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1.
PLoS One ; 11(7): e0159716, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27463372

RESUMO

CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Receptores de Hialuronatos/imunologia , Macrófagos/imunologia , Animais , Linhagem Celular Tumoral , Citocinas/genética , Citocinas/metabolismo , Humanos , Camundongos , Camundongos SCID , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Fagocitose
2.
Nanoscale Res Lett ; 7(1): 397, 2012 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-22805684

RESUMO

Silicon nanoparticles of three types (oxide-terminated silicon nanospheres, micron-sized hydrogen-terminated porous silicon grains and micron-size oxide-terminated porous silicon grains) were incorporated into silica aerogels at the gel preparation stage. Samples with a wide range of concentrations were prepared, resulting in aerogels that were translucent (but weakly coloured) through to completely opaque for visible light over sample thicknesses of several millimetres. The photoluminescence of these composite materials and of silica aerogel without silicon inclusions was studied in vacuum and in the presence of molecular oxygen in order to determine whether there is any evidence for non-radiative energy transfer from the silicon triplet exciton state to molecular oxygen adsorbed at the silicon surface. No sensitivity to oxygen was observed from the nanoparticles which had partially H-terminated surfaces before incorporation, and so we conclude that the silicon surface has become substantially oxidised. Finally, the FTIR and Raman scattering spectra of the composites were studied in order to establish the presence of crystalline silicon; by taking the ratio of intensities of the silicon and aerogel Raman bands, we were able to obtain a quantitative measure of the silicon nanoparticle concentration independent of the degree of optical attenuation.

3.
Nanoscale Res Lett ; 7(1): 378, 2012 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-22776697

RESUMO

: We report that porous silicon acoustic Bragg reflectors and AlN-based transducers can be successfully combined and processed in a commercial solidly mounted resonator production line. The resulting device takes advantage of the unique acoustic properties of porous silicon in order to form a monolithically integrated bulk acoustic wave resonator.

4.
Nanotechnology ; 22(30): 305402, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21719971

RESUMO

We report on the interaction of silicon nanocrystals with water/alcohol solutions which results in their complete oxidation, the hydrolysis of water and hydrogen generation in amounts close to the ideal scenario. Water acts as an oxidizer while alcohol is required for efficient wetting of nanosilicon. This process results in the formation of silicon-based alcogel which can be further transferred to aerogel.

5.
J Med Chem ; 54(1): 312-9, 2011 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-21128645

RESUMO

The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.


Assuntos
Antineoplásicos/síntese química , Ftalazinas/síntese química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazóis/síntese química , Administração Oral , Antineoplásicos/química , Antineoplásicos/farmacologia , Aurora Quinase B , Aurora Quinases , Disponibilidade Biológica , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Ftalazinas/química , Ftalazinas/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Relação Estrutura-Atividade
6.
J Med Chem ; 51(15): 4465-75, 2008 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-18630890

RESUMO

Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties of each parent and compares favorably to a previously reported Aurora inhibitor, 39 (VX-680). The inhibitor exhibits low nanomolar potency against both Aurora A and Aurora B enzymes, excellent cellular potency (IC50 < 100 nM), and good oral bioavailability. Phenotypic cellular assays show that both Aurora A and Aurora B are inhibited at inhibitor concentrations sufficient to block proliferation. Importantly, the cellular activity translates to potent inhibition of tumor growth in vivo. An oral dose of 5 mg/kg QD is well tolerated and results in near stasis (92% TGI) in an HCT116 mouse xenograft model.


Assuntos
Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Administração Oral , Animais , Aurora Quinase A , Aurora Quinase B , Aurora Quinases , Benzimidazóis/síntese química , Benzimidazóis/química , Disponibilidade Biológica , Linhagem Celular Tumoral , Cristalografia por Raios X , Cães , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Humanos , Lactamas/química , Camundongos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/síntese química , Proteínas Serina-Treonina Quinases/metabolismo , Ratos
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