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Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen
Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in …
Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky
Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky
Department of Neurology Faculty Papers
BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.
METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.
RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …
Ariel - Volume 10 Number 2, Edward G. Zurad, Jim O'Brien, Meg Trexler, Eric Singel, Jeffrey Banyas, Al Signorella, Stuart Singer
Ariel - Volume 10 Number 2, Edward G. Zurad, Jim O'Brien, Meg Trexler, Eric Singel, Jeffrey Banyas, Al Signorella, Stuart Singer
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