AIM: To study the effect of TNP-470 on cell growth,proliferation and apoptosis in human colon cancer xenograftsin nude mice.METHODS: Human colon cancer xenografts weretransplanted into 20 nude mice. Mice were randomly...AIM: To study the effect of TNP-470 on cell growth,proliferation and apoptosis in human colon cancer xenograftsin nude mice.METHODS: Human colon cancer xenografts weretransplanted into 20 nude mice. Mice were randomly dividedinto two groups. TNP-470 treated group received TNP-470(30 mg/kg, s.c) every other day and the control groupreceived a sham injection of same volume saline solution.They were sacrificed after 4 weeks and their tumors wereprocessed for histological examination. The expression ofproliferating cell nuclear antigen (PCNA) in tumors wasdetected using immunohistochemical method with imageanalysis, and apoptosis in tumor cells was measured by TdT-mediated biotinyated-dUTP nick end labeling (TUNEL)staining.RESULTS: Comparing with controls, tumor growth wassignificantly inhibited in TNP-470 treated group, the inhibitoryrate being 54.4 %. Expression of PCNA in tumors of TNP-470 treated group (PI 54.32±11.47) was significantly lowerthan that of control group (PI 88.54+12.36), P＜0.01.Apoptosis index (AI) of TNP-470 treated group (18.95±1.71)was significantly higher than that of control group(7.26+1.44),P＜0.001, typical morphological change of apoptosis in tumorcells was observed in TNP-470 treated group.CONCLUSION: Besides the anti-angiogenic effects, TNP-470 can inhibit tumor growth by inhibiting the proliferationand inducing apoptosis of tumor cells.展开更多
AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastri...AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastric cancer, who had only one lymph node involved, were regarded retrospectively as patients with a possible sentinel node metastasis, and the distribution of these nodes were assessed. Thirteen cases with jumping metastases were further studied and followed up. RESULTS: The single nodal metastasis was found in the nearest perigastric nodal area in 65.1% (56/86) of the cases and in 19.8% (17/86) of the cases in a fairly remote perigastric area. Out of 19 middle-third gastric cancers,3 tumors at the lesser or greater curvatures had transverse metastases. There were also 15.1% (13/86) of patients with a jumping metastasis to N2-N3 nodes without N1 involved. Among them, the depth of invasion was mucosal (M) in 1 patient, submucosal (SM) in 2, proper-muscular (MP) in 4, subserosal (SS) in 5, and serosa-exposed (SE) in 1. Five of these patients died of gastric cancer recurrence at the time of this report within 3 years aftersurgery. CONCLUSION: These results suggest that nodal metastases occur in a random and multidirectional process in gastric cancer and that not every first metastatic node is located in the perigastric region near the primary tumor. The rate of “jumping metastasis” in gastric cancer is much higher than expected, which suggests that the blind examination of the nodal area close to the primary tumor can not be a reliable method to detect the SLN and that a extended lymph node dissection (ELND) should be performed if the preoperative examination indicates submucosal invasion.展开更多
AIM: To evaluate the killing effect of double suicide gene mediated by adenovirus and regulated under kinase domain insert containing receptor (KDR) promoter on human umbilical vein endothelial cells. METHODS: By PCR ...AIM: To evaluate the killing effect of double suicide gene mediated by adenovirus and regulated under kinase domain insert containing receptor (KDR) promoter on human umbilical vein endothelial cells. METHODS: By PCR technology, human KDR promoter gene, Escherichia coli(E. coli) cytosine deaminase (CD) gene and the herpes simple virus-thymidine kinase (TK) gene were cloned. Plasmid pKDR-CDglyTK was constructed with them. Then, a recombinant adenoviral plasmid pAdKDRCDglyTK was constructed in a 'two-step transformation protocol'. The newly constructed plasmids were transfected to 293 packaging cells to grow adenoviruses, which were further propagated and purified. Human umbilical vein endothelial cells (HUVEC) were infected with a different multiplicity of infection (MOI) of resultant recombinant adenovirus, the infection rate was measured with the aid of (GFP) expression. Infected cells were cultured in culture media containing different concentrations of (GCV) and/or 5-(FC), and the killing effects were measured.RESULTS: Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed, and they infected HUVEC cells efficiently. Our data indicated that the infection rate was relevant to MOI of recombinant adenoviruses. HUVEC cells infected with AdKDR-CDglyTK were highly sensitive to the prodrugs, their survival rate correlated to both the concentration of the prodrugs and the MOI of recombinant adenoviruses. Our data also indicated that the two prodrugs used in combination were much more effective on killing transgeneic cells than GCV or 5-FC used alone. CONCLUSION: Prodrug/KDR-CDglyTK system is effective on killing HUVEC cells, its killing effect correlates to the concentration of prodrugs and recombinant adenovirus' MOI. Combined use of the two prodrugs confers better killing effects on transgeneic cells.展开更多
