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1.
Gut ; 71(2): 238-253, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34836916

RESUMO

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.


Assuntos
Saúde da Família , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Controle de Infecções/organização & administração , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Consenso , Técnica Delfos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/transmissão , Humanos , Lactente , Pessoa de Meia-Idade , Adulto Jovem
2.
Cancer Lett ; 434: 132-143, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30031117

RESUMO

To systematically unveil transcription factors (TFs) that are critical to lung carcinogenesis, here we conducted a genome-wide lethality screening in non-small cell lung cancer (NSCLC) cells and reported that among the 1530 TFs tested, 21 genes were required for NSCLC cell proliferation and were negatively or positively associated with overall survival (OS) of patients with NSCLC. These included 11 potential tumor suppressing genes (AFF3, AhR, AR, CBFA2T3, CHD4, KANK2, NR3C2, PTEN, PRDM16, RB1, and STK11) and 10 potential oncogenic TFs (BARX1, DLX6, ELF3, EN1, ETV1, FOXE1, HOXB7, IRX4, IRX5, and SALL1). The expression levels of IRX5 were positively associated with OS of smoker and inversely associated with OS of non-smoker patients with lung adenocarcinoma. We showed that tobacco carcinogen benzo(a)pyrene (BaP) induced upregulation of IRX5 in lung epithelial cells, and Cyclin D1 was a downstream target of IRX5. Furthermore, silencing of IRX5 by lentivirus mediated transfection of short hairpin RNA significantly inhibited tumor growth in nude mice. These results indicate that tobacco smoke can modulate TFs to facilitate lung carcinogenesis, and inhibition of IRX5 may have therapeutic potentials in NSCLCs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Neoplasias Pulmonares/genética , Fatores de Transcrição/genética , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/terapia , Linhagem Celular , Linhagem Celular Tumoral , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Camundongos Endogâmicos NOD , Camundongos SCID , Interferência de RNA , Terapêutica com RNAi/métodos , Fatores de Transcrição/metabolismo , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
3.
Sci Rep ; 8(1): 3255, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29459704

RESUMO

Previous studies have revealed significant differences in microbiome compositions between infants delivered via cesarean section (C-section) and natural vaginal birth. However, the importance of the delivery mode in the first days of life remains unclear. Importantly, this stage is minimally affected by infant feeding. Here, we used a metagenomic sequencing technique to characterize the meconium microbiome from the feces of a Chinese cohort of vaginally and C-section-delivered infants, including in vitro fertilization (IVF) newborns, during the first 24 h after birth. Meconium microbiome diversity was higher in vaginally delivered infants than that in C-section-delivered infants. Propionibacterium species were most abundant in the vaginally delivered infants, whereas the C-section group had high levels of Bacillus licheniformis. The two IVF newborns delivered by C-section harbored microbial communities similar to the vaginal microbiome in terms of taxonomic composition. Metabolic functions of the C-section group suffered more from the influence of the dominant group (B. licheniformis), whereas the vaginal group was more homogeneous, with a metabolism dominated by multi-microbes. Moreover, different modes of delivery affected the antibiotic resistance gene (ARG) prevalence. These findings provide novel information for the development of strategies to guide a healthy mode of delivery and promote the formation of healthy microbiota.


Assuntos
Bactérias/classificação , Parto Obstétrico/métodos , Mecônio/microbiologia , Microbiota , Bactérias/genética , Fezes/microbiologia , Feminino , Humanos , Recém-Nascido , Masculino , Metagenômica , Análise de Sequência de DNA
4.
Oncotarget ; 7(48): 79914-79924, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27825134

RESUMO

The regulatory B cells (Breg) are important in the body immunity. The differentiation process of Breg is not fully understood yet. Ubiquitin A20 has immune regulatory functions. This study aims to investigate the role of A20 in the regulation of interleukin (IL)-10 in B cells. In this study, B cells were isolated from the peripheral blood samples of healthy subjects and patients with food allergy (FA). The B cells were analyzed by flow cytometry, real time RT-PCR, Western blotting and chromatin immunoprecipitation. We observed that the frequency of Breg and the levels of A20 in B cells were markedly lower in FA patients than in healthy controls. In vitro deletion of A20 compromised the expression of IL-10. B cells in FA patients showed higher levels of histone deacetylase (HDAC)-11 than in healthy subjects. Exposure to IL-13 in the culture induced high levels of HDAC11 in B cells. IL-13 also repressed the expression of A20 in B cells, in which HDAC11 played a critical role via inducing the chromatin remoldeling at the IL-10 promoter locus. Mice with A20-deficient B cells are prone to FA. In summary, ubiquitin A20 can increase the IL-10 expression in B cells, which can be affected by the IL-13-induced HDAC11. To inhibit HDAC11 may have therapeutic potential for FA.


