Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676, has recently been introduced to clinics as a promising drug to treat patients with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60, NOMO-1, NB4, NKM-1, K562, Daudi, and the multidrug-resistant sublines, NOMO-1/ADR and NB4/MDR, was investigated by cell cycle distribution and morphology. These studies were done by a video-microscopic system, DNA fragmentation, dye exclusion and 3H-thymidine uptake after analysis of CD33, CD34, P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein and lung-related protein on these cells. A dose-dependent, selective cytotoxic effect of CMA-676 was observed in cell lines that expressed CD33, and was dependent on the amount of CD33 and the proliferative speed of the cells. Sensitive cells were temporally arrested at the G2/M phase before undergoing morphological changes. CMA-676 is not effective on P-gp-expressing multidrug-resistant sublines compared with parental cell lines. MDR modifiers, MS209 and PSC833, restored the cytotoxic effect of CMA-676 in P-gp-expressing sublines. CMA-676 is a promising agent in the treatment of patients with AML that expresses CD33. The combined use of CMA-676 and MDR modifiers may increase the selective cytotoxic effect in multidrug-resistant AML.

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Silk fibroin films in the random‐coil and β‐form conformations were immersed in water at temperatures from 2 to 130°C, and conformational changes were followed by x‐ray diffraction, infrared spectroscopy and differential scanning calorimetry. On treatment with water below 60°C, the random‐coil conformation is converted to the α form and above 70°C to mixtures of the α and β conformations. The β‐form content increases as the immersion temperature is raised. The β form is not affected by immersion in water in the temperature range studied.

FOXM1 is an important cell cycle regulator and regulates cell proliferation. In addition, FOXM1 has been reported to contribute to oncogenesis in various cancers. However, it is not clearly understood how FOXM1 contributes to acute myeloid leukemia (AML) cell proliferation. In this study, we investigated the cellular and molecular function of FOXM1 in AML cells. The FOXM1 messenger RNA (mRNA) expressed in AML cell lines was predominantly the FOXM1B isoform, and its levels were significantly higher than in normal high aldehyde dehydrogenase activity (ALDH(hi)) cells. Reduction of FOXM1 expression in AML cells inhibited cell proliferation compared with control cells, through induction of G(2)/M cell cycle arrest, a decrease in the protein expression of Aurora kinase B, Survivin, Cyclin B1, S-phase kinase-associated protein 2 and Cdc25B and an increase in the protein expression of p21(Cip1) and p27(Kip1). FOXM1 messenger RNA (mRNA) was overexpressed in all 127 AML clinical specimens tested (n = 21, 56, 32 and 18 for M1, M2, M4 and M5 subtypes, respectively). Compared with normal ALDH(hi) cells, FOXM1 gene expression was 1.65- to 2.26-fold higher in AML cells. Moreover, the FOXM1 protein was more strongly expressed in AML-derived ALDH(hi) cells compared with normal ALDH(hi) cells. In addition, depletion of FOXM1 reduced colony formation of AML-derived ALDH(hi) cells due to inhibition of Cdc25B and Cyclin B1 expression. In summary, we found that FOXM1B mRNA is predominantly expressed in AML cells and that aberrant expression of FOXM1 induces AML cell proliferation through modulation of cell cycle progression. Thus, inhibition of FOXM1 expression represents an attractive target for AML therapy.

The thermal behavior of films of amorphous silk fibroin in the random‐coil conformation has been investigated in the temperature range 25–220°C by differential scanning calorimetry (DSC), thermal expansion, dynamic mechanical measurements, x‐ray diffraction, and infrared spectroscopy. As the temperature is raised, water is lost up to about 100°C. Intramolecular and intermolecular hydrogen bonds are broken between 150 and 180°C. The glass transition is observed at 173°C by DSC. The random‐coil→β‐form transition accompanied by reformation of hydrogen bonds takes place above 180°C. Thermally induced crystallization to the β‐form crystals starts at about 190°C.

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Recent studies have shown that arsenic trioxide (As 2 O 3 ) can induce complete remission in patients with acute promyelocytic leukemia (APL). We tested the efficacy and safety of As 2 O 3 for the treatment of patients with APL who had relapsed from or become refractory to all-trans retinoic acid (ATRA) and conventional chemotherapy in a prospective study.