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AIM: This study was aimed to investigate the associations between single nucleotide polymorphisms of cancer stem cell marker genes, CD44 and CD133, and susceptibility and prognosis of gastric cancer. PATIENTS & METHODS: Five single nucleotide polymorphisms in CD44 and CD133 genes were genotyped in 898 gastric cancer cases and 992 controls. RESULTS: The A/C or C/C genotypes of CD133 rs2240688 were associated with decreased risk of gastric cancer comparing with the A/A genotype (odds ratio: 0.81; 95% CI: 0.67-0.97; p = 0.023). The T allele of CD133 rs3130 predicted a worse survival for gastric cancer patients receiving tumorectomy (hazard ratio: 1.28; 95% CI: 1.04-1.58; p = 0.020), independent from tumor node metastasis stage, vessel invasion and postoperational chemotherapy. CONCLUSION: CD133 polymorphisms are promising biomarkers for genetic susceptibility and prognosis prediction of gastric cancer.
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Antígeno AC133/genética , Biomarcadores Tumorais , Predisposição Genética para Doença , Células-Tronco Neoplásicas/metabolismo , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Idoso , Alelos , Feminino , Genótipo , Humanos , Receptores de Hialuronatos/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMO
Helicobacter pylori (H. pylori) is the definite carcinogen of gastric cancer. H. pylori infection induces chronic inflammation, causes DNA damage and aberrant methylation of genes and these pathways are involved in H. pylori-related gastric carcinogenesis. Polymorphisms of the genes involved in these pathways could alter susceptibility to gastric cancer. In this mini review, we focused on the role of polymorphisms in these genes on the susceptibility to gastric cancer, with a particular emphasis on their possible interactions with H. pylori infection. We found that many studies on this theme did not simultaneously report H. pylori infection and the interactions remained inconclusive.
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Carcinogênese , Variação Genética , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Neoplasias Gástricas/etiologia , Biomarcadores , Metilação de DNA , Reparo do DNA , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Inflamação/complicações , Inflamação/genética , Inflamação/metabolismo , Polimorfismo Genético , Neoplasias Gástricas/metabolismoRESUMO
AIM: Single nucleotide polymorphisms in miRNA-coding region may be involved in the development or progression of gastric cancer (GC). MATERIALS & METHODS: Six SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-27a rs895819, miR-423 rs6505162, miR-608 rs4919510, miR-149 rs2292832) were genotyped in 898 histologically confirmed GC cases and 992 controls in this hospital-based case-control study. RESULTS: The G/G genotype of rs2910164 was associated with reduced risk of GC (odds ratio: 0.76, 95% CI: 0.60-0.97; p = 0.024). Meanwhile, in 838 GC cases receiving radical tumorectomy, cases bearing the G/G genotype of rs2910164 had shorter survival time comparing to cases with C/C or C/G genotype (hazard ratio: 1.36, 95% CI: 1.04-1.78, p = 0.023). CONCLUSION: rs2910164 of miR-146a is associated with GC.
Assuntos
Alelos , Estudos de Associação Genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neovascularização Patológica , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: Previous studies have reported that different genotypes of PTPN11 gene (protein tyrosine phosphatase, non-receptor 11) were associated with different levels of serum lipids. The aim of this study was to explore the relationship between single nucleotide polymorphisms (SNPs) of PTPN11 and serum lipids in Northeast Chinese. METHODS: A total of 1003 subjects, 584 males and 419 females, were included in the study and their serum lipids were determined. Five htSNPs (rs2301756, rs12423190, rs12229892, rs7958372 and rs4767860) of PTPN11 gene were genotyped using TaqMan assay method. RESULTS: All of the five SNPs were in Hardy-Weinberg equilibrium. The male subjects had higher triglyceride (TG), higher low-density lipoprotein cholesterol (LDL-C) and lower high-density lipoprotein cholesterol (HDL-C) level than females. In males, rs4767860 was found to be associated with serum TG and total cholesterol (TC) levels and rs12229892 was associated with TC level. However, these significant associations could not be observed in females. In females, rs2301756 was found to be associated with TG and rs7958372 was associated with LDL-C level. Haplotype analysis showed that the GCGTG haplotype was associated with slightly higher TG level and ATGCG with higher TC level. CONCLUSIONS: SNPs of PTPN11 may play a role in serum lipids in a sex-specific pattern. However, more studies are needed to confirm the conclusion and explore the underlying mechanism.
Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Triglicerídeos/sangue , Adulto , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Caracteres SexuaisRESUMO
BACKGROUND: Most gastric cancer (GC) patients are diagnosed at middle or late stage because the symptoms in early stage are obscure, which causes higher mortality rates of GC. Helicobacter pylori (H. pylori) was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation. 5-hydroxymethylcytosine (5-hmC) plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation. AIM: To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H. pylori infection. METHODS: A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H. pylori infection status. A total of 144 GC patients were recruited. RESULTS: The levels of 5-hmC were significantly decreased in tumor tissues (0.076 ± 0.048) compared with the matched control tissues (0.110 ± 0.057, P = 0.001). A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients (hazard ratio = 0.61, 95% confidence interval: 0.38-0.98, P = 0.040), the H. pylori-negative GC subgroup (hazard ratio = 0.30, 95% confidence interval: 0.13-0.68, P = 0.004) and the GC patients with TNM stage â or â ¡ (hazard ratio = 0.32, 95% confidence interval: 0.13-0.77, P = 0.011). CONCLUSION: Increased 5-hmC is a favorable prognostic factor in GC, especially for H. pylori-negative subgroups.
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BACKGROUND: The lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited. AIM: To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population. METHODS: A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed. RESULTS: All the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3'-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3'-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters. CONCLUSION: The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/genética , Receptores de Interleucina/genética , Neoplasias Gástricas/genética , Regiões 3' não Traduzidas/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Neoplasias Gástricas/mortalidade , Análise de SobrevidaRESUMO
Toll-like receptors (TLRs) mediate the recognition of Helicobacter pylori (H. pylori) and initiate the innate immune response to infection. Genetic polymorphisms of TLRs play important roles in gastric carcinogenesis. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) in TLR genes and H. pylori infection in the prognosis of gastric cancer (GC). A total of 756 GC patients were included in this study. Nine SNPs (TLR2: rs3804100, rs7696323, and rs10116253; TLR4: rs10983755, rs11536878, rs1927914, and rs7873784; TLR5: rs5744174; and TLR9: rs187084) in TLR genes were genotyped by MassARRAY assay. Kaplan-Meier survival curves and Cox regression were employed to conduct the associations between SNPs in TLRs and the survival of GC. Multivariate Cox regression indicated that patients with the TLR2 rs3804100 TT genotype exhibited worse survival than those with the CCâ¯+â¯CT genotype (HRâ¯=â¯1.262, 95% CI: 1.006-1.582). No significant interaction between rs3804100 and H. pylori infection was observed for the prognosis of GC. Our results suggested that the TLR2 rs3804100 polymorphism may be a potential prognostic biomarker for GC independent of the H. pylori infection-related pathway.
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Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Receptores Toll-Like/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
K19-C2mE transgenic (Tg) mice, simultaneously expressing cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in the gastric mucosa under the cytokeratin 19 gene promoter, were here treated with N-methyl-N-nitrosourea (MNU) and inoculated with Helicobacter pylori (H. pylori) to investigate gastric carcinogenesis. Wild-type (WT) and Tg mice undergoing MNU treatment frequently developed tumors in the pyloric region (100% and 94.7%, respectively); multiplicity in Tg was higher than that in WT (P < 0.05) with H. pylori infection. Larger pyloric tumors were more frequently observed in Tg than in WT (P < 0.05). In addition, Tg developed fundic tumors, where WT did not. No gastric tumors were observed without MNU treatment. Transcripts of TNF-alpha, iNOS, IL-1beta, and CXCL14 were up-regulated with H. pylori infection in both genotypes and were also increased more in Tg than in WT within H. pylori-inoculated animals. Immunohistochemical analysis demonstrated significantly greater beta-catenin accumulation in pyloric tumors, compared with those in the fundus (P < 0.01) with mutations of exon 3; 18.2% and 31.6% in MNU-alone and MNU + H. pylori-treated WT, whereas 21.4% and 62.5% was observed in the Tg, respectively; the latter significantly higher (P < 0.05), suggesting the role of H. pylori in Wnt activation. In conclusion, K19-C2mE mice promoted gastric cancer in both fundic and pyloric regions. Furthermore beta-catenin activation may play the important role of pyloric carcinogenesis especially in H. pylori-infected Tg. Induction of various inflammatory cytokines in addition to overexpression of COX-2/mPGES-1 could be risk factors of gastric carcinogenesis and may serve as a better gastric carcinogenesis model.