Assuntos
Linfócitos B Reguladores/efeitos dos fármacos , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Interleucina-10/metabolismo , Interleucina-13/farmacologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Animais , Linfócitos B Reguladores/metabolismo , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Hipersensibilidade Alimentar/genética , Humanos , Interleucina-10/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hipersensibilidade a Leite/genética , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Adulto Jovem
5.
Int J Mol Med ; 38(4): 1055-62, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27573711

RESUMO

Vascular endothelial cells (ECs) appear to be one of the primary targets of hypoxia/reoxygenation (H/R) injury. In our previous study, we demonstrated that hepatocyte growth factor (HGF) exhibited a protective effect in cardiac microvascular endothelial cells (CMECs) subjected to H/R by inhibiting xanthine oxidase (XO) by reducing the cytosolic Ca2+ concentration increased in response to H/R. The precise mechanisms through which HGF inhibits XO activation remain to be determined. In the present study, we examined the signaling pathway through which HGF regulates Ca2+ concentrations and the activation of XO during H/R in primary cultured rat CMECs. CMECs were exposed to 4 h of hypoxia and 1 h of reoxygenation. The protein expression of XO and the activation of the phosphoinositide 3-kinase (PI3K), janus kinase 2 (JAK2) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways were detected by western blot analysis. Cytosolic calcium (Ca2+) concentrations and reactive oxygen species (ROS) levels were measured by flow cytometry. The small interfering RNA (siRNA)­mediated knockdown of XO inhibited the increase in ROS production induced by H/R. LY294002 and AG490 inhibited the H/R-induced increase in the production and activation of XO. The PI3K and JAK2 signaling pathways were activated by H/R. The siRNA­mediated knockdown of PI3K and JAK2 also inhibited the increase in the production of XO protein. HGF inhibited JAK2 activation whereas it had no effect on PI3K activation. The siRNA-mediated knockdown of JAK2 prevented the increase in cytosolic Ca2+ induced by H/R. Taken together, these findings suggest that H/R induces the production and activation of XO through the JAK2 and PI3K signaling pathways. Furthermore, HGF prevents XO activation following H/R primarily by inhibiting the JAK2 signaling pathway and in turn, inhibiting the increase in cytosolic Ca2+.


Assuntos
Células Endoteliais/citologia , Células Endoteliais/enzimologia , Fator de Crescimento de Hepatócito/farmacologia , Janus Quinase 2/metabolismo , Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Xantina Oxidase/metabolismo , Animais , Cálcio/metabolismo , Hipóxia Celular/efeitos dos fármacos , Citosol/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Fosfatidilinositol 3-Quinases/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
6.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(7): 892-7, 2016 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-27435764

RESUMO

OBJECTIVE: To identify the factors that affect the safety and efficacy of peroral endoscopic myotomy (POEM) for treatment of achalasia. METHODS: Data of consecutive patients undergoing POEM for confirmed achalasia between December, 2010 and December, 2015 were collected, including the procedure time, approach of tunnel entry incision, approach of myotomy, complications and follow-up data. RESULTS: Among the total of 439 patients enrolled, the overall complication rate was 28.7% (126/439). Treatment success (Eckardt score≤3) was achieved in 94.5% of 364 patients followed up for a median of 6 months (1-48 months), and the mean score was reduced significantly from 6.7∓1.5 before treatment to 1.2∓1.1 after the treatment (P<0.05). Logistic regression revealed that the year when POEM was performed and the approach of entry incision were two significant factors contributing to complications: with the year 2015 as the reference, the odds ratio (OR) was 9.454 (95% CI: 2.499-35.76) for the years before 2011, 2.177 (95% CI: 0.794-5.974) for 2012, 3.975 (95% CI: 1.904-8.298) for 2013, and 1.079 (95% CI: 0.601-1.940) for 2014; with the longitudinal entry incision as the reference, the OR was 0.369 (95% CI: 0.165-0.824) for inverted T entry incision and 0.456 (95% CI: 0.242-0.859) for transverse entry incision. The approach of myotomy was the significantly associated with symptomatic relapse: with full-thickness myotomy combined with indwelling an anti-reflux belt as the reference, the OR was 0.363 (95% CI: 0.059-2.250) for gradual full-thickness myotomy, 2.137 (95% CI: 0.440-10.378) for circular muscle myotomy, and 4.385 (95% CI: 0.820-23.438) for circular muscle myotomy in combination with balloon shaping; the recurrence rate was 0 with a full-thickness myotomy. CONCLUSION: The complication rates of POEM appears to decrease over time, and an inverted T entry incision is the best choice for controlling the complications. Gradual full-thickness myotomy is an excellent approach for treatment of achalasia in terms of the relapse rate, procedure time and the incidence of reflux esophagitis.


