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1.
Cancer Sci ; 111(4): 1375-1384, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958182

RESUMO

BRCAness is considered a predictive biomarker to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors. However, recent trials showed that its predictive value was limited in triple-negative breast cancer (TNBC) treated with platinum. Moreover, tumors with mutations of DNA damage response (DDR) genes, such as homologous recombination (HR) genes, could be sensitive to platinum and PARP inhibitors. Thus, we aim to explore the relationship between mutation status of DDR genes and BRCAness in TNBC. We sequenced 56 DDR genes in 120 TNBC and identified BRCAness by array comparative genomic hybridization. The sequencing results showed that 13, 14, and 14 patients had BRCA, non-BRCA HR, and non-HR DDR gene mutations, respectively. Array comparative genomic hybridization revealed that BRCA-mutated and HR gene-mutated TNBC shared similar BRCAness features, both having higher numbers and longer length of large-scale structural aberration (LSA, >10 Mb) and similar altered chromosomal regions of LSA. These suggested non-BRCA HR gene-mutated TNBC shared similar characteristics with BRCA-mutated TNBC, indicating non-BRCA HR gene-mutated TNBC sensitive to platinum and PARP inhibitors. Among tumors with mutation of non-HR DDR genes, 3 PTEN and 1 MSH6 mutation also contained significant LSAs (BRCAness); however, they had different regions of genomic alteration to BRCA and HR gene-mutated tumors, might explain prior findings that PTEN- and MSH6-mutated cancer cells not sensitive to PARP inhibitors. Therefore, we hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors. Direct sequencing DDR genes in TNBC should be applied to predict their sensitivity toward platinum and PARP inhibitors.


Assuntos
Dano ao DNA/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Recombinação Homóloga/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteína BRCA1/genética , Proteína BRCA2/genética , Dano ao DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação/genética , Platina/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genética
2.
Int J Mol Sci ; 17(6)2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27314333

RESUMO

R-spondin 1 (Rspo1) plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, which are responsible for Wnt signal potentiation, and a thrombospondin type 1 (TSR1) domain that can provide affinity towards heparan sulfate proteoglycans. Using chemical inhibitors, deglycosylase and site-directed mutagenesis, we found that human Rspo1 and Rspo3 are both N-glycosylated at N137, a site near the C-terminus of the furin repeat 2 domain, and Rspo2 is N-glycosylated at N160, a position near the N-terminus of TSR1 domain. Elimination of N-glycosylation at these sites affects their accumulation in media but have no effect on the ability towards heparin. Introduction of the N-glycosylation site to Rspo2 mutant at the position homologous to N137 in Rspo1 restored full glycosylation and rescued the accumulation defect of nonglycosylated Rspo2 mutant in media. Similar effect can be observed in the N137 Rspo1 or Rspo3 mutant engineered with Rspo2 N-glycosylation site. The results highlight the importance of N-glycosylation at these two positions in efficient folding and secretion of Rspo family. Finally, we further showed that human Rspo1 is subjected to endoplasmic reticulum (ER) quality control in N-glycan-dependent manner. While N-glycan of Rspo1 plays a role in its intracellular stability, it had little effect on secreted Rspo1. Our findings provide evidence for the critical role of N-glycosylation in the biogenesis of Rspo1.


Assuntos
Heparina/metabolismo , Processamento de Proteína Pós-Traducional , Via Secretória , Trombospondinas/metabolismo , Sítios de Ligação , Retículo Endoplasmático/metabolismo , Glicosilação , Células HEK293 , Humanos , Ligação Proteica , Dobramento de Proteína , Estabilidade Proteica , Trombospondinas/química
3.
Small ; 9(17): 2926-36, 2013 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-23427053

