Arsenic trioxide and all-trans-retinoic acid selectively exert synergistic cytotoxicity against FLT3-ITD AML cells via co-inhibition of FLT3 signaling pathways.

FLT3-ITD mutations occur in approximately 30% of acute myeloid leukemia (AML) and are associated with a poor outcome. Currently available FLT3 inhibitors have in vitro but limited clinical activity in FLT3-ITD AML. Reports have shown that an arsenic trioxide (ATO)/all-trans-retinoic acid (ATRA) combination improves prognosis in acute promyelocytic leukemia, especially with FLT3-ITD, and ATO or ATRA alone enhances apoptosis in FLT3-ITD AML cells treated with FLT3 inhibitors, providing a rationale to investigate the role of ATO/ATRA in FLT3-ITD AML. Here, we demonstrate that an ATO/ATRA combination selectively exerts synergistic cytotoxicity against FLT3-ITD AML cell lines (MV4;11/MOLM-13). The signaling pathways affected by ATO/ATRA include FLT3/STAT5/MYC, FLT3/STAT5/E2F1, FLT3/ERK/ATF5 and FLT3/AKT/ATF5.ATF5 may function as an oncogene in FLT3-ITD AML. Our findings provide experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination.

[Lumbar disc herniation treated with Shu-needle therapy and ozone injection of low concentration].

OBJECTIVE: To verify the efficacy on lumbar disc herniation treated with Shu-needle therapy in combination with ozone injection of low concentration. METHODS: One hundred and thirty cases of lumbar disc herniation were randomized into a Shu-needle therapy group and an acupotomy group, 65 cases in each one. In the Shu-needle therapy group, Shu-needle therapy was used in combination with ozone injection of low concentration. In the acupotomy group, the conventional acupotomy therapy was applied in combination with ozone injection of low concentration. The treatment was given once every 10 days, 3 treatments made one session. After one session treatment, the clinical efficacy of two groups was observed, scores of visual analogue scale (VAS) and Oswestry disability index (ODI) were counted before and after treatment. The long-term efficacy was followed up in half a year. RESULTS: The clinical curative rate was 69.2% (45/65) and the total effective rate was 96.9% (63/65) in the Shu-needle therapy group. The curative rate was 43.1% (28/65) and the total effective rate was 84.6% (55/65) in the acupotomy group. In comparison, the efficacy of the Shu-needle therapy group was superior to that of the acupotomy group (P < 0.01, P < 0.05). The scores of VAS and ODI were reduced obviously after treatment as compared with those before treatment in two groups (all P < 0.05). The improvements in the Shu-needle therapy group were superior to those in the acupotomy group (both P < 0.05). In the follow-up observation, the recurrence rate in the Shu-needle therapy group was lower than that in the acupotomy group [17.8% (8/45) vs 46.4% (13/28), P < 0.05]. CONCLUSION: Shu-needle therapy in combination with ozone injection of low concentration achieves the superior efficacy on lumbar disc herniation as compared with the acupotomy group.