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2.
Br J Cancer ; 109(2): 351-9, 2013 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-23799854

RESUMO

BACKGROUND: Breast cancer is the most common malignancy in women. Although chemotherapeutic agents, such as paclitaxel, are effective treatments for the majority of breast cancer patients, recurrence is frequent and often leads to death. Thus, there is an urgent need to identify novel therapeutic targets that sensitise tumour cells to existing chemotherapy agents. METHODS: The levels of leukotriene B4 receptor-2 (BLT2) in multidrug-resistant MCF-7/DOX cells were determined using quantitative PCR and FACS analysis. The potential role of BLT2 in the paclitaxel resistance of MCF-7/DOX cells was assessed using a pharmacological inhibitor and small interfering RNA knockdown, and the BLT2-associated resistance mechanism was assessed. RESULTS: The expression levels of BLT2 were markedly upregulated in MCF-7/DOX cells. The inhibition of BLT2 by pre-treatment with LY255283 or siBLT2 knockdown significantly sensitised MCF-7/DOX cells to paclitaxel and induced significant levels of apoptotic death, suggesting that BLT2 mediates paclitaxel resistance. We also demonstrated that BLT2-induced paclitaxel resistance was associated with the upregulation of P-glycoprotein. Finally, co-treatment with a BLT2 inhibitor and paclitaxel markedly reduced tumour growth in an MCF-7/DOX in vivo model. CONCLUSION: Together, our results demonstrate that BLT2 is a novel therapeutic target that sensitises drug-resistant breast cancer cells to paclitaxel.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Paclitaxel/uso terapêutico , Receptores do Leucotrieno B4/fisiologia , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos/genética , Sinergismo Farmacológico , Feminino , Humanos , Antagonistas de Leucotrienos/administração & dosagem , Antagonistas de Leucotrienos/farmacologia , Camundongos , Camundongos Nus , Paclitaxel/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Receptores do Leucotrieno B4/antagonistas & inibidores , Receptores do Leucotrieno B4/genética , Tetrazóis/administração & dosagem , Tetrazóis/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Science ; 280(5369): 1589-92, 1998 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-9616119

RESUMO

The free modulation of interlayer distance in a layered high-transition temperature (high-Tc) superconductor is of crucial importance not only for the study of the superconducting mechanism but also for the practical application of high-Tc superconducting materials. Two-dimensional (2D) superconductors were achieved by intercalating a long-chain organic compound into bismuth-based high-Tc cuprates. Although the intercalation of the organic chain increased the interlayer distance remarkably, to tens of angstroms, the superconducting transition temperature of the intercalate was nearly the same as that of the pristine material, suggesting the 2D nature of the high-Tc superconductivity.

4.
J Colloid Interface Sci ; 177(1): 198-207, 1996 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10479432

RESUMO

Morphology and internal structure of monodispersed pseudocubic hematite (alpha-Fe(2)O(3)) particles produced by the gel-sol method were investigated in detail through high-resolution electron microscopy on their thin sections prepared with an ultramicrotome. It was confirmed that the c-axis of a particle corresponded to the longest diagonal axis of the particle. High-resolution electron micrographs of thin sections directly revealed the polycrystallinity of the particles and clearly showed the arrangement of the subcrystals and their crystallographic orientations. The subcrystals near the surface of a particle were of a rectangular shape bound by the $ \{01\overline{1}2\} $ planes, and their width was about 12-16 nm with small variation of the length depending on the position in a particle. The subcrystals were radially developed from the center of a particle in all directions, but most preferentially in the longest diagonal axis of a particle. Besides, it was found from EDX analysis that the adsorbed Cl(-) ions as a shape controller were incorporated into the pseudocubic hematite particles during their growth.

6.
Phys Rev Lett ; 68(12): 1920-1922, 1992 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-10045254
7.
Phys Rev Lett ; 68(1): 134, 1992 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-10045132
8.
Phys Rev Lett ; 66(18): 2312-2315, 1991 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-10043453
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