Denileukin diftitox, a genetically engineered fusion protein combining the enzymatically active domains of diphtheria toxin and the full-length sequence for interleukin-2 (IL-2), efficiently targets lymphoma cells expressing the high-affinity IL-2 receptor (IL-2R) consisting of the alpha/p55/CD25, beta/p75/CD122, and gamma/p64/CD132 chains. In vitro studies demonstrated that the retinoid X rece...

Acquired drug resistance is a major obstacle in cancer therapy. As for many other drugs, this is also the case for gemcitabine, a nucleoside analogue with activity against non-small cell lung cancer (NSCLC). Here, we evaluate the ability of bexarotene to modulate the acquisition and maintenance of gemcitabine resistance in Calu3 NSCLC models. In the prevention model, Calu3 cells treated repeate...

A detailed understanding of the stability an active pharmaceutical ingredient and a dosage form is essential for drug-development process safe effective use medicines. Photostability testing as inherent part studies provides valuable knowledge on degradation pathways structures products generated under UV irradiation. particularly important topically administered drugs, they are more exposed to...

One of the prime features of Alzheimer's disease (AD) is the excessive accumulation of amyloid-β (Aβ) peptides in the brain. Several recent studies suggest that this phenomenon results from the dysregulation of cholesterol homeostasis in the brain and impaired bidirectional Aβ exchange between blood and brain. These mechanisms appear to be closely related and are controlled by the blood-brain b...

Activation of retinoid X receptors (RXRs) has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [(11)C]CO2 fixation and preliminary positron emission tomography (PET) neuroimaging that demonstra...

Cramer et al. (Reports, 23 March 2012, p. 1503; published online 9 February 2012) reported that bexarotene rapidly reduces b-amyloid (Ab) levels and plaque burden in two mouse models of Ab deposition in Alzheimer’s disease (AD). We now report that, although bexarotene reduces soluble Ab40 levels in one of the mouse models, the drug has no impact on plaque burden in three strains that exhibit Ab...

Alzheimer’s disease (AD) is a highly prevalent disorder for which there are no effective therapies. Accumulation of amyloid (A ) peptides in the brain is associated with impaired cognition and memory, pronounced inflammatory dysregulation, and subsequent amyloid plaque deposition. Thus, drugs that promote the clearance of A peptides and resolution of inflammation may represent viable therapeuti...

We report results of a randomized, vehicle-controlled, bilateral comparison pilot study of bexarotene gel 1% with narrowband UVB (NBUVB) phototherapy for moderate to severe psoriasis. In all, 9 patients applied drug or vehicle gel to comparable target lesions up to twice daily for 10 weeks. NBUVB was initiated 2 weeks after topical therapy began. Limitations include small sample size and interi...

BACKGROUND Concurrent and sequential administration of combinations of budesonide, bexarotene, suberoylanilide hydroxamic acid (SAHA) and atorvastatin were evaluated in A/J mice for prevention of lung tumors initiated by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol, NNK). MATERIALS AND METHODS Individual drugs and their combinations were administered for 26 weeks after NNK initiation. For s...

BACKGROUND Matrix metalloproteinase-9 (MMP-9) over-expression disrupts the blood-brain barrier (BBB) in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction. METHODS A total of 180 rats were rand...