Assuntos
Endoscopia , Acalasia Esofágica/cirurgia , Músculos/cirurgia , Esofagite Péptica/cirurgia , Refluxo Gastroesofágico , Humanos , Recidiva , Resultado do Tratamento
7.
Oncol Lett ; 9(1): 295-299, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25435978

RESUMO

The aim of the present study was to explore the effects of curcumin in combination with bevacizumab on the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)/K-ras pathway in hepatocellular carcinoma. A total of 30 Sprague Dawley (SD) rats were randomly divided into five groups: Control, model, curcumin, VEGF blocker, and curcumin + VEGF blocker groups. The mRNA levels of VEGF and VEGFR in all groups were subsequently measured by quantitative reverse transcriptase-polymerase chain reaction and the protein expression of K-ras was detected by western blot analysis. Compared with the control group, the mRNA levels of VEGF and VEGFR were revealed to be significantly increased in the model, curcumin and VEGF blocker groups. The VEGF mRNA levels in the curcumin, VEGF blocker and curcumin + VEGF blocker groups were all decreased when compared with the model group. In addition, the VEGF mRNA levels in the curcumin + VEGF blocker group were significantly lower compared with the curcumin group (P<0.05). The VEGF mRNA levels in the curcumin, VEGF blocker and curcumin + VEGF blocker groups were decreased when compared with the model group (P=0.0001). No significant differences in VEGF mRNA levels were identified between the VEGF blocker and curcumin groups (P=0.863), whereas the VEGF mRNA levels in the curcumin + VEGF blocker group were significantly lower than that of the curcumin group (P=0.025). Curcumin and the VEGF blocker are each capable of inhibiting hepatocellular carcinoma progression by regulating the VEGF/VEGFR/K-ras pathway. The combination of the two compounds has a synergistic effect on the inhibition of the effects of the VEGF signaling pathways in hepatocellular carcinoma progression.

8.
World J Gastroenterol ; 19(24): 3847-53, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23840124

RESUMO

AIM: To investigate mitochondrial ATP 6 and 8 polymorphisms in the colon and ileum of patients with irritable bowel syndrome with diarrhea (IBS-D). METHODS: Twenty-eight patients fulfilling the Rome III criteria for IBS-D and 28 healthy subjects were investigated. All study participants underwent screening colonoscopy and mucosal biopsies were obtained from the colon and/or terminal ileum. Genomic DNA was extracted from specimens based on standard protocols. Mitochondrial ATP (MT-ATP) 6 and 8 genes in specimens were polymerase chain reaction amplified and sequenced. Sequencing data were analyzed via Variant Reporter™ Software and compared with the reference sequence from Genbank (accession No. NC_012920) to indicate possible polymorphisms. The protocol was registered at www.clinicaltrials.gov as NCT01028898. RESULTS: Twenty-five polymorphic sites of MT-ATP 6 and 8 genes were detected and 12 of them were missense mutations. A median of two polymorphic sites in MT-ATP genes was found in colon specimens of controls while a median of three polymorphic sites was noted in patients with IBS-D (Mann-Whitney test, P = 0.012). The variants of the colon and ileum specimens from the same subjects were identical in all but one case. Symptom duration in IBS was not found to be a significant factor associated with the mtDNA polymorphism (Spearman correlation, P = 0.592). The mitochondrial DNA change at 8860 was present in all cases of both groups. The frequency of the 8701 polymorphism was found to be the second most frequent; however, no statistical difference was noted between the groups (χ(2) test, P = 0.584). CONCLUSION: Patients with IBS-D have a higher incidence of MT-ATP 6 and 8 polymorphisms than healthy subjects, implying that the mtDNA polymorphism may play a role in IBS-D.


