Dissertations / Theses on the topic 'Marophase Colony Stimulating Factors'
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Mohamad, Anuar Nur Najmi. "Regulation of vascular cells function by colony stimulating factors." Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702911.
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Ku, Chun-Ying. "Colony-Stimulating Factor from Umbilical Cord Endothelial Cells." Thesis, North Texas State University, 1987. https://digital.library.unt.edu/ark:/67531/metadc935638/.
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Conditioned media prepared from umbilical cord (UC) segments or endothelial cells (EC) contain colony stimulating activity, Both UCCM and ECCM were partially purified by DEAE-Sepharose and ACA44 gel filtration chromatography. The molecular weights were estimated as 25,000 and 31,000 for UC-CSF and EC-CSF, respectively. UC-CSF was further fractionated by Con A Sepharose, IEF and HPLC on a hydrophobic phenyl column. The highly purified CSF stimulates human macrophage and granulocyte colony formation, indicating it is GM-CSF in nature. Characterization studies have revealed that both CSFs are heat stable at 60°C for 30 min. They are sensitive to digestion by protease and to periodate oxidation but are stable to treatment with sulfhydryl reagents. The synthesis of CSF in endothelial cells is inhibited by actinomycin D, cycloheximide and puromycin, indicating that protein and RNA synthesis are required for CSF production. Among the mitogens tested, only LPS exhibited stimulatory activity on the production of CSF. Metabolic modulators such as dibutyryl cAMP, isobutylmethylxanthine, PGE2 and lactoferrin inhibit CSF production, while PGF2 enhances CSF production.
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Ku, Chun-Ying. "Regulation of Colony-Stimulating Factor-1 Biosynthesis." Thesis, University of North Texas, 1990. https://digital.library.unt.edu/ark:/67531/metadc332103/.
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Recent studies suggest that synthesis of the Colony-stimulating factor (CSF) is a well regulated process. However, the molecular mechanisms of the signal transduction of the various inducers of CSF such as monokines and lymphokines are not well understood. Using Interleukin 1 (IL-1) stimulation of CSF-1 in the MIA PaCa-2 cell line as a model system, the involvement of G-protein has been studied. The IL-1 induction of CSF-1 synthesis can be inhibited by both Pertussis toxin and Cholera toxin, which are known to modify the Gᵢ and Gₛ proteins respectively, thus activating adenylate cyclase to release more cAMP. The toxin inactivation can be prevented by inhibitors of the ADP-ribosylation such as, benzamide and MBAMG. Addition of dibutyryl-cAMP inhibits the IL-1 induced CSF production. Both Theophylline and Forskolin which increase cAMP by inhibiting phosphodiesterase and stimulating adenylate cyclase respectively, also inhibit CSF-1 production. Results from these studies have shown that cAMP level inversely regulates the biosynthesis of CSF-1. Preincubation of MIA PaCa-2 cells with IL-1 and 5'- guanylylimidodiphosphate (GppNHp) prevents the inhibitory effect of pertussis toxin on CSF-1 production. These data are consistent with the hypothesis that IL-1 binds to its receptor and couples to Gᵢ∝ resulting in the inhibition of adenylate cyclase and reducing cAMP level. Lowering of the' cAMP level leads to the activation of CSF-1 gene expression. The activity of another inducer of CSF-1 production in this system, 12-0-tetradecanoylphorbol-13-acetate (TPA), can be abolished by 1- (5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), which is a specific inhibitor of protein kinase C. However, H-7 failed to inhibit IL-1 stimulated CSF-1 production. Other known activators of protein kinase C namely, Ca²⁺ and L-α-l-oleoyl-2-acetoyl-sn- 3-glycerol (OAG), also increase CSF production. On the other hand, Indomethacin which is known to inhibit prostaglandin E (PGE), stimulates CSF-1 production in MIA PaCa-2 cells. These data suggest that different mechanisms for stimulation of CSF-1 synthesis exist in MIA PaCa-2 cells depending on the inducer. The IL-1 stimulated pathway which does not require PKC activity and appears to be associated with adenylyl cyclase regulation whereas phorbol ester induced pathway involves protein kinase C in the signaling process as expected.
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Liu, Mu-ya. "Induced CSF-1 Production and its Effects on C-FMS Transfected Monoblastic U937 Cells." Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc798317/.
