Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma

AIM: To investigate the significance of S phase kinase associated protein 2 (Skp2) expression in human gastric carcinoma and the relation between expressions of Skp2, p27 and PTEN. METHODS: Immunohistochemical analysis was performed on 138 gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, 10 chronic superficial gastritis specimens and 5 normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma specimens for p27 and PTEN expression. RESULTS: Skp2 labeling frequency was significantly higher in intestinal metaplasia (12.68±0.86) and adjacent mucosa (19.32±1.22) than in normal gastric mucosa (0.53±0.13) and chronic superficial gastritis (0.47±0.19) (P = 0.000); in dysplasia (16.74±0.82) than in intestinal metaplasia (P = 0.000); in gastric primary carcinoma (31.34±2.17) than in dysplasia and adjacent mucosa (P = 0.000); in metastasis gastric carcinoma in lymph nodes (39.76±2.00) than in primary gastric carcinoma (P = 0.037), respectively. Skp2 labeling frequency was positively associated with differentiation degree (rho = 0.315, P = 0.000), vessel invasion (rho = 0.303, P = 0.000) and lymph node metastasis (rho = 0.254, P = 0.000) of gastric cancer. Expression of Skp2 was negatively associated with p27 (rho = -0.451, P = 0.000) and PTEN (rho = -0.480, P = 0.000) expression in gastric carcinoma. p27 expression was positively associated with PTEN expression in gastric carcinoma (rho = 0.642, P = 0.000). CONCLUSION: Skp2 overexpression may be involved in carcinogenesis and progression of human gastric carcinoma in vivo, possibly via p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating Skp2 expression.     

Nuclear factor kappa B： A marker of chemotherapy for human stage Ⅳ gastric carcinoma

AIM： To detect the nuclear factor kappa B （NF-κB） condition in human stage IV gastric carcinoma patients and to explore the correlation between NF-κB activation and survival of these patients after chemotherapy. METHODS： Expression of NF-κB-p65 was determined by immunohistochemical analysis. Activity of NF-κB DNA-binding in carcinoma tissue was detected by electrophoretic mobility shift assay. Kaplan-Meier survival analysis was performed to show the relation between NF-κB and progression-free survival （PFS） or overall survival （OS） of the patients. RESULTS： The positive expression rate of NF-κB-p65 in 60 gastric cancer tissue samples was 76.7% （46160）. The expression of NF-κB-p65 was reduced in adjacent carcinoma and normal tissue samples. Electrophoretic mobility shift assay （EMSA） analysis showed a strong activation of NF-κB in cancer tissue samples. A survival difference was found in NF-κB-p65 positive and negative patients. NF-κB-p65 expression was negative in cancer tissue samples （n = 14）. PFS was 191.40 ± 59.88 d and 152.93 ±16.99 d, respectively, in patients with positive NF-κB-p65 expression （n = 46） （P = 0.4028）. The survival time of patients with negative and positive NF-κB-p65 expression was 425.16 ±61.61 d and 418.85 ±42.98 d, respectively （P = 0.7303）. Kaplan-Meier analysis showed no significant difference in PFS or OS. The 46 patient tissue which positive NF-κB-p65 expression was found in the tissue samples from the 46 patients whose PFS and OS were 564.89 ± 75.94 d and s 352.37 ±41.32 d, respectively （P = 0.0165）. CONCLUSION： NF-κB is activated in gastric carcinoma tissue, which is related to the OS after chemotherapy.     