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Carcinógenos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Oxirredutases Intramoleculares/metabolismo , Metilnitrosoureia/farmacologia , Neoplasias Gástricas/etiologia , beta Catenina/metabolismo , Animais , Transformação Celular Neoplásica/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ativação Enzimática , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Imuno-Histoquímica , Oxirredutases Intramoleculares/genética , Camundongos , Camundongos Transgênicos , Microssomos , Prostaglandina-E Sintases , Distribuição Aleatória , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
Postoperative adhesions are a common cause of adhesive small bowel obstruction (ASBO), and recognition of intestinal strangulation is important. The aim of this study is to analyze the clinical factors for strangulating obstruction and to identify the predictors for recurrence of ASBO.A retrospective study was conducted using the database in our department. Patients with ASBO from January 2013 to April 2016 were included in the study and were subject to follow-up. The clinical factors associated with strangulating obstruction and recurrence after treatment were analyzed by using univariate and multivariate logistic regression model.In total, 288 ASBO patients were included in the study. Of these, 37 (12.9%) patients had occurred strangulating obstructions, and 251 (87.1%) patients had simple obstructions. Four clinical parameters, including increasing heart rate (>100 bpm), increasing WBC count (>15â×â10/L), CT findings of thickening or swelling of the mesentery, and CT showing seroperitoneum were detected as independent clinical factors for intestinal strangulation. Eighty-four (29.2%) patients experienced recurrence of obstruction during the median 24 months of follow-up. Recurrence rates were reduced in patients who underwent surgical treatment compared with those who received conservative management [21.3% (26/122) vs 34.9% (58/166) (Pâ=â.010)]. Nevertheless, the recurrence rates were not significantly increased in patients with strangulating obstructions compared with those with simple ASBO [34.3% (12/35) vs 27.7% (72/253) (Pâ=â.186)].Four clinical parameters including tachycardia, leukocytosis, along with CT findings of thickening or swelling of the mesentery and CT showing seroperitoneum, associated with occurrence of intestinal strangulation in ASBO. ASBO patients who underwent surgical treatment had a reduced recurrence rate, but ASBO patients with strangulating obstructions had not increase the recurrence rates than those of patients with simple ASBO.
Assuntos
Obstrução Intestinal/patologia , Intestino Delgado , Complicações Pós-Operatórias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tratamento Conservador/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Modelos Logísticos , Masculino , Mesentério/diagnóstico por imagem , Mesentério/patologia , Pessoa de Meia-Idade , Análise Multivariada , Peritônio/diagnóstico por imagem , Peritônio/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Recidiva , Estudos Retrospectivos , Aderências Teciduais/etiologia , Aderências Teciduais/patologia , Aderências Teciduais/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Preoperational hemogram parameters have been reported to be associated with the prognosis of several types of cancers. This study aimed to investigate the prognostic value of hematological parameters in gastric cancer in a Chinese population. A total of 870 gastric cancer patients who underwent radical tumorectomy were recruited from January 2008 to December 2012. Preoperative hematological parameters were recorded and dichotomized by time-dependent receiver operating characteristic curves. The survival curves of patients stratified by each hematological parameter were plotted by the Kaplan-Meier method and compared by log-rank test. Multivariate Cox proportional hazards models were used to select parameters independently correlated with prognosis. The median age of the patients was 60 years. The median follow-up time was 59.9 months, and the 5-year survival rate was 56.4%. Results from the univariate analyses showed that low lymphocyte count (<2.05â×â10/L), high neutrophil-to-white blood cell ratio (NWRâ>â0.55), low lymphocyte-to-white blood cell ratio (LWRâ<â0.23), low lymphocyte-to-monocyte ratio (LMRâ<â5.43), high neutrophil-to-lymphocyte ratio (NLRâ>â1.44), and high platelet-to-lymphocyte ratio (PLRâ>â115) were associated with poor survival of gastric cancer patients. Multivariate analysis showed that low LMR (HR: 1.49, 95% CI: 1.17-1.89, Pâ=â.001) was the only hematological factor independently predicting poor survival. These results indicate that preoperational LMR is an independent prognostic factor for patients with resectable gastric cancer.
