Annals of medicine
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The metabolism and elimination of drugs is mainly mediated by cytochrome P450 (CYP) enzymes, aided by conjugative enzymes and transport proteins. An integral aspect of this elimination process is the induction of drug metabolism through activation of gene expression of metabolic and transport proteins. ⋯ This review outlines the basic properties of CAR and PXR, their ligands and target genes, and the mechanisms of the induction process. The implications of nuclear receptor-mediated induction for drug research are also discussed.
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Review
Targeting epidermal growth factor receptor signaling: early results and future trends in oncology.
Epidermal growth factor receptor (EGFR), a member of a family of membrane receptors with tyrosine kinase activity, is emerging as a target candidate for anti-cancer therapy, due to its overexpression in many carcinomas and its relationship with several hallmark properties of malignant behavior such as continuous cell proliferation, escape from apoptosis, cell migration and angiogenesis. Specially appealing is the overexpression of EGFR in tumors such as lung, colon, kidney and head and neck carcinomas which are mostly resistant to current chemotherapy. Several anti-EGFR agents are already in clinical testing: small molecule tyrosine kinases inhibitors, monoclonal antibodies and cancer vaccines. ⋯ Future investigations should clarify optimal schedules and explore combinations with standard onco-specific treatments. The ultimate challenge will be to combine diverse therapeutic interventions dealing with a regulatory system which is complex, highly redundant and robust. Combinations between vaccines and antibodies, or between vaccines to several molecular components of the system should be evaluated, as well as combinations between inhibitors of the EGFR signaling pathway and inhibitors of other regulatory pathways related to cell proliferation, apoptosis and angiogenesis.
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Surfactant protein A (SP-A) polymorphisms are associated with susceptibility to respiratory distress syndrome (RDS). According to present hypothesis the association between SP-A polymorphisms and RDS may not be applicable to the entire population of premature infants. ⋯ In twins, the association between SP-A polymorphism and RDS is different from that seen in premature singleton infants. The factor associated with SP-A genotype-specific susceptibility to RDS appears to be related to the size of uterus and the length of gestation at birth.
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It is well established that the obese gene product, leptin is an important circulating satiety factor that signals nutritional status to specific hypothalamic nuclei involved in body weight regulation. However, evidence is accumulating that, in addition to its pivotal role as an adiposity signal, leptin is a multi-faceted hormone that plays an important role in a plethora of CNS functions. In this review we summarize the recent advances made in leptin biology, with particular focus on its potential role as a cognitive enhancer and antiepileptic agent in the hippocampus.