Oral squamous cell cancer: early detection and the role of alcohol and smoking

Objective: Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. Data sources: A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010). Review Methods: In this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Results: The interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Conclusion: Published scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved

Drug Metabolism within the Brain Changes Drug Response: Selective Manipulation of Brain CYP2B Alters Propofol Effects

Drug-metabolizing cytochrome P450 (CYPs) enzymes are expressed in the liver, as well as in extrahepatic tissues such as the brain. Here we show for the first time that drug metabolism by a CYP within the brain, illustrated using CYP2B and the anesthetic propofol (2, 6-diisopropylphenol, Diprivan), can meaningfully alter the pharmacological response to a CNS acting drug. CYP2B is expressed in the brains of animals and humans, and this CYP isoform is able to metabolize centrally acting substrates such as propofol, ecstasy, and serotonin. Rats were given intracerebroventricularly (i.c.v.) injections of vehicle, C8-xanthate, or 8-methoxypsoralen (CYP2B mechanism-based inhibitors) and then tested for sleep time following propofol (80 mg/kg intraperitoneally). Both inhibitors significantly increased sleep-time (1.8- to 2-fold) and brain propofol levels, while having no effect on plasma propofol levels. Seven days of nicotine treatment can induce the expression of brain, but not hepatic, CYP2B, and this induction reduced propofol sleep times by 2.5-fold. This reduction was reversed in a dose-dependent manner by i.c.v. injections of inhibitor. Sleep times correlated with brain (r=0.76, P=0.0009), but not plasma (r=0.24, P=0.39) propofol concentrations. Inhibitor treatments increased brain, but not plasma, propofol levels, and had no effect on hepatic enzyme activity. These data indicate that brain CYP2B can metabolize neuroactive substrates (eg, propofol) and can alter their pharmacological response. This has wider implications for localized CYP-mediated metabolism of drugs, neurotransmitters, and neurotoxins within the brain by this highly variable enzyme family and other CYP subfamilies expressed in the brain