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Linfócitos/metabolismo , Monócitos/metabolismo , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Idoso , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
AIM: To investigate the role of single nucleotide polymorphisms (SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer (GC). METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3' untranslated region - using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy (GA) cases and 976 tumor-free controls. Serum immunoglobulin G antibodies to Helicobacter pylori (H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios (ORs) with 95% confidence intervals (95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test (recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median follow-up time for the 600 GC patients included in the survival analysis was 36.2 mo (range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival (HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years (HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC (including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes. CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.
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Biomarcadores Tumorais/genética , Antígeno CD24/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Regiões 3' não Traduzidas , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Éxons , Feminino , Loci Gênicos , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: To study the efficacy of the enhanced recovery after surgery (ERAS) program in laparoscopic radical gastrectomy for stomach carcinomas. METHODS: From June 2010 to December 2012, 61 gastric cancer patients who underwent laparoscopic-assisted radical gastrectomy with D2 lymphadenectomy at First Hospital of Jilin University were enrolled in this randomized controlled trial. (Clinical Trials.gov, registration ID: NCT01955096). The subjects were divided into the ERAS program group and the conventional control group. The clinical characteristics, recovery variables, and complications of patients were analyzed. RESULTS: The time to first ambulation, oral food intake, and time to defecation were significantly shorter in the ERAS group (n = 30), compared to the conventional group (n = 31; P = 0.04, 0.003, and 0.01, respectively). The postoperative hospital stay was less in the ERAS group (6.8 ± 1.1 d) compared to the conventional group (7.7 ± 1.1 d) (P = 0.002). There was no significant difference in postoperative complications between the ERAS (1/30) and conventional care groups (2/31) (P = 1.00). There were no readmissions or mortality during the 30-d follow-up period. CONCLUSION: The ERAS program is associated with a shorter hospital stay in gastric cancer patients undergoing laparoscopic radical gastrectomy. The ERAS protocol is useful in the treatment of gastric cancer.
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Carcinoma/cirurgia , Gastrectomia/métodos , Laparoscopia , Neoplasias Gástricas/cirurgia , Idoso , Carcinoma/secundário , China , Feminino , Gastrectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Prospectivos , Recuperação de Função Fisiológica , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: To explore the alteration of DNA methyltransferase expression in gastric cancer and to assess its prognostic value. METHODS: From April 2000 to December 2010, 227 men and 73 women with gastric cancer were enrolled in the study. The expression of DNA methyltransferases (DNMTs), including DNMT1, DNMT3a and DNMT3b, in the 300 cases of gastric carcinoma, of which 85 had paired adjacent normal gastric mucus samples, was evaluated by immunohistochemistry using a tissue microarray. Serum anti-Helicobacter pylori (H. pylori) IgG was detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the above results and the clinicopathological characteristics were analyzed. Their prognostic value was evaluated using the Cox proportional hazards model. RESULTS: In gastric cancer, expression of DNMTs was mainly seen in the nucleus. Weak staining was also observed in the cytoplasm. Expression of DNMT1, DNMT3a and DNMT3b in gastric cancer was significantly higher compared to that in the paired control samples (60.0% vs 37.6%, 61.2% vs 4.7%, and 94.1% vs 71.8%, P < 0.01). The overall survival rate was significantly higher in the DNMT3a negative group than in the DNMT3a positive group in gastric cancer patients (Log-rank test, P = 0.032). No significant correlation was observed between DNMT1 and DNMT3b expression and the overall survival time (Log-rank test, P = 0.289, P = 0.347). Multivariate regression analysis indicated that DNMT3a expression (P = 0.025) and TNM stage (P < 0.001), but not DNMT1 (P = 0.54) or DNMT3b (P = 0.62), were independent prognostic factors in gastric cancer. H. pylori infection did not induce protein expression of DNMTs. CONCLUSION: The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis.
