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1.
ACS Nano ; 18(5): 4559-4569, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38264984

RESUMO

The oxidation of copper and its surface oxides are gaining increasing attention due to the enhanced CO2 reduction reaction (CO2RR) activity exhibited by partially oxidized copper among the copper-based catalysts. The "8" surface oxide on Cu(111) is seen as a promising structure for further study due to its resemblance to the highly active Cu2O(110) surface in the C-C coupling of the CO2RR, setting it apart from other O/Cu(111) surface oxides resembling Cu2O(111). However, recent X-ray photoelectron spectroscopy analysis challenges the currently accepted atomic structure of the "8" surface oxide, prompting a need for reevaluation. This study highlights the limitations of conventional methods when addressing such challenges, leading us to adopt global optimization search techniques. After a rigorous process to ensure robustness, the unbiased global minimum of the "8" surface oxide is identified. Interestingly, this configuration differs significantly from other surface oxides and also from previous "8" models while retaining similarities to the Cu2O(110) surface.

2.
Sci Rep ; 13(1): 20649, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001140

RESUMO

Dielectric scatterers where Mie resonances can be excited in both electric and magnetic modes have emerged as a promising candidate for efficient light trapping (LT) in thin-film solar cells. We present that light absorption in organic solar cells (OSCs) can be significantly enhanced by a front-sided incorporation of a core-shell nanostructure consisting of a high-refractive-index dielectric nanosphere array conformally coated with a low-refractive-index dielectric layer. Strong forward light scattering of the all-dielectric LT structure enables the absorption in an organic semiconductor to be remarkably boosted over a broad range of wavelengths, which is attributed to interference of a simultaneous excitation of the electric and magnetic dipole resonant modes. The OSC with the LT structure shows the short-circuit current density (Jsc) of 28.23 mA/cm2, which is 10% higher than that of a flat OSC. We also explore how the LT structure affects scattering cross-sections, spectral multipole resonances, and far-field radiation patterns. The approach described in this work could offer the possibility for the improvement of characteristic performances of various applications, such as other thin-film solar cells, photodiodes, light-emitting diodes, and absorbers.

3.
ACS Appl Mater Interfaces ; 15(33): 39614-39624, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37556112

RESUMO

Bioelectronic devices that offer real-time measurements, biological signal processing, and continuous monitoring while maintaining stable performance are in high demand. The materials used in organic electrochemical transistors (OECTs) demonstrate high transconductance (GM) and excellent biocompatibility, making them suitable for bioelectronics in a biological environment. However, ion migration in OECTs induces a delayed response time and low cut-off frequency, and the adverse biological environment causes OECT durability problems. Herein, we present OECTs with a faster response time and improved durability, made possible by using a nanofiber mat channel of a conventional OECT structure. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/polyacrylamide (PAAm) nanofiber mat channel OECTs are fabricated and subjected to various durability tests for the first time based on continuous measurements and mechanical stability assessments. The results indicate that the nanofiber mat channel OECTs have a faster response time and longer life spans compared to those of film channel OECTs. The improvements can be attributed to the increased surface area and fibrous structure of the nanofiber mat channel. Furthermore, the hydrogel helps to maintain the structure of the nanofiber, facilitates material exchange, and eliminates the need for a crosslinker.

4.
Oncol Rep ; 49(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36866762

RESUMO

Colorectal cancer (CRC) is common cancer worldwide, and the 5­year relative survival rate of CRC patients with distant metastasis is as low as 14%. Therefore, identifying markers of CRC is important for the early detection of CRC and applying appropriate treatment strategies. The lymphocyte antigen 6 family (LY6 family) is closely related to the behavior of various cancer types. Among the LY6 family, the lymphocyte antigen 6 complex, locus E (LY6E), which is specifically highly expressed in CRC. Hence, the effects of LY6E on cell function in CRC and its role in CRC recurrence and metastasis were investigated. Reverse transcription­quantitative PCR, western blotting and in vitro functional studies were carried out using four CRC cell lines. Immunohistochemical analysis of 110 CRC tissues was performed to explore the biological functions and expression patterns of LY6E in CRC. LY6E was overexpressed CRC tissues compared with that in adjacent normal tissues. High expression of LY6E in CRC tissues was an independent prognostic factor of worse overall survival (P=0.048). Knockdown of LY6E using small interfering RNA inhibited CRC cell proliferation, migration, invasion, and soft agar colony formation, indicating some of its effects on CRC carcinogenic functions. High expression of LY6E may have oncogenic functions in CRC and be useful as a valuable prognostic marker and potential therapeutic target for CRC.


