n engl j med 369;2 nejm.org july 11, 2013 186 Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that is characterized by abnormal promyelocytes, a lifethreatening bleeding syndrome, and t(15;17) chromosomal translocation. APL used to be the worst form of leukemia.1,2 The introduction of anthracycline-based chemotherapy in the 1970s yielded a complete remis...

However, disparate reports in the literature contradict the described beneficial effects of ATRA on wound healing. For example, Kitano et al.17 reported a non-significant effect of ATRA on wound closure in normal mice, but a significant increase in closure in diabetic mice. Furthermore, the continuous treatment of wounds with ATRA, inhibited re-epithelisation18, disrupted collagen production an...

All-trans retinoic acid (ATRA) is valuable in differentiation therapy for acute promyelocytic leukemia (APL). However, ATRA has had limited success as a single agent, due to the development of resistance. We found that tamoxifen effectively enhanced the differentiation-inducing effect of ATRA. Tamoxifen alone inhibited the proliferation of myeloid leukemia cell lines while only slightly increas...

Treatment of human HL-60 leukemic cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with activation of protein kinase C (PKC) and induction of monocytic differentiation. An HL-60 variant cell line, termed HL-525, derived from long-term exposure to TPA (Homma et al, Proc Natl Acad Sci USA 83: 7316, 1986) is resistant to TPA-induced differentiation and displays decreased PKC bet...

All-trans retinoid acid (ATRA) is one of the most potent and most thoroughly studied differentiation inducers that induce the differentiation and apoptosis of glioma cells. However, the effect of ATRA on angiogenesis of glioma remains poorly understood. We examined the effect of ATRA on the expression of vascular endothelial growth factor (VEGF) in different glioma cell lines and investigated t...

OBJECTIVE We have shown previously that preterm infants are at risk of necrotizing enterocolitis (NEC), an inflammatory bowel necrosis typically seen in infants born prior to 32 weeks' gestation, because of the developmental deficiency of transforming growth factor (TGF)-β2 in the intestine. The present study was designed to investigate all-trans retinoic acid (atRA) as an inducer of TGF-β2 in ...

All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segmen...

Retinoids, the analogues of vitamin A, have a broad range of effects on different cell types. One biologically active form of vitamin A is all-trans-retinoic acid (ATRA), which binds to retinoic acid receptors, as does its intracellular metabolite, 9-cis-RA. Earlier studies have documented G1 cell cycle arrest and the induction of apoptosis in human adult T-cell leukemia cells after ATRA treatm...

A sensitive HPLC method for simultaneous determination of endogenous levels of all-trans-(ATRA), 13-cis-(13cRA), and 9-cis-retinoic acids (9cRA) was applied to serum samples from healthy volunteers and type II diabetes mellitus patients. Levels of 9cRA (around 0.2 ng/ml in both groups) were below the limit of quantification. The concentrations of ATRA and 13cRA were reliably quantified, and the...

Expression of tissue factor (TF) by activated monocytes in several diseases leads to disseminated intravascular coagulation. Lipopolysaccharide (LPS)-induced monocyte TF expression is downregulated by the nuclear hormone all-trans retinoic acid (ATRA). In this study, we examined the mechanism by which ATRA inhibits monocyte TF expression. We show that ATRA selectively inhibited LPS induction of...