Serum Of Gastric Cancer Patients Research Articles

Evaluation of Cu containing amine oxidase is sera of gastric cancer patients

Evaluation of Cu containing amine oxidase is sera of gastric cancer patients

The abnormal expression of microRNA-25 in the serum of gastric cancer patients and its clinical signification

Objective To investigate the abnormal expression of microRNA (miRNA)-25 in the serum of gastric cancer patients and its clinical significance. Methods In Xijing Hospital of Digestive Diseases,Fourth Military Medical University,86 gastric cancer patients with operation and completed follow-up data,70 gastric adenoma patients and 80 healthy controls were selected as study objects.Total RNA was isolated from the serum. After the stable and sensitive miRNA-25 absolute quantity detection method established,the serum levels of miRNA-25 in gastric carcinoma patients,gastric adenoma patients and healthy controls were tested according to this method. The expression differences of miRNA-25 in the serum of patients with gastric cancer and gastric adenoma and healthy controls were analyzed with statistic analysis,and the correlation between miRNA-25 expression level and clinic pathological features of gastric cancer was also analyzed. Results The expression level of miRNA-25 in the serum of gastric cancer patients (135. 6 fmol/μg total RNA) was significantly higher than that of gastric adenoma patients (67. 7 fmol/μg total RNA) and healthy controls (62. 2 fmol/μg total RNA)(P＜0. 01). The receiver operating characterisstic curve of miRNA-25 indicated that serum miRNA-25 with good specificity and sensitivity in gastric cancer diagnosis (AUC=0. 827). The serum level of miRNA-25 in gastric cancer patients with lymph node metastasis [(148. 3±10. 2) fmol/μg total RNA] or clinicopathological stage Ⅲ /Ⅳ patients [(146. 7±9.5) fmol/μg total RNA] was significantly higher than that of gastric cancer patients without lymph node metastasis [(120. 3±10. 1)fmol/μg total RNA] or clinicopathological stage Ⅰ/Ⅱpatients [(119. 4±12. 2) fmol/μg total RNA] (P＜0.05). The correlation statistical analysis result indicated that there was no significant difference in survival period between serum miRNA-25 highly expressed and lowly expressed gastric cancer patients (P＞0. 05).Conclusion Serum miRNA-25 testing maybe helpful in diagnosis and prognosis of gastric cancer. Key words: microRNAs; Tumor markers,biological; Stomach neoplasms; Sensitivity and Specificity; Prognosis

Serum Interleukin-33 Levels in Patients with Gastric Cancer

Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines, and it is closely related to IL-18, one of the best characterized members of the IL-1 family. It's been demonstrated that elevated levels of IL-18 are involved in a wide variety of tumors, especially in gastric cancer. The purpose of this study was to determine the correlations between serum IL-33 levels and the clinicopathologic features in gastric cancer patients. Serum samples were collected from 68 patients with gastric cancer and 57 controls. Serum IL-33 levels were measured by ELISA. Classical tumor markers of CEA and CA19-9 levels were routinely detected by chemiluminescence immunoassay. Western blot analysis was used to detect IL-33 expression in gastric cancer tissue samples and cell lines. The relationship between serum levels of IL-33 and clinical characteristics in patients was analyzed. IL-33 levels in the serum of gastric cancer patients were significantly elevated in comparison with that of healthy volunteers. Furthermore, higher serum levels of IL-33 in gastric cancer patients were found to correlate with several poor prognostic factors like depth of invasion, distant metastasis and advanced stage (stage III/IV). On the other hand, serum IL-33 levels did not correlate with CEA and CA19-9. The expression of IL-33 protein was upregulated in carcinoma tissues in comparison with matched normal tissues, and no statistically significant difference was found between the four gastric cancer cell lines and human gastric epithelial cell line GES-1. Serum IL-33 may be a useful biomarker for predicting the prognosis of gastric cancer.

