We found that pediatric glioblastoma (PED-GBM) cell lines from diffuse intrinsic pontine glioma (DIPG) carrying the H3K27M mutation or from diffuse hemispheric glioma expressing the H3G34R mutation are sensitive to the combination of vorinostat (a histone deacetylase inhibitor) and PARP-1 inhibitors. The combined treatment increased the phosphorylation of eIF2α (P-eIF2α) relative to each drug alone and enhanced the decrease in cell survival. To explore the role played by increased P-eIF2α in modulating PED-GBM survival and response to treatments, we employed brain-penetrating inhibitors of P-eIF2α dephosphorylation: salubrinal and raphin-1.
View Article and Find Full Text PDFBackground: Low 5-fluorouracil (5-FU) concentrations cause a significant increase in DNA synthesis in mitogen-activated human lymphocytes.
Materials And Methods: We explored 2.5 microM 5-FU-induced DNA synthesis by testing 5-FU activity in hypoxanthine-aminopterin-thymidine (HAT)-containing medium, and its effect on thymidylate synthase (TS) activity and CD25 expression in interleukin (IL)-2-activated human peripheral blood mononuclear cells (PBMCs) and the combined effects with prostaglandin E(2) (PGE(2)) and transforming growth factor (TGF)-beta3.
Background: The effect of 5-fluorouracil (5-FU) on activated lymphocytes was explored.
Materials And Methods: The in vitro effects of 5-FU on DNA synthesis in mitogen-activated lymphocytes from healthy volunteers were compared to those of the antimetabolites doxorubicin, cyclophosphamide and 6-mercaptopurine. These effects were assessed by alterations in the phenotypic profile and the percentage of cells in various phases of the cell cycle, as well as by the secretion of T helper (Th)1 and Th2 cytokines (ELISA).
Background: Studies on cancer patients undergoing chemotherapy have shown inhibitory effects of anticancer drugs on certain immune activities.
Materials And Methods: The in vitro effect of 5-(FU) fluorouracil was studied on both lymphocyte proliferation and natural killer (NK) cell antitumor cytotoxicity following incubation of peripheral mononuclear cells (PBMCs) from healthy donors with interleukin (IL)-2, phytohemagglutinin A (PHA) and pokeweed mitogen (PWM).
Results: Activation of PBMCs with IL-2, PHA and PWM in the presence of 250 and 2500 microM of 5-FU caused a marked decrease in both the induction of activated natural killer (ANK) cell cytotoxic activity and DNA synthesis, while 2.