11 knockdown in Mob2 overexpressed cells inhibited cell migration; however, Rab11 overexpression in Mob2 knockdown cells has no effect on cell migration. This study also showed that miR758 overexpression induced Rab11 and Mob2 expression. Taken together, Mob2 may regulate Rab11-mediated integrin recycling for fibrosarcoma cell migration, and miR758 might play as a upstream regulator of Mob2, however, their causal relationship needs to be further investigated.
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Liu, Yi Ching, and 劉怡青. "Human MOB2 Participates in Migration of Fibrosarcoma Cells." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/37257482382491250855.
Full textAbstract:
碩士東海大學
生命科學系
102
Mps One Binder proteins (MOB) are important components to control cellular processes, such as cell proliferation, cell migration, morphogenesis, and apoptosis. MOB family proteins can be found from yeast, Drosophila and mammals. In Drosophila, Mob1 protein acted as tumor suppressor to control the Hippo pathway and photoreceptor morphogenesis. In mammals, the human MOB protein family has six distinct members. Human (hMOB2) is known to bind with NDR1/2 and participates in regulating cell apoptosis and centrosome duplication. In mouse neuron cell, over-expression of MOB2 increases neurite formation. Cell migration is an important cellular process that occurs during embryo development, wound healing, inflammation and cancer metastasis. Cell migration involves cell protrusion at the leading edge and cell retraction at the rear end of cells. Although the mechanisms of cell migration have been widely studied, the regulation of cell migration remained unclear. To study whether hMOB2 participates in cell migration, we used human fibrosarcoma cell (HT1080) as a model system to study how hMOB2 participates in cell migration. Immunocytochemistry revealed that hMOB2 protein was mainly localized at the cytoplasm and at the leading edge of HT1080 cells. The localization of hMOB2 detected at the leading edge was colocalized with actin cytoskeleton at the lamellipodia. In wound healing and cell invasion assay, we found that the rate of cell invasion was reduced to 50% after knockdown of hMOB2. The invasion rate was restored as hMOB2 proetin was re-expressed in the hMOB2 knockdown cells. We also found that the rate of cell migration was slower in the hMOB2-knockdown cells. In addition, the expression of A107G, Y110A point mutation of hMOB2 in the hMOB2 knockdown cells showed no significant difference between hMOB2 knockdown cells in the rate of cell invasion and cell migration. These results suggest that hMOB2 plays an important function in cell invasion and cell migration.
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Wai, Daniel Hon-Hei. "Molecular characterization of the ETV6-NTRK3 fusion in congenital fibrosarcoma." Thesis, 1999. http://hdl.handle.net/2429/10554.
Full textAbstract:
The t(12;15)(pl3;q25) rearrangement detected in congenital fibrosarcoma
splices the ETV6 (TEL) gene on chromosome 12p13 in frame with the NTRK3
(TRKC) neurotrophin-3 receptor gene on chromosome 15q25. Resultant ETV6-
NTRK3 fusion transcripts encode the helix-loop-helix (HLH) dimerization domain
of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. We
hypothesize that chimeric proteins mediate transformation by dysregulating NTRK3
signal transduction pathways via ligand-independent dimerization and PTK
activation. To determine if the fusion protein has transforming activity, NIH3T3
cells were infected with recombinant retroviral vectors carrying the full-length
ETV6-NTRK3 cDNA. These cells exhibited a transformed phenotype and formed
macroscopic colonies in soft agar. In order to characterize the roles of specific ETV6-
NTRK3 domains, we expressed a series of ETV6-NTRK3 mutants in NIH3T3 cells
and assessed their transformation activities. Deletion of the ETV6 H L H domain
resulted in morphologically non-transformed NIH3T3 cells that failed to grow in
soft agar. Mutants of the three PTK activation-loop tyrosines (EN-Y513, EN-Y517,
and EN-Y518) had variable PTK activity but had limited to absent transformation
activity. The EN-Y513F mutant failed to transform NIH3T3 cells, while the
expression of either EN-Y517F or EN-Y518F resulted in a semi-transformed
phenotype. The simultaneous mutation of Y517 and Y518 (EN-Yx2F), or of all three
tyrosines (EN-Yx3F), resulted in a morphologically untransformed phenotype. The
ATP-binding mutant (EN-K380N) failed to autophosphorylate and completely
lacked transformation activity. In addition, a series of PTK-active mutants unable to
bind phospholipase-Cγ did not show defects in transformation activity. These
studies confirm that ETV6-NTRK3 is a transforming protein that requires both an
intact dimerization domain and a functional PTK domain for transformation
activity.
