OBJECTIVETo study the thymidine phosphorylase (TP) expression in different types of cancer and its correlation with tumor microvessel density (MVD).

METHODSThe expression of TP and MVD was detected by immunohistochemistry method. In a series of 251 cancer patients there were 48 patients with gastric cancer, 53 with colorectal cancer, 47 with breast cancer, 56 with cervical cancer, 47 with lung cancer. Normal gastric (n = 25), colorectal (n = 25), cervical (n = 17) and lung (n = 25) tissues around the cancer were also examined.

RESULTSThe TP expression rate was 64.6% in gastric cancer, 67.9% in colorectal cancer, 80.9% in breast cancer, 82.1% in cervical cancer, and 63.8% in lung cancer, which was significantly higher than that in normal tissues (P = 0.0000). TP expression was positively correlated with MVD in gastric, colorectal, breast, and cervical cancers. The correlation was not statistically significant in lung cancer.

CONCLUSIONThis study indicates that TP overexpression in cancer may be associated with tumor angiogenesis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; blood supply ; enzymology ; Colorectal Neoplasms ; blood supply ; enzymology ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; enzymology ; Thymidine Phosphorylase ; metabolism ; Uterine Cervical Neoplasms ; blood supply ; enzymology

OBJECTIVETo investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesis and progression of gastric cancer.

METHODSWe studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and primary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopathological features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.

RESULTSMMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113), less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancer was positively correlated with tumor size, invasive depth, metastasis and TNM staging (P<0.05), but not with differentiation or growth pattern of gastric cancer (P>0.05). Positive correlation of mean MVD with tumor size, invasive depth, metastasis and TNM staging was found (P<0.05), despite no relationship between mean MVD and differentiation of gastric cancer (P>0.05). Mean MVD was dependent on MMP-7 expression in gastric cancer (P<0.05).

CONCLUSIONUpregulated expression of MMP-7 played an important role in carcinogenesis and progression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 expression could be regarded as an effective and objective marker to reflect the biological behaviors of gastric cancer.

Biomarkers, Tumor ; metabolism ; Humans ; Lymphatic Metastasis ; Matrix Metalloproteinase 7 ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; pathology

OBJECTIVETo investigate the expression of transcription factor SP1, vascular endothelial growth factor(VEGF) and CD34 in serosa-infiltrating gastric cancer and their relationship with biological behavior and survival rate.

METHODSImmunohistochemical technique was used to detect the expression of SP1, VEGF and CD34(described by microvessel density, MVD) in 68 specimens with serosa-infiltrating gastric cancer.

RESULTSThe positive expression rates of SP1 and VEGF in serosa-infiltrating gastric cancer were 50.0% and 52.9% respectively. In positive SP1 specimens, the positive rate of VEGF(73.5%) was significantly higher than that of negative SP1 specimens (32.4%, chi(2)=11.57, P=0.01). The mean tumor MVD was correlated with the expression levels of SP1 and VEGF(P<0.01). There was a significant correlation of the SP1 expression with tumor size and growth pattern(P =0.01). The expression levels of VEGF and MVD were correlated with Borrmann types, cell differentiation, metastatic lymph nodes and growth pattern(P<0.01). Univariate analysis revealed that SP1 and VEGF expression, MVD, Borrmann types, lymph node metastasis, tumor size and growth pattern were significant prognostic factors related to survival time. Multivariate analysis showed that SP1 expression, MVD and growth pattern were independently prognostic factors of poor survival.

CONCLUSIONSThe activation of SP1 contributes to angiogenesis and metastasis in gastric cancer through the up-regulation of VEGF. SP1, VEGF and MVD may serve as valuable indicators of biological behavior of gastric cancer. SP1 protein expression is not related with the number of metastatic lymph nodes. SP1 expression and MVD may serve as valuable indicators of prognosis in gastric carcinoma.

