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Sullivan, Christopher James. "The role of fibroblast growth factor-2 (FGF2) in vascular remodeling and adaptation." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/284317.
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The goal of this dissertation was to test the hypothesis that fibroblast growth factor-2 (FGF2) is required during diseased-related vascular growth and remodeling in the adult organism. Given previous research, it is generally assumed that FGF2 is an important regulator of vessel growth during various pathophysiological processes (e.g. tissue ischemia, vessel injury, and flow-dependent remodeling). However, such studies only indirectly implicate FGF2 in vascular adaptation and remodeling. In contrast, experiments using mice with a targeted disruption of the Fgf2 gene have allowed direct determination of the biological roles of endogenous FGF2. Thus, experimental models of flow-dependent remodeling and ischemic revascularization were used to compare the responses of Fgf2⁻/⁻ and Fgf2⁺/⁺ mice to directly identify the function of FGF2 during vascular adaptation in the adult animal. Surprisingly, the lack of FGF2 did not appear to affect vascular growth in these models. First, using a novel model of flow-dependent remodeling, Fgf2⁻/⁻ mice had equivalent carotid artery adaptation in response to both high-flow and low-flow was as wildtype counterparts. Second, angiogenesis and arteriogenesis were not different between the ischemic limbs Fgf2⁺/⁺ and Fgf2⁻/⁻ mice, demonstrating that FGF2 is not required for vascular adaptation in response to ischemia. However, these experiments led to the observation that reactive hyperemia was impaired in ischemic limb of Fgf2⁻/⁻ mice. These results indicate that vessel responsiveness is altered in the collateral circulation of the ischemic Fgf2⁻/⁻ limb. This possible identification of FGF2 as a "functional" factor in the collateral circulation suggests a novel, non-mitogenic role for endogenous growth factors. Finally, Fgf2⁻/⁻ mice had altered gene expression in the ischemic limb as evaluated using cDNA microarrays. The significance of differential gene expression in the absence of FGF2 is unknown. It is unclear whether such changes in gene expression are related to the FGF2 hyperemia phenotype or whether they are related to an unknown phenotype present in the ischemic limb of Fgf2⁻/⁻ mice. Overall, this dissertation provides new evidence that endogenous FGF2 has important actions in the remodeling vasculature during ischemic revascularization. Specifically, endogenous FGF2 appears to modulate vascular reactivity of the collateral circulation of the hindlimb.
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Olson, Nels Eric. "FGF2 is weakly mitogenic for intimal smooth muscle cells : role of FGF receptor expression, cytoplasmic signaling and cell cycle regulation /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/6335.
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Kole, Denis. "Role of Fibroblast Growth Factor 2 in Maintenance of Multipotency in Human Dermal Fibroblasts Treated with Xenopus Laevis Egg Extract Fractions." Digital WPI, 2014. https://digitalcommons.wpi.edu/etd-dissertations/207.
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Current usage of human embryonic stem cells (hES) and induced pluripotent stem cells (iPS) in clinical therapies and personalized medicine are limited as a result of ethical, technical and medical problems that arise from isolation and generation of these cells. Isolation of hES cells faces ethical problems associated with their derivation from human pre-implantation embryos. The most controversial aspect of hES cell isolation targets the generation of autologous hES cell lines which requires the transfer of a somatic-cell nucleus from the patient to an enucleated oocyte. While already established embryonic stem cell lines from IVF embryos can be used in a similar manner, lack of genetic identity can cause therapy rejection from the host, and prevent their use in personalized medicine. Induced pluripotent stem cells on the other hand, are generated from somatic cells that have been reprogrammed in vitro to behave like stem cells. While these cells can potentially be used for personalized medicine without the risk of rejection by the host system, derivation methods prevent their therapeutic use. The most efficient method used to generate iPS cells involves usage of viral particles which can result in viral DNA being integrated in the host cell’s genome and render these cells non-compliant for clinical therapies. Other methods not involving viral particles exist as well, but the reprogramming efficiency is too low and technical problems with generating large enough numbers of cells prevent these methods from being feasible approaches for clinical therapies. Direct reprogramming of a differentiated cell into a developmentally more plastic cell would offer alternatives to applications in regenerative medicine that currently depend on either embryonic stem cells (ES), adult stem cells or iPS cells. We hypothesize that Xenopus laevis egg cytoplasmic extract contains critical factors needed for reprogramming that may allow for non-viral, chemically defined derivation of human induced pluripotent/multipotent cells which can be maintained by addition of exogenous FGF2. In this thesis we investigated a new method for generation of multipotent cells through determining the ability of select fractions of Xenopus laevis egg extract to induce multipotency in already differentiated cells. We were able to identify select fractions from the extract that in combination with exogenously added FGF2 can reprogram and maintain the reprogrammed cells in an undifferentiated state. The findings of this work also determined that Xenopus laevis egg extract mRNA is required for achieving full reprogramming. The body of work presented in this thesis showed the ability of FGF2 isoforms to bind and activate select FGF receptor tyrosine kinases, act as extracellular mitogenic factors to support growth of hES cells in an undifferentiated state as well bind to nuclear DNA and affect expression of endogenous genes. Moreover, we showed that all FGF2 isoforms can induce expression of stem cell specific proteins in human dermal fibroblasts as well as extend lifespan of human dermal fibroblasts in vitro. In this work we identified HECW1, the gene coding for E3 ubiquitin ligase NEDL1, as a novel nuclear target for all FGF2 isoforms and showed that overexpression of recombinant FGF2 isoforms in human dermal fibroblasts can down regulate expression of HECW1 gene.
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Kinkl, Norbert. "Mechanisms of action of fibroblast growth factor 2 (FGF2) in rat retinal cells : photoreceptor survival and intracellular signaling." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13166.
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La dégénérescence des photorécepteurs est à l'origine de nombreuses pathologies rétiniennes aboutissant à une malvoyance voire à la cécité. Les facteurs neurotrophiques représentent une approche thérapeutique potentielle. Au cours de cette thèse nous nous sommes intéressés aux mécanismes d'actions in vitro d'un facteur neurotrophique exprimé dans la rétine, le FGF2. Afin d'étudier les effets directs du FGF2 sur la survie des photorécepteurs, nous avons mis au point un nouveau modèle de culture pure en photorécepteurs à partir de rétine jeune de rat. La pureté en photorécepteurs des cultures est > 99,5%, les cellules gliales de Müller (CGM) représentant < 0,5% de la population cellulaire. Grâce à ce modèle, nous avons montré que le FGF2 stimule la survie des photorécepteurs in vitro et qu'un autre facteur neurotrophique, l'EGF, accélère leur dégénérescence, en activant leurs récepteurs respectifs à activité tyrosine kinase. Les FGFR1-4 ainsi que différentes protéines impliquées dans la transduction du signal du FGF2 (ERK1/2, MEK1, MEK2, PLCg1, SHPTP-2, SOS1, SOS2, Grb2, Shc, Akt), sont exprimés de façon ubiquitaire, mais possèdent des niveau d'expression distinct, selon les différentes populations de cellules rétiniennes (photorécepteurs, rétine interne et CGM) in vivo et in vitro. Néanmoins, le FGF2 y induit des cascades de signalisation distinctes. Ceci indique l'existence de différentes voies de transduction du signal au FGF2 dans la rétine aboutissant toutes à l'activation de ERK1/2. L'inhibition pharmacologique de MEK bloque l'activation de ERK1/2 dans les photorécepteurs et inhibe leur survie induit par le FGF2, alors qu'au niveau des cellules de la rétine interne et des CGM, le FGF2 stimule également des voies d'activation de ERK1/2 indépendantes de MEK. L'ensemble de ces résultats apporte des données originales concernant les effets du FGF2 sur la survie des photorécepteurs ainsi que sur sa signalisation dans la rétine de rat in vitro, et pourrait contribuer à une application potentielle du FGF2 dans une approche clinique.
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Hedlund, Eva-Maria. "Molecular mechanisms of angiogenic synergism between Fibroblast Growth Factor-2 and Platelet Derived Growth Factor-BB." Thesis, Södertörn University College, School of Life Sciences, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-932.
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RIZZO, ILARIA MARIA. "Biological role of sphingosine 1-phosphate in neuroblasts derived from otic vesicle." Doctoral thesis, Università di Siena, 2016. http://hdl.handle.net/11365/1009811.
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Hearing loss is a health and social problem, particularly common among older people. Deafness is
associated with an irreversible loss of sensory hair cells and spiral ganglion neurons, which don’t
have regenerative potential. To date, cochlear implants are the only possible therapy, even if not
always effective. Therefore, there is an enormous research interest aimed at identifying factors that
could prevent hearing loss.
Sphingosine 1-phosphate (S1P) is a bioactive lipid involved in the regulation of many physiological
and pathological processes. Most of S1P functions are mediated through a family of five G-protein
coupled receptors. Cytokines and growth factors cross-talk with S1P pathway via the regulation of
the expression levels and activity of the enzymes responsible for S1P production, sphingosine kinases
(SK1 and SK2), and S1P receptors (S1P1-5) in different cellular types.
Recently, a crucial role for S1P signaling axis has been demonstrated in hearing loss. S1P receptor 2
(S1p2) and Spinster-2 (Spns2, the S1P specific transporter) knock-out mice are deaf for defects in the
stria vascularis. Nevertheless, the exact role of S1P in sensory hair cells and spiral ganglion neurons
biology has not been clarified.