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This study examined how the monoblast-like human histiocytic lymphoma cell line U937 can be induced by phorbol 12-myristrate 13-acetate (PMA) to undergo differentiation. In order to study the mechanism of action of CSF-1, a CSF-1 receptor gene (c-fms) was transfected into U937 cells. Exogenous CSF-1 treatment induced an autocrine response in this CSF-1 was determined and all events were shown to be time dependent. CSF-1 stimulation also enhanced proto-oncogene c-jun and c-myc gene expression. Complementary DNA coding for Jun or Fos was introduced into U937 cells by transfection. The transfection did not generate a high level of CSF-1 gene expression which suggests that Fos and Jun alone are insufficient to induce CSF-1 synthesis.
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Tazi, Abdellatif. "Les colony-stimulating factors dans les réponses immunitaires et inflammatoires pulmonaires." Paris 5, 1993. http://www.theses.fr/1993PA05CD02.
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Hormis leurs actions sur les cellules hématopoïétiques médullaires, les colony-stimulating factors (C S F) jouent un rôle important dans les réponses immunitaires et inflammatoires. Dans ce travail, nous avons étudié la production du granulocyte-C S F (G-CSF) et du granulocyte-macrophage-CSF (GM-CSF) par les cellules inflammatoires/immunitaires et parenchymateuses pulmonaires, dans des situations physiologiques et pathologiques. Après avoir mis au point une méthode de dosage biologique spécifique du G-CSF, nous avons montré que les macrophages alvéolaires humains normaux produisent des quantités importantes de ce facteur en réponse à l'endotoxine in vitro. De plus, les cellules alvéolaires recueillies par lavage, provenant de sujets ayant une pneumopathie bactérienne secrètent spontanément du G-CSF en quantité notable, vraisemblablement du fait de leur exposition à l'endotoxine in vivo. Ces données suggèrent que ce facteur joue un rôle dans la régulation du nombre et de la fonction des polynucléaires neutrophiles dans le poumon au cours de processus infectieux. D'autre part, nous avons exploré le rôle du GM-CSF dans la distribution et l'état de différenciation de cellules essentielles à l'initiation des réponses immunitaires : les cellules dendritiques (CD) et les cellules de Langerhans (CL). A l'aide de techniques d'immunohistochimie et d'hybridation in situ, nous avons montré que le GM-CSF est produit par l'épithélium bronchiolaire normal, qui représente le seul site où l'on retrouve des CL. Dans les situations pathologiques qui s'accompagnent de l'accumulation d'un nombre important de CL dans le poumon (hyperplasie épithéliale alvéolaire, cancers bronchopulmonaires et histiocytose X pulmonaire), nous avons retrouvé une corrélation étroite entre la production de GM-CSF au sein de ces lésions et la présence ainsi que le nombre de CL infiltrant ces sites. L'ensemble de ces résultats suggère fortement que la synthèse locale de GM-CSF par certaines cellules pulmonaires normales ou pathologiques joue un rôle important dans la distribution et la différenciation des CD/CL dans le poumon humain.
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Hercus, Timothy Robert. "Structure-junction studies on human granulocyte-macrophage colony-stimulating factor /." Title page, table of contents and summary only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09phh539.pdf.
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Shieh, Jae-Hung. "Purification, Characterization and Receptor Binding of Human Colony-Stimulating Factor-1." Thesis, North Texas State University, 1987. https://digital.library.unt.edu/ark:/67531/metadc331991/.
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Human colony-stimulating factor-1 (CSF-1) was purified from the serum-free conditioned medium of a human pancreatic carcinoma cell line. The four-step procedure included chromatography on DEAE Sepharose, Con A Sepharose and HPLC on phenyl column and reverse-phase C-3 column. The purity of human CSF-1 was demonstrated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS—PAGE) as a single diffuse band with a molecular weight (Mr) of 42,000-50,000 and was further confirmed by a single amino-terminal amino acid residue of glutamate. Under reducing conditions, purified CSF-1 appeared on SDS-PAGE as a single protein band with a Mr of 21,000-25,000 and concurrently lost its biological activity, indicating that human CSF-1 consists of two similar subunits and that the intact quaternary structure is essential for biological activity. When treated with neuraminidase and endo-8~D~N—acetylglucosaminidase D, the Mr of CSF-1 was reduced to 36,000-40,000 and to a Mr of 18,000-20,000 in the presence of mercaptoethanol.
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Towers, Terri L. "Vitamin D3-mediated transcriptional repression : of the granulocyte-macrophage colony stimulating factor gene /." Access full-text from WCMC, 1998. http://proquest.umi.com/pqdweb?did=733066141&sid=3&Fmt=2&clientId=8424&RQT=309&VName=PQD.