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Choo, Lai Mun, and 朱麗雯. "The function of human MOB2 in cell spreading in fibrosarcoma cells." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/40238958167824388773.
Full textAbstract:
碩士東海大學
生命科學系
99
Cell spreading is an initial mechanism for cell migration which plays a vital role in cancer development. Cell spreading has been shown to act as one of the key regulating steps between static and metastatic transition of a cancer cell. Hence, by identifying regulatory networks controlling cell spreading, it may provide valuable information and therapeutic strategies for preventing tumor metastasis. Both cell spreading and cell migration involve actin polymerization at the leading edge of plasma membrane follow by cell retraction at the rear end of cells. The molecular mechanisms in regulating cell spreading and cell migration have been extensively studied but remain unclear. Studies from yeast, Drosophila to mammalian cells have shown that MOB2 protein plays an important role in controlling the cell morphology changes by affecting cell polarity and rearrangement of actin cytoskeleton. Currently there is no research done to study the function of Mob2 in cell spreading and cell migration. In this study, we identified hMOB2 protein which plays a significant role in promoting cell spreading in HT1080 human fibrosarcoma cells. Our results showed that hMOB2 was detected at the leading edge of migrating HT1080 human fibrosarcoma cell. To study whether hMOB2 was involved in cell motility, we downregulated hMOB2 expression using RNA interference and found that cell spreading was delayed in HT1080 cells. In addition, we observed that overexpression of hMOB2 enhanced cell spreading in HT1080 cells and enhanced its accumulation at the leading edge. Furthermore, to determine the possible functional domain in cell motility, we successfully generated A107G, Y110A point mutated hMOB2 stable cell lines. Over-expressed point mutated hMOB2 expression delayed cell spreading and suppressed its accumulation at the leading edge. These observations suggested that hMOB2 affects cell spreading by regulating its expression at leading edge. No significant difference was observed in the migration rate between the different HT1080 cell populations when the percentage of gap closure was determined. However, over-expressed wild type hMOB2 induced broad lamellipodial structures and moved as a coherent group when compared with parent cells. These studies provided additional information on the molecular mechanisms which control cell spreading.
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Lin, Jing-hua, and 林靖華. "Study on the cytotoxic mechanism of irradiation combined with arsenic trioxide in fibrosarcoma." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/65438917929453126109.
Full textAbstract:
碩士國立成功大學
環境醫學研究所
96
Fibrosarcoma is one of soft tissue sracoma which is resistance to radiotherapy and chemotherapy, and the prognosis is extremely poor. Currently, combined chemotherapy and radiotherapy has been shown in clinical to produced an improved survival and an improved disease control for cancer patients. Irradiation (IR) is thought to kill cells by causing DNA damage and inducing G2/M arrest. The anti-cancer effects of arsenic trioxide (ATO), a chemotherapeutic agent, has been attributed to the induction of apoptosis, inhibition of proliferation and angiogenesis, and promotion of differentiation. The major propose of this study is to investigate the cytotoxic mechanism of irradiation combined with arsenic trioxide in the treatment of fibrosarcoma HT1080 cells. In in vitro study, cell viability was detected by trypan blue. Cell cycle distribution, ROS, membrane potential and early apoptosis with annexin V-FITC apoptosis detection kit was analyzed by flow cytometry. DNA fragmentation was detected by agarose gel electrophoresis. In order to observe the expression of acidic vesicular organelle (AVOs) which is characteristic of autophagy; cells were stained with acridine orange. Western blotting was performed to analysis the expression of protein related to apoptosis and autophagy. In in vivo study, therapeutic efficacy of ATO and IR in HT1080 cells xenografts after treatment was assessed. Our results indicated the combination of IR and ATO was shown to be significantly more active than either treatment alone in two combination sequences comcomitant treatment, or sequential treatment with IR followed by ATO in HT1080 cells. Combined treatment decreased cell viability, caused membrane potential damage, and cell cycle G2/M arrest. They also increased the persentage of intracellular ROS, apoptosis and autophagy. The expression level of p53, p21, p-cdc2, cyclin B1, p-cdc25c and LC3 was increased significantly, however, p-ERK, Bax, Hsp70 and PARP were increased slightly. Decrement of cdc25c and bcl-2 expression was observed. Otherwise, no significantly change was found in the expression of cyclin A, cdc2, Akt and p-Akt. In in vivo study, combined treatment with IR and ATO inhibited tumor growth significantly than either treated alone. Taken together, this study demonstrated that IR combined with ATO may increase therapeuic efficacy of HT1080 cells. The cell death mechanisms induced by this combined treatment include apoptosis and autophagy.
