APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells.

APTO-253 is a phase I clinical stage small molecule that selectively induces CDKN1A (p21), promotes G-G cell-cycle arrest, and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. Differential gene expression analysis identified a pharmacodynamic effect on MYC expression, as well as induction of DNA repair and stress response pathways. APTO-253 was found to elicit a concentration- and time-dependent reduction in MYC mRNA expression and protein levels.

Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation.

Purpose: Transforming growth factor beta1 (TGF-beta) stimulates the differentiation of myofibroblasts as indicated by the nascent expression of alpha-smooth muscle (alpha-SM) actin protein and its organization into stress fibers. Downstream messengers of TGF-beta in the conversion from the fibroblast to the myofibroblast phenotype were investigated. Whether TGF-beta increases the transcription of a second growth factor, connective tissue growth factor 1 (CTGF), which could mediate myofibroblast differentiation, was evaluated.

Fibroblast growth factor reversal of the corneal myofibroblast phenotype.

Purpose: Keratocytes give rise to fibroblasts and myofibroblasts in wounded cornea. It is well established that treatment of fibroblasts with transforming growth factor (TGF) beta will induce myofibroblast differentiation. We investigated whether this differentiation could be reversed by the administration of fibroblast growth factor (FGF).

A mammalian severin replaces gelsolin in transformed epithelial cells.

A persisting paradox in cytoskeletal regulation of cell motility is the loss of the actin filament fragmenting protein, gelsolin, in transformed epithelial cells that have gained the ability to migrate. Either actin filament severing does not occur during motility of carcinoma cells or a novel fragmentation protein is expressed during transformation. Using an antibody specific for severin, the Mr 40,000 actin filament severing protein from Dictyostelium discoideum amoebae, we have identified a mammalian form of severin in murine LL/2 carcinoma cells lacking gelsolin.

Relationships between 222Rn dissolved in ground water supplies and indoor 222Rn concentrations in some Colorado front range houses.

Indoor 222Rn concentrations were measured in 37 houses with alpha track detectors placed in water-use rooms near water sources (bathrooms, laundry rooms, and kitchens) and in non-water-use living rooms, dining rooms, and bedrooms away from water sources. Results show that relative contributions of 222Rn to indoor air from water use are insignificant when soil-gas concentrations are high but become increasingly important as the ratio of 222Rn-in-water: 222Rn-in-soil gas increases. High soil-gas 222Rn concentrations may mask 222Rn contributions from water even when waterborne 222Rn concentrations are as high as 750 kBq m-3.