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Sydney Evans, V.M.D., M.S.
Professor of Radiation Oncology

Sydney Evans

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. A grant to study EF5 binding, with both immunohistochemical and PET endpoints in patients with brain tumors has been funded by the NIH.

Positions and Employment

1984-1986

Instructor, Dept. of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa.

1986-1998

Assistant Professor, Dept. of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa.

1998-2000

Associate Professor, Dept. of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa.

1998-2005

Associate Professor, Dept. of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pa.

2005-present Professor, Dept. of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pa.
Other Experience and Professional Memberships

2003-2007

Member Radiation and Tumor Biology (RTB) Study section

2001-2005

Editorial Board Cancer Letters

2004-2005

Editorial Board, Current Cancer Therapy Reviews

1996-2005

Radiation Research Society

2003-2005

American Society Therapeutic Radiology & Oncology

2002-2005

Society of Neuro Oncology
Selected peer-reviewed publications (in chronological order). (FROM 94 REFERENCES)

  1. Evans, S. M., Joiner, B., Jenkins, W. T., Laughlin, K. M., Lord, E. M., and Koch, C. J. Identification of hypoxia in cells and tissues of epigastric 9L rat glioma using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide]. British Journal of Cancer, 72: 875-882, 1995.

  2. Koch, C. J., Evans, S. M., and Lord, E. M. Oxygen dependence of cellular uptake of EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)a cet amide] : analysis of drug adducts by fluorescent antibodies vs bound radioactivity. British Journal of Cancer, 72: 869-874, 1995.

  3. Laughlin, K. M., Evans, S. M., Jenkins, W. T., Tracy, M., Chan, C. Y., Lord, E. M., and Koch, C. J. Biodistribution of the nitroimidazole EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide) in mice bearing subcutaneous EMT6 tumors. Journal of Pharmacology & Experimental Therapeutics, 277: 1049-1057, 1996.

  4. Evans, S. M., Jenkins, W. T., Joiner, B., Lord, E. M., and Koch, C. J. 2-Nitroimidazole (EF5) binding predicts radiation resistance in individual 9L s.c. tumors. Cancer Research, 56: 405-411, 1996.

  5. Evans, S. M., Laughlin, K. M., Pugh, C. R., Sehgal, C. M., and Saunders, H. M. Use of power Doppler ultrasound-guided biopsies to locate regions of tumour hypoxia. British Journal of Cancer, 76: 1308-1314, 1997.

  6. Evans, S. M., Koch, C. J., Laughlin, K. M., Jenkins, W. T., Van Winkle, T., and Wilson, D. F. Tamoxifen induces hypoxia in MCF-7 xenografts. Cancer Research, 57: 5155-5161, 1997.

  7. Evans, S. M., Jenkins, W. T., Shapiro, M., and Koch, C. J. Evaluation of the concept of "hypoxic fraction" as a descriptor of tumor oxygenation status. Advances in Experimental Medicine & Biology, 411: 215-225, 1997.

  8. Shapiro, I. M., Mansfield, K. D., Evans, S. M., Lord, E. M., and Koch, C. J. Chondrocytes in the endochondral growth cartilage are not hypoxic. American Journal of Physiology, 272: C1134-1143, 1997.

  9. Koch, C. J., Chasan, J. E., Jenkins, W. T., Chan, C. Y., Laughlin, K. M., and Evans, S. M. Co-localization of hypoxia and apoptosis in irradiated and untreated HCT116 human colon carcinoma xenografts. Advances in Experimental Medicine & Biology, 454: 611-618, 1998.

  10. Gee, M. S., Koch, C. J., Evans, S. M., Jenkins, W. T., Pletcher, C. H., Jr., Moore, J. S., Koblish, H. K., Lee, J., Lord, E. M., Trinchieri, G., and Lee, W. M. Hypoxia-mediated apoptosis from angiogenesis inhibition underlies tumor control by recombinant interleukin 12. Cancer Research, 59: 4882-4889, 1999.

  11. Bergeron, M., Evans, S. M., Sharp, F. R., Koch, C. J., Lord, E. M., and Ferriero, D. M. Detection of hypoxic cells with the 2-nitroimidazole, EF5, correlates with early redox changes in rat brain after perinatal hypoxia-ischemia. Neuroscience, 89: 1357-1366, 1999.