In this study, the mouse otocyst cell line US/VOT-N33 has been used as experimental model of
differentiation into neurons of the spiral ganglion. We have demonstrated that fibroblast growth
factor 2 (FGF2) was able to induce the proliferation of US/VOT-N33 and to act as pro-survival factor
in staurosporine-induced apoptosis. Moreover, SK1 and SK2 are required for FGF2-mediated
proliferation and cell survival, measured by 3HThymidine incorporation and caspase-3
activity/cleavage assay respectively, demonstrating an involvement of S1P signaling axis in these
effects. While S1P1 and S1P2 down-regulation affects proliferation, S1P receptor activation is not
required for cell survival induced by FGF2. Additionally, the ERK1/2 MAPK signaling pathway was
found to mediate the mitogenic action of FGF2.
The cell counting of neurite-bearing cells and Western blotting analysis for Islet1/2 neuronal marker
were performed to evaluate FGF2-induced neuronal differentiation of this cell line. Preliminary
results showed that this effect exerted by FGF2 was reduced by concomitant addition of exogenous
S1P. Furthermore, pro-differentiating role exerted by FGF2 was increased in presence of SK1
knockdown and when SPNS2 is silenced, presuming a negative role of S1P pathway in FGF2-induced
neuritogenesis.
Taken together, these findings demonstrate a crucial role for S1P signaling axis in proliferation and
survival of otic vesicle neuroprogenitors, however further studies will be necessary in order to clarify
the role of S1P pathway during the differentiation of the spiral ganglion neurons.
This work could help to identify possible novel therapeutical approaches to prevent neuronal
degeneration during hearing loss.
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Manning, Janet R. "Fibroblast growth factor 2-mediated cardioprotection: the kinase mediators and downstream targets of FGF2-induced protection from ischemia and reperfusion injury." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1331296684.
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Aguiar, Rodrigo Barbosa de. "Aplicação diagnóstica e terapêutica de um novo anticorpo anti-FGF2 em processos de angiogênese em melanoma experimental." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-29102014-162446/.
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Evidências sugerem que o fator de crescimento de fibroblasto 2 (FGF2), produzido por melanomas, possui importante papel no crescimento tumoral, angiogênese e metástase. Assim, o uso de anticorpo monoclonal (mAb) que reconhece e bloqueia a atividade de FGF2 é uma abordagem a ser considerada em oncologia. O propósito desse estudo foi avaliar a aplicação diagnóstica e terapêutica de um novo anticorpo anti-FGF2, 3F12E7 IgG1, em melanoma experimental B16-F10. Para isso, camundongos C57Bl/6 foram implantados subcutaneamente (ou intravenosamente, para ensaios de metástase) com células de melanoma murino B16-F10 (5x105 células/animal). Quando tumores alcançaram 3-4 mm de diâmetro (ou 24 h pós-inóculo de células B16-F10, no caso de ensaios de metástase), camundongos foram tratados com anti-FGF2 3F12E7 IgG. Animais controle receberam igual volume do veículo ou quantidade de anticorpo controle de isotipo. Grupos: animais tratados com (1) anti-FGF2 3F12E7 IgG1; (2) ligante de CEA IgG1 (controle de isotipo); e (3) veículo. O tratamento dos camundongos portadores de tumor com anti-FGF2 IgG resultou, comparado com os controles salina e de isotipo, em uma redução no número de focos metastáticos nos pulmões (ANOVA, p < 0,05), em ensaios de metástase experimental, bem como em uma menor taxa de crescimento de tumores subcutâneos (n=7/grupo). Esse resultado é acompanhado por uma redução na densidade vascular do tumor, conforme determinado por imunomarcação para CD34 ou CD31. A captação tumoral de anti-FGF2 3F12E7 IgG foi avaliada por métodos de medicina nuclear, usando esse anticorpo radiomarcado com tecnécio-99m. Estudos SPECT/CT in vivo e de biodistribuição ex vivo revelaram que 99mTc-anti-FGF2 3F12E7 IgG pode atingir eficientemente tumores subcutâneos e metastáticos de B16-F10. Assim, esses dados sugerem que anti-FGF2 3F12E7 IgG pode ser uma estratégia antitumoral promissora para melanoma, bem como uma potencial ferramenta de imagem a ser explorada, atuando como um possível traçador para rastrear tumores FGF2-positivos e mapear esse estímulo angiogênico no microambiente tumoral. Aprovado pelo comitê de ética (CAPPesq): número 0942/09Compelling evidence suggests that fibroblast growth factor 2 (FGF2), produced by melanomas, plays important role in tumor growth, angiogenesis and metastasis. Therefore, the use of a monoclonal antibody (mAb) that recognizes and blocks FGF2 activity is seen as an approach to be considered in oncology. The purpose of this study was to evaluate the diagnostic and therapeutic application of a new anti-FGF2 antibody, 3F12E7 IgG1, in experimental melanoma B16-F10. For this, C57Bl/6 mice were subcutaneously (or intravenously, for experimental metastasis assay) implanted with murine melanoma B16-F10 cells (5x105 cells/animal). When tumors reached 3-4 mm in diameter (or 24 h after B16-F10 cells injection, in the case of metastasis assay), mice started receiving anti-FGF2 3F12E7 IgG. Control mice received equal volume of vehicle or isotype control IgG amount. Groups: (1) anti-FGF2 3F12E7 IgG1-treated, (2) CEA-binding IgG1-treated (isotype control) and (3) vehicle-treated mice. The treatment of tumor-bearing mice with anti-FGF2 IgG, compared with saline and isotype controls, led to a reduction in the number of metastatic foci in the lungs (ANOVA test, p < 0.05), in experimental metastasis assays, as well as to a lower subcutaneous tumor growth rate (n=7 per group). This result is accompanied by a reduction in the tumor vascular density, as determined by CD34 or CD31 staining. The anti-FGF2 3F12E7 IgG tumor uptake was evaluated by nuclear medicine approaches, using this antibody radiolabeled with technetium-99m. In vivo SPECT/CT and ex vivo biodistribution studies reveled that 99mTc-anti-FGF2 IgG could efficiently achieved B16-F10 subcutaneous and metastatic tumors. Thus, these data suggest that the anti-FGF2 3F12E7 IgG may be a promising antitumor strategy for melanoma, as well as a potential imaging tool to be explored, working as a possible tracer to identify FGF2-positive tumors and map this angiogenic stimulus in the tumor microenvironment. Ethics committee (CAPPesq) approval number 0942/09
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Adeyemo, Adeola T. "The Roles of the High and Low Molecular Weight Isoforms of Fibroblast Growth Factor 2 in Ischemia-Induced Revascularization." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444581.
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Ehrenfels, Yvonne. "Mutationen in den "fibroblast growth factor" (FGF)-Rezeptorgenen FGFR 1, 2 und 3 bei primären Craniosynostosen." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=960357629.
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Kilkenny, Dawn M. "Fibroblast growth factor (FGF) receptor-1 and FGF-2 nuclear localization in proliferating growth plate chondrocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/NQ58142.pdf.
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Magnusson, Peetra. "Fibroblast Growth Factor Receptor-1 Function in Vasculo- and Angiogenesis." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5824.
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Wagner, Andreas. "Identifizierung von Genen, die durch fibroblast growth factor receptor 2 (FGFR2) reguliert werden." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=961705361.
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Maucher, Tobias [Verfasser]. "Regulation des glialen Glutamattransports durch den Wachstumsfaktor ''Fibroblast growth factor 2'' (FGF-2) / Tobias Maucher." Ulm : Universität Ulm. Medizinische Fakultät, 2004. http://d-nb.info/1015438520/34.
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SAKANAKA, MASAHIRO, SHIGERU KOBAYASHI, MINORU UEDA, TOSHIO SHIGETOMI, KENICHI KOSAKI, HIDEAKI KAGAMI, and YOSHIYUKI HIRAMATSU. "THE LOCALIZATION OF BASIC FIBROBLAST GROWTH FACTOR (FGF-2) IN RAT SUBMANDIBULAR GLANDS." Nagoya University School of Medicine, 1994. http://hdl.handle.net/2237/16076.
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Boulle, Nathalie. "Analyse du système des insulin-like growth factors (IGF) et du fibroblast growth factor-2 (FGF-2) dans la tumorigenèse corticosurrenalienne." Paris 11, 2000. http://www.theses.fr/2000PA11T006.