Assuntos
Carcinogênese , Neoplasias Colorretais , Humanos , Antígenos de Superfície , Western Blotting , Neoplasias Colorretais/genética , Proteínas Ligadas por GPI , Prognóstico
5.
Technol Cult ; 64(4): 1274-1291, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38588191

RESUMO

This review essay examines the ambitious thirty-volume series Science and Civilization in Korea (SCK), published between 2010 and 2022. Input from over sixty Korean scholars traces the evolution of Korean science and technology, from elementary tools to advanced semiconductor technology. Inspired by Joseph Needham's series Science and Civilization in China, SCK seeks to reveal the "universal value" embedded in Korean civilization, extending to the tumultuous eras of the nineteenth and early twentieth centuries. This review essay probes SCK's implications and boundaries, elucidating the influences molding its narrative and identifying omissions. It also considers alternative narratives. Albeit rooted in use-centered historiography, such narratives would not be restricted to the local but underscore an array of practices striving for compatibility with global resources. Moreover, they could bridge the "imagined discontinuity"-the notion of rupture around 1900-between "tradition" and "modern" and thus cultivate a more seamless chronicle of Korea's history of technology.


Assuntos
Livros , Civilização , Humanos , Coreia (Geográfico) , Publicações/história , República da Coreia
6.
Adv Sci (Weinh) ; 9(13): e2104569, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35253401

RESUMO

To expand the unchartered materials space of lead-free ferroelectrics for smart digital technologies, tuning their compositional complexity via multicomponent alloying allows access to enhanced polar properties. The role of isovalent A-site in binary potassium niobate alloys, (K,A)NbO3 using first-principles calculations is investigated. Specifically, various alloy compositions of (K,A)NbO3 are considered and their mixing thermodynamics and associated polar properties are examined. To establish structure-property design rules for high-performance ferroelectrics, the sure independence screening sparsifying operator (SISSO) method is employed to extract key features to explain the A-site driven polarization in (K,A)NbO3 . Using a new metric of agreement via feature-assisted regression and classification, the SISSO model is further extended to predict A-site driven polarization in multicomponent systems as a function of alloy composition, reducing the prediction errors to less than 1%. With the machine learning model outlined in this work, a polarity-composition map is established to aid the development of new multicomponent lead-free polar oxides which can offer up to 25% boosting in A-site driven polarization and achieving more than 150% of the total polarization in pristine KNbO3 . This study offers a design-based rational route to develop lead-free multicomponent ferroelectric oxides for niche information technologies.

7.
Sensors (Basel) ; 21(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198830

RESUMO

Recently, as technology has advanced, the use of in-vehicle infotainment systems has increased, providing many functions. However, if the driver's attention is diverted to control these systems, it can cause a fatal accident, and thus human-vehicle interaction is becoming more important. Therefore, in this paper, we propose a human-vehicle interaction system to reduce driver distraction during driving. We used voice and continuous-wave radar sensors that require low complexity for application to vehicle environments as resource-constrained platforms. The proposed system applies sensor fusion techniques to improve the limit of single-sensor monitoring. In addition, we used a binarized convolutional neural network algorithm, which significantly reduces the computational workload of the convolutional neural network in command classification. As a result of performance evaluation in noisy and cluttered environments, the proposed system showed a recognition accuracy of 96.4%, an improvement of 7.6% compared to a single voice sensor-based system, and 9.0% compared to a single radar sensor-based system.