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Deng, Edward F. "Molecular cloning of a gene from metastatic fibrosarcoma cells converted by viral insertional mutagenesis." 1996. http://hdl.handle.net/1993/19087.
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Coons, William J. "Involvement of T suppressor lymphocytes in the progression of UV-induced fibrosarcomas." 1985. http://hdl.handle.net/2097/27421.
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Li, Cho-Han, and 李卓涵. "Studies on Curcumin and its analogs on anti-metastatic activities of human fibrosarcoma cells (HT-1080)." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/00651349802485252607.
Full textAbstract:
碩士臺北醫學大學
生藥學研究所
97
Curcumin, a yellowish pigment existed in turmeric plant has been shown to exhibit numerous biological properties, such as anti-inflammation, antioxidation, anti-invasion, and antimetastatic activity. Chemical modifications of curcumin have been studied intensively in an attempt to find an analog with similar but enhanced biological activities of curcumin. In literatures, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) played important roles in cancer cell invasion by hydrolysing extracellular matrix (ECM). In this study, curcumin and 23 novel analogs were used to screen for inhibition of matrix metalloproteinase-9 (MMP-9) activities, protein and gene expression of highly metastatic HT-1080 human fibrosarcoma cells to explore the mechanisms of action. All tested compounds, except analog 24 and analog 31 at concentration of 2.5 μM showed no cytotoxic activities at 5 μM. The analog 2 (six methoxy substitutes in phenyl groups) and analog 7 (three hydroxyl and one methoxyl substitutes in phenyl groups) showed higher MMP-9 inhibitory activities than curcumin did at 5 μM in gelatin zymography analysis. We comparatively examined the influence of analog 2, 7, 24 (three hydroxyl substitutes in phenyl groups), and 31(two hydroxyl and two methoxyl substitutes in phenyl groups) on the expression of MMP-9 of HT-1080 cells at concentration of 2.5 μM. Analog 2, 7, 24 and 31 suppressed the gene expression of MMP-9 as the results of RT-PCR assay and Western blot assay, and decreased their corresponding activities in HT-1080 cells revealed by gelatin zymography assay, MMP-9 activity ELISA and fibrin zymography assay which resulted in inhibition of HT-1080 cell invasion and migration differentially. All in all, analog 2 and 7 showed higher anti-metastatic activities than analog 24 and analog 31 did. Heme oxygenase 1(HO-1), a stress-responsive enzyme, which was found to correlate with production of reactive oxygen species (ROS), suggesting a causative relationship on MMP inhibition. Therefore, the effect of curcumin and analog 2, 7, 24 and 31 on HO-1 protein expression were also studied. Interestingly, exposure to curcumin, analog 2 and 31 treatment maximally induce HO-1 protein expression in HT-1080 cells, however, analog 7 and 24 were less apparently. These data suggested that the inhibitory effects of curcumin and analog 2, 7, 24 and 31 on MMP-9 gene expression and uPA activity was closely related to tumor invasion and migration in vitro. Furthermore, analog 2 showed highly MMP-9 inhibitory activity which possibly involved mechanisms related to its ability to induce HO-1 to suppress PMA-induced ROS, which can activate MMP-9 gene expression. In summary, these data demonstrated that analog 2, 7, 24 and 31 show higher anti-metastasis potency than curcumin by the differentially down-regulation of MMP-9 and uPA.
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Wu, Shu-Ping, and 吳淑萍. "Pardaxin，a fish antimicrobial peptide, exhibits antitumor activity toward a murine fibrosarcoma in vitro and in vivo." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/42768439171685104172.
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碩士國立臺灣海洋大學
水產養殖學系
100
Pardaxin is a 33-amino acids antimicrobial peptide which first isolated from a mucosal secretion of the Red Sea Moses sole Pardachirus marmoratus in 1980. Besides the abilities of anti-bacterial and anti-viral, pardaxin also presents the antitumor activity. In this study, we hypothesize that pardaxin can inhibit murine fibrosarcoma cells growth. 13 μg/mL synthesized pardaxin caused 50% cytotoxicity in murine fibrosarcoma cell MN-11. We also revealed that pardaxin reduced anchorage-independent growth, cell migration ability, and caspase 3/7 activity in MN-11 cells. Moreover, intratumoral injection of pardaxin could attenuate tumor growth in vivo by inducing apoptosis, inhibiting inflammatory response, suppressing pro-inflammatory cytokines secretion, and diminishing angiogenesis. Due to the side effects of chemotherapy and increase in chemotherapy-resistant cancers, it is urged to develop therapies that provide specific toxicity in cancer cells and reduce damages to normal tissues without inducing drug resistance. This thesis exhibits that pardaxin has an antitumor activity with expect on its efficacy in clinical application in the future.
