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1.
J Transl Med ; 18(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000807

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

2.
Mol Med Rep ; 20(4): 3649-3660, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485619

RESUMO

The main purpose of the present study was to recognize the integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma (ESCC). The mRNA gene expression profile data of GSE38129 were downloaded from the Gene Expression Omnibus database, which included 30 ESCC and 30 normal tissue samples. The differentially expressed genes (DEGs) between ESCC and normal samples were identified using the GEO2R tool. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify the functions and related pathways of the genes. The protein­protein interaction (PPI) network of these DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes and visualized with a molecular complex detection plug­in via Cytoscape. The top five important modules were selected from the PPI network. A total of 928 DEGs, including ephrin­A1 (EFNA1), collagen type IV α1 (COL4A1),  C­X­C chemokine receptor 2 (CXCR2), adrenoreceptor ß2 (ADRB2), P2RY14, BUB1B, cyclin A2 (CCNA2), checkpoint kinase 1 (CHEK1), TTK, pituitary tumor transforming gene 1 (PTTG1) and COL5A1, including 498 upregulated genes, were mainly enriched in the 'cell cycle', 'DNA replication' and 'mitotic nuclear division', whereas 430 downregulated genes were enriched in 'oxidation­reduction process', 'xenobiotic metabolic process' and 'cell­cell adhesion'. The KEGG analysis revealed that 'ECM­receptor interaction', 'cell cycle' and 'p53 signaling pathway' were the most relevant pathways. According to the degree of connectivity and adjusted P­value, eight core genes were selected, among which those with the highest correlation were CHEK1, BUB1B, PTTG1, COL4A1 and CXCR2. Gene Expression Profiling Interactive Analysis in The Cancer Genome Atlas database for overall survival (OS) was applied among these genes and revealed that EFNA1 and COL4A1 were significantly associated with a short OS in 182 patients. Immunohistochemical results revealed that the expression of PTTG1 in esophageal carcinoma tissues was higher than that in normal tissues. Therefore, these genes may serve as crucial predictors for the prognosis of ESCC.


Assuntos
Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Perfilação da Expressão Gênica , Genômica , Humanos , Prognóstico , Mapas de Interação de Proteínas , Transdução de Sinais
3.
Mol Omics ; 15(1): 88-100, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30706927

RESUMO

Differentially methylated genes (DMGs) play a crucial role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). This study aimed to ascertain aberrant DMGs and pathways by comprehensive bioinformatics analysis. We downloaded the gene expression microarray of GSE51287 from the Gene Expression Omnibus (GEO). Aberrant DMGs were obtained using the GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were performed on selected genes by using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed with the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Then, the modules in the PPI networks were analyzed with Molecular Complex Detection, and the hub genes derived from the PPI networks were verified by using the Cancer Genome Atlas. A total of 271 DMGs, including 173 hypermethylated genes, were enriched in the biological processes of peptidyl-tyrosine phosphorylation, positive regulation of transcription from RNA polymerase II promoters, and autophosphorylation. Pathway analysis enrichment revealed cancer, PI3K-Akt, and Ras signaling pathways, and 98 hypomethylated genes were enriched in the biological processes of the immune response, extracellular matrix disassembly, and macrophage differentiation. Pathway enrichment showed rheumatoid arthritis, cytokine-cytokine receptor interaction, and toxoplasmosis. Furthermore, bioinformatics analysis indicated feasible aberrant DMGs and pathways in ESCC. The results provided valuable information on the pathogenesis of ESCC. The significant DMGs may provide novel insights into their potential predictive and prognostic value as methylation-based biomarkers for the precise diagnosis and treatment of ESCC.


Assuntos
Biologia Computacional/métodos , Metilação de DNA/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Bases de Dados Genéticas , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Análise de Sobrevida
4.
J Immunol Res ; 2018: 7498514, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175154

RESUMO

Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the first time that miR-34a expression was significantly downregulated in clinical CCa samples from oxaliplatin-resistant patients and in experimentally established multidrug-resistant CCa cells. By using histoculture drug response assay, we further confirmed that clinical CCa samples with lower miR-34a expression appeared to be more resistant to chemotherapy. Functionally, ectopic expression of exogenous miR-34a resensitized multidrug-resistant HCT-8/OR cells to oxaliplatin treatment, whereas miR-34a inhibition augmented the oxaliplatin resistance in chemosensitive HCT-8 cells. Mechanistically, miR-34a positively regulated the mRNA stability of the ornithine decarboxylase antizyme 2 (OAZ2) by directly targeting its three prime untranslated region (3'UTR). Consequently, suppression of the expression of miR-34a/OAZ2 signaling by chemotherapeutic agents significantly enhanced the activation of MDR-associated ATP-binding cassette (ABC) transporters and antiapoptosis pathways, thus leading to MDR development in CCa cells. Collectively, our combined analysis reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to CCa chemotherapy.


