GM-CSF Dotaz Zobrazit nápovědu

Grantový projekt je zaměřen na kombinovanou léčbu nádorů pomocí IL - 2 a GM-CSF využívající rekombinantních cytokinů a geneticky modifikovaných nádorových vakcin.

Konspekt
Patologie. Klinická medicína
NLK Obory
biologie
onkologie
NLK Publikační typ
závěrečné zprávy o řešení grantu IGA MZ ČR

Článek

Properties of bcr-abl-transformed mouse 12B1 cells secreting interleukin-2 and granulocyte-macrophage colony stimulating factor (GM-CSF): II. Adverse effects of GM-CSF

Granulocyte-macrophage colony stimulating factor (GM-CSF) is considered to be the most effective immunostimulating ...

International journal of oncology. 2012 ; 40 (6) : 1915-1922.

Int J Oncol
ISSN 1791-2423
Medvik
Zdroj

Granulocyte-macrophage colony stimulating factor (GM-CSF) is considered to be the most effective immunostimulating factor for the construction of gene-engineered anti-cancer vaccines. In some tumour cells, this type of genetic modification has resulted in the loss of the oncogenic potential. This was not the case with bcr-abl-transformed mouse 12B1 cells. A cell line, designated 12B1/GM-CSF/cl-5 producing more than 100 ng/106 cells/24 h, displayed higher pathogenicity than the parental, non-transduced cells. Although the tumours induced by the parental 12B1 cells and 12B1/GM-CSF/cl-5 cells appeared nearly at the same time and then grew at an approximately equal rate, the latter mice were in a much poorer clinical condition. In these animals the growth of the tumours was associated with gradually increasing blood levels of GM-CSF. In both groups of animals splenomegaly was observed; it was much more pronounced in the case of 12B1/GM-CSF/cl-5-inoculated animals. While in the case of animals inoculated with the parental cells the splenomegaly was probably mainly due to infiltration with tumour cells, in the animals inoculated with the GM-CSF-secreting cells splenomegaly and derangement of parenchymal organs, such as lungs, liver and kidneys, were more complex, including congestion and infiltration with hemopoietic cells, predominantly immature cells of myeloid lineage. The most conspicuous of these changes was the hyperaemia of the lungs. No such alterations were seen in animals inoculated with the parental cells. On the other hand, the contents of T regulatory cells were comparable in both groups and they increased in parallel at the end of the observation period. When GM-CSF neutralizing antibody was administered to animals inoculated with the 12B1/GM-CSF/cl-5 cells, the pathological changes observed within the organs were suppressed, this proving that the overproduced GM-CSF and not any other substance, played the key role in their induction.

MeSH
bcr-abl fúzové proteiny genetika metabolismus MeSH
experimentální nádory patologie MeSH
faktor stimulující granulocyto-makrofágové kolonie krev imunologie sekrece MeSH
interleukin-2 sekrece MeSH
játra patologie MeSH
ledviny patologie MeSH
leukemie patologie MeSH
myši inbrední BALB C MeSH
myši MeSH
nádorové buněčné linie MeSH
neutralizující protilátky aplikace a dávkování MeSH
plíce patologie MeSH
regulační T-lymfocyty imunologie MeSH
slezina imunologie patologie MeSH
transplantace nádorů MeSH
tumor burden MeSH
zvířata MeSH
Check Tag
myši MeSH
ženské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF

pathogen parapox Orf virus deploys GIF, a member of the poxvirus immune evasion superfamily, to antagonize GM-CSF ...

Nature communications. 2016 ; 7 (-) : 13228. [pub] 20161107

Nat Commun
ISSN 2041-1723
Medvik
Zdroj

Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen parapox Orf virus deploys GIF, a member of the poxvirus immune evasion superfamily, to antagonize GM-CSF (granulocyte macrophage colony-stimulating factor) and IL-2 (interleukin-2), two pleiotropic cytokines of the mammalian immune system. However, structural and mechanistic insights into the unprecedented functional duality of GIF have remained elusive. Here we reveal that GIF employs a dimeric binding platform that sequesters two copies of its target cytokines with high affinity and slow dissociation kinetics to yield distinct complexes featuring mutually exclusive interaction footprints. We illustrate how GIF serves as a competitive decoy receptor by leveraging binding hotspots underlying the cognate receptor interactions of GM-CSF and IL-2, without sharing any structural similarity with the cytokine receptors. Our findings contribute to the tracing of novel molecular mimicry mechanisms employed by pathogenic viruses.

MeSH
faktor stimulující granulocyto-makrofágové kolonie chemie imunologie metabolismus MeSH
HEK293 buňky MeSH
infekce vyvolané poxviry imunologie metabolismus virologie MeSH
interakce hostitele a patogenu imunologie MeSH
interleukin-2 chemie imunologie metabolismus MeSH
krystalografie rentgenová MeSH
lidé MeSH
molekulární modely MeSH
multiproteinové komplexy chemie imunologie metabolismus MeSH
Parapoxvirus imunologie metabolismus MeSH
vazba proteinů MeSH
virové proteiny chemie imunologie metabolismus MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Kniha

GM-CSF state of arts and future perspectives

Oxford : Elsevier Science, 1999

European journal of cancer, ISSN 0959-8049 vol. 35, suppl. 3, August 1999

S40 s. : il., grafy ; 30 cm

Článek

Adenosine potentiates stimulatory effects on granulocyte-macrophage hematopoietic progenitor cells in vitro of IL-3 and SCF, but not those of G-CSF, GM-CSF and IL-11

selected hematopoietic growth factors and cytokines, namely with granulocyte colony-stimulating factor (G-CSF ...

Physiological research. 2006 ; 55 (5) : 591-596.

ISSN 0862-8408
Medvik
Zdroj

The aim of the studies was to ascertain if adenosine is able to co-operate with selected hematopoietic growth factors and cytokines, namely with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), interleukin-3 (IL-3), and interleukin-11 (IL-11), in inducing the growth of colonies from hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) from normal bone marrow cells in vitro. Adenosine was found not to produce any colonies when present in the cultures as the only potential stimulator. All the tested cytokines and growth factors were observed to induce the growth of distinct numbers of GM-CFC colonies, with the exception of IL-11. When suboptimal concentrations of the evaluated cytokines and growth factors were tested in the cultures in which various concentrations of adenosine were concomitantly present, mutually potentiating effects were found in the case of IL-3 and SCF. These results confirm the role of adenosine in regulation of granulopoiesis and predict IL-3 and SCF as candidates for further in vivo studies of their combined administration with adenosine.

MeSH
adenosin farmakokinetika MeSH
cytokiny farmakokinetika chemie MeSH
faktor růstu kmenových buněk farmakokinetika fyziologie chemie MeSH
faktor stimulující granulocyto-makrofágové kolonie farmakokinetika fyziologie chemie MeSH
faktory růstu hematopoetických buněk farmakokinetika MeSH
financování vládou MeSH
interleukiny farmakokinetika fyziologie chemie MeSH
interpretace statistických dat MeSH
myši inbrední C57BL MeSH
myši inbrední CBA MeSH
zvířata MeSH
Check Tag
zvířata MeSH
Publikační typ
srovnávací studie MeSH

Kolekce

Publikováno

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GM-CSF Dotaz Zobrazit nápovědu

GM-CSF Dotaz Zobrazit nápovědu

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