胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

食管癌中抑癌基因PTEN表达及其对血管新生的影响

目的　探讨食管癌中抑癌基因PTEN(第 10号染色体同源丢失性磷酸酶—张力蛋白基因 )蛋白表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SABC法检测 60例食管鳞癌及其相应的癌旁正常组织中PTEN蛋白表达 ,用CD3 4 作为检测间质微血管密度 (MVD)标志物。结果　 60例癌旁正常组织PTEN蛋白全部阳性表达 ,食管癌组织中PTEN蛋白阳性表达率为 66.7% (P <0 .0 1)。PTEN蛋白表达与组织分化程度、淋巴结转移和浆膜浸润有明显相关性 (P <0 .0 5 )。PTEN蛋白表达强度与MVD呈负相关。PTEN蛋白阳性表达组的平均MVD值 ( 76.97± 4.98)明显低于阴性表达组 ( 89.5 0± 5 .67) ,P <0 .0 1。结论　PTEN有可能作为食管癌进展的肿瘤标志物 ,PTEN基因的丢失或突变可以促进肿瘤间质微血管生成 ,加速肿瘤浸润转移。     

SU5416抑制胃癌生长和肝转移的实验研究

目的　研究血管内皮细胞生长因子抑制物SU5 4 16对裸鼠原位种植人胃癌生长和肝转移抑制作用 ,探讨其对癌细胞凋亡的影响。方法　建立人胃癌裸鼠原位种植转移模型 ,随机分为 4组。种植后第 1周开始 ,分别自腹腔注射生理盐水 (对照组 )、5 氟尿嘧啶 (30mg·kg-1·d-1,5 FU组 )、SU5 4 16(15mg·kg-1·d-1,SU5 4 16组 )、5 FU与SU5 4 16联合应用 (5 FU 30mg·kg-1·d-1,SU5 4 16 15mg·kg-1·d-1,5 FU +SU5 4 16组 ) ,每天 1次 ,共 7周。第 8周处死动物 ,测量原位肿瘤瘤重、抑瘤率、微血管密度(MVD)、胃癌细胞凋亡指数 (AI) ,观察肿瘤细胞肝转移情况。结果　对照组、5 FU组、SU5 4 16组、5 FU+SU5 4 16组的原位肿瘤瘤重分别为 (1.35± 0 .4 2 )、(0 .75± 0 .33)、(0 .34± 0 .14 )及 (0 .2 1± 0 .15 ) g ;抑瘤率分别为 4 4 .5 % ,79.3% ,84 .4 % ;肝转移率分别为 90 .0 % ,36 .4 % ,2 5 .0 % ,0 %。MVD分别为 14 .6± 5 .8,13.1± 4 .7,3.9± 1.8,2 .1± 1.5 ;AI分别为 (3.76± 2 .2 5 ) % ,(6 .81± 4 .92 ) % ,(9.82± 3.76 ) % ,(17.6 5± 9.85 ) %。与对照组、5 FU组相比 ,SU5 4 16组、5 FU +SU5 4 16组胃癌生长、肝转移及MVD受到明显抑制 (P <0 .0 5 ) ,AI明显增高 (P <0 .0 5 )。结论　SU     

核转录因子/白细胞介素-8与胃癌血管生成及预后关系研究

目的　研究核转录因子 (NF κB)及白细胞介素 (IL) 8在人胃癌组织中表达与胃癌血管形成及预后的关系。方法　免疫组化法检测 4 1例胃癌组织中核转录因子NF κB、IL 8表达和微血管密度(MVD)。结果　 4 1例胃癌中NF κB和IL 8的阳性表达率分别为 6 8.3% (2 8例 )和 2 9.3% (12例 ) ,前者与MVD显著相关 (P =0 .0 0 2 ) ,但后者与MVD表达无关。NF κB和IL 8与TNM分期显著相关 (P<0 .0 5 ) ,阳性者多为进展期胃癌 ,而且表达阴性组预后均明显优于阳性组 (P <0 .0 5 )。结论　NF κB/IL 8旁路调控可能不是胃癌组织内的主要促血管生成途径 ,NF κB和IL 8阳性表达反映胃癌的恶性程度 ,并可作为判断预后的参考指标。     

