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Jasper, Melinda Jane. "Paracrine regulation of ovarian function by granulocyte-macrophage colony-stimulating factor (GM-CSF) & colony-stimulating factor-1 (CSF-1) /." Title page and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phj39.pdf.
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Schmidt-Mende, Jan Georg. "Apoptosis in the myelodysplastic syndromes : protective effect of G-CSF/." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-471-6/.
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Azoulay, Elie. "Approche expérimentale des circonstances de toxicité pulmonaire aigue͏̈ ou chronique du Granulocyte-Colony-Stimulating-Factor (G-CSF)." Paris 12, 2002. http://www.theses.fr/2002PA120005.
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INTRODUCTION : Le Granulocyte Colony Stimulating Factor (G-CSF) est largement prescrit chez les patients d'hématocancérologie pour raccourcir les durées de neutropénie après chimiothérapie. Le G-CSF est aussi évalué chez des patients non neutropéniques ayant des altérations fonctionnelles des polynucléaires neutrophiles (PN). Plusieurs observations de pneumopathies médicamenteuses au G-CSF ont été rapportées: il s'agit le plus souvent de patients âgés de plus de 65 ans, ayant reçu plus de trois cures de chimiothérapie pour lymphome non hodgkinien, présentant une pneumopathie interstitielle diffuse non infectieuse pendant ou après la sortie d'aplasie. Néanmoins, cette entité reste discutée du fait: (1) de sa rareté, (2) de l'évident bénéfice à prescrire du G-CSF contre un risque incertain de pneumopathie, (3) que les études randomisées comparant G-CSF à placebo n'ont pas démontré de surcroît de pneumopathies, (4) de l'innocuité du G-CSF chez les patients non neutropéniques. QUESTION POSEE : Quelles sont les situations à risque de toxicité pulmonaire du G-CSF? INTERVENTION: Le G-CSF (25 microg/kg/j) a été administré dans plusieurs situations d'agressions pulmonaires, à des rats non neutropéniques, neutropéniques ou en sortie d'aplasie. Les explorations ont comporté une quantification de l'oedème pulmonaire, des concentrations de protéines dans le lavage bronchoalvéolaire, du recrutement alvéolaire, de la séquestration pulmonaire en PN (myéloperoxydase), des concentrations sériques et pulmonaires en TNF-alpha et IL1-beta, de la pression artérielle pulmonaire (cathétérisme droit) de la compliance pulmonaire statique, des constatations anatomopathologiques (muscularisation, fibrose). Les rôles respectifs du PN et du macrophage ont été approchés par des expériences associant la lidocaine, les anticorps anti-TNF-alpha et te cyclophosphamide. . .
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Xiong, Yu. "Impact du G-CSF sur le phénotype et les fonctions des cellules NK dans le cadre d’une immunothérapie post-allogreffe de cellules souches hématopoïétiques." Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0106/document.
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Les cellules Natural Killer (NK) sont capables de lyser les cellules tumorales sans la nécessité de reconnaitre un antigène tumoral spécifique. Cette propriété leur confère un avantage par rapport aux lymphocytes T et les rend intéressantes à utiliser en tant que cellules effectrices pour l’immunothérapie adoptive. A ce jour, le potentiel thérapeutique des cellules NK n’a pas été complétement exploré notamment dans le contexte du traitement de la rechute post-allogreffe de cellules souches hématopoïétiques. Actuellement, les patients en rechute post-greffe sont traités avec des injections de lymphocytes du donneur (DLI) parfois issues de petites fractions du greffon de cellules souches hématopoïétiques congelées. Les cellules souches périphériques étant fréquemment utilisées comme source de cellules souches et parfois utilisées comme DLI, nous avons souhaité évaluer l’impact du G-CSF sur le phénotype et les fonctions des cellules NK présentes dans ces fractions. Dans cet objectif, nous avons comparé différentes sources de cellules NK isolées à partir de sang de donneurs sains, de sang mobilisé de donneurs sains ou de patients et observé l’évolution des différentes sous-populations de cellules NK issues de ces prélèvements au décours d’une expansion en présence d’IL-15. Nos résultats ont montré que l’administration de G-CSF diminuait la proportion de cellules NK CD56brightCD16+ au profit d’une population CD16-, diminuait la prolifération des cellules NK lors de l’expansion en culture, et modifiait les propriétés fonctionnelles des cellules NKThe ability of natural killer (NK) cells to kill tumor cells without the need to recognize a tumor-specific antigen provides advantages over T cells and makes them appealing for a use as effectors for adoptive immunotherapy. However, the full therapeutic potential of NK cell-based immunotherapy has not been fully investigated in the context of leukemic relapse after hematopoietic stem cell transplantation. Today, patients relapsing after hematopoietic stem cell transplantation are often treated with donor lymphocyte infusion (DLI) based on small cell fractions frozen at the time of the stem cell transplantation. Since peripheral blood stem cells are increasingly used as stem cell source and as source of cells for DLI, we aimed to evaluate the impact of G-SCF mobilization on NK cell phenotype and functions. Therefore, we compared the expansion capacity, the phenotype and the function of NK cells from blood for healthy donors, from allogeneic HSCT healthy donors or from autologous HSCT from patients. We also determine the impact of G-CSF on NK cell subset repartition before and after expansion in presence of IL-15. Our results showed that G-CSF administration to patients decreases CD56brightCD16+ NK cell population, proliferation and function. Overcoming this impairment in lymphoid capacity may be important to facilitate post-transplant immunotherapy
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Haenel, Claude. "Neutropenie cyclique et traitement par rg-csf : a propos d'une observation." Université Louis Pasteur (Strasbourg) (1971-2008), 1991. http://www.theses.fr/1991STR1M217.
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Held, Thomas. "Evaluation von Granulozyten Kolonie-stimulierendem Faktor (G-CSF) und einem monoklonalen Antikörper gegen Kapselpolysaccharid zur Therapie der experimentellen Klebsiella pneumoniae-Pneumonie." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2001. http://dx.doi.org/10.18452/13759.
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G-CSF besitzt direkte Effekte auf die Aktivierung bakterizider Eigenschaften neutrophiler Granulozyten und verbessert das Überleben bakteriell infizierter Tiere. Daher wurde in der hier vorliegenden Arbeit der Effekt einer prophylaktischen oder therapeutischen Gabe von G-CSF bei experimenteller Pneumonie durch Klebsiella pneumoniae in Mäusen untersucht. Unerwarteterweise verschlechterte aber eine prophylaktische G-CSF-Gabe das Überleben und führte dosisabhängig zu einer Steigerung der bakteriellen Dissemination von der Lunge in Leber und Milz. Im Gegensatz dazu konnte ein spezifisch gegen K2-Kapselpolysaccharid (K2-KPS) von K. pneumoniae gerichteter monoklonaler Antikörper signifikant die Vermehrung der Bakterien in Lunge, Leber und Milz reduzieren. Die Blockierung von TNF?? durch Pentoxifyllin hingegen verzögerte die Letalität nach Induktion der Pneumonie, verhinderte sie jedoch nicht. In vitro konnte hier nachgewiesen werden, daß G-CSF spezifisch an K. pneumoniae bindet und daß diese Bindung an mehrere Proteine mit einem Molekulargewicht von 41, 25 und 21 kDa erfolgt. Die Bindung von G-CSF an K. pneumoniae führte zu einer signifikant erhöhten Produktion des wichtigsten Virulenzfaktors, K2-KPS. Dies verminderte in vitro signifikant eine Phagozytose der Bakterien durch neutrophile Granulozyten. Damit gelang es zum ersten Mal, die Bindung von G-CSF an ein gram-negatives Bakterium, K. pneumoniae, nachzuweisen und zu zeigen, daß diese Bindung in vitro zu einer erhöhten Produktion des wichtigsten Virulenzfaktors und in vivo zur Verschlechterung einer experimentellen Pneumonie durch erhöhte bakterielle Disseminierung bei prophylaktischer Gabe von G-CSF vor Infektion führt. Die weitere Untersuchung dieser Phänomene hinsichtlich einer möglichen Bindung von G-CSF auch an andere Bakterien könnte zu einer differenzierten supportiven Therapie bakterieller Infektionen mit G-CSF in nicht neutropenischen Patienten führen.Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. The effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae was studied. Using a highly reproducible murine model, the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia could be demonstrated. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. Blocking of TNF-? with pentoxifylline, however, could not prevent increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in inreased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes. Further investigations of possible binding of G-CSF to other bacteria might influence a differentiated supportive therapy of bacterial infections in non-neutropenic patients with this growth factor.
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Liu, Hebin. "RUNX1/AML1 functions and mechanisms regulating granulocyte-macrophage colony-stimulating factor transcription." Doctoral thesis, Umeå : Department of Molecular Biology, Umeå University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-486.
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Robertson, Sarah A. "Granulocyte-macrophage colony stimulating factor (GM-CSF) : a paracrine regulator in the pre-implantation mouse uterus." Title page, abstract and contents only, 1993. http://web4.library.adelaide.edu.au/theses/09PH/09phr6515.pdf.
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McCormack, Matthew Paul. "The biological effects of constitutively active mutants of the common [beta] subunit of the human IL-3, IL-5 and GM-CSF receptors /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phm1305.pdf.
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Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999?Amendments to thesis in pocket on back cover. Copy of author's previously published article in pocket on back cover. Bibliography: leaves 124-172.
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Braunstein, Kirsten Daniela. "Untersuchungen zur Regulation von Interleukin-1ß (IL-1ß), Granulocyte Colony Stimulating Factor (G-CSF) und Vascular Endothelial Growth Factor (VEGF) in humanem Endometrium." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-65676.
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Pastor, Mélanie. "Modélisation pharmacocinétique/pharmacodynamique par une approche de population de l’effet du G-CSF chez des patients traités avec du carboplatine." Thesis, Toulouse, INPT, 2013. http://www.theses.fr/2013INPT0061/document.