Assuntos
Proteínas de Transporte/metabolismo , Colo/fisiologia , Neoplasias do Colo/genética , Resistência a Múltiplos Medicamentos/genética , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Antineoplásicos/farmacologia , Carcinogênese , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Estabilidade de RNA , RNA Mensageiro/genética , Transdução de Sinais
5.
Oncotarget ; 8(54): 92454-92469, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29190930

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors with poor prognosis worldwide. Identifying the prognostic biomarkers and potential mechanisms of such tumors has attracted increasing interest in esophageal cancer biology. Our previous study showed that phospholipase C elipson 1 (PLCE1) expression is up-regulated and associated with disease progression in esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its target gene expression. However, studies on miRNA-regulated PLCE1 expression and its cellular function are still very few. We found that miR-34a is significantly expressed lower in ESCC tissues. We further showed that PLCE1 is a direct functional target gene of miR-34a, and the functional roles of miR-34a in ESCC cell lines in vitro were also determined through gain- and loss-of-function analyses. Results revealed that miR-34a functions as a tumor suppressor by inhibiting the proliferation, migration, and EMT phenotype, as well as promoting apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and promotes tumorigenicity in vivo and vitro. PLCE1 expression is negatively correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a exerts its anti-cancer function by suppressing PLCE1. The newly identified miR-34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis and represents a new candidate therapeutic target for ESCC treatment.

6.
Oncotarget ; 8(13): 21526-21538, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28423526

RESUMO

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Macrófagos/imunologia , Neovascularização Patológica/patologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Ativação de Macrófagos/imunologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Superfície Celular/imunologia
7.
Exp Mol Pathol ; 102(1): 15-21, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27939650

RESUMO

Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Macrófagos/metabolismo , Fator C de Crescimento do Endotélio Vascular/biossíntese , Análise de Variância , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptores de Superfície Celular/metabolismo , Fatores Sexuais
8.
J Transl Med ; 14(1): 137, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27188458

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear. METHODS: PFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial-mesenchymal transition (EMT) were detected by Western blot analysis. RESULTS: Compared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Our findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Terapia de Alvo Molecular , Profilinas/metabolismo , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Linhagem Celular Tumoral , Movimento Celular , Forma Celular , Progressão da Doença , Transição Epitelial-Mesenquimal , Epitélio/metabolismo , Epitélio/patologia , Carcinoma de Células Escamosas do Esôfago , Grupos Étnicos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Fenótipo , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Prognóstico , Modelos de Riscos Proporcionais , RNA Interferente Pequeno/metabolismo , Curva ROC , Transfecção , Regulação para Cima
9.
Oncotarget ; 7(2): 1777-95, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26657507

RESUMO

Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3'UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.


Assuntos
Carcinoma de Células Escamosas/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Fosfoinositídeo Fosfolipase C/genética , Regiões 3' não Traduzidas/genética , Apoptose/genética , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Fosfoinositídeo Fosfolipase C/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Int J Clin Exp Pathol ; 8(8): 9293-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464679

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with a strong tendency toward familial aggregation and a higher incidence as well as mortality in Kazakh population. Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that plays a role in controlling the progression of lung cancer, hepatocellular cancer, breast cancer and gastric cancer. But the association between TNF-α-308G/A and ESCC still remains unclarified. MATERIALS AND METHODS: Here, we investigated the potential associations between the TNF-α-308G/A and susceptibility to ESCC in 212 cases and 200 controls from a pure ethnic population of Kazakh. DNA extraction and Real-time PCR were performed to detect the TNF-α-308G/A expression levels and odd ratios (ORs) with the corresponding 95% confidence interval (CI) were to evaluate their association with TNF-α-308G/A polymorphism. RESULTS: We found that the frequencies of TNF-α-308G/A in the cases were similar to that of the controls with no differences being statistically significant (χ(2)=1.23, P>0.05). Using the G allele as the reference genotype, individuals who carried A allele had a significantly increased risk of developing ESCC (OR=2.64, 95% CI=1.31~5.35). Especially, the G/A+A/A genotype are associated with increased risk of metastatic as compared with GG genotype individuals (OR=2.08, 95% CI=1.14-3.80, P=0.02). CONCLUSIONS: Our findings suggest that though the TNF-α-308G/A polymorphism may not be correlated with the susceptibility to Kazakh's ESCC in Xinjiang, patients who carry A allele tend to poorly differentiated and lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Alelos , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Cazaquistão , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
J Transl Med ; 13: 321, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26444413

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC. METHODS: Multiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied. RESULTS: SLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Combined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.


