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1.
Mol Med Rep ; 21(2): 883-893, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789407

RESUMO

Rearrangement of the mixed lineage leukemia (MLL; also known as lysine methyltransferase 2A) gene is a recurrent genomic aberration in acute myeloid leukemia (AML). MLLT3, super elongation complex subunit (AF9) is one of the most common MLL fusion partners in AML. The present study aimed to explore the aberrant expression of genes associated with the MLL­AF9 translocation and identified potential new targets for the therapy of AML with MLL­AF9 translocation. The transcriptomic and epigenetic datasets were downloaded from National Center of Biotechnology Information Gene Expression Omnibus (GEO) database. Differentially expressed genes were obtained from two independent datasets (GSE68643 and GSE73457). Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. MLL­AF9­associated chromatin immunoprecipitation sequencing (ChIP­Seq) data was analyzed and identified binding sites for MLL­AF9 and wild type MLL (MLL WT). The ChIP­Seq of histone modification data was downloaded from the GEO database, including histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 79 dimethylation (H3K79me2) and histone 3 lysine 27 acetylation (H3K27ac), was used for comparing histone modification marks between the MLL­AF9 leukemia cells and normal hematopoietic cells at MLL­AF9 and MLL WT binding sites. The differentially expressed genes with the same trend in H3K79me2, H3K27ac and H3K4me3 alteration were identified as potential MLL­AF9 direct target genes. Upon validation using RNA­Seq data from the Therapeutically Applicable Research to Generate Effective Treatments AML project, eight potential direct target genes of MLL­AF9 were identified and further confirmed in MLL­AF9 mouse model using reverse transcription­quantitative polymerase chain reaction. These genes may have a critical role in AML with MLL­AF9 translocation.

2.
Opt Express ; 27(23): 34484-34495, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31878495

RESUMO

We study the propagation dynamics of Janus vortex wave under the action of a focusing lens based upon the formula of focused circular vortex Airy beams. Two dark foci would be generated under the action of a lens, and thus a perfect light hollow bottle could be formed. By controlling corresponding parameters, we could control the focal position and the relative intensity between the two focal intensities. The off-axis optical vortex (OV) would rotate rapidly in two focal regions, but keep still in the lens focus region. The angular displacement of OV in each focusing process is nearly π/2. (Note that the angular displacement for an off-axis OV in single focusing process of Gaussian beam is nearly π.) Two same OVs would repel to each other, but two opposite OVs would attract each other and annihilate at first focus plane in Janus vortex waves.

3.
Oncol Rep ; 42(6): 2426-2434, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638261

RESUMO

RAD51, is a key homologous recombination protein that repairs DNA damage and maintains gene diversity and stability. Previous studies have demonstrated that the over­expression of RAD51 is associated with chemotherapy resistance of tumor cells to chemotherapy, and enhanced activity of DNA damage repair (DDR) systems contributes to resistance of adult T­cell leukemia­lymphoma (ATL) resistance to chemotherapy. Thus, targeting RAD51 is a potential strategy for the sensitization of ATL cells to chemotherapeutic drugs by inducing DNA damage. In general, cells can repair minor DNA damage through DDR; however, serious DNA damage may cause cell toxicity in cells which cannot be restored. In the present, down regulation of RAD51 by shRNA and imatinib sensitized Jurkat cells to etoposide by decreasing the activity of homologous recombination (HR). We found that the suppression of RAD51 by shRNA inhibited tumor cells proliferation and enhanced apoptosis of Jurkat cells after etoposide treatment. Importantly, downregulation of RAD51 by imatinib obviously increased the apoptosis of Jurkat cell after etoposide treatment. These results demonstrated that RAD51 may be of great value to as a novel target for the clinical treatment of adult T­cell leukemia­lymphoma (ATL), and it may improve the survival of leukemia patients.

4.
Cell Physiol Biochem ; 49(6): 2111-2123, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30273928

RESUMO

BACKGROUND/AIMS: T-Cell Acute Lymphoblastic Leukemia (T-ALL) [corrected] is an aggressive disease which is highly resistant to chemotherapy. Studies show that enhanced ability of DNA damage repair (DDR) in cancer cells plays a key role in chemotherapy resistance. Here, we suggest that defect in DDR related genes might be a promising target to destroy the genome stability of tumor cells. METHODS: Since KU70 is highly expressed in Jurkat cells, one of the most representative cell lines of ATL, we knocked down KU70 by shRNA and analyzed the impact of KU70 deficiency in Jurkat cells as well as in NOD-SCID animal models by western blot, immunofluorescence, flow cytometry and measuring DNA repair efficiency. RESULTS: It is observed that silencing of KU70 resulted in accumulated DNA damage and impaired DDR in Jurkat cells, resulting in more apoptosis, decreased cell proliferation and cell cycle arrest. DNA damage leads to DNA double-strand breaks (DSBs), which are processed by either non-homologous end joining(NHEJ) or homologous recombination(HR). In our study, both NHEJ and HR are impaired because of KU70 defect, accompanied with increased protein level of SHP-1, a dephosphorylation enzyme. In turn, SHP-1 led to dephosphorylation of SIRT1, which further impaired HR repair efficiency. Moreover, KU70 deficiency prolonged survival of Jurkat-xenografted mice. CONCLUSION: These findings suggest that targeting KU70 is a promising target for ATL and might overcome the existing difficulties in chemotherapy.