RESUMO

A new fabrication strategy in which Ag plasmonics are embedded in the interface between ZnO nanorods and a conducting substrate is experimentally demonstrated using a femtosecond-laser (fs-laser)-induced plasmonic ZnO/Ag photoelectrodes. This fs-laser fabrication technique can be applied to generate patternable plasmonic nanostructures for improving their effectiveness in hydrogen generation. Plasmonic ZnO/Ag nanostructure photoelectrodes show an increase in the photocurrent of a ZnO nanorod photoelectrodes by higher than 85% at 0.5 V. Both localized surface plasmon resonance in metal nanoparticles and plasmon polaritons propagating at the metal/semiconductor interface are available for improving the capture of sunlight and collecting charge carriers. Furthermore, in-situ X-ray absorption spectroscopy is performed to monitor the plasmonic-generating electromagnetic field upon the interface between ZnO/Ag nanostructures. This can reveal induced vacancies on the conduction band of ZnO, which allow effective separation of charge carriers and improves the efficiency of hydrogen generation. Plasmon-induced effects enhance the photoresponse simultaneously, by improving optical absorbance and facilitating the separation of charge carriers.


Assuntos
Eletrodos , Hidrogênio/química , Luz , Nanoestruturas/química , Fotoquímica/métodos , Prata/química , Óxido de Zinco/química
4.
Opt Express ; 21(6): 7240-9, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-23546108

RESUMO

A low-cost and efficient photocatalytic reactor for environmental treatment and green technology was presented. ZnO nanorods firmly growing on polycarbonate optical disk substrate are generally perpendicular to the substrate as the immobilized photocatalyst of the spinning disk reactor. The photocatalytic efficiency and durability of the ZnO nanorods are effectively demonstrated.


Assuntos
Compostos Azo/química , Compostos Azo/efeitos da radiação , Recuperação e Remediação Ambiental/instrumentação , Química Verde/instrumentação , Dispositivos Ópticos , Fotoquímica/instrumentação , Óxido de Zinco/química , Catálise , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Óxido de Zinco/efeitos da radiação
5.
Chem Soc Rev ; 41(17): 5654-71, 2012 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-22763382

RESUMO

This review concerns the efficient conversion of sunlight into chemical fuels through the photoelectrochemical splitting of water, which has the potential to generate sustainable hydrogen fuel. In this review, we discuss various photoelectrode materials and relative design strategies with their associated fabrication for solar water splitting. Factors affecting photoelectrochemical performance of these materials and designs are also described. The most recent progress in the research and development of new materials as well as their corresponding photoelectrodes is also summarized in this review. Finally, the research strategies and future directions for water splitting are discussed with recommendations to facilitate the further exploration of new photoelectrode materials and their associated technologies.

6.
J Am Chem Soc ; 134(51): 20849-57, 2012 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-23210614

RESUMO

Lanthanide-doped upconversion nanoparticles have been the focus of a growing body of investigation because of their promising applications ranging from data storage to biological imaging and drug delivery. Here we present the rational design, synthesis, and characterization of a new class of core-shell upconversion nanoparticles displaying unprecedented optical properties. Specifically, we show that the epitaxial growth of an optically inert NaYF(4) layer around a lanthanide-doped NaGdF(4)@NaGdF(4) core-shell nanoparticle effectively prevents surface quenching of excitation energy. At room temperature, the energy migrates over Gd sublattices and is adequately trapped by the activator ions embedded in host lattices. Importantly, the NaYF(4) shell-coating strategy gives access to tunable upconversion emissions from a variety of activators (Dy(3+), Sm(3+), Tb(3+), and Eu(3+)) doped at very low concentrations (down to 1 mol %). Our mechanistic investigations make possible, for the first time, the realization of efficient emissions from Tb(3+) and Eu(3+) activators that are doped homogeneously with Yb(3+)/Tm(3+) ions. The advances on these luminescent nanomaterials offer exciting opportunities for important biological and energy applications.


Assuntos
Fluoretos/química , Elementos da Série dos Lantanídeos/química , Substâncias Luminescentes/química , Nanopartículas/química , Ítrio/química , Transferência de Energia , Células Hep G2 , Humanos , Nanopartículas/ultraestrutura , Propriedades de Superfície
7.
Front Oncol ; 11: 736769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868925

RESUMO

BACKGROUND: Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT). METHODS: Plasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations. RESULTS: A total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 - 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 - 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 - 3, HR 3.753, 95% CI 1.146 - 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 - 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery. CONCLUSIONS: This study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.