  12. Evans, S. M., Hahn, S., Pook, D. R., Jenkins, W. T., Chalian, A. A., Zhang, P., Stevens, C., Weber, R., Weinstein, G., Benjamin, I., Mirza, N., Morgan, M., Rubin, S., McKenna, W. G., Lord, E. M., and Koch, C. J. Detection of hypoxia in human squamous cell carcinoma by EF5 binding. Cancer Research, 60: 2018-2024, 2000.

  13. Jenkins, W. T., Evans, S. M., and Koch, C. J. Hypoxia and necrosis in rat 9L glioma and Morris 7777 hepatoma tumors: comparative measurements using EF5 binding and the Eppendorf needle electrode. International Journal of Radiation Oncology, Biology, Physics, 46: 1005-1017, 2000.

  14. Evans, S. M., Kachur, A. V., Shiue, C. Y., Hustinx, R., Jenkins, W. T., Shive, G. G., Karp, J. S., Alavi, A., Lord, E. M., Dolbier, W. R., Jr., and Koch, C. J. Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1. Journal of Nuclear Medicine, 41: 327-336, 2000.

  15. Ziemer, L. S., Koch, C. J., Maity, A., Magarelli, D. P., Horan, A. M., and Evans, S. M. Hypoxia and VEGF mRNA expression in human tumors. Neoplasia (New York), 3: 500-508, 2001.

  16. Koch, C. J., Hahn, S. M., Rockwell, K., Jr., Covey, J. M., McKenna, W. G., and Evans, S. M. Pharmacokinetics of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] in human patients: implications for hypoxia measurements in vivo by 2-nitroimidazoles. Cancer Chemotherapy & Pharmacology, 48: 177-187, 2001.

  17. Evans, S. M., Hahn, S. M., Magarelli, D. P., and Koch, C. J. Hypoxic heterogeneity in human tumors: EF5 binding, vasculature, necrosis, and proliferation. American Journal of Clinical Oncology, 24: 467-472, 2001.

  18. Maity, A., Sall, W., Koch, C. J., Oprysko, P. R., and Evans, S. M. Low pO2 and beta-estradiol induce VEGF in MCF-7 and MCF-7-5C cells: relationship to in vivo hypoxia. Breast Cancer Research & Treatment, 67: 51-60, 2001.

  19. Koch, C. J., Oprysko, P. R., Shuman, A. L., Jenkins, W. T., Brandt, G., and Evans, S. M. Radiosensitization of hypoxic tumor cells by dodecafluoropentane: a gas-phase perfluorochemical emulsion. Cancer Research, 62: 3626-3629, 2002.

  20. Nadal-Desbarats, L., Poptani, H., Oprysko, P., Jenkins, W. T., Busch, T. M., Nelson, D. S., Glickson, J. D., Koch, C. J., and Evans, S. M. Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status of subcutaneous RIF-1 tumors. International Journal of Oncology, 21: 103-110, 2002.

  21. Koch, C. J. and Evans, S. M. Non-invasive PET and SPECT imaging of tissue hypoxia using isotopically labeled 2-nitroimidazoles. Advances in Experimental Medicine & Biology, 510: 285-292, 2003.

  22. Ziemer, L. S., Evans, S. M., Kachur, A. V., Shuman, A. L., Cardi, C. A., Jenkins, W. T., Karp, J. S., Alavi, A., Dolbier, W. R., Jr., and Koch, C. J. Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5. European Journal of Nuclear Medicine & Molecular Imaging, 30: 259-266, 2003.

  23. Evans, S., Judy, K., Dunphy, I., Jenkins, W., Nelson, P., Collins, R., Wileyt, E., Jenkins, K., Hahn, S., Stevens, C., Judkins, A., Phillips, P., and Koch, C. Measuring hypoxia in human brain tumors using needle electrodes and EF5 binding. Cancer Research, 2004.

  24. Busch, T., Hahn, S., Wileyto, E., Koch, C., Fraker, D., Zhang, P., Putt, M., Gleason, K., DB Shin, Emanuele, M., Jenkins, K., Glatstein, E., and Evans, S. Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients. Clinical Cancer Research, 2004.

  25. Evans, S., Judy, K. D., Dunphy, I., Jenkins, W. T., Hwang, W.-t., Nelson, P. T., Lustig, R. A., Jenkins, K., Magarelli, D. P., Hahn, S. M., Collins, R. A., Grady, M. S., and Koch, C. J. Hypoxia is Important in the Biology and Aggression of Human Glial Brain Tumors. Clinical Cancer Research, 10: 8177-8184, 2004.