Assuntos
Diarreia/epidemiologia , Diarreia/genética , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Biópsia , Estudos de Casos e Controles , Colo/patologia , Colonoscopia , Comorbidade , Feminino , Humanos , Íleo/patologia , Incidência , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Adulto Jovem
9.
J Pathol ; 231(2): 257-70, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23836524

RESUMO

In contrast to the well-recognized loss of adherens junctions in cancer progression, the role of desmosomal components in cancer development has not been well explored. We previously demonstrated that desmocollin-2 (DSC2), a desmosomal cadherin protein, is reduced in oesophageal squamous cell carcinoma (ESCC), and is associated with enhanced tumour metastasis and poor prognosis. Here, we report that restoration of DSC2 in ESCC cells impeded cell migration and invasion both in vitro and in vivo, whereas siRNA-mediated suppression of DSC2 expression increased cell motility. In E-cadherin-expressing ESCC cells, DSC2 restoration strengthened E-cadherin-mediated adherens junctions and promoted the localization of ß-catenin at these junctions, which indirectly inhibited ß-catenin-dependent transcription. These effects of DSC2 were not present in EC109 cells that lacked E-cadherin expression. ESCC patients with tumours that had reduced E-cadherin and negative DSC2 had poorer clinical outcomes than patients with tumours that lacked either E-cadherin or DSC2, implying that the invasive potential of ESCC cells was restricted by both DSC2 and E-cadherin-dependent junctions. Further studies revealed that DSC2 was a downstream target of miR-25. Enhanced miR-25 promoted ESCC cell invasiveness, whereas restoration of DSC2 abolished these effects. Collectively, our work suggests that miR-25-mediated down-regulation of DSC2 promotes ESCC cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Desmocolinas/metabolismo , Neoplasias Esofágicas/metabolismo , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Transdução de Sinais/fisiologia , beta Catenina/metabolismo , Junções Aderentes/genética , Junções Aderentes/metabolismo , Junções Aderentes/patologia , Adulto , Idoso , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Desmocolinas/genética , Regulação para Baixo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Transfecção , Transplante Heterólogo
10.
Cancer Prev Res (Phila) ; 6(8): 791-800, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23803417

RESUMO

In animals ranging from fish to mice, the function of DACT2 as a negative regulator of the TGF-ß/Nodal signal pathway is conserved in evolution, indicating that it might play an important role in human cancer. In this study, we showed that tumors with higher DACT2 protein level were correlated with better differentiation and better survival rate in patients with esophageal squamous cell carcinoma. Restored expression of DACT2 significantly inhibited growth, migration, and invasion of ESCC cells in vitro, and reduced tumorigenicity in vivo. Furthermore, when DACT2 expression was restored, the activity of TGF-ß/SMAD2/3 was suppressed via both proteasome and lysosomal degradation pathways, leading to F-actin rearrangement that might depend on the involvement of cofilin and ezrin-redixin-moesin (ERM) proteins. Taken together, we propose here that DACT2 serves as a prognostic marker that reduces tumor cell malignancy by suppressing TGF-ß signaling and promotes actin rearrangement in ESCC.


Assuntos
Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Proteínas de Transporte/metabolismo , Movimento Celular , Neoplasias Esofágicas/mortalidade , Proteínas de Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Diferenciação Celular , Proliferação de Células , Ensaio de Unidades Formadoras de Colônias , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Camundongos , Microscopia Confocal , Microscopia de Fluorescência , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Fator de Crescimento Transformador beta1/metabolismo
11.
Chin Med J (Engl) ; 126(8): 1532-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23595390

