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1.
Epidemiologic studies indicate that the incidence of gastric cancer is higher in males than in females. Although the mechanisms mediating this difference are unclear, a role for estrogens has been proposed. We used Western blotting to evaluate the role of estrogen receptor (ER) subtypes ERα and ERβ and proliferating cell nuclear antigen (PCNA) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in Wistar rats; ERα and ERβ mRNA levels also were analyzed by quantitative real-time RT-PCR analysis. The incidence of gastric cancer was significantly higher in male than female rats. In both sexes, ERα expression was similar in MNNG-treated cancerous and noncancerous tissues and normal gastric tissue. However, ERβ expression in MNNG-treated cancerous and noncancerous tissues was significantly lower in male rats and higher in female rats than that in normal gastric tissue; MNNG-induced cancerous tissue showed the highest ERβ expression. PCNA expression in MNNG-treated cancerous tissues was higher than that in noncancerous tissues, and was higher in male rats than female rats. Western blotting results were consistent with the mRNA changes determined by quantitative real-time RT-PCR. The present study provides evidence of a sex-associated difference in ERβ and PCNA expression in MNNG-induced gastric cancers in Wistar rats.  相似文献   

2.
目的:观察分析胃癌螺旋CT表现与组织蛋白酶D(Cath-D)蛋白和基质金属蛋白酶-9(MMP-9)表达的关系。方法:采集自2014年9月至2015年9月在医院经过胃癌手术治疗的54例患者自身胃癌组织标本进行本次研究。再选同期在医院就诊并经过手术治疗的54例胃溃疡患者自身胃黏膜组织进行对照。分别检测MMP-9以及Cath-D蛋白的表达,对所有胃癌患者给予螺旋CT诊断。结果:MMP-9及Cath-D蛋白在胃癌组织内的阳性表达率为74.07%及77.79%,显著高于在正常胃黏膜内的5.56%及9.26%,差异均有统计学意义(P0.05)。MMP-9及Cath-D表达存在明显正相关(r=0.693,P0.05)。胃癌组织内有淋巴结转移及Lauren分型为弥漫型的MMP-9及Cath-D阳性表达率均显著高于无淋巴结转移及Lauren分型为肠型者,差异有统计学意义(P0.05)。根据Logistic回归分析可知,有淋巴结转移以及Lauren分型为弥漫型是胃癌组织内MMP-9及Cath-D表达的螺旋CT表现相关因素。结论:胃癌患者组织内的MMP-9及Cath-D表达比正常胃黏膜组织更高,MMP-9及Cath-D二者的表达呈现正相关,且有淋巴结转移以及Lauren分型为弥漫型是胃癌组织内MMP-9及Cath-D表达的螺旋CT表现相关因素。  相似文献   

3.
Glyoxalase I (GLO1), a methylglyoxal detoxification enzyme, is implicated in the progression of human malignancies. The role of GLO1 in gastric cancer development or progression is currently unclear. The expression of GLO1 was determined in primary gastric cancer specimens using quantitative polymerase chain reaction, immunohistochemistry (IHC), and western blotting analyses. GLO1 expression was higher in gastric cancer tissues, compared with that in adjacent noncancerous tissues. Elevated expression of GLO1 was significantly associated with gastric wall invasion, lymph node metastasis, and pathological stage, suggesting a novel role of GLO1 in gastric cancer development and progression. The 5-year survival rate of the lower GLO1 expression groups was significantly greater than that of the higher expression groups (log rank P = 0.0373) in IHC experiments. Over-expression of GLO1 in gastric cancer cell lines increases cell proliferation, migration and invasiveness. Conversely, down-regulation of GLO1 with shRNA led to a marked reduction in the migration and invasion abilities. Our data strongly suggest that high expression of GLO1 in gastric cancer enhances the metastasis ability of tumor cells in vitro and in vivo, and support its efficacy as a potential marker for the detection and prognosis of gastric cancer.  相似文献   

4.

