acute promyelocytic leukemia (APL): The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first. acne vulgaris: RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: the liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it, to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in “pilling” of the gel, which minimizes the likelihood of over application by the patient.

Human bronchial SMCs were used and pretreated with or without tretinoin, also known as all-trans-retinoic acid (ATRA), (2 μM) for 20 min before the addition of PDGF (1 μg/ml), or ATRA alone. The neutral comet assay, which determines the incidence of double-stranded DNA breaks, was used to demonstrate that ATRA treatment induced apoptosis of bovine and human pulmonary artery SMC. In contrast, apoptotic cell death was not produced in response to ATRA in human bronchial airway SMC, as monitored by comet assay. Similarly, TUNEL assay and the measurement of mitochondrial membrane potential failed to demonstrate significant apoptosis by ATRA in airway SMCs. Positive controls, daunorubicin (DNR) and hydrogen peroxide, effectively elicited apoptosis in airway SMC. Because ATRA inhibited both morphologic and actin cytoskeletal changes induced by PDGF, it was characterized the effects of ATRA on PDGF-induced airway SMC migration using a modified Boyden chamber assay, which allows for determination of motility in random directions. PDGF caused a 4-fold increase in migration of airway SMCs after 24 h, and ATRA blocked these events. ATRA by itself had no effect. While the therapeutic level of ATRA in human plasma could reach 1–2 μM, the effects on airway SMC migration were observed with ATRA concentrations as low as 0.2 μM. DMSO, which is used as vehicle for ATRA and other retinoids, has no effect on PDGF-induced airway SMC migration. This does not appear to be due to the effects of ATRA on cell proliferation, as MTT assay showed that ATRA is not effective in inhibiting PDGF-induced cell proliferation; additionally, migration assay with 4 h of PDGF treatment also exhibits the ability of ATRA to inhibit migratory responses, as monitored using a modified Boyden chamber assay. Thus, although ATRA is ineffective in inhibiting proliferation and inducing apoptosis of airway SMCs, ATRA is an efficient inhibitor of airway SMC migration. Furthermore, using actinomycin D, a general inhibitor of gene transcription, showed that ATRA inhibition of SMC migration does not mediate gene transcriptional events.