AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male...AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice. METHODS: Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SC/D mice. The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group reo ceived i.v. injections of N-desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline (100 μL) twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluo ated histologically for metastasis under microscope. Intratumoral microvessel density (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SC/D mice was detected by real time PCR. RESULTS: The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group (P 〈 0.05). MVD was 8.0 ± 3.1 in normal saline group and 4.3 ± 1.8 in N-desulfated heparin group (P 〈 0.05). VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated hepa- rin treated group (90% vs 20%, P 〈 0.05). VEGF mRNA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group (Ct value 19.51 ± 1.01 vs 22.55± 1.36, P 〈 0.05). N-desulfated heparin significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding occurred in N-desulfated heparin group. CONCLUSION: N-desulfated heparin can inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious anticoagulant activity.展开更多
Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mu...Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary 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 clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-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 cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P<0.05), but notwith differentiation or growth pattern of gastric cancer (P>0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P<0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P>0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P<0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.展开更多
To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biologic...To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biological expression of rhIL-18 was tested by RT-PCR and ELISA method;nude mice were injected with Bcap37 cell with or without the hIL-18 gene.The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth.These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine;the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity.The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.展开更多
MicroRNAs (miRNAs) are a class of non-coding RNAs that are believed to have a significant role in tumorigenesis and cancer metastasis. Cancer stem cells play a major role in tumor recurrence, metastasis, and drug re...MicroRNAs (miRNAs) are a class of non-coding RNAs that are believed to have a significant role in tumorigenesis and cancer metastasis. Cancer stem cells play a major role in tumor recurrence, metastasis, and drug resistance. Research has shown that miRNAs can promote or inhibit the sternness of cancer stem cells and regulate the differentiation and self-renewal of cancer stem cells. In this article, the phenotype and regulatory mechanisms of miRNAs in cancer stem cells will be described, together with an explanation of their potential role in tumor diagnosis and treatment.展开更多
基金Supported by the Scientific Foundation of Shanghai Public Health Administration, No.034045
文摘AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice. METHODS: Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SC/D mice. The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group reo ceived i.v. injections of N-desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline (100 μL) twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluo ated histologically for metastasis under microscope. Intratumoral microvessel density (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SC/D mice was detected by real time PCR. RESULTS: The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group (P 〈 0.05). MVD was 8.0 ± 3.1 in normal saline group and 4.3 ± 1.8 in N-desulfated heparin group (P 〈 0.05). VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated hepa- rin treated group (90% vs 20%, P 〈 0.05). VEGF mRNA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group (Ct value 19.51 ± 1.01 vs 22.55± 1.36, P 〈 0.05). N-desulfated heparin significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding occurred in N-desulfated heparin group. CONCLUSION: N-desulfated heparin can inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious anticoagulant activity.
文摘Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary 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 clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-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 cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P<0.05), but notwith differentiation or growth pattern of gastric cancer (P>0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P<0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P>0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P<0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.
文摘To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biological expression of rhIL-18 was tested by RT-PCR and ELISA method;nude mice were injected with Bcap37 cell with or without the hIL-18 gene.The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth.These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine;the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity.The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.
文摘MicroRNAs (miRNAs) are a class of non-coding RNAs that are believed to have a significant role in tumorigenesis and cancer metastasis. Cancer stem cells play a major role in tumor recurrence, metastasis, and drug resistance. Research has shown that miRNAs can promote or inhibit the sternness of cancer stem cells and regulate the differentiation and self-renewal of cancer stem cells. In this article, the phenotype and regulatory mechanisms of miRNAs in cancer stem cells will be described, together with an explanation of their potential role in tumor diagnosis and treatment.