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Une des stratégies pour limiter les neutropénies induites par la chimiothérapie est l’utilisation de granulocyte-colony stimulating factor (G-CSF). Nous avons développé, par une approche de population, un nouveau modèle pharmacocinétique/pharmacodynamique capable de décrire la cinétique des neutrophiles des patients traités au carboplatine, qu’ils aient ou non reçu du G-CSF. Les simulations réalisées à partir de ce modèle ont montré que le G-CSF n’était pas bénéfique chez tous les patients et que la formulation à action longue semblerait plus efficace que les autres formulations. Nous avons également établi des règles de décision permettant d’une part de prédire le risque de neutropénie sévère, et d’autre part d’identifier précocement les patients pour lesquels le G-CSF peut avoir un effet bénéfiqueGranulocyte colony-stimulating factor (G-CSF) is often used in cancer patients receiving cytotoxic drugs to prevent or reduce high grade neutropenia. We developed a new population pharmacokinetic/pharmacodynamic model to describe neutrophil time-course in carboplatin-treated patients, whether or not they received G-CSF. Model simulations showed that G-CSF was not as beneficial as expected in some patients and that the onceper- cycle formulation was more efficient than other formulations. Model-based decision rules were also built to anticipate prolonged high grade neutropenia and early identify patients for whom G-CSF was beneficial
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Stöcker, Kai [Verfasser], and Wolf-Rüdiger [Akademischer Betreuer] Schäbitz. "Effekte des Granulocyte-Colony-Stimulating-Factors (G-CSF) nach Schlaganfall bei alten Ratten / Kai Stöcker. Betreuer: Wolf-Rüdiger Schäbitz." Münster : Universitäts- und Landesbibliothek der Westfälischen Wilhelms-Universität, 2012. http://d-nb.info/1027018777/34.
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LICARI, VERONIQUE. "Maladie de kaposi localisee chez un sujet hiv negatif : action antitumorale du gm-csf." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20131.
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Stomski, Frank Charles. "The molecular basis of IL-3, Il-5 and GM-CSF receptor activation /." Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phs8766.pdf.
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Wiik, H. (Heikki). "Inflammatory response following abdominal surgery and its modulation by recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim)." Doctoral thesis, University of Oulu, 2002. http://urn.fi/urn:isbn:9514268474.
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The effects of perioperative filgrastim (rhG-CSF) and surgery per se on the postoperative acute phase reaction were studied by assessing leukocyte functions, cytokine levels and tenascin-C (Tn-C) and procollagen propeptide (PINP, PIIINP) concentrations in different body fluid compartments in patients undergoing gastrointestinal surgery.
Thirty consecutive patients were randomized to receive either filgrastim or placebo for five days, starting 12 hours before colorectal surgery. Filgrastim treatment led to marked neutrophilia with decreased neutrophil migration in peripheral blood but not in peritoneal fluid 48 hours postoperatively. Neutrophil phagocytosis and bacterial killing did not differ between the groups. Filgrastim caused increased postoperative expression of neutrophil CD11b/CD18 in blood but not in peritoneal fluid or wound fluid. CD11b/CD18 expression was higher in both wound fluid and peritoneal fluid than in blood in the placebo group. The expression of neutrophil CD62L was higher in blood than in peritoneal fluid or wound fluid in both groups. The serum concentration of interleukin (IL)-8 was lower in the filgrastim group 5 hours postoperatively. The concentrations of IL-1β, IL-6, transforming growth factor (TGF)-β and IL-10 did not differ between the groups. The cytokine levels were markedly higher locally in the wound and in the peritoneal cavity compared to circulating blood. No adverse events attributable to filgrastim were seen.
Leukocyte counts, neutrophil and monocyte functions and the levels of IL-6, IL-8 and granulocyte colony-stimulating factor (G-CSF) were measured from 18 patients before and after colorectal surgery. Surgery caused an increase in neutrophil and monocyte counts along with lymphocytopenia. Neutrophil phagocytosis was decreased 4 and 24 hours postoperatively, but normalized after that. A distinct systemic cytokine response was seen postoperatively.
In a study with 24 patients, Tn-C concentration increased in wound fluid during the first postoperative week after abdominal surgery. The Tn-C level was markedly higher in wound fluid than in serum.
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Osborne, Cameron Stuart. "Transcriptional regulation of the GM-CSF gene in T lymphocytes /." Title page, contents and summary only, 1996. http://web4.library.adelaide.edu.au/theses/09PH/09pho81.pdf.
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Ulusans, Susann Meryem. "Zum Einsatz programmierbarer Medikamentenpumpen zur Förderung der Arteriogenese durch Granulocyte-Macrophage-Colony-Stimulating Factor (GM-CSF) im Modell am Schwein." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-42438.
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Gibaud, Stéphane. "Etude du ciblage des organes hematopoietiques a l'aide de nanoparticules : application a la doxorubicine et au g-csf (granulocyte colony-stimulating factor) vectorises a l'aide de nanoparticules de polyalkylcyanoacrylates." Paris 11, 1997. http://www.theses.fr/1997PA114823.
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Millot, Gaël. "Mécanismes et spécificité d'action des récepteurs homodimériques EpoR, Mpl et G-CSFR dans l'hématopoi͏̈èse." Paris 7, 2001. http://www.theses.fr/2001PA077220.
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Cheng, Allen Cheuk-Seng, and allencheng@ozemail com au. "MELIOIDOSIS: EPIDEMIOLOGY, PATHOPHYSIOLOGY AND MANAGEMENT." Flinders University. Medicine, 2005. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20051121.141305.
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In under a century, melioidosis, the infection due to Burkholderia pseudomallei, has emerged from Whitmores series of glanders-like infections amongst the morphia addicts in Burma to a major cause of mortality in northeastern Thailand and northern Australia. Also endemic in other parts of south-east Asia, melioidosis may have varied presentations ranging from severe, overwhelming infection to chronic, low grade disease.
Observational evidence had suggested that granulocyte colony stimulating factor (G-CSF), a naturally occurring substance produced by the body in response to infection, may have been useful in reducing the high mortality associated with the more severe forms of this infection. Other observations linked the occurrence of this disease to various environmental factors, such as contamination of drinking water and the annual rainfall. This thesis explores and attempts to quantify these associations.
There are three parts to this thesis. In the first part, I reviewed the epidemiology and management of patients with melioidosis. The use of G-CSF and meropenem was associated with a fall in mortality, although other factors may have at least partially contributed to this effect.
In the second part, I progressed towards a clinical trial of G-CSF. There was no other evidence supporting the use of G-CSF in severe sepsis and ethical issues precluded a trial in Darwin. There was not evidence from laboratory models of G-CSF action in melioidosis to support the use of G-CSF in patients, although there remained some doubt regarding the applicability of such models to human disease. I examined clinical methods to identify patients at high risk of death from melioidosis. A simple scoring system based on clinical and laboratory parameters was developed and externally validated. However, clinical definitions of severe sepsis appeared to be better predictors of mortality. A clinical trial based on clinical definitions was commenced in Thailand.
In the final part, I explored the question of whether different strains or B. pseudomallei or different environmental conditions caused different patterns of infection. There was no evidence that strain types of this bacterium determine the pattern or severity of disease, but weather conditions appeared to influence the distribution of disease in northern Australia.
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Boyd, Timothy David. "The Novel Use of Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) to Reverse Cerebral Amyloidosis and Cognitive Impairment in Alzheimer’s Disease Mouse Models: Insights from the Investigation of Rheumatoid Arthritis as a Negative Risk Factor for Alzheimer’s Disease." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3571.
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For many years, it has been known that Rheumatoid arthritis (RA) is a negative risk factor for the development of Alzheimer’s disease (AD). It has been commonly assumed that RA patients’ usage of non-steroidal anti-inflammatory drugs (NSAIDs) have helped prevent the onset and progression of AD pathogenesis. Furthermore, experiments in animal models of Alzheimer’s disease have looked to inhibit inflammation, and have demonstrated some efficacy against AD-like pathology in these models. Thus many NSAID clinical trials have been performed over the years, but all have proven unsuccessful in AD patients. This suggests that intrinsic factors within RA pathogenesis itself may underlie RA’s protective effect.
My dissertation research goal was to investigate this inverse relationship between RA and AD, in order to more precisely pinpoint critical events in AD pathogenesis toward developing therapeutic strategies against AD. It seemed improbable that any secreted factors, produced in RA pathogenesis, could maintain high enough concentrations in the circulatory system to cross the blood brain barrier and inhibit AD pathogenesis, without affecting all other organ systems. It did seem possible that the leukocyte populations induced in RA, could traverse the circulatory system, extravasate into the brain parenchyma, and impede or reverse AD pathogenesis. We thus investigated the colony-stimulating factors, which are up-regulated in RA and which induce most of RA’s leukocytosis, on the pathology and behavior of transgenic AD mice. We found that G-CSF and more significantly, GM-CSF, reduced amyloidosis throughout the treated brain hemisphere one week following bolus intrahippocampal administration into AD mice. We then found that 20 days of subcutaneous injections of GM-CSF (the most amyloid-reducing CSF in the bolus experiment) significantly reduced brain amyloidosis and completely reversed cognitive impairment in aged cognitively-impaired AD mice, while increasing hippocampal synaptic area and microglial density. These findings, along with two decades of accrued safety data using Leukine, the recombinant human GM-CSF analogue, in elderly leukopenic patients, suggested that Leukine should be tested as a treatment to reverse cerebral amyloid pathology and cognitive impairment in AD patients. It was also implied that age-related depressed hematopoiesis may contribute to AD pathogenesis.
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Edwards, Jane Ann. "Expression of antisense RNA to investigate the interaction between unique and shared receptor subunits in the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor." Thesis, St George's, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322069.
