PURPOSE: Malignant pleural effusion (MPE) is a common clinical problem in patients with advanced cancer. Evidence suggests that tumor-mediated angiogenesis and enhanced vascular permeability in the pleural wall are due to high levels of vascular endothelial growth factor (VEGF), which plays an important role in the pathogenesis of MPE. The present study was designed to test whether the recombinant adenovirus-mediated delivery of human endostatin (Ad-hEndo), one of the potent inhibitors of angiogenesis, would inhibit the formation and progression of MPE. METHODS: We developed a novel mouse model of MPE by injecting Lewis lung carcinoma (LLC) cells directly into pleural cavity of C57BL/6 mice. To evaluate the therapeutic effects of endostatin in this MPE model, we injected the Ad-hEndo into the pleural cavity of MPE-bearing mice three times with the 3-day interval. RESULTS: We found that this treatment resulted in significant reduction in pleural effusion volume, the number of pleural tumor foci, microvessel density, and vascular permeability, while it significantly prolonged the survival time. In addition, VEGF level of MPE in the group administered with the Ad-hEndo was obviously decreased as compared with that in the two control groups administered with null-adenovirus (Ad-null) or normal saline. CONCLUSIONS: Our work provides a rationale for future studies toward evaluating the effectiveness of the adenovirus-based endostatin therapy for MPE.
PURPOSE:Malignant pleural effusion (MPE) is a common clinical problem in patients with advanced cancer. Evidence suggests that tumor-mediated angiogenesis and enhanced vascular permeability in the pleural wall are due to high levels of vascular endothelial growth factor (VEGF), which plays an important role in the pathogenesis of MPE. The present study was designed to test whether the recombinant adenovirus-mediated delivery of humanendostatin (Ad-hEndo), one of the potent inhibitors of angiogenesis, would inhibit the formation and progression of MPE. METHODS: We developed a novel mouse model of MPE by injecting Lewis lung carcinoma (LLC) cells directly into pleural cavity of C57BL/6 mice. To evaluate the therapeutic effects of endostatin in this MPE model, we injected the Ad-hEndo into the pleural cavity of MPE-bearing mice three times with the 3-day interval. RESULTS: We found that this treatment resulted in significant reduction in pleural effusion volume, the number of pleural tumor foci, microvessel density, and vascular permeability, while it significantly prolonged the survival time. In addition, VEGF level of MPE in the group administered with the Ad-hEndo was obviously decreased as compared with that in the two control groups administered with null-adenovirus (Ad-null) or normal saline. CONCLUSIONS: Our work provides a rationale for future studies toward evaluating the effectiveness of the adenovirus-based endostatin therapy for MPE.
Authors: Daniel H Sterman; Adri Recio; Richard G Carroll; Colin T Gillespie; Andrew Haas; Anil Vachani; Veena Kapoor; Jing Sun; Richard Hodinka; Jennifer L Brown; Michael J Corbley; Michael Parr; Mitchell Ho; Ira Pastan; Michael Machuzak; William Benedict; Xin-qiao Zhang; Elaina M Lord; Leslie A Litzky; Daniel F Heitjan; Carl H June; Larry R Kaiser; Robert H Vonderheide; Steven M Albelda; Michelle Kanther Journal: Clin Cancer Res Date: 2007-08-01 Impact factor: 12.531
Authors: Georgios T Stathopoulos; Zhiwen Zhu; M Brett Everhart; Ioannis Kalomenidis; William E Lawson; Semra Bilaceroglu; Todd E Peterson; Daphne Mitchell; Fiona E Yull; Richard W Light; Timothy S Blackwell Journal: Am J Respir Cell Mol Biol Date: 2005-10-06 Impact factor: 6.914
Authors: Roy S Herbst; Kenneth R Hess; Hai T Tran; Jennifer E Tseng; Nizar A Mullani; Chusilp Charnsangavej; Timothy Madden; Darren W Davis; David J McConkey; Michael S O'Reilly; Lee M Ellis; James Pluda; Waun K Hong; James L Abbruzzese Journal: J Clin Oncol Date: 2002-09-15 Impact factor: 44.544
Authors: F W Van Ginkel; C Liu; J W Simecka; J Y Dong; T Greenway; R A Frizzell; H Kiyono; J R McGhee; D W Pascual Journal: Hum Gene Ther Date: 1995-07 Impact factor: 5.695