RESUMO
BACKGROUND AND AIMS: DJ-1 and PTEN have been shown to involve in multiple cell processes and play an important role in cancer development and progression. However, their relationship with gastric carcinoma (GC) has not been identified yet. The purpose of this study is to clarify the relationship of DJ-1 and phosphatase and tensin homolog (PTEN) with clinicopathological parameters and prognosis in GC. METHODS: 114 specimens were collected from GC patients and expression of DJ-1 and PTEN in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, follow-up data of patients, was analyzed statistically. RESULTS: High expression of DJ-1 was found in 66.7% (76/114) and associated with tumor depth (P=0.003), lymph node metastasis (P=0.011), distant metastasis (P=0.001) and advanced clinical stage (P=0.001). Loss or downregulation of PTEN was found in 58.7% (67/114) and associated with advanced clinical stage (P=0.018) and high expression of DJ-1 in tumor cells (P=0.006). In univariate survival analysis, high-expression of DJ-1 or loss of PTEN was significantly associated with poor prognosis of GC patients. However, only tumor depth (P=0.011) and coexistence of DJ-1 and PTEN abnormal expression (P=0.009) emerged as strong independent prognostic factors for overall survival of GC patients. CONCLUSIONS: the present study indicates that DJ-1 and PTEN may play their roles in progression of GC in a cooperating pattern. Co-existence of abnormal DJ-1 and PTEN expression is likely to serve as an independent predictive factor for prognosis of GC patients.
Assuntos
Carcinoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas Oncogênicas/biossíntese , PTEN Fosfo-Hidrolase/biossíntese , Neoplasias Gástricas/genética , Idoso , Carcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Proteínas Oncogênicas/genética , PTEN Fosfo-Hidrolase/genética , Inclusão em Parafina , Prognóstico , Modelos de Riscos Proporcionais , Proteína Desglicase DJ-1 , Neoplasias Gástricas/patologiaRESUMO
The prognosis and overall survival of castration-resistant prostate cancer (CRPC) patients are poor. The search for novel and efficient anti-CRPC agents is therefore extremely important. WM-3835 is a cell-permeable, potent and first-in-class HBO1 (KAT7 or MYST2) inhibitor. Here in primary human prostate cancer cells-derived from CRPC patients, WM-3835 potently inhibited cell viability, proliferation, cell cycle progression and in vitro cell migration. The HBO1 inhibitor provoked apoptosis in the prostate cancer cells. It failed to induce significant cytotoxicity and apoptosis in primary human prostate epithelial cells. shRNA-induced silencing of HBO1 resulted in robust anti-prostate cancer cell activity as well, and adding WM-3835 failed to induce further cytotoxicity in the primary prostate cancer cells. Conversely, ectopic overexpression of HBO1 further augmented primary prostate cancer cell proliferation and migration. WM-3835 inhibited H3-H4 acetylation and downregulated several pro-cancerous genes (CCR2, MYLK, VEGFR2, and OCIAD2) in primary CRPC cells. Importantly, HBO1 mRNA and protein levels are significantly elevated in CRPC tissues and cells. In vivo, daily intraperitoneal injection of WM-3835 potently inhibited pPC-1 xenograft growth in nude mice, and no apparent toxicities detected. Moreover, intratumoral injection of HBO1 shRNA adeno-associated virus (AAV) suppressed the growth of primary prostate cancer xenografts in nude mice. H3-H4 histone acetylation and HBO1-dependent genes (CCR2, MYLK, VEGFR2, and OCIAD2) were remarkably decreased in WM-3835-treated or HBO1-silenced xenograft tissues. Together, targeting HBO1 by WM-3835 robustly inhibits CRPC cell growth.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Animais , Camundongos , Humanos , Camundongos Nus , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Interferente Pequeno , Histona Acetiltransferases/metabolismo , Proteínas de NeoplasiasRESUMO
Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real-time RT-PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real-time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP-high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP-high gastric cancer showed significantly worse survival compared with that of CIMP-low/CIMP-negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP-high was an independent prognostic factor.