一氧化氮合酶和微血管生成与胃癌发展的关系

目的　研究诱导型一氧化氮合酶 (iNOS)在人胃癌组织中的表达及其与胃癌微血管形成、淋巴结转移及临床分期的关系。方法　采用免疫组化S P法检测 50例原发性胃癌组织、癌周组织及 2 0例正常胃黏膜组织中iNOS的表达 ,同时检测微血管密度 (MVD) ,以抗CD3 4标记血管内皮细胞 ,并分析其与肿瘤行为之间的关系。结果　 50例胃癌组织中iNOS阳性表达率为 70 .0 % ,MVD均值为 2 2 .0± 9 .8,显著高于癌周组织 (16.2 % ,6.1± 3 .4)和正常胃组织 (15.0 % ,5.5± 2 .6;P <0 .0 1)。按TNM分期 ,Ⅳ期胃癌组织iNOS阳性表达率为 93 .8% ,MVD为 42 .3± 3 .7,两者显著高于Ⅰ、Ⅱ、Ⅲ期 ,差异有显著性 (P <0 .0 1)。有淋巴结转移组iNOS的阳性表达率为 84.6% ,MVD均值为 2 7.4± 6.5;无淋巴结转移组iNOS阳性表达率为 54.2 % ,MVD均值为 15.3± 4.7,两组差异有显著性 (P <0 .0 5)。iNOS阳性表达组及高MVD值 (≥ 2 2 .0 )组的 3年生存率均显著低于iNOS阴性表达组及低MVD值 (<2 2 .0 )组 ,差异有显著性 (P <0 .0 5)。结论　胃癌组织中iNOS高阳性表达 ,随着iNOS阳性表达的增强 ,MVD值也增加 ,两者呈正相关。iNOS的表达及MVD与胃癌TNM分期、淋巴结转移及预后有密切关系。iNOS的表达及MVD值可作为判断胃癌预后的重要指标     

Smad4蛋白在胃癌组织中的表达及其临床意义

目的　探讨Smad4蛋白在胃癌组织中的表达及其临床意义。方法　应用S P免疫组织化学方法 ,对 64例胃癌及癌旁组织中的Smad4的表达进行检测。结果　在正常胃黏膜组织中 ,Smad4蛋白主要存在于腺体的体底部和细胞胞浆中 ;在胃癌组织中 ,Smad4表达于胞浆及少量细胞核中。Smad4在高、中、低分化胃癌中的阳性表达率分别为 65 .14 %、5 8.12 %和 3 2 .2 8% ,平均吸光度分别为 0 .2 44 0± 0 .0 4119,0 .1690± 0 .0 3 613和 0 .13 46± 0 .0 2 195。结论　随着分化程度的降低 ,Smad4在胃癌组织中表达明显减少 ,影响了TGF β信号的传导 ,使其对胃癌细胞的生长抑制作用减弱 ,这在一定程度上促进了胃癌的发展和转移     

缺氧诱导因子-1α表达与胰腺癌病理学特征及新生血管生成的关系

目的　研究胰腺癌组织中缺氧诱导因子 - 1α(HIF- 1α)的表达与胰腺癌病理学特征的关系 ,以及 HIF- 1α表达与血管内皮生长因子 (VEGF)和肿瘤微血管密度 (MVD)之间的相互关系。方法　应用免疫组织化学方法检测 4 7例胰腺癌和 10例正常胰腺组织中 HIF- 1α和 VEGF蛋白的表达。同时用CD34单克隆抗体标记胰腺癌和正常胰腺组织中的微血管。结果　 HIF- 1α和 VEGF蛋白在 4 7例胰腺癌组织中的阳性表达率分别为 5 5 .3% (2 6 / 4 7)和 6 1.7% (2 9/ 4 7) ,而在 10例正常胰腺组织中均未见表达。胰腺癌组织 MVD为 37.6 1± 14 .3,正常胰腺组织为 7.5 5 ± 2 .4 ,二者间有显著性差别 (t'=13.5 1,P<0 .0 0 1)。 HIF- 1α和 VEGF蛋白阳性表达率及 MVD均与胰腺癌的浸润和转移密切相关 (χ2 =4 .32 ,6 .0 1,4 .75 ,4 .6 2 ;t=2 .38,3.92 ;P<0 .0 5 ) ,而与胰腺肿块大小、组织学分级和患者术后 1年生存率无关 (P>0 .0 5 )。HIF- 1α与 VEGF(r=0 .32 9,χ2 =5 .71;P<0 .0 5 )、HIF- 1α与 MVD(r=0 .5 94 ,t=4 .96 ;P<0 .0 0 1)及 VEGF与 MVD(r=0 .36 6 ,t=2 .6 4 ;P<0 .0 5 )间在胰腺癌组织中的表达均呈显著的正相关性。结论　在缺氧状态下 ,胰腺癌组织中 HTF- 1α基因被激活 ,过量表达 HIF- 1α蛋白 ,并通过诱导 VEGF     

