目的探讨ABI家族成员3结合蛋白(ABI family member 3-binding protein,ABI3BP)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导内皮祖细胞功能障碍中的作用及机制。方法为探讨ABI3BP在AngⅡ诱导内皮祖细胞功能障碍中的作用,将细胞分为4组,sh-N...目的探讨ABI家族成员3结合蛋白(ABI family member 3-binding protein,ABI3BP)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导内皮祖细胞功能障碍中的作用及机制。方法为探讨ABI3BP在AngⅡ诱导内皮祖细胞功能障碍中的作用,将细胞分为4组,sh-NC组[转染阴性对照短发夹RNA(LV-scramble-shRNA)+磷酸盐缓冲液(phosphate buffered saline,PBS)]、sh-ABI3BP组[转染ABI3BP shRNA(LV-ABI3BP-shRNA)+PBS]、sh-NC+AngⅡ组(LV-scramble-shRNA+AngⅡ)和sh-ABI3BP+AngⅡ组(LV-ABI3BP-shRNA+AngⅡ)。采用Transwell实验检测细胞迁移能力,黏附实验检测细胞黏附能力,Matrigel检测细胞成管能力,原位末端标记法检测细胞凋亡。Western blot检测整合素β1-黏着斑激酶(focal adhesion kinase,FAK)-P53信号通路变化情况。结果与sh-NC组比较,sh-NC+AngⅡ组迁移细胞数量、黏附细胞数量、小管形成数量显著降低,细胞凋亡率、整合素β1、磷酸化FAK(p-FAK)/FAK及P53蛋白表达显著增高,差异有统计学意义(P<0.05)。与sh-NC+AngⅡ组比较,sh-ABI3BP+AngⅡ组迁移细胞数量[(88.67±8.33)个vs(62.33±7.37)个]、黏附细胞数量[(104.33±6.03)个vs(68.33±10.05)个]、小管形成数量[(36.33±3.21)个vs(19.33±3.06)个]显著增高,细胞凋亡率、整合素β1、p-FAK/FAK及P53蛋白表达水平显著降低,差异有统计学意义(P<0.05)。结论AngⅡ可上调ABI3BP表达,敲低ABI3BP基因表达可改善AngⅡ诱导的内皮祖细胞功能障碍,其机制可能与抑制整合素β1-FAK-P53信号通路有关。展开更多
Objectives. An early non- invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF- II levels can be effectively used for a specific early diagnosis of cervical cancer. Her...Objectives. An early non- invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF- II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF- B, VEGF- C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF- II and IGF- binding protein 3 (IGF- BP3). Material and methods. (a) Serum levels of IGF- II, IGF- BP3, VEGF- B (VEGF 165)and VEGF- C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN- I; 23 successfully treated CIN- I; 75 persistent CIN- I; 14 CIN- II/III pre-therapy; 14 successfully treated CIN- II/III; 70 persistent CIN- II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF- C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student s t test, chi-square analysis and linear regression analysis were used. Results. (a) As anticipated, serum IGF- II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF- II levels were normal in ASCUS with normal biopsy, successfully treated CIN- I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF- BP3 showed a significant decrease with advancing disease. Serum VEGF- B levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF- C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF- C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF- C and IGF- II and a negative correlation between IGF- BP3 and VEGF- C (P < 0.0001). Conclusion. Serum IGF- II up- regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF- C up- regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF- C and IGF- II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF- BP3 and VEGF- B appear to be common markers for all gynecological cancers.展开更多
文摘Objectives. An early non- invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF- II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF- B, VEGF- C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF- II and IGF- binding protein 3 (IGF- BP3). Material and methods. (a) Serum levels of IGF- II, IGF- BP3, VEGF- B (VEGF 165)and VEGF- C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN- I; 23 successfully treated CIN- I; 75 persistent CIN- I; 14 CIN- II/III pre-therapy; 14 successfully treated CIN- II/III; 70 persistent CIN- II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF- C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student s t test, chi-square analysis and linear regression analysis were used. Results. (a) As anticipated, serum IGF- II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF- II levels were normal in ASCUS with normal biopsy, successfully treated CIN- I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF- BP3 showed a significant decrease with advancing disease. Serum VEGF- B levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF- C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF- C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF- C and IGF- II and a negative correlation between IGF- BP3 and VEGF- C (P < 0.0001). Conclusion. Serum IGF- II up- regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF- C up- regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF- C and IGF- II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF- BP3 and VEGF- B appear to be common markers for all gynecological cancers.
基金the Research and Development Projects of Shenzhen,No.JCYJ20130402114702130the Program of Shenzhen Municipal Science and Technology Bureau,No.201302064~~