RESUMO

BACKGROUND: Ulcerative colitis (UC) is associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNA (miRNA) plays an important role in the pathogenesis of UC by regulating the gene expression at the post-transcriptional level and control crucial physiological processes. This study aimed to identify aquaporin 8 (AQP8) expression and its relationship with miRNA in UC patients. METHODS: Human colon samples, in this study, were obtained from 20 patients with UC and 16 healthy subjects undergoing diagnostic colonoscopy at the Chinese People's Liberation Army General Hospital between December 2009 and June 2010. We screened different genes from UC tissues and healthy subjects using genome-wide microarray, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Regulation of gene expression by miRNAs was assessed by luciferase reporter construct assays and transfection of specific miRNA mimics and inhibitor. RESULTS: We identified that 1596 genes were increased and 1301 genes were decreased in UC patients compared to healthy subjects. Among them, we focused on the analysis of AQP8 which was decreased three folds in UC tissues (P < 0.01). The expression of AQP8 mRNA and protein were decreased in UC tissue and tumor necrosis factor (TNF)-α treated HT29 cells compared with controls (P < 0.05). We searched candidate target miRNAs of AQP8 through bioformatics and the luciferase report assay analysis indicated that miR-424, miR-195, miR-330, miR-612, and miR-16 which has complementary site in the 3-untranslated region (3'UTR) of AQP8 could decrease the relative luciferase activities by 10% - 45%. CONCLUSION: AQP8 and its relationship with miRNAs may be involved in the pathogenesis of UC.


Assuntos
Aquaporinas/genética , Colite Ulcerativa/genética , Adulto , Idoso , Feminino , Regulação da Expressão Gênica , Células HT29 , Humanos , Masculino , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/farmacologia
12.
Chin Med J (Engl) ; 125(19): 3526-31, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23044318

RESUMO

BACKGROUND: SRY-related HMG-box 17 (SOX17) encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. Recently, it was considered as a tumor suppressor gene to inhibit canonical Wnt/ß-catenin signaling pathway in several malignancies. However, the function of SOX17 in thyroid cancer was unknown. Therefore, we investigated the epigenetic changes and the function of SOX17 in thyroid cancer. METHODS: The methylation status of the promoter region of SOX17 was detected using methylation-specific PCR in 63 papillary thyroid carcinoma (PTC) tissue, 10 normal thyroid tissue, and two thyroid cancer cell lines. Semi-quantitative RT-PCR was used to assess mRNA expression of SOX17 before and after 5-aza-2'-deoxycytidine treatment in thyroid cancer cell lines. Expression of SOX17 and ß-catenin were detected by immunohistochemistry in PTC and adjacent tissue. Luciferase reporter assay, colony formation, transfection, and Western blotting were employed to analyze the effect of SOX17 on thyroid cancer cell proliferation and the function of SOX17 in the Wnt signal pathway. RESULTS: Loss of SOX17 expression was correlated to the promoter region hypermethylation in thyroid cancer cell lines. Re-expression of SOX17 was found in TPC-1 cell line after 5-aza-2'-deoxycytidine treatment. In primary thyroid cancer, 60.3% (38/63) were methylated and 39.7% (25/63) unmethylated. But no methylation was found in noncancerous thyroid tissues. Methylation of SOX17 was associated reversely with ß-catenin expression in the cytoplasm or nucleus significantly in the PTC (P < 0.05). Colony formation was inhibited by re-expression of SOX17 in TPC-1 cells. SOX17 suppressed the Wnt signaling pathway and the HMG domain was essential for this effect. CONCLUSIONS: SOX17 was frequently methylated in human PTC. Loss of SOX17 expression was induced by promoter region hypermethylation. SOX17 inhibited thyroid cancer proliferation. Methylation of SOX17 activated the Wnt signaling pathway in human thyroid cancer.


Assuntos
Carcinoma/genética , Carcinoma/metabolismo , Epigênese Genética/genética , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Via de Sinalização Wnt/fisiologia , Western Blotting , Carcinoma Papilar , Linhagem Celular Tumoral , Metilação de DNA/genética , Epigênese Genética/fisiologia , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Câncer Papilífero da Tireoide , Células Tumorais Cultivadas , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
13.
World J Gastroenterol ; 18(34): 4771-80, 2012 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-23002348

RESUMO

AIM: To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnification endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS: Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and treatment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stomachs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with white-light imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI: 78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by ME-NBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI: 73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION: Higher diagnostic accuracy, sensitivity and specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.


