A majority of cancer patients preferred to receive terminal care at home. Cancer patients and family members with strong support groups were more likely to prefer the home as the place of terminal care and dying. Hence, improving support networks might increase the proportion of patients receiving home care and dying at home.
Arsenic trioxide (As 2 O 3 ) is used, in current practice, as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). However, the side effects and relatively low efficacy of As 2 O 3 in treating other leukemias have limited its wider use in therapeutic applications. In the present study, we found that the expression of carbonyl reductase 1 (CBR1) affects the resistance to As 2 O 3 in leukemias, including APL; As 2 O 3 upregulated CBR1 expression at the transcriptional level by stimulating the activity of the transcription factor activator protein-1. Moreover, CBR1 overexpression was sufficient to protect cells against As 2 O 3 through modulation of the generation of reactive oxygen species, whereas the attenuation of CBR1 was sufficient to sensitize cells to As 2 O 3 . A combination treatment with the specific CBR1 inhibitor hydroxy-PP-Me remarkably increased As 2 O 3 -induced apoptotic cell death compared with As 2 O 3 alone, both in vitro and in vivo. These results were confirmed in primary cultured human acute and chronic myeloid leukemia cells, with no significant cell death observed in normal leukocytes. Taken together, our findings indicate that CBR1 contributes to the low efficacy of As 2 O 3 and, therefore, is a rational target for the development of combination chemotherapy with As 2 O 3 in diverse leukemias including APL. Cancer Res; 72(16); 4214-24. Ó2012 AACR.
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