e combination of the endonuclease plus either purine analogue. The combination of doxorubicin with ONCONASE or R-Amph demonstrated an increase in pro-apoptotic activity when compared to single agent treatment, although the effect was not statistically significant. This is the first study showing cytotoxic, pro-apoptotic effects of ONCONASE and R-Amph in CLL, and synergism with the most widely used CLL therapies.
For the study in AML, leukemic cells isolated from 22 patients with newly diagnosed AML were cultured for 24-72 hours with either ONCONASE or R-Amph alone and in combination with doxorubicin or cytarabine arabinoside. In these experiments, both endoribonucleases showed significant activity against AML cells. The main mechanism of this action was shown to be the triggering of caspase-dependent apoptosis by activation of the mitochondrial pathway. The combination of ONCONASE or R-Amph with doxorubicin in AML exhibited significant synergistic cytotoxicity, and offers insights into the potential therapeutic enhancement for doxorubicin, from a class of drugs commonly used as first line therapy in AML.
"These ex vivo studies expand the potential of ONCONASE as a potential treatment for various leukemias," said Kuslima Shogen, Alfacell's chief executive officer. "Based on our knowledge of the impact of ONCONASE on cellular pathways involved in tumor cell growth, and also in resistance to chemotherapy, additional studies may further demonstrate ONCONASE's promising anti-leukemic activity."
AML (acute myeloblastic leukemia) is a cancer of the myeloid line of white blood cells, characterized by the rapid proliferation of abnormal cells which accumulate in the bone marrow and interfere with the production of normal blood cells. AML is a potentially curable disease; but only a minority of patients are cured with current therapy. AML is treated initially with chemoPage: 1 2 3 4 5 Related biology technology :1
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