Assuntos
Ilhas de CpG/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/genética , Feminino , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori/genética , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Metástase Linfática , Masculino , Proteínas de Membrana/genética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Fenótipo , Prognóstico , RNA Neoplásico , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Fator Natriurético Atrial/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/virologia , Taxa de Sobrevida , Fatores de Transcrição/genéticaRESUMO
BACKGROUND AND OBJECTIVES: The purpose of this study was to clarify the relationship of hepatocyte growth factor (HGF), c-Met, and E-cadherin with clinicopathological parameters and prognosis in gastric carcinoma (GC). METHODS: 114 specimens were collected from GC patients and expression of HGF, c-Met, and E-cadherin in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, follow-up data of patients, was analyzed statistically. RESULTS: Abnormal E-cadherin expression was found in 60.5% (69/114) and associated with tumor depth (P = 0.003), lymph node metastasis (P = 0.001) and advanced clinical stage (P = 0.001). High-expression of HGF and c-Met were found in 64.0% (73/114) and 82.4% (94/114), respectively. High c-Met expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.011) of GC. In univariate survival analysis, high-expression of HGF and c-Met, and abnormal E-cadherin were significantly associated with poor prognosis of GC patients. However, only abnormal E-cadherin expression (P = 0.001) and tumor depth (P = 0.010) emerged as strong independent prognostic factors for overall survival of GC patients. CONCLUSION: We found significant correlation among HGF/c-Met, E-cadherin expression and worse prognosis of patients with GC. Abnormal E-cadherin expression may serve as an independent predictive factor for prognosis of GC patients.
Assuntos
Caderinas/metabolismo , Carcinoma/metabolismo , Carcinoma/mortalidade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Citoplasma/metabolismo , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-met/metabolismo , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: To compare Borrmann type IV gastric cancer with other types of cancer and explore their clinicopathological features and prognostic factors. METHODS: We retrospectively reviewed the medical records of 893 consecutive advanced gastric cancer patients. They were divided into 2 groups: Borrmann type IV (n = 139) and other macroscopic Borrmann types of cancer (n = 754). Their clinicopathologic characteristics and overall survival data were analyzed. RESULTS: Borrmann type IV gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features. The incidence of preoperative biopsy-negative rate of Borrmann type IV gastric cancer was much higher (15.9%) than other Borrmann types of gastric cancer. The 5-year survival rate of Borrmann type IV cancer patients was 9.9% and it was significantly lower than that of other types. Moreover, the 5-year survival rate was higher in the patients with curative resection (18.7%) (P < 0.05). Stratified analysis revealed that when the tumor TNM stages were of II, III, the survival data of Borrmann type IV cancer were worse than others. Multivariate analyses revealed distant metastasis and curability were independent prognostic factors for Borrmann type IV gastric cancer. CONCLUSIONS: Borrmann type IV carcinoma has poor clinicopathological features and survival rate compared with other types. An early detection and curative resection may improve the prognosis for the patients with Borrmann type IV cancer.
Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/classificação , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the impact of surgical modality for gastric cancer on operational trauma. METHODS: A total of 1499 cases of gastric cancer undergoing surgical procedures were divided into the groups of radical resection (RR, n = 1344) and palliative resection group (NRR, n = 155) according to their surgical modalities. And they were further divided into sub-groups according to the profiles of gastrectomy, extent of lymphadenectomy and multi organic resection. The extent of operational trauma (as evaluated by operative duration, transfusion volume, postoperative hospital day and incidence of complications) was compared in different groups and subgroups. RESULTS: In RR and NRR groups, median transfusion volume (Q(1), Q(3)) was 0 (0, 600) vs 400 (0, 800) ml respectively. There was significant difference (P < 0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P > 0.05). In cases of distal gastrectomy, median transfusion volume was 0 (0, 400) vs 400 (200, 800) ml in RR and NRR groups (P < 0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P > 0.05). In cases of total gastrectomy, no significant difference existed in operative duration, postoperative hospital day, median transfusion volume or incidence of complications between two groups (all P > 0.05). In RR group, for the cases treated by D1, D2, D3 and paraaortic lymph node dissection (PAND), there were significant differences in operative duration ((248 ± 71), (271 ± 72), (309 ± 96), (351 ± 103) min), postoperative hospital day ((13 ± 4), (16 ± 12), (18 ± 11), (20 ± 19) days), median transfusion volume (0(0, 500), 0(0, 600), 400(0, 800), 600(200, 1000) ml) (all P < 0.05). But no significant difference existed in incidence of complications (P > 0.05). In RR group, operative duration, postoperative hospital day, median transfusion volume was (315 ± 96) vs (264 ± 66) min, (19 ± 15) vs (15 ± 11) days, 400 (0, 800) vs 0 (0, 400) ml in the patients with and without combined organic resection (all P < 0.05). But no significant difference existed in incidence of complications (P > 0.05). CONCLUSIONS: As compared with palliative resection, radical resection will not increase surgical trauma. For the cases of radical resection, extent of lymphadenectomy and organic resection increase surgical trauma.