Purpose

The present study investigated the clinical significance of transmembrane protease, serine 4(TMPRSS4) and extracellular signal-regulated kinases 1 (Erk1) in the development, progression and metastasis of gastric cancer.

Methods

Immunohistochemistry was employed to analyze TMPRSS4 and Erk1 expression in 436 gastric cancer cases and 92 non-cancerous human gastric tissues.

Results

Protein levels of TMPRSS4 and Erk1 were up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues. High expression of TMPRSS4 correlated with age, size, Lauren’s classification, depth of invasion, lymph node and distant metastases, regional lymph node stage and TNM stage, and also with expression of Erk1. In stages I, II and III, the 5-year survival rate of patients with high TMPRSS4 expression was significantly lower than in patients with low expression. Further multivariate analysis suggests that up-regulation of TMPRSS4 and Erk1 were independent prognostic indicators for the disease, along with depth of invasion, lymph node and distant metastasis and TNM stage.

Conclusions

Expression of TMPRSS4 in gastric cancer is significantly associated with lymph node and distant metastasis, high Erk1 expression, and poor prognosis. TMPRSS4 and Erk1 proteins could be useful markers to predict tumor progression and prognosis of gastric cancer.  相似文献   

5.
Real-time analyses of hepatocellular carcinoma were performed in living mice to assess the applicability of probe electrospray ionization–mass spectrometry (PESI–MS) in medical diagnosis. The number of peaks and the abundance of ions corresponding to triacylglycerols (TAGs) were higher in cancerous tissues than in noncancerous tissues. Multiple sequential scans of the specimens were performed along a predetermined line extending over the noncancerous region to detect the boundary of the cancerous region. Our system successfully discriminated the noncancerous and cancerous tissues based on the intensities of the TAG ions. These results highlight the potential application of PESI–MS for clinical diagnosis in cancer.  相似文献   

6.
CD40 signaling plays a critical role in the survival rate of gastric cancer patients. Tumour samples were collected from 73 patients with who were diagnosed as gastric cancer in general surgery department in the 1st affiliated hospital of Suzhou University between September 2002 and July 2003. All patients had not received radiotherapy and chemotherapy before operation. These patients include 46 male and 27 female. Here we show that CD40 is constitutively expressed in the human gastric carcinoma tissues, and CD40 protein and mRNA positive expression in gastric cancer tissues closely correlated with lymph node metastasis and tumour TNM stage. CD40 positive expression in gastric cancer patients with lymph node metastasis was markedly higher than that in gastric cancer patients without lymph node metastasis. CD40 positive expression in stage III-IV gastric cancer patients was markedly higher than that in stage I-II gastric cancer patients. Moreover, CD40 expression closely correlated with prognosis of gastric cancer patients. Therefore, CD40 was taken as grouping variable, and lymph node metastasis and clinical staging were taken as stratification variables, respectively, further analysis showed that prognosis in gastric cancer patients with lymph node metastasis and CD40 positive expression was markedly worse than that in gastric cancer patients without lymph node metastasis and CD40 negative expression (P = 0.0076). These results suggest that CD40 signaling plays a critical role in the survival of gastric cancer patients.  相似文献   

7.
Antioxidant potentials (AOP) of cancerous and noncancerous adjacent human kidney tissues from 12 patients were measured. AOP of the cancerous tissues was found to be significantly lower than that of noncancerous ones. However, tissue malondialdehyde (MDA) levels were significantly higher in the cancerous tissues compared with noncancerous ones. In the intra-correlation analysis, carried out between AOP and MDA levels, significant correlation was found in the cancerous tissues (r = 0.9) but no correlation observed in the noncancerous ones. In the inter-correlation analysis, negative correlation was found between AOP's of cancerous and noncancerous tissues (r = -0.49) and positive correlation between MDA levels (r = 0.51). Results suggest that antioxidant potential of cancerous kidney tissues is significantly reduced compared with noncancerous ones. Therefore, they expose to high oxidant stress and free radical-induced peroxidative attacks, the results of which are cellular deformations.  相似文献   