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Dans les tumeurs corticosurrénaliennes, des anomalies de la région 11p15 et une surexpression du gène d'IGF-11 sont contemporaines de l'acquisition du phénotype malin. Nous montrons que la surexpression du gène IGF-11 dans les tumeurs corticosurrénaliennes malignes s'accompagne d'une traduction efficace de la protéine, majoritairement sous forme de précurseurs d'IGF-11. Ces mêmes tumeurs surexpriment de manière spécifique IGFBP-2, protéine de liaison des IGF fréquemment associée à la prolifération tumorale. La caractérisation de la lignée H295R, dérivée d'un carcinome surrénalien, montre que celle-ci surexprime IGF-11 et IGFBP-2 et constitue un bon modèle in vitro d'ét•ude de la tumorigénèse corticosurrénalienne. Cette lignée a permis de démontrer qu'IGF-11 était impliqué dans la prolifération des cellules tumorales corticosurrénaliennes via le récepteur de type 1 des IGF. L'intérêt de I'IGFBP-2 plasmatique en tant que marqueur circulant des tumeurs corticosurrénaliennes malignes a été évalué. Nous montrons que les taux d'IGFBP-2 plasmatique s'élèvent spécifiquement chez les patients porteurs de tumeurs malignes mais que cette élévation survient à lin stade avancé de la maladie (stade métastatique), indiquant la faible sensibilité d'IGFBP-2 et son intérêt limité comme marqueur des carcinomes surrénaliens. Les effets de FGF-2 sur les cellules tumorales corticosurrénaliennes ont également été étudiés. Nos résultats montrent que FGF-2 a un effet prolifératif sur les cellules H295R mais que paradoxalement, il inhibe l'expression du système des IGF par ces cellules. L'inhibition d'IGFBP-2 se fait au niveau transcriptionnel, alors que celle d'IGF-11 est post-transcriptionnelle, par inhibition de la maturation des précurseurs d'IGF-11. Ainsi, si IGF-11 a un rôle indiscutable au stade tardif de la tumorigénèse corticosurrénalienne, différents facteurs sont susceptibles de moduler son expression (FGF-2) ou son activité (IGFBP-2) au sein du tissu tumoralLn adrenocortical tumors, malignant phenotype is associated with abnormalities at the 11p15 locus and overexpression of the IGF-11 gene. Here, we show that IGF-11 mRNA is efficiently translated and that malignant adrenocortical tumors contain large amounts of IGF-11 protein, mainly in its prohormone form. The same tumors exhibit a high content in IGFBP-2 protein, an IGFBP being frequently expressed in tumor cells. The H295R cell line, which is derived from a human adrenal carcinoma, express high levels of both IGF-11 and IGFBP-2 and represents a suitable in vitro model to study adrenocortical tumorigenesis. Using this cell line, we could demonstrate that IGF-11 is involved in the proliferation of adrenocortical tumor cells, after binding to the type 1 IGF receptor. The interest of plasma IGFBP-2 as a marker for adrenocortical carcinoma was evaluated. Our results show that high levels of IGFBP-2 are specifically detected in the plasma of patients with malignant adrenocortical tumors. However, the increase in IGFBP-2 levels occur at a late stage of tumor progression (metastatic stage). This indicates a poor sensitivity for plasma IGFBP-2, which may limit its interest as a tumor marker. We also studied the effects of FGF-2 on adrenocortical tumor cells. Our results indicate that FGF-2 is mitogenic for H295R cells, although it inhibits the expression of both IGF-11 and IGFBP-2 by these cells. The inhibition of IGFBP-2 expression occur at the transcriptional levels. Ln contrast, FGF-2 inhibits the secretion and the last steps of maturation of the IGF-11 precursor. Altogether, these results suggest that in malignant adrenocortical tumors, various factors may modulate the expression (FGF-2) or the effects (IGFBP-2) of IGF-11 on adrenocortical tumor cells
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Kirtland, David Rand. "Preparation of Heparin Surface for Quantification of Fibroblast Growth Factor-2 (FGF-2) Binding Using Surface Plasmon Resonance (SPR)." Thesis, Virginia Tech, 2005. http://hdl.handle.net/10919/33265.
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A mixed self assembling monolayer (mSAM) chip with attached heparin was developed to analyze heparin-protein interactions using a Reichert Inc, SR7000, surface plasmon resonance (SPR) instrument. The heparin was attached via streptavidin-biotin linkage where the streptavidin was covalently coupled to the mSAM and biotinylated heparin bound to it. These chips were then used to quantify the interactions of fibroblast growth factor-2 (FGF-2) with the surface bound heparin. Kinetic rate constants of association and disassociation were calculated. The association data of FGF-2 with heparin was fit to a single compartment, well-mixed model as the data did not exhibit mass transfer limitations. The results suggested that rebinding was prevalent and observed disassociation rates differed significantly in the presence of competing soluble heparin during disassociation. Our results indicate that the Reichert instrument and mSAM chips can be used to analyze heparin-protein interactions but that a careful protocol, outlined in this thesis, should be followed to obtain optimal data.Master of Science
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Liao, Siyun. "The Role of Fibroblast Growth Factor-2 Isoforms in Ischemia-reperfusion Injury and Cardioprotection." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1203690695.
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Filani, Oluwadamilola. "Expression and Purification of Unlabelled and Isotopically Labelled Human Fibroblast Growth Factor-1 and its Receptor Relevance in Cancer Research." TopSCHOLAR®, 2015. http://digitalcommons.wku.edu/theses/1549.
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Studies show that fibroblast growth factors (FGFs) control variety of cellular activities such as mitosis, cell differentiation, survival and angiogenesis. The FGF family consists of 23 different heparin-binding proteins. One of the most intensively studied members is human FGF-1 (hFGF-1) because of its critical role in the formation of blood vessels and cell proliferation in some types of cancer. The biological activities of FGFs are primarily mediated via interactions with fibroblast growth factor receptors (FGFR) and are a potent target in cancer. In this study, we report an efficient affinity column purification of hFGF-1 and the D2 domain of FGFR-2 from bacterial expression followed by SDSPAGE analysis. Steady state fluorescence results showed that both proteins were in their native conformation. The 1 H-15N HSQC NMR analysis of hFGF-1 was further performed. The data confirmed the purity and well-conserved native state of the protein. The findings of this study can be used in designing hFGF-1 antagonists with competitive inhibition characteristics. These antagonists could result in possible inhibition of hFGF-1 cell proliferation and angiogenesis associated in tumorigenesis.
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Gilbert, Emmanuelle. "L'épissage alternatif comme mécanisme de contrôle de l'expression du gène codant pour le récepteur-2 aux facteurs de croissance des fibroblastes." Nantes, 1994. http://www.theses.fr/1994NANT2096.
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Le gène FGFR2 code pour une famille de récepteurs des facteurs de croissance des fibroblastes (FGFS) dérivant du même pré-messager par le jeu d'épissages alternatifs. Quatre récepteurs à haute affinité pour ces facteurs ont été identifiés, de FGFR1 à FGFR4. Ces récepteurs sont tous bâtis sur le même modèle. Leur domaine extra-cellulaire est composé de trois boucles immunoglobuline-like et leur domaine intra-cellulaire possède une activité tyrosine kinase. La première partie de ce mémoire concerne la caractérisation des divers transcrits issus du gène FGFR2. Quatre extrémités carboxy-terminales FGFR2 différentes peuvent être générées par épissage alternatif. Elles peuvent co-exister dans une même cellule. Les protéines BEK et K-SAM, issues du gène FGFR2, sont identiques excepté au niveau des séquences codant pour la seconde moitié du troisième domaine immunoglobuline-like. Elles résultent de l'épissage alternatif mutuellement exclusif de deux exons, BEK et K-SAM. Le choix entre ces deux exons a pour conséquence, pour les récepteurs BEK et K-SAM, des différences d'affinité vis à vis des ligands. Ce choix est soumis à un contrôle strict: un type cellulaire donné exprime des transcrits soit BEK, soit K-SAM, mais quasiment jamais les deux ensembles. La seconde partie de ce mémoire concerne l'étude de la régulation de l'expression du gène codant pour le FGFR2. Mon travail de thèse a abouti à l'élaboration d'un modèle faisant intervenir une activation de l'exon K-SAM et d'une répression de l'exon BEK dans les cellules faisant le choix K-SAM. Mon travail s'est ensuite articulé autour de la définition précise des séquences en cis impliquées dans la répression de l'exon BEK.
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Machado, Aline Zamboni. "Pesquisa de mutações nos genes FGF9 e FGFR2 em pacientes portadores de distúrbios do desenvolvimento sexual 46,XY por anormalidades no desenvolvimento gonadal." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-18092012-143903/.