Assuntos
Gastrectomia/efeitos adversos , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Ferimentos e Lesões/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Adulto JovemRESUMO
OBJECTIVE: To explore the effects of fast-track surgery on postoperative humoral immune function in patients undergoing elective colorectal resection. METHODS: Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into fast-track group (n = 35) and conventional care group (n = 35). The clinical parameters and markers of humeral immune function were evaluated in both groups postoperatively. RESULTS: Sixty-two patients finally completed the study, including 32 in the fast-track group and 30 in the conventional care group. There was a significantly faster recovery of postoperative humoral immunity: blood levels of globulin (24.1 ± 2.4 vs 22.1 ± 3.3 g/L, P = 0.025), immunoglobulin G (10.79 ± 2.39 vs 8.66 ± 2.09 g/L, P = 0.007) and complement 4 (0.24 ± 0.09 vs 0.17 ± 0.05 g/L, P = 0.035) at Day 3 postoperation were higher in the fast-track group than in the conventional care group. And there was also a significantly shorter length of postoperative stay (6.0 ± 1.0 vs 11.7 ± 3.8 d, P < 0.001) in patients undergoing fast-track rehabilitation. CONCLUSION: Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.
Assuntos
Neoplasias Colorretais/imunologia , Imunidade Humoral , Idoso , Formação de Anticorpos/imunologia , Neoplasias Colorretais/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effects of fast track surgery on postoperative insulin sensitivity on the basis of clinical benefits in patients undergoing elective open colorectal resection. METHODS: During May 2008 to December 2008, Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups: a fast track group (35 cases) and a conventional care group (35 cases). All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters, stress markers and insulin sensitivity were evaluated in both groups. RESULTS: The 62 patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. The speed of recovery of postoperative insulin sensitivity on 7 days postoperative in the fast-track group (97% ± 9%) was significantly faster than the conventional care group (88.5% ± 9.0%, t = 2.552, P = 0.016). The hospitalization days in the fast-track group was 6 days (M(50)), and it was significantly shorter than the conventional care group ((11.7 ± 3.8) days, Z = 4.360, P = 0.000). The time of recovery of bowel function were faster in the fast-track group (time to pass flatus was 2 days (M(50))) than the conventional care group (4 days, Z = 3.976, P = 0.000). The Infectious complication rate in the fast-track group (2/32) is lower than the other group (8/30, P = 0.040). CONCLUSION: Fast track surgery accelerates recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a lower rate of postoperative infectious complications and a shorter length of postoperative hospital stay.
Assuntos
Neoplasias Colorretais/reabilitação , Resistência à Insulina , Assistência Perioperatória/métodos , Idoso , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Deciphering the crosstalk between RNA-binding proteins and corresponding RNAs will provide a better understanding of gastric cancer (GC) progression. The comprehensive bioinformatics study identified cytoplasmic polyadenylation element-binding protein 3 (CPEB3) might play a vital role in GC progression. Then we found CPEB3 was downregulated in GC and correlated with prognosis. In addition, CPEB3 suppressed GC cell proliferation, invasion and migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistic study demonstrated CPEB3 interacted with 3'-UTR of ADAR1 mRNA through binding to CPEC nucleotide element, and then inhibited its translation by localizing it to processing bodies (P bodies), eventually leading to the suppression of ADAR1-mediated RNA editing. Microscale thermophoresis assay further revealed that the direct interaction between CPEB3 and GW182, the P-body's major component, was through the 440-698AA region of CPEB3 binding to the 403-860AA region of GW182. Finally, AAV9-CPEB3 was developed and administrated in mouse models to assess its potential value in gene therapy. We found AAV9-CPEB3 inhibited GC growth and metastasis. Besides, AAV9-CPEB3 induced hydropic degeneration in mouse liver, but did not cause kidney damage. These findings concluded that CPEB3 suppresses GC progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies.