  26. Evans, S. M., Fraker, D. L., Hahn, S. M., Gleason, K., Jenkins, W. T., Jenkins, K., Hwang, W.-T., Zhang, P., and Koch, C. J. EF5 Binding and Clinical Outcome in Human Soft Tissue Sarcomas. International J. Radiation Oncology, Biology and Physics, 2005 (in press).

Grant support
Active
2 R01 CA75285 (Evans)
NIH

Does Hypoxia Predict Radiation/Surgical Tumor Response
The goal is to better understand the role of hypoxia as a predictive indicator of outcome in order to develop individualized therapies for each patient. In the Phase II trial patients with high grade soft tissue sarcomas and head and neck cancers of the oral cavity will be studied.

RO1 CA113561 (Evans)
NIH

Microenvironment In Brain Tumors: Imaging & Implications
The goal of this grant is to develop and study hypoxia in glial tumors. Both invasive and non-invasive studies will be performed. [18-F]-EF5 PET studies will be compared to immunohistochemical studies of EF5 binding in order to assess their predictive value for outcome. Immunohistochemical studies of proliferation, apoptosis and angiogenesis will be performed. Tissue microarrays will be made from formalin fixed tissues and probed for cytokines and molecular signalling proteins with reference to tissue oxygenation.

1 R01 CA87645 (Koch)
NIH

PET Imaging of Hypoxia with EF1 and EF5
This grant is intended to test several key aspects of non-invasive hypoxia imaging, including the effects of drug concentration, drug polarity and optimization of imaging algorithms and resolution. The overall hypothesis is that assessment of hypoxia using appropriate PET imaging agents will predict radiation response in individual tumors.

1 P01 CA87971 (E. Glatstein, S. Evans, Core Leader)
NIH

Photodynamic Therapy for Intraperitoneal Neoplastic Diseases
The goal of this P01 is to study the three major components of PDT (photosensitizer, oxygen and light) to optimize treatment of patients with abdominal sarcomas, ovarian and gastrointestinal carcinomas. Dr. Evans is the Core Leader of Core B. The goals of Project B are to order animals, implant tumors, monitor tumor growth, perform and maintain anesthesia, perform euthanasia and prepare tissues for histopathological examination.

R01 CA74071 (Koch)
NIH

Predicting Radiation Response by Tumor p02
The goal is to make an analysis, using rat tumors, of the relationship between radiation therapy resistance and newly-developed diagnostic assays for hypoxia, thiols, cell respiration and tumor blood flow. The following hypotheses will be tested: 1) Reliable estimates of radiation therapy resistance depend directly on the thiol concentration and inversely on the oxygen concentration. 2) Low oxygen concentrations are a direct result of diminished blood flow. 3) Non-invasive ultrasound Doppler imaging can select areas of tumors most likely to contain hypoxic cells. 4) Non-invasive methods for imaging can provide quantitative analysis of tissue hypoxia.

Completed Research Support
1 R21 CA93007 (Evans)
NIH

Assessment of Hypoxia in Gliomas
The overall goal is to determine whether the presence, levels and patterns of EF5 binding are important in the prognosis and therapy response in patients with de novo supratentorial malignant gliomas (SMG).

R21 CA099346 (Evans)
NIH

Evaluation of Hypoxia by EF5 Binding in Cervix Cancer
The goals of this grant are to extend the immunohistochemistry and flow cytometry results of the R21, (described above) and extend these finding to non-invasive imaging of EF5 using Positron Emission Tomography (PET). The PET studies will be Phase I (pharmacokinetics and toxicity) as well as correlation to immunohistochemstry in individual patients.

1 P50 AT00428 (S.Thom, A. Chalian, Proj. Leader)
NIH (SCOR)

Specialized Center of Research in Hyperbaric Oxygen Therapy
The research theme of this proposal is to examine the mechanisms, action, safety, and clinical efficacy of hyperbaric oxygen therapy relative to the treatment of head and neck cancerThe goal of this specialized center grant is to investigate the mechanisms of hyperbaric oxygen efects on normal and tumor tissues. Dr. Evans is a co-investigator on Project 1 (A. Chalian, Project Leader)

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