Adult ; Aged ; Antigens, CD34 ; metabolism ; Female ; Humans ; Male ; Microcirculation ; Middle Aged ; Prognosis ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUND/AIMS: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a recently clarified tumor suppressor gene located in 10q23.3. Alterations of this gene are associated with tumor progression and unfavorable outcome in various human cancers. Recently, PTEN has a possible role in angiogenesis by modulating angiogenic factor including vascular endothelial growth factor (VEGF). The aim of this study was to investigate the roles of PTEN and VEGF status for angiogenesis in human gastric cancer. METHODS: We conducted an immunohistochemical investigation of PTEN and VEGF expression in 90 cases of paraffin section obtained from gastric cancer patients undergone surgical treatment. RESULTS: Negative expression of PTEN and positive expression of VEGF in gastric cancer tissues, were demonstrated in 40.0% and 77.8% of cases, respectively. However, no significant correlation was found between PTEN, VEGF expression and various clinicopathological parameters. PTEN expression did not correlate significantly with VEGF expression (p=0.301). High microvessel density (MVD) was significantly associated with lymph node metastasis and poor survival (p=0.014, 0.011, respectively). The mean MVD value of PTEN negative tumors was 90.4+/-43.0 and significantly higher than that of PTEN positive tumors (p=0.028). The mean MVD value of VEGF positive tumors was 86.4+/-36.7 and significantly higher than that of VEGF negative tumors (p=0.002). The mean MVD value of PTEN negative and VEGF positive tumors was 98.0+/-42.2, and significantly higher than those of the others. CONCLUSIONS: These results suggest that loss of PTEN expression may play a critical role in tumor progression and metastasis by stimulating tumor angiogenesis in human gastric cancer.
Adult ; Aged ; Carcinoma/*blood supply/metabolism/mortality/secondary ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Male ; Microcirculation/pathology ; Middle Aged ; Neovascularization, Pathologic/*metabolism ; PTEN Phosphohydrolase/*metabolism ; Stomach Neoplasms/*blood supply/metabolism/mortality ; Survival Rate ; Vascular Endothelial Growth Factor A/metabolism

OBJECTIVETo investigate whether correlation exists between mRNA expression of IGF-II and hepatocyte growth factor (HGF) and tumor progression and prognosis in gastric cancer.

METHODSIn situ hybridization technique was used to examine mRNA expression of IGF-II and HGF, and immunohistochemical technique was used to examine protein expression of CD34 in 105 specimens of gastric carcinoma.

RESULTSIn situ hybridization revealed that the positive rates of IGF-II mRNA and HGFmRNA were 49.5% and 57.1%, respectively. In stage T3-T4 cases, positive mRNA expression rates of IGF-II and HGF, the frequencies of vessel invasion, lymph node metastasis and distant metastasis were significantly higher than those in stage T1-T2 cases. The mean microvascular density (MVD) in stage T3-T4 tumors, vessel invasion, lymph node metastasis and distant metastasis were significantly more frequent than those in stage T1-T2 tumors. The mean MVD in tumors with positive IGF-II and HGF expressions was significantly higher than that in tumors without IGF-II and HGF expression. There were positive correlations between MVD and expression of IGF-II and HGF. The mean survival time and 5-year survival rate in cases with positive IGF-II and HGF expression and MVD value > or = 39.5 were significantly shorter those that in cases with negative IGF-II and HGF expression and MVD value < 39.5.

CONCLUSIONIGF-II and HGF promote angiogenesis in gastric cancer, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.

Adenocarcinoma, Papillary ; blood supply ; metabolism ; secondary ; Adult ; Aged ; Carcinoma, Ductal ; blood supply ; metabolism ; secondary ; Carcinoma, Signet Ring Cell ; blood supply ; metabolism ; secondary ; Disease Progression ; Female ; Hepatocyte Growth Factor ; biosynthesis ; genetics ; Humans ; Insulin-Like Growth Factor II ; biosynthesis ; genetics ; Liver Neoplasms ; blood supply ; metabolism ; secondary ; Lymphatic Metastasis ; Male ; Microcirculation ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Peritoneal Neoplasms ; blood supply ; metabolism ; secondary ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Survival Rate

OBJECTIVETo investigate the regulatory effect of jianpi jiedu Recipe (JJR) on the microvessel density (MVD) and cyclooxygenase-2 (COX-2) in long-term infection of Helicobacter pylori induced gastric cancer of C57BL/6 mice, thus providing experimental bases for its treatment of the H. pylori correlated gastropathy.

