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J Pathol ; 248(1): 103-115, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30666650


Liver metastasis is the main cause of death in patients with colorectal cancer (CRC). Here, we searched for CRC metastasis-associated circular RNA in a mouse model of liver metastasis of CRC by using RNA (transcriptome)-sequencing. We identified a novel and conserved circular RNA, circ-NSD2, functioning as a promoter of CRC metastasis. Circ-NSD2 expression was elevated in CRC tissues and was markedly increased in advanced stages or metastatic tumours of CRC patients. Gain-of-function and loss-of-function experiments demonstrated that circ-NSD2 promoted migration and metastasis of CRC in vitro and in vivo. Mechanistically, circ-NSD2 acted as a sponge for the tumour suppressor miR-199b-5p and activated DDR1 (discoidin domain receptor tyrosine kinase 1) and JAG1 (Jagged 1) genes, which synergistically helped with cell-matrix interaction, migration and metastasis of CRC cells. Taken together, our findings highlight a novel oncogenic function of circ-NSD2 and uncover a key mechanism for the circ-NSD2/miR-199b-5p/DDR1/JAG1 axis in CRC metastasis, which may serve as a prognostic factor and therapeutic target for antimetastatic therapy in CRC patients. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Zhonghua Zhong Liu Za Zhi ; 34(3): 192-5, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22780972


OBJECTIVE: To investigate the influence of ICAM-1 469K/E gene polymorphisms on the risk of atrophic gastritis and dysplasia. METHODS: The ICAM-1 469K/E gene polymorphisms in a total of 372 subjects were detected by polymerase chain reaction-direct sequencing. All of the subjects were from Linqu County, a high risk area of gastric cancer in Shandong Province of northern China. All cases were initially diagnosed as normal or superficial gastritis at the beginning of this study. After a 5-year follow-up, the cases were subdivided into no progression group (no histological progression, n=137), progression group I (progressed to severe chronic atrophic gastritis, n=194) and progression group II (progressed to low-grade dysplasia, n=41). RESULTS: In all 372 subjects, the frequencies of KK, KE or EE genotype of ICAM-1 K469E were 50.5%, 39.2% and 10.2%, respectively. No significant differences were observed in the ICAM-1 469K/E genotype frequencies between the progression group I and no progression group (P>0.05). The frequencies of KK genotype (68.3%) were significantly higher in the progression group II than in the no progression group (49.6%, P=0.035), and also than in the progression group I (47.4%, P=0.015). An increased risk of the progressing to dysplasia from normal or superficial gastritis was found in the individuals with ICAM-1 469KK genotype [odds ratio (OR)=2.21, 95%CI, 1.10-4.42]. CONCLUSION: ICAM-1 469K/E gene polymorphisms are significantly associated with the risk of gastric low-grade dysplasia, but not related with severe chronic atrophic gastritis in a population with high risk of gastric cancer in Linqu County, Shandong Province, China.

Gastrite Atrófica/genética , Molécula 1 de Adesão Intercelular/genética , Polimorfismo Genético , Lesões Pré-Cancerosas/genética , Neoplasias Gástricas/genética , Adulto , Feminino , Seguimentos , Gastrite/genética , Gastrite/patologia , Gastrite Atrófica/patologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Lesões Pré-Cancerosas/patologia , Risco , Neoplasias Gástricas/patologia
World J Gastroenterol ; 18(4): 368-74, 2012 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-22294843


AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. METHODS: The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed. RESULTS: Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage IV had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). CONCLUSION: Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment.

Predisposição Genética para Doença , Molécula 1 de Adesão Intercelular/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Grupo com Ancestrais do Continente Asiático/genética , Sequência de Bases , Biomarcadores Tumorais/genética , Progressão da Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia
Chin J Cancer Res ; 24(1): 18-22, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23359758


OBJECTIVE: To investigate the value of c-Met in predicting progression of precancerous gastric lesions. METHODS: A population-based study was conducted to detect the overexpression of c-Met by immunohisto- chemical analysis in 124 subjects with precancerous gastric lesions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for the association of c-Met overexpression with the risk of advanced gastric lesions. RESULTS: The positive rates of c-Met were 55.7% in intestinal metaplasia (IM) and 64.8% in dysplasia (DYS), respectively. Stratified analysis indicated that the proportion of c-Met overexpression was 71.4% for IM progressive group, significantly higher than that for IM persistent group (40.0%, P<0.05). Compared to the IM persistent group, unconditional logistic regression showed that OR of c-Met overexpression for the IM progressive group was 7.416 (95% CI: 2.084-26.398). CONCLUSION: c-Met plays an important role in gastric carcinogenesis. Detection of c-Met is of value in predicting progression of precancerous gastric lesions from IM to DYS.

World J Gastroenterol ; 16(14): 1788-94, 2010 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-20380014


AIM: To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Citocinas/genética , Gastrite Atrófica/etiologia , Intestinos/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Interleucina-8/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Metaplasia/etiologia , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Neoplasias Gástricas/etiologia , Adulto Jovem
World J Gastroenterol ; 13(23): 3189-98, 2007 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-17589897


AIM: To distinguish subtypes of gastric signet ring cell (SRC) carcinoma by investigating the expression of gastric and intestinal phenotypic markers, and to study the significance of phenotypic classification in predicting tumor progression and outcome. METHODS: Immunohistochemistry was performed in 66 cases of SRC carcinoma with MUC2, VILLIN, CDX2, Li-cadherin antibodies as intestinal phenotype markers and MUC5AC, HGM, MUC6 antibodies as gastric phenotype markers, and the relationship was analyzed between the phenotypic expression pattern and clinicopathologic parameters, as well as the 3-year survival rate. RESULTS: Expression of intestinal phenotypic markers was positively associated with tumor size, wall invasion, vascular invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. Cases expressing one or more intestinal markers had a significant lower survival rate than cases expressing none of the intestinal markers. CONCLUSION: The SRC carcinomas expressing intestinal phenotype markers exhibited a high proliferative potential, bad biological behaviors and poor prognosis. Examination of phenotype expression may be useful in distinguishing histological type and in predicting the prognosis of gastric SRC carcinoma.

Carcinoma de Células em Anel de Sinete/classificação , Neoplasias Gástricas/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Caderinas/análise , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Feminino , Mucosa Gástrica/patologia , Glicoproteínas/análise , Humanos , Receptores de Hialuronatos/análise , Antígeno Ki-67/análise , Masculino , Metaplasia , Pessoa de Meia-Idade , Mucina-2 , Mucinas/análise , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , beta Catenina/análise