Annals of medicine
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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.
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Genetic defects affecting the hypothalamic-pituitary-target organ axes can cause a variety of diseases involving restricted or broad disruptions of human development and physiology. At the level of the anterior pituitary gland, mutations in the genes encoding key transcription factors, hypothalamic releasing and inhibiting hormone receptors, and the pituitary hormones themselves, can all result in the loss of action of one or more of the specialized hormone-secreting cell types. ⋯ Mutations in the genes encoding the HESX1, PITX2, LHX3, LHX4, PROP1, PIT1, SF1, and TPIT developmental transcription factors are associated with combined pituitary hormone deficiency diseases. By contrast, deleterious alterations in the genes that encode hypothalamic releasing hormone receptors or pituitary hormones, such as the growth hormone releasing hormone receptor or growth hormone genes, usually result in phenotypes that reflect specific defects in the hormone-secreting capacities of individual anterior pituitary cell types.
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Pathophysiology of sepsis is characterised by a whole body inflammatory reaction and concurrent activation of the host's anti-inflammatory mechanisms. The balance between pro- and anti-inflammatory reactions is critical for the outcome of the patient. Strongly activated phagocytes and high levels of proinflammatory cytokines occur in patients who are at risk of developing circulatory shock and multiple organ dysfunction. ⋯ Such patients could possibly benefit from a mode of therapy aimed at modifying the course of inflammatory response. The use of inflammatory markers may also improve diagnosis of severe infection. The present review summarises the studies on markers of inflammation and immune suppression used, first, as predictors of organ dysfunction in patients with systemic inflammation, and, second, as indicators of infection in adults and neonates.