细胞间粘附分子1、血管细胞粘附分子1和肿瘤坏死因子α在人动脉粥样硬化病灶中的表达及意义

为研究细胞间粘附分子 1、血管细胞粘附分子 1和肿瘤坏死因子α在人正常冠状动脉与冠状动脉粥样硬化组织中的表达及病理学意义 ,采用免疫组织化学SP法 ,分别检测细胞间粘附分子 1、血管细胞粘附分子 1和肿瘤坏死因子α在人正常冠状动脉与冠状动脉粥样硬化组织中的表达情况。结果发现 ,细胞间粘附分子 1、血管细胞粘附分子 1和肿瘤坏死因子α在动脉粥样硬化组织中的内皮细胞、平滑肌细胞、巨噬细胞均有表达。三者在脂纹期的表达分别为 5 0 .0± 10 .9、5 1.8± 6 .0和 13.9± 2 .8,在纤维斑块期分别为 2 3.1± 7.3、37.2± 9.7和 2 3.0± 6 .0 ,在粥样斑块期分别为 17.5± 4 .9、18.6± 5 .5和 38.0± 10 .0 ,明显高于对照组 (2 .2± 1.4、2 .2± 1.2和 7.8± 2 .2 ,分别为P<0 .0 1)。细胞间粘附分子 1和血管细胞粘附分子 1与肿瘤坏死因子α呈正相关 (前者r=0 .344、P <0 .0 1,后者r=0 .5 2、P <0 .0 1)。实验结果提示 ,细胞间粘附分子 1和血管细胞粘附分子 1在内皮细胞、平滑肌细胞和巨噬细胞高表达可能参与动脉粥样硬化发生发展过程中的某些环节。肿瘤坏死因子α的表达与细胞间粘附分子 1和血管细胞粘附分子 1的表达及动脉粥样硬化病变程度具有相关性。     

胃癌组织中细胞FLICE抑制蛋白基因的表达研究

目的　本研究检测细胞FLICE抑制蛋白 (c-FLIP)基因在胃癌中的表达及其与临床病理特征的关系,初步探讨c-FLIP在胃癌发生、发展中的意义。方法　收集 48例胃癌及相应癌旁正常组织标本,以免疫组化、Western印迹法检测c FLIP蛋白表达;半定量RT PCR法检测c FLIPmRNA表达;原位末端标记法检测胃癌细胞凋亡指数。结果　胃癌及癌旁正常组织均表达c FLIPmRNA,平均相对吸光度值分别为(0. 59±0. 16)和 ( 0. 24±0. 13 ),前者显著高于后者 (P<0. 01 )。免疫组化结果表明c FLIP蛋白在胃癌中表达的阳性率为 100% (48 /48),且 68. 8% (33 /48)呈强阳性表达,而在癌旁正常组织中的阳性率为 75%,且未见强阳性表达,癌组织中的表达水平 ( 6. 93±0. 58 )显著高于癌旁正常组织(3. 19±0. 26,P<0. 01)。较低表达c FLIP蛋白的癌组织其平均凋亡指数 [ (2. 96±0. 15)% ]明显高于高表达c FLIP的癌组织[ (1. 36±0. 11)%,P<0. 01]。另外,在有淋巴结转移组中c FLIPmRNA(0. 64±0. 18)和蛋白(7. 15±0. 63)的表达水平明显高于无淋巴结转移组的c FLIPmRNA( 0. 52±0. 13,P<0. 05)和蛋白水平(6. 69±0. 47,P<0. 01)。Western印迹分析表明,胃癌组织中长型和短型c FLIP蛋白的水平分别为癌旁正常组织的 2. 6倍(P<0. 01)和 2. 8倍 (P<0. 01     

