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1.
Adv Biol Regul ; 52(3): 389-405, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22884032

RESUMO

Epidemiological studies have established a positive correlation between cancer and metabolic disorders, suggesting that aberrant cell metabolism is a common feature of nearly all tumors. To meet their demand of building block molecules, cancer cells switch to a heavily glucose-dependent metabolism. As insulin triggers glucose uptake, most tumors are or become insulin-dependent. However, the effects of insulin and of other similar growth factors are not only limited to metabolic control but also favor tumor growth by stimulating proliferation and survival. A key signaling event mediating these metabolic and proliferative responses is the activation of the phosphatidylinositol-3 kinases (PI3K) pathway. In this review, we will thus discuss the current concepts of tumor metabolism and the opportunity of PI3K-targeted therapies to exploit the "sweet tooth" of cancer cells.


Assuntos
Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Proliferação de Células , Complicações do Diabetes/metabolismo , Dieta/efeitos adversos , Glucose/metabolismo , Humanos , Insulina/metabolismo , Modelos Biológicos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Transdução de Sinais
2.
Bioelectromagnetics ; 22(6): 419-28, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11536283

RESUMO

The ability of static and extremely low frequency (ELF) Magnetic Fields (MF) to interfere with neoplastic cell function has been evaluated. In vitro experiments were carried out to study the role of MF characteristics (intensity, frequency, and modulation) on two transformed cell lines (WiDr human colon adenocarcinoma and MCF-7 human breast adenocarcinoma) and one nontransformed cell line (MRC-5 embryonal lung fibroblast). Increase in cell death morphologically consistent with apoptosis was reported exclusively in the two transformed cell lines. Cell-death induction was observed with MF of more than 1 mT. It was independent of the MF frequency and increased when modulated MF (static with a superimposition of ELF at 50 Hz) were used. Based on the in vitro results, four different MF exposure characteristics were selected and used to treat nude mice xenografted with WiDr cells. The treatment of nude mice bearing WiDr tumors subcutaneously. with daily exposure for 70 min to MF for 4 weeks caused significant tumor growth inhibition (up to 50%) by the end of the treatment when modulated MF were used for at least 60% of the whole treatment period and the time-averaged total MF intensity was higher than 3.59 mT. No toxic morphological changes induced by exposure were observed in renewing, slowly proliferating, or static normal cells. A discussion on the possible biophysical mechanism at the base of the observed biological results is also offered.


Assuntos
Adenocarcinoma/patologia , Apoptose/efeitos da radiação , Neoplasias da Mama/patologia , Divisão Celular/efeitos da radiação , Neoplasias do Colo/patologia , Campos Eletromagnéticos , Magnetismo , Adenocarcinoma/ultraestrutura , Animais , Neoplasias da Mama/ultraestrutura , Linhagem Celular Transformada , Neoplasias do Colo/ultraestrutura , Feminino , Fibroblastos , Humanos , Marcação In Situ das Extremidades Cortadas , Rim/patologia , Rim/efeitos da radiação , Fígado/patologia , Fígado/efeitos da radiação , Pulmão , Camundongos , Camundongos Nus , Baço/patologia , Baço/efeitos da radiação , Transplante Heterólogo , Células Tumorais Cultivadas
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