胃癌组织中MTA1,PTEN,E-cadherin的表达及其相互关系

目的:观察MTA1,PTEN,E-cadherin蛋白在胃癌和正常胃黏膜组织中的表达,探讨其与胃癌浸润、转移和生物学行为的关系.方法:应用免疫组织化学方法检测54例胃癌手术切除标本和15例正常胃黏膜组织中MTA1,PTEN,E-cadherin的表达.各指标之间相关因素的差异性比较采用χ2检验,相关性研究采用Spearman相关分析:结果:与正常胃组织相比,MTA1蛋白在胃癌组织中高表达(46.3% vs 6.7%,P＜0.01),PTEN和E-cadherin蛋白在胃癌组织中表达下调或缺失(51.9% vs 100%,42.6% vs 100%,均P＜0.01).MTA1和PTEN的阳性表达率与肿瘤浸润深度(P=0.003,P=0.001)、病理分期(P=0.004,P=0.008)、淋巴转移(P=0.000,P=0.001)、远隔转移(P=0.004,P=0.006)、临床分期有关(P=0.001,P=0.000);E-cadherin的正常表达率与肿瘤浸润深度(P=0.027)、病理分化程度(P=0.006)、淋巴转移(P=0.044)、临床分期有关(P=0.000).Spearman相关分析显MTA1与PTEN蛋白、MTA1与E-cadherin蛋白的表达呈负相关(r=-0.518,r=-0.424,均p＜0.05).PTEN蛋白与E-cadherin蛋白的表达呈正相关(r=0.53,P＜0.05).结论:MTA1蛋白水平高表达和PTEN,E-cadherin蛋白水平低表达可能与胃癌浸润和转移有关,且联合检测可以用于判断胃癌的生物学行为.     

Growth,invasion, metastasis,differentiation, angiogenesis and apoptosis of gastric cancer regulated by expression of PTEN encoding products

AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9％ vs89.4％; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 ％ vs 50.4 ％; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.     

Relationship between the expression of iNOS,VEGF,tumor angiogenesis and gastric cancer

AIM：To in vestigate the relationship between the expression of inducible nitric oxide synthase(iNOS),vascular endothelial growth factor(VEGF),the microvascular density(MVD)and the pathological features and clinical staging of gastric cancer.METHODS:Immunohistochemical staining was used for detecting the expression of iNOS and VEGFin46resected specimens of gastric carcinoma;the monoclonal antibody against CD34 was used for displaying vascular endothelial cells,and MVD was detected by counting of CD34-positive vascular endothelial cells.RESULTS:Of 46resected specimens of gastric carcinoma,the rates of expressions of iNOS and VEGF were 58.70%and76.09%,respectively,and MVDaveraged55.59±19.39,Judged by the standard TNM criteria,the rate of expression of iNOS in stageⅣ（84.46%)was higher than those in stageⅠ,Ⅱ,Ⅲ（Fish exact probabilities test,P=0.019,0.023and 0.033,respectively);the rates of expression of VEGFin stage Ⅲ,Ⅳ（76.0%,92.31%,respectively)were higher than those in stageⅠ,Ⅱ（Fis exact probabilities test,P=0.031,0.017,0.022and0.019).MVDs in stageⅢ,Ⅳ（64.72±14.96,67.09±18.29,respectively)were higher than those in stageⅠ,Ⅱ(t\2.378,4.015,2.503and2.450,P<0.05,P<0.001,P<0.001,P<0.05,respectively),In37gastric carcinoma specimens with lymph node metastasis,MVD(68.69±18.07)and the rates of expression of iNOS and VEGF(70.27%,83.78%,respectively)were higher than those in the specimens with absence of metastasis(t=2.205,X^2=6.3587,X^2=6.2584,P<0.01,P<0.05,P<0.05,respectively),MVD and the expressions of iNOS and EGF were not correlated to the location,size or grade of tumor,nor with the depth of invasion of tumor;MVDs in the positive iNOS and VEGF specimens(59.88±18.02,58.39±17.73,repectively)were higher than those in the negative iNOS and VEGF specimens(X^2=6.3587and 6.1574,P<0.05,P<0.05,respectively);thus the expressions of iNOS and VEGF was correlated to MVD,but the expression of iNOS was not correlated to that of VEGF,In addition.of the 46 surviving patients,the 5-year survival rate of patients with positive iNOS or VEGF tumors was significantly less than that of patients with negative iNOS-or VEGF tumors(X^2=4.3842and 5.4073,P<0.05,P<0.05.respectively).CONCLUSION:The expressions of iNOS and VEGF are colosely related to tumor angiogenesis,and are involved in the advancement and the lymph node metastasis;thusMVD and the expressions of iNOS and EGF may serve indexes for evaluating staging of gastric carcinoma and forecasting its risk of metastasis,which will help establish a comprehensive therapeutical measure of post-operative patients and provide a new approach to tumor therapy.     