Assuntos
Edição de RNA , Neoplasias Gástricas , Regiões 3' não Traduzidas/genética , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Animais , Camundongos , Nucleotídeos , Edição de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: To compare the reconstructing safety of pancreaticogastrostomy (PG) versus pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). METHODS: The articles of prospectively controlled trials published until late December 2010 comparing PJ and PG after PD were searched by the means of MEDLINE, EMBASE, Cochrane Controlled Trials Register databases and Chinese Biomedical Database. After quality assessment of all included prospective controlled trials, a meta-analysis was performed with Review Manager 5.0 for statistic analysis. RESULTS: A total of 6 prospective controlled trials were included. Among 867 patients analyzed, 440 underwent PG and 426 PJ. A meta-analysis of 6 prospective controlled trials (including randomized control trial (RCT) and non-randomized prospective trial) revealed significant differences between PJ and PG regarding the overall postoperative complication rates [OR 0.53, 95%CI (0.30, 0.95), P = 0.03], pancreatic fistula [OR 0.47, 95%CI (0.22, 0.97), P = 0.04] and intra-abdominal fluid collection [OR 0.42, 95%CI (0.25, 0.72), P = 0.001]. The differences in biliary fistula, intra-abdominal (IAC) complications and mortality were of no significance. Meta-analysis of 4 RCTs revealed significant differences between PJ and PG regarding intra-abdominal fluid collection [OR 0.46, 95%CI (0.26, 0.79), P = 0.005]. The differences in pancreatic fistula, overall postoperative complications, biliary fistula, intra-abdominal complications and mortality were of no statistical significance. CONCLUSION: Through a meta-analysis of 6 prospective controlled trials, there are significant differences between PJ and PG regarding overall postoperative complications, pancreatic fistula and intra-abdominal fluid collection. Significant differences exist between PJ and PG regarding intra-abdominal fluid collection. The safety profiles of PG and PJ are comparable.
Assuntos
Gastrostomia , Pâncreas/cirurgia , Pancreaticoduodenectomia , Pancreaticojejunostomia , Ensaios Clínicos Controlados como Assunto , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: The platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been found to be associated with prognosis in several solid tumours. However, the prognostic roles of PLR and NLR in gastrointestinal stromal tumours (GISTs) remain controversial. The aim of this meta-analysis was to assess the prognostic roles of PLR and NLR in GISTs. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library for relevant articles. A systematic review was performed to calculate pooled hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) by fixed-effects/random-effects models. RESULTS: Fourteen studies containing 3,151 subjects were finally enrolled in this meta-analysis. Eight studies including 2,560 patients investigated the prognostic effect of PLR, and thirteen studies with 2,751 subjects explored the prognostic effect of NLR. Both elevated PLR (HR: 1.29, 95% CI: 1.10-1.52, P=0.002) and NLR (HR: 1.37, 95% CI: 1.15-1.63, P=0.0005) were significantly associated with decreased DFS. The pooled HR for PLR was not significantly different from that for NLR. High PLR and NLR correlated with increased tumour sizes, more advanced tumour stages and mitotic index (>5/50 HPF). In addition, elevated PLR was related to adjuvant tyrosine kinase inhibitor (TKI) therapy. CONCLUSIONS: Elevated preoperative PLR and NLR are associated with poor outcomes in patients with GISTs.
RESUMO
OBJECTIVE: To investigate clinicopathological characteristics and the pattern of lymph node metastasis of patients with gastric remnant cancer. METHODS: The data of the clinicopathological characteristics and the pattern of lymph node metastasis in 56 patients with gastric remnant cancer treated from March 1994 to December 2008 was investigated and compared with those in 1171 patients with primary gastric cancer treated over the same period. RESULTS: Fifty-six patients (4.6%) with gastric remnant cancer were enrolled in this study during the period. Compared with patients with primary gastric cancer, the age of cancer onset was older [(64.3+/-9.0) vs. (58.3+/-12.6) yrs], lymph node metastasis rate was higher (31.8% vs. 25.5%), Borrmann's classification was later and neighbor organ resection rate was higher (57.1% vs. 26.4%) in patients with gastric remnant cancer; the differences were all significant (chi2=18.800, 11.679, 9.177, 25.190; P<0.05). Patients with gastric remnant cancer who underwent lymph node dissection tended to have a higher incidence of No.10 (splenic hilar lymph node) and No.11 (splenic artery lymph node) group lymph node metastasis than those in primary gastric cancer (chi2=5.558, 6.099; P<0.05). In contrast, patients with primary gastric cancer had a higher incidence of No. 2 (left cardiac lymph node), No.3 (lesser curvature lymph node) and No.8 (common hepatic artery lymph node) group lymph node metastasis than those in gastric remnant cancer (chi2=15.508, 6.003, 4.084; P<0.05). The jejunal mesentery lymph node metastasis was 24.0% (6/25) in patients with gastric remnant cancer and the peripheral connective tissue infiltration rate was 14.3% (8/56). CONCLUSIONS: It suggested that patients with gastric remnant cancer has different clinicopathologic characteristics and the pattern of lymph node metastasis from those with primary gastric cancer. D2 lymph node dissection of proximate gastric cancer and jejunal mesentery lymph node dissection should be the standard operation for these patients; but combined neighboring organ resection should be taken into consideration.
