Biomedical subjects

Guo-Wang Xu

Publications and source records attributed to Guo-Wang Xu.

11 recordsLinked to original sources

PubMed2005

Effect of Helicobacter pylori infection on p53 expression of gastric mucosa and adenocarcinoma with microsatellite instability.

AIM: To investigate the relationship between Helicobacter pylori (H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to H pylori infection. METHODS: One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocarcinoma. Peripheral blood samples of these patients were also collected. H pylori infection and p53 expressions were detected by means of streptavidin-peroxidase (SP) immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26, D17S261, D3S1283, D2S123, and D3S1611. MSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were characterized as high MSI (MSI-H) if they manifested instability at two or more markers, low MSI (MSI-L) if unstable at only one marker, and microsatellite stable (MSS) if they showed no instability at any marker. RESULTS: H pylori infection was detected in the samples of gastritis, intestinal metaplasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no H pylori infection was detected in the samples of normal control. There was a significant difference in the infection rates between gastritis and carcinoma samples (P = 0.035). No MSI was detected in gastritis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas. In those gastric carcinomas, the MSI-H frequency in H pylori-positive group was significantly higher than that in H pylori-negative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in H pylori-positive samples were higher than those in the negative group when the carcinoma samples were subdivided into H pylori-positive and -negative groups (P = 0.013). Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with H pylori infection and no p53 expression could be seen in the H pylori-negative samples. CONCLUSION: H pylori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.

Adenocarcinoma↗

PubMed2005

Urinary nucleosides as biological markers for patients with colorectal cancer.

AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke's stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer.

Adult↗

PubMed2005

HMLH1 gene mutation in gastric cancer patients and their kindred.

AIM: To study the status of hMLH1 gene point mutations of gastric cancer kindreds and gastric cancer patients from northern China, and to find out gene mutation status in the population susceptible to gastric cancer. METHODS: Blood samples of 120 members from five gastric cancer families, 56 sporadic gastric cancer patients and control individuals were collected. After DNA extraction, the mutations of exon 8 and exon 12 of hMLH1 gene were investigated by PCR-SSCP-CE, followed by DNA sequencing. RESULTS: In the five kindreds, the mutation frequency was 25% (5/16) for the probands and 18% (19/104) for the non-cancerous members, which were significantly higher than the controls (P<0.01 chi2 = 7.71, P<0.01 chi2 = 8.65, respectively). In the sporadic gastric cancer, the mutation frequency was 7% (4/56), which was similar to that (5/100) in the healthy controls. The mutation point of exon 8 was at 219 codon of hMLH1 gene (A-G), resulting in a substitution of Ile-Val (ATC-GTC), whereas the mutation of exon 12 was at 384 codon of hMLH1 gene (T-A) resulting in a substitution of Asp-Val (GTT-GAT), which were the same as previously found in hereditary nonpolyposis colorectal carcinoma. CONCLUSION: The members of gastric cancer families from northern China may have similar genetic background of hMLH1 gene mutation as those of hereditary nonpolyposis colorectal carcinoma.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Clinical significance and prognostic value of urinary nucleosides in breast cancer patients.

OBJECTIVE: Thirteen urinary nucleosides, primarily degradation products of tRNA, were evaluated as potential tumor markers for breast cancer patients. DESIGN AND METHODS: The micellar electrokinetic chromatography (MEKC) method has been used to analyze the urinary nucleosides in 41 healthy controls, 20 patients with benign breast tumors, and 26 breast cancer patients. RESULTS: Urinary nucleoside concentrations of breast cancer patients were found to increase significantly compared to those of patients with benign breast tumors and healthy controls. By using 13 nucleoside concentrations as data vectors for principal component analysis (PCA), 73% (19/26) of breast cancer patients were correctly identified from healthy controls, while only 20% (4/20) of patients with benign breast tumors were indistinguishable from breast cancer patients. The mean level of all forms of urinary nucleosides in patients with metastatic breast cancer was higher than that in patients with primary breast cancer. The levels of modified nucleosides tended to decrease and return to normal after surgery. CONCLUSION: The results indicate that urinary nucleosides may be useful as tumor markers for breast cancer.