Pathobiological significance of vascular endothelial growth factor and Maspin expressions in human gastric carcinoma

AIM: To investigate the correlation between expression of vascular endothelial growth factor (VEGF) and cell differentiation, invasion, metastasis and Maspin expression in gastric carcinoma.METHODS: Formalin-fixed paraffin-embedded tissue specimens from 73 cases of gastric carcinoma were studied with SP immunohistochemistry, using anti-VEGF monoclonal antibody, and thirty-nine of them were studied using antiMaspin monoclonal antibody. VEGF expression was compared with the clinical stage, lymph node metastasis, and Borrmann‘s and WHO‘s classification of gastric carcinoma.RESULTS: The positive rate of VEGF expression was significantly higher in adjacent non-carcinoma epithelia (ANCE) than in non-metaplastic, non-carcinoma gastric epithelia (NMNCE), which were at least 4 cm distant from the primary tumor (P = 0.000, x^2= 73.03). The positive rate of VEGF expression was significantly higher in advanced gastric carcinoma (AGC) than in early gastric carcinoma (EGC) (P = 0.032, x^2 = 4.62). The positive rate of VEGF expression in gastric carcinomas with lymph node metastases was significantly higher than that in those without metastasis (P = 0.006, x^2 = 7.47). Maspin was weakly expressed in 16 out of 39 cases of NMNCE, and the positive immunoreaction was limited to gland cells of the stomach body. There was no significant correlation between the expression of VEGF and histological or gross classifications, and correlation between the expressions of VEGF and Maspin in gastric carcinoma (P = 0.648, x^2 = 0.21).CONCLUSION: Expression of VEGF is significantly correlated to the malignant biological behaviors of gastric carcinoma,but there is no significant correlation between the expression of VEGF and Maspin.     

非小细胞肺癌组织中核因子κB的活性及其与肿瘤细胞增殖的关系

目的研究非小细胞肺癌组织中核因子κB（nuclear Factor-κB，NF—κB）的活性及其与细胞增殖、自发性细胞凋亡的关系。方法2006年5至10月收集30例非小细胞肺癌组织标本及15例肺癌患者癌旁5cm肺组织标本。NF—κB活性通过凝胶电泳迁移率改变试验（EMSA）检测，用RT—PCR和Western blot方法检测CyclinD1含量，免疫组织化学染色法检测增殖细胞核抗原（PCNA）蛋白含量，TUNEL法检测细胞凋亡。结果癌旁肺组织、鳞癌组织、腺癌组织中NF—κB活性（吸光度，A值）分别为24826±3724、28028±4204、35425±5317，三组比较差异有统计学意义（F=78．96，P〈0．01）。鳞癌组织、腺癌组织中NF—κB活性高于癌旁肺组织中NF—κB活性，腺癌组织中NF—κB活性高于鳞癌组织中NF—κB活性。健康肺组织、鳞癌组织、腺癌组织中CyclinD1 mRNA表达量分别为2．04±0．24、2．91±0．37、4．13±0．36，三组比较差异有统计学意义（F=62．43，P〈0．01）。癌旁肺组织、鳞癌组织、腺癌组织中Cyclin D1蛋白表达量分别为0．31±0．06、0．43±0．07、0．58±0．08，三组比较差异有统计学意义（F=89．24，P〈0．01）。癌旁肺组织、鳞癌组织、腺癌组织中PCNA蛋白表达量分别为0．32±0．09、0．42±0．10、0．54±0．16，三组比较差异明显。癌旁肺组织、鳞癌组织、腺癌组织中凋亡指数分别为（2．58±0．39）％、（2．27±0．34）％、（2．92±0．59）％，三组比较无明显差异。鳞癌组织中NF—κB活性与CyclinD1 mRNA、CyclinD1蛋白、PCNA蛋白均呈正相关（r值分别为0．51、0．54和0．60，P均〈0．05）；腺癌组织中NF—κB活性与CyclinD1mRNA、CyclinD1蛋白、PCNA蛋白均呈正相关（r值分别为0．60、0．64和0．68，P均〈0．05）；鳞癌、腺癌组织中NF—κB活性与细胞凋亡指数无相关关系。结论在非小细胞肺癌组织中NF—κB活性增高。非小细胞肺癌组织中NF—κB的异常活化可能与细胞增殖有关，但不影响自发性细胞凋亡。     

