RESUMO
PURPOSE: To explore the regulatory relationship between Chloride intracellular channel 1 (CLIC1) and Angiomotin (AMOT)-p130, and reveal the role of AMOT-p130 in gastric cancer (GC). METHODS: Immunohistochemistry was performed to analyze the expression of CLIC1 and AMOT-p130 in GC tissues and adjacent tissues. The expression of AMOT-p130 upon CLIC1 silencing was analyzed using RT-PCR, western blot, and immunofluorescence in GC cells. Transwell and wound-healing assays were performed to detect migration and invasion in GC cells. The changes in EMT-related proteins were detected using western blot. RESULTS: Our study found that high CLIC1 expression was significantly associated with low AMOT-p130 expression in GC tissues. Silencing CLIC1 expression in MGC-803 cells (MGC-803 CLIC1 KO) and AGS cells (AGS CLIC1 KO) decreased the invasive and migratory abilities of tumor cells, which were induced by the upregulation of AMOT-p130. Subsequently, we demonstrated that AMOT-p130 inhibits the invasive and migratory abilities of GC cells by inhibiting epithelial-mesenchymal transition. CONCLUSIONS: Our study suggests that AMOT-p130 could inhibit epithelial-mesenchymal transition in GC cells. CLIC1 may participate in the metastatic progression of GC by downregulating the expression of AMOT-p130.
Assuntos
Canais de Cloreto/metabolismo , Transição Epitelial-Mesenquimal , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Angiomotinas , Linhagem Celular Tumoral , Movimento Celular , Canais de Cloreto/genética , Feminino , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima , CicatrizaçãoRESUMO
Cytogenetic analysis remains a powerful and cost-effective technology, and has wide applicability in genetic counseling for infertile males. Chromosomal rearrangements are thought to be one of the major genetic factors that influence male infertility. Some carriers with balanced reciprocal translocation have been identified as having oligozoospermia or azoospermia, and there is an association between balanced translocation and recurrent abortion. Researchers have reported the involvement of chromosome 4 translocations in male factor infertility and recurrent miscarriages. A translocation breakpoint might interrupt the structure of an important gene, and it is associated with reproductive failure. However, the clinical characteristics of the breakpoints in chromosome 4 translocations have not been studied. Here, we report the breakpoints in chromosome 4 translocation and the clinical features presented in carriers to enable informed genetic counseling of these patients. Of 82 patients with balanced reciprocal translocations, 14 were carriers of the chromosome 4 translocation: four presented with pregestational infertility (clinical manifestations: oligozoospermia, severe oligozoospermia, or azoospermia), whereas 10 presented with gestational infertility (able to conceive but with a tendency to miscarry). The breakpoint at 4q12 was associated with pregestational infertility, whereas the breakpoints at 4q13, 4q21, 4q25, and 4q32 were associated with gestational infertility. However, the breakpoint at 4q35 was associated with both pregestational and gestational infertility. Chromosome 4 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the different technologies available to assist reproduction.
Assuntos
Aborto Espontâneo/genética , Azoospermia/genética , Pontos de Quebra do Cromossomo , Cromossomos Humanos Par 4/genética , Oligospermia/genética , Feminino , Aconselhamento Genético , Heterozigoto , Humanos , Masculino , Gravidez , Translocação GenéticaRESUMO
Balanced reciprocal translocations are associated with reproductive failure. Some reciprocal translocation carriers exhibit azoospermia or oligozoospermia, and an association exists between these chromosomal abnormalities and recurrent abortion. Previous reports have indicated the involvement of chromosome 7 translocations in male infertility and recurrent miscarriage. A translocation breakpoint can occur within an important gene, interrupting its structure and leading to male infertility. However, clinical characteristics resulting from chromosome 7 translocation breakpoints have not been studied. Here, we report such breakpoints and their associated clinical features, to enable informed genetic counseling of carriers. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among these 82 individuals, 14 (17.07%) carried a chromosome 7 translocation, of which, five presented with pregestational infertility and clinical manifestations of oligozoospermia or necrospermia, while nine presented with gestational infertility (i.e., were able to conceive, but often resulting in miscarriage). Breakpoints at 7q31 and 7q36 were associated with pregestational infertility, whereas those at 7p10, 7q21.2, 7q22, and 7q32 were connected to gestational infertility. However, the breakpoint at 7p15 was associated with both. Chromosome 7 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the various molecular technologies available for assisted reproduction.