血管内皮生长因子的表达与胃癌浸润和转移的关系

目的　研究血管内皮生长因子165(VEGF)mRNA在胃癌中的表达 ,探讨VEGF与胃癌浸润和转移的关系。方法　采用RT PCR方法 ,对 31例胃癌及非癌组织手术标本中VEGF165mRNA的表达进行相对定量研究。结果　胃癌组织中VEGF165mRNA表达的平均相对量 (1.12 5± 0 .35 6 )明显高于非癌组织的表达量 (0 .76 0± 0 .2 78,P <0 .0 5 ) ,其中淋巴结转移组 (1.2 19± 0 .377)和Ⅲ、Ⅳ期组 (1.2 6 2±0 .386 )分别高于无淋巴结转移组 (0 .92 7± 0 .2 0 5 )和Ⅰ、Ⅱ期组 (0 .934± 0 .194 ,P均 <0 .0 5 )。VEGF高表达者中淋巴结转移率为 83.3% ,Ⅲ和Ⅳ期占 77.8% ,均明显高于VEGF低表达者的 4 6 .2 %和 33.8%(P <0 .0 5 )。结论　胃癌组织中有VEGF的高表达 ,VEGF的表达在胃癌浸润和转移过程中发挥重要作用。     

DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma

AIM: To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS: Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS: The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P<0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs66.7%, P<0.01). The expression of TIMP-2 was significantly correlated with Borrmann's classification, LN metastasis, and the depth of invasion (all P<0.05), The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P<0,01 or P<0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs87.5%, P<0.01). There was a positive correlation between MMP-9 and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION: With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.     

胃癌及癌前病变组织CD44V6表达的研究

目的:检测细胞粘附分子(CD44V6)在胃癌及癌前病变的表达,探索其与胃癌的发生、转移及预后的相关性.方法:用免疫组化方法检测30例浅表性胃炎,34例中重度萎缩性胃炎、34例不典型增生胃粘膜及64例胃癌组织中的CD44V6的表达.结果:CD44V6的阳性表达率在浅表性胃炎、中重度萎缩性胃炎、不典型增生胃粘膜及胃癌组织分别为3.33%(1/30)、14.71%(5/34)、44.12%(15/34)及60.94%(39/64).不典型增生及胃癌组阳性率明显高于浅表性胃炎组及中重度萎缩性胃炎组(均P＜0.01),中重度萎缩性胃炎与浅表性胃炎组比较差异无统计学意义;CD44V6的表达与胃癌的远处转移有关(P＜0.05),与TNM分期有关(P＜0.01),与淋巴结转移无关,与性别、肿瘤大小、大体类型、组织学分型、浸润深度间差异均无统计学意义.结论:用免疫组织化学方法检测胃活检标本中的CD44V6可能有助于胃癌早期诊断和远处转移趋势推测.     

Correlation between expression of cyclooxygenase-2 and angiogenesis in human gastric adenocarcinoma

