Wen-Yu Cheng1,2, Chiung-Chyi Shen3,4,5,6,7, Ming-Tsang Chiao3, Yea-Jiuan Liang3, Tsuo-Fei Mao7, Bai-Shuan Liu8, Jun-Peng Chen9. 1. Division of Minimally Invasive Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, 40705, Taiwan, ROC. wycheng07@yahoo.com.tw. 2. Department of Physical Therapy, Hung Kuang University, No. 160, Sec. 3 Taichung-Kang Rd., Taichung 407, Taichung, 43302, Taiwan, ROC. wycheng07@yahoo.com.tw. 3. Division of Minimally Invasive Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, 40705, Taiwan, ROC. 4. Department of Physical Therapy, Hung Kuang University, No. 160, Sec. 3 Taichung-Kang Rd., Taichung 407, Taichung, 43302, Taiwan, ROC. 5. Department of Medicine, National Defense Medical Center, Taipei, 114, Taiwan, ROC. 6. Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, ROC. 7. Department of Game and Product Design, Chienkuo Technology University, Changhua, Taiwan, ROC. 8. Department of Medical Imaging and Radiological Sciences, Central Taiwan, ROC University of Science and Technology, Taichung, 40601, Taiwan, ROC. 9. Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Abstract
INTRODUCTION: A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear. METHODS: In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis. RESULTS: The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro. CONCLUSIONS: Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment.
INTRODUCTION: A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear. METHODS: In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis. RESULTS: The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro. CONCLUSIONS: Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment.
Entities:
Keywords:
Bevacizumab; GBM Prognosis; Mitogen; Novel VEGF isoform; Nucleolus protein
Authors: David N Louis; Hiroko Ohgaki; Otmar D Wiestler; Webster K Cavenee; Peter C Burger; Anne Jouvet; Bernd W Scheithauer; Paul Kleihues Journal: Acta Neuropathol Date: 2007-07-06 Impact factor: 17.088