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Olivares, Fontt Elizabeth. "Rôle du granolocyte-macrophage colony-stimulating factors lors de l'infection expérimentale à Trypanosoma cruzi." Doctoral thesis, Universite Libre de Bruxelles, 1995. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/212546.
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Elliott, Michael J. H. "The interactions of interleukin-3 and granulocyte-macrophage colony-stimulating factor with human monocytes /." Title page, table of contents and abstract only, 1989. http://web4.library.adelaide.edu.au/theses/09PH/09phe464.pdf.
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Chiou, Chuang-Jiun. "Expression of Granulocyte-Macrophage Colony-Stimulating Factor Gene in Insect Cells by a Baculovirus Vector." Thesis, University of North Texas, 1989. https://digital.library.unt.edu/ark:/67531/metadc798471/.
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The focus of this research is to describe the production and characterization of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) in insect cells, using Autographa californica buclear polyhedrosis virus (AcNPV) as an expression vector. All three forms of biological activity of hGM-CSF. Following N-glycanase treatment, the two glycosylated hGM-CSF proteins (15.5 and 16.5 KDa) which bound to Concanavalin A affinity column ran as a 14.5-15.5 KDa band on SDS-PAGE. Western blot analysis of expression in Sf9 cells treated with tunicamycin revealed only the presence of the 14.5 KDa species. The N-terminal amino acid sequence of the recombinant hGM-CSF was identical to that of natural hGM-CSF deduced from cDNA. These results demonstrate that baculovirus-produced hGM-CSF could be N-glycosylated in Sf9 cells, the signal peptide of recombinant hGM-CSF could be recognized and cleaved by infected insect cells and the resultant molecule secreted into the medium.
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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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Stanford, Salome Jane. "Role of colony-stimulating factors synthesised by human vascular smooth muscle in the regulation of neutrophil survival." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341915.
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Bernstone, Laura. "Characterisation of HIV-1 infection and M-CSF and GM-CSF macrophages." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572833.
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Macrophages are a natural target cell for HIV-1 infection, and they contribute to the development of disease as they are important for transmission, dissemination and persistence of the virus in an infected patient. Macrophages are less well-studied than T cells and cell lines in relation to HIV-1 infection, yet macrophages are highly specialised and key aspects of the HIV-1 life cycle in these cells are already known to differ compared to other cell types. HIV-1 entry into macrophages has been suggested to occur by macropinocytosis, however the entry route in these cells has not been fully characterised. In this thesis I have tested a panel of pharmacological inhibitors of cellular proteins and uptake pathways, in order to delineate the requirements for HIV-1 entry into macrophages and to determine the nature of the entry route. My findings suggest that the following host factors are important for entry; membrane cholesterol, actin rearrangements, dynamin, sodium-hydrogen exchange, Pak1, and Rac. Other factors including clathrin, PI-3 kinase, Rho kinase and some isoforms of PKC were found to be dispensable for infection or to inhibit infection. Macrophages are a heterogeneous group of cells, and tissue macrophages from different parts of the body differ in their morphology, phenotype and function. I have used the growth factors M-CSF and GM-CSF to direct monocytes to differentiate into distinct types of macrophage. This allowed me to determine that different macrophages differ in their susceptibility to infection and in their ability to support replication. This is likely to be due to variation in HIV-1 receptor expression and the levels of key HIV-1 transcription factors, respectively. Overall this thesis contributes to existing knowledge regarding HIV-1 infection of macrophages. These findings may assist with the design of entry inhibitors, and with therapies designed to eradicate HIV-1 from infected individuals.
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Rahmati, Mona. "Granulocyte-Colony Stimulating Factor and Embryo Implantation Process : Effects on Human Endometrium and on Murine Abortion Prone Model CBA/J x DBA/2." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T048/document.