Assuntos
Carcinoma in Situ/diagnóstico , Endoscopia Gastrointestinal/métodos , Microscopia Confocal/métodos , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia
14.
Chin Med J (Engl) ; 125(13): 2329-33, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22882857

RESUMO

BACKGROUND: Id3 plays a key role in the progression of breast cancer. Previously, four and a half LIM protein (FHL2) was identified as a repressor of Id family proteins by interacting with them. This study aimed to investigate the effects of FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human breast cancer cells. METHODS: Cell transfection was performed with SuperFect reagent. Stable transfectants that overexpressed Id3 were obtained by selection on G418. The level of Id3 protein was determined by Western blotting analysis. Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47-mediated transcriptional activity in MCF-7 human breast cancer cells. The MTT assay was used to measure cell proliferation. The transwell assay was used to measure the invasive capacity of MCF-7 cancer cells. RESULTS: Id3 markedly repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47 in MCF-7 cells. This Id3-mediated repression was effectively antagonized by FHL2. Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however, these effects were significantly suppressed by the overexpression of FHL2. CONCLUSIONS: FHL2 can inhibit the proliferation and invasive growth of human breast cancer cells by repressing the functional activity of Id3. The functional roles of FHL2-Id3 signaling in the development of human breast cancer need further research.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas Inibidoras de Diferenciação/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Proteínas Musculares/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Western Blotting , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteínas Inibidoras de Diferenciação/genética , Proteínas com Homeodomínio LIM/genética , Células MCF-7 , Proteínas Musculares/genética , Proteínas de Neoplasias/genética , Fator 3 de Transcrição/genética , Fator 3 de Transcrição/metabolismo , Fatores de Transcrição/genética
15.
Zhonghua Nei Ke Za Zhi ; 51(5): 390-3, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22883340

RESUMO

OBJECTIVE: To study the association of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) promoter region methylation with human esophageal cancer. METHODS: Promoter region methylation of UCHL1 was detected by methylation specific PCR (MSP) in esophageal cancer cell lines and tissue samples. The expression of UCHL1 was detected by semi-quantitative RT-PCR and Western blot in esophageal cancer cell lines. 5-Aza-2'-deoxycytidine (5-Aza) was applied to reactivate methylated cell lines. RESULTS: Complete methylation of UCHL1 promoter region was detected in 8 cell lines (KYSE30, KYSE150, KYSE140, KYSE450, KYSE510, TE3, TE7, TE10). Loss of UCHL1 expression was found in 7 cell lines (KYSE30, KYSE150, KYSE140, KYSE450, KYSE510, TE3, TE7). Reduced expression was found in TE10 cell line. Promoter region hypermethylation was correlated with UCHL1 expression in esophageal cancer cell lines. Re-expression of UCHL1 was induced by 5-Aza treatment in KYSE150 and TE3 cell lines. UCHL1 was frequently methylated in human primary esophageal cancer (74.51%, 38/51), while no methylation was detected in normal esophageal mucosa(0/10). No association was found between promoter region methylation and age, gender, tumor location, tumor stage or lymph node metastasis. CONCLUSIONS: UCHL1 is silenced by promoter region hypermethylation in human esophageal cancer. Methylation of UCHL1 is frequently happened to primary esophageal cancer and may play an important role in the tumorigenesis.


Assuntos
Metilação de DNA , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Regiões Promotoras Genéticas , Ubiquitina Tiolesterase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquitina Tiolesterase/genética
16.
World J Gastroenterol ; 18(22): 2844-9, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22719195