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Pinto, Tulio Queto de Souza. "Mecanismos celulares e sistêmicos de regulação da eosinopoiese: efeitos estimulatórios dos cisteinil-leucotrienos e dos glicocorticóides e efeitos inibitórios da via inos/cd95l e do g-csf." Instituto Oswaldo Cruz, 2011. https://www.arca.fiocruz.br/handle/icict/6402.
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A provocação por via respiratória com ovalbumina (OVA) em camundongos sensibilizados promove, na medula óssea (MO), eosinopoiese, resposta exacerbada à Interleucina(IL)-5, e mudanças no padrão de resposta em cultura à eotaxina, à IL- 13 e aos antiinflamatórios não esteroidais (NSAIDs). Em cultura de MO, a Prostaglandina (PG) E2 induz apoptose de eosinófilos, por via dependente de NO sintase indutível (iNOS) e ligante de CD95 (CD95L), enquanto a dexametasona (DEXA) promove eosinopoiese, gerando eosinófilos agregados e morfológicamente imaturos e protege contra da apoptose induzida por PGE2, provavelmente por mecanismos que regulem a expressão ou ativação de integrinas. No presente trabalho avaliamos se: a) in vitro, os efeitos dos NSAIDs, da IL-13 e da eotaxina dependem da produção de cisteinil-leucotrienos (CisLT) e da sinalização via receptor 1 de CisLT (CysLT1R); b) in vitro, a DEXA regula expressão de VLA-4, que promoveria a agregação e imaturidade dos eosinófilos, e se PGE2 contrapõe a ação da DEXA; c) in vivo, G-CSF e dietilcarbamazina (DEC) promoveriam eosinopenia medular e sistemica e se inibiriam a inflamação pulmonar alérgica. Resultados: a) NSAIDs, eotaxina e IL-13 potencializam a eosinopoiese via produção de CisLT e sinalização via CysLT1R. Os NSAIDs ainda protegem os eosinófilos da apoptose induzida por PGE2 exógena. b) A interação farmacológica entre PGE2 e DEXA modificam a ação de ambas, de forma estreitamente relacionada sobre a expressão de VLA-4 e, em condições específicas, esses agentes sinergizam gerando quantidades aumentadas de eosinófilos maduros. c) A DEC, inibidor da síntese de LTs, que na filariose experimental possivelmente atua via iNOS, inibe a eosinopoiese e os efeitos da provocação sobre o pulmão e a MO, através da via iNOS-CD95L. O Fator Estimulante de Colônias de Granulócitos (G-CSF), estimulante da neutropoiese, igualmente inibiu a inflamação pulmonar alérgica através da inibição da eosinopoiese. Este trabalho é parte do projeto intitulado "Eosinofilia na Asma Experimental", licenciado pela Comissão de Ética no Uso de Animais (CEUA) da Fiocruz, sob nos L010/04 e L002/09.
Our laboratory has previously shown that airway allergen challenge in ovalbumin-sensitized mice rapidly induces an increase in bone-marrow (BM) eosinophil production (eosinopoiesis), along with an increased response to Interleukin(IL)-5 in BM culture, changes in the ex vivo responses to cytokines and immunomodulators, including nonsteroidal anti-inflammatory drugs (NSAIDs) and cysteinyl-leukotrienes (CysLT), and colonization of the lungs by eosinophil progenitors. Early in the course of IL-5-induced eosinophil differentiation in BM culture, Prostaglandin E2 (PGE2) induces apoptosis, through a pathway dependent on the inducible isoform of NO synthase (iNOS) and the ligand for CD95 (CD95L). NSAIDs enhance eosinopoiesis and protect eosinophils in this critical period from exogenous PGE2, through a novel mechanism of action at the celular level. In this study, we show that indomethacin and aspirin act through endogenously synthesized CysLT, by establishing the essential roles of 5-lipoxygenase, LTC4 synthase and CysLT1R receptors, as well as the cytoprotective effect of CysLT against exogenous PGE2. The similarity between the effects of NSAIDs and those of eotaxin and IL-13 prompted us to reevaluate the contribution of endogenous CysLT to the effects of these cytokines. We confirmed that eotaxin and IL-13 act through this mechanism, and expand therefore the list of agents that, through CysLT, enhance eosinopoiesis, protecting immature eosinophils from apoptosis induced through the iNOS-CD95L pathway. Dexamethasone promotes BM eosinopoiesis, generating aggregated, cytologically immature eosinophils, which are nevertheless protected from PGE2- induced apoptosis. We examined therefore the possibility that dexamethasone upregulates integrin expression/activation, thereby maintaining an immature celular phenotype in cultured eosinophils, while PGE2 would have opposite effects on both integrin function and cytological maturation. We show that the proapoptotic effects of PGE2 are profoundly modified by its pharmacological interaction with dexamethasone, paralleling the effects of both drugs on integrins, and leading to a synergic generation of increased numbers of mature eosinophils, in very specific experimental conditions. Diethylcarbamazine (DEC) is an antihelminthic drug that blocks leukotriene synthesis, and possibly acts in experimental filarial infection through iNOS. We have examined, for the first time, the effects of DEC in a model of allergic pulmonary inflammation, showing that DEC is very effective in preventing the impact of airway allergen challenge on BM and lungs, through the in vivo operation of the iNOS-CD95L pathway. Granulocyte Colony-stimulating Factor (G-CSF), which stimulates neutropoiesis, mobilizes CD34+ hemopoietic progenitors from BM, and exerts complex immunoregulatory effects, was shown in our study to have a strong impact in a murine model of allergic pulmonary inflammation. Like DEC, G-CSF suppressed BM eosinopoiesis, although through a different mechanism, since DEC suppressed neutrophilia in the lungs with no effect on BM neutrophilia/neutropoiesis, while G-CSF promoted neutropoiesis and induced blood neutrophilia, even though it suppressed eosinopoiesis. This work was part of the Research Project “Eosinophilia in Experimental Asthma”, licensed by the Committee on the Ethical Use of Laboratory Animals (CEUA) at FIOCRUZ, under numbers L010/04 and L002/09.
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Kaspar, Michael. "IEV (Ifosfamid/ Epirubicin/ Vepesid) gefolgt von G-CSF (Granulocyte colony stimulating factor) zur Mobilisierung von peripheren Stammzellen bei Lymphom- und Myelompatienten. Wirksamkeit in der Tumorreduktion und klinischer Faktoren, die die Mobilisierung beeinflussen." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-67183.
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Pradella, Fernando 1987. "Efeito da administração do G-CSF nos mecanismos efetores e imunorreguladores na neurite experimental autoimune induzida em ratos Lewis = Effect of the administration of the G-CSF onto the effector and immuneregulatory mechanisms of the experimental autoimmune neuritis induced in Lewis rats." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316429.
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Orientadores: Alessandro dos Santos Farias, Leonilda Maria Barbosa dos SantosDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Abstract: The abstract is available with the full electronic document
Mestrado
Imunologia
Mestre em Genética e Biologia Molecular
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Junior, Alfredo Mendrone. "Coleta de células progenitoras hematopoéticas de sangue periférico após administração de ciclofosfamida e fator estimulador de colônias de granulócitos (G-CSF): uma análise de 307 pacientes." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-08072008-154313/.