Detection of gastric carcinoma-associated antigen MG7-Ag in human sera using surface plasmon resonance sensor

Background: MG7-Ag is a kind of gastric cancer-specific tumor-associated antigen and has been investigated to serve as a marker of gastric cancer for early diagnosis. Methods: Surface plasmon resonance (SPR) sensor was used for the detection of MG7-Ag in the sera of gastric cancer patients to develop an innovative, simple and rapid assay method for early diagnosis. The specific monoclonal MG7 antibodies were used as capture and detection receptors which were immobilized on the surface of SPR sensor chips for MG7-Ag identification in the human sera. The measurements include 9 cases of gastric cancer patients and 2 cases of healthy blood donors and a MKN45 cancer cell lysate solution sample for positive control. Results: The binding of MG7-Ag onto the sensor surface was observed from SPR spectra. The sera of most gastric cancer patients revealed much higher expression level of MG7-Ag than healthy human sera did in SPR measurement. Conclusion: The initial results demonstrate that the SPR biosensor has the potential for its application in the early diagnosis of gastric cancer. However, more tests need to be done to confirm the detection limitation and the criterion for cancer risk evaluation in early diagnosis.

The diagnostic value of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) measurement in the sera of gastric cancer patients

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in gastric cancer cells (GC). Moreover, the activity of total ADH and class IV isoenzymes is significantly higher in cancer tissue than in healthy mucosa. The activity of these enzymes in cancer cells is probably reflected in the sera and could thus be helpful for diagnostics of gastric cancer. The aim of this study was to investigate a potential role of ADH and ALDH as tumor markers for gastric cancer. We defined diagnostic sensitivity, specificity, predictive value for positive and negative results, and receiver-operating characteristics (ROC) curve for tested enzymes. Serum samples were taken from 168 patients with gastric cancer before treatment and from 168 control subjects. Total ADH activity and class III and IV isoenzymes were measured by photometric but ALDH activity and ADH I and II by the fluorometric method, with class-specific fluorogenic substrates. There was significant increase in the activity of ADH IV isoenzyme and ADH total in the sera of gastric cancer patients compared to the control. The diagnostic sensitivity for ADH IV was 73%, specificity 79%, positive and negative predictive values were 81 and 72% respectively. Area under ROC curve for ADH IV was 0.67. The results suggest a potential role for ADH IV as marker of gastric cancer.

Measurements of serum C-reactive protein levels in patients with gastric cancer and quantification using silicon nanowire arrays

We examined the levels of serum α-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen in 83 of 400 patients who had undergone surgery for gastric cancer and correlated these markers with stages of the disease. In addition, we measured C-reactive protein (CRP) concentrations in the sera of gastric cancer patients with silicon nanowire field-effect transistors (SiNW FETs) to determine whether SiNW FETs could be used to accurately sense CRP, a marker of inflammation and possible indicator of future progression of the cancer. We designed and fabricated SiNWs to be responsive to CRP. Of the 83 patients examined, six who showed marked elevation of CRP (>3 to 10 mg/dL, according to hospital laboratory measurements) were selected and subjected to measurement with the SiNW FETs. Our findings showed that SiNW-based sensors could be highly sensitive and specific in measuring CRP in the sera of postoperative patients and thus could represent a simple and quick method of prognostic evaluation in patients. From the Clinical Editor In this study, silicon nanowire field effect transistors were fabricated to be responsive to C-reactive protein. The new technology resulted in highly sensitive and specific CRP sensors, which may greatly simplify this serum test for a variety of conditions where rapid, accurate and easily repeatable CRP measurements are needed.

Detection of Serum Gastric Cancer-Associated MG7-Ag from Gastric Cancer Patients Using a Sensitive and Convenient ELISA Method