Assuntos
Proteínas de Transporte de Cátions/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/etnologia , Carcinoma/metabolismo , Carcinoma/terapia , Proliferação de Células , China , Estudos de Coortes , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , RNA Interferente Pequeno/metabolismo , Análise Serial de Tecidos , Resultado do Tratamento , Regulação para Cima
12.
Rev Sci Instrum ; 86(7): 076101, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26233415

RESUMO

An energy harvester based on a round acoustic fence (RAF) has been proposed and studied. The RAF is composed of cylindrical stubs stuck in a circular array on a thin metal plate, which can confine the acoustic energy efficiently. By removing one stub and thus opening a small gap in the RAF, acoustic leakage with larger intensity can be produced at the gap opening. With the vibration source surrounded by the RAF, the energy harvesting at the gap opening has a wide bandwidth and is insensitive to the position of the vibration source. The results may have potential applications in harvesting the energy of various vibration sources in solid structure.

13.
Kaohsiung J Med Sci ; 31(2): 70-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25645984

RESUMO

Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Receptor Notch1/metabolismo , Fatores de Transcrição/metabolismo , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Caderinas/metabolismo , Carcinoma Ductal de Mama/secundário , Transição Epitelial-Mesenquimal , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Fatores de Transcrição da Família Snail
14.
Int J Clin Exp Pathol ; 8(10): 13156-65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26722514

RESUMO

BACKGROUND: Many studies have suggested a relationship between human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma (ESCC). However, findings are inconclusive, potentially because of geographic heterogeneity and variations in detection methods. OBJECTIVES: We sought to further investigate the prevalence of HPV with a new detection method, the MassARRAY Sequenom technique, in esophageal squamous cell carcinomas occurring in patients belonging to Kazakh populations in Xinjiang, China. STUDY DESIGN: In the present study, a novel genotyping method for detecting 30 HPV genotypes, specifically by genotyping both the HPV E6 and L1 genes with multiplex PCR using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS) was first adopted to evaluate HPV genotypes in 89 esophageal cancer samples and 49 matched adjacent normal esophageal tissues. RESULTS: Six HPV genotypes (HPV6, HPV16, HPV33, HPV39, HPV51, and HPV82) were present in at least 51.7% of the esophageal carcinoma tissues, which was significantly greater than 28.6% prevalence among controls (P < 0.05). HPV16 was the most common of all the genotypes investigated (HPV16 prevalence in carcinoma tissue: 49.4%; odds ratio 3.02, 95% confidence interval 1.39-6.53). HPV-positive ESCC patients were generally younger than HPV-negative patients (P = 0.04). In addition, HPV infection was more common in cases of well-differentiated and shallower invasive depth. CONCLUSIONS: Based on this new detection method, our findings reiterate the possibility that HPV infection (especially HPV16) may be involved in the etiology of esophageal carcinoma in the Kazakh populations and that HPV E6 gene positivity may be associated with prognosis of patients.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Esofágicas/virologia , Proteínas Oncogênicas Virais/análise , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Prevalência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
15.
Asian Pac J Cancer Prev ; 15(22): 9661-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25520085

RESUMO

BACKGROUND: A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). However, the results of PLCE1 expression in esophageal and gastric cancer remain inconsistent and controversial. Moreover, the effects on clinicopathological features remain undetermined. This study aimed to provide a precise quantification of the association between PLCE1 expression and the risk of ESCC and GCA through meta-analysis. MATERIALS AND METHODS: Eligible studies were identified from PubMed, Wanfang Data, ISI Web of Science, and the Chinese National Knowledge Infrastructure databases. Using RevMan5.2 software, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of PLCE1 expression with clinicopathological features relative to ESCC or GCA. RESULTS: Seven articles were identified, including 761 esophageal and gastric cancer cases and 457 controls. Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7). Moreover, invasion depth (pooled OR=3.62; 95%CI=2.30 to 5.70) and lymph node metastasis (pooled OR=4.21; 95%CI=2.69 to 6.59) were linked with PLCE1 expression in gastric cancer. However, no significant associations were determined between PLCE1 overexpression and the histologic grade, invasion depth, and lymph node metastasis in esophageal cancer. CONCLUSIONS: Our meta- analysis results indicated that upregulated PLCE1 is significantly associated with an increased risk of tumor progression in ESCC and GCA. Therefore, PLCE1 expression can be appropriately regarded as a promising biomarker for ESCC and GCA patients.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Fosfoinositídeo Fosfolipase C/biossíntese , Fosfoinositídeo Fosfolipase C/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Cárdia/patologia , Carcinoma de Células Escamosas do Esôfago , Predisposição Genética para Doença , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Trato Gastrointestinal Superior/patologia
16.
Int J Clin Exp Pathol ; 7(9): 6165-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25337265