8.
Cathepsin X, a recently discovered lysosomal cysteine protease, shares common structural features and activity properties with cysteine protease cathepsin B. Based on its widespread mRNA distribution in primary tumors and tumor cell lines, a redundant function in tumor progression has been proposed. In this study, we have shown that these two related proteases exhibit different profiles with respect to their protein distribution in cells and tissues and to their possible roles in malignancy. Protein level of cathepsin X did not differ significantly between matched pairs of lung tumor and adjacent lung tissue obtained from patients with lung cancer whereas that of cathepsin B was 9.6-fold higher in tumor compared to adjacent lung tissue. Immunohistochemical analysis of lung tumor cathepsin X revealed very faint staining in tumor cells but positive staining in infiltrated histiocytes, alveolar macrophages, bronchial epithelial cells, and alveolar type II cells. Cathepsin X stained positive also in CD68+ cells in germinal centers of secondary follicles in lymph nodes, corresponding to tingible body macrophages. Two cell lines with proven invasive behavior, MCF-10A neoT and MDA-MB 231, showed positive staining for cathepsin B, but negative for cathepsin X. We showed that the invasive potential of MCF-10A neoT cells can be impaired by specific inhibitor of cathepsin B but not by that of cathepsin X. Cathepsin X was found in large amounts in the pro-monocytic U-937 cell line, in monocytes and in dendritic cells, generated from monocytes in vitro. Our results show that cathepsin X is not involved in degradation of extracellular matrix, a proteolytic event leading to tumor cell invasion and metastasis. Its expression, restricted to immune cells suggests a role in phagocytosis and the regulation of immune response.  相似文献   

9.
Chen CD  Wang CS  Huang YH  Chien KY  Liang Y  Chen WJ  Lin KH 《Proteomics》2007,7(1):155-167
Gastric cancer is the second most common cancer worldwide and the fifth leading cause of cancer-related death in Taiwan. Identification of biomarkers is essential to improve patient survival. Fifty aberrantly expressed proteins were identified using 2-DE combined with MALDI TOF MS and were grouped based on their function. The overexpression of proteins was confirmed using real-time quantitative RT-PCR, Western blot, and immunohistochemical analysis. The clinicopathological correlations and prognostic significance of these aberrantly expressed proteins were evaluated to determine the novel gastric cancer biomarkers. In this study, expression of chloride intracellular channel 1 (CLIC1) is significantly up-regulated in 67.9% of gastric patients and was selected for further study. The CLIC1 expression in tumor tissues was increased by 1.95-fold (range, 0.01-6.19-fold) compared with that expressed by adjacent noncancerous mucosa. Elevated CLIC1 expression was strongly correlated with lymph node metastasis, lymphatic invasion, perineural invasion, and pathological staging. Additionally, the 5-year survival rate for the low CLIC1 expression group (n = 28; <1.72-fold) was higher than that for the high CLIC1 expression group (n = 28; >or=1.72-fold) (log rank, p = 0.0300). Experimental results indicate that overexpression of CLIC1 is a potential prognostic marker for gastric cancer.  相似文献   

