【Abstract】 Objective To investigate the relationship between methylation of tumor suppressor gene and gastric cancer. Methods The literatures in recent years about the concept of methylation, its biological significance and the relationship between DNA methylation/demethylation and gastric cancer were reviewed. The effects of methylation of different tumor suppressor genes on gastric cancer were also analyzed. Results The effect of aberrant methylation on the development and the progression of gastric cancer was still unclear but it was supposed that the inactivation of genes related with cell cycle regulation, mitotic checkpoint, apoptosis, DNA mismatch repair, metastasis suppression and so on might be attributable to the aberrant methylation in gastric cancer. Conclusion Aberrant methylation of tumor suppressor genes plays an important role in the development and progression of gastric cancer. The status of methylation of tumor suppressor genes may be used as a useful molecule marker for diagnosis, assessing metastasis and evaluating prognosis, and demethylation could possibly be a new therapy for gastric cancer.
Objective To investigate the expression and clinical significance of S100A4 protein in tumorstroma of nonsmall cell lung cancer（NSCLC） to study its correlation with invasion, metastasis and prognosis. Methods Immunohistochemical staining（SP method）for S100A4 protein expression was performed in tissue sections from 130 patients with NSCLC operated and to analyze association of S100A4 protein with clinicopathological parameters in lung cancer and prognosis. Results The total positive expression rates of S100A4 protein in stroma of NSCLC was 72.3%. The positive expression rates of S100A4 protein in stroma of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell lung cancer were 84.3%，59.6%，70.0% and 75% respectively.The expression of S100A4 protein was significantly associated with lymph node metastasis (χ2=18.91, P=0.000), distant metastasis(χ2=5.51, P=0.019) and TNM stage (χ2=21.54, P=0.000). The 3 years survival rates of patients whose tumourstroma stained positive for S100A4 was lower than that of patients whose tumourstroma stained negative (36.2% vs. 63.9%, P=0.003). Cox’ risk ratio model analysis indicated that age ≤50 years (OR=1.866), lymph node metastasis(OR=1.826), distant metastasis(OR=6.224), lower histology differentiation and undifferentiation (OR=1.793), TNM stage Ⅲ-Ⅳ (OR=2.573) and positive expression of S100A4 protein in stroma of NSCLC(OR=1.776) were significantly independent prognostic factors which affected survival. Conclusion Expression of S100A4 protein in stroma of NSCLC is significantly associated with invasion, metastasis, TNM stage and prognosis. S100A4 protein might become a marker for prediction of tumor progression of disease and clinical therapy.
Objective To explore the association of macrophages with carcinogenesis and development of gastric cancer. Method The related literatures at home and abroad were consulted and reviewed. Results The microenvironment of gastric cancer could induce the polarization of macrophages，and then the activated macrophages，especially the tumor associated macrophages，could in turn motivate the growth，invasion，and metastasis of tumor cells by secreting a series of active substances. Conclusions Macrophages，especially the tumor associated macrophages play an importantrole in the carcinogenesis and development of gastric cancer. Investigating the macrophages and their interaction with gastric cancer may lead to a profound understanding of carcinogenesis of gastric cancer as well as opening up a new prospectfor treatment.
ObjectiveTo explore the regulation of nuclear factorκB (NFκB) on tumor necrosis factorα (TNFα) expression in the liver and its role in liver injury in rats with acute pancreatitis.MethodsSeventytwo Wistar rats were randomly divided into three groups: acute pancreatitis group (AP), acute pancreatitis treated with pyrrolidine dithiocarbamate (PDTC) group (APP) and sham operation group (SO). The hepatic NFκB activities were determined with electrophoretic mobility shift assays. The expressions of hepatic TNFα mRNA were detected with RTPCR. The levels of serum alanine aminotransferase (ALT) were also measured.ResultsThe NFκB activities were significantly higher in AP and APP groups than those in SO group 3-6 hours after operation. The expressions of TNFα mRNA were ber in AP and APP groups than those in SO group 3-24 hours after operation. The levels of serum ALT were also significantly higher in these two groups than those in SO group 3-24 hours after operation. However, compared with AP group, the activities of NFκB, the expressions of TNFα mRNA and the levels of ALT significantly decreased in APP group.ConclusionThe activation of hepatic NFκB is associated with the liver injury by regulating TNFα mRNA expression in acute pancreatitis.
