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Br J Cancer ; 80(7): 946-53, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10362101

RESUMO

Benzoporphyrin derivative monoacid (BPD-MA) photosensitization was examined for its effects on cellular adhesion of a human ovarian cancer cell line, OVCAR 3, to extracellular matrix (ECM) components. Mild BPD-MA photosensitization (approximately 85% cell survival) of OVCAR 3 transiently decreased adhesion to collagen IV, fibronectin, laminin and vitronectin to a greater extent than could be attributed to cell death. The loss in adhesiveness was accompanied by a loss of beta1 integrin-containing focal adhesion plaques (FAPs), although beta1 subunits were still recognized by monoclonal antibody directed against human beta1 subunits. In vivo BPD-MA photosensitization decreased OVCAR 3 adhesiveness as well. Photosensitized adhesion was reduced in the presence of sodium azide and enhanced in deuterium oxide, suggesting mediation by singlet oxygen. Co-localization studies of BPD-MA and Rhodamine 123 showed that the photosensitizer was largely mitochondrial, but also exhibited extramitochondrial, intracellullar, diffuse cytosolic fluorescence. Taken together, these data show that intracellular damage mediated by BPD-PDT remote from the FAP site can affect cellular-ECM interactions and result in loss of FAP formation. This may have an impact on long-term effects of photodynamic therapy. The topic merits further investigation.


Assuntos
Proteínas da Matriz Extracelular/metabolismo , Integrina beta1/biossíntese , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Animais , Catalase/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/efeitos da radiação , Óxido de Deutério/farmacologia , Feminino , Humanos , Integrina beta1/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/radioterapia , Porfirinas/metabolismo , Azida Sódica/farmacologia , Superóxido Dismutase/farmacologia
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