10.
目的:分析同源异型盒基因B7(Homeobox B7,HOXB7)在人胃癌组织中的表达情况,并探讨HOXB7的表达与胃癌患者临床病理特征和预后的关系。方法:收集行手术切除的胃癌组织及对应癌旁组织共120例,采用实时定量PCR(q RT-PCR)技术、蛋白印迹(Western blot)和免疫组化染色分别检测HOXB7m RNA水平及蛋白水平在胃癌及对应癌旁组织中的表达,通过卡方检验分析HOXB7表达水平与胃癌患者临床病理因素间的相关性,采用单因素及多因素Cox回归模型评估HOXB7在胃癌风险评估中的作用,Kaplan-Meier生存曲线分析HOXB7表达水平与胃癌患者无瘤生存期和总生存期的关系。结果:胃癌组织中HOXB7 m RNA和蛋白表达水平均显著高于对应癌旁组织(P0.05);HOXB7蛋白表达与肿瘤临床分期、浸润深度及淋巴结转移均具有显著相关性(P0.05),而与患者性别、年龄、分化程度及远处转移均无显著相关性(P0.05)。单因素和多因素Cox分析提示HOXB7可以作为评估胃癌患者预后的独立风险因素。Kaplan-Meier生存分析结果显示高表达HOXB7的胃癌患者无瘤生存时间和总生存时间均显著低于HOXB7低表达患者组(P0.01)。结论:HOXB7蛋白在胃癌组织中高表达,并与胃癌的恶性表型有关,可能参与胃癌发生及恶性进展过程,可作为判断胃癌患预后的重要参考指标。  相似文献   

11.
本研究选取病理科收集的自2016年1月至2016年12月的90例术后胃癌组织标本(胃癌组)、45例癌旁组织标本(对照组),采用免疫组化染色法检测两组标本中的Y框蛋白(Sox2)、胶原三股螺旋重叠蛋白-1表达,并分析其与肿瘤TNM分期、淋巴结转移、浸润深度、分化程度的关系,采用Spearman秩相关检验检测两种蛋白的相互关系,试图探讨胃癌患者癌组织中性别决定区Y框蛋白(Sox2)、胶原三股螺旋重叠蛋白-1(CTHRC-1)的表达及其相关性。研究结果表明:胃癌组的Sox2蛋白阳性表达率63.33%显著低于对照组的93.33%(p<0.05),胃癌组的CTHRC-1蛋白阳性表达率78.89%显著高于对照组的24.44%(p<0.05);胃癌组的Sox2蛋白阳性表达与胃癌的分化程度、发生淋巴结转移具有相关性(p<0.05);胃癌组的CTHRC-1蛋白阳性表达与胃癌的淋巴结转移、TNM分期、肿瘤浸润深度具有显著的相关性(p<0.05);胃癌组的Sox2蛋白与CTHRC-1蛋白呈显著的负相关表达(Spearman相关系数r=-0.322, p=0.002<0.05)。本研究的初步结论表明:胃癌组织中Sox2蛋白低表达和CTHRC-1蛋白高表达,并且与肿瘤发展密切相关,且二者表达呈负相关。  相似文献   

12.
13.
目的:明确胃癌原发灶与其转移淋巴结中Her2过表达或扩增的差异性,为临床胃癌治疗方案的选择提供参考依据。方法:选择112例经术后病理检查证实为胃癌原发灶Her2强阳性(Her2阳性表达为3+)表达并伴有淋巴结转移的患者样本,应用免疫组化方法并参照《胃癌Her2检测指南》中规定的检测流程重新判定有Her2过表达或扩增的胃癌原发病灶其相应的转移淋巴结中Her2有无过表达或扩增,再将检测结果进行比较。结果:112例患者中,胃癌组织Her2的阳性率为74.11%,淋巴结Her2的阳性表达为66.07%,二者共同阳性表达率为61.61%,差异无统计学意义(P=0.064)。两,二者一致率为83.04%,kappa检验结果为(Z=6.452,P0.001)。胃癌组织Her2的基因表达与年龄、性别、肿瘤位置和肿瘤大小以及远端转移均无显著相关性,而与Lauren分型、组织学分级、浸润深度、淋巴结转移以及TNM分期有关(P0.05)。结论:胃癌原发病灶中Her2过表达或扩增与其相应的转移淋巴结中Her2过表达或扩增具有一致性。胃癌组织Her2状态与Lauren分型、组织学分级、浸润深度、淋巴结转移以及TNM分期有关。  相似文献   

