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1.
EMBO Mol Med ; 13(7): e12872, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34062049

RESUMO

Radiotherapy (RT) plus the anti-EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR-9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT-induced cell death. Mechanistically, by targeting KLF5, miR-9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo. Intriguingly, high miR-9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR-9 expression correlated with Sp1 mRNA levels and high miR-9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR-9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy.


Assuntos
Neoplasias de Cabeça e Pescoço , MicroRNAs , Linhagem Celular Tumoral , Cetuximab/farmacologia , Receptores ErbB/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
2.
Sensors (Basel) ; 12(12): 17023-45, 2012 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-23235445

RESUMO

In this work we report on metal oxide (MOX) based gas sensors, presenting the work done at the SENSOR laboratory of the CNR-IDASC and University of Brescia, Italy since the 80s up to the latest results achieved in recent times. In particular we report the strategies followed at SENSOR during these 30 years to increase the performance of MOX sensors through the development of different preparation techniques, from Rheotaxial Growth Thermal Oxidation (RGTO) to nanowire technology to address sensitivity and stability, and the development of electronic nose systems and pattern recognition techniques to address selectivity. We will show the obtained achievement in the context of selected applications such as safety and security and food quality control.


Assuntos
Metais/isolamento & purificação , Nanoestruturas , Óxidos/isolamento & purificação , Análise de Alimentos , Qualidade dos Alimentos , Gases/química , Itália , Nanofios/química
3.
Beilstein J Nanotechnol ; 3: 368-77, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23016141

RESUMO

Surface coating with an organic self-assembled monolayer (SAM) can enhance surface reactions or the absorption of specific gases and hence improve the response of a metal oxide (MOx) sensor toward particular target gases in the environment. In this study the effect of an adsorbed organic layer on the dynamic response of zinc oxide nanowire gas sensors was investigated. The effect of ZnO surface functionalisation by two different organic molecules, tris(hydroxymethyl)aminomethane (THMA) and dodecanethiol (DT), was studied. The response towards ammonia, nitrous oxide and nitrogen dioxide was investigated for three sensor configurations, namely pure ZnO nanowires, organic-coated ZnO nanowires and ZnO nanowires covered with a sparse layer of organic-coated ZnO nanoparticles. Exposure of the nanowire sensors to the oxidising gas NO(2) produced a significant and reproducible response. ZnO and THMA-coated ZnO nanowire sensors both readily detected NO(2) down to a concentration in the very low ppm range. Notably, the THMA-coated nanowires consistently displayed a small, enhanced response to NO(2) compared to uncoated ZnO nanowire sensors. At the lower concentration levels tested, ZnO nanowire sensors that were coated with THMA-capped ZnO nanoparticles were found to exhibit the greatest enhanced response. ΔR/R was two times greater than that for the as-prepared ZnO nanowire sensors. It is proposed that the ΔR/R enhancement in this case originates from the changes induced in the depletion-layer width of the ZnO nanoparticles that bridge ZnO nanowires resulting from THMA ligand binding to the surface of the particle coating. The heightened response and selectivity to the NO(2) target are positive results arising from the coating of these ZnO nanowire sensors with organic-SAM-functionalised ZnO nanoparticles.

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