RESUMO

AIM: To explore epigenetic changes in the gene encoding X chromosome-linked inhibitor of apoptosis-associated factor 1 (XAF1) during esophageal carcinogenesis. METHODS: Methylation status of XAF1 was detected by methylation-specific polymerase chain reaction (MSP) in four esophageal cancer cell lines (KYSE30, KYSE70, BIC1 and partially methylated in TE3 cell lines), nine cases of normal mucosa, 72 cases of primary esophageal cancer and matched adjacent tissue. XAF1 expression was examined by semi-quantitative reverse transcriptional polymerase chain reaction and Western blotting before and after treatment with 5-aza-deoxycytidine (5-aza-dc), a demethylating agent. To investigate the correlation of XAF1 expression and methylation status in primary esophageal cancer, immunohistochemistry for XAF1 expression was performed in 32 cases of esophageal cancer and matched adjacent tissue. The association of methylation status and clinicopathological data was analyzed by logistic regression. RESULTS: MSP results were as follows: loss of XAF1 expression was found in three of four esophageal cell lines with promoter region hypermethylation (completely methylated in KYSE30, KYSE70 and BIC1 cell lines and partially in TE3 cells); all nine cases of normal esophageal mucosa were unmethylated; and 54/72 (75.00%) samples from patients with esophageal cancer were methylated, and 25/72 (34.70%) matched adjacent tissues were methylated (75.00% vs 34.70%, χ(2) = 23.5840, P = 0.000). mRNA level of XAF1 measured with semi-quantitative reverse transcription polymerase chain reaction was detectable only in TE3 cells, and no expression was detected in KYSE30, KYSE70 or BIC1 cells. Protein expression was not observed in KYSE30 cells by Western blotting before treatment with 5-aza-dc. After treatment, mRNA level of XAF1 was detectable in KYSE30, KYSE70 and BIC1 cells. Protein expression was detected in KYSE30 after treatment with 5-aza-dc. Immunohistochemistry was performed on 32 cases of esophageal cancer and adjacent tissue, and demonstrated XAF1 in the nucleus and cytoplasm. XAF1 staining was found in 20/32 samples of adjacent normal tissue but was present in only 8/32 samples of esophageal cancer tissue (χ(2)= 9.143, P = 0.002). XAF1 expression was decreased in cancer samples compared with adjacent tissues. In 32 cases of esophageal cancer, 24/32 samples were methylated, and 8/32 esophageal cancer tissues were unmethylated. XAF1 staining was found in 6/8 samples of unmethylated esophageal cancer and 2/24 samples of methylated esophageal cancer tissue. XAF1 staining was inversely correlated with XAF1 promoter region methylation (Fisher's exact test, P = 0.004). Regarding methylation status and clinicopathological data, no significant differences were found in sex, age, tumor size, tumor stage, or metastasis with respect to methylation of XAF1 for the 72 tissue samples from patients with esophageal cancer. CONCLUSION: XAF1 is frequently methylated in esophageal cancer, and XAF1 expression is regulated by promoter region hypermethylation.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Epigênese Genética , Neoplasias Esofágicas/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Proteínas Reguladoras de Apoptose , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Distribuição de Qui-Quadrado , China , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Decitabina , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas de Neoplasias/metabolismo , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
World J Gastroenterol ; 18(6): 563-9, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22363124

RESUMO

AIM: To explore the potential risk factors related to gastrointestinal cancer in northern China. METHODS: A total of 3314 cases of gastrointestinal cancer (esophageal, gastric, pancreatic and biliary) and 2223 controls (including healthy individuals, glioma and thyroid cancer) were analyzed by case-control study. Multivariable logistic regression analysis was applied to evaluate the association between different cancers and hepatitis B surface antigen, sex, age, blood type, diabetes, or family history of cancer. RESULTS: Type 2 diabetes was significantly associated with gastric, biliary and pancreatic cancer with an OR of 2.0-3.0. Blood type B was significantly associated with esophageal cancer [odd ratio (OR) = 1.53, 95% confidence interval (CI) = 1.10-2.14] and biliary cancer (OR = 1.49, 95% CI = 1.09-2.05). The prevalence of type 2 diabetes was significantly higher in gastric, biliary and pancreatic cancers compared with other groups, with ORs ranging between 2.0 and 3.0. Family history of cancer was strongly associated with gastrointestinal compared with other cancers. CONCLUSION: Blood type B individuals are susceptible to esophageal and biliary cancer. Type 2 diabetes is significantly associated with gastric, biliary and especially pancreatic cancer.