RESUMO

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. However, only some high risk human papillomavirus (HR-HPV)-infected women progress to cervical cancer, host immunogenetic factors human leukocyte antigen (HLA) may account for viral antigens presenting individually or together in the progression to cervical cancer. This study examined the association between the development of invasive cervical cancer (ICC) and the determinant factors including HLA-DRB1*1501 and DQB1*0602, HR-HPV infection among Chinese Uighur and Han populations. Blood samples, cervical swabs and biopsies were obtained from 287 patients with ICC (192 Uighurs and 95 Hans) and 312 healthy controls (218 Uighurs and 94 Hans). HPV DNA was detected by PCR and HLA-DRB1*1501 and DQB1*0602 alleles were performed using PCR-SSP method. HPV16 infection rates was significantly higher among Uighur and Han with ICC as compared to healthy controls (OR = 58.317; 95% CI: 39.663-85.744; OR = 33.778; 95% CI: 12.581-90.691; P < 0.05 for all). HLA-DRB1*1501 (OR = 0.305; 95% CI: 0.115-0.813; P < 0.05) and HLA-DRB1*1501-DQB1*0602 haplotype frequencies (OR = 0.274; 95% CI: 0.086-0.874; P < 0.05) were significantly reduced in Han ICC. The HLA-DQB1*0602 frequency significantly decreased among Uighur women with ICC (OR = 0.482; 95% CI: 0.325-0.716; P < 0.05). Similar tendencies were observed for DQB1*0602 with HPV16-positive ICC (OR = 0.550; 95% CI: 0.362-0.837; P < 0.05). This study suggests that HLA-DRB1*1501 and DQB1*0602 alleles may influence the immune response to HPV16 infection and decrease the risk of ICC among Uighurs and Hans in Xinjiang, China.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , DNA Viral/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Testes de DNA para Papilomavírus Humano , Papillomavirus Humano 16/genética , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Razão de Chances , Infecções por Papillomavirus/etnologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Fenótipo , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Fatores de Proteção , Fatores de Risco , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-25078861

RESUMO

Ultra-flow liquid chromatography/quadrupole-time-of-flight mass spectrometry (UFLC/Q-TOF MS) method combined with metabolitepilot(MT) software was used for analysis of the metabolites of liguzinediol in dogs. Urine, bile, feces and plasma samples were collected after intravenous administration of 8 mg/kg liguzinediol to healthy dogs. Besides liguzinediol, seven metabolites were detected and identified by UFLC/Q-TOF MS method. The results showed that liguzinediol had some main metabolic pathways in dogs including oxidation, sulfation, cysteine conjugation, N-acetylcysteine conjugation and glucuronidation.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Pirazinas/química , Pirazinas/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Bile/química , Cães , Fezes/química , Redes e Vias Metabólicas , Pirazinas/análise
18.
Int J Clin Exp Pathol ; 7(7): 3673-83, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25120743

RESUMO

Inflammatory myofibroblastic tumour (IMT) is a relatively rare soft tissue malignancy. It exhibits locally aggressive behavior with a tendency for local recurrence and rare metastasis, and rare recurrent IMTs may show histological progression. The genetic hallmark of IMT is ALK rearrangement from chromosome arm 2p, but gene mutations involved in IMT remain poorly understood. The aim of the present study was to perform a pairwise comparison of the gene mutations occurring in primary and recurrent IMT from the same patient. We conducted a high-throughput analysis of 238 known mutations of 19 oncogenes in pairwise comparison primary and recurrent samples from 2 patients of IMT using Sequenom MassARRAY technology. Our results revealed 2 mutations in 2 recurrent lesion samples, including one in exon 11 of the KIT gene, resulting in a T-C substitution at position 1727 (L576P), the recurrent sample underwent histologic progression with "pleomorphic undifferentiated sarcoma-like" transformation; the other mutation was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624 (E542K). Moreover, no any mutation was found in the primary lesion samples from 2 patients. Our findings suggest that variable genome changes might be present in IMT, especially during the progression from a primary tumour to recurrence. To the best of our knowledge, no such longitudinal study of IMT has been undertaken previously.


Assuntos
Mutação , Miofibroma/genética , Recidiva Local de Neoplasia/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Feminino , Genótipo , Ensaios de Triagem em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miofibroma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia
19.
Int J Clin Exp Pathol ; 7(7): 4391-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25120824

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as "eczema". The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months.


Assuntos
Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Equimose/etiologia , Neoplasias Hematológicas/complicações , Humanos , Masculino , Neoplasias Cutâneas/complicações
20.
Asian Pac J Cancer Prev ; 15(11): 4513-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24969878

RESUMO

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteína BRCA1/genética , Neoplasias da Mama/genética , Éxons , Mutação , Adolescente , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Adulto Jovem
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