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Chen, Chia-Jung, and 陳珈融. "Construction of the solution-phase derived nucleoside library and screening of its cytotoxicity against HSV1-tk transfected murine fibrosarcoma cells." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/08706433629818907754.
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Chen, Sheng-Han, and 陳聖翰. "Study on the structure of electrospun chitosan/ poly(DL-lactide) composite fibrous scaffold for human fibrosarcoma cells (HT1080) attachment and proliferation." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/29700187425549394987.
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碩士中原大學
化學工程研究所
98
In this study, the effect of morphology design of chitosan/ poly(DL-lactide) electrospun composite fibrous scaffold on the attachment and proliferation of human fibrosarcoma cells (HT1080)were investigated. The bead-free and the most uniformity of PDLLA fibers could be fabricate through adjusting spinning parameters, e.g. under the condition of polymer concentration: 15wt%, working distance: 30 cm and needle diameter: 0.16 mm. Otherwise, the degradation test of chitosan spunning solution were also investigated. The result showed that the viscosity of chitosan solution decrease with increasing the degradation time. After 10 days of degradation, the spinnability and morphology of chitosan fibers were dramatically improved. The better alignment of chitosan fibers were collected successfully at 1000 rpm of rotating-drum collector. MTT assay results indicated the 3D structure of chitosan/ PDLLA composite fibrous scaffold could promote the ability of human fibrosarcoma cells proliferation compare with the 2D structure of PDLLA film and cover slip. When the collecting amount of chitosan aligned fibers increased to 12.66 g/cm2, the growth of cells were guided and elongated by the aligned chitosan fibers. And the 3D conforcal images showed that the cell growth could infiltration to the inside of fibrous scaffold, it’s consistent with the structure design of chitosan/PDLLA composite fibrous scaffold. According to the principle of tissue engineering, chitosan/PDLLA composite fibrous scaffold could have excellent potential for tissue regeneration and wound healing applications in the future.
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Huang, Hwa-Chen, and 黃譁宸. "The study of cytotoxicity and mechanism of Co60 and beta-lapachone in mouse fibrosarcoma cell line and human umbilical vein endothelial cell." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/35298189242687544741.
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碩士國立陽明大學
醫學生物技術研究所
93
β-lapachone is a natural plant derivative from the lapacho tree. It was reported that β-lapachone induced cell death of several cancer cell lines, and β-lapachone was then suggested to be a potential anti-cancer drug. Based on its severe toxicity on HUVEC cells, we are interested to know whether β-lapachone is an anti-angiogenic compound. The goal of this thesis is to find out the cytotoxicity and mechanism of Co60 and β-lapachone in mouse fibrosarcoma cell line and human umbilical vein endothelial cell. Final, we used animal model to study its tumor therapy effect. Single treatment with Co60 or β-lapachone has its effective result for different cancer cell. We used KHT and HUVEC cell as the way of this study. First, we used MTS assay to study the cytotoxicity of Co60 and β-lapachone. The results indicate that KHT is more sensitive to Co60 and HUVEC is more sensitive to β-lapachone. Additive effects were found in the combination of pre- or post- treatment of β-lapachone and Co60 in KHT cells, and also in post-treatment of β-lapachone and Co60 in HUVECs. In other hand, synergistic effect was found in the combination of pre-treatment β-lapachone and Co60 in HUVECs. Next, we utility flow cytometry to understand the cell cycle distribution, PI and LDH to study the cell death model. The results found that treatment with Co60 causes cell cycle delay in G2/M phase of KHT cells, and in G0/G1 phase of HUVECs; treatment with β-lapachone causes cell cycle delay in G0/G1 phase of KHT cells, but not in HUVECs. Both cells treated with both drugs were delayed at multiple checkpoints before committing to necrosis. To understand the mechanism of Co60 and/or β-lapachone on the cells, the alteration of several gene expressions were analyzed. Co60 was found to be able to turn on VEGF gene and protein expression, and only slight influence on other genes; β-lapachone was found to be able to turn on HIF gene expression, but no significant influence was found on other genes. In migration assay, β-lapachone significant effect neither. In animal model, we used β-lapachone pre-treatment plus Co60 for tumor therapy. The combined therapeutic effect is greater than single therapy. In conclusion, β-lapachone enhanced the killing effect of Co60 in vitro and in vivo.
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Chang, Meng-Lun, and 張孟倫. "Studies on the Regulation of MMP-2, -9 in HT-080 Human Fibrosarcoma cells by Chemical Constituents of the Leaves of Chamaecyparis formosensis." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/72912755133685454956.
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