基金the Natural Science Foundation of Guangdong Province,No.013072
文摘AIM: To study the effect of TNP-470 on cell growth,proliferation and apoptosis in human colon cancer xenograftsin nude mice.METHODS: Human colon cancer xenografts weretransplanted into 20 nude mice. Mice were randomly dividedinto two groups. TNP-470 treated group received TNP-470(30 mg/kg, s.c) every other day and the control groupreceived a sham injection of same volume saline solution.They were sacrificed after 4 weeks and their tumors wereprocessed for histological examination. The expression ofproliferating cell nuclear antigen (PCNA) in tumors wasdetected using immunohistochemical method with imageanalysis, and apoptosis in tumor cells was measured by TdT-mediated biotinyated-dUTP nick end labeling (TUNEL)staining.RESULTS: Comparing with controls, tumor growth wassignificantly inhibited in TNP-470 treated group, the inhibitoryrate being 54.4 %. Expression of PCNA in tumors of TNP-470 treated group (PI 54.32±11.47) was significantly lowerthan that of control group (PI 88.54+12.36), P＜0.01.Apoptosis index (AI) of TNP-470 treated group (18.95±1.71)was significantly higher than that of control group(7.26+1.44),P＜0.001, typical morphological change of apoptosis in tumorcells was observed in TNP-470 treated group.CONCLUSION: Besides the anti-angiogenic effects, TNP-470 can inhibit tumor growth by inhibiting the proliferationand inducing apoptosis of tumor cells.
基金Supported by the Natural Science Foundation of Guangdong Province,No.032204
文摘AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastric cancer, who had only one lymph node involved, were regarded retrospectively as patients with a possible sentinel node metastasis, and the distribution of these nodes were assessed. Thirteen cases with jumping metastases were further studied and followed up. RESULTS: The single nodal metastasis was found in the nearest perigastric nodal area in 65.1% (56/86) of the cases and in 19.8% (17/86) of the cases in a fairly remote perigastric area. Out of 19 middle-third gastric cancers,3 tumors at the lesser or greater curvatures had transverse metastases. There were also 15.1% (13/86) of patients with a jumping metastasis to N2-N3 nodes without N1 involved. Among them, the depth of invasion was mucosal (M) in 1 patient, submucosal (SM) in 2, proper-muscular (MP) in 4, subserosal (SS) in 5, and serosa-exposed (SE) in 1. Five of these patients died of gastric cancer recurrence at the time of this report within 3 years aftersurgery. CONCLUSION: These results suggest that nodal metastases occur in a random and multidirectional process in gastric cancer and that not every first metastatic node is located in the perigastric region near the primary tumor. The rate of “jumping metastasis” in gastric cancer is much higher than expected, which suggests that the blind examination of the nodal area close to the primary tumor can not be a reliable method to detect the SLN and that a extended lymph node dissection (ELND) should be performed if the preoperative examination indicates submucosal invasion.
基金Supported by the Natural Science Foundation of Guangdong Province, No. 013072and the 863 Program, No. 2001AA217171
文摘AIM: To evaluate the killing effect of double suicide gene mediated by adenovirus and regulated under kinase domain insert containing receptor (KDR) promoter on human umbilical vein endothelial cells. METHODS: By PCR technology, human KDR promoter gene, Escherichia coli(E. coli) cytosine deaminase (CD) gene and the herpes simple virus-thymidine kinase (TK) gene were cloned. Plasmid pKDR-CDglyTK was constructed with them. Then, a recombinant adenoviral plasmid pAdKDRCDglyTK was constructed in a 'two-step transformation protocol'. The newly constructed plasmids were transfected to 293 packaging cells to grow adenoviruses, which were further propagated and purified. Human umbilical vein endothelial cells (HUVEC) were infected with a different multiplicity of infection (MOI) of resultant recombinant adenovirus, the infection rate was measured with the aid of (GFP) expression. Infected cells were cultured in culture media containing different concentrations of (GCV) and/or 5-(FC), and the killing effects were measured.RESULTS: Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed, and they infected HUVEC cells efficiently. Our data indicated that the infection rate was relevant to MOI of recombinant adenoviruses. HUVEC cells infected with AdKDR-CDglyTK were highly sensitive to the prodrugs, their survival rate correlated to both the concentration of the prodrugs and the MOI of recombinant adenoviruses. Our data also indicated that the two prodrugs used in combination were much more effective on killing transgeneic cells than GCV or 5-FC used alone. CONCLUSION: Prodrug/KDR-CDglyTK system is effective on killing HUVEC cells, its killing effect correlates to the concentration of prodrugs and recombinant adenovirus' MOI. Combined use of the two prodrugs confers better killing effects on transgeneic cells.