Adolescent↗

PubMed2005

Normal and modified urinary nucleosides represent novel biomarkers for colorectal cancer diagnosis and surgery monitoring.

BACKGROUND: Up to now, there is still no ideal tumor marker in early diagnosis and effective monitoring, especially for surgical resection of colorectal cancer (CRC). The aim of the present study was to evaluate the application of urinary normal and modified nucleosides in diagnosis and surgery monitoring of CRC. METHODS: Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were enrolled. Spontaneous urine samples were collected 1 day before surgery and on day 8 postoperatively, and 14 urinary nucleosides were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Another 62 healthy people were also studied as control. The clinical routine tumor markers, serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, and alpha-fetoprotein (AFP) of CRC patients, were correspondingly evaluated by electrochemiluminescent immunoassay. RESULTS: The levels of 11 out of 14 of the determined urinary nucleosides in the CRC group were much higher than those of normal controls. Through the principal component analysis of these 14 nucleosides, 76.9% of CRC patients were correctly classified. The sensitivity of this analysis was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%; P < 0.01). Receiver operating characteristic (ROC) curve analysis of 1-methylguanosine (m1G) and pseudouridine (Pseu) showed good sensitivity-specificity profiles of the diagnosis of CRC. The elevated levels of the nine nucleosides significantly decreased after curative resection of 40 CRC cases. The data also showed that the preoperative levels of some nucleosides were positively related with tumor size and Dukes staging of CRC. CONCLUSION: The evaluation of normal and modified urinary nucleosides might become novel tumor markers, which will be facilitated in the clinical setting and helpful in the diagnosis, management and follow up of CRC. Pseu and m1G may be more promising for clinical use and be worthy of further studies in the near future.

Adult↗

PubMed2005

[Methylation of hMLH1 gene promoter in gastric carcinoma with microsatellite instability].

BACKGROUND & OBJECTIVE: Mismatch repair (MMR) deficiency, characterized by microsatellite instability (MSI), is a major cause of hereditary nonpolyposis colorectal carcinoma (HNPCC). Our previous study showed that loss of MMR protein expression can also be seen in gastric carcinoma, but MMR gene mutation seldom occur. Promoter methylation, a main cause of suppressor gene inactivation, might also lead to defect of MMR gene function. This study was designed to investigate the relationship of hMLH1 gene promoter methylation status to MSI in gastric carcinoma, and analyze its action as a risk factor of carcinogenesis. METHODS: DNA was extracted from 52 samples of gastric carcinoma and their adjacent non-cancerous gastric mucosa. Polymerase chain reaction (PCR) was used to amplify microsatellite loci BAT-26, D17S261, D3S1283, D2S123, and D3S1611. MSI was studied by capillary electrophoresis. Methylation of hMLH1 gene promoter was detected by restrictive endonuclease digestion, expression of hMLH1 protein was detected by immunohistochemistry. RESULTS: Of the 52 specimens of gastric carcinoma, 13 with high MSI (MSI-H), 2 with low MSI (MSI-l), and 37 with microsatellite stability (MSS). Frequency of hMLH1 promoter methylation was significantly higher in the 13 specimens of gastric carcinoma with MSI-H than in the 39 specimens of gastric carcinoma with MSI-L or MSS (100% vs. 2.6%, P<0.01). Furthermore, frequency of hMLH1 promoter methylation was significantly higher in the 13 specimens of adjacent non-cancerous gastric mucosa of gastric carcinoma with MSI-H than in the 39 specimens of adjacent non-cancerous gastric mucosa of gastric carcinoma with MSI-L or MSS (46.2% vs. 2.6%, P<0.01). The methylation status was accordant with loss of hMLH1 protein expression. Methylation of hMLH1 gene promoter had no relation with differentiation and clinical stage of gastric carcinoma. CONCLUSION: Methylation of hMLH1 gene promoter exists in gastric carcinoma tissues with MSI-H, and their adjacent non-cancerous gastric mucosa, it may be a risk factor of carcinogenesis of gastric carcinoma.