Assuntos
Coto Gástrico , Neoplasias Gástricas/patologia , Idade de Início , Idoso , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVE: To investigate the protein expression, methylation promoter, somatic and germ-line mutations of E-cadherin gene (CDH1) in hereditary gastric cancer in China and to investigate its possible roles. METHODS: Eight probands diagnosed with ICG-HGC criterion were enrolled in our database from June 1994 to October 2007. Tumor tissues were detected for CDH1 expression by using immunohistochemistry (IHC) methods. CDH1 DNA sequencing was performed for all its 16 exons both in tumor and normal tissues of the same patients to detect somatic and germ-line mutations. Methylation promoter study was performed by using specific primers and polymerase chain reaction (PCR) methods. RESULTS: IHC analysis confirmed that the CDH1 expression was negative in 7 probands and downregulated in the other on proband. Six mutations in five probands were found with DNA sequencing: two silent mutations and four missense mutations. All six mutations were absent in normal tissues, thereby excluded its presence in germ-line cells. Both DNA missense mutations and gene silencing through promoter methylation was found in 4 probands. Two probands has only promoter methylation and one proband had only silent mutation. No DNA missense mutations or promoter methylation was found in one proband. CONCLUSIONS: CDH1 gene germ-line mutations are relatively rare in hereditary gastric cancer in China, and whereas CDH1 somatic mutations and promoter methylation synergistically induce CDH1 downregulation in these patients.
Assuntos
Caderinas/genética , Mutação em Linhagem Germinativa , Neoplasias Gástricas/genética , Antígenos CD , Metilação de DNA , Análise Mutacional de DNA , Humanos , Regiões Promotoras Genéticas/genéticaRESUMO
Enzymatic hydrolysis of lignocellulose to produce bioethanol by cellulase is an important method to alleviate the energy crisis. In this paper, in order to overcome the shortcomings of low efficiency, high cost and easy deactivation of cellulase in the process of bio-refinery, pH-responsive lignin-based magnetic nanoparticles (Fe3O4/LSQA) were synthesized to immobilize and recover cellulase. It was shown that a high immobilization ratio of 55.52% for cellulase was obtained. Meanwhile, the desorption ratio was 68.27% by adjusting the pH of the system. After five reusing cycles, the desorbed cellulase retained 31.79% of the relative activity due to the pH responsiveness of Fe3O4/LSQA. These results not only provide a new idea for the recycling of cellulase, but also broaden the application of industrial lignin and increase the extra value.
