Alisertib, an Aurora kinase A inhibitor, induces apoptosis and autophagy but inhibits epithelial to mesenchymal transition in human epithelial ovarian cancer cells.

Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear.

Involvement of tristetraprolin in transcriptional activation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase by insulin.

Several AU-rich RNA binding element (ARE) proteins were investigated for their possible effects on transcription of hepatic 3-hydroxy-3-methyglutaryl coenzyme A reductase (HMGR) in normal rats. Using in vivo electroporation, four different siRNAs to each ARE protein were introduced together with HMGR promoter (-325 to +20) luciferase construct and compared to saline controls. All four siRNAs to tristetraprolin (TTP) completely eliminated transcription from the HMGR promoter construct.

Retinal gene expression and visually evoked behavior in diabetic long evans rats.

Purpose: Patients with diabetic retinopathy may experience severe vision loss due to macular edema and neovascularization secondary to vascular abnormalities. However, before these abnormalities become apparent, there are functional deficits in contrast sensitivity, color perception, and dark adaptation. The goals of this study are to evaluate early changes (up to 3 months) in retinal gene expression, selected visual cycle proteins, and optokinetic tracking (OKT) in streptozotocin (STZ)-induced diabetic rats.

Differentiating intraocular glucocorticoids.

Background: Natural corticosteroids (e.g. hydrocortisone) and synthetic selective glucocorticoid (GC) agonists have been used by ophthalmologists for decades to treat various forms of ocular inflammation.

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells.

Background: In addition to their well-documented ocular therapeutic effects, glucocorticoids (GCs) can cause sight-threatening side-effects including ocular hypertension presumably via morphological and biochemical changes in trabecular meshwork (TM) cells. In the present study, we directly compared the glucocorticoid receptor (GR) potency for dexamethasone (DEX), fluocinolone acetonide (FA) and triamcinolone acetonide (TA), examined the expression of known GRalpha and GRbeta isoforms, and used gene expression microarrays to compare the effects of DEX, FA, and TA on the complete transcriptome in two primary human TM cell lines.

Methods: GR binding affinity for DEX, FA, and TA was measured by a cell-free competitive radio-labeled GR binding assay.

Strain-dependent increases in retinal inflammatory proteins and photoreceptor FGF-2 expression in streptozotocin-induced diabetic rats.

Purpose: Inflammation is thought to play a role in disease progression and vision loss in diabetic retinopathy (DR). However, the level of inflammation and the role of cytokines and growth factors in the early stages of this disease are poorly understood. Streptozotocin (STZ)-induced hyperglycemia in rats is widely used as a model of diabetic retinopathy, and therefore this model was used to better define the inflammatory response and the impact of the genetic background.

Intravitreal steroids for macular edema: the past, the present, and the future.

Macular edema, a condition usually associated with an underlying disease process, is a common cause of severe visual loss. There have been a variety of approaches to the treatment of macular edema; within the past few years, however, intravitreal corticosteroid treatments have emerged as an increasingly used treatment option for patients with macular edema. Intravitreal delivery allows the steroid to bypass the blood-retinal barrier, leading to a more concentrated dose of steroid for a prolonged period of time.

Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown.

Purpose: Recent clinical studies show that a single intravitreal injection of the corticosteroid triamcinolone acetonide (TAA) may reduce edematous retinal swelling and improve visual acuity in patients with diabetic macular edema (DME). In addition, clinical and experimental studies strongly suggest that blood-retinal barrier breakdown in diabetes is induced by vascular endothelial growth factor (VEGF). These results suggest that corticosteroids may modulate VEGF-mediated responses in vivo.

Effect of COX inhibitors on VEGF-induced retinal vascular leakage and experimental corneal and choroidal neovascularization.

The primary objective of this study was to evaluate the effect of cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), in two in vivo models of VEGF-dependent corneal and choroidal angiogenesis and two in vivo models of VEGF-mediated vascular leakage. Non-selective COX inhibitors (the NSAIDs indomethacin and flunixin, p.o.