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Introdução: Várias evidências em estudos de animais knockout sugerem a efetiva participação dos genes Fgf9-Fgfr2 no processo de determinação testicular. Animais XY knockout para os genes Fgf9 e Fgfr2 apresentam reversão sexual como consequência da alteração na cascata de eventos masculinizantes nas gônadas fetais. Até o momento, mutações inativadoras dos genes FGF9-FGFR2 não foram descritas em pacientes 46, XY portadores de disgenesia gonadal. Objetivos: Pesquisar a presença de mutações inativadoras nos genes FGF9 e FGFR2 em pacientes portadores de DDS 46,XY por anormalidades do desenvolvimento gonadal. Casuística e Métodos: Trinta e três pacientes com disgenesia gonadal 46, XY, 11 com a forma completa e 22 com a forma parcial. As regiões codificadoras dos genes FGF9 e FGFR2 de todos os pacientes foram amplificadas e sequenciadas. As investigações quanto a presença de deleções foram realizadas usando-se a técnica de MLPA (Multiplex ligation-dependent probe amplification). Resultados: Mutações ou deleções nos genes FGF9 não foram encontradas em nenhum dos pacientes estudados, apenas alguns polimorfismos previamente descritos. No gene FGFR2 não foram encontradas deleções. Uma nova variante não sinônima em heterozigose, c.1358 C>T (p.Ser453Leu), localizada no exon 10 do FGFR2 foi encontrada em duas irmãs com disgenesia gonadal parcial 46,XY. A mãe é portadora da variante alélica e o estudo de 147 indivíduos controles não identificou a presença desta variante. A análise da variante em sites de previsão, PolyPhen, SIFT e Mutation Taster indicou que a nova proteína FGFR2 é possivelmente danificada. Conclusões: Se esses resultados dos sites de previsão forem confirmados em estudos funcionais futuros a participação do gene FGFR2 na determinação gonadal masculina em humanos estará comprovadaIntroduction: Several evidence in animal studies \"knockout\" suggest the effective participation of Fgf9-Fgfr2 genes in testicular determination process. Animals XY \"knockout\" for Fgf9 and Fgfr2 genes exhibit sex reversal as a result of the change in the cascade of masculinizing events in fetal gonads. To date, So far inactivating mutations of FGF9 and FGFR2 genes have not been described in 46,XY patients with gonadal dysgenesis. Objectives: To investigate the presence of inactivating mutations in the FGF9 and FGFR2 gene in patients with 46,XY DSD by gonadal abnormalities. Casuistic and Methods: Thirty-three patients with 46,XY gonadal dysgenesis, 11 with the full form and 22 with the partial form. The coding regions of FGF9 and FGFR2 genes of all patients were amplified and sequenced. Investigations on the presence of deletions were made using the MLPA technique (\"Multiplex ligation-dependent probe amplification\"). Results: Mutations or deletions in the FGF9 gene were not found in any of the patients studied, only a few polymorphisms previously described. FGFR2 gene deletions were not found. A new non-synonymous variant in heterozygosis, c.1358 C> T (p.Ser453Leu) located in exon 10 of FGFR2 was found in two sisters with 46,XY partial gonadal dysgenesis. The mother is a carrier of the variant allele and the study of 147 control subjects did not identify the presence of this variant. The analysis of the variant on prediction sites, \"PolyPhen\", \"SIFT\" and \"Mutation Taster\" indicated that the new FGFR2 protein is possibly damaged. Conclusions: If the results of the prediction sites are confirmed by future functional studies the participation of the FGFR2 gene in human male gonadal determination will be proven
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Santiago, Jon-Jon. "Studies on high molecular weight fibroblast growth factor-2 isoforms produced by rat and human cardiac myofibroblasts." Oxford Journals, 2011. http://hdl.handle.net/1993/23867.
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Fibroblast growth factor-2 (FGF-2) is expressed as high molecular weight (> 20 kDa, Hi-FGF-2), or low molecular weight, (18 kDa, Lo-FGF-2) isoforms with distinct functions in the heart and other tissues. Studies to-date have focused on Lo-FGF-2, while the biology of Hi-FGF-2 is less well understood. This work investigated potential autocrine and paracrine effects of rat and human Hi-FGF-2 on cardiac myocytes and non-myocytes (myofibroblasts).
Using rat ventricular myofibroblast cultures stimulated with angiotensin II (Ang II), in the absence or presence of YVAD, a peptide inhibitor of caspase-1, it was shown that caspase-1 activity was required for the Ang II-stimulated Hi-FGF-2 secretion. Secreted rat Hi-FGF-2 was shown to be biologically active and capable of stimulating neonatal as well as adult cardiomyocyte hypertrophy in vitro. The effect of extracellular-acting Hi- versus Lo-FGF-2 on the secretome profile of rat cardiac myofibroblasts was compared. Conditioned media collected after stimulation with rat Hi- or Lo-FGF-2 were analyzed by mass spectroscopy (LC-MS/MS). Secretome profiles suggested that Hi-FGF-2 was more potent than Lo-FGF-2 in upregulating several matricellular and fibrosis-associated proteins, most prominently periostin, follistatin-like protein 1, plasminogen activator inhibitor-1, and tenascin.
Human heart (atrial) tissue, pericardial fluid, and human heart-derived myofibroblasts were shown to accumulate predominantly Hi-FGF-2. Ang II up-regulated Hi-FGF-2 in human cells, via activation of: type 1 or type 2 Ang II receptors (AT-1R, AT-2R); the ERK pathway; and matrix metalloprotease-2. Neutralizing antibodies specific for Hi-FGF-2 (neu-AbHi-FGF-2) reduced expression of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis. Blocking the autocrine action of Hi-FGF-2 on human cells with neu-AbHi-FGF-2 resulted in down-regulation of periostin, as well as α-smooth muscle actin, pro-collagen, embryonic smooth muscle myosin, and extra domain A fibronectin, consistent with a reversal from activated myofibroblast to fibroblast phenotype. Stimulation of human myofibroblasts with human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating pro-interleukin-1β and plasminogen activator inhibitor-1, considered to be pro-inflammatory proteins.
It is concluded that exported, extracellular-acting Hi-FGF-2 has pro-fibrotic, pro-inflammatory, and pro-hypertrophic properties, contributes to the ‘activated fibroblast’ phenotype, and represents a therapeutic target for prevention of maladaptive cardiac remodeling in humans.
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Burger, Patricia E. "The effects of fibroblast growth factor-2 (FGF-2) on haematopoietic cells and the identification of those cells expressing FGF receptors." Doctoral thesis, University of Cape Town, 2002. http://hdl.handle.net/11427/3110.
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Tassone, Evelyne. "Extracellular matrix-degrading enzymes and control of fibroblast growth factor-2 (FGF-2) signaling in pediatric glioma cell lines." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422194.
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The main purpose of my research project was to investigate the role of two extracellular matrix-degrading enzymes, heparanase (HPSE) and membrane-type 1 matrix metalloproteinase (MT1-MMP), in pediatric gliomas. I spent the first two years of my PhD program in Dott. Maurizio Onisto’s laboratory (University of Padua). Then I continued my work at New York University School of Medicine, under the supervision of Prof. Paolo Mignatti, whose experimental work focuses on the molecular mechanisms of proteolysis-independent signaling by MT1-MMP and its physiological inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2).
Gliomas, the most common primary brain tumors, comprise a heterogeneous group of neoplasms that originate from glial cells. Despite recent advances in the management of these tumors, children affected by gliomas, particularly the more aggressive forms, have a poor prognosis. Gliomas can diffusely penetrate throughout the brain, even though they remain localized in this organ. One of the most important events during glioma cell invasion is extracellular matrix (ECM) degradation, a complex mechanism that involves both glycosidic and proteolytic enzymes. HPSE is an endo-β-D-glucuronidase secreted in the ECM, where it cleaves the heparan sulfate side chains of both soluble and membrane-bound proteoglycans. MT1-MMP, a cell membrane-bound proteinase with an extracellular catalytic domain and a short cytoplasmic tail, has been implicated in the proteolytic degradation of extracellular and transmembrane proteins. High levels of HPSE and MT1-MMP are present in a variety of aggressive malignancies, a finding that highlights their important role in cancer invasion and metastasis.
In this study we characterized pediatric glioma cell lines derived from different types of gliomas: two glioblastoma multiforme, one anaplastic astrocytoma, one diffuse astrocytoma and one pilocytic astrocytoma. In addition, we used a human breast adenocarcinoma cell line to examine the role of MT1-MMP, because these cells do not express this proteinase and thus represent an ideal model for the regulation of its expression.
The data reported here show that MT1-MMP controls activation of intracellular signaling by fibroblast growth factor-2 (FGF-2) and FGF-2 binding to the breast adenocarcinoma cells. We found no clear correlation between HPSE, MT1-MMP or FGF-2 expression and the aggressiveness of the pediatric astrocytoma cells. Gene silencing of HPSE in a pediatric glioblastoma cell line does not affect vascular endothelial growth factor (VEGF) expression or cell proliferation, but upregulates matrix metalloproteinase-2 (MMP-2) and MT1-MMP expression. Moreover, ERK1/2 activation by FGF-2 does not correlate with MT1-MMP expression and is modified by an MMP inhibitor in these pediatric glioma cells. Finally, TIMP-2 controls ERK1/2 activation in all glioma cells.
