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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.
World J Clin Cases ; 7(23): 4163-4171, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832423

RESUMO

BACKGROUND: Gallbladder squamous cell carcinoma (GBSCC) is a rare subtype of malignancy and accounts for only 2%-3% of gallbladder malignancies. Due to its rapid development, most patients with GBSCC initially present with an advanced stage of the disease and hence a poor prognosis. The clinicopathological and biological features of SCC remain to be fully elucidated, owing to its uncommon occurrence. The majority of currently available data only described individual case reports or series analyses of trivial cases. CASE SUMMARY: A 64-year-old man was admitted for progressively poor abdominal distension and pain. Liver computed tomography (CT) showed infiltration of gallbladder carcinoma into the adjacent liver, and enlarged retroperitoneal lymph nodes. The patient underwent radical cholecystectomy. Part of the mass was grey and soft, and the neoplastic section showed a purulent-necrotic lesion. Hematoxylin and eosin staining revealed a moderately differentiated SCC. Immunohistochemical studies showed strong staining of the tumor for AE1/3 and CK5/6. Staining for CK19, CK7, and CAM5.2 was positive in the cytoplasm. Systemic chemotherapy was not administered because of the patient's poor physical condition. After five months, CT and magnetic resonance cholangiopancreatography showed multiple metastases in the liver and abdominal cavity. CONCLUSION: Squamous components of GBSCC may explain the complex biological behavior, and CD109 may be involved in the pathogenesis.

3.
Sci Rep ; 9(1): 8401, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182739

RESUMO

Mitogen-activated protein kinase kinase kinase 3 (MAP3K3), a member of the serine/threonine protein kinase family, is ubiquitously expressed and acts as an oncogene. However, the expression and exact molecular mechanism of MAP3K3 in ovarian carcinoma (OC) remain unclear. Here, we found that MAP3K3 protein was highly expressed in 70.5% of high-grade serous ovarian carcinoma (HGSOC) samples. MAP3K3 overexpression was significantly associated with the FIGO stage and chemotherapy response. Additionally, MAP3K3 overexpression was associated with reduced disease-free survival and overall survival. In vitro experiments showed that MAP3K3 overexpression promoted cell proliferation, inhibited apoptosis, and enhanced the migration and invasion of OC cells. Moreover, in vivo tumourigenesis experiments confirmed that silencing MAP3K3 significantly reduced the growth rate and volume of transplanted tumours in nude mice. Drug sensitivity experiments demonstrated that differential expression of MAP3K3 in OC cell lines correlates with chemotherapy resistance. Functionally, the MAP3K3 gene regulated the malignant biological behaviour of OC cells by mediating NF-κB signalling pathways, affecting the downstream epithelial-mesenchymal transition and cytoskeletal protein expression. Our results unveiled the role of MAP3K3 in mediating NF-κB signalling to promote the proliferation, invasion, migration, and chemotherapeutic resistance of OC cells, highlighting a potential new therapeutic and prognostic target.

4.
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
5.
Oncotarget ; 8(20): 33911-33921, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28430610

RESUMO

Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.


Assuntos
Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/complicações , Células Neoplásicas Circulantes/patologia , Veia Porta/patologia , Trombose Venosa/etiologia , Trombose Venosa/terapia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Terapia Combinada , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Prognóstico , Avaliação de Sintomas , Resultado do Tratamento , Trombose Venosa/diagnóstico , Trombose Venosa/mortalidade
6.
Oncotarget ; 8(17): 28455-28462, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28415705

RESUMO

Numerous epidemiological studies have evaluated the association between polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1) protein and the risk of female reproductive system cancer, but results are inconclusive. To gain a comprehensive picture of available evidence, we searched for relevant studies in the PubMed, EMBASE, Scopus, and Chinese National Knowledge Infrastructure databases up to December 17, 2016. A total of 26 case-control studies were picked out. The pooled odds ratio (OR) with its 95% confidence interval (CI) was calculated to estimate the association. Based on data of all study participants, we did not find a positive association of rs25487 or rs1799782 polymorphism with risk of female reproductive cancer risk. Subgroup analysis, however, identified two alleles as being associated with an increased risk of female reproductive system cancer in Asians: the A allele of rs25487 (heterozygous genetic model, OR 1.16, 95%CI 1.00-1.36), and the T allele of rs1799782 (homozygous model, OR 2.30, 95%CI 1.39-3.82; dominant model, OR 1.28, 95%CI 1.10-1.50; recessive model, OR 2.11, 95%CI 1.33-3.34). Moreover, the AA genotype at rs25489 was determined to be a risk factor for cervical cancer etiology (homozygous model, OR 2.91, 95%CI, 1.17-7.26; recessive model, OR 3.16, 95%CI 1.91-5.24). This meta-analysis suggests that no association between rs25487 or rs1799782 gene polymorphism and risk of female reproductive cancer risk was found. These results should be validated in larger studies.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias dos Genitais Femininos/genética , Polimorfismo de Nucleotídeo Único , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Alelos , Feminino , Genótipo , Humanos , Razão de Chances
7.
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
8.
Yao Xue Xue Bao ; 51(2): 248-56, 2016 02.
Artigo em Chinês | MEDLINE | ID: mdl-29856578

