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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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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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.
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Severe sepsis is a common disease process affecting some 2-11% of hospital admissions in the US. Severe sepsis and septic shock are associated with considerable morbidity and mortality, and account for a large part of intensive care unit costs. ⋯ In the last couple of years these advances have come to fruition with the development of a drug, drotrecogin alfa, which specifically reduces mortality from this all too often fatal disease. While intensive early resuscitation remains the cornerstone of management, new approaches are beginning to form part of sepsis management protocols and will lead to improved outcomes for patients with this disease process.
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Severe sepsis and septic shock are relatively common problems in intensive care. The mortality in septic shock is still high, and the main causes of death are multiple organ failure and refractory hypotension. Impaired tissue perfusion due to hypovolemia, disturbed vasoregulation and myocardial dysfunction contribute to the multiple organ dysfunction. ⋯ In septic shock, vasopressin levels are low, and therefore, vasopressin has been advocated as a vasopressor. Its effectiveness and safety have not yet been documented, and so far it is regarded as an experimental treatment Recent data support the use of corticosteroid, at least in some of the patients with septic shock. Also, activated protein C, a drug with anti-inflammatory and antithrombotic properties, decreases mortality in patients with septic shock.