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Mobilização inadequada de células progenitoras hematopoéticas (CPH) tem sido observada em 10 - 30% dos pacientes submetidos a transplante de medula óssea (TMO) autogênico para tratamento de doenças onco-hematológicas. Os fatores relacionados com má resposta à mobilização ainda não estão totalmente estabelecidos. Apresentamos uma análise retrospectiva de pacientes submetidos à TMO autogênico com o objetivo de identificar variáveis associadas com resposta ruim ao regime de mobilização utilizado. Casuística e Métodos: Fizeram parte desta análise 307 pacientes com diferentes diagnósticos, tratados com TMO autogênico em uma única Instituição, no período de Abril de 2001 a Abril de 2007. Todos os pacientes incluídos no estudo foram submetidos a um único regime de mobilização baseado na administração de ciclofosfamida (dose total de 60-120 mg/kg de peso IV) e fator estimulador de colônias de granulócitos (G-CSF) (dose diária de 6 - 17 ug/(kg de peso)/dia SC). O sucesso na resposta ao regime de mobilização foi definido quando um número maior ou igual a 2,0x10 (6) células CD34 + /(kg de peso) foi coletado do sangue periférico com até três procedimentos de leucaférese. Resultados: Dos pacientes analisados, 260 apresentaram sucesso na mobilização (84,7%). Nestes pacientes, um número mediano de 3,67 (2,0 - 46,0) células CD34+ /(kg de peso) foi coletado por paciente com um número mediano de 1 (1-3) procedimento de leucaférese. O insucesso na mobilização foi observado em 47 pacientes (15,3%): 24 (7,8%) que foram submetidos à coleta de CPH de sangue periférico, porém não coletaram número maior ou igual 2,0x10 (6) células CD34+/(kg de peso) com pelo menos três procedimentos de leucaférese; e, 23 (7,5%) foram submetidos à coleta de CPH por punção da medula óssea, por não terem atingido número mínimo de 10 células CD34+/mm3 no sangue periférico para realização de leucaférese. De acordo com análise univariada, os fatores associados com o insucesso foram: diagnóstico (P < 0,0001), tempo de doença (P < 0,0001), número prévio de ciclos de quimioterapia (P = 0,0001), exposição prévia a agentes alquilantes (P = 0.0003) e a mitoxantrone (P = 0,0006), contagem de plaquetas pré-mobilização <150.000/mm3 (P = 0,0006) e intervalo entre o início da mobilização e o pico de células CD 34+ no sangue periférico (P < 0,0001). Idade, sexo, atividade da doença e envolvimento medular ao início da mobilização, tratamento prévio com radioterapia e exposição a análogos da platina não mostraram correlação significativa na resposta à mobilização. Após análise multivariada, as variáveis que permaneceram associadas com insucesso na mobilização foram: diagnóstico (P = 0,0232), número prévio de ciclos da quimioterapia (P = 0,0167), tratamento prévio com mitoxantrone (P = 0,0285) e contagem de plaquetas pré-mobilização < 150.000/mm3 (P = 0,0423). Conclusão: A carga cumulativa de quimioterapia administrada, exposição prévia à mitoxantrone, contagem de plaquetas pré-mobilização e diagnóstico foram os fatores independentes relacionados com a falha na resposta à mobilização. Os achados obtidos podem auxiliar no reconhecimento de pacientes de risco para resposta ruim à mobilização e permitir um planejamento alternativo ou mais agressivo no regime de mobilização para este grupo de pacientes.Inadequate stem cells mobilization is seen in 10-30% of patients undergoing autotransplantation for hematologic malignancies. Factors affecting peripheral blood progenitor cell (PBSC) mobilization have not been clearly established. We retrospectively reviewed the data of patients treated by autologous bone marrow transplantation (BMT) with the aim to identify factors associated with poor PBSC mobilization. Design and Methods: We evaluated 307 patients with different diagnoses, submitted to autologous BMT between April 2001 and April 2007. PBSC were collected following mobilization with cyclophosphamide (60-120 mg/kg of weight IV) and granulocyte-colony stimulating factor (G-CSF) (dose of 6-17 ug/kg of weight/day SC). Success in mobilization was defined when > ou = a 2,0x10(6) CD34+ cells/(kg weight) could be collected from the peripheral blood with a maximum of three leukapheresis procedures. Clinical and laboratory parameters at the time of mobilization were analyzed for correlations with the number of CD34+ cells collected. Results: Two hundred and sixty patients (84.7%) presented success in mobilization. In this group, a median of 3.67 (2.0-46.0) CD34+ cells/(kg weight) was collected per patient in a median of 1(1-3) leukapheresis procedure. Poor response to mobilization was observed in 47 patients (15.3%): 24 (7.8%) were submitted to PBSC collection but didn\'t collected at least 2.0 x 106 CD34+ cells/(kg weight) with three leukapheresis procedures and 23 (7.5%) didn\'t reach an absolute number count of 10 CD34+ cells/mm3 in the peripheral blood to start collection by leukapheresis. In univariate analysis poorer PBSC mobilization was associated with diagnosis (Pp < 0.0001), time interval from the diagnosis to mobilization (P < 0.0001), number of cycles of previous chemotherapy (P = 0.0001), previous treatment with alkylating agents (P = 0.0003) and mitoxantrone (P = 0.0006), platelet count <150.000/mm3 before mobilization (P = 0.0006) and interval between mobilization and peak of CD34+ cells in peripheral blood (P < 0.0001). No significant correlation was found with age, gender, disease status, marrow involvement at mobilization, prior radiation therapy and exposition to platin analogues. In the stepwise regression model, diagnosis (P = 0.0232), number of cycles of previous chemotherapy (P = 0.0167), previous treatment with mitoxantrone (P = 0.0285) and platelet count <150.000/mm3 before mobilization (P = 0.0423) were found to be independent negative predictive factors for CD34+ cells mobilization. Conclusion: Cumulative load of chemotherapy, exposition to Mitoxantrone, platelet count just prior to mobilization and diagnosis were independent factors related to poor progenitor cells mobilization. These results could help in the previously recognition of patients at risk for poor or no response to mobilization and allow to plan an alternative or more aggressive regimen for this group of patients.
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Mouchache, Seye Myriam. "La neutropénie fébrile a-t-elle une incidence sur le pronostic des cancers bronchiques à petites cellules disséminés traités par PEVEP dose standard versus PEVEP haute dose + Gm-CSF." Montpellier 1, 1997. http://www.theses.fr/1997MON11103.
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Eid, Katia Aparecida de Brito 1964. "Mobilização e coleta de CD34+ para transplante autólogo de células progenitoras periféricas hematopoiética em pediatria : análise de duas doses diferentes de G-CSF." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312104.
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Orientador: Simone dos Santos AguiarTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: As células progenitoras periféricas hematopoiéticas (CPHP) é uma das alternativas de enxerto para a realização de transplante autólogo em crianças, adolescente e adulto jovem portadores de tumores sólidos e linfomas. Na mobilização, a dose clássica de G-CSF é 10µg/kg/peso do paciente SC em dose única. Acredita-se que doses maiores de G-CSF aplicadas duas vezes ao dia aumentariam o número de CD34+ coletadas com o menor número de leucaféreses. A tecnologia atual permite que seja realizado leucaférese em crianças com baixo peso (<10 kg). Objetivo: o mote do estudo foi avaliar se o G-CSF na dose de 15µg/kg peso do paciente ao dia e fracionado em duas doses, 10µg/kg e 5µg/kg, diminuiria o número de leucaférese realizada para atingir o mínimo de 3x106/kg/peso do paciente de CD34+ quando comparada com G-CSF na dose convencional, 10µg/kg/peso do paciente em dose única. Métodos: Os pacientes foram divididos em dois grupos. Grupo 10 formado por pacientes que receberam G-CSF 10µg/kg/peso SC ao dia em dose única às 6h e grupo 15 formado por pacientes que receberam G-CSF 15µg/kg/peso SC ao dia dividido em duas vezes, 10µg/kg SC às 6h e 5µg/kg SC às 18h. As leucaféreses foram realizadas em um separador celular automático de fluxo contínuo com anticoagulante ACD-A, foram processados 4 volemias em cada leucaférese. Pacientes com < 20 kg receberam priming de concentrado de hemácias filtradas e irradiadas (CHFI) durante as leucaféreses. A realização do transplante autólogo ocorreu com o número mínimo de 3x106/kg/peso de CD34+. Resultados: Sessenta e cincos pacientes portadores de tumores sólidos e linfomas foram avaliados, 39 pacientes receberam 10µg/kg/peso SC ao dia em dose única às 6h de G-CSF e 26 pacientes receberam 10µg/kg SC às 6h e 5µg/kg SC às 18h de G-CSF. Foram realizadas 146 leucaféreses, 110 (75,3%) no grupo 10 e 36 (24,7%) leucaféreses no grupo 15. No grupo 10 foi obtido uma mediana de 3 (1-7) leucaféreses e coletado uma média de 8,89x106/kg (± 9,59) de CD34+, o grupo 15 realizou uma mediana de 1 (1-3) leucaféreses e coletado uma média de 5,29x106/kg (± 4,95) de CD34+. Uma diferença estatística importante foi o número de leucaféreses (p<0,0001). Nenhum paciente apresentou intercorrências durante as leucaféreses. Os pacientes que receberam CHFI (<20 kg) não apresentaram hipovolemia nas leucaféreses realizadas. Conclusão: Para coletar o mínimo de 3x106/kg/peso de CD34+, a aplicação de G-CSF 15µg/kg/peso fracionada diminuiu significativamente o número de leucaférese realizada
Abstract: Introduction: The peripheral hematopoietic progenitor cells are a graft choice for performing autologous transplantation. In the mobilization, the classical dose of G-CSF is 10?g/kg of the patient in a single dose. There is a theory that higher doses of G-CSF applied twice daily could increase the number of collected CD34+ cells with a smallest number of leukapheresis. Objective: The aim of this study is to evaluate if a fractionated-dose of G-CSF at 15?g/kg of patient may reduce the number of leukapheresis for achieving the minimum target of 3 x 106/kg of CD34+ cells as compared to conventional dose of G-CSF. Methods: Patients were divided into two groups. Group 10: patients who received a single dose daily of G-CSF 10?g/kg and Group 15: patients who received twice dose daily of G-CSF 15?g/kg. The leukapheresis were processed in an automated cell separator. The autologous transplantation happened when the minimum number of 3x106/kg CD34+ was reached. Results: Group 10 enrolled 39 patients who received 10?g/kg of G-CSF and group 15 had 26 patients who received 15?g/kg fractionated of G-CSF. There were a total of 146 aphaeresis; 110 (75.3%) in group 10 and 36 (24.7%) group 15. Group 10 collected a median of 3 (1-7) leukapheresis and a mean of 8.89 x106/kg (± 9.59) CD34+, whereas group 15 had a median of 1 (1-3) leukapheresis and collected a mean of 5.29 x106/kg (± 4.95). The relevant difference statistic was the number of aphaeresis (p<0.0001). Conclusion: To collect a minimum target of 3x106/kg of CD34 +, the application of fractionated-dose of 15?g/kg G-CSF decreased significantly the number of leukapheresis performed
Doutorado
Saude da Criança e do Adolescente
Doutora em Ciências
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Van, Cauwenberge Margot G. A. [Verfasser], and Peter [Akademischer Betreuer] Young. "The effect of granulocyte colony-stimulating factor on the peripheral nerve and the progress of Charcot-Marie-Tooth neuropathy type 1A in a rat model / Margot G. A. Van Cauwenberge ; Betreuer: Peter Young." Münster : Universitäts- und Landesbibliothek Münster, 2017. http://d-nb.info/1142115089/34.
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Gonçalves, Gabrielle Viana Martins Gonçalves. "Geração e caracterização de linhagens de células-tronco mesenquimais de camundongo geneticamente modificadas para expressão ectópica de hIGF-1 ou hG-CSF." reponame:Repositório Institucional da FIOCRUZ, 2015. https://www.arca.fiocruz.br/handle/icict/12758.
