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1.
Polymers (Basel) ; 13(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672060

RESUMO

Typical polyol-based synthesis of silver nanowire employs insulating polymer as a surfactant for the silver nanowire growth, which limits direct contact between each nanowire and thus its optoelectronic properties. We herein demonstrate that a simple solvent treatment effectively removes the insulating polymer around Ag NWs, leading to significantly decreased sheet resistance (~12 Ω/sq) with an increased transmittance (81% @ T550), as compared to other post-treatments. We successfully demonstrate the transparent film heaters using the solvent-treated Ag NWs network, which rapidly exhibited 150 °C under a bias of 5 V. Flexible film heaters on plastic substrate is also demonstrated, suggesting a great potential of the solvent treatment process of Ag NWs for flexible transparent electrode and film heater applications.

2.
Polymers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158285

RESUMO

For the immediate detection of strong gaseous alkalis and acids, colorimetric textile sensors based on halochromic dyes are highly valuable for monitoring gas leakages. To date, colorimetric textile sensors for dual-gas detection have usually been fabricated by electrospinning methods. Although nanofibrous sensors have excellent pH sensitivity, they are difficult to use commercially because of their low durability, low productivity, and high production costs. In this study, we introduce novel textile sensors with high pH sensitivity and durability via a facile and low-cost screen-printing method. To fabricate these textiles sensors, Dye 3 and RhYK dyes were both incorporated into a polyester fabric. The fabricated sensors exhibited high detection rates (<10 s) and distinctive color changes under alkaline or acidic conditions, even at low gas concentrations. Furthermore, the fabricated sensors showed an outstanding durability and reversibility after washing and drying and were confirmed to contain limited amounts of hazardous materials. Thus, our results show that the fabricated textile sensors could be used in safety apparel that changes its color in the presence of harmful gases.

3.
J Nanosci Nanotechnol ; 18(3): 2026-2031, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448705

RESUMO

A series of ordered mesoporous silica (OMS) SBA-15 supports with different morphologies were prepared by different synthetic methods to investigate the effect of the characteristics of the morphology of OMS on the ethylene dimerization outcomes. After additions of Ni and Al species into the SBA-15 support, a dimerization reaction of ethylene was performed using a fixed-bed reactor. Rod-type Ni-Al-SBA-15 with a small micron size showed better catalytic performance compared to those of the other catalysts. From these catalytic results, the particle size and morphology of a SBA-15 support critically influenced the catalytic activities and lifetimes of the dimerization catalysts. The optimum reaction pathway in the Ni-Al-SBA-15 catalyst enhanced the overall catalytic performance due to the suppression of the further oligomerization of ethylene and butenes. Moreover, ethylene dimerization was investigated over the rod-type Ni-Al-SBA-15 catalyst to discover an optimum reaction condition. The maximum yield of butenes was 24.7% at 300 °C at 11.5 bar with a WHSV of 1.5 h-1.

5.
Toxicol Appl Pharmacol ; 287(1): 17-25, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25981168

RESUMO

Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H+ ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/enzimologia , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Gefitinibe , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lapatinib , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Macrolídeos/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Quinazolinas/farmacologia , Interferência de RNA , Transfecção , ATPases Vacuolares Próton-Translocadoras/metabolismo
6.
Ann Clin Lab Sci ; 45(2): 193-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25887874

RESUMO

We report three cases of plasma cell myeloma with obscure and discordant data for a monoclonal component. In this study, the results of serum heavy/light chain (sHLC) were retrospectively compared with those of conventional methods during disease monitoring. All three patients achieved a complete response and experienced a relapse during follow-up, and the sHLC ratio allowed early prediction of disease relapse and correlated well with other electrophoretic methods compared with the free light chain ratio. Therefore, we suggest that the sHLC assay may be useful as a complementary tool; it has a good correlation with conventional methods and sensitivity in assessing disease status and treatment response in patients with plasma cell myeloma.