Taken together, the results show that MT1-MMP does not have the same effects in breast carcinoma and pediatric glioma cells, indicating a different and more complex control mechanism of intracellular signaling. This initial characterization of these unique pediatric astrocytoma cell lines provides new insights into the knowledge of this poorly studied group of tumors.L’obiettivo principale del mio progetto di ricerca è stato analizzare il ruolo di due enzimi che degradano la matrice extracellulare, l’“heparanase” (HPSE) e la “membrane-type 1 matrix metalloproteinase” (MT1-MMP), nei gliomi pediatrici. Ho trascorso i primi due anni di Dottorato nel laboratorio del Dott. Maurizio Onisto (Università di Padova). Ho poi continuato il mio lavoro presso la New York University School of Medicine, sotto la supervisione del Prof. Paolo Mignatti, il cui lavoro sperimentale è focalizzato sull’approfondimento dei meccanismi molecolari alla base dell’attivazione del segnale intracellulare da parte di MT1-MMP e del suo inibitore fisiologico, il “tissue inhibitor of metalloproteinases-2” (TIMP-2). I gliomi, i più comuni tumori cerebrali primari, comprendono un gruppo eterogeneo di neoplasie che originano dalle cellule gliali. Nonostante i recenti progressi raggiunti nel trattamento e nel controllo di tali tumori, la prognosi dei bambini affetti da glioma, ed in particolare dalle sue forme più aggressive, rimane tuttora infausta. Pur essendo confinati nell’organo nel quale originano, i gliomi possono invadere tutte le aree del cervello. Uno degli eventi più importanti che caratterizzano l’invasività dei gliomi è costituito dalla degradazione della matrice extracellulare, un complesso meccanismo che coinvolge enzimi sia glicosidici sia proteolitici. HPSE è una endo-β-D-glucuronidasi secreta nella matrice extracellulare, nella quale taglia le catene di eparan solfato dei proteoglicani solubili e legati alla membrana. MT1-MMP, una proteasi legata alla membrana e composta da un dominio catalitico extracellulare e da una piccola coda citoplasmatica, è coinvolta nella degradazione proteolitica di proteine extracellulari e di membrana. Elevati livelli di HPSE e MT1-MMP sono stati riscontrati in numerosi tipi di tumore e tale evidenza sottolinea il ruolo chiave che essi svolgono nell’invasività tumorale e nella formazione di metastasi. In questo studio sono state caratterizzate cinque linee cellulari di glioma pediatrico derivanti da diversi tipi di glioma: due glioblastomi multiformi, un astrocitoma anaplastico, un astrocitoma diffuso ed un astrocitoma pilocitico. Con lo scopo iniziale di esaminare il ruolo di MT1-MMP nell’attivazione del segnale indotto dall’FGF-2, è stata inoltre utilizzata una linea cellulare di carcinoma mammario, la quale non esprime MT1-MMP e perciò rappresenta un modello ideale per studiare la regolazione della sua espressione. I dati riportati mostrano che, nelle cellule di carcinoma mammario, MT1-MMP regola l’attivazione del segnale intracellulare da parte del “fibroblast growth factor-2” (FGF-2) e controlla il legame di questo fattore di crescita alla superficie delle cellule. Nelle cellule di astrocitoma pediatrico non è stata identificata alcuna chiara correlazione tra espressione di HPSE, MT1-MMP o FGF-2 ed aggressività tumorale. I risultati inoltre dimostrano che il silenziamento genico di HPSE in una linea cellulare di glioblastoma pediatrico non influenza l’espressione del “vascular endothelial growth factor” (VEGF) o la proliferazione cellulare, ma determina la sovraespressione della “matrix metalloproteinase-2” (MMP-2) e di MT1-MMP. Inoltre, nelle cellule di glioma, l’attivazione di ERK1/2 da parte di FGF-2 non correla con l’espressione di MT1-MMP e risulta modificata dal trattamento con un inibitore di MMP. Infine, in tutte le cellule di glioma, anche TIMP-2 regola l’attivazione del segnale intracellulare. In conclusione, i risultati ottenuti mostrano che MT1-MMP non ha gli effetti nelle cellule di carcinoma mammario e di glioma pediatrico, indicando l’esistenza di un differente e più complesso meccanismo di controllo del segnale intracellulare. La caratterizzazione delle linee cellulari di astrocitoma pediatrico presentata in questa tesi offre una più completa conoscenza di questo gruppo di tumori ancora poco studiati.
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Robbez-Masson, Luisa. "Investigating the functional significance of an FGFR2 intronic SNP in breast cancer." Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8539.
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Single nucleotide polymorphisms present in the second intron of the fibroblast growth factor receptor 2 (FGFR2) gene have been linked with increased risk of breast cancer in several genome wide association studies. The potential effect of those SNPs appeared to be mediated through the differential binding of cis-regulatory elements, such as transcription factors, since all the SNPs in linkage disequilibrium were located in a regulatory DNA region. Preliminary studies have shown that a Runx2 binding site is functional only in the minor, disease associated allele of rs2981578, resulting in increased expression of FGFR2 in cancers from patients homozygous for that allele. Moreover, the increased risk conferred by the minor FGFR2 allele is associated most strongly in oestrogen receptor alpha positive (ERα) breast tumours, suggesting a potential interaction between ERα and FGFR signalling. Here, we have developed a human cell line model system to study the effect of those SNPs on cell behaviour. In an ERα positive breast cancer cell line, rs2981578 was edited using Zinc Finger Nucleases. Unexpectedly, the acquisition of the single risk allele in MCF7 cells failed to affect proliferation or cell cycle progression. Binding of Runx2 to the risk allele was not observed. However FOXA1 binding, an important ERα partner, appeared decreased at the rs2981578 locus in the risk allele cells. Additionally, differences in allele specific expression (ASE) of FGFR2 were not observed in a panel of 72 ERα positive breast cancer samples. Thus, the apparent increased risk of developing ERα positive breast cancer is not caused by rs2981578 alone. Rather, the observed increased risk of developing breast cancer might be the result of a coordinated effect of multiple SNPs forming a risk haplotype in the second intron of FGFR2.
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Brooks, Nicole E. "Fibroblast Growth Factor 21 Expression in Mice with Altered Growth Hormone Action: Links to Obesity, Type 2 Diabetes Mellitus, and Increased Longevity." Ohio University Honors Tutorial College / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461161246.
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Dehkhoda, Farhad. "Identification and validation of FGFR2 mutations providing resistance to pan-FGFR inhibitor BGJ398." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/114506/1/Farhad%20Dehkhoda%20Thesis.pdf.
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Endometrial cancer (EC) is the most commonly diagnosed gynaecological cancer, and is responsible for ~370 deaths per year in Australia and 8600 deaths annually in the USA. Fibroblast growth factor receptor 2 (FGFR2) mutations have been identified in ~ 12% of endometrial cancer patients and research confirms it is a valid therapeutic target. Tyrosine kinase inhibitors (TKIs) have been used in the last few years to treat patients with mutant receptor tyrosine kinases (RTKs). Despite patients showing an initial response to these TKIs, acquired resistance associated with cancer relapse often occurs. Acquired resistance is frequently caused by secondary mutations in the kinase domain that either directly hinder drug binding or stabilise a conformation not conducive to drug binding.
In recent years, the Ba/F3 cell line model system has been used to identify mutations causing resistance to these inhibitors and many of these mutations have subsequently been identified in patients treated with these TKIs. We sought to identify FGFR2 kinase domain mutations that confer resistance to the pan-FGFR inhibitor BGJ398. We cultured Ba/F3 cells expressing FGFR2 in high doses of BGJ398 and identified 6 resistant clones harbouring either the FGFR2E566A or FGFR2V565I mutations in the kinase domain. Ba/F3 cells carrying each mutations, together with the FGFR2N550K mutation commonly seen in patients, were used to assess if these mutations were cross-resistant to other FGFR inhibitors (PD173074, ponatinib, AZD4547 and LY2874455). Only LY2874455 inhibited all the resistant FGFR2 mutations. In addition, lentiviral transduction of the endometrial cancer cell line JHUEM2 with the same FGFR2 resistance mutations resulted in heterozygous expression of the resistance alleles confirmed by sequencing cDNA. Transduced JHUEM2 cell lines were tested against the panel of FGFR inhibitors, however, the same level of resistance that was seen in Ba/F3 cells was not always observed in the JHUEM2 cell lines. We also used the myeloma cell line KMS11-R, which harbours a heterozygous FGFR3V565I mutation, and showed these cells conferred resistance to all inhibitors except LY2874455. From these data we propose that tumours harbouring FGFR mutations should be treated with LY2874455, as it effectively inhibits all identified FGFR mutations that cause resistance to other FGFR inhibitors.
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Elahouel, Rania. "Le Fibroblast Growth Factor 2 ( FGF-2 ) et la neuropiline-1 (NRP-1) : nouveaux partenaires moléculaires de Heparin Affin Regulatory Peptide ( HARP)." Thesis, Paris Est, 2012. http://www.theses.fr/2012PEST0066.