Assuntos
Sistema ABO de Grupos Sanguíneos , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/etiologia , Adulto , Idoso , Tipagem e Reações Cruzadas Sanguíneas , Estudos de Casos e Controles , China , Feminino , Neoplasias Gastrointestinais/patologia , Antígenos de Superfície da Hepatite B , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
18.
Gastroenterology ; 142(4): 812-823.e15, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22240482

RESUMO

BACKGROUND & AIMS: Dysregulation of Wnt signaling has been involved in gastric tumorigenesis by mechanisms that are not fully understood. The receptor for activated protein kinase C (RACK1, GNB2L1) is involved in development of different tumor types, but its expression and function have not been investigated in gastric tumors. METHODS: We analyzed expression of RACK1 in gastric tumor samples and their matched normal tissues from 116 patients using immunohistochemistry. Effects of knockdown with small interfering RNAs or overexpression of RACK1 in gastric cancer cell lines were evaluated in cell growth and tumor xenograft. RACK1 signaling pathways were investigated in cells and zebrafish embryos using immunoblot, immunoprecipitation, microinjection, and in situ hybridization assays. RESULTS: Expression of RACK1 was reduced in gastric tumor samples and correlated with depth of tumor infiltration and poor differentiation. Knockdown of RACK1 in gastric cancer cells accelerated their anchorage-independent proliferation in soft agar, whereas overexpression of RACK1 reduced their tumorigenicity in nude mice. RACK1 formed a complex with glycogen synthase kinase Gsk3ß and Axin to promote the interaction between Gsk3ß and ß-catenin and thereby stabilized the ß-catenin destruction complex. On stimulation of Wnt3a, RACK1 repressed Wnt signaling by inhibiting recruitment of Axin by Dishevelled 2 (Dvl2). Moreover, there was an inverse correlation between expression of RACK1 and localization of ß-catenin to the cytoplasm/nucleus in human gastric tumor samples. CONCLUSIONS: RACK1 negatively regulates Wnt signaling pathway by stabilizing the ß-catenin destruction complex and act as a tumor suppressor in gastric cancer cells.


Assuntos
Complexo de Sinalização da Axina/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Superfície Celular/metabolismo , Neoplasias Gástricas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Via de Sinalização Wnt , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Complexo de Sinalização da Axina/genética , Estudos de Casos e Controles , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Desgrenhadas , Feminino , Proteínas de Ligação ao GTP/genética , Regulação Neoplásica da Expressão Gênica , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Fosfoproteínas/metabolismo , Interferência de RNA , Receptores de Quinase C Ativada , Receptores de Superfície Celular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Fatores de Tempo , Transfecção , Proteínas Supressoras de Tumor/genética , Via de Sinalização Wnt/genética , Proteína Wnt3A/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , beta Catenina/metabolismo
19.
J Histochem Cytochem ; 59(7): 711-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21525190

RESUMO

The aim of this study was to evaluate HDPR1 expression in esophageal squamous cell carcinoma (ESCC) and the relationship between HDPR1 and beta-catenin by immunohistochemical analysis. The clinical relevance of these proteins was also analyzed. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 184 ESCC patients to detect the expression of HDPR1 and beta-catenin. The correlation between the results of immunoexpression and the clinicopathologic features was processed statistically. Increased cytoplasmic and nuclear HDPR1 expression was noted in 100 (54.3%) and 131 (71.2%) of 184 specimens, respectively. Statistical analysis showed significant associations of cytoplasmic HDPR1 with regional lymph node metastasis (p = 0.021) and P-stage (p = 0.004). The increased nuclear staining was only correlated with P-stage (p = 0.047). Significant associations of coexpression of cytoplasmic and nuclear HDPR1 with regional lymph node metastasis (p = 0.015) or P-stage (p = 0.002) were observed. Enhanced cytoplasmic expression of HDPR1 was positively correlated with increased cytoplasmic but not reduced membranous beta-catenin expression (r = 0.239, p = 0.027 and r = 0.126, p = 0.089, respectively). These finding suggested that cytoplasmic HDPR1 protein expression was associated with tumor malignant progression via beta-catenin accumulation. It implicated that cytoplasmic HDPR1 expression may serve as a potential predictive factor for lymph node metastasis and tumor development in ESCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Linfonodos/patologia , Proteínas Nucleares/biossíntese , beta Catenina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Citoplasma/metabolismo , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
20.
World J Gastroenterol ; 17(4): 526-33, 2011 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-21274384

RESUMO

AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development. METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2'-deoxycytidine treatment. RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2'-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000). CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2'-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.


Assuntos
Citocinas/genética , Citocinas/metabolismo , Metilação de DNA , Inativação Gênica , Regiões Promotoras Genéticas , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Animais , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Linhagem Celular Tumoral , Decitabina , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico
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