Antitumoral efficacy of DNA nanoparticles in murine models of lung cancer and pulmonary metastasis.

Polyethylenimine (PEI)-DNA complexes are nanoparticles that are able to efficiently transfer plasmids to the lungs. Interleukin-12 (IL12) gene transfer using PEI may represent an important strategy for lung cancer treatment. In this study, we evaluated the antitumoral efficacy of the administration of PEI-DNA nanoparticles carrying IL12 gene (PEI-IL12) for the treatment of lung cancer and pulmonary metastases in animal models. After inoculation of tumor cells, mice were treated intravenously with a single dose of PEI-IL12, PEI nanoparticles carrying the reporter gene beta-galactosidase (PEI-LacZ) or vehicle. Transgene expression, survival rates and immune response were analyzed in both models. Administration of PEI-LacZ and PEI-IL12 nanoparticles controlled tumor growth and prolonged survival times in both animal models. Although PEI-IL12 and PEI-LacZ administration showed similar antitumoral effects in the lung cancer model, the efficacy of PEI-IL12 was significantly superior in the inhibition of the development of pulmonary metastases. Furthermore, the administration of PEI-DNA nanoparticles results in the production of high levels of proinflammatory cytokines. Our results showed that PEI-DNA nanoparticles are an efficient vector for mediating gene transfer to the lungs, are a potent inducer of the innate immune response and represents an interesting strategy for the treatment of bronchogenic carcinoma and metastatic lung carcinoma.

[Clinical manifestations associated with antiphospholipid antibodies]. / Manifestaciones clínicas asociadas a anticuerpos antifosfolípido.

The antiphospholipid antibodies are immunoglobulins able to join negative charge phospholipids. The have been related to a great variety of conditions, specially among connective tissue illness although the idiopathic form seems to be the most frequent. Their presence must be ruled out in cases of young patients with stroke, deep veins thrombosis, acute heart attack and woman suffer multiple abortions and foetal death. These antibodies appear to be related to different clinical entities like Sneddon syndrome. Evans syndrome, "chorea gestationis", migraine. The laboratory determinations are based in direct methods (ELISA, RIA, ...) as well as in indirect ones (activated partial thromboplastin time, reptilase time, ...). The appropriate management and treatment may be based upon clinical expression, in case of arterial thrombosis (type II APS), or deep vein thrombosis (Type II) long term anticoagulation is indicated; Association with pentoxifylline in the case of retinal thrombosis (type IIIa), Stroke (type IIIb) cases may require long term anticoagulation as well as aspirin. Type IV cases are better managed with an individualised treatment.