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HARP (Heparin Affin regulatory peptide) est un facteur de croissance qui constitue avec la midkine une sous-famille des Heparin Binding Growth Factors (HBGFs). HARP est impliqué dans de nombreux processus physiologiques comme la neurogenèse et la vasculogenèse mais aussi dans des processus physiopathologiques comme l’angiogenèse et la progression tumorale. HARP interagit avec différents récepteurs (N-syndécan, RPTPβ/ζ, et ALK). Plus récemment, il a été montré au laboratoire que la nucléoline, protéine navette entre le noyau, le cytoplasme, et la surface cellulaire est un nouveau récepteur à HARP. Malgré les avancées dans ce domaine, l’interaction de HARP avec ses récepteurs n’est pas totalement élucidée. L'objectif de ce projet de thèse était la recherche de nouveaux partenaires moléculaires qui interagissent avec HARP, de comprendre le mécanisme de leurs interaction et d’analyser les effets biologiques. A ce titre, j’ai participé à l’étude de l’interaction de HARP avec le facteur de croissance des fibroblastes, le FGF-2. Ce facteur liant l’héparine est également mitogène et angiogène. En utilisant des techniques de biocapteurs optiques et d’interaction protéine-protéine, nous avons montré une interaction directe entre HARP et le FGF-2 et qui implique les domaines C-TSR-I et C-terminale de HARP. De plus, cette interaction inhibe la migration et la prolifération des cellules endothéliales, induites par le FGF-2 ou par HARP seuls. En parallèle, j’ai mis en évidence l’interaction entre HARP et la NRP-1. NRP-1 est une protéine transmembranaire, ayant comme ligands principaux, les sémaphorines de classe 3 (SEMA 3A), le facteur de croissance endothélial vasculaire (VEGF) et le FGF-2. En plus de son rôle crucial dans le développement des systèmes nerveux et cardiovasculaires, la NRP-1 est impliquée dans les processus physiopathologiques tels que l’angiogenèse et l’invasion tumorale. Ainsi, la NRP-1 présente un profil biologique similaire à HARP. En utilisant des tests d’ELISA, d’immunoprécipitation et de « pull-down », nous avons montré que HARP interagit avec la NRP-1. Cette interaction semble être directe et s’effectue via les domaines de liaison à l’héparine TSR-I. HARP induit l’internalisation de la NRP-1 au bout de 15 minutes et son recyclage partiel à la surface cellulaire au bout d’une heure. L’internalisation de la NRP-1 s’accompagne par la phosphorylation des voies MAPK (ERK1/2), Akt et FAK. L’interaction HARP/NRP-1 est cruciale pour la migration des cellules endothéliales et l’invasion des cellules tumorales. En conclusion, ces résultats apportent de nouvelles avancées concernant les partenaires moléculaires de HARP en particulier et montrent également la complexité des interactions des facteurs de croissance entre eux et avec leurs récepteurs. Plus généralement, cette étude permet d'envisager des stratégies thérapeutiques ciblant l’interaction de la NRP-1 avec HARP et aussi les autres facteurs de croissanceHARP (Heparin Affin regulatory peptide) is a growth factor that constitutes with midkine a subfamily of Heparin Binding Growth Factors (HBGFs). HARP is involved in many physiological processes such as neurogenesis and vasculogenesis but also in pathophysiological processes such as angiogenesis and tumor progression. HARP interacts with different receptors (N-syndecan, RPTPβ / ζ and ALK). More recently, it has been shown in the laboratory that nucleolin, a protein shuttle between the nucleus, cytoplasm, and cell surface, is a new HARP receptor. Despite the advances in this field, the interaction of HARP with its receptors is not fully understood. The aim of this thesis was the search for new molecular partners that interact with HARP, to understand the mechanism of their interaction and analyze the biological effects. My work was firstly to participate to the study of the interaction of HARP with the fibroblast growth factor-2, FGF-2. This factor is also an heparin-binding factor, with mitogenic and angiogenic activities. Using techniques of optical biosensors and protein-protein interaction, we have shown a direct interaction between HARP and FGF-2 that involves C-TSR-I and C-terminus domains of HARP. In addition, HARP inhibits the migration and proliferation of endothelial cells induced by FGF-2. In parallel, I highlighted the interaction between HARP and NRP-1. NRP-1 is a transmembrane protein having as main ligands, semaphorins class 3 (SEMA 3A), the vascular endothelial growth factor (VEGF) and FGF-2. In addition to its crucial role in the development of the nervous and cardiovascular systems, the NRP-1 is involved in physiopathological processes such as angiogenesis and tumor invasion. Thus, NRP-1 has a biological profile similar to HARP. Using ELISA, immunoprecipitation and "pull-down" tests, we have shown that HARP interacts with NRP-1. This interaction appears to be direct and occurs via heparin binding domains of HARP: TSR-I. HARP induces internalization of NRP-1 after 15 minutes and partial recycling to the cell surface after one hour. The internalization of the NRP-1 is accompanied by the phosphorylation of MAPK pathways (ERK1 / 2), Akt and FAK. HARP/NRP-1 interaction is crucial for endothelial cell migration and invasion of tumor cells. In conclusion, these results provide new advances on molecular partners of HARP in particular and also show the complexity of the interactions between these growth factors and their receptors. More generally, this study allows considering therapeutic strategies targeting the interaction of NRP-1 with HARP as well as other growth factors
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Krajewski, Anna Christina. "Die Regulation der Synthese und Freisetzung von FGF-2 aus humanen dermalen Mastzellen." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2006. http://dx.doi.org/10.18452/15404.
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Die Synthese und -Freisetzung von FGF-2 aus humanen dermalen Mastzellen Fibroblast growth factor-2 (FGF-2) ist ein Mitglied einer großen Familie von Wachstumsfaktoren. FGF-2 fördert das Wachstum und die Entwicklung von Blutgefäßen (Angiogenese) und nimmt somit Einfluss auf Wundheilungsprozesse, Gewebeentwicklung, als auch verschiedene pathologische Vorgänge im Organismus. Mastzellen wurden lange Zeit allein als Effektorzellen der Typ I Allergiereaktion betrachtet. Mittlerweile betrachten man sie auch als wichtige Zellen für die Gewebe Homöostase und Wundheilung. In der vorliegenden Arbeit wurden MC aus humenen dermalen Gewebe isoliert, um deren FGF-2 Synthese und –Freisetzung zu untersuchen. Die Zellen wurden mit verschiedenen proinflammatorischen Mediatoren stimuliert. FGF-2 wurde mit ELISA und PCR Methoden bestimmt. Durch Stimulationen mit a–IgE, SP, IL–4, IL–6 und IL–8 wurde eine gesteigerte FGF–2–Synthese induziert. Weiterhin zeigten die vorliegenden Ergebnisse, dass bei der Degranulation der MC FGF-2 freigesetzt wird, auch wenn der zugrunde liegende Mechanismus für die Freisetzung weiterhin unklar bleibt. UVA1–und PUVA1–Bestrahlung hatten einen inhibieren Effekt auf die Sekretion des Proteins.Synthesis and release of FGF-2 from human dermal mast cells Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins. FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. atherosclerosis), normal wound healing and tissue development. Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. In this present investigation we isolated MC from human tissue to investigate their FGF-2 synthesis and release after stimulation with different proinflammatory mediators. To detect FGF-2 we used ELISA and PCR technique. We could show the up-regulation of FGF-2 synthesis after stimulation with a-IgE, SP, IL-4, IL-6 and IL-8. Within the degranulation of MC there was a release of FGF-2 even though the mode of release still remains unclear. Through UV-light radiation we could show a downregulation of FGF-2 release.
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Kefalakes, Ekaterini Sofia [Verfasser]. "Role and putative therapeutic implications of fibroblast growth factor-2 (FGF-2)-dependent interplay of neurotrophic factors and signaling cascades in amyotrophic lateral sclerosis / Ekaterini Sofia Kefalakes." Hannover : Stiftung Tierärztliche Hochschule Hannover, 2018. http://d-nb.info/1178008851/34.
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Wang, Jie. "Fibroblast growth factor-2 protects neonatal rat cardiac myocytes from doxorubicin-induced damage via protein kinase C- dependent effects on efflux drug transporters." Cardiovascular Research, 2013. http://hdl.handle.net/1993/18318.
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Introduction: Therapeutic agents like doxorubicin, an anthracycline antibiotic drug, are widely used in cancer chemotherapy. The use of doxorubicin is limited however by an increased risk of cardiac damage as a side effect, and an increased cancer cell drug resistance mediated by efflux drug transporters. Strategies are needed to protect the heart and still allow the benefits of drug treatment. “Basic” fibroblast growth factor-2 (FGF-2) is a multi-functional protein. It is angiogenic and cardioprotective against ischemia-reperfusion injury. FGF-2 can also regulate cancer cell drug resistance or sensitivity, however, so far, there is no evidence that FGF-2 protects against doxorubicin-induced cardiac damage through effects on efflux drug transporter levels or function.
Aims: To investigate whether: (1) FGF-2 can increase resistance to doxorubicin-induced neonatal rat cardiac myocyte damage; and if so whether (2) an effect on efflux drug transporters might contribute to this cardioprotection by FGF-2.
Methods: Neonatal rat cardiac myocyte cultures were treated with doxorubicin in the absence or presence of pre-treatment with FGF-2. To assess cell damage: (i) culture medium was tested for lactate dehydrogenase (LDH) activity as an indication of plasma membrane disruption; (ii) cells were stained with fluorescent apoptosis and necrosis biomarkers as well as (iii) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and acridine orange to assess DNA fragmentation or compaction. The role of FGF receptor (FGFR) or protein kinase C (PKC) was addressed through use of inhibitors including SU5402, or chelerythrine as well as bisindomaleimide. Multidrug resistance gene 1a and 1b (MDR1a, 1b), multidrug resistance gene 2 (MDR2) and multidrug resistance-related protein 1 (MRP1) gene expression, as well as the function of MDRs and MRPs protein products were assessed by real-time reverse transcriptase-polymerase chain reaction (qPCR), as well as retention/extrusion of (fluorescent) doxorubicin/calcein in cardiac myocytes, respectively. Efflux drug transporter inhibitors, including 20 µM cyclosporine A (CsA), 2 µM verapamil and 1 µM Tariquidar (XR9576) were used to asssess for a direct effect of FGF-2 on transporter function. Fluorescence-activated cell sorting (FACS) was used to measure fluorescent doxorubicin/calcein levels inside treated cardiac myocytes.
Results: Doxorubicin increased the incidence of programmed cell death, DNA damage, and lysosome and LDH activity, while decreasing cell number at 24 hours. FGF-2 prevented the detrimental effects of doxorubicin. In turn, the protective effects of FGF-2 were blocked in the presence of FGFR or PKC inhibitors. FGF-2 treatment significantly increased MDR1a, MDR1b, MDR2, MRP1 RNA levels by qPCR, and protein levels as assessed by function, and specifically extrusion of doxorubicin/calcein, in the presence of doxorubicin when compared to doxorubicin treatment alone. Furthermore, inhibition of efflux drug transporters with CsA and Tariquidar (XR9576) significantly reduced the ability of FGF-2 to protect against doxorubicin-induced damage; the beneficial effect of FGF-2 was completely blocked by pretreatment with verapamil.