Gastric mucosal injury due to hemorrhagic reperfusion and efficacy of Salvia miltiorrhizae extract F and cimetidine

AIM: To observe the gastric mucosal injury caused by hemorrhagic shock and reperfusion and to compare the effect between Salvia miltiorrhizae extract F (SEF) and cimetidine (CI) on it. METHODS: A model of hemorrhage/reperfusion injury was produced by Itoh method. Wistar rats were randomly divided into three groups: 0.9% sodium chloride treatment group (NS group), SEF treatment group (SEF group), and CI treatment group (CI group). Saline, SEF and CI were injected respectively. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesion area in the gastric mucosa. The degree of gastric mucosal lesions was categorized into grades 0, 1, 2, 3. Atom absorption method was used to measure the intracellular calcium content. Radioimmunoassay was used to measure the concentrations of prostaglandins. RESULTS: IGML (%) and grade 3 (%) were 23.18±6.82, 58.44±9.07 in NS group, 4.42±1.39, 20.32±6.95 in SEF group and 3.74±1.56, 23.12±5.09 in CI group, and the above parameters in SEF group and CI group decreased significantly (IGML: SEF vs NS, t=6.712, P=0.000<0.01; CI vs NS, t=6.943, P=0.000<0.01; grade 3: SEF vs HS, t=8.386, P=0.000; CI vs HS, t=8.411, P= 0.000), but the grade 0 and grade 1 damage in SEF group (22.05±5.96, 34.12±8.12) and CI group (18.54±4.82, 30.15±7.12) were markedly higher than those in NS group (3.01±1.01, 8.35±1.95; grade 0: SEF vs HS, t=8.434, P=0.000<0.01; CI vs NS, t=7.950, P=0.000<0.01; grade 1: SEF vs NS, t =8.422, P=0.000<0.01; CI vs NS, t=8.448, P=0.000<0.01). The intracellular calcium content (μg/mg) in SEF group (0.104±0.015) and CI group (0.102±0.010) was markedly lower than that in NS group (0.131±0.019, SEF vs NS, t=2.463, P=0.038<0.05; CI vs HS, t=3.056, P=0.017<0.05). The levels (pg/mg) of PGE_2, 6-keto-PGF_(1α) and 6-keto-PGF_(1α)/TXB_2 were 540±183, 714±124,17.38±5.93 in NS group and 581±168, 737±102, 19.04±8.03 in CI group, 760±192,1 248±158, 33.42±9.24 in SEF group, and the above parameters in SEF group markedly raised (PGE_2: SEF vs NS, t=2.282, P=0.046<0.05; SEF vs CI, t=2.265, P=0.047<0.05; 6-keto-PGF_(1α): SEF vs NS, t=6.583, P=0.000<0.000; SEF vs CI, t=6.708, P=0.000<0.01; 6-keto-PGF_(1α)/TXB_2: SEF vs NS, t=3.963, P=0.003<0.001; SEF vs Cl, t=3.243, P=0.009<0.01), whereas TXB_2 level in SEF group (45.37±7.54) was obviously lower than that in NS group (58.28±6.74, t=3.086, P=0.014<0.05) and CI group (54.32±6.89, t=2.265, P=0.047<0.05). No significant difference was shown between NS group and CI group (PGE_2: t=0.414, P=0.688>0.05; 6-keto-PGF_(1α): t=0.310, P=0.763>0.05; TXB_2: t=1.099, P=0.298>0.05; 6-keto-PGF_(1α)/TXB_2: t=0.372, P=0.718>0.05). CONCLUSION: Both SEF and CI could inhibit reperfusioninduced injury in gastric mucosa, but with different mechanisms. SEF could not only enhance the protective effect of gastric mucosa, but also abate the injury factors, while CI can only abate the injury factors.     

