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Prasad S. Adusumilli, MD, Brendon M

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Presentation on theme: "Prasad S. Adusumilli, MD, Brendon M"— Presentation transcript:

1 Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer 
Prasad S. Adusumilli, MD, Brendon M. Stiles, MD, Mei-Ki Chan, BS, Ting-Chao Chou, PhD, Richard J. Wong, MD, Valerie W. Rusch, MD, Yuman Fong, MD  The Annals of Thoracic Surgery  Volume 80, Issue 2, Pages (August 2005) DOI: /j.athoracsur Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Cytotoxic effect of NV1066, radiation therapy, or both on A549 and H1299 cells in vitro. A549 (A) or H1299 (B) cells were treated with radiation therapy (4 Gy), NV1066 (multiplicity of infection, 0.2), or the combination. Results for the treated groups are expressed as cell survival compared with untreated control cells grown under identical conditions. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 GADD34 elevation after radiation. A549 cells (A) or H1299 (B) cells were radiated (5 Gy), and GADD34 expression was measured by real-time reverse transcription-polymerase chain reaction at various times. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Knock-down of GADD34 upregulation by small inhibitory RNA (siRNA). (A) GADD34 levels were determined by real-time reverse transcription–polymerase chain reaction in A549 cells with and without siRNA transfection. In cells transfected with siRNA, GADD34 levels were indistinguishable from control (no radiation) cells, whereas nontransfected cells had a sixfold increase in GADD34 levels. (B) A549 cells were treated with radiation therapy (2 Gy), NV1066 (multiplicity of infection [MOI], 0.05), or the combination, with or without transfection with siRNA. Knock-down of GADD34 upregulation by siRNA eliminated the synergistic cytotoxicity in transfected cells. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Western blot analysis to confirm GADD34 upregulation after radiation and its inhibition by GADD34 small inhibitory RNA (siRNA). A549 nontransfected and GADD34 siRNA-transfected cells were radiated with 5 or 10 Gy. Cells with no radiation served as control. GADD34 protein expression was quantified by Western blot analysis. Radiation upregulated GADD34 protein expression, and GADD34 siRNA knocked down the upregulation in siRNA-transfected cells. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Antitumor effect of radiation, NV1066, or the combination on H1299 flank tumor volume in vivo. Flank tumors were grown in athymic mice and treated with (1) no treatment, (2) 5 Gy of external beam radiation, (3) single injection of 1 × 107 plaque-forming units of NV1066 intratumorally, or (4) combination of therapies. Tumors treated with a combination of therapies had smaller average tumor volume than either treatment alone. Results represent the average of the sample group (n = 6 per group) and are shown with standard errors of mean. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions


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