RESUMO

Drug metabolism research plays an essential role in drug discovery and development. Great efforts have been made domestically to be line with the international standardized research on drug metabolism. In this article, we will review new-generation of tyrosine kinase inhibitors(TKIs), these TKIs include icotinib, apatinib, famitinib, flumatinb, allitinib, fruquintinib, and selatinib, among which icotinib and apatinib have been approved by China food and drug administration(CFDA) to reach the market, while others are in clinical trials. For these TKIs, the structural modified sites are active metabolic centers and CYP3A4 is identified as the primary metabolic enzyme. Considering the active intermediates, the crown ether ring of icotinib is oxidated to open to form an aldehyde; the indolylidene ring of famitinib is oxidated followed by rearrangement to form a quinone- imine; the α, ß-unsaturated carbonyl group of allitinib is oxidated to form an epoxide, these intermediates are capable of covalently binding biomolecules and generating toxicity. In addition, human (14)C radioactive trials of most of these TKIs have not been conducted, and the data of drug-drug interactions in clinic are also absent, which indicate our deficiency compared to the international regular approaches in metabolic research.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Acrilamidas , Compostos de Anilina , Benzofuranos , China , Éteres de Coroa , Interações Medicamentosas , Humanos , Indóis , Proteínas Tirosina Quinases , Pirróis , Quinazolinas
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.
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
13.
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
14.
Int J Clin Exp Pathol ; 6(12): 2787-99, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24294365

RESUMO

Synovial sarcoma (SS) is a malignant tumor of soft tissue and is noted for late local recurrence and metastasis. Aberrant epithelial-mesenchymal transition (EMT) has been implicated in the pathogenesis of diverse human malignancies. Immunohistochemical techniques were used to assess EMT-related proteins (E-cadherin, N-cadherin, ß-catenin, Snail, and Slug) and the TGF-ß1 pathway (TGF-ß1 and Smad2/3) proteins expression in different histological subtypes and epithelial mesenchymal compositions of SS. The expression of cell-surface (E-cadherin) and cytoskeletal proteins (ß-catenin) were higher significantly in biphasic SSs (BSSs) (70.4%, 51.9%) than MFSSs (both for 10%). Among monophasic fibrous SSs (MFSSs) samples, E-cadherin protein expression was negatively correlated with expression Snail, Slug, TGF-ß1, and Smad2/3. The expression levels of Snail and Smad2/3 were correlated with the pTNM stage (I-II vs. III-IV; P=0.047, P=0.021) and TGF-ß1 exhibited a tendency toward a positive correlation with pTNM stage (I-II vs. III-IV; P=0.052), but did not correlate with the histological grade (p>0.05). Interestingly, our data showed that expression of E-cadherin protein correlated with greater survival in SS patients. Overexpression of Snail, and TGF-ß1 is associated with suppressed expression of E-cadherin in MFSSs, which supports the hypothesis that the MFSS subtype may have developed via neoplastic EMT.


Assuntos
Biomarcadores Tumorais/análise , Transição Epitelial-Mesenquimal , Sarcoma Sinovial/química , Neoplasias de Tecidos Moles/química , Fator de Crescimento Transformador beta1/análise , Adolescente , Adulto , Idoso , Antígenos CD/análise , Caderinas/análise , Criança , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Sarcoma Sinovial/mortalidade , Sarcoma Sinovial/patologia , Transdução de Sinais , Proteína Smad2/análise , Proteína Smad3/análise , Fatores de Transcrição da Família Snail , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Fatores de Transcrição/análise , Adulto Jovem , beta Catenina/análise
15.
Gene ; 530(2): 315-22, 2013 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-23981775