Expression of Fas ligand and caspase-3 contributes to formation of immune escape in gastric cancer

AIM: To study the role of Fas ligand (FasL) and Caspase-3 expression in carcinogenesis and progression of gastric cancer and molecular mechanisms of relevant immune escape. METHODS: FasL and Caspase-3 expression was studied in adjacent epithelial cells, cancer cells and lymphocytes of primary foci, and cancer cells of metastatic foci from 113 cases of gastric cancer by streptavidin-biotin-peroxidase(S-P) immunohistochemistry. Expression of both proteins in cancer cells of primary foci was compared with clinicopathological features of gastric cancer. The relationship between Fas L expression in cancer cells and Caspase-3 expression in cancer cells or infiltrating lymphocytes of primary foci was investigated. RESULTS: Cancer cells of primary foci expressed FasL in 53.98 % (61/113) of gastric cancers, more than their adjacent epithelial cells (34.51%, 39/113) (P=0.O03,χ2=8.681), while the expression of Caspase-3 in cancer cells of primary foci was detected in 32.74 % (37/113) of gastric cancers, less than in the adjacent epithelial cells (50.44 %, 57/113)(P=0.O07, χ2=7.286). Infiltrating lymphocytes of the primary foci showed positive immunoreactivity to Caspase-3 in70.80 % (80/113) of gastric cancers, more than their corresponding adjacent epithelial cells (P=0.O01, χ2=10.635) or cancer cells of primary loci (P=-O.O00, χ2=32.767). FasL was less expressed in cancer cells of metastases (51.16 %,22/43) than in those of the corresponding primary foci( 81.58 %, 31/38) (P=0.O03, χ2=9.907). Conversely, Caspase-3 was more expressed in cancer cells of metastases(58.14 %, 25/43) than in those of the corresponding primary foci (34.21%, 13/38) (P=0.031, χ2=4.638). FasL expression was significantly correlated with tumor size (P=0.035,rs=0.276), invasive depth (P=0.039, rs=0.195), metastasis(P=0.039, rs=0.195), differentiation (P=0.015, rs=0.228)and Lauren‘‘s classification (P=0.038, rs=0. 196), but not with age or gender of patients, growth pattern or TNM staging of gastric cancer (P&gt;0.05). In contrast, Caspase-3 expression showed no correlation with any dinicopathological parametersdescribed above in cancer cells of the primary foci (p&gt;0.05).Interestingly, FasL expression in primary gastric cancer cells paralleled to Caspase-3 expression in infiltrating lymphocytes of the primary foci (P=0.016, χ2=5.825).CONCLUSION: Up-regulated expression of FasL and downregulated expression of Caspase-3 in cancer cells of primary foci play an important role in gastric carcinogenesis. As an effective marker to reveal the biological behaviors, FasL is implicated in differentiation, growth, invasion and metastasis of gastric cancer by inducing apoptosis of infiltrating lymphocytes. Chemical substances derived from bhe primary foci and metastatic microenvironment can inhibit t~e growth of metastatic cells by enhancing Caspase-3 expression and diminishing FasL expression.     