ObjectiveTo explore the relationship of levels of serum interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP) with lung function in elderly patients with stable COPD and whose pulmonary function classification was levelⅡor above. MethodsSixty elderly patients with stable COPD and with the pulmonary function classification of levelⅡor above and 35 age-matched healthy subjects in the Gansu Provincial Hospital from November 2012 to March in 2014 were recruited in the study.Serum IL-6, TNF-αand CRP levels were detected by electro-chemiluminescence immunoassay (ECLI), enzyme-linked immunosorbent assay and immunoturbidimetric assay, respectively.And their relationships with lung function were explored by Spearman correlation analysis. ResultsThe levels of serum IL-6[(33.0±15.1) mg/L vs.(15.9±8.7) mg/L], TNF-α[(53.8±20.1) pg/mL vs.(22.2±8.0) pg/mL] and CRP[(8.7±3.9) mg/L vs.(5.8±2.3) mg/L] were significantly higher in the stable COPD patients than those in the healthy controls (P < 0.01).With the increase of COPD severity grade, the levels of serum IL-6, TNF-αand CRP increased gradually, and the lung function of FEV1%pred and FEV1/FVC decreased gradually (P < 0.05).The levels of serum IL-6, TNF-αand CRP were negatively correlated with lung function (P < 0.05). ConclusionsThere is airway inflammation in elderly patients with stable COPD.Airway inflammation may be the reason of the decline of pulmonary function in patients with stable COPD.
Objective To investigate the mechanism of dexamethasone in the treatment of acute necrotizing pancreatitis (ANP). Methods The ANP of 48 SD rats were induced by retrograde infusion of sodium taurocholate through biliopancreatic duct.After 30 minutes,the therapy group was administrated with dexamethasone at a dose of 0.2 mg/100 g alone. The control group was administrated with the same amount of 0.9% saline solution.At fourth hour and twelfth hour,8 rats of each group were sacrificed to examine the levels of serum tumor necrosis factor-alpha(TNFα) and serum amylase,to score the degree of pancreatic necrosis and to evaluate acinar cell apoptosis by in situ hybridization by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL). The survial period of 8 rats in each group were observed. Results In therapy group, the level of TNFα was (17.8±2.7) pg/ml and (8.5±1.6) pg/ml,the apoptosis index was （36.94±4.12）% and （ 32.79±3.31）%,the survival period was (33.4±21.5) h.While the control group with the indexes mentioned above were as follows: (53.6±18.7) pg/ml and (37.2±11.1) pg/ml ( P＜0.01),（4.37±1.24）% and （5.12±2.11）% （P＜0.01）,(14.6±5.7) h (P＜0.01) ,the histologic scoring for ANP between therapy group and control group was a significantly distinct (P＜0.01). Conclusion Dexamethasone can induce pancreatic acinar cell apoptosis in this model. Proper leves of TNFα may play an important role in regulating the apoptosis.Apoptosis can protect pancreas from necrosis in ANP.
