RESUMO
In contrast to most traditional cell culture systems, spheroids represent a unique opportunity to recapitulate aspects of cell homeostasis and as such better reflect in vivo tumor biology. This review highlights recent spheroid-based studies which have defined a role for intercellular adhesion in dictating cellular fate. Critical roles for adhesion molecules, such as the integrin and cadherin families, have been established. In addition, it appears that components of the signaling pathways that control cellular proliferation may also influence the cellular decision to live or die. Further complexity arises from the action of soluble factors, like epidermal growth factor, and three-dimensional culture systems are providing insights into how integration of these multiple signals is achieved. Given that cellular adhesion may serve as a regulator of apoptosis, and in particular that correct receptor engagement can activate signaling pathways promoting cell survival, additional implications for our understanding of tumor biology are discussed.
Assuntos
Comunicação Celular , Técnicas de Cultura de Células/métodos , Neoplasias Experimentais/patologia , Neoplasias/patologia , Esferoides Celulares/patologia , Animais , Apoptose , Adesão Celular , Sobrevivência Celular , HumanosAssuntos
Marca-Passo Artificial , Animais , Arritmias Cardíacas/terapia , Cães , Eletrocardiografia , Eletrodos Implantados , HumanosAssuntos
Taquicardia/terapia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/terapia , Flutter Atrial/tratamento farmacológico , Flutter Atrial/terapia , Glicosídeos Digitálicos/uso terapêutico , Cardioversão Elétrica , Sistema de Condução Cardíaco , Humanos , Lidocaína/uso terapêutico , Ligadura , Neostigmina/uso terapêutico , Marca-Passo Artificial , Fenitoína/uso terapêutico , Propranolol/uso terapêutico , Quinidina/uso terapêutico , Taquicardia/tratamento farmacológico , Taquicardia Paroxística/tratamento farmacológico , Taquicardia Paroxística/terapia , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/terapia , Síndrome de Wolff-Parkinson-White/tratamento farmacológico , Síndrome de Wolff-Parkinson-White/cirurgia , Síndrome de Wolff-Parkinson-White/terapiaRESUMO
3H-d-amphetamine (5 mg/kg, free base) was injected i.p. to male and non-pregnant female mice and to pregnant female mice on day 16 of gestation. The tissue levels of amphetamine were examined as a function of time. Peak concentrations in matured tissues occurred at 15 min, those in placenta, whole fetus, fetal brain and liver at 1 hr. No notable differences were detected in tissue levels of amphetamine in males and non-pregnant females. Disappearance of amphetamine from tissues of pregnant animals was slower than those of other groups. At 15 min, the fetal brain and liver accumulated 1/6 amounts of amphetamine compared to corresponding maternal tissues. Pregnant animals excreted significantly lower amount of total radioactivity compared to non-pregnant females. It is concluded that amphetamine was transported across the placenta and that the lower concentrations in fetal tissues compared to maternal tissues appear to be due to several physico-chemical factors that regulate the transplacental transfer of a foreign chemical compound.