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L’immunologie de la reproduction englobe les principes de l’immunologie générale et les aspects spécifiques de la reproduction et du développement. Les Colony Stimulating Factors (CSFs) sont une illustration de l'application médicale de ce domaine. Dans la famille des CSFs, le Granulocyte-Colony Stimulating Factor (G-CSF) apparaît aujourd'hui comme une thérapie innovante dans divers cas d'échec de la reproduction, bien que ses cibles et ses effets ne soient pas encore clairement établis. Dans ce travail, à travers une revue sur les CSFs dans la reproduction, une étude consacrée aux gènes cibles du G-CSF dans l'endomètre humain, et une étude consacrée aux effets de la supplémentation systémique en G-CSF sur l’implantation embryonnaire murine, nous avons essayé d'approcher certains mécanismes d'action possibles pour cette cytokine. Dans les modèles murins fertiles et pro-abortifs, la supplémentation systémique en G-CSF, ciblant spécifiquement l’endomètre préimplantatoire, modifie les taux d’implantation embryonnaire. Dans l’endomètre humain, certaines dérégulations préimplantatoires de gènes cibles du G-CSF ont également été observées chez les patients infertiles. L'influence du G-CSF sur ces gènes cibles a été également illustrée dans un modèle ex-vivo de culture endométriale. Ces cibles dont l’expression est influencée par le G-CSF sont décrites comme des molécules clés dans le processus implantatoire, intervenant sur l’adhésion embryonnaire, la migration cellulaire, le remodelage des tissus et l'angiogenèse locale. Ces données suggèrent des possibilités de diagnostic préventif et pré-conceptionnel de certains échecs de reproduction, considérés jusqu’à maintenant comme idiopathiques, et de thérapies innovantes orientées, afin d’optimiser la réceptivité du biosenseur endométrial afin de permettre une implantation embryonnaire harmonieuse et une grossesse évolutiveReproductive Immunology involves general immunology principles and special aspects of reproduction and development. Colony Stimulating Factors (CSFs) are an illustration of the medical application of this domain. In the CSF family, Granulocyte-Colony Stimulating Factor (G-CSF) appears today as a promising therapy in various cases of reproductive failure although its targets and effects are not clearly established. In this work, through a review on CSFs in reproduction, a study dedicated to human endometrial targets of G-CSF, and a study dedicated to systemic G-CSF supplementation effects on murine embryo implantation, we tried to approach some possible mechanisms of action of this cytokine. In the considered non-abortive and abortion-prone murine models, the timed systemic G-CSF supplementation, targeting specifically the pre implantation endometrium, influenced the embryo implantation process. Some pre conceptual human endometrial dysregulations of G-CSF target genes were also observed in infertile patients. The endometrial influence of G-CSF on these target genes was also illustrated in an ex-vivo model. These molecules under G-CSF influence are described as critically involved in embryo implantation process, by influencing embryo adhesion, cell migration, tissue remodelling and angiogenesis. These data suggest possible pre-conceptual preventive diagnosis of such reproductive failures and future orientated therapies to optimise the endometrial biosensor and the further embryo implantation and ongoing pregnancy
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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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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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BOUCHER, ARSENTA VALERIE. "Utilisation des facteurs de croissance granulocytaire dans les agranulocytoses medicamenteuses." Nice, 1994. http://www.theses.fr/1994NICE6546.
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Geary, Sean Michael. "Manipulation of the immunostimulatory capacity of a human myeloid leukaemia cell line HL-60 /." Title page, contents and abstract only, 1993. http://web4.library.adelaide.edu.au/theses/09PH/09phg292.pdf.
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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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Violante, Ana Cristina Martins da. "Contribuição para o estudo da utilização de fatores estimuladores de colónias de granulócitos no maneio de doenças associadas a neutropénia em cães e gatos : estudo retrospetivo de 30 casos clínicos (2011 – 2016)." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2016. http://hdl.handle.net/10400.5/12721.
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Dissertação de Mestrado Integrado em Medicina VeterináriaA neutropénia é um achado hematológico que se encontra associado a várias afeções no cão e no gato e, ao ser responsável pelo estabelecimento de um estado de imunossupressão, contribui de modo significativo para o agravamento da morbilidade e mortalidade dos doentes. No sentido de reverter a neutropénia e prevenir as suas consequências, podem ser administrados fatores estimuladores de colónias de granulócitos recombinantes humanos (rhG-CSF) que aceleram a produção e diferenciação dos neutrófilos na medula óssea e causam a sua saída para o sangue. Assim, esta dissertação teve como objetivo avaliar retrospetivamente a utilização de rhG-CSF em várias doenças em canídeos e felídeos, de modo a contribuir para um maior conhecimento do seu uso em medicina veterinária. Neste estudo, os rhG-CSF foram administrados a animais com neutropénia induzida pela infeção por parvovírus canino e felino (60,0%), por fármacos citotóxicos (20,0%) e hipoplasia da medula óssea (20,0%). A maioria destes animais apresentou-se com neutropénia grave (46,7%), seguida de neutropénia moderada (33,3%) e ligeira (20,0%). A utilização dos rhG-CSF foi avaliada através de hemogramas realizados antes da primeira administração e após 48 horas. Em todos os grupos foram encontrados aumentos significativos nas contagens absolutas dos leucócitos totais e neutrófilos. No grupo amostral de animais com infeção por parvovírus foi também observado um aumento significativo no número de monócitos, linfócitos e eosinófilos. Uma diminuição na contagem dos eritrócitos foi ainda encontrada no grupo de animais com infeção por parvovírus e mielotoxicidade secundária a fármacos citotóxicos, mas o seu significado é questionável. Como segunda parte deste estudo foi feita uma análise individual dos casos clínicos, na qual se verificou que a taxa de resposta aos rhG-CSF foi de 73,3%. Para além disto, foi ainda investigada a existência de associação entre a taxa de resposta e outras variáveis registadas, tendo-se encontrado uma associação com a etiologia (p = 0,041) e o desfecho clínico, classificado como alta médica ou óbito (p = 0,001). Apesar do pequeno tamanho da amostra estudada, os resultados da presente dissertação sugerem que a utilização de rhG-CSF em cães e gatos apresenta efeitos terapêuticos benéficos a nível hematológico, sendo bem tolerados quando administrados em protocolos de curta duração.