RESUMO

Although recent genome-wide association studies of esophageal squamous cell carcinoma (ESCC) identified a susceptibility locus in phospholipase C epsilon 1 (PLCE1) in Chinese Han populations, few studies further confirmed these findings in pure Kazakh population in which there are higher incidence and mortality of ESCC. Here, we investigated the potential associations between 19 SNPs of PLCE1 and susceptibility to ESCC in 222 cases and 326 controls from a pure ethnic population of Kazakh. Real-time PCR and immunohistochemistry were performed to detect the PLCE1 expression levels and evaluate their association with PLCE1 polymorphism. We found that only 4 SNPs (rs753724, rs11187842, rs2274223, and rs12263737) with moderate linkage disequilibrium (LD) confer significantly increased risk of ESCC, with the ORs ranging from 1.43 to 2.04, and there was a risk allele dose-dependent increase in ESCC risk (P-trend=0.043). Especially, the risk effects of rs2274223 were more evident in poor differentiation and advanced clinical stages of Kazakh ESCC. Additionally, the significantly lowest PLCE1 mRNA expression was found in the KYSE-150 cell line having no risk alleles compared with other three cell lines having risk alleles, and the normal tissues of both homozygous mutant type of PLCE1 rs12263737 and rs2274223 had a higher PLCE1 staining score than that of homozygous wild type. Our findings suggested that genetic variants in PLCE1 might serve as candidate markers for Kazakh ESCC susceptibility, and these LD variants might influence ESCC risk individually and jointly by promoting the messenger RNA and protein expression of the gene.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Expressão Gênica , Predisposição Genética para Doença , Fosfoinositídeo Fosfolipase C/genética , Polimorfismo Genético , Idoso , Alelos , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , Linhagem Celular , China/epidemiologia , Neoplasias Esofágicas/etnologia , Feminino , Frequência do Gene , Humanos , Cazaquistão/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Risco
16.
PLoS One ; 8(5): e62971, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690972

RESUMO

Soft tissue sarcomas (STSs) are a rare and fascinating group of diseases that can be subdivided into specific reciprocal translocations in STSs (SRTSs) and nonspecific reciprocal translocations in STSs (NRTSs). PTEN mutations are rare in STSs, suggesting that PTEN expression may be lost by alternative mechanisms such as methylation. In order to reveal whether aberrant PTEN methylation occurs in STSs, MassARRAY Spectrometry was carried to detect methylation patterns of PTEN in STSs. We evaluated methylation levels in 41 CpG sites from -2,515 to -2,186 bp (amplicon A) and -1,786 to -1,416 bp (amplicon B) relative to the translation initiation site in 110 different cases (46 cases of SRTSs, 40 cases of NRTSs, and 24 cases of normal controls). In addition, immunohistochemistry (IHC) was used to detect the loss of PTEN to determine whether PTEN alterations were responsible for decreased PTEN expression. Our data showed that expression of PTEN was diminished in 49 (57%) STSs, whereas the remaining cases (43%) were classified as high expression. Our previous results found that only 2 of 86 cases (2.3%) had a PTEN mutation suggesting that PTEN may be mainly downregulated in STSs by methylation, but not by mutation of PTEN itself. We observed that amplicon A was hypermethylated in STSs with low PTEN expression, whereas normal controls had low methylation levels (P<0.0001), which was not present in amplicon B (P>0.05), nor were there significant differences in the methylation levels in PTEN between SRTS and NRTS cases. The majority of individual CpG units within two amplicons was demonstrated to be hypermethylated. These findings indicate that PTEN hypermethylation is a common event in STSs suggesting that the inactivation of PTEN may be due to hypermethylation in the promoter of PTEN. The aberrant methylation of the CpG sites within PTEN promoter may serve as a potential candidate biomarker for STSs.


Assuntos
Regulação Neoplásica da Expressão Gênica/fisiologia , Espectrometria de Massas/métodos , PTEN Fosfo-Hidrolase/metabolismo , Sarcoma/metabolismo , Análise de Variância , Ilhas de CpG/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Metilação , PTEN Fosfo-Hidrolase/genética , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Sarcoma/genética , Sarcoma/patologia
17.
PLoS One ; 8(3): e58082, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23505456