Clinicopathological significance of B-cell-specific Moloney murine leukemia virus insertion site 1 expression in gastric carcinoma and its precancerous lesion

AIM： To explore the relation between B-cell-specific Moloney murine leukemia virus insertion site 1 （Bmi-1） expression and the clinicopathological features of gastric carcinoma （GC）.METHODS： Immunohistochemistry was used to detect the expression of Bmi-1 and ki-67. Doublelabeling staining was used to display the distribution of Bcl-2^＋/ki-67 cells in 162 cases of GC and its matched normal mucosa and precancerous lesion.RESULTS： The positive rate of Bmi-1 expression in GC（52.5%） was significantly higher than that in normal gastric mucosa （21.6%, X^2 = 33.088, P 〈 0.05）. The Bmi-1 expression in GC was closely related with the Lauren＇s and Borrmann＇s classification and clinicalstage （X^2 = 4.400, 6.122 and 11.190, respectively, P〈 0.05）. The expression of ki-67 was related to the Borrmann＇s classification （X^2 = 13.380, P 〈 0.05）.Bcl-2 expression was correlated with the Lauren＇s classification （Z2 = 4.725, P 〈 0.05）, and the Bmi-1 expression both in GC （rk = 0.157, P 〈 0.05） and inintestinal metaplasia （rk = 0.270, P 〈 0.05）.CONCLUSION： Abnormal Bmi-1 expression in GCmay be involved in cell proliferation, apoptosis andcancerization. This marker can objectively indicate theclinicopathological characteristics of GC.     

三氧化二砷联合Ad-IκBαM诱导胃癌细胞凋亡的研究

目的研究三氧化二砷（As2O3）对胃癌SGC-7901细胞作用过程中细胞内核转录因子KB（NF-κB）的激活及重组腺病毒Ad—IκBαM通过抑制NF-κB的活化增强As2O3的诱导凋亡作用。方法培养胃癌SGC-7901细胞,以非感染组及感染Ad—IκBα组为对照,采用凝胶电泳迁移率实验（EMSA）及免疫组化法检测As2O3处理后细胞核内NF-κB的激活情况,以及感染Ad—IκBαM对NF-κB活性的影响;四甲基偶氮唑盐（MTT）法、Hoechest染色、原位末端标记（TUNEL）法分别检测感染Ad—IκBαM对As2O3诱导细胞凋亡的影响。结果EMSA及免疫组化法显示As2O3作用于胃癌细胞可使细胞内NF-κB激活,感染Ad—IκBαM使NF-κB活性受到明显抑制;MTT法证明,As2O3作用后,感染Ad—IκBαM细胞的凋亡率（59．2±2．5）％较感染Ad-IκBα组（47．5±2．3）％及未感染组（40．0±1．2）％明显升高,各组间比较P〈0．01;Hoechest法显示,感染Ad—IκBαM组的凋亡率为（27.7±2．6）％,明显高于感染Ad—IκBα组（18．3±1．5）％及未感染组（11.0±1．7）％（P〈0．05）。TUNEL法结果与Hoechest法一致,感染Ad—IκBαM组的凋亡率为（31．1±2．5）％,高于感染Ad-IκBα组（20.7±2．1）％及未感染组（13.0±1、7）％（P〈0．05）。可见,感染Ad—IκBαM可明显提高As2O3诱导的细胞凋亡。结论As2O3作用于胃癌细胞可使细胞内NF-κB激活,从而表明NF-κB激活可能为胃癌细胞抗诱导凋亡作用的重要机制;感染Ad．IKBctM可有效抑制NF-κB的活性,并增强As2O3的诱导凋亡作用。     

组织芯片检测β-连环蛋白、c-erbB2在胃腺癌中的表达及其临床意义

近年来组织芯片已越来越多地应用于恶性肿瘤的相关研究,但用于胃癌研究的报道较少。目的：探讨胃腺癌、癌旁组织和外周正常黏膜组织中β-连环蛋白和c—erbB2的表达及其临床意义。方法：取102例胃腺癌、97例癌旁组织和98例外周正常黏膜组织分别制成含282点、156点和156点的3块组织芯片。以免疫组化法检测组织芯片中β-连环蛋白和c—erbB2的表达,并分析其与胃腺癌临床病理特征的关系。结果：胃腺癌组织中β-连环蛋白和c—erbB2阳性表达率显著高于癌旁组织和外周正常黏膜组织（57．0％对22．1％和7．3％,P=0．000;29．0％对5．3％和0％,P=0．000）。β-连环蛋白和c-erbB2异常表达与胃腺癌的分化程度（P=0．027,P=0．001）和浸润深度（P=0．033,P=0．011）有关,与其他临床病理特征无关。胃腺癌中β-连环蛋白表达与c—erbB2表达呈明显正相关（P〈0．05）。结论：c-erbB2异常表达可能导致靶基因β-连环蛋白异常表达,从而在胃腺癌的发生、发展中起重要作用。     

