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Does nicotine exposure inhibit convective drug delivery? 

Principal Investigator: Ugur Ozerdem

Lung cancer remains the leading cause of cancer death in both men and women in California. Despite aggressive efforts, drug treatments are unsatisfactory and survival rates dismal. One of the causes of ineffectiveness of the chemotherapy results from the high pressure within the tumor, which prevents the drugs in the tiny blood vessels to flow into the core of the tumor particularly into the fluid between the tumor cells which is called interstitial fluid. In lung cancer, the interstitial fluid pressure (IFP) is higher than normal lung tissue. We measure IFP with high precision in lung cancer by using novel methods (transducer-tipped catheter method and other novel bioengineering tools). The mechanisms that determine the increased tumor IFP are not fully understood. An increase in IFP causes inefficient transport of drugs by decreasing flow of drugs from the tiny blood vessels into the tissues

The ideas and experiments in this research plan are designed to identify the mechanism by which the pressure in the tumor increases in response to nicotine. We propose to unveil a novel adverse effect of nicotine exposure by which IFP is increased, which consequently reduces the flow of drugs into the lung cancer. The proposed research is focused on a novel, potentially adverse effect of nicotine exposure in lung cancer; and is relevant to “Lung Cancer” primary research priority of TRDRP.

The benefits of the proposed research will be two-fold: First, patients receiving any drug could benefit from improved drug delivery by avoiding continuous primary or second hand smoke exposure, which contains nicotine. This newly discovered detrimental effect (reduction of drug delivery) caused by nicotine will be unveiled as an additional public health problem related to smoking. Second, we propose to stop nicotine-driven drug delivery problems by inhibiting pericytes (Rouget cells, mural cells, or perivascular cells) in lung cancer tissues through their nicotinic acetylcholine receptors.