Assuntos
Condução de Veículo , Voz , Algoritmos , Humanos , Redes Neurais de Computação , Radar
8.
Adv Sci (Weinh) ; 8(10): 2001544, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34026425

RESUMO

Organic neuromorphic computing/sensing platforms are a promising concept for local monitoring and processing of biological signals in real time. Neuromorphic devices and sensors with low conductance for low power consumption and high conductance for low-impedance sensing are desired. However, it has been a struggle to find materials and fabrication methods that satisfy both of these properties simultaneously in a single substrate. Here, nanofiber channels with a self-formed ion-blocking layer are fabricated to create organic electrochemical transistors (OECTs) that can be tailored to achieve low-power neuromorphic computing and fast-response sensing by transferring different amounts of electrospun nanofibers to each device. With their nanofiber architecture, the OECTs exhibit a low switching energy of 113 fJ and operate within a wide bandwidth (cut-off frequency of 13.5 kHz), opening a new paradigm for energy-efficient neuromorphic computing/sensing platforms in a biological environment without the leakage of personal information.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/métodos , Nanofibras/química , Polímeros/química , Sinapses/fisiologia , Transistores Eletrônicos/normas , Redes Neurais de Computação
9.
Adv Sci (Weinh) ; 7(11): 1903638, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32537409

RESUMO

Protein quantification techniques such as immunoassays have been improved considerably, but they have several limitations, including time-consuming procedures, low sensitivity, and extrinsic detection. Because direct surface-enhanced Raman spectroscopy (SERS) can detect intrinsic signals of proteins, it can be used as an effective detection method. However, owing to the complexity and reliability of SERS signals, SERS is rarely adopted for quantification without a purified target protein. This study reports an efficient and effective direct SERS-based immunoassay (SERSIA) technique for protein quantification and imaging. SERSIA relies on the uniform coating of gold nanoparticles (GNPs) on a target-protein-immobilized substrate by simple centrifugation. As centrifugation induces close contact between the GNPs and target proteins, the intrinsic signals of the target protein can be detected. For quantification, the protein levels in a cell lysate are estimated using similarity analysis between antibody-only and protein-conjugated samples. This method reliably estimates the protein level at a sub-picomolar detection limit. Furthermore, this method enables quantitative imaging of immobilized protein at a micrometer range. Because this technique is fast, sensitive, and requires only one type of antibody, this approach can be a useful method to detect proteins in biological samples.

10.
ACS Nano ; 14(5): 5435-5444, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32286793

RESUMO

Lung cancer has a high mortality rate, but an early diagnosis can contribute to a favorable prognosis. A liquid biopsy that captures and detects tumor-related biomarkers in body fluids has great potential for early-stage diagnosis. Exosomes, nanosized extracellular vesicles found in blood, have been proposed as promising biomarkers for liquid biopsy. Here, we demonstrate an accurate diagnosis of early-stage lung cancer, using deep learning-based surface-enhanced Raman spectroscopy (SERS) of the exosomes. Our approach was to explore the features of cell exosomes through deep learning and figure out the similarity in human plasma exosomes, without learning insufficient human data. The deep learning model was trained with SERS signals of exosomes derived from normal and lung cancer cell lines and could classify them with an accuracy of 95%. In 43 patients, including stage I and II cancer patients, the deep learning model predicted that plasma exosomes of 90.7% patients had higher similarity to lung cancer cell exosomes than the average of the healthy controls. Such similarity was proportional to the progression of cancer. Notably, the model predicted lung cancer with an area under the curve (AUC) of 0.912 for the whole cohort and stage I patients with an AUC of 0.910. These results suggest the great potential of the combination of exosome analysis and deep learning as a method for early-stage liquid biopsy of lung cancer.


Assuntos
Aprendizado Profundo , Exossomos , Neoplasias Pulmonares , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares/diagnóstico , Análise Espectral Raman
11.
ACS Appl Mater Interfaces ; 12(2): 2842-2853, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887004