Conclusion(s): These data indicate for the first time that exogenous FGF-2 can increase resistance to doxorubicin-induced neonatal rat cardiac myocyte damage, and implicate PKC and regulation of efflux transporter protein levels and/or function in the mechanism.
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Baron, Olga [Verfasser]. "Role of basic fibroblast growth factor (FGF-2) during development of mesencephalic dopaminergic neurons of substantia nigra in mice / Olga Baron." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2011. http://d-nb.info/1018928502/34.
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Kamali, Salar [Verfasser]. "Evaluation of the Fibroblast Growth Factor Receptor 2 (FGFR2) in Experimental Autoimmune Encephalomyelitis (EAE) and its Possible Role in Multiple Sclerosis (MS) / Salar Kamali." Gießen : Universitätsbibliothek, 2016. http://d-nb.info/1096137763/34.
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Ferraro, Bernadette. "Intradermal Delivery of Plasmids Encoding Angiogenic Growth Factors by Electroporation Promotes Wound Healing and Neovascularization." [Tampa, Fla] : University of South Florida, 2009. http://purl.fcla.edu/usf/dc/et/SFE0002823.
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Kashpur, Olga. "Oxygen-mediated basic fibroblast growth factor (FGF2) effects on adult human dermal fibroblasts." Digital WPI, 2015. https://digitalcommons.wpi.edu/etd-dissertations/546.
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This thesis investigates the effects of low oxygen culture conditions and fibroblast growth factor-2 (FGF2) on adult human dermal fibroblasts.
It was previously shown that low oxygen and FGF2 culture conditions lead to an extension of proliferative lifespan, low-level activation of stem cell genes, and global transcriptional changes in adult human dermal fibroblasts. Additionally, an increased in vivo tissue regenerative response can be observed when human muscle-derived fibroblasts grown with FGF2 and low oxygen are implanted into mouse muscle injury, leading to a decrease in collagen deposition and scar formation and increase of functional skeletal muscle regeneration, including formation of Pax7+ muscle stem cells.
These findings led to an analysis of key cellular oxygen sensors, hypoxia inducible factors (HIFs) and their role in this regenerative response. Directly linking these factors with the regenerative response, I have shown, with knockdown experiments, that HIF-2α is required for the increased proliferative capability and decreased senescence of human dermal fibroblasts (hDFs) induced by hypoxia. I have also determined that low oxygen causes an early and transient increase of HIF-1α and late and sustained increase of HIF-2α protein accompanied by increased nuclear translocation. Using overexpression and knockdown approaches via lent-virus, I determined that HIF-2α appears to modulate FGF2 signaling through the FGF receptors. First, under low oxygen conditions, exogenous FGF2 led to downregulation of endogenous FGF2, which can be mimicked by overexpression of HIF-2α. In ambient oxygen we didn't see this effect. Second, HIF-2α overexpression appears to lead to increases in FGFR1 phosphorylation and consequently increased ERK1/2 phosphorylation, and increases in the expression of heparan sulfate modifying enzymes (NDST1, NDST2, and EXTL2). Lastly, sustained supplementation with FGF2 in low oxygen inhibits receptor-mediated FGF2 signaling.
To understand these effects at the transcriptional level, using microarray technology, we identified oxygen-mediated FGF2 effects on genes involved in cell survival and proliferation.
Through bioinformatics analyses, I determined that genes involved in wound healing (extracellular matrix genes, adhesion molecules, cytokines) are upregulated in FGF2 treated fibroblasts grown under low oxygen. By utilizing a gain-of-function approach, we were able to assess the effects of altered HIF-2α activity on the expression of Oct4, Sox2, Nanog, Rex1, and Lin28 in adult hDFs. The results indicate that overexpression of the HIF-2α transcription factor increases Oct4 mRNA, but not Oct4 protein, levels, and had no effect on Nanog and Lin28 proteins. HIF-2α overexpression also mediated FGF2 induction of Sox2 and Rex1 proteins of higher molecular weight.
This thesis expands our knowledge about effects of low oxygen and FGF2 on adult human dermal fibroblasts and explains in part, how FGF2 under low oxygen conditions may lead to increased proliferation, extended life span, regenerative competency and increased developmental plasticity of adult hDFs.
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Merle, Pierre-Laurent. "Effets du facteur de croissance basique des fibroplastes (FGF-2) sur la perméabilité membranaire et l'homéostasie calcique de cardiomyocytes de rats." Université Joseph Fourier (Grenoble), 1997. http://www.theses.fr/1997GRE10126.
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Le facteur de croissance basique des fibroblastes (fgf-2) participe au developpement embryonnaire des cardiomyocytes et semble etre implique dans l'hypertrophie des cardiomyocytes adultes. Dans differents types cellulaires, les cascades d'activation initiees par les facteurs de croissance passent par une elevation de la concentration intracellulaire en calcium. L'objectif de ce travail a ete d'etudier les effets du fgf-2 sur l'homeostasie calcique de cardiomyocytes de ventricules de rats nouveau-nes et adultes. Nous avons montre que les cardiomyocytes de rats nouveau-nes expriment des recepteurs au fgf-2 dont l'activation entraine une augmentation de l'activite contractile. La technique du patch-clamp nous a permis de mettre en evidence des canaux de la membrane plasmique des cardiomyocytes activables par le fgf-2, permeables au calcium, ayant une faible conductance (15 ps) et insensibles au voltage. L'activation de ces canaux par le fgf-2 est en partie mediee par l'ip3. La mesure, par la technique de spectrofluorimetrie, de la teneur en ca#2#+ montre que le fgf-2 provoque une augmentation progressive de la concentration basale en calcium des cardiomyocytes neonataux. Cette observation est confirmee par visualisation en microscopie confocale laser de la concentration en ca#2#+ dans le cytoplasme et le noyau des cardiomyocytes adultes. En outre, le fgf-2 stimule l'apparition des augmentations locales et transitoires en calcium (sparks). L'ensemble des resultats suggere l'existence, dans la membrane plasmique des cardiomyocytes, de canaux permeables au calcium, dont l'ouverture est stimulee en reponse au fgf-2. Cet influx de calcium semble etre un des elements precoces des cascades d'activation initiees par les facteurs de croissance et pourrait jouer un role important dans le controle de l'expression genetique.
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Prabhudesai, Shirish G. "Fibroblast growth factor-2, chemoresistance and colorectal cancer." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/10163.
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Introduction: The role of fibroblast growth factor-2 (FGF-2) on colorectal cancer (CRC) cells exposed to chemotherapy has not been studied extensively. This thesis investigated whether FGF-2 mediates chemoresistance in primary (SW480) and metastatic (SW620) colon adenocarcinoma cell lines. Methods: Proliferation assays were used to assess the response of SW480 and SW620 colon cancer cell lines to varying concentrations of FGF-2 and to optimise the dose of 5- FU at which 50% cell death was observed. Cell survival assays were performed following 96 hours exposure to 5-FU ± FGF-2. Levels of chemotherapy induced apoptosis were determined using Caspase-3/7 assay. Expression of anti-apoptotic proteins (Bcl-2 and Bcl-XL) and FGFRs at both protein and gene level were determined to see if these contributed to the difference in chemoprotection observed. Results: At 0.25 ng/ml, FGF-2 did not affect proliferation in either cell lines. 25μM of 5-FU resulted in 50% kill in both cell lines. Significant cell survival was observed when FGF-2 (0.25 ng/ml) pre-treated SW620 cells were exposed to 5-FU (25 μM) compared to cells exposed to 5-FU alone (81% vs 60%, p=0.015). This chemoresistance was associated with attenuation of cellular apoptosis (p=0.04) with no significant change in expression of Bcl-2 and Bcl-XL at gene or protein level. This survival advantage was not seen in SW480 cells (59% vs 55%, p=0.35). There were no observed differences in the expression of FGFR1-4 in either cell lines. Conclusion: FGF-2 offers chemoresistance to SW620 and not to SW480 cells exposed to 5-FU. Both cell lines expressed fgf2 and fgfr1-4 genes, suggesting that fgfr expression does not account for the difference in chemoresistance. FGF-2 offered protection by causing significant reduction in chemotherapy induced apoptosis in SW620 colon cancer cell line; however this was not due to increased expression of anti-apoptotic proteins. The molecular mechanisms for this selective chemoprotection need to be investigated further.
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Rennel, Emma. "Molecular Mechanisms in Endothelial Cell Differentiation." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4059.
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Shi-Lu, Chia. "The role of fibroblast growth factor-2 in articular cartilage degradation." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501425.
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Osteoarthritis (OA) is the most common form of joint disease and a leading cause of physical disability woridwide. Cartilage degradation in OA is due to an imbalance between synthesis and degradation of the extracellular matrix. Recent work from our laboratory has shown that the heparin-binding growth factor fibroblast growth factor2 (FGF-2) mediates key responses in cartilage following mechanical trauma and loading. It has also been shown that FGF-2 is localised within the pericellular matrix, attached to the heparan sulphate proteoglycan perlecan. The spatial modulator of chondrocyte function. The primary aim of this research was to define the role of FGF-2 in cartilage degradation in vivo. Mice with deletion of Fgf2, whilst morphologically indistinguishable from wild-type animals, exhibited accelerated spontaneous and surgically-induced OA. Surgically-induced OA in Fgf2 mice was suppressed to wild type levels by subcutaneous administration of recombinant FGF-2. Increased disease in Fgf2 mice was associated with increased expression of ADAMTS-5, the key murine aggrecanase, but not other matrix metalloproteinases. Explants from Fgf2 mice showed increased aggrecanolysis and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motif, type 5; aggrecanase-2) gene expression following interleukin-1 (IL-1) stimulation, and exogenous FGF-2 suppressed IL-1 induced aggrecanolysis in wild-type explants. These data identify FGF-2 as a novel endogenous chondroprotective agent, and as an inhibitor of aggrecan breakdown acting through suppression of ADAMTS-5.
