AIM： To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells （MDSC） in human colorectal carcinoma （CRC）. METHODS： Samples of peripheral blood and tumor tis- sue from 49 C...AIM： To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells （MDSC） in human colorectal carcinoma （CRC）. METHODS： Samples of peripheral blood and tumor tis- sue from 49 CRC patients were analyzed. Mononuclear cells were isolated by FicolI-Hypaque density gradient centrifugation and were subjected to a flow cytometry- based immunophenotypic analysis. RESULTS： A considerable increase in the percentage of CD33＋HLA-DR MDSCs was observed in the periph- eral blood （1.89% ：1= 0.75%） and tumor tissues （2.99%±1.29%） of CRC patients as compared with that in theperipheral blood of healthy controls （0.54%±0.35%）. This expanded CD33＋HLA-DR subset exhibited imma- ture myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Fur- ther studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis （P = 0.023）, whereas that in tumor tissues was cor- related with nodal/distant metastasis （P = 0.016/P = 0.047） and tumor stage （P = 0.028）, suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION： Characterization of MDSCs in CRC sug- gests the clinical significance of circulating and tumor- infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.展开更多
AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density ...AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density （LVD） and microvessel density （MVD） in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor （vWF）. RESULTS： （1） The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without （P 〈 0.001）. （2） For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. （3） Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. （4） Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient＇s poor disease-free survival （Puni 〈 0.05）; multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer, CONCLUSION： D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, coaccounting of LVD and MVD might be a useful prognostic factor in SCRC.展开更多
AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1)αexpression in human colorectal carcinomas. METHODS: The tissue microa...AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1)αexpression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1αwas detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1αexpression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (X2 = 43.166, P < 0.01; X2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (X2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (X2 = 18.141, P < 0.01), invasive depth (X2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1αwas correlated with infiltrating depth (X2 = 4.397, P < 0.05), Duke's staging (X2= 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1αin colorectal carcinoma is correlated with the biological character MVD.展开更多
目的探讨结直肠癌患者中多配体蛋白聚糖-1(Syndecan-1)与表皮生长因子受体(EGFR)表达及鼠类肉瘤病毒癌基因(KRAS)突变的关系。方法选择原发性结直肠癌标本160例,结肠部肿瘤112例,直肠部肿瘤48例;病理类型为腺癌156例,其它病理类型4例。...目的探讨结直肠癌患者中多配体蛋白聚糖-1(Syndecan-1)与表皮生长因子受体(EGFR)表达及鼠类肉瘤病毒癌基因(KRAS)突变的关系。方法选择原发性结直肠癌标本160例,结肠部肿瘤112例,直肠部肿瘤48例;病理类型为腺癌156例,其它病理类型4例。利用免疫组化法检测组织标本中Syndecan-1和EGFR的表达情况,运用直接测序法检测组织标本中KRAS基因外显子2第12、第13位密码子的突变状态。采用Spearman相关分析Syndecan-1的表达与EGFR表达及KRAS基因突变的关系。结果肿瘤标本中Syndecan-1表达阳性41例,主要位于细胞膜20例,主要位于细胞浆16例,细胞膜与细胞浆同时表达5例。EGFR在结直肠癌中的阳性表达率69.4%,所有结直肠癌患者中发生KRAS突变率为37.5%。Synd e c a n-1的表达在肿瘤区域淋巴结有无转移、有无远处转移中差异均无统计学意义(均P>0.05)。Syndecan-1的表达与EGFR表达呈显著相关(r=1.488,P<0.01),而与KRAS状态无相关性(r=9.278,P>0.05)。结论 Syndecan-1的表达可能对结直肠癌患者的进展及预后判断有一定价值。展开更多
文摘AIM： To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells （MDSC） in human colorectal carcinoma （CRC）. METHODS： Samples of peripheral blood and tumor tis- sue from 49 CRC patients were analyzed. Mononuclear cells were isolated by FicolI-Hypaque density gradient centrifugation and were subjected to a flow cytometry- based immunophenotypic analysis. RESULTS： A considerable increase in the percentage of CD33＋HLA-DR MDSCs was observed in the periph- eral blood （1.89% ：1= 0.75%） and tumor tissues （2.99%±1.29%） of CRC patients as compared with that in theperipheral blood of healthy controls （0.54%±0.35%）. This expanded CD33＋HLA-DR subset exhibited imma- ture myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Fur- ther studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis （P = 0.023）, whereas that in tumor tissues was cor- related with nodal/distant metastasis （P = 0.016/P = 0.047） and tumor stage （P = 0.028）, suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION： Characterization of MDSCs in CRC sug- gests the clinical significance of circulating and tumor- infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.
基金Supported by the a grant from the Sciences and Techni-que Development Foundation of Shanghai, No. 064119512, 024119010
文摘AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density （LVD） and microvessel density （MVD） in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor （vWF）. RESULTS： （1） The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without （P 〈 0.001）. （2） For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. （3） Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. （4） Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient＇s poor disease-free survival （Puni 〈 0.05）; multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer, CONCLUSION： D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, coaccounting of LVD and MVD might be a useful prognostic factor in SCRC.
基金the Science Department of Qingdao City, No.03-1-NY-14-2
文摘AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1)αexpression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1αwas detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1αexpression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (X2 = 43.166, P < 0.01; X2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (X2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (X2 = 18.141, P < 0.01), invasive depth (X2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1αwas correlated with infiltrating depth (X2 = 4.397, P < 0.05), Duke's staging (X2= 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1αin colorectal carcinoma is correlated with the biological character MVD.
文摘目的探讨结直肠癌患者中多配体蛋白聚糖-1(Syndecan-1)与表皮生长因子受体(EGFR)表达及鼠类肉瘤病毒癌基因(KRAS)突变的关系。方法选择原发性结直肠癌标本160例,结肠部肿瘤112例,直肠部肿瘤48例;病理类型为腺癌156例,其它病理类型4例。利用免疫组化法检测组织标本中Syndecan-1和EGFR的表达情况,运用直接测序法检测组织标本中KRAS基因外显子2第12、第13位密码子的突变状态。采用Spearman相关分析Syndecan-1的表达与EGFR表达及KRAS基因突变的关系。结果肿瘤标本中Syndecan-1表达阳性41例,主要位于细胞膜20例,主要位于细胞浆16例,细胞膜与细胞浆同时表达5例。EGFR在结直肠癌中的阳性表达率69.4%,所有结直肠癌患者中发生KRAS突变率为37.5%。Synd e c a n-1的表达在肿瘤区域淋巴结有无转移、有无远处转移中差异均无统计学意义(均P>0.05)。Syndecan-1的表达与EGFR表达呈显著相关(r=1.488,P<0.01),而与KRAS状态无相关性(r=9.278,P>0.05)。结论 Syndecan-1的表达可能对结直肠癌患者的进展及预后判断有一定价值。