Assuntos
Reparo do DNA por Junção de Extremidades , Autoantígeno Ku/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Reparo de DNA por Recombinação , Sirtuína 1/metabolismo , Animais , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Pontos de Checagem do Ciclo Celular , Quebras de DNA de Cadeia Dupla , Humanos , Células Jurkat , Autoantígeno Ku/antagonistas & inibidores , Autoantígeno Ku/genética , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 6/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Rad51 Recombinase/metabolismo
5.
Opt Express ; 26(18): 23084-23092, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30184964

RESUMO

The abruptly autofocusing properties of partially coherent circular Airy beam (CAB) with different spatial coherent length are theoretically investigated in this paper. It is found that, as spatial coherent length decreases, the size of the focal spot would increase and the focal intensity would decrease. But the abruptly autofocusing property for partially coherent CAB is still quite obvious, when comparing with the common partially coherent Gaussian beam under the same conditions; and its autofocusing position is less easily influenced by coherence. The influences of initial radius r0 and decaying parameter a on the autofocusing property have also been investigated in the end.

6.
J Opt Soc Am A Opt Image Sci Vis ; 35(6): 890-894, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29877331

RESUMO

Controlling the trajectory of circular Airy beams (CABs) by negative launch angles would greatly reduce their abruptly autofocusing property. By numerically simulating the propagation of a circular Airy vortex beam with different initial launch angles, we demonstrate in this paper that a larger topological charge of optical vortex (OV) is quite helpful to enhance the abruptly autofocusing property under different launch angles (especially for negative launch angles), without affecting the focal position and trajectory. Two opposite OVs would attract each other and partially overlap in the focal plane of CAB under different launch angles, causing even stronger autofocusing. As the distance between two OVs increases, the focal intensity contrast would decrease, especially for a beam with positive launch angles, whose autofocusing property decreases much more quickly with the distance.

7.
Mol Med Rep ; 18(2): 1473-1484, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901168

RESUMO

Long non-coding RNAs (lncRNAs) are transcripts characterized by >200 nucleotides, without validated protein production. Previous studies have demonstrated that certain lncRNAs have a critical role in the initiation and development of acute myeloid leukemia (AML). In the present study, the subtype­specific lncRNAs in AML was identified. Following the exclusion of the subtype­specific lncRNAs, the prognostic value of lncRNAs was investigated and a three­lncRNA expression­based risk score [long intergenic non­protein coding RNA 926, family with sequence similarity 30 member A and LRRC75A antisense RNA 1 (LRRC75A­AS1)] was developed for AML patient prognosis prediction by analyzing the RNA­seq data of AML patients from Therapeutically Available Research to Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) projects. In the training set obtained from TARGET, patients were divided into poor and favorable prognosis groups by the median risk score. The prognostic effectiveness of this lncRNA risk score was confirmed in the validation set obtained from TCGA by the same cut­off. Furthermore, the lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis. As further verification of the independent prognostic power of the lncRNA risk score, stratified analysis was performed by a cytogenetics risk group and revealed a consistent result. The prognostic predictive ability of the risk score was compared with the cytogenetics risk group by time­dependent receiver operating characteristic curves analysis. It was revealed that the combination of the lncRNA risk score and cytogenetics risk group provided a higher prognostic value than a single prognostic factor. The present study also performed co­expression analysis to predict the potential regulatory mechanisms of these lncRNAs in a cis/trans/competing endogenous RNA manner. The results suggested that LRRC75A­AS1 was highly associated with the target genes of transcription factors tumor protein 53 and ETS variant 6. Overall, these results highlighted the use of the three­lncRNA expression­based risk score as a potential molecular biomarker to predict the prognosis in AML patients.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Leucemia Mieloide Aguda/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Atlas como Assunto , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Análise Multivariada , Prognóstico , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Risco , Transdução de Sinais , Análise de Sobrevida , Transcriptoma , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
8.
Opt Express ; 23(23): 29834-41, 2015 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-26698466

RESUMO

We have proposed a kind of modified circular Airy beam (MCAB) based upon a modification of the Fourier spectrum of circular Airy beams (CAB) in this paper. Unlike most abruptly autofocusing beams, the position of peak intensity of MCAB can be moved to any rings behind. Two apodization parameters are introduced to describe the propagation characteristics of MCAB. It is found that the focal position, focal trajectory and the size of focal spot do not change with the apodization parameters; but the abruptly autofocusing property will be greatly enhanced if appropriately apodization parameters are chosen. Comparing with the common CAB and the previous blocked CAB, the MCAB shows better abruptly autofocusing property. It may have more applications in various fields.