14.
We aimed to validate an analytical approach based on proteomics on gastric cancer specimens for the identification of new putative diagnostic or prognostic markers. Primary screening was performed on gastrectomy specimens obtained from ten consecutive patients with gastric cancer. Gastric epithelial cells were obtained with an epithelial cell enrichment technique, homogenized and then separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The differential protein expression pattern was verified stepwise by Western blotting and immunohistochemistry on samples from 28 and 46 cancer patients, respectively. The putative clinical applicability and prognostic use were tested by an enzyme-linked immunoabsorbent assay on serum samples obtained from 149 cancer patients. One hundred-ninety-one differentially expressed protein spots were found by 2-D PAGE and identified by mass spectrometry, including cathepsin B, which was over-expressed in six (60%) patients. Western blotting confirmed that the active form of cathepsin B is over-expressed, while immunohistochemistry showed strong cytoplasmic staining in cancer tissues of 45 (98%) patients. The serum level of cathepsin B was increased in patients with gastric cancer compared to healthy controls (P = 0.0026) and correlated with T-category and the presence of distant metastases (P < 0.05). Serum levels above 129 pmol x L(-1) were associated with a reduced survival rate (P = 0.0297). Proteome analysis is a valuable tool for the identification of prognostic markers in gastric cancer: Increased cathepsin B serum levels are associated with advanced tumor stages and progressive disease, which enables the classification of some gastric cancer patients into a subgroup that should undergo aggressive therapy.  相似文献   

15.
Peripheral blood lymphocytes (PBL) of gastric cancer patients in advanced stages showed lymphokine activated killer (LAK) activities comparable to those of healthy donors, suggesting potential applicability of LAK cells induced from PBL stimulated with recombinant interleukin-2 (rIL-2) in adoptive immunotherapy (AIT) for gastric cancer. In order to generate a large number of LAK cells from PBL, lymphocytes were cultured with both rIL-2 and phytohemagglutinin (PHA). In this culture, the numbers of cells increased to a greater extent than those in culture with rIL-2 alone but cytotoxic activity did not augment, thus suggesting that this procedure would not afford sufficient clinical effects. On the other hand, a large number of LAK cells with high anti-tumor activities were efficiently induced from spleen cells of the patients by culture of rIL-2; hence clinical usefulness of these LAK cells is anticipated. In regional lymph node lymphocytes (RLNL) cultured with rIL-2, the cytotoxic activities were lower than in those induced in PBL, and a characteristic increase of CD8 + CD11 + suppressor T cells was observed after incubation with rIL-2. Nevertheless, an increase of CD4 + 4B4+ helper inducer T cells was also observed in RLNL after the culture with rIL-2. Furthermore, high cytotoxic activities were induced in RLNL in some cases in which metastasis to the regional lymph nodes was not detected. When gastric cancer patients were pretreated with biological response modifiers (BRM), especially with Lentinan, LAK cells from PBL showed higher NK and LAK activities as compared with those of patients without BRM pretreatment.This work was partly supported by a grant from Hokkoku Cancer Research Foundation.  相似文献   

16.
In this study, the preliminary analyses were conducted of enzymatic activities of uridine phosphorylase (UP) and thymidine phosphorylase (TP) in normal tissues and cancer tissues of the uterine cervix. The study was performed on 27 patients of cervical cancer, treated first in our hospital. Normal cervical tissues obtained from 15 patients undergoing hysterectomy for benign diseases were used as controls. The supernatant of the homogenated cervical tissues and the stroma (5-FU and ribose-1-P or deoxyribose-1-P) were analyzed by high performance liquid chromatography, and then the UP and TP activities calculated. TP activity was significantly greater than UP activity (P < 0.0001). Both UP and TP showed significantly greater activity in cancer tissues than in normal tissues (P < 0.0001). In the TP activity of the cancer tissues, there was no significant difference among the histological types, while the TP activity tended to be significantly higher in the cases with lymph node metastasis. These results showed that the TP-mediated route seemed important as the 5FU metabolic pathway in the uterine cervical tissues, and TP enzymatic activity might be associated with lymph node metastasis.  相似文献   

