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1.
Ann Oncol ; 30(6): 990-997, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30916311

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Genômica/métodos , Neoplasias Hepáticas/genética , Mutação , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/classificação , Carcinoma Hepatocelular/patologia , Evolução Clonal , Variações do Número de Cópias de DNA , Heterogeneidade Genética , Humanos , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/patologia , Filogenia , Prognóstico , Microambiente Tumoral , Sequenciamento do Exoma/métodos
2.
Water Sci Technol ; 67(7): 1620-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23552253

RESUMO

The feasibility of using raw diatomite and aluminum hydroxide-modified diatomite (Al-diatomite) for removal of aniline and phenol from water was investigated. Their physicochemical characteristics such as pHsolution, point of zero charge (pHPZC), surface area, Fourier transform infrared (FT-IR) and scanning electron microscopy was determined. After the raw diatomite was modified, the surface area of Al-diatomite increases from 26.67 to 82.65 m(2) g(-1). The pHPZC and pHsolution (10%) occurred around pH 5.2 and pH 8.6, respectively. The removal rates of aniline and phenol on diatomite and Al-diatomite decreased with increasing solution pH, while surface charge density decreased. The adsorption of aniline and phenol on diatomite presented a good fit to the Langmuir and Freundlich models, but the models are not fit to forecast the adsorption of aniline and phenol on Al-diatomite. The study indicated that electrostatic interaction was a dominating mechanism of aniline and phenol sorption onto Al-diatomite.


Assuntos
Hidróxido de Alumínio/química , Compostos de Anilina/isolamento & purificação , Terra de Diatomáceas/química , Fenol/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Concentração de Íons de Hidrogênio , Termodinâmica
3.
Water Sci Technol ; 67(1): 152-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23128633

RESUMO

The single-solute and bisolute sorption behaviour of phenol and trichloroethylene, two organic compounds with different structures, onto cetyltrimethylammonium bromide (CTAB)-montmorillonite was studied. The monolayer Langmuir model (MLM) and empirical Freundlich model (EFM) were applied to the single-solute sorption of phenol or trichloroethylene from water onto monolayer or multilayer CTAB-montmorillonite. The parameters contained in the MLM and EFM were determined for each solute by fitting to the single-solute isotherm data, and subsequently utilized in binary sorption. The extended Langmuir model (ELM) coupled with the single-solute MLM and the ideal adsorbed solution theory (IAST) coupled with the single-solute EFM were used to predict the binary sorption of phenol and trichloroethylene onto CTAB-montmorillonite. It was found that the EFM was better than the MLM at describing single-solute sorption from water onto CTAB-montmorillonite, and the IAST was better than the ELM at describing the binary sorption from water onto CTAB-montmorillonite.


Assuntos
Bentonita/química , Fenóis/química , Tricloroetileno/química , Purificação da Água/métodos , Água/química , Adsorção , Poluentes Químicos da Água/química
4.
Neurochem Res ; 29(11): 2153-61, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15662850

RESUMO

This study examined the relationship between the distance of axotomy and the death of injured retinal ganglion cells (RGCs) in adult hamsters and the relationship of cytochrome c and caspase-3 on the death pathway of RGCs. The left optic nerve (ON) of adult hamsters was transected either at 1 or 3 mm away from the optic disc, and retrogradely labeled with Flurogold on the ON stump. After a predetermined period of postoperative time, the surviving RGCs were counted by retina flat-mount, and the activation of cytochrome c and caspase-3 were investigated by immunohistochemistry. Cell loss was found to be much faster (P < 0.01), more cells with cytochrome c were observed (P < 0.05) and the activation of caspase-3 was earlier when ON was transected 1 mm away from the optic disc than when was transected 3 mm away from the optic disc. Distance of axotomy affects the axotomized cell death rate where more RGCs died when the ON transection was applied closer to the eye. The timing of activation of caspase-3 in the RGCs may be linked to the distance of axotomy.


Assuntos
Axotomia , Caspases/metabolismo , Citocromos c/metabolismo , Nervo Óptico/fisiologia , Células Ganglionares da Retina/enzimologia , Animais , Caspase 3 , Sobrevivência Celular/fisiologia , Cricetinae , Fragmentação do DNA , Ativação Enzimática/fisiologia , Imuno-Histoquímica , Masculino , Mesocricetus
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