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Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
As células-tronco mesenquimais (CTM) constituem uma ferramenta promissora para o campo de terapia celular. Além de seu potencial de diferenciação em diferentes tipos celulares, as CTM apresentam a habilidade de secretar moléculas bioativas e, assim, exercer múltiplos efeitos biológicos, tais como indução da regeneração de tecidos lesionados, redução de fibrose e modulação do sistema imune. A superexpressão dos fatores de crescimento G-CSF e IGF-1, conhecidos por seus efeitos sobre os processos de imunomodulação, sobrevivência celular e reparo tecidual, pode ampliar as ações terapêuticas das CTM. O objetivo deste trabalho consiste em gerar e caracterizar linhagens de CTM de camundongo superexpressando hGCSF ou hIGF-1. Um sistema lentiviral de segunda geração foi utilizado para modificação de CTM para expressão ectópica dos genes de interesse. As sequências codificantes de hG-CSF e hIGF-1 foram amplificadas por PCR e subclonadas em um vetor lentiviral de transferência, contendo um promotor constitutivo. As partículas lentivirais foram produzidas a partir da cotransfecção de células da linhagem HEK293FT com os vetores constituintes do sistema lentiviral. Em seguida, as CTM obtidas da medula óssea de camundongos transgênicos para proteína fluorescente verde (GFP) foram transduzidas com partículas lentivirais infectantes contendo hG-CSF ou hIGF-1. A expressão gênica de hG-CSF ou hIGF-1 pelas linhagens geradas foi quantificada por qRTPCR, e a produção da proteína por ELISA. As linhagens foram caracterizadas por imunofenotipagem e avaliadas quanto ao seu potencial de diferenciação celular. Foram geradas duas linhagens de CTM superexpressando hG-CSF e três linhagens superexpressando hIGF-1. Todas demonstraram por qRTPCR, estar efetivamente expressando os genes de interesse. Foi possível detectar e quantificar a síntese proteica de G-CSF e IGF-1. Todas as linhagens geradas foram capazes de se diferenciar em osteócitos, condrócitos e adipócitos, demonstrando a manutenção de seu fenótipo estromal. Neste contexto, este trabalho resultou em ferramentas funcionais para a avaliação dos efeitos terapêuticos de IGF-1 e G-CSF combinados à CTM, em modelos de lesões animais, em comparação com CTM não-modificadas geneticamente. Além disso, estas ferramentas poderão ser empregadas em estudos de pesquisa básica, para melhor compreensão dos efeitos de hIGF-1 e hG-CSF sobre a biologia das CTM.
Mesenchymal stem cells (MSCs) are a promising tool for the cell therapy field. In addition to their potential for differentiation into different cell types, MSCs have the ability to secrete bioactive molecules and thus exert multiple biological effects such as induction of the injured tissue regeneration, fibrosis reduction and modulation of the immune system. The overexpression of the growth factors G-CSF and IGF-1, known for their effects on immune modulation processes, cell survival and tissue repair, can result in a magnification of MSCs' therapeutic actions. The objective of this work is to generate and characterize mouse MSCs lines overexpressing hG-CSF or hIGF-1. A second generation lentiviral system was used to modify MSCs derived from mice for the ectopic expression of the genes of interest. The coding sequences of hG-CSF and hIGF-1 were amplified by PCR and subcloned into a lentiviral transfer vector containing a constitutive promoter. The lentiviral particles were produced from the co-transfection of HEK293FT lineage cells with the lentiviral vectors. Subsequently, MSCs obtained from the bone marrow of transgenic mice for green fluorescent protein (GFP) were transduced with infectious lentiviral particles containing hG-CSF or hIGF-1. The gene expression of hG-CSF or hIGF-1 by the generated cell lines was quantified by qRTPCR, and the protein production by ELISA. The lineages were characterized by immunophenotyping and evaluated for their potential of cellular differentiation. Two lines of MSCs overexpressing hG-CSF and three lines overexpressing hIGF-1 were generated. All the cell lines demonstrated to be effectively expressing the genes of interest by qRTPCR. It was possible to detect and quantify the protein synthesis of G-CSF and IGF-1. Moreover, all the generated lines were capable of differentiating into osteocytes, chondrocytes and adipocytes, indicating the conservation of their stromal phenotype even after genetic modification. In this context, this study resulted in functional tools for evaluating the IGF-1 and G-CSF therapeutic effects when combined with MSCs, to be tested in experimental animal models in comparison to non-genetically modified MSCs. Furthermore, these tools may be employed for basic research studies, for a better understanding of the effects of hIGF-1 and hG-CSF on MSCs' biology
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Chopra, Rajesh. "The expression and regulation of the granulocyte macrophage colony- stimulating factor receptor (GM-CSFR)." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362585.
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CHEN, TZU-LING, and 陳姿伶. "Potential effects of granulocyte colony-stimulating factor (G-CSF) on erythrocytic differentiation and mobilization." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/98768540177257546575.
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碩士慈濟大學
分子生物暨人類遺傳學系碩士班
104
Granulocyte colony-stimulating factor (G-CSF) is a multifunctional cytokine that mainly is required for the generation of granulocytes and the mobilization of hematopoietic stem cells (HSC). However, we found that G-CSF could promote not only count of white blood cells but red blood cells level. Our previous study had demonstrated that G-CSF promoted the mobilization of newly synthesized erythroid cells to peripheral blood and it was used for recovering anthrax lethal toxin (LT)-induced erythrocytopenia. This study aims to determine whether G-CSF can improve erythropoiesis and what is the different mechanism between G-CSF and erythropoietin (EPO), an essential and well known cytokine to improve erythropoiesis and to produce red blood cells. The mechanism of G-CSF improved-erythropoiesis was identified by analyzing bone marrow and spleen of mice via flow cytometry. We demonstrated that G-CSF promotes erythropoiesis by distinct mechanism from EPO. Furthermore, the model of acute anemia had been established in mice by intraperitoneal injection of phenylhydrazine (PHZ) to test the effect of G-CSF on acute hemolytic anemia. We found that G-CSF ameliorates PHZ-induced acute anemia at early stage. This study makes a thorough inquiry further in G-CSF’s alternative function and it might be useful for hematological diseases.
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許智凱. "Regulatory effect of natural killer cell-mediated cytotoxicity by granulocyte-colony stimulating factor (G-CSF) treatment." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/77434723215268995082.
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Jasper, Melinda Jane. "Paracrine regulation of ovarian function by granulocyte-macrophage colony-stimulating factor (GM-CSF) & colony-stimulating factor-1 (CSF-1) / Melinda Jane Jasper." Thesis, 1998. http://hdl.handle.net/2440/19338.
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Bibliography: leaves 165-193.xxvi, 193 leaves, [61] leaves of plates : ill. (chiefly col.) ; 30 cm.
Investigates the role of colony-stimulating factors in the murine ovary utilising mice genetically deficient in GM-CSF (GM-/-). In addition, the expression of components of the GM-CSF and CSF-1 signalling systems in the normal mouse ovary has been investigated.
Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1998
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McClure, Barbara Jean. "Molecular Assembly of the Activated Granulocyte-Macrophage Colony-Stimulating Factor Receptor." Thesis, 2017. http://hdl.handle.net/2440/119329.
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Chien, Ming-Yang, and 簡名揚. "Expression and Purification of Recombinant Human Granulocyte Colony Stimulating Factor (hG-CSF)." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/38920327020134970623.
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碩士淡江大學
化學學系碩士班
96
The recombinant human granulocyte colony stimulating factor (hG-CSF) is a hematopoietic cytokine that has been widely used for the treatment of neutropenia after chemotherapy and bone marrow transplantation. It can stimulate both proliferation, differentiation of neutrophils. In this study, we cloned the G-CSF encoding gene into pPIC9K vector and transformed it into SMD1168 yeast cells. The transformed cells were selected on the plate containing 4 mg/ml of G-418. The recombinant hG-CSF was found to be secreted in the medium, and molecular weight was as predicted at 20 kDa on SDS-PAGE, corresponding to the commercial standard. Comparing with bioreactor and shake flask, the specific hG-CSF protein production increased 7 times. After medium was concentrated, both DEAE Sepharose Fast Flow and Sephadex G-50 column chromatography were used to purify the hG-CSF protein. It resulted in the recovery of 76.5 % and 65.7 % respectively, and the purification of 3.6 and 10.4 fold respectively. By using HL-60 cell (Human promyelocytic cell), the bioactivity of hG-CSF can be observed. For one: The effect of the purified hG-CSF to promote the total cell numbers to 2 fold when 100 ng of the purified hG-CSF was added to the cells. The proliferation rate was hG-CSF-dependent. The most efficient was at the inoculation size of 1 × 105 cells/ml for 100 ng of purified hG-CSF. The other was the MTT assay to estimate the stimulation of the cellular succinate dehydrogenase activity. When the addition of 2~100 ng purified hG-CSF to the cells, the enzyme activity increased 9~10 times.
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Chiang, Ya-Wen, and 姜雅文. "Effects of post-treatments of granulocyte-colony stimulating factor (G-CSF) on anthrax lethal toxin induced anemia." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/50684328811208315482.
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碩士慈濟大學
分子生物暨人類遺傳學系碩士班
99
Anthrax, a disease caused by Bacillus anthracis infection, usually coincides with anemia, hypoxic tissue damages and hemorrhage, causes animal and human death through unknown mechanisms. Lethal toxin (LT), a mitogen-activated protein kinase kinase (MAPKKs) inhibitor, is the major virulence factor of B. anthracis. LT treatments cause lethality and certain anthrax-like pathogenesis of experimental mice; this made it an idea molecular tool to study anthrax-mediated pathogenesis. Our previous studies indicated that LT could suppress erythropoiesis in vitro and in vivo and granulocyte-colony stimulating factor (G-CSF) pre-treatments could reduce LT-mediated mortality in mice. For therapeutic application, it might be useful for G-CSF to rescue mice after LT injection. Our data suggested that G-CSF post-treatments could also increase the survival rate after injection of LT and this effect was associated with amelioration of anemia response. Since G-CSF is a pleiotropic cytokine playing a major role as regulator of hematopoiesis, we found that G-CSF post-treatments could ameliorate LT induced erythropoiesis suppression not through increasing erythropoietin (EPO) secretion. The underlining mechanisms will be further investigated.
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Baqui, A. A. M. Abdullahel. "Characterization of the response of GM-CSF supplemented THP-1 human monocytes to LPS of oral microorganisms." 1996. http://catalog.hathitrust.org/api/volumes/oclc/47363636.html.
