Tomoko Kuno

Antioxidant Vitamin Levels in Plasma and Low Density Lipoprotein of Obese Girls

To investigate the antioxidant status of obese children, we analyzed beta-carotene and alpha-tocopherol levels in plasma and low density lipoprotein (LDL). We also analyzed the fatty acid composition of LDL as a substrate for oxidative stress. The plasma beta-carotene and alpha-tocopherol levels were relatively lower in obese girls than in normal controls. However, the plasma alpha-tocopherol/lipids ratio was significantly lower in obese girls than in normal controls. Both LDL beta-carotene and LDL alpha-tocopherol levels were significantly lower in obese girls than in normal controls, although no obvious differences were observed in plasma levels. In obese girls LDL contained more polyunsaturated fatty acid (PUFA) compared with normal controls. When the peroxidizability index (PI) was calculated to estimate the susceptibility of lipids to oxidative stress, obese girls had significantly higher PI values than normal controls. Both the LDL beta-carotene/PI ratio and the LDL alpha-tocopherol/PI ratio were significantly lower in obese girls than in normal controls. These results indicate the increased susceptibility of LDL to oxidative stress in obese girls which may promote atherosclerosis later in life.

Induction of Apoptosis by γ-Tocotrienol in Human Cancer Cell Lines and Leukemic Blasts From Patients: Dependency on Bid, Cytochrome c, and Caspase Pathway

Tocotrienols (Toc3) have been suggested to possess anticancer effects besides antioxidant and antiinflammatory effects. Previous studies have demonstrated that Toc3 induce apoptosis in epithelial carcinoma. However, the effects of Toc3 on malignant hematopoietic cells have not yet been thoroughly investigated. We investigated Toc3-induced apoptosis in human hematological cancer cell lines. α-, δ-, and γ-Toc3 induced concentration-dependent apoptosis, and γ-Toc3 demonstrated more effective induction than the other Toc3 derivatives in HL-60 cells. γ-Toc3 may have induced apoptosis by activation of the caspase cascade, cytochrome c (Cyt.c) release, Bid cleavage, and mitochondorial membrane depolarization in HL-60, NB-4, Raji, and SY-5Y cells. Furthermore, 10–30 μM γ-Toc3 showed cytotoxicity for leukemic cells from various patients regardless of lymphoblastic, myeloblastic, or relapsed leukemia, but the cytotoxic effect was weak in normal mononuclear cells, interestingly. γ-Toc3 may have a role in cancer prevention and potential for treating hematological malignancies.

Plasma All-Trans Retinoic Acid Level in Neonates of Mothers with Acute Promyelocytic Leukemia

We have encountered 3 cases of APL in pregnancy as shown in table 1 . All 3 mothers were diagnosed as having APL in the third trimester. They received standard oral induction therapy with ATRA (45 mg/m 2 divided into 2 doses) for 2–4 weeks. Chemotherapy was performed after cesarean section. All of them achieved complete remission after this additional chemotherapy. None of the mothers suffered any toxicity during ATRA therapy. All the neonates were delivered safely, but had the complications shown in table 1 . All of them required intubation for respiratory distress syndrome (RDS). Their complications improved with appropriate treatment. Case 2 was reported previously because this neonate had premature atrial contraction [5] . Laboratory data were within the normal range and none of the neonates had dermatitis, dry skin, or cheilitis, which are known toxicities of ATRA. We measured the plasma ATRA level in umbilical cord blood, as well as in the mothers and neonates ( fi g. 1 A). The method of measuring ATRA levels has been described previously [8] . ATRA was detected in the maternal plasma of case 2, and in the maternal and neonatal plasma of case 3. Transfer of ATRA to the fetus occurred as shown in fi gure 1 B. 9cis RA and 13cis RA, which are Alltrans retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL) achieves a high complete remission rate with mild side effects during induction therapy. APL is characterized by the chromosomal translocation (15; 17), which results in fusion of the PML gene and the retinoic acid receptor (RAR) gene. Recently, this translocation has been related to oncogenesis in APL, and identifi cation of the molecular mechanism of oncogenesis is underway. The administration of chemotherapy during the fi rst trimester is associated with a high rate of fetal malformation [1] . However, it has been reported that pregnant women with APL can be treated by ATRA and control of disseminated intravascular coagulation during the second and third trimesters allowing safe delivery of the fetus with no serious complications [2–6] . Although vitamin A and its derivatives are known to be teratogenic in early pregnancy, little is known about its effects in late pregnancy [7] . In this study, we measured plasma ATRA levels in the umbilical cord blood of neonates born to mothers treated with ATRA during pregnancy. These neonates were followed up after delivery. Received: August 26, 2004 Accepted after revision: February 8, 2005

Expression of retinoic acid receptor-target genes during retinoic acid therapy for acute promyelocytic leukemia.

Expression of retinoic acid receptor–target genes during retinoic acid therapy for acute promyelocytic leukemia