9.
Oncol Rep ; 34(6): 2935-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26398583

RESUMO

Most chemotherapy drugs used for the treatment of adult T-cell leukemia-lymphoma (ATL) cause cell death directly by inducing DNA damage, which can be repaired via several DNA repair pathways. Enhanced activity of DNA damage repair systems contributes to ATL resistance to chemotherapies. Targeting DNA repair pathways is a promising strategy for the sensitization of ATL cells to chemotherapeutic drugs. in the present study, inhibition of SIRT1 deacetylase by shRNA sensitized Jurkat cells to etoposide by reducing the activity of non-homologous end joining (NHEJ) and homologous recombination (HR). Silencing of SIRT1 deacetylase by shRNA resulted in enhanced apoptosis and cell cycle arrest, while reduced colony formation of Jurkat cells after etoposide treatment was accompanied by elevated acetylation of FOXO1. Furthermore, inhibition of SIRT1 led to decreased activity of DNA damage repair by NHEJ and HR, accompanied by increased Ku70 acetylation. Furthermore, SIRT1 downregulation prolonged the survival time of Jurkat-xenografted mice. These results suggested that SIRT1 promotes DNA double­strand repair pathways in Jurkat cells by deacetylating Ku70, and increases cell proliferation by deacetylating FOXO1. The results suggest that SIRT1 is a potential target for the development of combinatorial treatment for ATL.


Assuntos
Reparo do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia-Linfoma de Células T do Adulto/genética , Sirtuína 1/genética , Adulto , Animais , Antígenos Nucleares/genética , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Dano ao DNA/genética , Reparo do DNA por Junção de Extremidades/genética , Proteínas de Ligação a DNA/genética , Etoposídeo/administração & dosagem , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Recombinação Homóloga/genética , Humanos , Células Jurkat , Autoantígeno Ku , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Camundongos , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/biossíntese , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Opt Express ; 20(14): 14857-63, 2012 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-22772180

RESUMO

We report on the photoluminescence (PL) and lasing characteristics of ZnO nanorod arrays (NRAs) fabricated by hydrothermal process on nanocrystalline ZnO seeded Si and post-growth annealing. The morphology of the ZnO NRAs was examined by field emission scanning electron microscopy and the structure was characterized by x-ray diffraction, Fourier-transform infrared and Raman scattering spectroscopy. The properties of light emission were studied by continuous wave (CW) and 30 ps pulsed ultraviolet excitation. The ZnO NRAs consist of aligned nanorods and are nanocrystalline with wurtzite structure and c-axis orientation. At room temperature, the ZnO NRAs are capable of emitting strong CW PL and pulsed stimulated emission, with the latter showing obvious lasing characteristics. The threshold for lasing was observed to be ~16 kW/cm(2).

11.
Appl Spectrosc ; 65(5): 522-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21513595

RESUMO

Plasma-assisted pulsed laser deposited zirconia (ZrO(2)) films were studied by Fourier transform infrared (FT-IR) and Raman spectroscopy for structural characterization and thermal stability in combination with optical characterization by spectroscopic ellipsometry and optical transmission measurements. Only the monoclinic ZrO(2) phase was positively identified from the infrared and Raman spectra of the as-deposited ZrO(2) films, which show excellent optical transparency from the ultraviolet to the near infrared as revealed by optical characterization. The as-deposited ZrO(2) films are free of any SiO(x) interfacial layer when deposited on silicon. The prepared ZrO(2) films exhibit good thermal stability in their structural, optical, and interfacial properties up to 900 °C. Upon annealing above 1100 °C, a silicon oxide interfacial layer forms due to the oxidation of the silicon substrate surface by the oxygen diffused from the oxide film to the silicon substrate at high temperatures.

12.
Phys Chem Chem Phys ; 13(13): 6211-22, 2011 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-21365094

RESUMO

Nanocrystalline iron-doped tin dioxide (Sn(1-x)Fe(x)O(2)) films with x from 0 to 0.2 were prepared on c-sapphire substrates by pulsed laser deposition. X-ray diffraction and Raman scattering analysis show that the films are of the rutile structure at low compositions and an impurity phase related to Fe(2)O(3) appears until the x is up to 0.2, suggesting the general change of lattice structure due to the Fe ion substitution. The dielectric functions are successfully determined from 0.0248 to 6.5 eV using the Lorentz multi-oscillator and Tauc-Lorentz dispersion models in the low and high photon energy regions, respectively. With increasing Fe composition, the highest-frequency transverse optical phonons E(u) shifts towards a lower energy side and can be well described by (608 - 178x) cm(-1). From the transmittance spectra, the fundamental absorption edge is found to be decreased with the Fe composition due to the joint contributions from SnO(2) and Fe(2)O(3). It can be observed that the doped films exhibit evident excitonic excitation features, which are strongly related to the Fe doping. Among them, the 6A(1g)→ 4T(2g) transition contributes to the onset of optical absorption. Moreover, the remarkable intensity reduction and a red-shift trend with the doping composition, except for the pure film, can be testified by the photoluminescence spectra. It can be concluded that the replacement of Sn with the Fe ion could induce the 2p-3d hybridization and result in the electronic band structure modification of the Sn(1-x)Fe(x)O(2) films.

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