Jann N. Sarkaria, MD, Paul Schwingler, Steven E. Schild, MD, Patrick T

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Phase I Trial of Sirolimus Combined with Radiation and Cisplatin in Non-small Cell Lung Cancer Jann N. Sarkaria, MD, Paul Schwingler, Steven E. Schild, MD, Patrick T. Grogan, Ann C. Mladek, BS, Sumithra J. Mandrekar, PhD, Angelina D. Tan, BS, Takao Kobayashi, BS, Randolph S. Marks, MD, Hirohito Kita, MD, Robert C. Miller, MD, Andrew H. Limper, MD, Edward B. Leof, PhD Journal of Thoracic Oncology Volume 2, Issue 8, Pages 751-757 (August 2007) DOI: 10.1097/JTO.0b013e3180cc2587 Copyright © 2007 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Inhibition of ribosomal S6 phosphorylation. Isolated PBMC from patients were treated ex vivo with or without 100 nM sirolimus before stimulation with PHA and PMA. (A) S6 is phosphorylated only in those samples treated with PMA/PHA in a patient sample obtained before starting therapy. (B) The results from all patients evaluated on this trial are shown from both pre- and posttreatment blood samples. The corresponding sirolimus blood level determined at the time of the posttreatment sampling is shown if available. *Samples were processed after shipping via an overnight courier. Journal of Thoracic Oncology 2007 2, 751-757DOI: (10.1097/JTO.0b013e3180cc2587) Copyright © 2007 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Effects of radiation and drug treatment on pulmonary toxicity in mice. (A) Average breathing rates for groups of mice treated with sham radiation (RT), RT alone, or RT combined with sirolimus are shown. (B) Kaplan-Meier survival curves for the mice after treatment are shown. All sham-treated mice survived to the end of the experiment. Journal of Thoracic Oncology 2007 2, 751-757DOI: (10.1097/JTO.0b013e3180cc2587) Copyright © 2007 International Association for the Study of Lung Cancer Terms and Conditions