Sosnovsky Lecturers

Thursday, March 6, 2014, 3:00pm

Professor Lawrence J. Marnett, Vanderbilt University

Targeting Cyclooxygenases as a Strategy for Improved Cancer Detection and Therapy

Significant reductions in mortality from cancer have been made in the past 25 years principally from reduced smoking and improved detection methods. Some notable achievements have been made in treating particular cancers but major breakthroughs in the treatment of most solid tumors remain elusive. The onset of molecularly targeted therapies offers hope for future advances but the heterogeneity of most late-stage tumors will reduce their efficacy. Early detection remains the most effective way to reduce cancer mortality. Advances in molecular imaging suggest that it may be possible to detect and profile cancers early in their development using agents targeted to specific molecules expressed in the cancers. Cyclooxygenase-2 (COX-2) is an important player in inflammation and is expressed at high levels in many cancers and t heir precursor lesions. Thus, COX-2 is a potentially general target for imaging cancer and pre-malignancy. This lecture will describe the chemistry, biochemistry an in vivo proof-of-concept for COX-2-targeting imaging of cancer. It will also describe attempts to target COX-2 for selective delivery of chemotherapeutic agents.

Location: Chemistry 180
Host: Prof. Sosnovsky

Friday, March 7, 2014, 3:00pm

Professor Lawrence J. Marnett, Vanderbilt University

Oxygenation of Endocannabinoids by Cyclooxygenase-2: Novel Bioactive Lipid and Therapeutic Opportunities

The active component of marijuana is 9-tetrahydrocannabinol (THC). THC mimics endogenous ligands (i.e., endocannabinoids) in binding to the cannabinoid receptors, CB1 and CB2. The two best-characterized endocannabinoids are the arachidonic acid derivatives, 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). 2-AG and AEA are substrates for oxygenation by cyclooxygenase-2 (COX-2) and are converted to prostaglandin glycerol esters and prostaglandin ethanolamide, respectively. These compounds exert potent activities by binding to receptors that appear distinct from CB receptors or prostaglandin receptors and thereby represent a novel class of bioactive lipids. The Marnett laboratory has developed a series of non-steroidal anti-inflammatory drug derivatives that selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation by COX-2. These compounds exhibit interesting pharmacological activities in vivosuch as anxiolytic activity and analgesic activity.

Location: Chemistry 180
Host: Prof. Sosnovsky


Thursday, April 26, 2012, 3:00pm

Peng Huang, University of Texas MD Anderson Cancer Center

Metabolic Alterations in Cancer: Mechanisms and Therapeutic Implications

Cancer metabolism is an important area of research.This lecture will focus on two major metabolic changes frequently observed in cancer cells: increased aerobic glycolysis (the Warburg effect) and oxidative stress. The potential mechanisms that contribute to these metabolic alterations, including oncogenic signals, mitochondrial dysfunction, and tumor tissue microenvironment will be discussed.  The role of such metabolic alterations in affecting cancer cell viability and drug sensitivity will also be explored in the context of developing new therapeutic strategies to effectively and preferentially kill cancer cells.Special emphasis will focus on mitochondrial dysfunction as a key event that links malignant transformation to metabolic alterations, and the relevant biochemical basis for developing novel therapeutic strategies.

Location: Chemistry 180
Host: Prof. Sosnovsky

Friday, April 27, 2012, 3:00pm

Peng Huang, University of Texas MD Anderson Cancer Center

Novel Strategies to Target Metabolic Alterations in Cancer with Improved Therapeutic Selectivity

Increased glycolysis and oxidative stress are two prominent metabolic alterations in cancer cells.These biochemical changes may provide an important basis for developing new therapeutic strategies to selectively kill cancer cells. It is hypothesized that since cancer cells with mitochondrial dysfunction and compromised ability to produce ATP through oxidative phosphorylation may be more dependent on glycolysis for generation of ATP and metabolic intermediates for cell survival and proliferation, inhibition of this metabolic pathway by targeting the key glycolytic enzymes may preferentially impact cancer cells.Similarly, due to the active generation of reactive oxygen species (ROS), cancer cells are more dependent on antioxidants such as glutathione to counteract oxidative stress, rendering them highly vulnerable to redox-modulating agents.This seminar will focus on two metabolic intervention strategies for potential cancer treatment: (1) the use of glycolytic inhibitors such as 3-bromopyruvate and its analogs to block energy production in cancer cells, aiming at preferential killing of malignant cells with mitochondrial dysfunction, and (2) the use of redox-modulating agents such as PEITC to selectively target cancer cells with elevated ROS stress.Experimental evidence will be presented to illustrate the mechanisms of action of these two classes of compounds and their potential combination with conventional anticancer agents to improve therapeutic activity and overcome drug resistance.

Location: Chemistry 180
Host: Prof. Sosnovsky