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Biomarcadores Tumorais/análise , DNA (Citosina-5-)-Metiltransferases/análise , Neoplasias Gástricas/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , DNA (Citosina-5-)-Metiltransferase 1 , DNA Metiltransferase 3A , Ensaio de Imunoadsorção Enzimática , Feminino , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/sangue , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/sangue , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade , Fatores de Tempo , DNA Metiltransferase 3BRESUMO
AIM: To introduce transvaginal or transanal specimen extraction in laparoscopic total mesorectal excision surgery to avoid an abdominal incision. METHODS: Between January 2009 and December 2011, 21 patients with rectal cancer underwent laparoscopic radical resection and the specimen was retrieved by two different ways: transvaginal or transanal rectal removal. Transvaginal specimen extraction approach was strictly limited to elderly post-menopausal women who need hysterectomy. Patients aged between 30 and 80 years, with a body mass index of less than 30 kg/m², underwent elective surgery. The surgical technique and the outcomes related to the specimen extraction, such as duration of surgery, length of hospital stay, and the complications were retrospectively reviewed. RESULTS: Laparoscopic resection using a natural orifice removal approach was successful in all of the 21 patients. Median operating time was 185 min (range, 122-260 min) and the estimated blood loss was 48 mL. The mean length of hospital stay was 7.5 d (range, 2-11 d). One patient developed postoperative ileus and had an extended hospital stay. The patient complained of minimal pain. There were no postoperative complications or surgery-associated death. The mean size of the lesion was 2.8 cm (range, 1.8-6.0 cm), and the mean number of lymph nodes harvested was 18.7 (range, 8-27). At a mean follow-up of 20.6 mo (range, 10-37 mo), there were no functional disorders associated with the transvaginal and transanal specimen extraction. CONCLUSION: Transvaginal or transanal extraction in L-TME is a safe and effective procedure. Natural orifice specimen extraction can avoid the abdominal wall incision and its potential complications.
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Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Neoplasias Retais/cirurgia , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. METHODS: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. RESULTS: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. CONCLUSIONS: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.
Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Predisposição Genética para Doença/genética , Infecções por Helicobacter/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA Metiltransferase 3A , Feminino , Gastrite Atrófica/genética , Genótipo , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Gastric cancer remains the fourth most commonly diagnosed cancer and is the second leading cause of cancer-related mortality worldwide. The aim of this study was to investigate the effects of canolol on the proliferation and apoptosis of SGC-7901 human gastric cancer cells and its relevant molecular mechanisms. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to observe the effect of canolol on the proliferation of SGC-7901 human gastric adenocarcinoma cells. The results showed that SGC-7901 cells exhibited a marked dose-dependent reduction in the proliferation rate. The survival rate of the cells was 88.86±1.58% at 50 µmol/l, decreasing to 53.73±1.51% at 800 µmol/l (P<0.05). By contrast, canolol had no significant toxicity on the human gastric mucosal epithelial cell line GES-1. The vivid images of cell morphology using an inverted microscope provided confirmation of the MTT assay. Treatment of SGC-7901 cells with canolol resulted in apoptosis demonstrated by flow cytometry. Furthermore, canolol downregulated the mRNA levels of COX-2, but had no significant effect on the mRNA expession of the Bax and Bcl-2 genes. These findings suggest that canolol has potential to be developed as a new natural anti-gastric carcinoma agent.
RESUMO
AIM: To explore the alteration of tyrosine phosphatase SHP-2 protein expression in gastric cancer and to assess its prognostic values. METHODS: Three hundred and five consecutive cases of gastric cancer were enrolled into this study. SHP-2 expression was carried out in 305 gastric cancer specimens, of which 83 were paired adjacent normal gastric mucus samples, using a tissue microarray immunohistochemical method. Correlations were analyzed between expression levels of SHP-2 protein and tumor parameters or clinical outcomes. Serum anti-Helicobacter pylori (H. pylori) immunoglobulin G was detected with enzyme-linked immunosorbent assay. Cox proportional hazards model was used to evaluate prognostic values by compassion of the expression levels of SHP-2 and disease-specific survivals in patients. RESULTS: SHP-2 staining was found diffuse mainly in the cytoplasm and the weak staining was also observed in the nucleus in gastric mucosa cells. Thirty-two point five percent of normal epithelial specimen and 62.6% of gastric cancer specimen were identified to stain with SHP-2 antibody positively (P < 0.001). Though SHP-2 staining intensities were stronger in the H. pylori (+) group than in the H. pylori (-) group, no statistically significant difference was found in the expression levels of SHP-2 between H. pylori (+) and H. pylori (-) gastric cancer (P = 0.40). The SHP-2 expression in gastric cancer was not significantly associated with cancer stages, lymph node metastases, and distant metastasis of the tumors (P = 0.34, P = 0.17, P = 0.52). Multivariate analysis demonstrated no correlation between SHP-2 expression and disease-free survival (P = 0.86). CONCLUSION: Increased expression of SHP-2 protein in gastric cancer specimen suggesting the aberrant up-regulation of SHP-2 protein might play an important role in the gastric carcinogenesis.
