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

Adenosines, endogenous purine nucleosides, appear in the extracellular space under metabolically stressful conditions associated with ischemia, inflammation, and cell damage. Their activity on innate immunity is prevalently inhibitory and can develop both in infectious and neoplastic diseases. During cancer development, tumor cells that release high concentrations of adenosines can impair the function of tumor-infiltrating lymphocytes and assist tumor growth by neo-angiogenesis. We evaluated the influence of A(2) adenosine receptor (A(2)AR) agonist on cytotoxic-cell response comparing human with other mammalian species (rodents, pigs, goats), both in healthy and in cancer conditions. The A(2)AR agonist developed dose-dependent inhibition of the cytotoxic activity of immune effector cells in all studied species. However, variability of the response was observed in relation to the species and the target cells that were used. Altogether, our data indicate that the A(2)AR plays a central role in adenosine-mediated inhibition of immune response to tumors.

• MeSH
• adenosin analogy a deriváty   imunologie   farmakologie   MeSH
• agonisté adenosinového receptoru A2 * MeSH
• buňky NK účinky léků   imunologie   MeSH
• cytotoxicita imunologická účinky léků   MeSH
• hlodavci MeSH
• kozy MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory imunologie   MeSH
• potkani Wistar MeSH
• prasata MeSH
• receptory adenosinové A2 imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosin MeSH
• agonisté adenosinového receptoru A2 * MeSH
• N-cyclopropyl adenosine-5'-carboxamide MeSH Prohlížeč
• receptory adenosinové A2 MeSH