RESUMO

Selective chemical control of multiple reactions is incredibly important for the fabrication of sophisticated nanostructures for functional applications. A representative example is the synthesis of plasmonic nanomaterial-silver chloride (AgCl) conjugates, where metal ions should be selectively reduced into metallic nanostructures for plasmon-enhanced catalytic activity, while the reducible AgCl nanomaterials remain intact despite the presence of a chemical reductant. In addition to the selectively controlled reduction, the plasmonic nanostructures should be appropriately designed for the high stability and photoefficiency of catalysts. In this study, we demonstrate how AgCl nanocubes and nanospheres could be comprehensively wrapped by plasmonic three-dimensional nanomesh structures consisting of gold, silver, and palladium by the selective reduction of their ionic precursors while the AgCl nanostructures remain intact. Complete trimetallic wrapping provided the absorption of visible light, while the porosity of the nanomesh structures exposed the photocatalytic AgCl surface to catalyze desired reactions. Platinum in place of palladium was examined to demonstrate the versatility of the wrapping scheme, resulting in an extraordinary catalytic activity. Importantly, the detailed chemical mechanism behind the trimetallic wrapping of the AgCl nanostructures was systematically investigated to understand the roles of each reaction component in controlling the chemical selectivity. The synthesized AgCl-trimetal nanoconjugates excellently exhibit both metal-based and plasmon-enhanced catalytic properties for the removal of environmentally harmful Cr6+. Moreover, their applications as surface-enhanced Raman-scattering (SERS) probes for the in situ monitoring of catalytic reduction in real-time and as single-nanoparticle SERS probes for molecular detection are thoroughly demonstrated.

13.
Cancer Biomark ; 24(4): 485-495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932884

RESUMO

Defensin alpha 6 (DEFA6) is a member of the alpha defensin family of microbicidal and cytotoxic peptides that defend against bacteria and viruses. Here, we provide a novel function of DEFA6 in tumorigenesis of colorectal cancer (CRC) in vitro and in vivo. Specifically, DEFA6 is highly expressed in both CRC cancer cell lines as well as patient-derived samples at the level of RNA and protein. By shRNA-mediated loss of function of DEFA6, we found that proliferation, migration, invasion, colony forming ability of CRC cell lines were impaired in the absence of DEFA6 in vitro. Furthermore, DEFA6-deficient cancer cells exhibited significantly reduced growth rates compared to control cells in vivo. More importantly, by analyzing 352 patient-derived samples, we revealed that DEFA6 is associated with overall survival rate of CRC patients and thus an independent prognostic marker for CRC. These results suggest that DEFA6 plays an essential oncogenic role in CRC and serves a good therapeutic target for the disease.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , alfa-Defensinas/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Modelos Animais de Doenças , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , alfa-Defensinas/metabolismo
14.
Oncol Rep ; 39(6): 2829-2836, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29658598

RESUMO

The protein kinase, membrane­associated tyrosine/threonine 1 (PKMYT1) is known to inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15 residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC) remains unknown. Thus, it is important to elucidate whether PKYMT1 is indispensable in the tumorigenesis of CRC. To investigate the functional importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1­depleted CRC cells were analyzed to determine proliferation, migration, invasion and colony forming ability. In addition, 179 patient­derived samples were used to find the correlation of the expression of PKMYT1 with the prognosis of CRC patients. By siRNA­mediated loss of function of PKMYT1, we observed that proliferation, migration, invasion and colony forming ability of CRC cell lines were significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by analyzing patient­derived samples, we revealed the association of PKMYT1 with the overall survival rate of CRC patients. These results indicated that PKMYT1 plays an essential oncogenic role in CRC and could serve as a good therapeutic target for the treatment of CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Regulação para Cima , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Células HT29 , Humanos , Masculino , Análise de Sobrevida
15.
J Cancer Res Clin Oncol ; 143(12): 2493-2503, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28875407

