Publications by authors named "Robert H Denlinger"
Toxicol Pathol
September 2014
Article Synopsis
- The study investigated the impact of dexamethasone alongside the gamma secretase inhibitor (GSI), PF-03084014, on goblet cell hyperplasia (GCH) in the intestines of Sprague-Dawley rats.
- Two dosing regimens were analyzed: a pretreatment with dexamethasone followed by GSI, and concurrent intermittent treatment with both substances.
- Results showed that dexamethasone reduced the severity of GCH temporarily, but there were safety concerns, including morbidity and mortality linked to high doses of GSI and dexamethasone coadministration.
Mol Cancer Ther
June 2010
Article Synopsis
- Aberrant Notch signaling is linked to cancer development, particularly in T-cell acute lymphoblastic leukemia (T-ALL), making gamma-secretase a key target for cancer therapy.
- PF-03084014, a selective gamma-secretase inhibitor, effectively reduces the Notch intracellular domain (NICD) levels and inhibits tumor cell growth, leading to cell cycle arrest and apoptosis in T-ALL cell lines.
- Studies also indicated that PF-03084014 has broad antitumor effects in various models while minimizing gastrointestinal toxicity, making it a promising candidate for treating Notch-dependent cancers, and it is currently in phase I clinical trials.
