OBJECT: In the present study, the authors analyzed the ANGPT1/ANGPT2 balance in the context of therapeutic outcome in 62 patients with primary glioblastomas multiforme (GBMs). METHODS: The tumor tissue used was obtained in adult patients who underwent neurosurgical debulking. Microvessel density was assessed by morphometric analysis. Double immunostaining for Ki 67/CD34 and cleaved caspase-3/CD34 was used to investigate the proliferation and apoptotic fraction of both endothelial and tumor cells. The expression of VEGFs (A-D) was evaluated on immunohistochemistry. To measure tumor vascular stabilization, the ANGPT1/ANGPT2 mRNA balance was determined using real-time reverse transcriptase polymerase chain reaction. RESULTS: Within the hypoxic perinecrotic tumor area, the apoptotic fraction of endothelial cells was positively correlated with VEGFA expression (p < 0.001). Higher levels of VEGFA correlated with greater proliferation of endothelial cells in the intermediate tumor area (p = 0.031). Vascular endothelial growth factor D was significantly more highly expressed within the perinecrotic tumor area compared with the intermediate tumor area (p < 0.001). Multivariate analysis showed a significant association between the ANGPT1/ANGPT2 balance and the survival time of patients with GBMs (p = 0.035). CONCLUSIONS: The results of the present study suggest that the ANGPT1/ANGPT2 balance has prognostic value in patients with primary GBMs. The authors' findings support the need for further studies of the feasibility of antiangiogenic therapy in primary GBMs, with a special focus on the normalization of tumor vasculature.
OBJECT: In the present study, the authors analyzed the ANGPT1/ANGPT2 balance in the context of therapeutic outcome in 62 patients with primary glioblastomas multiforme (GBMs). METHODS: The tumor tissue used was obtained in adult patients who underwent neurosurgical debulking. Microvessel density was assessed by morphometric analysis. Double immunostaining for Ki 67/CD34 and cleaved caspase-3/CD34 was used to investigate the proliferation and apoptotic fraction of both endothelial and tumor cells. The expression of VEGFs (A-D) was evaluated on immunohistochemistry. To measure tumor vascular stabilization, the ANGPT1/ANGPT2 mRNA balance was determined using real-time reverse transcriptase polymerase chain reaction. RESULTS: Within the hypoxic perinecrotic tumor area, the apoptotic fraction of endothelial cells was positively correlated with VEGFA expression (p < 0.001). Higher levels of VEGFA correlated with greater proliferation of endothelial cells in the intermediate tumor area (p = 0.031). Vascular endothelial growth factor D was significantly more highly expressed within the perinecrotic tumor area compared with the intermediate tumor area (p < 0.001). Multivariate analysis showed a significant association between the ANGPT1/ANGPT2 balance and the survival time of patients with GBMs (p = 0.035). CONCLUSIONS: The results of the present study suggest that the ANGPT1/ANGPT2 balance has prognostic value in patients with primary GBMs. The authors' findings support the need for further studies of the feasibility of antiangiogenic therapy in primary GBMs, with a special focus on the normalization of tumor vasculature.
Authors: Sung-Suk Chae; Walid S Kamoun; Christian T Farrar; Nathaniel D Kirkpatrick; Elisabeth Niemeyer; Annemarie M A de Graaf; A Gregory Sorensen; Lance L Munn; Rakesh K Jain; Dai Fukumura Journal: Clin Cancer Res Date: 2010-05-25 Impact factor: 12.531
Authors: Simone Kreth; Jens Heyn; Stefan Grau; Hans A Kretzschmar; Rupert Egensperger; Friedrich W Kreth Journal: Neuro Oncol Date: 2010-02-05 Impact factor: 12.300
Authors: Teresa E Peterson; Nathaniel D Kirkpatrick; Yuhui Huang; Christian T Farrar; Koen A Marijt; Jonas Kloepper; Meenal Datta; Zohreh Amoozgar; Giorgio Seano; Keehoon Jung; Walid S Kamoun; Trupti Vardam; Matija Snuderl; Jermaine Goveia; Sampurna Chatterjee; Ana Batista; Alona Muzikansky; Ching Ching Leow; Lei Xu; Tracy T Batchelor; Dan G Duda; Dai Fukumura; Rakesh K Jain Journal: Proc Natl Acad Sci U S A Date: 2016-04-04 Impact factor: 11.205