This Core Component is focused on providing and coordinating the pharmacology support critical for the success of the clinical trial in Project 1 as well as many of the specific Laboratory Project goals proposed in this P01. The Pharmacology CORE will be responsible for determination of Celecoxib drug levels in plasma of patients as well as drug levels in BAL in order to assess compliance and tissue exposure levels of this COX-2 selective inhibitor. The efficacy of Celecoxib in reducing cyclooxygenase-2 activity will be assessed through determination of PGE2 levels in patient serum samples. The Pharmacology CORE will also provide dedicated phlebotomy service for the accurate collection and processing of plasma samples for preparation of peripheral blood mononuclear cells from patients for use in determining the relative activation status of NF-kB. We are also proposing that a new technique of determining overall ecosanoid metabolism be explored for use in the study of chemoprevention of lung cancer. This method, being developed in our lab at MDACC, uses LC/MS/MS electrospray ionization to simultaneously examine the relative content of LOX HETE products (5-, 8-, 11-, 12- and 15-HETE) as well as selected prostaglandins (e.g. PGD2 and PGE2) extracted from biological samples. The method has proven to be promising in pilot studies based on lung cancer cell extractions but needs to be further developed and validated before application to other Projects (such as Project 2) within this program project and possible application to measurement of other relative determinants of inflammation (e.g. epoxyeicosatrienoic acids; EETs) in actual patient tissues.)
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