Assuntos
Celulase , Nanopartículas de Magnetita , Concentração de Íons de Hidrogênio , Hidrólise , LigninaRESUMO
AIM: To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer (HNPCC) in suspected Chinese patients. METHODS: Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC). Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool (BLAST), and tested in the corresponding family members by direct DNA sequencing. RESULTS: Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A-->G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC (HNPCC5) kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A-->G was identified in the HNP2 kindred's proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION: Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Testes Genéticos/métodos , Testes Genéticos/normas , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Adulto , Idoso , Povo Asiático/genética , Sequência de Bases , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/etnologia , Feminino , Predisposição Genética para Doença/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteína 1 Homóloga a MutL , Mutação de Sentido Incorreto , Linhagem , Fatores de RiscoRESUMO
PURPOSE: This study was designed to evaluate the impact of laparoscopic converted to open colectomy on short-term and oncologic outcomes and to identify risk factors for long-term survival in patients undergoing colectomy for non-metastatic colon cancer. METHODS: A prospective database of consecutive operations for non-metastatic colon cancer was reviewed. Patients were grouped as conversion (CONV) group, completed laparoscopic resection (LAP) group, or open resection (OPEN) group. The clinical and perioperative parameters, pathologic features, and oncologic outcomes were collected. Univariate analysis was performed for comparing these data. Patients without evidence of recurrence at last follow-up or still alive at the end of study period were censored. Kaplan-Meier curves were utilized to analyze survival. A multivariate analysis was performed to identify predictors of poor disease-free survival (DFS) and overall survival (OS). RESULTS: The conversion rate was 15.2 %. The most common reason for conversion was locally advanced cancer (45.5 %). Converted patients were associated with a longer operative time (188 ± 29.1 min, P < 0.001), greater blood loss (147 ± 14 mL, P < 0.001), and a higher rate of intra-operative complications (15.2 %, P = 0.042) compared to the completely laparoscopic or open patients. Days to flatus, early ambulation, and length of hospitalization were significantly shorter in completed laparoscopic resection (LAP) group (P < 0.001); however, the outcomes were comparable between conversion (CONV) and open resection (OPEN) groups. The incidence of wound infection was significantly higher in the OPEN group than in the LAP group (P = 0.005), whereas there were no significant differences observed between the CONV group and the OPEN group (P = 1.000) or between the LAP group and the CONV group (P = 0.073). The 5-year DFS in CONV patients (46.5 %) was comparable to LAP patients (55.5 %, P = 0.138) and OPEN patients (59.1 %, P = 0.113). Moreover, there were no significant differences noted in terms of the 5-year OS in the CONV group (56.7 %) compared to the LAP group (67.3 %, P = 0.317) or the OPEN group (66.3 %, P = 0.420). The multivariate analysis showed that pT3-4 cancer (P < 0.001) and poor differentiation (P < 0.001) were independent predictors of both lower OS and lower DFS, whereas leakage (P = 0.008) and lack of adjuvant chemotherapy (P = 0.023) were independent risk factors only of lower DFS. CONCLUSION: Conversion to open colectomy from an initial laparoscopic approach does not worsen the long-term survival in patients with non-metastatic colon cancer.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Conversão para Cirurgia Aberta , Laparoscopia , Adenocarcinoma/tratamento farmacológico , Idoso , Quimioterapia Adjuvante , Colectomia/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Conversão para Cirurgia Aberta/efeitos adversos , Intervalo Livre de Doença , Deambulação Precoce , Feminino , Trato Gastrointestinal/fisiologia , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Duração da Cirurgia , Hemorragia Pós-Operatória , Recuperação de Função Fisiológica , Infecção da Ferida Cirúrgica/etiologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AC electroosmosis (ACEO) flow and label-free electrochemical impedance spectroscopy are employed to increase the hybridization rate and specifically detect target DNA (tDNA) concentrations. A low-ionic-strength solution, 6.1µS/cm 1mM Tris (pH 9.3), was used to produce ACEO and proved the feasibility of hybridization. Adequate voltage parameters for the simultaneous ACEO driving and DNA hybridization in the 1mM Tris solution were 1.5 Vpp and 200Hz. Moreover, an electrode set with a 1:4 ring width-to-disk diameter ratio exhibited a larger ACEO velocity above the disk electrode surface to improve collecting efficiency. The ACEO-integrated DNA sensing chips could reach 90% saturation hybridization within 117s. The linear range and detection limit of the sensors was 10aM-10pM and 10aM, respectively. The label-free impedimetric DNA sensing chips with integrated ACEO stirring can perform rapid hybridization and highly-sensitive detections to specifically measure tDNA concentrations.
