Nejvíce citovaný článek - PubMed ID 12851676
Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo
The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca2+-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal > Man. These findings established for rat Nkrp1a have been extrapolated to all additional Nkrp1 receptors and have been supported by numerous studies over the past two decades. However, since 1996 there has been controversy and another article showed lack of interactions with saccharides in 1999. Nevertheless, several high affinity saccharide ligands were synthesized in order to utilize their potential in antitumor therapy. Subsequently, protein ligands were introduced as specific binders for Nkrp1 proteins and three dimensional models of receptor/protein ligand interaction were derived from crystallographic data. Finally, for at least some members of the NK cell C-type lectin-like proteins, the "sweet story" was impaired by two reports in recent years. It has been shown that the rat Nkrp1a and CD69 do not bind saccharide ligands such as GlcNAc, GalNAc, chitotetraose and saccharide derivatives (GlcNAc-PAMAM) do not directly and specifically influence cytotoxic activity of NK cells as it was previously described.
- MeSH
- buňky NK * chemie imunologie metabolismus MeSH
- CD antigeny * chemie imunologie metabolismus MeSH
- diferenciační antigeny T-lymfocytů * chemie imunologie metabolismus MeSH
- krysa rodu Rattus MeSH
- lektinové receptory NK-buněk - podrodina B * chemie imunologie metabolismus MeSH
- lektiny typu C * chemie imunologie metabolismus MeSH
- lidé MeSH
- oligosacharidy * chemie imunologie metabolismus MeSH
- terciární struktura proteinů MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CD antigeny * MeSH
- CD69 antigen MeSH Prohlížeč
- diferenciační antigeny T-lymfocytů * MeSH
- KLRB1 protein, human MeSH Prohlížeč
- lektinové receptory NK-buněk - podrodina B * MeSH
- lektiny typu C * MeSH
- oligosacharidy * MeSH
The binding of monosaccharides and short peptides to lymphocyte receptors (human CD69 and rat NKR-P1A) was first reported in 1994 and then in a number of subsequent publications. Based on this observation, numerous potentially high-affinity saccharide ligands have been synthesized over the last two decades in order to utilize their potential in antitumor therapy. Due to significant inconsistencies in their reported binding properties, we decided to re-examine the interaction between multiple ligands and CD69 or NKR-P1A. Using NMR titration and isothermal titration calorimetry we were unable to detect the binding of the tested ligands such as N-acetyl-D-hexosamines and oligopeptides to both receptors, which contradicts the previous observations published in more than twenty papers over the last fifteen years.
- MeSH
- CD antigeny metabolismus MeSH
- diferenciační antigeny T-lymfocytů metabolismus MeSH
- krysa rodu Rattus MeSH
- lektiny typu C metabolismus MeSH
- lidé MeSH
- oligopeptidy chemická syntéza farmakologie MeSH
- polysacharidy chemická syntéza farmakologie MeSH
- receptory imunologické metabolismus MeSH
- rekombinantní proteiny metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CD antigeny MeSH
- CD69 antigen MeSH Prohlížeč
- diferenciační antigeny T-lymfocytů MeSH
- Klrb1a protein, rat MeSH Prohlížeč
- lektiny typu C MeSH
- oligopeptidy MeSH
- polysacharidy MeSH
- receptory imunologické MeSH
- rekombinantní proteiny MeSH
N-Acetyl-D-glucosamine-substituted glycoconjugates (GCJs) with the polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold represent ligands for NKR-P1 molecule and induce NK cell-mediated cytotoxicity in vitro. The in vivo effect of these GCJs on mouse melanoma model was determined when administered either alone or in combination with non-specific immunostimulator keyhole limpet hemocyanin (KLH). All types of treatment significantly reduced the tumor growth on day 23, while GN4C as well as KLH were effective continuously (from day 14). The GN4C also induced the longest mean survival time (46.3 ± 11.1 d), followed by KLH+GN4C (36.4 ± 12.1), KLH (35.6 ± 6.5), KLH+GN8P (35.6 ± 6.7), and GN8P (32.4 ± 7.0), compared to controls (29.8 ± 3.6). The B16F10 specific cytotoxicity of peripheral blood cells was significantly elevated by both KLH and GN8P, whereas not by GN4C. KLH increased the effect of the GN4C, but did not influence that of GN8P. GN4C was proved to exert anticancer activity in mouse melanoma model. The combination of KLH with GCJs did not generate synergism.
- MeSH
- acetylglukosamin chemie MeSH
- adjuvancia imunologická terapeutické užití MeSH
- glykokonjugáty chemie terapeutické užití MeSH
- hemokyanin terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- melanom farmakoterapie patologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory kůže farmakoterapie patologie MeSH
- protinádorové látky terapeutické užití MeSH
- synergismus léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylglukosamin MeSH
- adjuvancia imunologická MeSH
- glykokonjugáty MeSH
- hemokyanin MeSH
- keyhole-limpet hemocyanin MeSH Prohlížeč
- protinádorové látky MeSH