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1.
J Int Med Res ; 48(6): 300060520925948, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32600079

RESUMO

OBJECTIVE: This study investigated the frequency of T-helper (Th)17 lymphocytes and production of cytokine interleukin (IL)-17 in peripheral blood of patients with non-small-cell lung cancer (NSCLC) and their use as a marker of clinical value. METHODS: Sixty patients with NSCLC and 60 healthy volunteers were enrolled in the study. Flow cytometry was used to detect the frequency of Th17 lymphocytes in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of IL-17. We analyzed the association of Th17 lymphocytes and IL-17 levels in the peripheral blood of patients with their clinicopathological features. RESULTS: Frequency of Th17 lymphocytes and production of IL-17 were significantly higher in the NSCLC group than in the control group and were higher in patients with a smoking history compared with non-smokers. Moreover, Th17 lymphocyte and IL-17 expression levels were higher in patients with squamous cell carcinoma than in patients with adenocarcinoma, and significantly higher in patients with stage III and IV cancers than in patients at stage I or II. CONCLUSION: Th17 lymphocytes and IL-17 play an important role in the development of NSCLC in patients and may have clinical value as markers for treatment of NSCLC.

2.
Cell Res ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398863

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a poor-prognosis cancer type with limited understanding of its molecular etiology. Using 508 ESCC genomes, we identified five novel significantly mutated genes and uncovered mutational signature clusters associated with metastasis and patients' outcomes. Several functional assays implicated that NFE2L2 may act as a tumor suppressor in ESCC and that mutations in NFE2L2 probably impaired its tumor-suppressive function, or even conferred oncogenic activities. Additionally, we found that the NFE2L2 mutations were significantly associated with worse prognosis of ESCC. We also identified potential noncoding driver mutations including hotspot mutations in the promoter region of SLC35E2 that were correlated with worse survival. Approximately 5.9% and 15.2% of patients had high tumor mutation burden or actionable mutations, respectively, and may benefit from immunotherapy or targeted therapies. We found clinically relevant coding and noncoding genomic alterations and revealed three major subtypes that robustly predicted patients' outcomes. Collectively, we report the largest dataset of genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment.

3.
Sensors (Basel) ; 20(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218357

RESUMO

We explore a one-stage method for surface anomaly detection in industrial scenarios. On one side, encoder-decoder segmentation network is constructed to capture small targets as much as possible, and then dual background suppression mechanisms are designed to reduce noise patterns in coarse and fine manners. On the other hand, a classification module without learning parameters is built to reduce information loss in small targets due to the inexistence of successive down-sampling processes. Experimental results demonstrate that our one-stage detector achieves state-of-the-art performance in terms of precision, recall and f-score.

4.
Theranostics ; 10(4): 1798-1813, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042337

RESUMO

Background: Cancer genomic studies have identified Zinc Finger Protein 750 (ZNF750) was a novel significantly mutated gene in esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of ZNF750 in the development of ESCC. Methods: Genomic data from 4 reported ESCC cohorts were used to analyze the mutation profile of ZNF750. Tissue microarrays were used to detect its expression in 308 ESCC samples. Furtherly, the effects of ZNF750 on proliferation, colony formation, migration and invasion were tested in ESCC cells. PCR-array, chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay were used to explore the mechanism of ZNF750. Correlation of ZNF750 with its target genes was analyzed in TCGA data from various SCC types. Results: ZNF750 was frequently mutated in ESCC and the most common type was nonsense mutation. Its nucleus/cytoplasm ratio in ESCC was significantly lower than that in paired non-tumor tissues; it was an independent and potential predictor for survival in ESCC patients. Furtherly, ZNF750 knockdown significantly promoted proliferation, colony formation, migration and invasion in ESCC cells. PCR-array showed epithelial-to-mesenchymal transition (EMT) was the main biologic process affected by ZNF750. Moreover, ZNF750 directly bound to the promoter region of SNAI1 and depressed its activity. Decreased ZNF750 up-regulated SNAI1 expression and promoted EMT phenotype. SNAI1 knockdown partially reversed the malignant phenotype induced by ZNF750 knockdown. Further TCGA data analyses showed ZNF750 expression was positively correlated with E-cadherin and negatively correlated with SNAI1, N-cadherin and Vimentin in ESCC and other SCC samples. Conclusion: Our results suggest that ZNF750 may act as a tumor suppressor by directly repressing SNAI1 and inhibiting EMT process in ESCC and other types of SCC.

5.
Thorac Cancer ; 11(2): 224-231, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31860783

RESUMO

BACKGROUND: The objective of this study was to compare three kinds of lymphadenectomy methods along the recurrent laryngeal nerve (RLN) and assess the safety and effectiveness of the new method. METHODS: A total of 194 patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE) at our institution from May 2013 to May 2017 were analyzed retrospectively. According to the method of lymphadenectomy along the left RLN, the patients were divided into three groups: 75 cases underwent the conventional method (A group), 80 cases the skeletonized method (B group) and 39 cases the modified Bascule method (C group). The number of dissected lymph nodes and surgical outcomes were recorded and compared to identify differences among the three groups. RESULTS: The frequency of metastasis to the LRLN lymph node was 18.6% among all patients, and 12%, 20% and 28% in groups A, B and C, respectively. The number of harvested lymph nodes (total/chest/LRLN/LRLN+) in group B and group C were significantly greater than that of group A, but not significant between group B and group C. The hoarseness rate in group C was 15.4%, which was lower than the rate in group B (21.3%) and higher than the rate in group A (13.3%), but there was no statistical significance. CONCLUSIONS: The new method for lymphadenectomy along the left RLN during MIE in the semi-prone position is safe and reliable. It provides sufficient lymph node dissection along the left RLN.