8.
Int J Biol Sci ; 15(5): 1080-1090, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182927

RESUMO

Up-regulation of ASB6 has been previously associated with late-stage and poor prognosis of oral squamous cell carcinoma (OSCC) patients. To explore the cellular and molecular basis of how ASB6 enhances the malignancy of OSCC, we employed the clonogenicity and migration assays, murine pulmonary metastasis model, Western blot, and immunofluorescence microscopy to characterize the phenotypes of OSCC cells with lentiviral-based stable overexpression or knockdown of ASB6. We found that ASB6 overexpression increases, whereas ASB6 knockdown decreases, the potential of tumor-sphere formation, colony formation, and expression of Oct-4 and Nanog. While knockdown of ASB6 decreases cell migration in vitro and lung metastasis in mice, the migratory potential was however not promoted by ASB6 overexpression. ASB6 knockdown down-regulates the level of vimentin, and the loss of filopodia formation became more prominent following CRISPR/Cas9-directed knockout of ASB6. Moreover, ASB6 was up-regulated when cells were grown in selective condition featured with a collateral effect of enhancing intracellular stress, and the level of endoplasmic reticulum (ER) stress was further increased by knockdown of ASB6. Thus, ASB6 may attenuate ER stress that would otherwise accumulate and subsequently impede the potential of cells to acquire or sustain the stemness properties and metastatic capacity, thereby enhancing the malignancy of OSCC by increasing the population of cancer stem or stem-like cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Animais , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Estresse do Retículo Endoplasmático/genética , Estresse do Retículo Endoplasmático/fisiologia , Imunofluorescência , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Microscopia Confocal , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo
10.
Chem Commun (Camb) ; 51(3): 549-52, 2015 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-25412283

RESUMO

We prepared Ag-Si microflowers as the photocathode for water splitting through a facile chemical method. The photocurrent and the hydrogen evolution rate of partially Ag particle decorated-Si microwires were enhanced through the synergistic effects of Ag co-catalytic and plasmonic assistance.

11.
ACS Appl Mater Interfaces ; 6(24): 22701-8, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25437918

RESUMO

A successive preparation of FeCo2O4 nanoflakes arrays on nickel foam substrates is achieved by a simple hydrothermal synthesis method. After 170 cycles, a high capacity of 905 mAh g(-1) at 200 mA g(-1) current density and very good rate capabilities are obtained for lithium-ion battery because of the 2D porous structures of the nanoflakes arrays. The distinctive structural features provide the battery with excellent electrochemical performance. The symmetric supercapacitor on nonaqueous electrolyte demonstrates high specific capacitance of 433 F g(-1) at 0.1 A g(-1) and 16.7 F g(-1) at high scan rate of 5 V s(-1) and excellent cyclic performance of 2500 cycles of charge-discharge cycling at 2 A g(-1) current density, revealing excellent long-term cyclability of the electrode even under rapid charge-discharge conditions.

12.
Chem Commun (Camb) ; 49(72): 7917-9, 2013 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-23900347

RESUMO

We report the near-infrared-driven photoelectrochemical water splitting using a ZnO nanorod-array decorated with CdTe quantum dots and plasmon-enhanced upconversion nanoparticles. The plasmon enhanced the intensity of the upconversion emission, which improved the photocurrent and the gas evolution rate of the photoelectrochemical reaction greatly.