ABSTRACT - Contribution to the study of the use of granulocyte colony-stimulating factors in the management of diseases associated with neutropenia in dogs and cats: retrospective study of 30 clinical cases (2011 – 2016) - Neutropenia is a hematological finding that can be caused by a diversity of diseases in dogs and cats and, by being responsible for an immunocompromised state, contributes significantly to patient morbidity and mortality. In order to reverse neutropenia and prevent its consequences, human recombinant granulocyte colony-stimulating factors (rhG-CSF) can be used, which are drugs that increase neutrophil production and differentiation in the bone marrow and their release into the blood. The aim of this dissertation was to retrospectively evaluate the use of rhG-CSF in various clinical conditions in canine and feline patients, contributing to a greater knowledge of their use in veterinary medicine. In this study rhG-CSF were administrated to animals with neutropenia induced by canine and feline parvovirus infection (60,0%), by cytotoxic drugs (20,0%) and bone marrow hypoplasia (20,0%). The majority of these animals presented with severe neutropenia (46,7%), followed by moderate (33,3%) and mild neutropenia (20,0%). The use of these drugs was evaluated through complete blood counts performed before the first administration and after 48 hours. In all groups significant increases on total leukocyte and neutrophil counts were observed. In the sample group of animals with parvovirus infection a significant increase in the number of monocytes, lymphocytes and eosinophils was also found. A decrease in the number of erythrocytes was also seen in the group of animals with parvovirus infection and myelotoxicity secondary to cytotoxic drugs, but its meaning is questionable. As a second part of this study, an individual analysis of the clinical cases was made, which showed that the overall response rate to rhG-CSF was 73,3%. Moreover, associations between the response rate and other variables were investigated and it was encountered an association with etiology (p = 0,041) and clinical outcome, classified as hospital discharge or patient death (p = 0,001). Despite the small sample size, the results of the present dissertation suggest that the use of rhG-CSF in dogs and cats brings beneficial therapeutic effects on a hematological level and are well tolerated when administered in short protocols.
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Tehranchi, Ramin. "Apoptosis in myelodysplastic syndromes : effects of hemopoietic growth factors /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-045-1/.
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Liutkauskienė, Sigita. "P53 baltymo raiškos ir kitų veiksnių prognozinės vertės tyrimas, gydant krūties vėžį chemoterapija ir granuliocitų kolonijas stimuliuojančiais faktoriais." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2010~D_20101122_113300-78280.