Adaptor Proteins, Signal Transducing↗

PubMed2005

[Metabonomics and its applications].

The concept, characteristics and history of metabonomics are introduced. The techniques used in data acquisition and data analysis in metabonomics including their advantages and disadvantages are summarized. In data acquisition platform, NMR, GC/MS, LC/MS (/MS) are the prevalent techniques although at present, none of them is a perfect technique that could meet with the requirement of the metabonomics for measuring all metabolites. While in data analysis, the PCA, PLS and ANN are the major techniques. The researchers could select them according to the research destination. Recent advances and applications of metabonomics in disease diagnosis, drug toxicity evaluation, plant metabolomics and microbial metabolomics are reviewed. In addition, by giving the situation on the establishment of the related corporations, the conferences about metabonomics and proclamation of NIH roadmap the current boom of the metabonomics is reflected. It can be expected that with the development of the function genomics, metabonomics will play a major role in the discovery of the phynotype of the genome and searching for the disease diagnostic biomarkers, and it will also bring much benefit to the drug discovery, clinical diagnosis and nutrition science.

Humans↗

PubMed2004

[Expression of hMSH2 and hMLH1 in stomach cancer and their correlation with Helicobacter pylori infection].

BACKGROUND & OBJECTIVE: The carcinogenesis of gastric carcinoma is related to many factors. Helicobacter pylori (HP) infection is one of the factors causing gastric carcinoma, but the exact molecular mechanism is not clear. Mismatch repair genes are important in keeping the accuracy of DNA replication. They are associated with carcinogenesis of alimentary canal. In order to investigate the role of hMSH2 and hMLH1 in stomach cancer and the possible mechanism of carcinogenesis caused by HP infection, we tested cancer tissue, surrounding mucosa and chronic superficial gastritic mucosa with and without HP infection. METHODS: HP infection was determined with quick-ureolytase method. Immunohistochemistry staining was used to exam the expression of hMSH2 and hMLH1 in tumor tissue and their surrounding mucosa and gastric mucosa. Chi-square was used for statistic analysis. RESULTS: The positive rate (67.1%) of hMSH2 expression in cancer tissue was significantly higher than those of surrounding mucosa (35.5%) and gastritic mucosa (42.1%) (P< 0.05); the positive rate (81.1%) of hMSH2 expression in poor differentiation group was significantly higher than those in well middle differentiation group (54.5%) and mucoid carcinoma group (54.5%) (P< 0.05), but there was no significant difference between the latter two groups. There was no significant difference among the positive rates of hMLH1 expression in cancer tissue (81.6%), in surrounding mucosa (90.8%), and in gastritic mucosa (89.5%) (P>0.05). The positive rate (47.1%) of hMLH1 expression in mucoid carcinoma group was significantly higher than those in well middle differentiation group (81.8%) and poor differentiation group (97.3%) (P< 0.05), but there was no significant difference between the latter two groups (P>0.05). In cancer tissue, the positive rate (56.8%) of hMSH2 expression in HP infection group was significantly lower than that without HP infection group (81.3%) (P< 0.05); the positive rates of hMLH1 expression was 77.2% in HP infection group and 87.5% in without HP infection group, but there was no significant difference between two groups (P >0.05). In surrounding mucosa, the positive rate of hMSH2 expression was 29.5% in HP infection group and 43.8% in without HP infection group, as well as those of hMLH1 were 86.4% and 96.9%, there were no significant differences between the groups. In gastritic mucosa, the positive rate of hMSH2 expression was 38.5% in HP infection group and 50.5% in HP-negative group, as well as those of hMLH1 were 88.5% and 91.7%; there was no significant difference between the groups. CONCLUSION: The expression of hMSH2 is associated with carcinogenesis of stomach cancer, and its high expression may be a potential marker of stomach cancer; HP infection inducing low expression of hMSH2 and hMLH1 may be one of molecular mechanisms by which HP infection leads to stomach cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Capillary electrophoresis with end-column amperometric detection of urinary 8-hydroxy-2'-deoxyguanosine.

Urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) is an excellent marker of oxidative DNA damage. Until now, urinary 8OHdG has been measured by high-performance liquid chromatography with electrochemical detection. A simple and sensitive method for the analysis of urinary 8OHdG by capillary electrophoresis with end-column amperometric detection has been developed in our laboratory. A single-step solid-phase extraction procedure was optimized and used for extracting 8OHdG from human urine. To improve the sensitivity of this method, a new focusing technique based on a dynamic pH junction was used. The limit of detection was 20 nM (signal-to-noise ratio S/N = 3), the linear range was 50 nM-10 microM, and the correlation coefficient was better than 0.999. The relative standard deviation (RSD) was found to be 0.57% for migration time, and 4.79% for peak current. To show the usefulness of the method, the urinary concentration of 8OHdG in nine healthy persons and ten cancer patients was determined. The urinary concentration of 8OHdG in cancer patients was significantly higher than that in healthy persons.

Biomarkers↗

PubMed2003

[Significance of urinary nucleosides in diagnosis of gastric carcinoma].

BACKGROUND & OBJECTIVE: It was reported that urinary modified nucleosides with abnormally high amounts were found in many cancer patients. This study was designed to investigate the usefulness of urinary nucleosides in the diagnosis of gastric carcinoma. METHODS: The concentrations of 15 kinds of urinary nucleosides from 50 healthy persons and 48 patients with gastric carcinoma were determined by high-performance liquid chromatography (HPLC). Of 48 patients with gastric carcinoma, 25 underwent serum CEA examination. RESULTS: The average levels of 14 kinds of urinary nucleosides, m5U excepted, from patients with gastric carcinoma were higher than those from health persons (P< 0.05). Pseu 22.91+/-4.90, 34.87+/-21.41; U 0.34+/-0.32, 0.62+/-0.82; A 0.58+/-0.16, 0.96+/-0.75; C 0.17+/-0.15,0.24+/-0.19; m5U 0.03+/-0.07,0.07+/-0.06; I 0.26+/-0.10, 0.43+/-0.36; m1I 1.34+/-0.34, 2.44+/-1.39; ac4C 0.75+/-0.24, 1.08+/-0.72; G 0.09+/-0.04, 0.14+/-0.10; X 1.20+/-0.42, 1.90+/-1.09; m2G 0.61+/-0.16, 1.00+/-0.69; m6A 0.04+/-1.13, 0.07+/-0.08; m1A 2.26+/-0.56, 3.71+/-2.21; m22G 1.34+/-0.27, 2.25+/-1.39; m1G 0.80+/-0.25, 1.41+/-0.86. The level of nucleoside I was positively correlated with the tumor size (P< 0.05). The level of nucleoside X was positively correlated with lymph node metastasis (P< 0.05). Using the concentrations of 15 nucleosides as the data vectors, principal component analysis was applied to classify gastric cancer patients and normal adults, 63%(30/48) of cancer patients were correctly classified, in which the identification rate was higher than that of CEA method (12%). CONCLUSION: Urinary modified nucleoside increased in the patients with gastric carcinoma, and it may be helpful in the diagnosis of gastric carcinoma.

Adult↗

PubMed2002

Study of urinary nucleosides as biological marker in cancer patients analyzed by micellar electrokinetic capillary chromatography.

Thirteen normal and modified nucleosides, primarily degradation products of transfer ribonucleic acid (tRNA), were evaluated as potential tumor markers for cancer patients. Their urinary concentrations were determined by means of micellar electrokinetic capillary chromatography (MEKC) in the urine from 54 healthy adults and 70 cancer patients, then quantitatively expressed as a function of creatinine excretion. It was found that urinary nucleosides for cancer patients were on the average significantly higher than those for healthy controls, however, no significant differences were found between male and female or between different ages. Based on 13 urinary nucleoside concentrations, principal component analysis (PCA) could be used to classify 72% of cancer patients from the healthy controls. The present study shows that the precise measurement of urinary nucleosides by MEKC in combining with PCA technique may provide a clinically useful approach for diagnosis of cancer.

Adult↗