13.
ACS Nano ; 6(8): 7362-72, 2012 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-22849358

RESUMO

Artificial photosynthesis using semiconductors has been investigated for more than three decades for the purpose of transferring solar energy into chemical fuels. Numerous studies have revealed that the introduction of plasmonic materials into photochemical reaction can substantially enhance the photo response to the solar splitting of water. Until recently, few systematic studies have provided clear evidence concerning how plasmon excitation and which factor dominates the solar splitting of water in photovoltaic devices. This work demonstrates the effects of plasmons upon an Au nanostructure-ZnO nanorods array as a photoanode. Several strategies have been successfully adopted to reveal the mutually independent contributions of various plasmonic effects under solar irradiation. These have clarified that the coupling of hot electrons that are formed by plasmons and the electromagnetic field can effectively increase the probability of a photochemical reaction in the splitting of water. These findings support a new approach to investigating localized plasmon-induced effects and charge separation in photoelectrochemical processes, and solar water splitting was used herein as platform to explore mechanisms of enhancement of surface plasmon resonance.


Assuntos
Hidrogênio/química , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Oxigênio/química , Ressonância de Plasmônio de Superfície/métodos , Água/química , Campos Eletromagnéticos , Luz , Raios X
14.
J Clin Immunol ; 28(5): 405-10, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18481160

RESUMO

BACKGROUND: Although some previous studies have reported that genetic and immunological factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiological factors of this enigmatical pediatric disease are still poorly understood. PURPOSE: This study aims to investigate whether polymorphisms of the CD40 ligand (CD40L) gene are associated with KD and the development of coronary artery lesions (CAL) in the Taiwanese children. MATERIALS AND METHODS: The CD40L -3459 A/G and IVS4+121 A/G single nucleotide polymorphisms (SNPs) were genotyped in 167 children with KD and 1,010 ethnically matched healthy controls by TaqMan assay. RESULTS: None of the CD40L polymorphisms was associated with susceptibility or CAL development of KD, and this finding was supported by the haplotype analysis. CONCLUSION: In summary, these results provide little support for specific CD40L SNPs in the susceptibility or CAL development of KD in Taiwanese children. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.


Assuntos
Ligante de CD40/genética , Estenose Coronária/genética , Síndrome de Linfonodos Mucocutâneos/genética , Adulto , Povo Asiático , Ligante de CD40/imunologia , Criança , Pré-Escolar , Estenose Coronária/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Polimorfismo de Nucleotídeo Único , Taiwan
15.
Carcinogenesis ; 28(6): 1237-40, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17341658

RESUMO

Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer. The host immunogenetic background plays an important role in the persistence of HPV infection and subsequent development of cervical cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed mainly on activated T cells and is important in the down-regulation of T-cell activation. The aim of this study was to determine if polymorphisms of the CTLA-4 gene are associated with HPV-induced cervical cancer in Taiwanese women. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype -318 C/T, +49 A/G and CT60 A/G polymorphisms in 144 women with cervical squamous cell carcinoma (CSCC) and 378 ethnicity-matched healthy control women. The presence and genotypes of HPV in CSCC were determined by E6-, E7-based nested polymerase chain reaction. The frequency of C/T genotype of -318 C/T polymorphism was significantly higher in patients with HPV-16-positive CSCC compared with controls (odds ratio = 1.99, 95% confidence interval = 1.16-3.42, P(c) = 0.03). No significant associations were found for +49 A/G and CT60 A/G polymorphisms. Analysis of haplotypes, computationally inferred from genotype data, also revealed no significant differences in distribution among all subjects with CSCC, those with HPV-16-positive CSCC and controls. Our results suggest that the -318 C/T variant in the promoter region of the CTLA-4 gene is associated with HPV-16-associated CSCC in Taiwanese women.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação/genética , Carcinoma de Células Escamosas/etiologia , Predisposição Genética para Doença , Papillomavirus Humano 16/fisiologia , Infecções por Papillomavirus/etiologia , Neoplasias do Colo do Útero/etiologia , Antígenos CD/fisiologia , Antígenos de Diferenciação/fisiologia , Antígeno CTLA-4 , Carcinoma de Células Escamosas/genética , Feminino , Haplótipos , Humanos , Infecções por Papillomavirus/genética , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Taiwan , Neoplasias do Colo do Útero/genética
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