Romy Mueller1, Sayeda Yasmin-Karim2, Kaylie DeCosmo3, Ana Vazquez-Pagan4, Srinivas Sridhar5, David Kozono6, Juergen Hesser7, Wilfred Ngwa8. 1. Data Analysis and Modeling in Medicine, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Heidelberg University, 69117 Heidelberg, Germany; Heidelberg University, 69117 Heidelberg, Germany; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: rmueller1@bwh.harvard.edu. 2. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. 3. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Health Science, Northeastern University, Boston, MA 02115, USA. 4. Department of Biology, Northeastern University, Boston, MA 02115, USA. 5. Harvard Medical School, Boston, MA 02115, USA; Northeastern University, Boston, MA 02115, USA. 6. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA. 7. Data Analysis and Modeling in Medicine, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Heidelberg University, 69117 Heidelberg, Germany; Heidelberg University, 69117 Heidelberg, Germany; Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany; Central Institute for Computer Engineering (ZITI), Heidelberg University, 68159 Mannheim, Germany. 8. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Abstract
PURPOSE: Tumor-associated antigens are a promising target of immunotherapy approaches for cancer treatments but rely on sufficient expression of the target antigen. This study investigates the expression of the carcinoembryonic antigen (CEA) on the surface of irradiated lung cancer cells in vitro using gold nanoparticles as radio-enhancer. METHODS: Human lung carcinoma cells A549 were irradiated and expression of CEA on the cell surface measured by flow cytometry 3 h, 24 h, and 72 h after irradiation to doses of 2 Gy, 6 Gy, 10 Gy, and 20 Gy in the presence or absence of 0.1 mg/ml or 0.5 mg/ml gold nanoparticles. CEA expression was measured as median fluorescent intensity and percentage of CEA-positive cells. RESULTS: An increase in CEA expression was observed with both increasing radiation dose and time. There was doubling in median fluorescent intensity 24 h after 20 Gy irradiation and 72 h after 6 Gy irradiation. Use of gold nanoparticles resulted in additional significant increase in CEA expression. Change in cell morphology included swelling of cells and increased internal complexity in accordance with change in CEA expression. CONCLUSIONS: This study showed an increase in CEA expression on human lung carcinoma cells following irradiation. Increase in expression was observed with increasing radiation dose and in a time dependent manner up to 72 h post irradiation. The results further showed that gold nanoparticles can significantly increase CEA expression following radiotherapy.
PURPOSE:Tumor-associated antigens are a promising target of immunotherapy approaches for cancer treatments but rely on sufficient expression of the target antigen. This study investigates the expression of the carcinoembryonic antigen (CEA) on the surface of irradiated lung cancer cells in vitro using gold nanoparticles as radio-enhancer. METHODS:Humanlung carcinoma cells A549 were irradiated and expression of CEA on the cell surface measured by flow cytometry 3 h, 24 h, and 72 h after irradiation to doses of 2 Gy, 6 Gy, 10 Gy, and 20 Gy in the presence or absence of 0.1 mg/ml or 0.5 mg/ml gold nanoparticles. CEA expression was measured as median fluorescent intensity and percentage of CEA-positive cells. RESULTS: An increase in CEA expression was observed with both increasing radiation dose and time. There was doubling in median fluorescent intensity 24 h after 20 Gy irradiation and 72 h after 6 Gy irradiation. Use of gold nanoparticles resulted in additional significant increase in CEA expression. Change in cell morphology included swelling of cells and increased internal complexity in accordance with change in CEA expression. CONCLUSIONS: This study showed an increase in CEA expression on humanlung carcinoma cells following irradiation. Increase in expression was observed with increasing radiation dose and in a time dependent manner up to 72 h post irradiation. The results further showed that gold nanoparticles can significantly increase CEA expression following radiotherapy.
Authors: Panagiotis Tsiamas; Bo Liu; Fulya Cifter; Wilfred F Ngwa; Ross I Berbeco; Constantin Kappas; Kiriaki Theodorou; Karen Marcus; Mike G Makrigiorgos; Erno Sajo; Piotr Zygmanski Journal: Phys Med Biol Date: 2013-01-10 Impact factor: 3.609