Purpose: To seek a high sensitive and convenient method for early diagnosis of gastric cancer by testing MG7-Ag in serum of gastric cancer patients and some other control groups using a convenient ELISA method. Experiment Design: The expression of serum MG7-Ag was detected in 116 preoperative gastric cancer patients, 63 postoperative gastric cancer patients, 78 precancerous lesion patients, 50 healthy blood donors and patients of other cancers by a convenient ELISA method. For comparison, serum CEA, CA 50, CA 19-9 and TAG-72 were also detected in preoperative gastric cancer patients. Meanwhile, the expression of MG7-Ag was detected by immunohistochemical analysis in the groups of patients with gastric cancer or precancerous lesion mentioned above. Results: The positive rate of Mg7-Ag determined by ELISA was 83. 6% of preoperative gastric cancer patients, 54.8% of lung cancer patients, 45.5% of rectal cancer patients, 17.6% of colonic cancer patients, 14.2% of breast cancer patients, 47.6% of postoperative gastric cancer patients, 12.8% of precancerous lesions patients and 0% of healthy blood donors, respectively. The sensitivity of ELISA (83.6%) was found to be similar with that of immunohistochemistry (94%, p > 0. 01), while the false positive rate was lower (12.8% vs. 51.3%). MG7-Ag expression level in gastric cancer was correlated with tumor differentiation (p < 0. 01) and pathological stage (p < 0. 01). Conclusion: This ELISA method may be a non-invasive candidate method for screening of large population with high risk of gastric cancer.

Prohibitin: a potential biomarker for tissue-based detection of gastric cancer

Prohibitin (PHB) was found to be overexpressed in breast cancer and thus is suggested as a biomarker in that disease. A few studies have investigated the PHB expression pattern in gastric cancer by two-dimensional gel electrophoresis. Uncertainties still existed on whether PHB expression could indicate the differentiation and apoptosis degree of gastric cancer and whether PHB protein as well as anti-PHB antibody could be a biomarker in the serum of the gastric cancer patient. In this study, the expression levels of PHB protein and mRNA of the tissues as well as PHB antigen and anti-PHB antibody in serum of patients with gastric cancer were systemically examined. Immunohistochemistry and real-time PCR were used to detect expression levels of PHB protein and mRNA in gastric cancer tissues. Recombinant PHB antigen was identified by Western blotting. The expression of PHB antigen and anti-PHB antibody was investigated by ELISA and TRFIA. Bcl-2 expression was examined by immunohistochemistry. By immunohistochemistry and real-time PCR analyses, PHB protein and mRNA were both overexpressed in gastric cancer tissues compared to adjacent normal gastric tissues (P < 0.01). Moreover, an elevated PHB expression pattern paralleled the differentiation degree and Bcl-2 protein expression in gastric cancer. However, no significant differences of PHB protein and anti-PHB antibody expression were detected in serum of gastric cancer patients and that of healthy volunteers. These results indicated that PHB could be a potential diagnostic and differentiation biomarker of gastric cancer for tissue-based detection by immunohistochemistry and real-time PCR, but not for serum-based detection.

Characteristics in Raman spectrum of serum of gastric cancer patients

To investigate the characters of Raman spectrum in gastric cancer patients through comparing serum of functional dyspepsia patients, serum of gastric cancer patients with SGC7901 cell culture fluid, correlation with culturing time of cell line, and research the recourse of these special Raman peak. Peripheral blood samples were collected from 25 gastric cancer patients and 10 functional dyspepsia (FD) patients. Human gastric cancer cells of the line SGC7901 were cultured. The serum samples of the gastric cancer patients and of the FD patients, and the culture fluid of SGC7901 cell underwent Raman spectroscopy with 230 nm and 100 nm as the least peaks respectively. Serum of normal person, lysate, and 1604 culture fluid were used as controls. Seven reproducible Raman peaks at the wavelengths of 583, 633, 656, 674, 707, 773 and 799 nm were detected, with 230 nm as the least peak, in the serum samples of gastric cancer patients. Raman peaks at the wavelengths of 633, 656, and 674 nm were detected only in the serum samples of gastric cancer patients, and the Raman peaks at the wavelengths of 533, 707, 773, and 799 nm of the serum of gastric cancer patients (96.5 +/- 6.0, 76.9 +/- 4.7, 63.7 +/- 4.5, 285.7 +/- 18.6) were all remarkably higher than those of the serum samples of FD patients (40.3 +/- 1.8, 27.9 +/- 1.9, 22.9 +/- 1.4, 113.2 +/- 7.7, all P < 0.01). Similar condition, with 100 nm as the least peak, could detected in the Ramon peaks at the above mentioned wavelengths between the serum samples of the gastric cancer patients and the 1640 culture medium. The Raman peak of the cell culture fluid was positively correlated with the time of cell culture. The Raman peaks of the gastric cell lysate at the wavelengths of 583, 633, and 656 nm were significantly different from those of the cell culture fluid (P = 0.027, 0.029, and 0.043 respectively). The serum of gastric cancer patients has specific reproducible Raman spectrum. The cell content possibly is part of the reason of the special characters in Raman spectrum of gastric cancer serum.