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Disertaciniame darbe analizuojama ankstyvo ir metastazavusio krūties vėžio prognozė priklausomai nuo skirtos chemoterapijos dozės ir molekulinių žymenų. Tyrimas susidėjo iš trijų etapų. I tyrimo etape buvo atlikta molekulinių žymenų (p53 baltymo, HER2, estrogeno ir progesterono receptorių) prognozinės vertės analizė retrospektyviojo ankstyvo krūties vėžio tyrimo metu, kartu įvertinta sumažintos chemoterapijos dozės įtaka ligos išeitims. II tyrimo etape ištirtas naujo rGKSF filgrastimo saugumas ir veiksmingumas gydant chemoterapija metastazavusį krūties vėžį. III tyrimo etape atlikta molekulinių žymenų prognozinės vertės analizė, eliminavus chemoterapijos dozės įtaką klinikinėms ligos išeitims, gydymą optimalia cheminio preparato doze užtikrinus prospekyviajame daugiacentriame naujo rGKSF saugumo ir veiksmingumo tyrime. Darbo uždaviniai 1. Nustatyti antraciklinų dozės įtaką sergančiųjų ankstyvu krūties vė¬žiu išgyvenamumui. 2. Ištirti p53 baltymo raiškos, kitų molekulinių žymenų ir gydymo ypatumų įtaką ankstyvo krūties vėžio prognozei. 3. Įvertinti febrilios neutropenijos profilaktikai skiriamo naujo rGKSF saugumą, gydant metastazavusį krūties vėžį. 4. Įvertinti febrilios neutropenijos profilaktikai skiriamo naujo rGKSF veiksmingumą, gydant metastazavusį krūties vėžį. 5. Nustatyti metastazavusiu krūties vėžiu sergančių pacienčių išgyvenamumo priklausomybę nuo atsako į skiriamą gydymą. 6. Įvertinti krūties vėžio prognozę įtakojančių molekulinių žymenų tarpusavio sąsajas.This study investigated the clinical outcomes in early and metastatic breast cancer patients depending on chemotherapy and molecular markers. The study comprised of 3 parts: Part I - retrospective investigation of molecular markers (p53 protein, HER2 receptors, estrogene and progesterone receptors) and chemotherapy dose reduction in early stage breast cancer; Part II - prospective open-label multicenter phase IV clinical trial on safety and effectiveness of GCSF used in chemotherapy of metastatic breast cancer; Part III - investigation of prognostic value of p53 protein expression and other molecular markers in metastatic breast cancer when optimal chemotherapy dose was adjusted in prospective multicenter trial of new rGCSF on safety and effectiveness used in chemotherapy of metastatic breast cancer. Objectives: 1. To establish the influence of anthracycline dose on survival of early stage breast cancer patients. 2. To evaluate the influence of p53 protein expression and other molecular markers as well as treatment on prognosis of early stage breast cancer. 3. To establish the safety of new rGCSF prescribed for prevention of febrile neutropenia in chemotherapy of metastatic breast cancer. 4. To analyze the effectiveness of new rGCSF prescribed for prevention of febrile neutropenia in chemotherapy of metastatic breast cancer. 5. To establish the relationship between response to treatment and survival in metastatic breast cancer patients. 6. To evaluate the associations among... [to full text]
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Rafei, Moutih. "Fusokine design as novel therapeutic strategy for immunosuppression." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115882.
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The societal burden of autoimmune diseases and donor organ transplant rejection in developed countries reflects the lack of effective immune suppressive drugs. The main objective of my thesis was to develop novel fusion proteins targeting receptors linked to autoimmunity; strategies that will allow the suppression of autoreactive cells while sparing resting lymphocytes. Interleukin (IL) 15 has been demonstrated to exert its effects mainly on activated T-cells triggered via their T-cell receptor (TCR). Since we found that the fusion of granulocyte-macrophage colony stimulating factor (GMCSF) to IL15 - aka GIFT15 - paradoxically leads to aberrant signalling downstream of the IL15R and blocks interferon (IFN)-gamma secretion in a mixed lymphocyte reaction (MLR), we hypothesized to use this fusokine in proof-of-principle cell transplantation models and shown that GIFT15 can indeed block the rejection of allogeneic and xenogeneic cells in immunocompetent mice. Additionally, we found that ex vivo GIFT15 treatment of mouse splenocytes lead to the generation of regulatory B-cells (Bregs). These Bregs express high levels of MHCII, IL10 and are capable to block antigen (Ag)-presentation in vitro as third party bystander cells. Moreover, a single injection of these GIFT15-generated Bregs in mice with pre-developed experimental autoimmune encephalomyelitis (EAE) leads to long lasting remission of disease.Along those lines, we also found that mesenchymal stromal cells (MSCs) lead to the paracrine conversion of CCL2 to an antagonist form capable of specifically inhibiting plasma cells and activated Th17 cells. This mechanistic insight informed the design of a second class of suppression fusokine. Namely, the fusing of antagonist CCL2 to GMCSF - aka GMME1. We tested its potential use in autoimmune diseases such as EAE and rheumatoid arthritis (RA). We demonstrated that GMME1 leads to asymmetrical signalling and inhibition of plasma cells as well as Th17 EAE/RA-reactive CD4 T-cells. The net outcome of these pharmacological effects is the selective depletion of CCR2-reactive T-cells as demonstrated both in vitro and in vivo.
Overall, our data support the use of our fusion proteins as part of a powerful and specific immunosuppressive strategy either as directly injectable protein biopharmaceuticals or through the ex vivo generation of autologous Bregs in the case of GIFT15.