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Mohamed, Tasneem. "An evaluation of the use of G-CSF as an adjunct to IVF in women who have previously failed attempts at pregnancy with IVF." Thesis, 2017. https://hdl.handle.net/10539/25821.
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A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Obstetrics and Gynaecology.
Johannesburg, 2017Background Recurrent IVF failures may result from implantation defects of which a thin endometrium is often implicated. Studies show that improved endometrial thickness increases the probability of successful IVF. Objectives To evaluate the effects of transcervical instillation of G-CSF as an adjunct to IVF. The study looked at the influence of G-CSF on the endometrium and on the achievement of pregnancy. Methods A retrospective cross-sectional study of women attending Bio ART Fertility Centre, who had two or more failed IVFs previously. Results There were a total of 49 women studied with a mean age of 38.9. Mean number of previous IVFs were 3.1. Comparison between those that achieved pregnancy and those that did not showed that age was a statistically significant factor (p-value 0.0005). Mean endometrial thickness pre and post-GCSF between the groups was not statistically significant (p-values >0.05). Conclusion With the use of G-CSF we achieved a clinical pregnancy rate of 34.69% and a statistically significant overall expansion of endometrial thickness (p-value 0.0029). However we failed to show any association between endometrial expansion and pregnancy outcome.
MT 2018
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Huang, Yu-Chin, and 黃昱欽. "Production of Mouse Granulocyte Macrophage -Colony Stimulating Factor (mGM-CSF) in Sweet Potato." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/60750323644031256441.
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碩士元智大學
生物科技與工程研究所
99
Sweet potato, Ipomoea batatas (L.) Lam., is the 7th most important crop in the world. The tuberous roots and leaves for certain varieties of sweet potato are good nutrient source for human beings. Because of low requirement for growth environments, sweet potato becomes one of prospective host for plant molecular farming. We successfully developed gene transformation system in sweet potato. Therefore, we offer a new approach to increase the economic value of sweet potato in Taiwan through molecular farming proposed here. We apply this gene transformation system to produce the recombinant mouse Granulocyte-macrophage colony stimulating factor (mGM-CSF)proteins in transgenic sweet potato, the mouse GM-CSF can affect the mouse white blood increase and growth, In rent year, the mGM-CSF use in mouse modern rescute, including therapy cancer and tumor, It is so expensive and necessary much more to research and rescute. It，s 5 ug sold NT 8000 dollars now. by either constitutive strong ubiquitin promoter or root overexpression promoters. (SPOA1 or PGI1) transformation to sweet potato, hope to overexpression recombination protein mGM-CSF. In our research, we establish five sweet potato transgenic cell lines pUBI::mGMCSF, use the genomic DNA PCR、RT-PCR、GUS reporter gene check and western blot analysis to check the recombination protein overexpression in sweet potato also succeed regeneration two lines to a sweet potato transgenic lines (CSF-4 and CSF-25),analysis had two regeneration transgenic sweet potato lines, the two lines still have the mGMCSF overxpression. In the other hand, we succeed construction the SPOA1::mGMCSF，and try to use the sweet potato transformation system, and try to obtain the transgenic line.In other hand,we use the PGI promoter from the Arabidopsis, we hope use the transformation of sweet potato system, try to understand where the PGI1 driven GUS can overexpression in sweet potato. In future, we hope to overexpression in sweet potato tuberous root. To use the advantage of tuberous root production of mGM-CSF protein.
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Chou, Chun-Wei, and 邱俊瑋. "Molecular Cloning for Human granulocyte Colony Stimulating Factor (hG-CSF) in Pichia pastoris." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/18246030410898501261.
Full textAbstract:
碩士淡江大學
生命科學研究所碩士班
94
Human granulocyte colony stimulating factor (hG-CSF) is a 18.7 kDa glycoprotein , consisting 174 amino acids. It can stimulate granulocyte colony formation and affects proliferation, differentiation and activation of mature neutrophilic granulocytes. It was widely for treatment of neutropenia in cancer therapy. We cloned the hG-CSF gene into P. pastoris and hope to see the recombinant hG-CSF can secrete into medium. It will make the purification procedure much easiler. We amplified the hG-CSF gene from pET25b-hG-CSF by polymerase chain reaction (PCR). The size of the hG-CSF DNA contains 522 bp, and histidine tag (His6) and enterokinase cleavage site (Asp4Lys) were added at the N-terminus of the protein. The PCR product was first cloned to pOPtima™ cloning vector (TA- Cloning). The “insert” was further cloned into pPIC9K vector. pPIC9K-hG-CSF plasmid was integrated into the alcohol oxidase region of the SMD1168 genome. We selected the transformants that were selected from medium contains 4 mg/ml of G-418. Based on it can be selected from the plate contains 0.2 mg/ml of G-418 having 1 copy of insertion. We can predict this is a multicopy clone. Under on culturing condition, the recombinant hG-CSF was able to be secreted into the medium, 10 mg/L of culture medium. After the medium was concentrated, we obtained the protein from FPLC-gel filtration column (Hiperp Sephacryl S-200). There were two fractions . 「Fraction I and Fraction II」 From SDS-PAGE, both were located at 20 kDa. But from the biological activity study for stimulation of granulocyte. We only found Fraction II has the activity. We concluded that Fraction I was obtain in the early portion of the gel filtration column. So it may exist as the aggregated form.
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Tsai, Rong-Kung, and 蔡榮坤. "Neuroprotective Effects of Recombinant Human Granulocyte Colony-stimulating Factor (G-CSF) in Neurodegeneration after Optic Nerve Crush in Rats." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/26541734318948377035.
Full textAbstract:
博士高雄醫學大學
醫學研究所
96
Purpose: The purpose of the present study was to investigate the effects of granulocyte colony-stimulating factor (G-CSF) on neurodegeneration of optic nerve (ON) and retinal ganglion cells (RGCs) in a rat model of ON crush. Materials and Methods: The ONs of adult male Wistar rats (150-180 g) were crushed by a standardized method. The control eyes received a sham operation. G-CSF(100 µg/kg/day in 0.2 ml phosphate buffered saline) or phosphate buffered saline (PBS control) was immediately administered after ON crush for 5 days by subcutaneous injection. Rats were sacrificed at one or two weeks after the crush injury. RGC density was counted by retrograde labeling with Fluorogold application to the superior colliculus, and visual function was assessed by flash visual evoked potentials (FVEP). TUNEL assay, Western blot analysis and immunohistochemistry of p-Akt in the retina and ED1 (marker of macrophage/microglia) in the ON and Fluoro-Jade B in both the retina and the ON were conducted. RT-PCR of TNF-α mRNA in the retinas was also evaluated. Results: Two weeks after the insult, the RGC densities in the central and mid-peripheral retinas in ON crushed, G-CSF-treated rats were significantly higher than that of the corresponding ON crushed, PBS-treated rats (survival rate was 60% vs. 19.6% in the central retina; 46.5% vs. 23.9% in mid-peripheral retina, respectively; p<0.001). FVEP measurements showed a significantly better preserved latency of the p1 wave in the ON crushed, G-CSF-treated rats than the ON crushed, PBS-treated rats (78±9 ms in the sham operation group, 98±16 ms in the G-CSF-treated group, and 174±16 ms in the PBS-treated group; p<0.001). TUNEL assays showed fewer apoptotic cells in the retinal sections in the ON crushed, G-CSF-treated rats. P-Akt immunoreactivity was up-regulated in the retinas of the ON crushed, G-CSF-treated rats at one and two weeks. In addition, the number of ED1-positive cells was attenuated at the lesion site of the optic nerve in the ON crushed, G-CSF-treated group. Fluoro-Jade B immunoreactivity also decreased in both the retina and the ON in the ON crushed, G-CSF-treated group. The RT-PCR of TNF-α mRNA showed the expression of TNF-α mRNA in the retinas also inhibited in the G-CSF-treated group. Conclusions: Administration of G-CSF is neuroprotective in the rat model of optic nerve crush, as demonstrated both structurally by RGC density and functionally by FVEP. G-CSF may work by being anti-apoptotic involving the p-Akt signaling pathway as well as by attenuation of the inflammatory responses at the injury site as evidenced by less ED1-positive cell infiltration in the optic nerve and inhibited expression of TNF-α mRNA in the retinas. Key words: granulocyte colony-stimulating factor, rat model, optic nerve crush, ocular neuroprotection, flash visual-evoked potential, RGC density.
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Hung, Chung-Chih, and 洪忠志. "Production of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (hGM-CSF) by Methylotrophic Yeast." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/07678299183153847480.
Full textAbstract:
碩士國立陽明大學
醫學生物技術研究所
89
Human granulocyte/macrophage colony-stimulating factor (hGM- CSF) is a glycoprotein of 127 amino acid residues that is essential for the proliferation and differentiation of precursor cells into mature granulocytes and macrophages. We had cloned hGM-CSF cDNA into an expression vector pPIC9. The recombinant vector was then transfected into Pichia pastoris GS115 (his4) by electroporation. Clones of stable insertions were identified based on the phenotype of His+. The secreted rhGM-CSF was obtained from the minimal methanol (MM) medium which was used to the culture transformed P. pastoris and shown to be a glycosylated protein by treatment with glycosidases. The rhGM-CSF was concentrated by DEAE-resin and purified by reverse phase HPLC. The secondary structure of rhGM-CSF was calculated by CD spectrum and was shown to have 39﹪-helix, similar to previous x-ray data published by Walter in 1992. The intrachain disulfide bonds were shown to be essential for maintaining native conformation as reduction with dithiothreitol resulted in protein unfolding. The biological activities of rhGM-CSF were demonstrated by the proliferation of TF-1 cells, a hGM-CSF dependent cell line, and by colony forming assay using stem cells derived from cord blood. The efficacy of our rhGM-CSF is equivalent to the commercial hGM-CSF expressed in E. coli.
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Perugini, Michelle. "Dissecting signalling contributions of the alpha and beta subunits of the GM-CSF receptor." 2007. http://hdl.handle.net/2440/37897.