Down-regulated expression of complement factor I: A potential suppressive protein for gastric cancer identified by serum proteome analysis

BackgroundScreening tests are needed for gastric cancer. In order to find serologic biomarkers for gastric cancer screening, we used proteomics to search for protein biomarkers that may be detected in serum of gastric cancer patients. MethodsFour groups of serum samples (from 20 gastric cancer patients) included pTNM stages I to IV were compared with two control groups of serum samples. The serum samples were first chromatographed using an immunoaffinity column to selectively remove albumin and IgG. Then serum proteins separated by 2-DE and identified by MALDI–TOF/TOF–MS. ResultsThere were 3 proteins including complement C4-B precursor, complement factor I (CFI) precursor and haptoglobin precursor were found significantly different between the healthy and gastric cancer patients. Further validation study by Western blot showed that the detection of CFI precursor was under-expressed in gastric cancer sera compared to normal sera (p<0.05), in addition to a declining expression with the advanced pTNM stage from stage I to IV of gastric cancer patients. Area under the receiver operating characteristic (ROC) curve was 0.78 for the expression of CFI precursor (p<0.01). Conclusions2-DE-based serum proteome analysis may be useful in the screening of serum biomarkers for gastric cancer. CFI precursor could aid in the diagnosis and indicate the advancement of gastric cancer.

Diagnosis of Gastric Cancer by Serum Proteomic Fingerprinting

Accurate serum biomarkers for gastric cancer currently are lacking. We attempted to identify potential diagnostic serum markers for gastric cancer with the use of the surface-enhanced laser desorption/ionization ProteinChip technology. The study was divided into 3 phases: (1) discovery of potential diagnostic markers using sera of gastric cancer patients and controls, (2) development of a diagnostic model, and (3) independent validation of the diagnostic model using a different cohort of gastric cancer and control patients. The serum proteins/peptides were analyzed with 2 types of ProteinChip arrays, IMAC30 arrays loaded with copper (II) ion and CM10 (weak cation exchange) arrays. In the discovery set, peak intensities of 31 surface-enhanced laser desorption/ionization proteomic features were significantly higher in gastric cancer patients. The tumor-specific nature of 6 proteomic features with the mass/charge (m/z) values of 5098, 8592, 8610, 11,468, 11,804, and 50,140 was verified by their lower peak intensities in postoperative sera. After excluding the sodium adduct peak (8610 m/z) of the 8592 m/z protein, the peak intensities of the tumor-specific proteomic features were used to develop a linear regression model for calculating a diagnostic index. The area under the receiver operating characteristic curve of the corresponding diagnostic index was 0.92 (95% confidence interval, 0.85-0.99) in the independent validation set. At a specificity of 95%, the sensitivity for gastric cancer detection was 83%. A unique serum proteomic fingerprint can be detected in the sera of gastric cancer patients, which may be useful in the noninvasive diagnosis of gastric cancer.

Detection of gelatinase B activity in serum of gastric cancer patients

To determine the proteolytic activity and expression of gelatinase B in serum of gastric cancer patients and their correlation with the stage of the tumor. Sera from 23 patients who underwent surgery for primary gastric cancer as the experimental group and from 11 as the control group were used to determine the proteolytic activity and its inhibition by EDTA and 1,10-phenanthroline. Gelatinase B activity was detected by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-PAGE zymography. Proteolytic enzyme activity was increased in gastric cancer patients when compared to the control group (P < 0.05). The proteinases were determined to be metalloproteinases upon inhibition test with specific metalloproteinase inhibitors 1,10-phenanthroline (P < 0.05) and EDTA (P < 0.01). SDS-PAGE and SDS-PAGE zymography revealed gelatinase B (proMMP-9) activity and its molecular mass of 92 ku. Proteinase activity is overexpressed in serum of gastric cancer patients. Gelatinase B in serum plays an important role in the progression of gastric cancer. ProMMP-9 can be used as a marker for invasiveness of gastric cancer.

Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer

While there is no reliable serum biomarker for the diagnosis and monitoring of patients with gastric cancer, we tested the potential diagnostic and prognostic values of detecting methylation changes in the serum of gastric cancer patients. DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%) and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P=0.08), TIMP3 (P=0.005) and hMLH1 (P=0.03) in the serum. In all, 33 cancers (55%) had methylation detected in the serum in at least one of these four markers, while three normal subjects had methylation detected in the serum (specificity 86%). The combined use of APC and E-cadherin methylation markers identified a subgroup of cancer patients with worse prognosis (median survival 3.3 vs 16.1 months, P=0.006). These results suggest that the detection of DNA methylation in the serum may carry both diagnostic and therapeutic values in gastric cancer patients.

Lewis Epitopes on Outer Membrane Vesicles of Relevance to Helicobacter pylori Pathogenesis

Helicobacter pylori extrudes protein- and lipopolysaccharide-enriched outer membrane vesicles from its cell surface which have been postulated to act to deliver virulence factors to the host. Lewis antigen expression by lipopolysaccharide of H. pylori cells has been implicated in a number of pathogenic roles. The aim of this study was to further characterize the expression of lipopolysaccharide on the surface of these outer membrane vesicles and, in particular, expression of Lewis antigens and their association with antibody production in the host. H. pylori strains were examined for outer membrane vesicle production using transmission electron microscopy and Lewis antigen expression probed using immunoelectron microscopy. Sera from patients were analyzed for cross-reacting anti-Lewis antibodies and, subsequently, absorbed using outer membrane vesicle preparations to remove the cross-reacting antibodies. The formation of outer membrane vesicles by H. pylori was observed in both in vitro and in vivo samples. Furthermore, vesicles were produced following culture in either liquid or solid medium by all strains examined. Moreover, we observed the presence of Lewis epitopes on outer membrane vesicles using immunoelectron microscopy and immunoblotting. Circulating anti-Lewis antibodies were found in the sera of gastric cancer patients but not in the sera of H. pylori-negative control subjects. Absorption of patient sera with outer membrane vesicles decreased the levels of anti-Lewis autoantibodies. Our results demonstrate the ability of H. pylori to generate outer membrane vesicles bearing serologically recognizable Lewis antigens on lipopolysaccharide molecules which may contribute to the chronic immune stimulation of the host. The ability of these vesicles to absorb anti-Lewis autoantibodies indicates that they may, in part, play a role in putative autoimmune aspects of H. pylori pathogenesis.

589 The dependence of the in vitro HUVECs proliferation of the TGF-beta concentration in the serum of gastric cancer patients

589 The dependence of the in vitro HUVECs proliferation of the TGF-beta concentration in the serum of gastric cancer patients

Enzynomics moves into Toulouse

MicroRNA (miRNA) is riveting nowadays due to its close relevance to human malignancies. Exploiting a fast and convenient biosensor for sensitive and specific detecting miRNA is necessary and it has significant meaning for oncology. In this work, to understand the relationship between miRNA-21 and gastric cancer, we employ T4 RNA ligase 2 to initiate specific ligation reaction depending on the sequence of target RNA, and T7 exonuclease to catalyze the first stage cyclic enzymatic amplification method (CEAM) specifically, which also resting on the target RNA sequence, and the second stage CEAM to further amplify the response resulting from the initial target RNA. Our two-stage CEAM strategy can detect miRNA-21 as low as 0.36 fM with remarkable specificity, and most importantly, it can be used to inspect the expression level of miRNA-21 in blood serum of gastric cancer patients. This will offer new perspective for figuring out the pathways of miRNA-21 involving in cancer.

Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery.

To evaluate the clinical usefulness of serum vascular endothelial growth factor (VEGF) levels in gastric cancer patients. Vascular endothelial growth factor plays an important role in the formation of new blood vessels involved in the growth and metastatic spread of solid tumors, but there is limited information regarding the clinical significance of serum VEGF levels in cancer patients. Serum VEGF concentrations were measured by an enzyme linked immunosorbent assay in 61 healthy controls and in 58 gastric cancer patients before surgery, and then again at 7 and 30 days after surgery. The association between preoperative serum VEGF levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. Serum VEGF levels in gastric cancer patients were significantly higher than those in controls. There was a significant association between serum VEGF levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases. Serum VEGF levels decreased significantly after radical resection of the primary tumor and increased in patients with unresectable tumors. Multivariate regression analysis showed that serum VEGF level is an independent prognostic factor for survival. Serum VEGF levels in gastric patients are significantly higher compared with normal controls and correlate with local tumor extent, disease stage, and the presence of distant metastases. Preoperative serum VEGF concentration decreases significantly after radical resection of the primary tumor and is an independent prognostic factor for patient survival suggesting that determination of serum VEGF levels may be clinically useful.

In vitro HUVECs proliferation activity after the influence of the recombinant TNF-α and the supernatants of the primary culture of the tumors and serum of gastric cancer patients

In vitro HUVECs proliferation activity after the influence of the recombinant TNF-α and the supernatants of the primary culture of the tumors and serum of gastric cancer patients

Significant correlation between serum level of hepatocyte growth factor and progression of gastric carcinoma.

Hepatocyte growth factor (HGF) can promote proliferation of many types of tumor cells including gastric cancer cells. To study the role of HGF in the progression of gastric carcinoma, HGF levels were measured by an enzyme immunoassay (EIA) system in sera of gastric cancer patients and followed up the levels after the operation. The mean serum HGF level in 212 healthy control subjects, 140 patients with primary gastric cancer, and 13 patients with recurrent gastric cancer were 0.199 +/- 0.073, 0.325 +/- 0.209, and 0.578 +/- 0.258 ng/ml, respectively. The increase of the levels was significantly correlated with the progression of tumor stage. The levels decreased to normal levels 1 month after curative resection of the tumors. However, the levels did not decrease significantly in nonresected cases. During the follow-up of the patients for several months, the level was significantly increased in recurrent gastric cancer patients, whereas there was no increase in nonrecurrent patients. In conclusion, the serum HGF levels significantly correlated with the aggressiveness of the tumors, suggesting an important role of HGF in the progression of gastric carcinoma.

Serum concentrations of vascular endothelial growth factor and nitrite as an estimate of in vivo nitric oxide in patients with gastric cancer.

The importance of tumour angiogenesis in the process of tumour growth and progression in solid tumours has been widely accepted. Among many angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to play a major role in the development and dissemination of the malignant tumours. Nitric oxide (NO) production was also observed in solid tumour tissues. NO has been reported to play an important role for the mitogenic effect of VEGF in the angiogenic process. However, little is known about the correlation between VEGF and NO in circulating levels. Therefore, we investigated serum VEGF and NO concentrations in human gastric cancers as well as healthy individuals, and examined the influence of tumour stage on circulating level of VEGF. The study consisted of 11 healthy individuals and 37 patients with primary gastric cancer who did not receive any prior therapy. Patients were categorized into four groups according to TNM classification. The level of VEGF165 in preoperative sera of gastric cancer patients and healthy donors was assayed using the quantitative sandwich enzyme immunoassay technique. NO concentration was estimated indirectly from serum nitrite. The ANOVA test showed a significant difference in serum VEGF165 concentrations between tumour stages (P < 0.001). A striking relationship was found between serum NO levels and tumour stage (P < 0.001). A significant difference was also seen between healthy individuals and patients with stage 1 disease. The present study suggested that large tumour burden was associated with significantly increased levels of VEGF165 and NO. © 1999 Cancer Research Campaign