原创力文档r1507, an anti-insulin-like growth factor-1 receptor (igf-1r) antibody, and ewsfli-1 sirna in ewings sarcoma convergence at the igfigfrakt axisr1507,anti-insulin-like生长因子- 1受体(igf-1r)抗体,在尤文氏肉瘤融合和ewsfli-1 sirna igfigfrakt轴.pdfVIP
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r1507, an anti-insulin-like growth factor-1 receptor (igf-1r) antibody, and ewsfli-1 sirna in ewings sarcoma convergence at the igfigfrakt axisr1507,anti-insulin-like生长因子- 1受体(igf-1r)抗体,在尤文氏肉瘤融合和ewsfli-1 sirna igfigfrakt轴
R1507, an Anti-Insulin-Like Growth Factor-1 Receptor
(IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing’s
Sarcoma: Convergence at the IGF/IGFR/Akt Axis
1. 1. 1,2 1 3
Helen J. Huang , Laura S. Angelo , Jordi Rodon , Michael Sun , Klaus-Peter Kuenkele , Henrique A.
1 4 1
Parsons , Jonathan C. Trent , Razelle Kurzrock *
1 Phase I Program, Department of Investigational Cancer Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America,
2 Servei d’Oncologia Medica, Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 3 Roche Diagnostics GmbH, Penzberg, Germany,
4 Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America
Abstract
A subset of patients with Ewing’s sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies.
Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway
that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing’s
sarcoma. The growth of two Ewing’s sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R
antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573
Ewing’s cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71
cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalizati
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