Full textAbstract:
Normal tissue homeostasis and appropriate responses to injury and infection are dependent on cellular communication mediated by cell surface receptors that respond to extrinsic stimuli. The GM-CSF receptor was the major focus of this project. This receptor shares a common signalling subunit, β [subscript c], with the IL-3 and IL-5 receptors. The unique GM-CSF receptor α-subunit ( GMRα ) confers ligand binding specificity to the complex and is essential for GM-CSF receptor signalling, although the full complement of signalling events mediated by GMRα remains elusive. Through cloning of candidate interacting proteins, expression and co-immunoprecipitation studies, we have confirmed interactions for two proteins previously reported to interact with the GMRα, p85 and IKKβ. Additionally, we identified the Src family kinase, Lyn, as a novel direct interacting partner of GMRα and provide insights into possible roles of this kinase in initiating signalling from the GM-CSF receptor. In addition to GMRα associated events we aimed to further characterise the role of the common β [subscript c] subunit in GM-CSF mediated signalling. We utilised two classes of consitutively active β [subscript c] mutants ( extracellular or transmembrane ) which transform the bi-potential myeloid FDB1 cell line to either factor-independent growth and survival, or granulocyte-macrophage differentiation, respectively. Here we report a comprehensive biochemical analysis of signalling by these two classes of mutants in this cell line. The two activated GMR mutants displayed distinct and non-overlapping signalling capacity. In particular, expression of a mutant with a substitution in the transmembrane domain ( V449E ) selectively activated JAK / STAT5 and MAPK pathways resulting in a high level of sensitivity to JAK and MEK inhibitors. In contrast, expression of a mutant with a 37 amino acid duplication in its extracellular domain ( FI Δ ) selectively activates the PI3K / AKT and IKKβ / NFkB pathways. Cells responding to this mutant display a relative high level of sensitivity to two independent PI3K inhibitors and relative resistance to inhibition of MEK and JAK2. The non-overlapping nature of signalling by these two activated mutants suggests that there are alternative modes of receptor activation that differentially dependent on JAK2 and that act synergistically in the mature liganded cytokine receptor complex. Further detailed analysis of these mutants will facilitate the dissection of the signalling pathways involved in the GM-CSF response that mediate proliferation, survival and differentiation.Thesis (Ph.D.)--School of Medicine, 2007.
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Lee, Wen-Hsun, and 李玟勳. "Risk of Developing Venous Thromboembolism Associated with Granulocyte-Colony Stimulating Factors (G-CSF) in Colorectal Cancer Patients." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/19978293377271706067.
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碩士高雄醫學大學
藥學系碩士在職專班
104
Background: Chemotherapy (CT) is an effective treatment for increasing survival rates in various cancer patients. Usually, the bone marrow suppressive effect of CT may also cause severe febrile neutropenia, and granulocyte colony-stimulating factor (G-CSF) is often used for reducing the risk, severity, and duration of febrile neutropenia. However, some studies reported that G-CSF may also be associated with venous thromboembolism (VTE) in patients with cancer. Colorectal cancer is ranked the 3rd cancer death in Taiwan, and the association between G-CSF and VTE has not yet been investigated. Objective: To investigate whether the use of G-CSF in colorectal cancer (CRC) patients who received CT is associated with an increased risk of VTE. Methods: We conducted a retrospective cohort study using National Health Insurance Research Database (NHIRD) from 2002 to 2012. Patients who were diagnosed with CRC in 2003-2011 and received CT within 1 year after CRC diagnosis were included. We excluded patients who (1) were diagnosed with cancer within 1 year before the date of colorectal cancer diagnosis, (2) died within 1 year of colorectal cancer diagnosis, or were > 90 years old, (3) were diagnosed with VTE within 1 year before the first date of receiving CT, or before the date of receiving G-CSF, (4) received G-CSF within 1 year before the date of receiving CT, or received G-CSF without receiving CT. The remaining patients were further classified into two groups: (1) non-users of G-CSF (as reference group), (2) users of G-CSF. Patients were also divided into subgroups according to the status of receiving surgery or radiation therapy. Cox proportional hazards models were performed to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CI). Results: Among 41,736 eligible patients, there were more men (n =23,837, 57.11%) then women, and the average age was 62.76 (± 13.01) years old. 39,345 patients were non-users of G-CSF (94.27%), only 2,391 (5.73%) patients received G-CSF. The risk of VTE was not significantly different between users and non-users of G-CSF (HR 1.02, 95% CI 0.95-1.10). Among 30,510 (73.10%) patients who received surgery, similar HR was observed between users and non-users of G-CSF (HR 1.05, 95% CI 0.97-1.13). Among 11,226 (26.90%) patients without surgery, the HR became less than 1.0 (HR 0.96, 95% CI 0.84-1.11). Among 6,663 (15.96%) patients who received radiation therapy, the HR of VTE in users of G-CSF was 0.97 (HR 0.97, 95%CI 0.82-1.16), compared to non-users. Among 35,073 (84.04%) patients without radiation therapy, the HR of VTE was 1.03 (HR 1.03, 95%CI 0.96-1.12). However, all analyses of subgroups still revealed null effects. Conclusion: The risk for developing VTE was not significantly different between users and non-users of G-CSF in colorectal cancer patients who received CT. Patients with high-risk for developing VTE, the use of G-CSF should be reserved for patients for whom the benefits outweigh the risks.
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Lee, Jung-Shun, and 李榮順. "The Effect of Granulocyte Colony-Stimulating Factor (G-CSF) on the subacute stage of Severe Spinal Cord Injury in Rat." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/20511274349201049203.
Full textAbstract:
碩士國立成功大學
細胞生物及解剖學研究所
97
Background: Spinal cord injury (SCI) is known as one of the most physically disabling and psychologically devastating conditions to humans. Although there is advancement in understanding of its pathophysiology, current treatments are still disappointed. Granulocyte Colony-Stimulating Factor (G-CSF), a hemotopoietic growth factor, has been demonstrated to have neuroprotective effect in the nervous system, especially in stroke. Objective: To assess whether G-CSF exerts neuroprotective effect during the subacute stage of severe SCI. Materials and methods: Animals with contusion induced severe SCI were divided into two groups: G-CSF group that received serial subcutaneous injection of G-CSF and saline control group on post-contusion day (PCD) 9 th to 13 th. Functional evaluations with Basso-Beattie-Bresnahan (BBB) scale and cortical somatosensory evoked potentials (SSEPs) were recorded weekly. The neural tissues were harvested at PCD 9 th, 16 th, 23 th, 37 th for protein analyse. Besides, at the end of the study (PCD 37 th), specimens were analyzed by electron microscopy and immunohistochemistry. Results: The volumes of dorsal column of the G-CSF group were larger than that of control group. Both the sensory and motor functions were improved after administration of G-CSF. Detachment and disruption of the myelin sheets in the myelinated axons was significantly decreased. Axonal regeneration/sprouting were also noted. The numbers of activated microglia/macrophage were lower than those of the control group. The levels of BDNF were comparable between the two groups. Conclusion: In the subacute stage of severe SCI, G-CSF improves the functional outcomes by shortening the inflammatory period, attenuating the extent of demyelination and further promoting remyelination and axonal regeneration.
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"Transgenic expression of human granulocyte colony-stimulating factor (hG-CSF) in tobacco and Arabidopsis seeds." 2002. http://library.cuhk.edu.hk/record=b5891145.
Full textAbstract:
by Lee Juon Kiu.Thesis (M.Phil.)--Chinese University of Hong Kong, 2002.
Includes bibliographical references (leaves 139-152).
Abstracts in English and Chinese.