6.
Opt Express ; 27(11): 16195-16205, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31163803

RESUMO

The optical properties of hexagonal GaN microdisk arrays grown on sapphire substrates by selective area growth (SAG) technique were investigated both experimentally and theoretically. Whispering-gallery-mode (WGM) lasing is observed from various directions of the GaN pyramids collected at room temperature, with the dominant lasing mode being Transverse-Electric (TE) polarized. A relaxation of compressive strain in the lateral overgrown region of the GaN microdisk is illustrated by photoluminescence (PL) mapping and Raman spectroscopy. A strong correlation between the crystalline quality and lasing behavior of the GaN microdisks was also demonstrated.

7.
Nat Commun ; 10(1): 1670, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975989

RESUMO

Esophageal squamous cell carcinoma (ESCC) ranks fourth among cancer-related deaths in China due to the lack of actionable molecules. We performed whole-exome and T-cell receptor (TCR) repertoire sequencing on multi-regional tumors, normal tissues and blood samples from 39 ESCC patients. The data revealed 12.8% of ERBB4 mutations at patient level and functional study supported its oncogenic role. 18% of patients with early BRCA1/2 variants were associated with high-level contribution of signature 3, which was validated in an independent large cohort (n = 508). Furthermore, knockdown of BRCA1/2 dramatically increased sensitivity to cisplatin in ESCC cells. 5% of patients harbored focal high-level amplification of CD274 that led to massive expression of PD-L1, and might be more sensitive to immune checkpoint blockade. Finally, we found a tight correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH). Collectively, we reveal high-level ITH in ESCC, identify several potential actionable targets and may provide novel insight into ESCC treatment.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , China , Estudos de Coortes , Variações do Número de Cópias de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Amplificação de Genes , Perfilação da Expressão Gênica , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T/genética , Transcriptoma/genética , Sequenciamento Completo do Exoma/métodos
8.
Nanotechnology ; 29(45): 45LT01, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30160239

RESUMO

Enhanced photoluminescence and improved internal quantum efficiency were demonstrated for ultraviolet light emitting diodes (UV-LEDs) with Al nanohole arrays deposited on the top surface. The effects of the thickness and periodicity of the plasmonic structures on the optical properties of UV-LEDs were studied, and an optimized nanohole array parameter was illustrated. Classical electrodynamic simulations showed that the radiated power is mostly concentrated along the edge of the Al nanohole arrays. Even though no obvious dip was observed in the transmission spectra associated with localized surface plasmon resonance, significant improvements in radiatiative recombination and light extraction efficiency were demonstrated, indicating the influence of Al nanohole arrays on the light emission control of UV-LEDs. It is anticipated that the enhanced luminescence can be obtained for various emitting wavelengths by directly adjusting the periodicity and morphology of the Al nanohole arrays and this new technology can alleviate crystal quality requirements of III-nitride thin films in the development of high efficiency UV optoelectronic devices.

9.
Oncotarget ; 8(68): 112770-112782, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29348864

RESUMO

Understanding the evolutionary processes operative in cancer genome may provide insights into clinical outcome and drug-resistance. However, studies focus on genomic signatures, especially for macro-evolutionary events, in esophageal squamous cell carcinoma (ESCC) are limited. Here, we integrated published genomic sequencing data to investigate underlying evolutionary characteristics in ESCC. We found most of ESCC genomes were polyploidy with high genomic instability. Whole genome doubling that acts as one of mechanisms for polyploidy was predicted as a late event in the majority of ESCC genome. Moreover, loss of heterozygosity events were more likely to occur in chromosomes harboring tumor suppressor genes in ESCC. The 40% of neutral loss of heterozygosity events was not a result of genome doubling, suggesting an alternative mechanism for neutral loss of heterozygosity formation. Importantly, deconstruction of copy number alterations extending to telomere revealed that telomere-bounded copy number alterations play a critical role for amplification/deletion of oncogenes/suppressor genes. For well-known genes SOX2, PIK3CA and TERT, nearly all of their amplifications were telomere bounded, which was further confirmed in a Japanese ESCC cohort. Furthermore, we provide evidence that karyotype evolution was mostly punctuated in ESCC. Collectively, our data reveal the potential biological role of whole genome doubling, neutral loss of heterozygosity and telomere-bounded copy number alterations, and highlight mecro-evolution in ESCC tumorigenesis.

