The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A...The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.展开更多
On day 3 of gestation, one uterine horn of fe-male pregnant mouse was injected intraluminally with 5 mL 0.1 mg/mL lactacystin, a specific inhibitor of ubiquitin-pro- teasome pathway (UPP), while the contralateral horn...On day 3 of gestation, one uterine horn of fe-male pregnant mouse was injected intraluminally with 5 mL 0.1 mg/mL lactacystin, a specific inhibitor of ubiquitin-pro- teasome pathway (UPP), while the contralateral horn served as control. Animals were sacrificed by cervical dislocation on day 5, 6, 7 of gestation, respectively. Then the number of implanted embryos in each uterine horn was calculated, and the expression of VEGF and its receptors was examined. The data showed that the number of implanted embryos was decreased significantly after treatment with lactacystin. The results of RT-PCR and Western blot indicated that expres-sion of VEGF and its receptors at mRNA and protein levels was significantly decreased in the treated uterus, meanwhile, the expression of HIF-1a (the a subunit of HIF, a transcrip-tional factor of VEGF) was reduced at both mRNA and pro-tein levels. These data suggested that the effect of UPP on VEGF expression was realized through regulating HIF-1a expression. In addition, UPP is likely to take part in the modulation of VEGF receptors expression. These changes may be one of the reasons for the reduction of implanted embryos.展开更多
As a homodimeric glycoprotein, vascular en- dothelial growth factor (VEGF) is a highly specific mitogen of vascular endothelial cells. It can induce proliferation and migration, and inhibit apoptosis of endothelial ce...As a homodimeric glycoprotein, vascular en- dothelial growth factor (VEGF) is a highly specific mitogen of vascular endothelial cells. It can induce proliferation and migration, and inhibit apoptosis of endothelial cell. VEGF is involved in many processes in the female reproductive sys-tem, such as ovulation, periodical changes of endometrium, embryo implantation and development. VEGF plays impor-tant roles in some reproductive diseases, including pree-clampsia and fetal hypoevolutism in uterus. Based on our studies on angiogenesis and its relevant factors in the female reproductive system these years, the functions of VEGF in female reproductive system are reviewed, and the research prospect and application of VEGF are also discussed.展开更多
基金funded partly by a program grant from the National Health and Medical Research Council of Australia(NH&MRC)supported by Senior Research Fellowships from the NH&MRCsupport of the Pfizer Australia Fellowship
文摘The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.
基金supported by the State Major Basic Research Project(Grant No.G1999055903)the 2002 Knowledge Innovation Project of the Chinese Academy of Sciences
文摘On day 3 of gestation, one uterine horn of fe-male pregnant mouse was injected intraluminally with 5 mL 0.1 mg/mL lactacystin, a specific inhibitor of ubiquitin-pro- teasome pathway (UPP), while the contralateral horn served as control. Animals were sacrificed by cervical dislocation on day 5, 6, 7 of gestation, respectively. Then the number of implanted embryos in each uterine horn was calculated, and the expression of VEGF and its receptors was examined. The data showed that the number of implanted embryos was decreased significantly after treatment with lactacystin. The results of RT-PCR and Western blot indicated that expres-sion of VEGF and its receptors at mRNA and protein levels was significantly decreased in the treated uterus, meanwhile, the expression of HIF-1a (the a subunit of HIF, a transcrip-tional factor of VEGF) was reduced at both mRNA and pro-tein levels. These data suggested that the effect of UPP on VEGF expression was realized through regulating HIF-1a expression. In addition, UPP is likely to take part in the modulation of VEGF receptors expression. These changes may be one of the reasons for the reduction of implanted embryos.
基金supported by the State Key Basic Research Project(Grant No.1999055903)2002 CAS Knowledge Innovation Progress.
文摘As a homodimeric glycoprotein, vascular en- dothelial growth factor (VEGF) is a highly specific mitogen of vascular endothelial cells. It can induce proliferation and migration, and inhibit apoptosis of endothelial cell. VEGF is involved in many processes in the female reproductive sys-tem, such as ovulation, periodical changes of endometrium, embryo implantation and development. VEGF plays impor-tant roles in some reproductive diseases, including pree-clampsia and fetal hypoevolutism in uterus. Based on our studies on angiogenesis and its relevant factors in the female reproductive system these years, the functions of VEGF in female reproductive system are reviewed, and the research prospect and application of VEGF are also discussed.