Assuntos
Técnicas Biossensoriais/instrumentação , DNA/análise , DNA/genética , Espectroscopia Dielétrica/instrumentação , Microfluídica/instrumentação , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Coloração e Rotulagem , Integração de SistemasRESUMO
OBJECTIVE: To investigate the effect of postoperative early oral feeding on humoral immune function and clinical outcome in colorectal cancer patients. METHODS: Seventy patients with colorectal carcinoma requiring elective colorectal resection were prospectively enrolled and randomized into two groups: early oral feeding group(n=35) and conventional oral feeding group(n=35). The patients in early oral feeding group were started on oral feeding within 12 hours after operation, while patients in conventional group were started on oral feeding after the postoperative first passage of flatus. Postoperative parameters of clinic and humeral immune function were compared between two groups. RESULTS: Sixty-two patients eventually completed the study, including 32 cases in early oral feeding group and 30 cases in conventional oral feeding group. The average time to first passage of flatus[(2±1) d vs. (4±2) d, P<0.01], the first passage of stool [(3.8±1.6) d vs. (6.4±2.5) d, P<0.01], resumption of regular diet [(4±2) d vs. (8.2±2.2) d, P<0.01] and the postoperative hospital stay [(6±1) d vs. (11.7±3.8) d, P<0.01] were significantly shorter in early oral feeding group as compared to conventional oral feeding group. Significantly faster recovery of postoperative humoral immunity was found. Plasma levels of globulin [(24.1±2.4) g/L vs. (22.1±3.3) g/L, P<0.05], immunoglobulin G[(10.8±2.4) g/L vs. (8.7±2.1) g/L, P<0.01] and complement 4 [(0.24±0.09) g/L vs. (0.17±0.05) g/L, P<0.05] on postoperative day 3 were higher in early oral feeding group as compared to conventional oral feeding group. CONCLUSION: Application of postoperative early oral feeding in patients undergoing elective colorectal resection is safe and effective, which can lead to faster recovery of postoperative humoral immune function and bowel function, and shorter postoperative hospital stay.
Assuntos
Neoplasias Colorretais/imunologia , Nutrição Enteral , Imunidade Humoral , Neoplasias Colorretais/cirurgia , Defecação , Procedimentos Cirúrgicos Eletivos , Humanos , Tempo de Internação , Período Pós-OperatórioRESUMO
BACKGROUND: Few clinical studies or randomized clinical trial results have reported the impact of fast track surgery on postoperative insulin sensitivity. This study aimed to investigate the effects of fast track surgery on postoperative insulin sensitivity in patients undergoing elective open colorectal resection. METHODS: Controlled, randomized clinical trial was conducted from November 2008 to January 2009 with one-month post-discharge follow-up. Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups: a fast track group (35 cases) and a conventional care group (35 cases). All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters (complication rates, return of gastrointestinal function and postoperative length of stay), stress index and insulin sensitivity were evaluated in both groups perioperatively. RESULTS: Sixty-two patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. Our findings revealed a significantly faster recovery of postoperative insulin sensitivity on postoperative day 7 in the fast-track group than that in the conventional care group. We also found a significantly shorter length of postoperative stay and a significantly faster return of gastrointestinal function in patients undergoing fast-track rehabilitation. CONCLUSION: Fast track surgery accelerates the recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.
Assuntos
Resistência à Insulina/fisiologia , Assistência Perioperatória/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the effects of oral intake of glucose solution before surgery on the pH at the lower esophagus, perioperative blood glucose level, and plasmic protein in patients undergoing radical resection for colorectal cancer. METHODS: Between January 2008 and December 2008, 60 patients undergoing radical surgery for colorectal cancer were enrolled and randomized into three groups using the table of random digits. Four patients were withdrawn from the study. Patients in group A (n=19) were given 800 ml of 12.5% glucose solution for oral intake the night before surgery, and 200 ml two hours before surgery. Patients in group B (n=19) were given distilled water instead of glucose. Patients in group C (n=18) were asked to fast for 8-12 hours before operation. Combined general and epidural anesthesia was used. pH at the lower esophagus was monitored during intubation and extubation. Albumin, transferrin, prealbumin, insulin, and fasting blood glucose were measured before surgery and at postoperative day 1, 3, and 7. RESULTS: pH at the lower esophagus was 8.05±0.43 in group A, 7.98±0.41 in group B, and 7.94±0.41 in group C. There were no perioperative acid regurgitations (P>0.05). Serum insulin in group A at postoperative day 1 was (16.32±16.11) µU/L, which was significantly lower than that in group B (30.65±41.74) µU/L and group C (34.01±52.91) µU/L. Log HOMA-IR in group A at postoperative day 1 was significantly lower than that in group B and group C (0.49±0.35 vs. 0.59±0.56 and 0.60±0.63, P<0.05). Transferrin in group C at postoperative day 3 and 7 was significantly lower than that in the other two groups, as was albumin at postoperative day 3 (P<0.05). CONCLUSION: Oral liquid intake 2 hours before surgery is not associated with increased risk of regurgitation or aspiration during intubation and extubation, and may glucose solution intake reduce insulin resistance and protein degradation after colorectal surgery.