International immunopharmacology
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Int. Immunopharmacol. · Apr 2011
Randomized Controlled TrialCord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies.
This study investigated the efficacy of cord blood-derived cytokine-induced killer (CB-CIK) biotherapy combined with second-line chemotherapy in treating advanced solid malignancies after first-line chemotherapy failure. Forty patients with advanced solid malignancies after first-line chemotherapy failure were divided into two groups: CB-CIK cells transfusion plus second-line chemotherapy (CB-CIK+Chemotherapy) group and second-line chemotherapy alone (Chemotherapy) group. The ORR and DCR were 30% and 80% in CB-CIK + Chemotherapy group compared with 15% and 70% in Chemotherapy group (P = 0.451 for ORR and P = 0.716 for DCR) respectively. ⋯ In vitro studies further revealed that CB-CIK cells could overcome drug resistance in cisplatin-resistant lung adenocarcinoma cell line A549/CDDP through downregulating ABCG-2 and P-gp and induce cytotoxicity through the high level expression of CD3, CD56, FasL, and CD69. This could explain why CB-CIK could have synergistic effects with second-line chemotherapy shown in this clinical study. We concluded CB-CIK cells combined with second-line chemotherapy can significantly improve PFS and median survival compared with second-line chemotherapy alone in patients with advanced solid malignancies after first-line chemotherapy failure.
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Int. Immunopharmacol. · Apr 2011
Sildenafil attenuates LPS-induced pro-inflammatory responses through down-regulation of intracellular ROS-related MAPK/NF-κB signaling pathways in N9 microglia.
Excessive activation of microglial cells has been implicated in various neuroinflammation. The present study showed that sildenafil, a PDE5 inhibitor, significantly suppressed NO, interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) production induced by LPS in microglial cells through decreasing the protein and/or mRNA expressions of inducible NO synthase (iNOS), IL-1β and TNF-α in a concentration-dependent manner. ⋯ Moreover, the increase of the expression of gp91phox, a critical and catalytic subunit of NADPH oxidase, and the levels of intracellular reactive oxygen species (iROS) induced by LPS were markedly inhibited by sildenafil. In summary, these data suggest that sildenafil exerts its in vitro anti-inflammatory effect in LPS-activated N9 microglial cells by blocking nuclear factor-κB (NF-κB) and MAPKs activation, which may be partly due to its potent down-regulation of the NADPH-derived iROS production.