17.
Background: Over-expression of long non-coding RNA HOTAIR has been reported in several types of cancer. Yet its involvement in gastric cancer (GC) has not been well understood. The aim of present study was to examine the expression pattern of HOTAIR in GC patients, then, explore its role in promoting cancer invasion and underlying molecular mechanism. Methods: The expression level of HOTAIR in the tumor specimens of GC patients was quantified by Realtime RT-PCR. The correlation between HOTAIR level and clinicopathological factors as well as prognosis was then examined. Down-regulation of HOTAIR by RNA interference was applied to investigate its roles in tumor invasiveness via the view of Epithelial-to-mesenchymal transition (EMT). Results: The expression level of HOTAIR in cancer tissues was higher than that in adjacent noncancerous tissues. Expression level of HOTAIR was significantly correlated with lymph node metastasis and TNM stage. Furthermore, high expression level of HOTAIR was a predictor of poor over-all survival in GC patients. In vitro, inhibition of HOTAIR in GC cells could reduce invasiveness, as well as the expression of MMP1 and MMP3. In addition, suppression of HOTAIR could reverse EMT process. Conclusions: HOTAIR could act as a potential predictor for over-all survival in patients with GC. Inhibition of HOTAIR could reduce invasiveness and reverse EMT process in GC cells, indicating the potential role of HOTAIR in GC diagnostics and therapeutics.  相似文献   

18.
In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizations may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P < 0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis.  相似文献   

19.
目的:研究microRNA-221及E-cadherin在胃癌组织中的表达及其临床意义。方法:选取哈尔滨医科大学附属四院2014年-2016年收治的的胃癌患者50例,分别取胃癌及癌旁正常组织作为研究组及对照组。分别应用实时荧光定量PCR及免疫组织化学方法检测其中microRNA-221及E-cadherin的表达。结果:micro RNA-221在胃癌组织中的表达较正常组织显著增高(P0.05),E-cadherin在胃癌组织中的阳性表达率较正常组织显著降低。胃癌组织中microRNA-221的表达与患者的TNM分期、淋巴结转移及远处转移具有显著相关性(P0.05),E-cadherin的表达与患者淋巴结转移及远处转移具有显著相关性(P0.05)。胃癌患者中E-cadherin阴性表达者microRNA-221的相对表达量明显高于E-cadherin阳性表达者(P0.05)。结论:microRNA-221在胃癌组织中呈高表达,E-cadherin在胃癌组织中呈低表达,二者在胃癌组织中的表达呈负相关。microRNA-221可能通过影响上皮细胞间充质转化影响胃癌的浸润与转移。  相似文献   

20.
摘要 目的:研究ASC型氨基酸转运体2(ASCT2)和L型氨基酸转运体1(LAT1)在胃癌组织中的表达情况,并探讨其临床价值。方法:收集70例进展期胃癌组织以及相对应的肿瘤旁组织,采用免疫组化方法检测ASCT2和LAT1在相应组织中的表达水平,并研究其表达与患者临床病理参数和预后的相关性。结果:与癌旁组织相比,胃癌组织中ASCT2或LAT1的高表达率均有统计学差异,但其各自的表达率与癌旁组织相比无明显差异。LAT1和ASCT2在胃癌组织中的共表达率与癌旁组织相比有明显统计学差异。胃癌组织中ASCT2高表达与肿瘤体积、T分期、N分期、TNM分期和Ki-67指数显著相关;LAT1的高表达与肿瘤体积、N分期和TNM分期相关。胃癌组织中ASCT2与LAT1共表达与肿瘤体积、T分期、N分期、TNM分期和Ki-67指数显著相关。胃癌组织中ASCT2和LAT1的高表达呈正相关。胃癌组织中ASCT2高表达、LAT1高表达及ASCT2与LAT1共表达与患者不良预后有关。结论:胃癌组织中ASCT2高表达、LAT1高表达以及ASCT2与LAT1共表达提示患者预后不良,有一定临床价值。  相似文献   

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