title: Antiangiogenesis therapy of endometriosis using PAMAM as a gene vector in a noninvasive animal model.
abstract: OBJECTIVE
  To evaluate the characteristics and antiangiogenic effects of endostatin-loaded PAMAM on endometriosis in a noninvasive animal model.
  
  
  METHODS
  A noninvasive animal model was established by injecting adenovirus-GFP transfected endometrial stromal and glandular epithelial cells subcutaneously into nude mice. Endostatin-loaded PAMAM was prepared and identified by transmission electron microscopy. For in vitro studies, the DNA protection and cytotoxicity of PAMAM were investigated and compared with Lipofectamine 2000. For in vivo study, endostatin-loaded PAMAM was injected into the noninvasive model and evaluated by continuously observing the fluorescent lesion, lesion weight, microvessel density and VEGF immunostaining.
  
  
  RESULTS
  Compared with Lipofectamine 2000, PAMAM and HC PAMAM-ES group, MC PAMAM-ES group and LC PAMAM-ES group demonstrated a better stromal cells protective such that MC PAMAM-ES group of CCK8 was 0.617 ± 0.122 at 24 hr and 0.668 ± 0.143 at 48 hr and LC PAMAM-ES group of CCK8 was 0.499 ± 0.103 at 24 hr and 0.610 ± 0.080 at 48 hr in stromal cells (P < 0.05) but similar cytotoxicity in glandular epithelial cells in vitro. After 16 hrs of digestion, DNA decreased slightly under the protection of PAMAM. Endostatin-loaded PAMAM of HD PAMAM-ES group and LD PAMAM-ES group inhibited the growth of the endometriotic lesion in vivo at days 15, 20, 25 and 30 detected by noninvasive observation after injecting one dose endostatin of various medicines into the endometrial lesion in each mouse on day 10 (P < 0.05) and confirmed by lesion weight at day 30 with HD PAMAM-ES group being 0.0104 ± 0.0077 g and LD PAMAM-ES group being 0.0140 ± 0.0097 g (P < 0.05). Immunohistochemistry results showed that endostatin-loaded PAMAM reduced the microvessel density 3.8 ± 2.4 especially in HD PAMAM-ES group in the lesion (P < 0.05).
  
  
  CONCLUSIONS
  Endostatin-loaded PAMAM inhibits the development of endometriosis through an antiangiogenic mechanism and can be observed through the noninvasive endometriosis model.
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Ningning
authors: N
authors: Wang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Bin
authors: B
authors: Liu
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Lili
authors: L
authors: Liang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Yanxin
authors: Y
authors: Wu
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Hongzhe
authors: H
authors: Xie
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Jiaming
authors: J
authors: Huang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Xu
authors: X
authors: Guo
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Jinfeng
authors: J
authors: Tan
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Xuejun
authors: X
authors: Zhan
authors: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, No. 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Yongdong
authors: Y
authors: Liu
authors: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, No. 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Liantang
authors: L
authors: Wang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan 2nd Road, Guangzhou 510080, China.
authors: Peiqi
authors: P
authors: Ke
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D043169:Endostatins; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D050091:Dendrimers; D043169:Endostatins; C104700:PAMAM Starburst; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D003850:Deoxyribonuclease I