Assuntos
Biomarcadores Tumorais/análise , Infecções por Helicobacter/enzimologia , Helicobacter pylori/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 11/análise , Neoplasias Gástricas/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Biópsia , Intervalo Livre de Doença , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/sangue , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Fatores de Tempo , Análise Serial de Tecidos , Regulação para CimaRESUMO
AIM: To investigate screening makers for gastric cancer, we assessed the association between gastric cancer and serum pepsinogens (PGs). METHODS: The subjects comprised 450 patients with gastric cancer, 111 individuals with gastric atrophy, and 961 healthy controls. Serum anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG), PGI and PG II were detected by enzyme-linked immunosorbent assay. Gastric atrophy and gastric cancer were diagnosed by endoscopy and histopathological examinations. Odds ratios and 95%CIs were calculated using multivariate logistic regression. RESULTS: Rates of H. pylori infection remained high in Northeastern China. Rates of H. pylori IgG positivity were greater in the gastric cancer and gastric atrophy groups compared to the control group (69.1% and 75.7% vs 49.7%, P < 0.001). Higher levels of PG IIâ (15.9 µg/L and 13.9 µg/L vs 11.5 µg/L, P < 0.001) and lower PGI/PG II ratio (5.4 and 4.6 vs 8.4, P < 0.001) were found in patients with gastric cancer or gastric atrophy compared to healthy controls, whereas no correlation was found between the plasma PGI concentration and risk of gastric cancer (P = 0.537). In addition, multivariate logistic analysis indicated that H. pylori infection and atrophic gastritis were independent risk factors for gastric cancer. Lower plasma PGI/PG II ratio was associated with higher risks of atrophy and gastric cancer. Furthermore, plasma PG II level significantly correlated with H. pylori-infected gastric cancer. CONCLUSION: Serum PG II concentration and PGI/PG II ratio are potential biomarkers for H. pylori-infected gastric disease. PG II is independently associated with risk of gastric cancer.
Assuntos
Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Pepsinogênio C/sangue , Neoplasias Gástricas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Endoscopia , Ensaio de Imunoadsorção Enzimática , Feminino , Gastrite Atrófica/sangue , Gastrite Atrófica/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiologiaRESUMO
AIM: To investigate the role of expressions of Ki-67, p53, epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in gastrointestinal stromal tumor (GIST) grading and prognosis. METHODS: Tumor tissue was collected retrospectively from 96 patients with GIST. Antibodies against Ki-67, p53, EGFR and COX-2 were used for immunohistochemical staining. Tumor grading was designated according to a consensus system and the staining was quantified in 3 categories for each antibody in the statistical analysis. RESULTS: The Ki-67 expression in GISTs was significantly associated with the size of the tumors, mitotic rate and the risk of malignancy (χ(2) = 15.51, P = 0.02; χ(2) = 22.27, P < 0.001; χ(2) = 20.05; P < 0.001). The p53 expression was also significantly correlated with mitotic rate and the risk of malignancy (χ(2) = 9.92, P = 0.04; χ(2) = 9.97; P = 0.04). Over-expression of Ki-67 was strongly correlated with poor survival (χ(2) = 10.44, P = 0.006), but no correlation was found between the expression of p53, EGFR or COX-2 and survival. Multivariate analysis further demonstrated that Ki-67 expression (relative risk = 15.78, 95% CI: 4.25-59.37) could be used as an independent prognostic value for GIST patients. Adjuvant imatinib therapy could improve clinical outcomes in the patients with high risk and intermediate risk of recurrence after complete tumor resections (median survival time: 52 mo vs 37 mo, χ(2) = 7.618, P = 0.006). CONCLUSION: Our results indicated that the expression of Ki-67 could be used as an independent prognostic factor for GIST patients.