Assuntos
Cadeias Pesadas de Imunoglobulinas/sangue , Cadeias Leves de Imunoglobulina/sangue , Monitorização Fisiológica/métodos , Mieloma Múltiplo/sangue , Plasmócitos/patologia , Adulto , Idoso , Feminino , Humanos , Masculino
7.
Mol Cells ; 38(4): 327-35, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25813625

RESUMO

Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic α,ß-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Dioxolanos/farmacologia , Heme Oxigenase-1/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Indução Enzimática/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
Oncotarget ; 6(28): 26528-40, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25605253

RESUMO

In the present study, we found that selective inhibition of histone deacetylase 2 (HDAC2) with small inhibitory RNA (siRNA) induced survivin downregulation in a p53-dependent manner. Interestingly, suberoylanilide hydroxamic acid (SAHA) or knockdown of HDAC2 induced downregulation of Mdm2, a negative regulator of p53, at the protein level. SAHA and/or HDAC2 siRNA increased Mdm2 ubiquitination, and MG132, an inhibitor of proteosome function, prevented HDAC2 inhibition-induced degradation of Mdm2. Clinically, the mRNA levels of HDAC2 and survivin were prominently overexpressed in lung cancer patients compared to normal lung tissues. Silencing of HDAC2 enhanced the cell death caused by ionizing radiation in lung cancer cells. Collectively, our results indicate that selective inhibition of HDAC2 causes survivin downregulation through activation of p53, which is mediated by downregulation of Mdm2. They further suggest that HDAC2 may exert a dominant effect on lung cancer cell survival by sustaining Mdm2-survivin levels.


Assuntos
Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Regulação para Baixo , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Humanos , Proteínas Inibidoras de Apoptose/genética , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Complexo de Endopeptidases do Proteassoma/genética , Inibidores de Proteassoma/farmacologia , Proteólise , Proteínas Proto-Oncogênicas c-mdm2/genética , Interferência de RNA , Survivina , Transfecção , Proteína Supressora de Tumor p53/genética , Ubiquitinação
9.
Biochem Biophys Res Commun ; 453(3): 438-42, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25281537

RESUMO

Cyclin A1 is an A-type cyclin that directly binds to CDK2 to regulate cell-cycle progression. In the present study, we found that doxorubicin decreased the expression of cyclin A1 at the protein level in A549 lung cancer cells, while markedly downregulating its mRNA levels. Interestingly, doxorubicin upregulated caspase-1 in a concentration-dependent manner, and z-YAVD-fmk, a specific inhibitor of caspase-1, reversed the doxorubicin-induced decrease in cyclin A1 in A549 lung cancer and MCF7 breast cancer cells. Active caspase-1 effectively cleaved cyclin A1 at D165 into two fragments, which in vitro cleavage assays showed were further cleaved by caspase-3. Finally, we found that overexpression of cyclin A1 significantly reduced the cytotoxicity of doxorubicin, and knockdown of cyclin A1 by RNA interference enhanced the sensitivity of cells to ionizing radiation. Our data suggest a new mechanism for the downregulation of cyclin A1 by DNA-damaging stimuli that could be intimately involved in the cell death induced by DNA damage-inducing stimuli, including doxorubicin and ionizing radiation.


Assuntos
Caspases/metabolismo , Morte Celular/genética , Ciclina A1/metabolismo , Dano ao DNA , Sequência de Bases , Linhagem Celular Tumoral , Primers do DNA , Humanos , Proteólise , Reação em Cadeia da Polimerase em Tempo Real
10.
J Cancer Res Clin Oncol ; 140(12): 2039-46, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25023940

RESUMO

PURPOSE: Piperlongumine (PL) has been shown to selectively induce apoptotic cell death in cancer cells via reactive oxygen species (ROS) accumulation. In this study, we characterized a molecular mechanism for PL-induced cell death. METHODS: Cell viability and cell death were assessed by MTT assay and Annexin V-FITC/PI staining, respectively. ROS generation was measured using the H2DCFDA. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein expression were analyzed by RT-PCR and Western blot analysis, respectively. RESULTS: We found that PL promotes C/EBP homologous protein (CHOP) induction, which leads to the up-regulation of its targets Bim and DR5. Pretreatment with the ROS scavenger N-acetyl-cysteine abolishes the PL-induced up-regulation of CHOP and its target genes, suggesting an essential role for ROS in PL-induced CHOP activation. The down-regulation of CHOP or Bim with siRNA efficiently attenuates PL-induced cell death, suggesting a critical role for CHOP in this cell death. Furthermore, PL potentiates TRAIL-induced cytotoxicity in breast cancer cells by upregulating DR5, as DR5 knockdown abolished the sensitizing effect of PL on TRAIL responses. CONCLUSIONS: Overall, our data suggest a new mechanism for the PL-induced cell death in which ROS mediates CHOP activation, and combination treatment with PL and TRAIL could be a potential strategy for breast cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Dioxolanos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Fator de Transcrição CHOP/metabolismo , Proteínas Reguladoras de Apoptose/fisiologia , Proteína 11 Semelhante a Bcl-2 , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas de Membrana/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/fisiologia
11.
Biomed Rep ; 2(5): 737-742, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25054020