RESUMO

AIM: To evaluate the chemopreventive efficacy of vitamin K2 (VK2) analog in patients with hepatocellular carcinoma (HCC) after curative hepatic resection or local ablation, since a recent randomized control trial (RCT) and systematic review have given contradictory results. METHODS: MEDLINE, EMBASE and Cochrane library databases were systematically searched through the end of May 2012. Meta-analysis of RCTs and cohort studies was performed to estimate the effects of the VK2 analog on tumor recurrence rate and overall survival (OS). Risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Six RCTs and one cohort study involving a total of 930 patients were included. VK2 analog therapy did not reduce the 1-year recurrence rate, with a pooled RR of 0.67 (95% CI 0.39-1.13, p = 0.13). However, VK2 analog therapy was associated with a significant reduction in the 2- and 3-year tumor recurrence rates, with respective pooled RRs of 0.65 (95% CI 0.51-0.83, p<0.001) and 0.70 (95% CI = 0.58-0.85, p<0.001). The therapy was also associated with a significant improvement in 1-, 2-, and 3-year OS, with respective pooled RRs of 1.03 (95% CI 1.01-1.05, p = 0.02), 1.11 (95% CI 1.03-1.19, p = 0.005) and 1.14 (95% CI 1.02-1.28, p = 0.02). None of the studies reported adverse effects attributable to VK2 analog therapy. CONCLUSION: The VK2 analog may reduce recurrence rate after 1 year and improve OS in HCC patients as early as 1 year. However, these findings should be considered preliminary since the majority of patients came from an RCT with survival data out to only 1 year. More extensive studies with larger sample sizes and longer follow-up are needed.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Quimioprevenção , Neoplasias Hepáticas/tratamento farmacológico , Vitamina K 2/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Cuidados Pós-Operatórios , Viés de Publicação , Recidiva , Risco , Resultado do Tratamento , Vitamina K 2/efeitos adversos , Vitamina K 2/análogos & derivados
18.
World J Gastroenterol ; 15(29): 3611-20, 2009 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-19653338

RESUMO

AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cells during liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alu-positive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)(+), CD34(+) and CD45(+) cells were observed in the chimeric liver on day 10 after PHx-induced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver. CONCLUSION: HRC liver provides a tool for investigating human liver regeneration in a humanized animal model.


Assuntos
Regeneração Hepática , Fígado/citologia , Quimeras de Transplante , Elementos Alu , Animais , Proliferação de Células , Hepatectomia , Humanos , Hibridização In Situ , Leucócitos Mononucleares/transplante , Fenótipo , Ratos
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 25(2): 217-20, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-21189556

RESUMO

AIM: CCK is one of the strongest endogenous anti-opioid substances and suppresses morphine tolerance which results from long term use of morphine. This study explores the modulatory effect of CCK on pain formalin-induced. METHODS: The effect of formalin-induced pain on CCK immunoreactivity in rat sensory neurons was observed through immunohistochemistry technique. RESULTS: After 1 h of subcutaneous injection of formalin in one paw of rats, the number of positive neurons of CCK immunoreactivity in spinal cord neurons was obviously increased and greater than that of non-injection side (P <0.01). The semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.397 +/- 0.014 and 0.295 +/- 0.007 in injection side and non-injection side respectively, the difference was obvious (P < 0.01). After 3 h of subcutaneous injection of formalin in one paw of rats, the semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.366 +/- 0.009 and 0.303 +/- 0.005 in injection side and noninjection side respectively, the difference was significant (P < 0.01). CONCLUSION: Formalin-induced pain can significantly change semi-quantitative optical density average value of CCK immunoractivity in spinal cord neurons, this indicates CCK participates in modulation of pain.


Assuntos
Colecistocinina/fisiologia , Neurônios/metabolismo , Dor/fisiopatologia , Medula Espinal/metabolismo , Animais , Colecistocinina/metabolismo , Feminino , Formaldeído , Masculino , Dor/induzido quimicamente , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores da Colecistocinina/metabolismo , Receptores da Colecistocinina/fisiologia , Medula Espinal/patologia
20.
Zhonghua Bing Li Xue Za Zhi ; 38(12): 806-9, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20193454

RESUMO

OBJECTIVE: To explore the Notch1 mRNA and protein expression in human breast cancers and normal mammary tissues, and their relationship with the clinical indicators of breast cancers were analyzed. METHODS: Notch1 gene of human breast invasive ductal carcinoma (IDC) and normal mammary gland tissues were amplified by RT-PCR, and the expression of Notch1 protein was detected by immunohistochemical Streptavidin-Biotin Complex (SP) stain in 60 IDC, 30 ductal carcinoma in situ (DCIS) and 60 normal mammary tissues. RESULTS: Notch1 gene of human IDC and normal mammary tissues both could express in a transcription level; the positive rates of Notch1 protein expression in normal mammary tissues and DCIS were 55% and 70%. Respectively, which did not differ statistically (P > 0.05), while the positive rate in IDC was 90%, significantly higher than that of the normal mammary tissues and DCIS (P < 0.05). The high expression of Notch1 protein in IDC correlate significantly with lymph node metastasis, pathological grades and TNM stages. CONCLUSIONS: Notch1 protein was over expressed in breast IDC. A high Notch1 protein expression is considered associating with the evolution and malignant transformation of the breast tumor. The expression of Notch1 gene maybe impact the effect of on the progression of breast cancers.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Glândulas Mamárias Humanas/metabolismo , Receptor Notch1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Receptor Notch1/genética
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