RESUMO
A miniaturized taste sensor chip was designed for use in a portable-type taste sensing system. The fabricated sensor chip (40 mm × 26 mm × 2.2 mm) has multiple taste-sensing sites consisting of a poly(hydroxyethyl methacrylate) hydrogel with KCl as the electrolyte layer for stability of the membrane potential and artificial lipid membranes as the taste sensing elements. The sensor responses to the standard taste substances showed high accuracy and good reproducibility, which is comparable with the performance of the sensor probe of the commercialized taste sensing system. Thus, the fabricated taste sensor chip could be used as a key element for the realization of a portable-type taste sensing system.
Assuntos
Técnicas Biossensoriais/instrumentação , Miniaturização/instrumentação , Paladar , Calibragem , Desenho de Equipamento , Modelos Lineares , Lipídeos/química , Membranas Artificiais , Reprodutibilidade dos TestesRESUMO
The prognosis of patients with pancreatic cancer is very poor because of late diagnosis and the lack of response to various therapies. Pancreatic cancer is generally resistant to chemotherapy and is highly fatal. Gemcitabine (GEM) appears to be the only effective agent for treatment of pancreatic cancer. However, a high level of inherent and acquired tumor resistance makes the clinical impact of GEM modest. Proteomic differential display analysis for GEM-sensitive human pancreatic adenocarcinoma cell line KLM1 and GEM-resistant KLM1-R cells by using two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry produced 33 protein spots. Of these, 23 were up-regulated and 10 were down-regulated in KLM1-R compared to KLM1 cells. The up-regulated proteins include acidic leucine-rich nuclear phosphoprotein 32 family member A, reticulocalbin-1, gamma-synuclein, microtubule-associated protein RP/EB family, sialic acid synthase, peptidyl-prolyl cis-trans isomerase A, far upstream element-binding protein 2 and catalase. The down-regulated proteins include far upstream element-binding protein 1, gamma-synuclein, galectin-1 and stathmin. Two spots of heat-shock protein 27 were up-regulated in KLM1-R cells. These results suggest an important complementary role for proteomics in the identification of proteins which may play a role in the poor response of pancreatic cancer to GEM.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pancreáticas/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Regulação para Baixo , Eletroforese em Gel Bidimensional , Humanos , Espectrometria de Massas , Proteômica , Regulação para Cima , GencitabinaRESUMO
BACKGROUND: Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine: Gemzar) (GEM) appears to be the only effective anticancer drug for pancreatic cancer, but it has little impact on outcome due to a high level of inherent and acquired tumor resistance. Our previous proteomic study demonstrated that the expression of three spots of heat-shock protein 27 (HSP27) was increased in GEM-resistant pancreatic cancer cells and could play a role in determining the sensitivity of pancreatic cancer to GEM. MATERIALS AND METHODS AND RESULTS: In the present study, using one-dimensional and two-dimensional Western blotting, we elucidated that these three spots of HSP27 were phosphorylated in GEM-resistant pancreatic cancer cell line, KLM1-R. CONCLUSION: Phosphorylated HSP27 may play an important role in the resistance to GEM, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with GEM.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Proteínas de Choque Térmico HSP27/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Western Blotting , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Eletroforese em Gel Bidimensional , Humanos , Fosforilação , Isoformas de Proteínas , Regulação para Cima , GencitabinaAssuntos
Antimetabólitos Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Proteínas de Choque Térmico HSP27/antagonistas & inibidores , Interferon gama/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Humanos , Chaperonas Moleculares , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
Pancreatic cancer remains a devastating disease and >96% of patients with pancreatic cancer do not survive for more than 5 years. Gemcitabine (2'-deoxy-2'-difluoro-deoxycytidine: Gemzar) appears to be the only clinically effective drug for pancreatic cancer, but it has little impact on outcome. Proteomic analysis of gemcitabine-sensitive cells (KLM1) and resistant pancreatic cells (KLM1-R) was performed to identify target proteins of the gemcitabine. We found seven proteins, HSP27, peroxiredoxin 2, endoplasmic reticulum protein ERp29 precursor, 6-phosphogluconolactonase, triosphospate isomerase, alpha enolase, and nucleophosmine that could play a role in determining the sensitivity of pancreatic cancer to gemcitabine. We knocked down HSP27 in KLM1-R and the sensitivity to gemcitabine was restored. In addition, increased HSP27 expression in tumor specimens was related to higher resistibility to gemcitabine in patients of pancreatic cancer. HSP27 may play an important role in the resistibility to gemcitabine, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with gemcitabine.