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Mamatha, B. N. "Proteomics-based Identification of Serum Biomarkers : Role of Secreted MCSF and CRP in Glioma Pathogenesis." Thesis, 2015. https://etd.iisc.ac.in/handle/2005/4810.
Full textAbstract:
Gliomas are the neoplasia of glial cells present in the brain and comprises of
more than 70% of all the neoplasms of the central nervous system. They consist of
a family of primary brain tumors that are categorized based on the cell type of origin.
Astrocytoma, a tumor of astrocytic glial cells has the highest frequency of occurrence
as compared to other glioma types and often referred to as glioma. Based
on the malignancy of the tumor,World Health Organization (WHO) has classified
astrocytoma into Grade I/Pilocytic Astrocytoma (PA), Grade II/ Diffuse Astrocytoma
(DA), Grade III/Anaplastic Astrocytoma (AA) and Grade IV/Glioblastoma
(GBM). GBM is the most frequent and malignant primary brain tumor in adults.
The standard treatment for GBM includes surgical resection of the tumor followed
by radiation and temozolomide therapy. In spite of such mutlimodal treatment
protocol followed, the median survival of the GBM remains as low as 15 months.
While multiple markers with potential utility in diagnosis, prognosis and therapy
of GBM have been reported based on profiling of gene expression, protein expression,
miRNA and methylation pattern using tumor tissue, serum-based markers
are scanty. Serum biomarkers have great potential in clinical decision making and
management of glioma. Serum is an attractive source for biomarker mining since
it can be obtained easily by less invasive method. Further, they have wide range
of application which includes diagnosis, disease classification, prognosis, predicting
risk and outcome of the disease. More importantly, serum can be obtained
easily during follow-up of disease which could make it useful to detect tumor
recurrence. This is particularly beneficial because glioma diagnosis and monitoring
tumor recurrence are carried out by Magnetic Resonance Imaging (MRI)
and Computed Tomography (CT) scan, which is time consuming and less cost
effective. The current study was designed to identify serum biomarkers of glioma
by using proteomic approaches and to understand the functional role of selected
biomarkers in glioma pathogenesis. This study has been divided into three parts.
In part I, we profiled cytokines using bead array method and by applying various
statistical analyses we derived an 18-cytokine signature. In part II, Macrophage
Colony Stimulating Factor (MCSF), one of the proteins elevated in GBM sera as
identified by bead array method was investigated for its regulation and function
in glioma. In part III, serum profiling by antibody microarray was performed and
developed a serum based three-marker panel for distinguishing GBM from normal
samples. Further, the role of C-Reactive Protein (CRP), a highest abundant serum
protein in GBM, was investigated in detail.
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Elliott, Michael J. H. "The interactions of interleukin-3 and granulocyte-macrophage colony-stimulating factor with human monocytes / Michael J.H. Elliott." Thesis, 1989. http://hdl.handle.net/2440/19108.
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Lee, Mei-Hsuan, and 李美萱. "The Role of Granulocyte-Macrophage Colony-Stimulating Factors (GM-CSF) in Galectin-3-Mediated Tumorigenesis." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/75249965323079942811.
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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.
Full textAbstract:
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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Huang, Ya-Ching, and 黃雅菁. "Cloning and Expression of Porcine Granulocyte/Macrophage Colony- Stimulating Factors (GM-CSF) by Chinese Hamster Ovary (CHO) Cells." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/04956550900552191903.
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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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Zhang, Yuan Heidi. "Mass spectrometric analysis of proteins and peptides : elucidation of the folding pathways of recombinant human macrophage colony stimulating factor beta." Thesis, 2002. http://hdl.handle.net/1957/37223.
Full textAbstract:
Recombinant human macrophage colony stimulating factor beta
(rhm-CSFβ) is a glycoprotein that stimulates the proliferation, differentiation
and survival of cells belonging to the monocyte-macrophage lineage. It
contains nine inter-subunit and intra-subunit disulfide bonds and represents
an excellent model system for studying disulfide bond formation during
protein folding because the assembly of its monomeric subunits and the
maturation of its biological activity depend on the progressive formation of
the correct disulfide structure during in vitro folding. Knowledge obtained
from these studies can be potentially useful in understanding the roles of
disulfide bond formation during protein folding in general.
rhm-CSF8 was modified by partial reduction of disulfide bonds,
yielding CN¹⁵⁷'¹⁵⁹-modified rhm-CSFβ. The modification did not affect the
biological activity, stability, or the overall conformation of the protein.