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Vailes, McCauley T. "Post-Transfer Outcomes in Cultured Bovine Embryos Supplemented with Epidermal Growth Factor, Fibroblast Growth Factor 2, and Insulin-Like Growth Factor 1." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/86273.
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The high incidence of pregnancy loss is a major issue facing the cattle industry. Use of in vitro fertilized (IVF) bovine embryos has become increasingly popular to help alleviate several of these reproductive issues and provide a means to enhance genetic gain for production traits. An uterine paracrine factor cocktail containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF1) (collectively termed EFI) was recently identified as a means for improving in vitro derived bovine embryo development and trophectoderm cell numbers. The objectives of this work were to determine if EFI treatment during in vitro bovine embryo culture improves transferable embryo quality and post-transfer placental and fetal development. For each replicate (3 total), slaughterhouse-derived bovine oocytes were matured and fertilized in vitro. At day 4 post-fertilization, ≥8 cell embryos were harvested, pooled, and exposed to either the EFI treatment (10ng/ml EGF, 10ng/ml FGF2, 50ng/ml IGF1) or carrier only (1% Bovine Serum Albumin). At day 7, individual embryos were transferred to estrous synchronized beef cattle. Artificial insemination (AI) was completed on a subset of cows. The EFI treatment increased (P<0.05) the percentage of transferable embryos. Pregnancy rate at day 28 post-estrus was similar among treatments. Circulating concentrations of pregnancy-associated glycoproteins (PAGs) were determined from plasma harvested at day 28, 42 and 56. Transrectal ultrasonography was used to measure fetal crown-rump length (CRL) at day 42 and 56 and to determine fetal sex at day 60. There were no main effect differences observed across days for PAG concentration. Fetus sex by ET/AI group interactions were absent at day 28 but existed at days 42 and 56 (P<0.05). At both days, this interaction reflected fetus sex-dependent changes within the ET control group, where PAG concentrations were greater (P<0.05) in male fetuses than female fetuses. No CRL differences or interactions existed among fetal sex and pregnancy group. In summary, addition of the EFI cocktail during bovine embryo culture improved the quality of transferable embryos, but did not affect placental function or embryonic/fetal development. Increasing the numbers of transferable embryos is of value given the cost of in vitro embryo production, but no apparent increases in embryo or placental competency were detected. The EFI treatment increased (P<0.05) the percentage of transferable embryos.Master of Science
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Dinsdale, Jennifer Anne. "In vivo effects of fibroblast growth factor - 2 on oligodendrocytes and myelin." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407573.
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Hannocks, Melanie-Jane. "The effects of fibroblast growth factor-2 om human bone marrow cells." Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/2836.
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HOUSE, STACEY LYNN. "ROLE OF FIBROBLAST GROWTH FACTOR 2 IN CARDIAC ISCHEMIA-REPERFUSION INJURY AND HYPERTROPHY." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1132336027.
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Cha, Jiyoung Der Channing J. "The role and mechanism of fibroblast growth factor receptor 2 in cellular transformation." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1513.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Sep. 16, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pharmacology." Discipline: Pharmacology; Department/School: Medicine.
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Fletcher, Michael. "Network analysis of fibroblast growth factor receptor 2-regulated gene expression in breast cancer." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608087.
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Moatacim-Berrada, Saadia. "Effet in vitro d'un dextrane biofonctionnel sur la croissance et l'expression du phénotype de l'ostéoblaste humain : modulation par le Fibroblast-Growth-Factor (FGF2)." Bordeaux 2, 1993. http://www.theses.fr/1993BOR28230.
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Henry, Rebecca Ann. "The effect of AAV1/2 mediated delivery of brain-derived neurotrophic factor and fibroblast growth factor-2 on adult rodent neurogenesis." Thesis, University of Auckland, 2007. http://hdl.handle.net/2292/1492.
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Neurogenesis is the process by which functionally integrated neurons are generated from progenitor cells. In the adult mammalian brain two sites of high density cell division have been identified that contain neural progenitor cells retaining the ability to generate new neurons: the subgranular zone of the hippocampus (SGZ) and the subventricular zone (SVZ) lining the lateral ventricles in the forebrain. Several studies have suggested that SVZ neural progenitor cells in the adult brain can migrate into regions other than the olfactory bulb after either administration of growth factors, induction of neuronal cell loss or injury. Brain-derived neurotrophic factor (BDNF) and fibroblast growth factor (FGF-2) play major roles in regulating the survival and fate of progenitor cells in the adult mammalian brain. To determine the effect of BDNF or FGF-2 on neurogenesis in the injured adult brain, BDNF or FGF-2 were over-expressed in the subventricular zone (SVZ) via recombinant adeno-associated virus (AAV1/2) delivery and newly generated cells were identified using bromodeoxyuridine (BrdU; 150mg/kg intraperitoneal) labelling. Selective striatal cell loss was induced in a subgroup of rats by unilateral striatal injection of the excitotoxin quinolinic acid (QA) 21 days after AAV1/2 injection and 24 hours prior to BrdU labeling. The results of this thesis demonstrate that BDNF augments the recruitment, neuronal differentiation and survival of progenitor cells in both neurogenic and non-neurogenic regions of the unlesioned or QA lesioned brain. BDNF also appears to contribute to the persistence of newly generated neurons in the QA lesioned striatum. Our results provide the first evidence demonstrating the neurogenic effect of BDNF on compensatory striatal neurogenesis in the injured adult brain and suggest that enhanced BDNF expression may be a viable strategy for inducing or augmenting endogenous neural progenitor cell neurogenesis. Unlike the effect of BDNF, FGF-2 appears to have no effect on proliferation and/or survival of neural progenitor cells in either the normal or damaged brain. FGF-2 appears to be unable to act as a positive mediator of SVZ progenitor cell proliferation and neurogenesis in this study. However, FGF-2 may be having an inhibitory effect on progenitor cell differentiation. The negative result of the FGF-2 study may be of major significance in indicating the potential requirement of additional factors interacting with FGF-2 to influence neurogenesis. The results from the FGF-2 study contribute to the research field in highlighting the complexity of the mammalian neurogenic process. This thesis highlights the need for further investigation into multiple factor interactions, tighter regulation of the transgenic protein expression from the AAV1/2 delivery vector or alternative progenitor cell labelling paradigms. However, it does show that if neurogenesis can be induced or augmented exogenously, neural progenitor cells may provide a substrate for repair in the adult brain and dramatically change therapeutic approaches towards the treatment of neurodegenerative diseases.
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Böhm, Friederike. "Cooperative functions of fibroblast growth factor receptors 1 and 2 in liver homeostasis and regeneration /." [S.l.] : [s.n.], 2009. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=18385.
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Debiais, Françoise. "Effets et mecanismes d'action du fibroblast growth factor-2 sur les osteoblastes de calvaria humaine." Paris 7, 2000. http://www.theses.fr/2000PA077058.
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Plusieurs arguments laissent penser que le fgf-2 joue un role important dans le controle de la formation osseuse. Cependant, les mecanismes cellulaires et moleculaires par lesquels le fgf-2 peut moduler l'osteogenese sont peu connus. Nous avons etudie les effets de ce facteur de croissance et ses mecanismes d'action en utilisant des cellules osteoblastiques issues de la voute cranienne de nourrissons, constituant un nouveau modele osteogenique recemment developpe dans le laboratoire. Nous avons montre que ces cellules humaines de calvaria expriment les recepteurs fgfr1 et fgfr2 et sont donc des cellules cibles pour le fgf-2. Nous avons precise que le fgf-2 a un effet mitogene, module la differenciation de ces osteoblastes humains de calvaria de facon differente en fonction du stade de maturation cellulaire et peut donc augmenter l'osteogenese par les cellules differenciees. Nous avons mis en evidence pour la premiere fois que la n-cadherine est un gene cible pour le fgf-2 dans ces cellules. Le fgf-2 stimule l'expression de la n-cadherine et augmente l'agregation cellulaire ; cet effet implique les voies de signalisation pkc et src. Les resultats preliminaires de notre etude concernant l'apoptose suggerent un effet initial anti-apoptotique, qui pourrait etre suivi d'un effet pro-apoptotique. Le fgf-2 pourrait ainsi reguler l'osteogenese de la calvaria en favorisant l'adhesion des cellules osteoblastiques au stade precoce de condensation mesenchymateuse. Le fgf-2 augmente la proliferation puis la differenciation des cellules osteoblastiques de facon variable en fonction du stade de differenciation cellulaire, et enfin regule l'apoptose de ces cellules. Ces resultats contribuent a expliquer les effets anaboliques du fgf-2 retrouves
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Sheikh, Farah. "Regulation of the fibroblast growth factor-2 axis in cardiac cells, effects on cardioprotection and cardiac muscle cell growth." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ62665.pdf.
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