METHODSC57BL/6 mouse gastric cancer model induced by H. pylori infection was established by gastrogavage of H. pylori standard strain SS1. Mice were divided into the control group, the model group, low dose JJR group, and the high dose JJR group, 40 in each group. Mice were sacrificed after 72-week medication. Changes of the gastric mucosa MVD of mice in each group were detected by immunohistochemical method. Expressions of COX-2 mRNA and protein were detected by Real-time fluorescent quantitative polymerase chain reaction and immunohistochemical method.

RESULTSThe occurrence rate of gastric cancer in the control group, the model group, the low dose JJR group, and the high dose JJR group was 0, 22.2%, 11.1%, and 10.0%, respectively. The gastric mucosa MVD (number/cm2) of mice in each group was 2.50 +/- 1.54, 18.56 +/- 2.62, 14.61 +/- 3.60, and 7.39 +/- 1.75, respectively. The gastric mucosa MVD in the model group increased more obviously than that in the control group (P < 0.01). The gastric mucosa MVD significantly decreased in the low dose JJR group and the high dose JJR group (P < 0.01). Expressions of COX-2 mRNA and protein in the model group increased more obviously than those in the control group (P < 0.01). Low dose JJR and high dose JJR could decrease their expressions in a dose dependent manner.

CONCLUSIONSH. pylori infection could increase the gastric mucosa MVD of C57BL/6 mice and promote COX-2 expressions, which might play a promoting effect in the incidence of H. pylori induced gastric cancer. JJR could decrease the gastric mucosa MVD and inhibit COX-2 expressions, which might be one of its important mechanisms of preventing and treating gastric cancer.

Animals ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gastric Mucosa ; blood supply ; drug effects ; metabolism ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; microbiology

Angiogenesis, formation of new microvessels providing oxygen and nutrient supply, is essential for tumor growth. It is dependent on the production of angiogenic growth factors by tumor cells. Angiopoietin 1 (Ang-1) and 2 (Ang-2) and their common receptor, Tie2, are thought to be critical regulators of tumor angiogenesis. We examined expression of Ang-1, Ang-2, and their common receptor Tie2 mRNAs and proteins in gastric cancers using in situ hybridization and immunohistochemistry. We also investigated the relationship between their expression and differentiation of cancer cells, lymph node metastasis, tumor size, depth of cancer cell invasion, TNM staging and microvessel density (MVD). The expression of Ang-1, Ang-2, and Tie2 mRNA in cancer cells significantly correlated with the MVD (p<0.001, <0.001 and =0.019, respectively). Ang-1 and Tie2 positivity correlated with advanced gastric cancers (p<0.05) and larger cancers had higher positive rates of Ang-1, Ang-2, and Tie2 mRNA expression (p<0.001, =0.010 and =0.039, respectively). Significant positive correlations were also found between mRNA expression of Tie2 and those of Ang-1 and Ang-2 (p<0.01 and <0.001, respectively). These findings indicate that the expression of Ang-1 and Ang-2 is important for tumor angiogenesis, and suggest a possible role of autocrine/paracrine function of angiopoietin/Tie2 system in gastric cancer progression.
Stomach Neoplasms/blood supply/*genetics/*metabolism/pathology ; Receptor, TIE-2/*genetics/*metabolism ; RNA, Neoplasm/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Neovascularization, Pathologic ; Middle Aged ; Male ; In Situ Hybridization ; Immunohistochemistry ; Humans ; Gene Expression ; Female ; Carcinoma, Signet Ring Cell/blood supply/genetics/metabolism/pathology ; Angiopoietin-2/*genetics/*metabolism ; Angiopoietin-1/*genetics/*metabolism ; Aged ; Adult ; Adenocarcinoma/blood supply/genetics/metabolism/pathology

OBJECTIVETo investigate the expression of Versican in gastric carcinoma and its relationship with tumor angiogenesis.

METHODSProtein expression of Versican, vascular endothelial growth factor and CD34 was evaluated by immunohistochemistry (EliVision method) in 80 cases of gastric carcinoma and 30 samples of normal gastric tissue.