Thesis committee --- p.i
Statement --- p.ii
Acknowledgements --- p.iii
Abstract --- p.v
Table of contents --- p.ix
List of figures --- p.xv
List of tables --- p.xvii
List of graphs --- p.xviii
List of abbreviations --- p.xix
Chapter Chapter 1: --- General Introduction --- p.1
Chapter Chapter 2: --- Literature Review --- p.4
Chapter 2.1 --- Human granulocyte colony-stimulating factor (hG-CSF) --- p.4
Chapter 2.1.1 --- Physiological roles --- p.4
Chapter 2.1.2 --- Molecular properties --- p.8
Chapter 2.1.3 --- Biochemical properties --- p.9
Chapter 2.1.4 --- Comparison to G-CSF of other specie --- p.10
Chapter 2.1.5 --- Clinical application --- p.11
Chapter 2.1.6 --- Economic value --- p.13
Chapter 2.2 --- Expression systems producing recombinant hG-CSF --- p.15
Chapter 2.2.1 --- Bacteria --- p.15
Chapter 2.2.2 --- Yeasts --- p.17
Chapter 2.2.3 --- Animal cell lines --- p.18
Chapter 2.2.4 --- Transgenic animals --- p.19
Chapter 2.2.5 --- Transgenic plants --- p.20
Chapter 2.3 --- Plant as bioreactors --- p.21
Chapter 2.3.1 --- Characteristics of using plant as bioreactors --- p.22
Chapter 2.3.2 --- Transgenic plants producing hematopoietic growth factors --- p.24
Chapter 2.3.2.1 --- Granulocyte-macrophage colony-stimulating factor (GM-CSF) --- p.24
Chapter 2.3.2.2 --- Erythropoietin (Epo) --- p.26
Chapter 2.3.3 --- Arabidopsis and tobacco as model plants --- p.27
Chapter 2.3.3.1 --- Arabidopsis --- p.28
Chapter 2.3.3.2 --- Tobacco --- p.28
Chapter 2.3.4 --- Phaseolin and its regulatory sequences --- p.29
Chapter 2.4 --- Plant transformation methods --- p.31
Chapter 2.4.1 --- Agrobacterium-mediated transformation --- p.31
Chapter 2.4.1.1 --- Tissue culture methods --- p.31
Chapter 2.4.1.2 --- Non-tissue culture (In planta) methods --- p.32
Chapter 2.4.2 --- Direct DNA uptake transformation --- p.33
Chapter 2.4.2.1 --- Chemical methods --- p.33
Chapter 2.4.2.2 --- Electrical methods --- p.34
Chapter 2.4.2.3 --- Physical methods --- p.34
Chapter Chapter 3: --- Materials and Methods --- p.36
Chapter 3.1 --- Introduction --- p.36
Chapter 3.2 --- Chemicals --- p.37
Chapter 3.3 --- Bacterial strains --- p.37
Chapter 3.4 --- Chimeric gene construction --- p.37
Chapter 3.4.1 --- Cloning of pTZ/Phas/His/EK/hG-CSF --- p.41
Chapter 3.4.2 --- Cloning of pBK/Phas/SP/His/EK/hG-CSF --- p.44
Chapter 3.4.3 --- Cloning of pBK/Phas/SP/hG-CSF --- p.47
Chapter 3.4.4 --- Confirmation of sequence fidelity of chimeric genes --- p.50
Chapter 3.4.5 --- Cloning of chimeric genes into Agrobacterium binary vector --- p.51
Chapter 3.5 --- Expression in Arabidopsis --- p.52
Chapter 3.5.1 --- Agrobacterium GV3101/pMP90 transformation --- p.52
Chapter 3.5.2 --- Arabidopsis transformation --- p.53
Chapter 3.5.2.1 --- Plant materials --- p.53
Chapter 3.5.2.2 --- Vacuum infiltration --- p.54
Chapter 3.5.3 --- Screening of successful R1 transformants --- p.55
Chapter 3.5.4 --- Screening of hemizygous and homozygous transgenic Arabidopsis --- p.56
Chapter 3.5.5 --- GUS assay --- p.57
Chapter 3.5.6 --- Genomic DNA extraction --- p.57
Chapter 3.5.7 --- Southern blot analysis --- p.58
Chapter 3.5.8 --- Total RNA extraction from developing siliques --- p.59
Chapter 3.5.9 --- Northern blot analysis --- p.60
Chapter 3.5.10 --- Protein extraction and Tricine SDS-PAGE --- p.61
Chapter 3.5.11 --- Western blot analysis --- p.62
Chapter 3.5.12 --- Functional analysis --- p.63
Chapter 3.5.12.1 --- Culture ofNFS-60 cells --- p.64
Chapter 3.5.12.2 --- MTT assay --- p.65
Chapter 3.6 --- Expression in tobacco --- p.67
Chapter 3.6.1 --- Agrobacterium LBA4404/pAL4404 transformation --- p.67
Chapter 3.6.2 --- Tobacco transformation --- p.68
Chapter 3.6.2.1 --- Plant materials --- p.68
Chapter 3.6.2.2 --- Tobacco transformation using leaf-disc technique --- p.68
Chapter 3.6.3 --- Regeneration of transgenic tobacco --- p.69
Chapter 3.6.4 --- GUS assay --- p.70
Chapter 3.6.5 --- Genomic DNA extraction --- p.70
Chapter 3.6.6 --- Southern blot analysis --- p.70
Chapter 3.6.7 --- Total RNA extraction from immature seeds --- p.70
Chapter 3.6.8 --- Northern blot analysis --- p.71
Chapter 3.6.9 --- Protein extraction and Tricine SDS-PAGE --- p.71
Chapter 3.6.10 --- Western blot analysis --- p.71
Chapter 3.6.11 --- Functional analysis --- p.71
Chapter 3.6.11.1 --- Culture of NFS-60 cells --- p.72
Chapter 3.6.11.2 --- MTT assay --- p.72
Chapter Chapter 4: --- Results --- p.73
Chapter 4.1 --- Chimeric gene construction --- p.73
Chapter 4.1.1 --- Cloning of pTZ/Phas/His/EK/hG-CSF --- p.73
Chapter 4.1.2 --- Cloning of pBK/Phas/SP/His/EK/hG-CSF --- p.75
Chapter 4.1.3 --- Cloning of pBK/Phas/SP/hG-CSF --- p.77
Chapter 4.1.4 --- Cloning of chimeric genes into Agrobacterium binary vector --- p.79
Chapter 4.2 --- Expression in Arabidopsis --- p.81
Chapter 4.2.1 --- Agrobacterium GV3101/pMP90 transformation --- p.81
Chapter 4.2.2 --- Arabidopsis transformation and screening of R1 transformants --- p.83
Chapter 4.2.3 --- Screening of hemizygous transgenic R1 Arabidopsis --- p.84
Chapter 4.2.4 --- Screening of homozygous transgenic R2 Arabidopsis --- p.86
Chapter 4.2.5 --- GUS assay --- p.88
Chapter 4.2.6 --- Genomic DNA extraction --- p.89
Chapter 4.2.7 --- Southern blot analysis --- p.91
Chapter 4.2.8 --- Total RNA extraction from developing siliques --- p.93
Chapter 4.2.9 --- Northern blot analysis --- p.94
Chapter 4.2.10 --- Protein extraction and Tricine SDS-PAGE --- p.96
Chapter 4.2.11 --- Western blot analysis --- p.99
Chapter 4.2.12 --- Functional analysis --- p.103
Chapter 4.3 --- Expression in tobacco --- p.108
Chapter 4.3.1 --- Agrobacterium LBA4404/pAL4404 transformation --- p.108
Chapter 4.3.2 --- Tobacco transformation and regeneration of transformants --- p.109
Chapter 4.3.3 --- GUS assay --- p.111
Chapter 4.3.4 --- Genomic DNA extraction --- p.112
Chapter 4.3.5 --- Southern blot analysis --- p.114
Chapter 4.3.6 --- Total RNA extraction from immature seeds --- p.116
Chapter 4.3.7 --- Northern blot analysis --- p.116
Chapter 4.3.8 --- Protein extraction and Tricine SDS-PAGE --- p.118
Chapter 4.3.9 --- Western blot analysis --- p.120
Chapter 4.3.10 --- Functional analysis --- p.123
Chapter Chapter 5: --- Discussion --- p.126
Chapter 5.1 --- Introduction --- p.126
Chapter 5.2 --- Successful in producing biologically active rhG-CSF from transgenic plants --- p.128
Chapter 5.2.1 --- Production level --- p.129
Chapter 5.2.2 --- O-glycosylation --- p.130
Chapter 5.2.3 --- Phaseolin signal peptide --- p.131
Chapter 5.2.4 --- Functional analysis --- p.131
Chapter 5.3 --- Comparison of the productivity of other expression systems producing rhG-CSF --- p.132
Chapter 5.4 --- Comparison of the productivity of plants producing different human proteins --- p.135
Chapter 5.5 --- Future perspectives --- p.137
Chapter Chapter 6: --- Conclusion --- p.138
References --- p.139
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Xing-LuJiang and 姜幸呂. "Utilization of the Granulocyte Colony-stimulating Factors (G-CSF) for Managing Chemotherapy-induced Neutropenia in Breast Cancer Patients." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/21087784198942209781.
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Gao, Jhen-I., and 高振壹. "The role of PI3K/AKT/mTOR signaling pathway in LPS-induced increase of granulocyte colony stimulating factor (G-CSF) in macrophages." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/52321730893146443337.
Full textAbstract:
碩士國立臺灣大學
生物化學暨分子生物學研究所
95
The Oct-2 factor was originally identified on the basis of its ability to bind to the octamer motif ATGCAAAT which is found in the promoters of several genes. Oct-2 belongs to the POU family composed of Oct-1, Oct-2, Pit-1, and Unc-86. In the previous studies, Oct-2 has been known as an important transcription factor for B cells and neuron cells. However, expression and function of Oct-2 in the macrophages is mostly unknown. Our recent results showed that expression of Oct-2 in the macrophages was induced by LPS. Moreover, our data suggest that LPS-induced increase of Oct-2 protein is through PI3K/AKT/mTOR signaling pathway. Therefore, Oct-2 may act as a mediator in response to inflammatory stimuli. Granulocyte colony stimulating factor (G-CSF) is a hematopoietic growth factor. It supports the survival and stimulates the proliferation of neutrophil progenitors and promotes their differentiation into mature neutrophils. Inflammatory stimuli such as IL-1, LPS, and TNF-α can induce G-CSF production in macrophages, endothelial cells, and fibroblast, but the molecular mechanism was not clear. In our studies, we tested if LPS induces G-CSF expression through PI3K/AKT/mTOR pathway, and if Oct-2 plays a role in LPS-induced G-CSF expression. RAW264.7 macrophages were pretreated with inhibitors of PI3K, AKT, or mTOR before LPS was added for 6 hours and then G-CSF mRNA was determined by RT-PCR and protein in medium was determined by ELISA assay, and its RNA was determined by RT-PCR. The results showed that different concentration of PI3K, AKT, and mTOR inhibitors gradually prevented LPS-induced increase of G-CSF and inhibitors also downregulated LPS-induced Oct-2 expression. Additionally, NF-κB transactivation activity and DNA binding affinity was reduced by these inhibitors. Chromatin immunoprecipitation (ChIP) assay showed that in LPS-treated cells, Oct-2, but not Oct-1 was recruited to the octamer motif of the G-CSF promoter. Furthermore, pretreated with inhibitors of PI3K, AKT, or mTOR before LPS was added resulted in less Oct-2 binding to the promoter of G-CSF. When shRNA was transfected into cells to knockdown Oct-2, LPS-induced G-CSF expression was significantly reduced. Taken together, our data suggest that LPS-induced G-CSF expression depends on the activation of PI3K/AKT/mTOR pathway and besides NF-κB, Oct-2 plays an important role in the transcription regulation of G-CSF expression induced by LPS.
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Chiu, I.-Hsiang, and 邱意翔. "The Anti-inflammatory and Neuroprotective Effect of Granulocyte Colony Stimulating Factor (G-CSF) on Olfactory Bulb after Acute Spinal Cord Injury." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/3mtkn2.
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