Apoptosis induced by preoperative oral 5′-DFUR administration in gastric adenocarcinoma and its mechanism of action

AIM: To study the apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action. METHODS: Sixty gastric cancer patients were divided randomly into three groups (20 each group) before operation: group one:5'-DFUR oral administration at the dose of 800-1200 mg/d for 3 - 5 d, group two: 500 mg 5-FU + 200 mg/d CF by venous drip for 3 - 5 d,group three (control group). One or two days after chemotherapy, the patients were operated. Fas/FasL,PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5'-DFUR group, 16 cases in CF+5-FU group, and 20 cases in control group were analyzed. RESULTS: There was no significant difference in patient mean age, gender, white blood cell count, haematoglobin (HB),thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth (T), lymphonode involvement (N),metastasis (M) and TNM staging among the three groups. However,the PCNA index (PI) in 5'-DFUR group (40.51+/-12.62) and 5-FU+CF group (41.12+/-15.26) was significantly lower than that in control group (58.33+/-15.69) (F=9.083, P=0.000). The apoptotic index (AI) in 5'-DFUR group (14.39+/-9.49) and 5-FU+CF group (14.11+/-9.68)was significantly higher than that in control group (6.88+/-7.37) (F=4.409, P=0.017).The expression rates of Fas and FasL in group one and group three were 66.7% (12/18) and 50% (9/18), 43.8% (7/16) and 81.3% (13/16), 45.0% (9/20) and 85% (17/20), respectively. The expression rate of FasL in 5'-DFUR group was significantly lower than that in the other two groups (chi2=6.708, P=0.035). Meanwhile, the expression rate of PD-ECGF was significantly lower in 5'-DFUR group (4/18,28.6%) than in CF+5-FU group(9/16,56.3%)and control group (13/20,65.0%) (chi2=7.542, P=0.023). The frequency of Fas expression was significantly correlated with palliative or radical resection (chi2=7.651, P=0.006), invasion depth (chi2=8.927, P=0.003), lymphatic spread (chi2=4.488, P=0.034) and UICC stages (chi2=8.063, P=0.045) respectively. By the end of March 2005,45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%,73%,60%,48%, respectively, which were related with T, N, M and Fas expression, but not with PD-ECGF and FasL expression. CONCLUSION: Preoperative oral 5'-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index,but cannot improve the prognosis of patients with gastric cancer.Down-regulation of FasL and PD-ECGF expression mediated by 5'-DFUR may be one of its anti-cancer mechanisms.Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.     

慢性萎缩性胃炎黏膜上皮中P53和C-erbB-2表达的临床意义

目的:探讨慢性萎缩性胃炎(CAG)黏膜上皮中P53及C-erbB-2的表达及意义．方法:用免疫组化技术(SP法)检测正常胃黏膜56例、慢性萎缩性胃炎429例(腺体囊性扩张61例,大肠型化生73例,轻、中、重度不典型增生各120、91和84例)和早期胃癌57例中P53和C-erbB-2的表达,分析P53和C-erbB-2表达及其与CAG胃黏膜病变类型的关系．结果:正常胃黏膜,囊性扩张腺体,轻、中度不典型增生,大肠型化生,重度不典型增生,早期胃癌P53和C-erbB-2表达的阳性率呈上升趋势．前三组间表达率差异无统计学意义(P>0．05);正常胃黏膜与中度不典型增生、大肠型化生、重度不典型增生及胃癌组P53和C-erbB-2的表达差异有统计学意义(P<0．01)．Spearman等级相关分析显示P53和C-efbB-2表达呈正相关(r=0．867,P<0．05)．年龄<40岁和≥40岁组间、性别组间P53表达阳性率差异有统计学意义(x2=12．393,P<0．01;x2=8．799, P<0．01)．C-erbB-2的表达在上述年龄组间差异有统计学意义(x2=7．706,P<0．01),而在性别组间无统计学意义(P>0．05)．结论:检测慢性萎缩性胃炎中P53和C-erbB-2的表达,有助于监测CAG癌前病变的进展及胃癌的早期发现．     