RESULTSThere were statistically significant differences in the expression of Versican, vascular endothelial growth factor and CD34 between gastric carcinoma and normal gastric tissue (P < 0.05). The expression of Versican was seen mainly in fibroblasts of the tumor and was correlated with tumor differentiation, clinical stage and lymph node metastasis (P < 0.05), whereas vascular endothelial growth factor was primarily seen in the cytoplasm of the tumor cells and correlated with tumor differentiation, clinical stage, Lauren classification and lymph node metastasis (P < 0.05). MVD was correlated with tumor differentiation, clinical stage, Lauren classification, depth of tumor invasion and lymph node metastasis (P < 0.05). In addition, positive correlation of Versican and VEGF protein expression was found in tumor cells (r = 0.467, P < 0.01).

CONCLUSIONThe expression of both Versican and vascular endothelial growth factor is closely associated with tumor angiogenesis in gastric carcinoma.

Antigens, CD34 ; metabolism ; Fibroblasts ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Proteins ; metabolism ; Neovascularization, Pathologic ; Prognosis ; Stomach ; metabolism ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Versicans ; metabolism

BACKGROUND: Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer. METHODS: In this study, we conducted an immunohistochemical investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. RESULTS: High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor. CONCLUSION: VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.
Adult ; Aged ; Endothelial Growth Factors/*biosynthesis ; Female ; Human ; Immunohistochemistry ; Male ; Middle Aged ; *Neovascularization, Pathologic ; Protein p53/*biosynthesis ; Stomach Neoplasms/*blood supply/metabolism/pathology ; Support, Non-U.S. Gov't

OBJECTIVETo investigate mRNA expression of integrin beta3 in gastric carcinoma, its correlation with microvascular density (MVD), growth-pattern, invasion, metastasis and prognosis.

METHODSIn situ hybridization and immunohistochemistry techniques were used to study the expression of integrin beta3 mRNA and CD34 protein in 105 gastric carcinoma specimens.

RESULTSIn situ hybridization revealed a 30% (6/20) positive rate of integrin beta3 mRNA in non-tumor gastric mucosa, which was significantly lower than that of the gastric cancer group (61.0%, 64/105, chi(2) = 8.85, P = 0.037); In infiltrating type cases (70.2%, 40/57), stage III - IV (72.1%, 44/61), lymphatic metastasis (68.6%, 48/70) and distant metastasis (85.7%, 36/42), the positive expression rates were significantly higher than those of the expanding type (chi(2) = 14.97, P = 0.002), stage I - II (chi(2) = 15.21, P = 0.015), non-lymphatic metastasis (chi(2) = 17.89, P = 0.025) and non-distant metastasis (chi(2) = 20.22, P = 0.005; chi(2) = 21.35, P = 0.035); its mean MVD was also significantly higher than that of the expanding type (t = 10.105, P = 0.001), stage I approximately II (t = 5.961, P = 0.001), non-lymphatic metastasis (t = 3.819, P = 0.01)and non-distant metastasis (t = 10.578, P = 0.001; t = 7.882, P = 0.001), respectively; The mean MVD (41.02 +/- 8.55)/0.72 mm(2) of the integrin beta3 mRNA positive expression group was significantly higher than (25.26 +/- 11.25)/0.72 mm(2) of the negative expression group. There was a positive relation between MVD and integrin beta3 mRNA expression in the tumor (r(s) = 0.316, P = 0.001). The mean survival time in cases with positive integrin beta3 mRNA expression or MVD value >or= 39.5 was significantly shorter than that in cases with negative expression or MVD value < 39.5.

CONCLUSIONSIntegrin beta3 expression correlates with enhanced tumor angiogenesis and may play a role in the invasion and nodal metastasis of gastric carcinoma, therefore it may serve as a prognostic marker of gastric cancer.

Adult ; Aged ; Disease Progression ; Female ; Humans ; Integrin beta3 ; genetics ; Male ; Middle Aged ; Neovascularization, Pathologic ; etiology ; Prognosis ; RNA, Messenger ; analysis ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Survival Rate