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Tobacco smoking is the main single cause of human cancer worldwide (IARC 2004) and the largest cause of death and disease. It is the key cause of lung cancer, and a major cause of cancers of the oral cavity, pharynx, nasal cavity, larynx, oesophagus, stomach, pancreas, uterine cervix, kidney and bladder, as well as of myeloid leukemia. In high-resource countries, tobacco smoking causes approximately 30 % of all human cancers (Doll and Peto 2005). In many medium- and low-income countries, the burden of tobacco-related cancer is still lower, given the relatively recent start of the epidemics of smoking, which will however result in a greater numbers of cancer in the future, in the absence of adequate intervention to control tobacco. [ABSTRACT FROM AUTHOR]

Opioid tolerance can limit the clinical utility of opioids for pain management. It is a neuroadaptive response to the repeated administration of an opioid. Opioid tolerance is predominantly of the pharmacological (nonassociative) and pharmacodynamic type. Possible contributions to tolerance at the receptor level include receptor desensitization, internalization, and recycling. Alterations of G proteins, other intracellular signaling cascades and receptor–receptor interactions also may be involved. At the systems level, opioid-induced hyperalgesia, N-methyl-d-aspartate receptor mechanisms, activation of the immune system, and genetic factors have all been implicated. Each of these potential contributors is discussed. Establishing the mechanism(s) of tolerance remains an elusive as well as a continuing challenge. However, some of the mechanisms discussed in this chapter appear to have the potential to provide new approaches for reducing or eliminating the development of opioid tolerance. [ABSTRACT FROM AUTHOR]