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Marie Lipoldová Helena Havelková Jana Badalová Jarmila Vojtíšková Lei Quan Magdaléna Krulová Yahya Sohrabi Alphons P. Stassen Peter Demant 《Cancer immunology, immunotherapy : CII》2010,59(2):203-213
Low infiltration of lymphocytes into cancers is associated with poor prognosis, but the reasons why some patients exhibit
a low and others a high infiltration of tumors are unknown. Previously we mapped four loci (Lynf1–Lynf4) controlling lymphocyte infiltration of mouse lung tumors. These loci do not encode any of the molecules that are involved
in traffic of lymphocytes. Here we report a genetic relationship between these loci and the control of production of IFNγ
in allogeneic mixed lymphocyte cultures (MLC). We found that IFNγ production by lymphocytes of O20/A mice is lower than by
lymphocytes of OcB-9/Dem mice (both H2
pz
) stimulated in MLC by irradiated splenocytes of C57BL/10SnPh (H2
b
) or BALB/cHeA (H2
d
) mice, or by ConA. IFNγ production in MLCs of individual (O20 × OcB-9)F2 mice stimulated by irradiated C57BL/10 splenocytes and genotyped for microsatellite markers revealed four IFNγ-controlling
loci (Cypr4-Cypr7), each of which is closely linked with one of the four Lynf loci and with a cluster of susceptibility genes for different tumors. This suggests that inherited differences in certain
lymphocyte responses may modify their propensity to infiltrate tumors and their capacity to affect tumor growth. 相似文献
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Algirdas Mikalkėnas Bazilė Ravoitytė Daiva Tauraitė Elena Servienė Rolandas Meškys 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):384-389
Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors. 相似文献
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