139th National Cancer Advisory Board
first objective was to determine whether or not they maintained their NSAID efficacy; they all inhibited the PGE2 synthesis. Dr. Wink observed that a very preliminary result with the S-NSAID revealed an 80 percent reduction of one of the compounds for the growth rate of the PC3 cells; additional studies will utilize a number of different cellular- and tissue-based assays by Dr. Dave Roberts. The redox faculty also is drawing on the work of Dr. Robert’s group (Matrix Biol 2005), who has grown a tumor in media and seen new vessel formation; pro-angiogenic or anti-angiogenic potential can be determined by measuring the growth or the width of the growth. Salient conclusions reached to date include that: (1) S-NSAIDs have anti-angiogenic properties and (2) NO-based NSAIDs have pro-angiogenic properties.
Dr. Wink next explained Drs. Murali Krishna and James Mitchell’s work on oxygen and redox EPR and MRI imaging with nitroxides. They focused on imaging free radicals in tissue. They can take the relative rates of induction of these nitroxides, and they can decipher the different pixels. Dr. Wink showed this through an oxygen map and a redox map, illustrating the benefit of imaging as a diagnostic tool. Dr. Wink said that Dr. Larry Marnett, Vanderbilt University, was able to derivatize indomethicin with a fluorophore and, upon feeding it to the animal, found that in cells that were specifically expressing COX-2, the fluorophore was taken up. He measured the concentration and found it to be up to 100 µM, which is similar to the range for imaging.
Dr. Wink concluded with a model for testing redox-based compounds. He noted the enthusiasm of all the people who have been involved. The redox faculty and collaborators have been able to ask basic biology questions and then translate them into cellular models. The faculty now has the capacity to now screen different therapeutic agents, and serves as a fulcrum for this science.
The Trans-NIH Angiogenesis Research Program—Dr. Steven K. Libutti
Dr. Libutti explained that he would describe the Trans-NIH Angiogenesis Research Program (TARP) in general, and then highlight the CCR’s contribution to the program. TARP began in 2003, when representatives of the Juvenile Diabetes Research Foundation met with then NCI Director, Dr. Andrew von Eschenbach. They postulated that angiogenesis and perturbations of vascular development underpin a number of different diseases, and are important for cancer progression and metastases, diabetic retinopathy, heart disease, rheumatoid arthritis, and other disease processes. They suggested a collaboration to leverage information across disciplines and to speed the progress of the understanding of vascular biology. That meeting became the impetus for a working group that discussed areas of possible collaboration. Initially comprised of the NCI, Juvenile Diabetes Research Foundation International (JDRF), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the working group quickly incorporated other institutes, such as the National Heart, Lung, and Blood Institute (NHLBI), the National Eye Institute (NEI), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Child Health and Human Development (NICHHD). The working group held a workshop in the spring of 2004, and experts from various disciplines, in both the extramural and intramural communities, attended to discuss where there might be collaboration and how to move the field forward. This workshop resulted in suggestions for a number of initiatives, from which a mission statement for the TARP was formulated.
TARP’s mission is to: (1) encourage and facilitate the study of the underlying mechanisms controlling blood vessel growth and development; (2) identify specific targets and to develop therapeutics against pathologic angiogenesis to reduce the morbidity due to abnormal blood vessel proliferation in a variety of disease states; (3) better understand the process of angiogenesis and vascularization to improve states of decreased vascularization; (4) encourage and facilitate the study of the processes of lymphangiogenesis; and (5) achieve these goals through a multidisciplinary approach, bringing together