RESUMO

Lung cancer is one of the main causes of cancer-related mortality. The identification of early diagnostic biomarkers improved outcomes for lung cancer patients. Serum fibrin-fibrinogen degradation products (FDP) levels are elevated in numerous malignancies due to hemostatic alterations. The serum FDP levels were compared to the levels of cytokeratin 19 fragment antigen (CYFRA 21-1), another well-established biomarker. The serum samples from 193 lung cancer patients, 84 healthy controls and 106 patients with benign respiratory diseases were obtained. The serum FDP level was measured using the DR-70 immunoassay and the CYFRA 21-1 level was measured by electrochemiluminescence using the Roche Analytics E170. Receiver operating characteristics curves were used to assess the predictive sensitivity and specificity. The mean serum FDP level in lung cancer patients (35.01±229.02 µg/ml) was significantly higher compared to the 190 non-cancerous subjects (0.60±0.75 µg/ml; P=0.039). The mean serum CYFRA 21-1 level in lung cancer patients (4.50±6.67 ng/ml) was also significantly higher compared to the non-cancerous subjects (1.40±0.83 ng/ml; P<0.05). FDP exhibited clinical sensitivity and specificity of 86 and 75%, respectively, at an optimal cut-off at 0.67 µg/ml. CYFRA 21-1 exhibited clinical sensitivity and specificity of 77 and 74%, respectively, at a cut-off of 1.65 ng/ml. The serum FDP area under the curve (0.87) was slightly higher compared to CYFRA 21-1 (0.83). Therefore, it is apparent that serum FDP is comparable to CYFRA 21-1 as a lung cancer biomarker and can be used for clinical practice.

12.
Biochem Biophys Res Commun ; 449(4): 490-5, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-24845567

RESUMO

TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.


Assuntos
Proteínas Nucleares/genética , Proteína 1 Relacionada a Twist/genética , Acetilcisteína/farmacologia , Trióxido de Arsênio , Arsenicais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Nucleares/biossíntese , Óxidos , RNA Interferente Pequeno/farmacologia , Radiação Ionizante , Espécies Reativas de Oxigênio/metabolismo , Proteína 1 Relacionada a Twist/biossíntese
13.
Biochem Biophys Res Commun ; 444(4): 502-8, 2014 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-24472538

RESUMO

The PI3K/Akt/mTOR axis in lung cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for lung cancer. However, non-small cell lung cancer cells are resistant to BEZ235, a dual inhibitor of PI3K and mTOR. Interestingly, blockage of Stat3 with a selective inhibitor, S3I-201, or siRNA dramatically sensitized the BEZ235-induced cell death, as evident from increased PARP cleavage. Furthermore, inhibition of Stat3 led to enhancement of cell death induced by LY294002, a PI3K inhibitor. Treatment of cells with a combination of BEZ235 and S3I-201 significantly induced the proapoptotic transcription factor, CHOP, and its targets, Bim and DR4. Knockdown of CHOP or Bim suppressed cell death stimulated by the combination treatment, implicating the involvement of these BEZ235/S3I-201-induced factors in pronounced cell death. Moreover, the BEZ235/S3I-201 combination enhanced TRAIL-induced cell death. Our results collectively suggest that blockage of Stat3 presents an effective strategy to overcome resistance to PI3K/Akt/mTOR inhibition.


Assuntos
Benzenossulfonatos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imidazóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ácidos Aminossalicílicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
14.
Biochem Biophys Res Commun ; 437(3): 463-8, 2013 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-23838288

RESUMO

Resistance of estrogen receptor-positive breast cancer cells to tamoxifen represents a major barrier to the successful treatment of breast cancer. In the present study, we found that vacuolar H+ ATPase (vATPase) inhibitors, bafilomycin A1 and concanamycin A, sensitize tamoxifen-induced cell death. siRNA targeting ATP6V0C, a 16-kDa hydrophobic proteolipid subunit of vATPase that plays a central role in H+ transport, markedly increased cell death induced by tamoxifen. Interestingly, bafilomycin A1 induced up-regulation of DR4/DR5 and CHOP. Knock-down of CHOP by siRNA suppressed the cell death induced by bafilomycin A1 and tamoxifen, suggesting that bafilomycin A1-mediated CHOP activation sensitizes to tamoxifen. In addition, we found that bafilomycin A1 enhances TRAIL-induced cell death in breast cancer cells. Furthermore, we showed that combination of vATPase inhibitors with tamoxifen also effectively induced cell death in HER2- and ERα-overexpressing breast cancer cells. Overall, our results demonstrate that inhibition of vATPase can potentiate the apoptotic effects of tamoxifen through up-regulation of CHOP.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Tamoxifeno/farmacologia , Fator de Transcrição CHOP/biossíntese , Regulação para Cima/efeitos dos fármacos , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Tamoxifeno/toxicidade , Fator de Transcrição CHOP/antagonistas & inibidores , Fator de Transcrição CHOP/genética , Regulação para Cima/fisiologia
15.
Cancer Lett ; 336(2): 319-24, 2013 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-23528835

