In vitro combined effects of a triazene compound and interferon-beta on natural immunity against lymphoblastoid cells: studies at effector and target cell level.
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY(2008)
摘要
It was shown that Dacarbazine and other triazene compounds render murine leukemias highly immunogenic and susceptible to natural immunity (NI). In addition a pilot clinical study revealed that Dacarbazine can be cytotoxic for bone marrow blasts in patients with acute non-lymphoblastic leukemias through a mechanism that could be, at least in part, of immunological origin. However triazenes depress antigen-dependent responses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex interaction between triazenes and IFN on NI effector (i.e. NK) lymphocytes and human target lymphoblastoid cells has been investigated. The results show that: (a) IFN increases NK activity and antagonizes the depressive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the Mt function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased growth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regulates the susceptibility of lymphoblastoid cells to NK effecters; (d) however a net "therapeutic gain" was found if the overall influence of MTBA + IFN on target and effector cells is considered.
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