AIM: To evaluate the expression of cyclooxygenase (COX2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma.METHODS: Immunohistochemical stain was used for detecting the expression of COX-2 in 45 resected specimens of gastric adenocarcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of CD34-positive vascular endothelial cells. Paracancerous tissues were examined as control.RESULTS: Immunohistological staining with COX-2-specific polyclonal antibody showed cytoplasmic staining in the cancer cells, some atypical hyperplasia and intestinal metaplasia,as well as angiogenic vasculature present within the tumors and prexisting vasculature adjacent to cancer lesions. The rate of expression of COX-2 and MVD index in gastric cancers were significantly increased, compared with those in the paracancerous tissues (77.78 vs 33.33 %, 58.13±19.99 vs 24.02±10.28, P＜0.01, P＜0.05, respectively). In 36 gastric carcinoma specimens with lymph node metastasis, the rate of COX-2 expression and MVD were higher than those in the specimens without metostasis (86.11 vs 44.44 %,58.60±18.24 vs 43.54±15.05, P＜0.05, P＜0.05, respectively).The rate of COX-2 expression and MVD in the specimens with invasive serosa were significantly higher than those in the specimens without invasion to serosa (87.88 vs 50.0 %,57.01±18.79 vs42.35±14.65, P＜0.05, P＜0.05). Moreover,MVD in COX-2-positive specimens was higher than that in COX-2-negative specimens (61.29±14.31 vs 45.38±12.42,P＜0.05). COX-2 expression was positively correlated with MVD (r=0.63, P＜0.05).CONCLUSION: COX-2 expression might correlate with the occurance and advancement of gastric carcinoma and is involved in tumor angiogenesis in gastric carcinoma. It is likely that COX-2 by inducing angiogenesis can be one of mechanisms which promotes invasion and metastasis of gastric carcinoma. It may become a new therapeutic target for anti-angiogenesis.     

Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma

AIM: To investigate integrin 133 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS: In situ hybridization(ISH) of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS: The positive rate of integrin 133 mRNA in non- tumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, x2 = 10.20, P ＜ 0.01). In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type (P ＜ 0.01), stage T1-T2 (P ＜ 0.01), non-vessel invasion (P ＜ 0.01), without lymphatic metastasis (P ＜ 0.01), without hepatic and peritoneal metastasis (P ＜ 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type (P ＜ 0.01), stage T1-T2 (P ＜ 0.01), non-vessel invasion (P ＜ 0.01), without lymphatic metastasis (P ＜ 0.01), without hepatic and peritoneal metastasis (P ＜ 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P ＜ 0.01), stage T1-T2 (P ＜ 0.01), non-vessel invasion (P ＜ 0.01), without lymphatic metastasis (P ＜ 0.01), without hepatic and peritoneal metastasis (P ＜ 0.01), respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein (P ＜ 0.01) and MVD (P ＜ 0.05), meanwhile the positive expression rate of VEGF protein was positively related to NVD (P ＜ 0.05). The mean survival period in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm2 was significantly shorter than that in patients with negative expression of integrin β3 mRNA (P ＜ 0.05) and VEGF (P ＜ 0.01), and MVD ＜ 54.9/mm2 (P ＜ 0.01). Five-year survival rate in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm2 was significantly lower than those with negative expression of integrin β3 mRNA (P ＜ 0.05), VEGF (P ＜ 0.05), and NVD ＜ 54.9/mm2 (P ＜ 0.01). CONCLUSION: Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.     

Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer

AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman’s correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biom     

Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

AIM: To investigate the expression of PTEN/MMAC1/TEP1 and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated. RESULTS: PTEN expression significantly decreased (t= 3.98, P&lt;0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P&lt;0.01) in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t=1.95, P&lt;0.05) whereas VEGF expression (t = 2.37, P&lt;0.05) and MVD (t= 3.28, P&lt;0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P&lt;0.01), invasion depth (t= 1.95, P&lt;0.05) and age (t= 4.69, P&lt;0.01). MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t=3.69, P&lt;0.01), and there was a negative correlation betweenPTEN expression and MVD (γ=-0.363, P&lt;0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P&lt;0.01), lymph node metastasis (t= 2.31, P&lt;0.05) and TNM stage (t= 3.04, P&lt;0.01). MVD in VEGF-positive gaslyic cancer was significantly higher than that in VEGF-negative gastric cancer (t=4.62, P&lt;0.01), and there was a positive correlation between VEGF expression of and MVD (y = 0.512, P&lt;0.05). VEGF expression in PTEN-negative gaslyic cancer was significantly stronger than that in PTEN-positive gastric cancer (t=2.61, P&lt;0.05), and there was a significantly negative correlation between the expression of VEGF and PTEN (γ=-0.403, P&lt;0.05).CONCLUSION: Our results imply that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTEN-related angiogenesis might be attributed to its up-regulation of VEGF expression. PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.