RESUMO

PURPOSE: Adjuvant chemotherapy (AC) is frequently considered in patients with high-risk stage II colorectal cancer (CRC). Among patients with stage II CRC who do not receive AC because they are not considered to be at high risk, 20-25% will develop recurrence and die from the disease. Elevated levels of KPNA2 have been observed in various cancers, and overexpression of KPNA2 is related to CRC progression. METHODS: We examined the expression of KPNA2 using 293 CRC tissues, including 118 with stage II CRC, and investigated the applicability of KPNA2 as a biomarker to predict high-risk stage II CRC. Moreover, we further investigated the role of KPNA2 as an oncogene in CRC carcinogenesis using in vitro functional studies. RESULTS: High KPNA2 expression was associated with vascular (p = 0.027) and lymphatic invasion (p = 0.009) in patients with stage II CRC. On multivariate analysis, high KPNA2 expression (HR 3.174, 95% CI 2.060-4.889; p < 0.001) was independently associated with survival in patients with CRC. The overall survival rate in patients with high KPNA2 expression was higher than that in patients with low KPNA2 expression in CRC (p < 0.001), even in patients with stage II CRC (p = 0.001). Additionally, KPNA2 was associated with tumorigenesis and cancer progression in CRC cells; high KPNA2 expression was associated with increased cell proliferation (p < 0.05), migration (p = 0.03), invasion (p = 0.001), and semisolid agar colony formation (p < 0.001). CONCLUSION: KPNA2 expression is useful for identification of patients with high-risk stage II CRC who could benefit from AC and that KPNA2 may also be a promising therapeutic target.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Colorretais/metabolismo , alfa Carioferinas/biossíntese , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Células HCT116 , Células HT29 , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Fatores de Risco , Análise Serial de Tecidos , alfa Carioferinas/genética
16.
Eur J Med Chem ; 142: 416-423, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28870452

RESUMO

In this study, we propose doxorubicin (DOX) loaded oligonucleotides (ONTs) attached to gold nanoparticles (AuNPs) as a drug delivery system for cancer chemotherapy. DOX is one of the representative cancer chemotherapy agents and is widely used by many researchers as a chemotherapy agent in the drug delivery system. Due to the advantages of AuNPs such as simple steps in synthesis, high surface-area-to-volume ratio, and biocompatibility, we utilized AuNPs as drug delivery vehicle. AuNPs were synthesized by chemical reduction to be 13 nm diameter. The G-C rich oligonucleotides were used both for drug loading sites and AuNPs capping agents. 80% of DOX in solution could be bound to ONTs on AuNPs to became DOX-loaded AuNPs coated with ONTs (Doxorubicin-Oligomer-AuNP, DOA), and about 28% of loaded DOX was released from the as-prepared DOA. Confocal microscopy observation showed that DOA was well transported into cells, and finally the DOX was released into the cell nucleus. The drug's efficacies such as in vitro cytotoxicity and in vivo tumor growth inhibition were demonstrated with SW480 colon cancer cell line and a xenograft mouse model. MTT assay was performed to see the cytotoxicity effect on SW480 cells treated with DOA for 24 h, and the cell viability was determined to be 41.77% (p < 0.001). When DOA was administered regularly to a tumor bearing mouse, the tumor growth inhibition degree was examined by measuring the tumor size. The treatment-control (T/C) ratio was found to be 0.69. Thus, our results suggest the use of DOAs as promising drug delivery systems for colorectal cancer therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Ouro/química , Nanopartículas Metálicas/química , Oligonucleotídeos/química , Animais , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/patologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Reto/efeitos dos fármacos , Reto/patologia
17.
Sci Rep ; 7(1): 8649, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819306

RESUMO

We examined the prognostic significance of Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3) expression and its correlations with mesenchymal phenotype and microvessel density in non-small cell lung carcinoma (NSCLC). A total of 268 NSCLC specimens were evaluated retrospectively by immunohistochemical staining for EDIL3, EMT markers (e-cadherin, ß-catenin, and vimentin), and CD31 to measure microvessel density. EDIL3, e-cadherin, ß-catenin, and vimentin were expressed in 16%, 22.8%, 3.7%, and 10.1% of the specimens, respectively. The mRNA level of EDIL3 in tumor was correlated with the level of EDIL3 protein expression using immunohistochemistry. In lung adenocarcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression, high vimentin expression, and increased microvessel density (P < 0.001, P = 0.001, and P = 0.023, respectively). In lung squamous cell carcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression and high vimentin expression (P = 0.021 and P = 0.002, respectively). In lung adenocarcinoma patients, EDIL3 was an independent prognostic factor for overall survival in a multivariate analysis (hazard ratio: 2.552, P = 0.004). EDIL3 is significantly correlated with mesenchymal phenotype, angiogenesis, and tumor progression in lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Proteínas de Transporte/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neovascularização Patológica/genética , Fenótipo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Proteínas de Ligação ao Cálcio , Moléculas de Adesão Celular , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
18.
Free Radic Biol Med ; 101: 384-392, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27825965

