RESUMO
BACKGROUND: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. METHODS: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. RESULTS: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. CONCLUSIONS: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.
Assuntos
Anoctaminas/genética , Anoctaminas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Receptores ErbB/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas de Transferência de Fosfolipídeos/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/uso terapêutico , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese , Carcinoma Ductal Pancreático/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Intervalo Livre de Doença , Doxiciclina/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/farmacologia , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Ensaio Tumoral de Célula-Tronco , GencitabinaRESUMO
The crystallization kinetics in BaTiO3 synthesis from hydrate precursors via microwave-assisted heating (MWH) were investigated. The structural and chemical features of powders synthesized via MWH and conventional heating (CH) were compared. The charged radicals generated under microwave irradiation were identified by chemical analysis and real-time charge flux measurements. Using Ba(OH)2âH2O (BH1), Ba(OH)2 (BH0), and BaCO3 (BC) as the precursors for a Ba source, and TiO2â4H2O (TH) for a Ti source, three different mixture samples, BH1TH (BH1 + TH), BH0TH (BH0 + TH), and BCTH (BC + TH), were heat-treated in the temperature range of 100-900 °C. BaTiO3 powders were synthesized at temperatures as low as 100 °C when sample BH1TH was subjected to MWH. Based on the growth exponent (n), the synthesis reactions were inferred to be diffusion-controlled processes (3 ≤ n ≤ 4) for MWH and interface-controlled processes (2 ≤ n ≤ 3) for CH. Current densities of approximately 0.073 and 0.022 mA/m2 were measured for samples BH1TH and BH0TH, respectively, indicating the generation of charged radicals by the interaction between the precursors and injected microwaves. The radicals were determined as OH- groups by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy.
RESUMO
This study investigated the effects of heat treatment on changes in the nanostructure of amorphous silicon oxycarbide thin films. Hydrogenated amorphous silicon oxycarbide (a-Si0.6C0.3O0.1:H) thin films were prepared via plasma-enhanced chemical vapor deposition. The films were subjected to post-deposition heat treatments via microwave-assisted heating, which resulted in the formation of nanocrystals of SiC and Si in the a-Si0.6C0.3O0.1:H matrix at temperatures as low as ~800 °C. The crystallization activation energies of SiC and Si were determined to be 1.32 and 1.04 eV, respectively lower than those obtained when the sample was heat-treated via conventional heating (CH). Microwaves can be used to fabricate nanocrystals at a temperature approximately ~300 °C lower than that required for CH. The optical and nanostructural evolutions after post-deposition heat treatments were examined using photoluminescence (PL) and X-ray diffraction. The position of the PL peaks of the nanocrystals varied from ~425 to ~510 nm as the annealing temperature was increased from 800 to 1000 °C. In this study the optical band gap of SiC and Si varied from ~2.92 to ~2.40 eV and from ~2.00 to ~1.79 eV, as the size of the SiC and Si nanocrystals varied with respect to the heating temperature and isothermal holding time, respectively.