RESUMO

Herein, we show that the constitutive overexpression of Redd1, a negative regulator of mTORC1, induces Akt activation in lung cancer cells. Akt phosphorylation was reduced to basal levels by Rictor siRNA, suggesting the involvement of mTORC2 in this process. Perifosine and PP242, selective inhibitors of Akt and mTORC1/2, respectively, efficiently suppressed the Akt phosphorylation that was induced by the sustained overexpression of Redd1 and increased the sensitivity of the cells to cisplatin. Therefore, the sustained overexpression of Redd1 leads to mTORC1 inhibition and to consequent Akt activation that is involved in cell survival. This finding highlights the importance of Akt activation as a therapeutic target to overcome resistance to chemotherapy.


Assuntos
Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/biossíntese , Sobrevivência Celular/fisiologia , Cisplatino/farmacologia , Ativação Enzimática , Humanos , Neoplasias Pulmonares/enzimologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Complexos Multiproteicos/antagonistas & inibidores , Complexos Multiproteicos/metabolismo , Fosforilação , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção
16.
Mol Med Rep ; 7(1): 11-5, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23064681

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for many nosocomial and community-acquired infections, resulting in significant morbidity and mortality. A practical way to limit the spread of MRSA is early detection and proper treatment. However, screening culture for MRSA typically requires 2-3 days. The Xpert MRSA assay (Cepheid, Sunnyvale, CA, USA) is a real-time polymerase chain reaction-based assay developed for screening an MRSA-specific DNA sequence within the staphylococcal cassette chromosome in 2 h. Lower respiratory tract specimens, such as transtracheal aspirates (TTAs) and bronchoalveolar lavage fluid (BALF), are commonly obtained from intubated patients. Therefore, using the lower respiratory tract specimens with the Xpert MRSA assay may be a practical tool for patient care. We performed the Xpert MRSA assay on 108 TTA and 21 BALF specimens from 92 patients and compared the results to those obtained by culture. The two assays showed concordant results in 120 (93.0%) cases and discordant results in 9 (7.0%) cases, which were culture­negative and Xpert MRSA-positive. Among the discordant cases, 5 patients developed culture-positive samples 2-15 days after the Xpert MRSA detected MRSA. We conclude that the Xpert MRSA assay is a rapid, sensitive and clinically useful test, particularly for the early detection of MRSA.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Infecções Estafilocócicas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
J Thorac Oncol ; 6(8): 1313-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21642861

RESUMO

INTRODUCTION: Histone deacetylase inhibitors (HDACIs) induce growth arrest and apoptosis in cancer cells. In addition to their intrinsic anticancer properties, HDACIs modulate cellular responses to ionizing radiation (IR). We examined the molecular mechanism(s) associated with the radiosensitizing effects of HDACIs in human lung cancer cells. METHODS: Lung cancer cells were pretreated with the appropriate concentrations of suberoylanilide hydroxamic acid or trichostatin A. After 2 hours, cells were irradiated with various doses of γ-IR, and then we performed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence-activated cell sorting analysis, clonogenic assay, and Western blotting to detect cell viability or apoptosis and changes of specific proteins expression levels. RESULTS: In this study, we showed that HDACIs (including suberoylanilide hydroxamic acid and trichostatin A) and IR synergistically trigger cell death in human non-small cell lung cancer cells. Cell viability and clonogenic survival were markedly decreased in cultures cotreated with HDACIs and IR. Interestingly, p53 acetylation at lysine 382 was significantly increased, and c-myc expression simultaneously down-regulated in cotreated cells. Radiosensitization by HDACIs was inhibited on transfection with small interfering RNA against p53 and c-myc overexpression, supporting the involvement of p53 and c-myc in this process. Furthermore, c-myc down-regulation and apoptotic cell death coinduced by IR and HDACI were suppressed in cells transfected with mutant K382R p53 and C135Y p53 displaying loss of acetylation at lysine 382 and DNA-binding activity, respectively. CONCLUSIONS: Our results collectively demonstrate that the degree of radiosensitization by HDACIs is influenced by acetyl p53-mediated c-myc down-regulation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Pulmonares/terapia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Radiação Ionizante , Radiossensibilizantes/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Acetilação/efeitos dos fármacos , Acetilação/efeitos da radiação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Regulação para Baixo , Citometria de Fluxo , Humanos , Ácidos Hidroxâmicos/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos da radiação , Mutagênese Sítio-Dirigida , Mutação/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteína Supressora de Tumor p53/genética , Vorinostat
18.
Biochem Pharmacol ; 82(3): 216-26, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21601561