However, the C-terminal regions near the modification sites were shown to
exhibit faster deuterium exchange behavior as a result of the chemical
modification, indicating that the C-terminal regions became more flexible.
Folding kinetics of rhm-CSFβ and CN¹⁵⁷'¹⁵⁹-modified rhm-CSFβ were shown
to be essentially the same, suggesting that the modification did not affect
the folding kinetics of the oxidized rhm-CSFβ.
The denatured and reduced rhm-CSFβ was refolded with the aid of a
chemical oxidant. The data indicated that the in vitro folding rhm-CSFβ
proceeded via multiple pathways involving monomeric and dimeric
intermediates. Disulfide bond shuffling catalyzed by GSH/GSSG
represented an important isomerization step in folding. A dimeric
intermediate, D-SS8-cam2, was isolated and identified as a kinetic trap,
perhaps requiring significant structural arrangement to convert to the native
protein. The heterogeneous folding mixture detected by both disulfide bond
quenching and H/D pulsed labeling indicate that rhm -CSFβ folding is a
diffusion like process as described by the folding funnel model.Graduation date: 2003
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Geary, Sean Michael. "Manipulation of the immunostimulatory capacity of a human myeloid leukaemia cell line HL-60 / by Sean Michael Geary." Thesis, 1993. http://hdl.handle.net/2440/21505.
Full textAbstract:
Includes nine pages of amendments.Bibliography: leaves 140-211.
211, [200] leaves, [12] leaves of plates : ill. (some col.) ; 30 cm.
Aims to determine the reason for the lack of ability of many myeloid leukaemic cell populations to stimulate allogeneic lymphocytes in mixed leucocyte culture (MLC), with a view to manipulating the immunogenicity of these cells for therapeutic purposes.
Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1995
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Osborne, Cameron Stuart. "Transcriptional regulation of the GM-CSF gene in T lymphocytes / Cameron Stuart Osborne." Thesis, 1996. http://hdl.handle.net/2440/18868.
Full textAbstract:
Addendum pasted on front end papers.Includes bibliographies.
109, [99] leaves, [5] leaves of plates : ill. ; 30 cm.
Describes the investigation as to whether the mouse granulocyte-macrophage colony-stimulating factor and interleukin-3 genes are regulated in a similar manner as those of the human, focussing on regulation through an enhancer.
Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1996
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Shirvaikar, Neeta Chandan. "Role of membrane-type 1 matrix metalloproteinase in hematopoietic stem/progenitor cell trafficking." Phd thesis, 2010. http://hdl.handle.net/10048/1146.
Full textAbstract:
Thesis (Ph.D.)--University of Alberta, 2010.A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Medicine. Title from pdf file main screen (viewed on April 27, 2010). Includes bibliographical references.
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Byts, Nadiya. "Signalling of hematopoietic growth factors in mammalian neural cells." Doctoral thesis, 2007. http://hdl.handle.net/11858/00-1735-0000-0006-B36E-9.
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Pham, Duy. "Twist1 and Etv5 are part of a transcription factor network defining T helper cell identity." Thesis, 2014. http://hdl.handle.net/1805/4657.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)CD4 T helper cells control immunity to pathogens and the development of inflammatory disease by acquiring the ability to secrete effector cytokines. Cytokine responsiveness is a critical component of the ability of cells to respond to the extracellular milieu by activating Signal Transducer and Activator of Transcription factors that induce the expression of other transcription factors important for cytokine production. STAT4 is a critical regulator of Th1 differentiation and inflammatory disease that attenuates the gene-repressing activity of Dnmt3a. In the absence of STAT4, genetic loss of Dnmt3a results in de-repression of a subset of Th1 genes, and a partial increase in expression that is sufficient to observe a modest recovery of STAT4-dependent inflammatory disease. STAT4 also induces expression of the transcription factors Twist1 and Etv5. We demonstrate that Twist1 negatively regulates Th1 cell differentiation through several mechanisms including physical interaction with Runx3 and impairing STAT4 activation. Following induction by STAT3-activating cytokines including IL-6, Twist1 represses Th17 and Tfh differentiation by directly binding to, and suppressing expression of, the Il6ra locus, subsequently reducing STAT3 activation. In contrast, Etv5 contributes only modestly to Th1 development but promotes Th differentiation by directly activating cytokine production in Th9 and Th17 cells, and Bcl6 expression in Tfh cells. Thus, the transcription factors Twist1 and Etv5 provide unique regulation of T helper cell identity, ultimately impacting the development of cell-mediated and humoral immunity.