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Research paper thumbnail of Correlations between Cyclooxygenase-2 Expression and Angiogenic Factors in Primary Tumors and Liver Metastases in Colorectal Cancer

Japanese Journal of Clinical Oncology, 2007

Background: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and se... more Background: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer. Methods: Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD. Results: The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P ¼ 0.005, rs ¼ 0.428), VEGF-A (P ¼ 0.039, rs ¼ 0.314), TP (P ¼ 0.005, rs ¼ 0.422) and MVD (P ¼ 0.046, rs ¼ 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P ¼ 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P ¼ 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P ¼ 0.247; P ¼ 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P ¼ 0.033) as well as in primary tumors (P ¼ 0.008). Conclusion: The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstretaed here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.

Research paper thumbnail of Coexpression of VEGF-C and Cox-2 in Human Colorectal Cancer and its Association With Lymph Node Metastasis

Diseases of the Colon & Rectum, 2006

Several lines of experimental evidence indicated that over-expression of vascular endothelial gro... more Several lines of experimental evidence indicated that over-expression of vascular endothelial growth factor-C and cyclooxygenase-2 genes promotes angiogenesis and lymphangiogenesis, both of which are essential for the growth and spreading of tumor cells. This study was designed to evaluate the coexpression of vascular endothelial growth factor-C and cyclooxygenase-2 in human colorectal carcinoma to determine their relationships and correlations with lymph node metastasis and prognosis. Tissue samples of primary tumors and metastatic lymph nodes from 150 patients undergoing intentionally curative surgical resections for colorectal adenocarcinoma were immunohistochemically examined for vascular endothelial growth factor-C, cyclooxygenase-2, and CD34 expressions. Then, we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time. The positivity rate of vascular endothelial growth factor-C and cyclooxygenase-2 in the primary tumor was 68 and 72.7 percent, respectively, and in the metastatic lymph nodes was 93.3 and 80 percent, respectively. A significant correlation was found between the expression scores of vascular endothelial growth factor-C and cyclooxygenase-2 (P < 0.0001), and both also were correlated to microvessels density and several clinicopathologic parameters, including primary tumor size, lymph node metastasis, lymphatic invasion, and TNM stage. Patients with vascular endothelial growth factor-C-positive and/or cyclooxygenase-2-positive tumors had a significant shorter survival time than those with negative tumors did. However, in a multivariate analysis, only cyclooxygenase-2 expression was recognized as an independent prognostic factor (P = 0.0412; relative risk ratio, 3.067; 95 percent confidence interval, 1.046-8.994). These data show that in human colorectal carcinoma, vascular endothelial growth factor-C and cyclooxygenase-2 are coexpressed and significantly associated with lymph node metastasis and prognosis.

Research paper thumbnail of Benign schwannoma of the pancreas

American Journal of Roentgenology, 1992

Research paper thumbnail of Expression of 5Lipoxygenase in human colorectal cancer

AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens... more AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens in order to determine its clinicopathologic significance in human tumorigenesis. METHODS: The relative quantity of 5-Lox mRNA in paired 91 colorectal tumor and adjacent normal mucosa samples was determined by real time quantitative PCR. Additionally, the expression of 5-Lox and cyclooxygenase (Cox)-2 proteins was also examined using

Research paper thumbnail of Cyclooxygenase-2 Expression: A Significant Prognostic Indicator for Patients With Colorectal Cancer

Clinical Cancer Research, 2004

Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carc... more Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated. Experimental Design: Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed. Results: Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2-positive tumors had a significant shorter survival time than those with negative tumors did (P ‫؍‬ 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P ‫؍‬ 0.0103; relative risk 4.114; 95% confidence interval, 1.397-12.120). Cox-1 status had no statistically effect on patient survival time. Conclusions: Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.

Research paper thumbnail of Correlations between Cyclooxygenase-2 Expression and Angiogenic Factors in Primary Tumors and Liver Metastases in Colorectal Cancer

Japanese Journal of Clinical Oncology, 2007

Background: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and se... more Background: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer. Methods: Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD. Results: The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P ¼ 0.005, rs ¼ 0.428), VEGF-A (P ¼ 0.039, rs ¼ 0.314), TP (P ¼ 0.005, rs ¼ 0.422) and MVD (P ¼ 0.046, rs ¼ 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P ¼ 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P ¼ 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P ¼ 0.247; P ¼ 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P ¼ 0.033) as well as in primary tumors (P ¼ 0.008). Conclusion: The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstretaed here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.

Research paper thumbnail of Coexpression of VEGF-C and Cox-2 in Human Colorectal Cancer and its Association With Lymph Node Metastasis

Diseases of the Colon & Rectum, 2006

Several lines of experimental evidence indicated that over-expression of vascular endothelial gro... more Several lines of experimental evidence indicated that over-expression of vascular endothelial growth factor-C and cyclooxygenase-2 genes promotes angiogenesis and lymphangiogenesis, both of which are essential for the growth and spreading of tumor cells. This study was designed to evaluate the coexpression of vascular endothelial growth factor-C and cyclooxygenase-2 in human colorectal carcinoma to determine their relationships and correlations with lymph node metastasis and prognosis. Tissue samples of primary tumors and metastatic lymph nodes from 150 patients undergoing intentionally curative surgical resections for colorectal adenocarcinoma were immunohistochemically examined for vascular endothelial growth factor-C, cyclooxygenase-2, and CD34 expressions. Then, we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time. The positivity rate of vascular endothelial growth factor-C and cyclooxygenase-2 in the primary tumor was 68 and 72.7 percent, respectively, and in the metastatic lymph nodes was 93.3 and 80 percent, respectively. A significant correlation was found between the expression scores of vascular endothelial growth factor-C and cyclooxygenase-2 (P < 0.0001), and both also were correlated to microvessels density and several clinicopathologic parameters, including primary tumor size, lymph node metastasis, lymphatic invasion, and TNM stage. Patients with vascular endothelial growth factor-C-positive and/or cyclooxygenase-2-positive tumors had a significant shorter survival time than those with negative tumors did. However, in a multivariate analysis, only cyclooxygenase-2 expression was recognized as an independent prognostic factor (P = 0.0412; relative risk ratio, 3.067; 95 percent confidence interval, 1.046-8.994). These data show that in human colorectal carcinoma, vascular endothelial growth factor-C and cyclooxygenase-2 are coexpressed and significantly associated with lymph node metastasis and prognosis.

Research paper thumbnail of Benign schwannoma of the pancreas

American Journal of Roentgenology, 1992

Research paper thumbnail of Expression of 5Lipoxygenase in human colorectal cancer

AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens... more AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens in order to determine its clinicopathologic significance in human tumorigenesis. METHODS: The relative quantity of 5-Lox mRNA in paired 91 colorectal tumor and adjacent normal mucosa samples was determined by real time quantitative PCR. Additionally, the expression of 5-Lox and cyclooxygenase (Cox)-2 proteins was also examined using

Research paper thumbnail of Cyclooxygenase-2 Expression: A Significant Prognostic Indicator for Patients With Colorectal Cancer

Clinical Cancer Research, 2004

Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carc... more Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated. Experimental Design: Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed. Results: Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2-positive tumors had a significant shorter survival time than those with negative tumors did (P ‫؍‬ 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P ‫؍‬ 0.0103; relative risk 4.114; 95% confidence interval, 1.397-12.120). Cox-1 status had no statistically effect on patient survival time. Conclusions: Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.