Objective To study whether carbon dioxide used to establish pneumoperitoneum has an influence on port-site and intraperitoneal implantation and metastasis of tumor cells. Methods R15 hepatic cancer cells were injected into 30 Wistar rats’ peritoneal cavities 1 hour before operation, then the 30 Wistar rats were randomly divided into 3 groups: gasless group, helium group and carbon dioxide group. The suspension was exposed to the gas environment for 2 hours, all animals were killed after 28 days and the port-site and intraperitoneal implantation and metastasis of tumor cells were examined. Results On port-site, intestinal serous coat, mesentery, greater omentum and diaphragm, the weights of tumor cells, in carbon dioxide group were (326.7±230.3) mg， （626.2±215.9） mg，（476.2±204.8） mg，（2 536.5±906.7） mg and （384.5±149.9） mg respectively； in helium group were (235.6±107.3) mg， （414.2±148.4） mg, （261.8±92.6） mg, （1 633.4±247.3） mg and（220.0±57.9） mg； in gasless group were (145.0±42.4) mg， （221.5±108.2） mg， （212.5±109.6） mg, （797.5±335.9） mg and 113.0 mg.The weights of carbon dioxide group showed a significant increase, compared with helium group and gasless group (P＜0.05). The weights of helium group were greater than gasless group，but there was no significance in statistics (Pgt;0.05). Conclusion The insufflation of carbon dioxide promotes intraperitoneal tumor implantation and growth compared with helium and gaslessness in a rat model.
【Abstract】ObjectiveTo investigate whether tumor necrosis factor-α (TNF-α) enhance the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9(MMP-9) in hepatic cancer cell line HepG2 or not. Methods Cultured HepG2 cells were treated by TNF-α with various concentration and time. The morphological changes of HepG2 cells were studied microscopically and the proliferation of HepG2 were detected by methyl thiazolyl tetrazolium (MTT). The expression of VEGF and MMP-9 mRNA in cultured HepG2 were determined by relative quantitative reverse transcription polymerase chain reaction. The VEGF and MMP-9 protein level in supernatants and in cytoplasm were determined by enzymelinked immunosorbent assay (ELISA) and by immunocytochemical staining, respectively.Results There was a little morphological changes in HepG2 with TNF-α treatment, but no change of cell proliferation in corresponding time. The expression of VEGF and MMP-9 mRNA was enhanced gradually with the TNF-α concentration increasing, the VEGF and MMP-9 protein level in supernatants and in cytoplasm was elevated gradually with the concentration increasing. There was a dependance on the concentration when the concentration of TNF-α was lower than or equal to 104 U/L. Furthermore, the effect of promotion was close to peak when the TNF-α concentration up to 104 U/L; but no timeeffect pattern observed. Conclusion TNF-αJP can enhance the expression of VEGF and MMP-9 at the level of mRNA and protein in hepatic cancer cell line.
ObjectiveTo discuss the feasibility of treating noumenon tumor by antiangiogenesis.MethodsRelated literatures of recent 5 years was reviewed.ResultsTumor angiogenesis were related closely with growth, development, metastasis and prognosis of noumenon tumor. It was possible to inhibit the growth and metastasis of noumenon tumor with antiangiogenesis in vitro and vivo.ConclusionAntiangiogenesis will be a new therapy of treating noumenon tumor.
Objective To observe the levels of malonaldehyde (MDA) , interleukin-8 (IL-8) and tumor necrosis factor-α(TNF-α) in lung tissues of subjects with or without chronic obstructive pulmonary disease (COPD) , and investigate their roles in the the pathogenesis of COPD. Methods The content of MDA, IL-8 and TNF-αin lung tissues of smokers with COPD (n=9) , ex-smokers with COPD (n=8) , non-smokers with COPD (n=7) , healthy smokers (n=9) , healthy ex-smokers (n=8) and healthy nonsmokers (n=6) was measured with enzyme-linked immunosorbent assay ( ELISA) and corrected by creatinine. Results The levels of MDA, IL-8 and TNF-α in lung tissues of the COPD patients were significantly higher than those in the healthy subjects (Plt;0.05) , which were also significantly higher in the smokers when compared with the non-smokers (Plt;0.05) , whether suffering from COPD or not. In the COPD patients, not the levels of IL-8 but MDA and TNF-αin lung tissues of the smokers were significantly higher than those in the ex-smokers (Plt;0.05) ; whereas in the healthy cases, no statistical significance was revealed between the smokers and the ex-smokers on the levels of MDA and IL-8 in lung tissues except TNF-α( Pgt;0.05) . Conclusion The abnormal increase of MDA, IL-8 and TNF-αin lung tissues caused by chronic smoking may play an important role in the the pathogenesis of COPD.