Measuring hypoxia in vivo; Animal Models of human disease; Cancer physiology, proliferation; Cancer physiology; tumor vasculature
The primary emphasis of the work in the Evans laboratory is to determine causes of treatment resistance in human cancer. The treatment resistance factor that is emphasized is hypoxia. The presence, level and distribution of hypoxia is measured using a 2-nitroimidazole agent, EF5, developed by Dr. Cameron Koch, also from the Department of Radiation Oncology, at PENN. EF5 can be used for in vitro or in vivo studies. The majority of studies in the Evans laboratory involve in vivo studies in animals or humans. Given intravenously, this agent is reduced and bound in hypoxic cells. The adducts thus formed are recognized by a specific fluorescent monoclonal antibody. Tumor tissue or cells are studied either using immunohistochemistry or flow cytometry. This fluorescence can be measured and converted into tissue pO2 based upon previously published in vitro studies. We have performed studies using EF5 in animal models of cancer and, since 1998 have been performing clinical trials to evaluate the presence and level of hypoxia in various human cancers. We are currently funded by the NIH to perform studies in human brain tumors, head and neck cancers, sarcomas, cervix, and intraperitoneal cancers. We have shown that hypoxia, as measured by EF5 binding correlates to the level of tumor aggression in glial brain tumors, soft tissue sarcomas and head/neck squamous cell cancers. We have recently been able to produce [F-18]-EF5, which can be analyzed with positron emission tomography, PET imaging. Grants to study EF5 binding, with both immunohistochemical and PET endpoints in patients with brain tumors and head and neck cancer have been funded by the NIH.
Measuring hypoxia and predicting treatment response in brain tumors
Measuring hypoxia and predicting treatment responsein cervix cancer
Measuring hypoxia and predicting treatment responsein head and neck squamous cell carcinoma
Measuring hypoxia and predicting treatment responsein carcinomatosis and sarcomatosis
Measuring hypoxia and predicting treatment responsein pleural cancers
Measuring hypoxia and predicting treatment response in soft tissue sarcomas
Mentoring junior faculty
Evans SM, Putt M, Yang XY, Lustig RA, Martinez-Lage M, Williams D, Desai A, Wolf R, Brem S, Koch CJ.: Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients. Journal of Neuro-Oncology 127(2): 391-400, Apr 2016.
Lao Z, Kelly CJ, Yang XY, Jenkins WT, Toorens E, Ganguly T, Evans SM, Koch CJ.: Improved Methods to Generate Spheroid Cultures from Tumor Cells, Tumor Cells & Fibroblasts or Tumor-Fragments: Microenvironment, Microvesicles and miRNA. PLoS One 10(7): e0133895, Jul 24 2015
Morgans AK, van Bommel AC, Stowell C, Abrahm JL, Basch E, Bekelman JE, Berry DL, Bossi A, Davis ID, de Reijke TM, Denis LJ, Evans SM, Fleshner NE, George DJ, Kiefert J, Lin DW, Matthew AG, McDermott R, Payne H, Roos IA, Schrag D, Steuber T, Tombal B, van Basten JP, van der Hoeven JJ, Penson DF: Development of a Standardized Set of Patient-centered Outcomes for Advanced Prostate Cancer: An International Effort for a Unified Approach. European Urology 68(5): 891-8, Nov 2015.
Koch CJ, Evans SM: Pharmacokinetic and pharmacodynamic modifiers of EF5 uptake and binding. Journal of Nuclear Medicine 56(4): 653, Apr 2015.
Koch CJ, Evans SM: Optimizing Hypoxia Detection and Treatment Strategies. Seminars in Nuclear Medicine 45(2): 163-76, Mar 2015.
Koch CJ, Lustig RA, Yang XY, Jenkins WT, Wolf RL, Martinez-Lage M, Desai A, Williams D, Evans SM: Microvesicles as a Biomarker for Tumor Progression versus Treatment Effect in Radiation/Temozolomide-Treated Glioblastoma Patients. Translational Oncology 7(6): 752-8, Dec 2014.
Koch CJ, Jenkins WT, Jenkins KW, Yang XY, Shuman AL, Pickup S, Riehl1 CR, Paudya R, Poptani H, Evans SM: Mechanisms of Blood Flow and Hypoxia Production in Rat 9L Epigastric Tumors. Tumor Microenvironment and Therapy 1(1): 1-13, Jan 2013.
Sood N, Jenkins WT, Yang XY, Shah NN, Katz JS, Koch CJ, Frail PR, Therien MJ, Hammer DA, Evans SM.: Biodegradable polymersomes for the delivery of Gemcitabine to Panc-1 cells. Journal of Pharmaceutics. Hindawi Publishing Company, 2013: 932797, 2013.
Lilie L Lin, LL
James B Stubbs
Jonathan M. Sorger
Michael G. Stabin
Stephen M. Hahn
Sydney M Evans
Cameron J. Koch
Heikki Minn: Radiation Dosimetry and Biodistribution of the Hypoxia Tracer 18F-EF5 in Oncologic Patients. Cancer Biotherapy & Radiopharmaceuticals 27(7): 412-9, Sep 2012.
Marotta D, Karar J, Jenkins WT, Kumanova M, Tobias JW, Baldwin D, Hadjigeorgiou A, Alexiou P, Evans SM, Alarcon R, Maity A, Koch CJ, Koumenis C: In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection. Cancer Research
(eds.). 71(3): 779-89, Feb 2011
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Last updated: 03/23/2016
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