RESUMO

Cancer cells have been suggested to be more susceptible to oxidative damages and highly dependent on antioxidant capacity in comparison with normal cells, and thus targeting antioxidant enzymes has been a strategy for effective cancer treatment. Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of sulfinylated peroxiredoxins and thereby reactivates them. In this study we developed a Srx inhibitor, K27 (N-[7-chloro-2-(4-fluorophenyl)-4-quinazolinyl]-N-(2-phenylethyl)-ß-alanine), and showed that it induces the accumulation of sulfinylated peroxiredoxins and oxidative stress, which leads to mitochondrial damage and apoptotic death of cancer cells. The effects of K27 were significantly reversed by ectopic expression of Srx or antioxidant N-acetyl cysteine. In addition, K27 led to preferential death of tumorigenic cells over non-tumorigenic cells, and suppressed the growth of xenograft tumor without acute toxicity. Our results suggest that targeting Srx might be an effective therapeutic strategy for cancer treatment through redox-mediated cell death.


Assuntos
Adenocarcinoma Bronquioloalveolar/tratamento farmacológico , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/antagonistas & inibidores , Quinazolinas/farmacologia , Espécies Reativas de Oxigênio/agonistas , beta-Alanina/análogos & derivados , Células A549 , Acetilcisteína/farmacologia , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Animais , Antineoplásicos/síntese química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Inibidores Enzimáticos/síntese química , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Terapia de Alvo Molecular , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Quinazolinas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta-Alanina/síntese química , beta-Alanina/farmacologia
19.
Mol Med Rep ; 14(2): 1809-16, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27315510

RESUMO

Soy milk, which is produced from whole soybeans, contains a variety of biologically active components. Isoflavones are a class of soy-derived phytoestrogens with beneficial effects, among which genistein (GEN) has been previously indicated to reduce the risk of prostate cancer. The present study evaluated the effects of soy milk digestion extract (SMD) on the progression of prostate cancer via the estrogen receptor (ER)ß in human LNCaP prostate cancer cells. To evaluate the effects of SMD (daizein, 1.988 mg/100g, glycitein, 23.537 mg/100 g and GEN, 0.685 mg/100g) on cell proliferation, LNCaP cells were cultured in media containing vehicle (0.1% dimethyl sulfoxide), 17ß­estradiol (E2; 2.7x10­7 mg/ml), GEN (2.7x10-2 mg/ml) of SMD (total aglycon concentration, 0.79 mg/ml), after which the cell viability was examined using an MTT assay. The cell viability was significantly elevated by E2 (by 45±0.18%), while it was markedly reduced by GEN (73.2±0.03%) or SMD (74.8±0.09%). Semi­quantitative reverse transcription polymerase chain reaction analysis was performed to assess the mRNA expression levels of target genes, including ERß, prostate cancer­specific antigen (PSA) and cell cycle regulators p21, Cyclin D1 and cyclin-dependent kinase (CDK)4. The expression of ERß was almost completely diminished by E2, whereas it was significantly elevated by SMD. In addition, the expression levels of PSA were considerably reduced by SMD. The expression of p21 was significantly elevated by SMD, while it was markedly reduced by E2. Of note, the expression levels of Cyclin D1 and CDK4 were considerably elevated by E2, while being significantly reduced by GEN and SMD. All of these results indicated that SMD may inhibit the proliferation of human prostate cancer cells via regulating the expression of ERß, PSA, p21, Cyclin D1 and CDK4 in an ER-dependent manner.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antígeno Prostático Específico/genética , Leite de Soja , Biomarcadores , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Extratos Vegetais/química , Antígeno Prostático Específico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Leite de Soja/química
20.
Nat Commun ; 6: 8499, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26465273

RESUMO

Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Fator de Crescimento Insulin-Like II/metabolismo , Neoplasias Experimentais/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Microambiente Tumoral , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Linhagem Celular Tumoral , Reprogramação Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-8/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Invasividade Neoplásica , Neoplasias Experimentais/tratamento farmacológico , Neovascularização Patológica , Comunicação Parácrina , Receptor IGF Tipo 2/metabolismo
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