Assuntos
Quebra Cromossômica , Cromossomos Humanos Par 7/genética , Aconselhamento Genético , Translocação Genética , Heterozigoto , Humanos , Cariotipagem , MasculinoRESUMO
Published data regarding the association between aryl hydrocarbon receptor (Ahr) rs2066853 polymorphism and the risk of breast cancer shows conflicting results. We performed a meta-analysis on 2999 patients and 3050 controls from three related case-control studies to estimate the association between Ahr rs2066853 polymorphism and the risk of breast cancer. The protocol was approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Florida (America NIH Publication No. 86-231985 Revision). According to the three eligible populations, the odds ratios (ORs), 95% confidence intervals (CIs) on the risk of breast cancer for the genotypes GA vs GG, AA vs GG, and A vs G were 1.06 (0.81-1.40), 0.96 (0.81-1.13), and 1.02 (0.85-1.22), respectively. The OR (95%CI) for GA + AA vs GG was 1.05 (0.80-1.37). Furthermore, after multi-variates adjustment, the ORs (95%CIs) were 1.05 (0.80-1.38) for GA vs GG, and 0.92 (0.76-1.10) for AA vs GG. This meta-analysis suggests that Ahr (rs2066853) polymorphism would not modify the risk of breast cancer. However, further research should be conducted to provide more evidence.
Assuntos
Alelos , Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores de Hidrocarboneto Arílico/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Razão de Chances , Viés de PublicaçãoRESUMO
The aim of this study was to observe levels of blood brain natriuretic peptides (BNPs) in patients with persistent atrial fibril-lation (AF) before and after catheter ablation. Thirty-six patients with persistent AF (28 successful surgeries and eight recurrent cases) and 36 healthy controls with normal sinus rhythm were recruited for this study. BNP levels in the AF and control groups were measured before and after catheter ablation. BNP levels before surgery were significantly higher in the persistent AF group than in the control group (P < 0.01). The successful surgery group had distinctly lower BNP levels before ablation than the recurrent group (P < 0.01). In the recurrent group, BNP levels 2 h after ablation were significantly lower than those be-fore ablation (P < 0.01); these levels increased after AF recurrence (P < 0.01) and were comparable with those before ablation (P < 0.01). Logistic regression analysis indicated that the BNP level was an inde-pendent factor for and predictor of AF recurrence (P < 0.01). The BNP level in patients with persistent AF is clinically important in predicting and evaluating AF recurrence after ablation.
Assuntos
Fibrilação Atrial/sangue , Ablação por Cateter , Átrios do Coração/metabolismo , Peptídeo Natriurético Encefálico/sangue , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Expressão Gênica , Átrios do Coração/fisiopatologia , Átrios do Coração/cirurgia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/genética , Recidiva , Resultado do TratamentoRESUMO
The human X-ray repair cross-complementing protein 1 (XRCC1) gene is a potentially gene determining hepatocellular carcinoma (HCC) susceptibility. The purpose of this study was to evaluate the association between XRCC1 and susceptibility to HCC. The association of XRCC1 polymorphisms with HCC susceptibility was investigated in 460 HCC patients and 463 controls using the created restriction site-polymerase chain reaction method. Our results indicate that the c.1471G>A variant could be detected and that the allele and genotype frequencies were statistically different between cases and controls. The AA genotype was strongly associated with increased HCC susceptibility as compared with the GG wild genotype (OR = 2.214, 95%CI = 1.493-3.283, χ(2) = 15.97, P < 0.0001). In addition, significantly increased HCC susceptibility was also found in a dominant and recessive model (P < 0.01). The allele A could contribute to HCC susceptibility compared with the G allele (OR = 1.480, 95%CI = 1.224-1.789, χ(2) = 16.44, P = 0.0001). Results from this study indicate that the XRCC1 c.1471G>A polymorphism is associated with HCC susceptibility in the Chinese Han population. Future studies on larger populations are essential to confirm this association.