核因子κB、细胞间粘附分子1在吸烟大鼠气道上皮细胞中的表达

目的　探讨核因子κB (NF κB)和细胞间粘附分子 1 (ICAM 1 )在吸烟大鼠气道上皮细胞中表达的变化及其在气道炎症形成过程中的作用。方法　Wistar大鼠 39只 ,随机分为不吸烟组、吸烟1个月组、3个月组 ,每组 1 3只。采用免疫组织化学染色和原位杂交技术半定量检测各组NF κB亚单位p65和ICAM 1的表达。结果　 (1 )吸烟 1个月组、3个月组细支气管上皮细胞NF κB核染色阳性细胞百分比为 (63± 4) %、(51± 5) % ,与不吸烟组 [(2 7± 5) % ]比较 ,差异有显著性 (P分别 <0 .0 1 ) ;(2 )吸烟 1个月组、3个月组主、细支气管气道上皮细胞ICAM 1mRNA的表达为 0 .645± 0 .0 38、0 .747±0 0 4 1、0 .688± 0 .0 62、0 .80 9± 0 .0 2 3 ,与不吸烟组 (0 .52 6± 0 .0 2 3、0 .635± 0 .0 4 4 )比较差异有显著性 (P分别 <0 .0 1 ) ;而且 3个月组与 1个月组比较差异也有显著性 (P分别 <0 .0 5、0 .0 1 ) ;(3)吸烟 1个月组、3个月组主、细支气管气道上皮细胞ICAM 1蛋白表达为 0 .73± 0 .0 4、0 .94± 0 .0 5、0 .77± 0 .0 4、0 .99± 0 .0 3 ,与不吸烟组 (0 .57± 0 .0 4、0 .83± 0 .0 4 )比较 ,差异也有显著性 (P分别 <0 .0 1 ) ;而且 3个月组与 1个月组比较差异也有显著性 (P分别 <0 .0 5) ;(4)各组细支气管上皮     

胃癌组织血小板衍化内皮细胞生长因子的表达与血管生成和凋亡的关系

目的探讨血小板衍化内皮细胞生长因子（PD．ECGF）在胃癌组织中的表达及与血管生成和凋亡的关系。方法应用免疫组化技术对67例胃癌组织进行PD－ECGF表达、肿瘤组织微血管密度（MVD）检测，流式细胞技术检测胃癌组织细胞凋亡指数（川，凋亡百分率八结果＊r＊＊＊F的表达与胃癌淋巴结转移（P＜0．oj）。分化程度（P＜0．05）及组织分型（P＜0．05）显著相关，与＊V则尸＜001）和胃癌细胞凋亡指数（P＜001）显著相关。＊＊D和＊1与淋巳结转移（P＜001）显著相关。结论胃癌组织中P＊。 ECGF可促进血管生成，抑制胃癌细胞凋亡，促进胃癌的增殖与转移。     

RhoC基因的过量表达在胃癌中的意义

目的探讨RhoC基因在胃癌中的表达及其与临床病理因素之间的关系。方法采用免疫组化S-P法检测97例胃癌组织及89例癌旁组织中RhoC的表达。结果在89例癌旁组织中82例不表达RhoC,97例胃癌组织中,75例(77.31%)表达RhoC。两者之间有显著差异(P=0.00)。RhoC蛋白的过量表达与患者性别及肿瘤分级、分化和淋巴结转移未见相关性,与肿瘤浸润深度,肿瘤分期存在相关性(P<0.05)。结论RhoC蛋白在胃癌中过量表达与胃癌的发生发展密切相关,可以作为胃癌的预后判断指标之一。