RESUMO

Sorafenib, a multikinase inhibitor, is emerging as a promising targeted agent that may possess antitumor activity against a broad range of cancers. The mechanism by which sorafenib induces lung cancer cell death and apoptosis, however, is not understood. In the present study, we provide evidence that sorafenib acts through inhibition of mammalian target of rapamycin (mTOR) to down-regulate survivin and promote apoptotic cell death in human non-small cell lung cancer (NSCLC) cells. Sorafenib induced ATF4-mediated Redd1 expression, leading to mTOR inhibition-the upstream signal for down-regulation of survivin. Overexpression of survivin reduced sorafenib-induced apoptosis, whereas silencing survivin using small interfering RNA (siRNA) enhanced it, supporting the interpretation that down-regulation of survivin is involved in sorafenib-induced cell death in human NSCLC cells. Furthermore, sorafenib abolished the induction of survivin that normally accompanies IGF-1-stimulated mTOR activation. We further found that Redd1-induced mTOR down-regulation and ATF4/CHOP-induced expression of the TRAIL receptor DR5 associated with sorafenib treatment helped sensitize cells to TRAIL-induced apoptosis. Our study suggests that sorafenib mediates apoptotic cell death in human NSCLC cells through Redd1-induced inhibition of mTOR and subsequent down-regulation of survivin, events that are associated with sensitization to TRAIL-induced apoptotic cell death.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzenossulfonatos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/metabolismo , Piridinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Proteínas Inibidoras de Apoptose/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia , Sorafenibe , Survivina , Serina-Treonina Quinases TOR/genética
19.
Biochem Biophys Res Commun ; 407(3): 507-11, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21414293

RESUMO

Redd1 acts as a negative regulator of mTOR in response to various stress conditions, but its specific physiological role is currently unclear. In the present study, we showed that Redd1 inhibits the invasive activity of non-small cell lung cancer (NSCLC) cells. Interestingly, expression of Redd1 was extremely low in H1299 cells displaying high invasiveness, compared with that in H460 cells with lower invasive activity. Overexpression of Redd1 inhibited the invasive activity of H1299 cells, while suppression with specific siRNAs enhanced the invasiveness of H460 cells. Knockdown of the mTOR downstream substrate, S6K, resulted in a decrease in the invasive property of H1299 cells. Our results provide preliminary evidence that Redd1 inhibits the invasive activity of NSCLC cells via suppression of the mTOR downstream pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Transcrição/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Células HeLa , Humanos , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética
20.
Korean J Lab Med ; 30(6): 575-9, 2010 Dec.
Artigo em Coreano | MEDLINE | ID: mdl-21157141

RESUMO

BACKGROUND: Late-onset neutropenia (LON) following rituximab therapy has been reported in recent years. However, its incidence has not been reported in Korea. The aim of this study is to investigate the incidence of LON after rituximab therapy in Korean patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-eight cases of DLBCL treated with rituximab between 2004 and 2008 were evaluated. We identified LON as defined by the neutrophil count of <1.5 × 10(9)/L without apparent cause after the recovery of neutrophil count following rituximab therapy. Bone marrow aspiration and biopsy specimens at the time of neutropenia were available for retrospective review in only 5 of the patients. RESULTS: LON was observed in 15 (15.3%) of the 98 patients. In the bone marrow specimens of the 5 patients, promyelocytes were relatively increased and the maturation index of the granulopoiesis was 2:1-3:1, which reflects maturation arrest. CONCLUSIONS: The incidence of LON following rituximab therapy was 15.3% in Korean patients with DLBCL. Although there are several hypotheses about the causative mechanisms of LON, we suggest that maturation arrest at the promyelocyte stage of granulopoiesis may be one of the mechanisms involved in the development of LON.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neutropenia/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Células da Medula Óssea/patologia , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/diagnóstico , Estudos Retrospectivos , Rituximab
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