Professor
Department of Biochemistry and Microbiology
Department of Radiation Medicine
School of Medicine
Loma Linda University & Medical Center
Loma Linda, CA 92354
Phone: (909) 558-4000, extension 88361
Fax: (909) 558-0825
Email: dgridley@dominion.llumc.edu
Cancer remains a formidable challenge, in spite of significant improvements in the three major treatment modalities (radiation, surgery, and chemotherapy). There are more than 1.3 million newly diagnosed cancer cases and more than 560,000 cancer-related deaths every year in the United States alone. Recent advances in genetic engineering, radiation delivery, and our understanding of immunological anti-tumor mechanisms have greatly increased the possibility for curing cancers that heretofore have been refractory to conventional therapies.
A major focus of our research is to develop preclinical models in which radiation (protons and gamma-rays) and new modalities such as gene therapy can be evaluated and optimized. Normal tissue radioprotectants and tumor radiosensitizers are often included in our studies. The tumor systems being studied include a highly aggressive glioma (brain tumor), and human prostate, lung, and colon tumors growing as xenografts in athymic rodents. The hope is that the data generated from these investigations will help refine protocols for maximum benefit and also identify any safety concerns that might arise due to combination therapies.
A second goal of our studies is to utilize animal models to determine radiation-associated health risks to astronauts on extended missions in space. Immune depression or dysfunction after whole-body exposure to space radiation may have serious consequences. Increased risk for infection and development of cancer are among the greatest concerns. Regimens consisting of low-dose rate radiation, alone and together with acute radiation, are being implemented to mimic the low-level background and solar flare events that astronauts are likely to experience. Investigations on the influence of altered gravity on immunological parameters are also in progress. These studies involve close collaboration with the National Aeronautics and Space Administration (NASA).Luo X, Slater JM, Gridley DS. Enhancement of radiation effects by pXLG-mEndo in a lung carcinoma model. Int J Radiat Oncol Biol Phys, In press, 2005.
Gridley DS , Bush DA, Bonnet RB, Franke C, Cheek GA, Slater JD, Slater JM. Time course of serum cytokines in patients receiving proton or combined photon/proton beam radiation for resectable but medically inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 60(3):759-766, 2004.
Gridley DS , Slater JM. Combining gene therapy and radiation against cancer. Curr Gene Ther 4:231-248, 2004. (invited review)
Gridley DS , Miller GM, Luo X, Cao JD, Timiryasova TM, Fodor I, Slater JM. Proton radiation and TNF- a /Bax gene therapy for orthotopic C6 brain tumor in Wistar rats. Technol Cancer Res Treat 3(2):217-227, 2004.
Pecaut MJ, Miller GM, Nelson GA, Gridley DS. Hypergravity-induced immunomodulation in a rodent model: Hematological and lymphocyte function analysis. J Appl Physiol 97:29-38, 2004.
Pecaut MJ, Nelson GA, Bateman TA, Stodieck LS, Simske SJ, Peters LL, Morony S, Kostenuik PJ, Gridley DS. Effects of spaceflight on immunity in the C57BL/6 mouse, Part I: Immune population distributions. J Appl Physiol 94:2085-2094, 2003.
Gridley DS , Nelson,GA, Bateman TA, Stodieck LS, Simske SJ, Peters LL, Morony S, Kostenuik PJ, Pecaut MJ. Effects of spaceflight on immunity in the C57BL/6 mouse, Part II: Activation, cytokines, erythrocytes, and platelets. J Appl Physiol 94:2095-2103, 2003.
Miller GM, Kim DW, Andres ML, Green LM, Gridley DS. Changes in the activation and reconstitution of lymphocytes resulting from total-body irradiation correlate with slowed tumor growth. Oncology 65(3):229-241, 2003.
Gridley DS , Pecaut MJ, Green LM, Miller GM, Nelson, G.A. Hypergravity-induced immunomodulation in a rodent model: Lymphocytes and lymphoid organs. J Gravitational Physiol 9(2):15-28, 2002.
Kim DW, Andres ML, Miller GM, Cao JD, Green LM, Seynhaeve ALB, ten Hagen TLM, Gridley DS. Immunohistological analysis of immune cell infiltration of a human colon tumor xenograft after treatment with Stealth ® liposome-encapsulated tumor necrosis factor- a and radiation. Int J Oncol 21:973-979, 2002.
Gridley DS , Pecaut MJ, Nelson GA. Total-body irradiation with high-LET particles: Acute and chronic effects on the immune system. Am J Physiol - Regul Integr Comp Physiol 282:R677-R688, 2002.
Last Revised: Wed, Jun 28, 2006