10.
Am J Hum Genet ; 98(2): 256-74, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26833333

RESUMO

Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Estudos de Associação Genética/métodos , Variação Genética , Linhagem Celular , Ciclina D1/genética , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Carcinoma de Células Escamosas do Esôfago , Deleção de Genes , Rearranjo Gênico , Genes p16 , Genoma Humano , Genômica , Humanos , Hibridização in Situ Fluorescente , Receptor ErbB-2/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Notch1/genética , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Translocação Genética
11.
Gigascience ; 5: 1, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26759717

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples. RESULTS: Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC. CONCLUSIONS: Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Genoma Humano/genética , Proteínas de Neoplasias/genética , Receptores Notch/genética , Análise de Sequência de DNA/métodos , Transdução de Sinais/genética , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Deleção Cromossômica , Variações do Número de Cópias de DNA , Progressão da Doença , Neoplasias Esofágicas/patologia , Predisposição Genética para Doença/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/genética , Interferência de RNA
12.
Oncotarget ; 7(3): 3599-613, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26528858

RESUMO

BACKGROUND: Recurrent genetic abnormalities that correlate with clinical features could be used to determine patients' prognosis, select treatments and predict responses to therapy. Esophageal squamous cell carcinoma (ESCC) contains genomic alterations of undefined clinical significance. We aimed to identify mutually exclusive mutations that are frequently detected in ESCCs and characterized their associations with clinical variables. METHODS: We analyzed next-generation-sequencing data from 104 ESCCs from Taihang Mountain region of China; 96 pairs were selected for deep target-capture-based validation and analysis of clinical and pathology data. We used model proposed by Szczurek to identify exclusive mutations and to associate these with pathology findings. Univariate and multivariate analyses with Cox proportional hazards model were used to examine the association between mutations and overall survival and response to chemotherapy. Findings were validated in an analysis of samples from 89 patients with ESCC from Taihang Mountain. RESULTS: We identified statistically significant mutual exclusivity between mutations in NOTCH1 and PIK3CA in ESCC samples. Mutations in NOTCH1 were associated with well-differentiated, early-stage malignancy and less metastasis to regional lymph nodes. Nonetheless, patients with NOTCH1 mutations had shorter survival times than patients without NOTCH1 mutations, and failed to respond to chemotherapy. In contrast, patients with mutations in PIK3CA had better responses to chemotherapy and longer survival times than patients without PIK3CA mutations. CONCLUSIONS: In a genetic analysis of ESCCs from patients in China, we identified mutually exclusive mutations in NOTCH1 and PIK3CA. These findings might increase our understanding of ESCC development and be used as prognostic factors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/patologia , Mutação/genética , Recidiva Local de Neoplasia/patologia , Fosfatidilinositol 3-Quinases/genética , Receptor Notch1/genética , Idoso , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Proliferação de Células/efeitos dos fármacos , China , Cisplatino/administração & dosagem , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Genômica/métodos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas
13.
Fitoterapia ; 79(7-8): 501-4, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18621113

RESUMO

Investigation on Morinda angustifolia resulted in the isolation of a new anthraquinone, 1,8-dihydroxy-2-methyl-3,7-dimethoxyanthraquinone (1), along with five known analogues, lucidin 3-O-beta-primeveroside (2), 1,3-dihydroxy-2-methylanthraquinone (3), lucidin- omega -ethyl ether (4), lucidin-omega-butyl ether (5) and damnacanthol (6). The new compound demonstrated significant antimicrobial activity against Bacillus subtilis, Escherichia coli, Micrococcus luteus, Sarcina lutea, Candida albicans and Saccharomyces sake.


Assuntos
Antraquinonas/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Morinda/química , Extratos Vegetais/farmacologia , Antraquinonas/isolamento & purificação , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Candida albicans/efeitos dos fármacos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Saccharomyces/efeitos dos fármacos
14.
Zhonghua Zhong Liu Za Zhi ; 29(2): 151-3, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17645858

RESUMO

OBJECTIVE: To evaluate the efficacy of esophagogastrostomy in the neck using circular mechanical stapler through the esophageal bed. METHODS: From March 1998 to June 2004 subtotal esophagectomy and mechanical anastomosis with stomach in the neck through the esophageal bed was carried out in 346 esophageal cancer patients. RESULTS: In this series, the positive rate of detecting residual cancer cells in the esophageal stump was 1.2% (4/346); anastomotic fistula was observed in 5.5% (19/346) causing one patient died; the overall operative mortality rate was 0.6% (2/346); esophageal anastomotic stricture developed in 3.8% (13/346), which were cured by endoscopic dilatation. CONCLUSION: This modified operation mode has low rate of complication, reducing impairement to pulmonary function due to the transposed thoracic stomach within the mediastinum instead of the thoracic cavity. Using mechanical circular stapler for anastomosis in the neck simplifies the operation and reducing the postoperative risk caused by anastomotic leak.


Assuntos
Anastomose Cirúrgica/métodos , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Grampeadores Cirúrgicos , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/instrumentação , Carcinoma de Células Escamosas/mortalidade , Fístula Esofágica/etiologia , Neoplasias Esofágicas/mortalidade , Estenose Esofágica/etiologia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Esôfago/patologia , Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Estômago/cirurgia , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento
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