This application is submitted as a competitive renewal of a midcareer investigator award in patient-orientedresearch (K24CA82450). The PI is Randall F. Holcombe, MD. This application details the experience,qualifications and short- and long-term patient-oriented research plans of Dr. Holcombe, as well as reviewsprogress during the period of support under the current award. Details about current and planned patient-oriented research is provided. These studies are focused on patient-oriented research in colon cancer andinclude studies related to the Wnt signaling pathway, elucidation of immunologic events in conjunction withadministration of chemotherapy for colon cancer and definition of the mechanisms and potential therapeuticand cancer preventive effects of resveratrol, a naturally occuring compound found in the skin of grapes.Patients with inflammatory bowel disease, having or at high risk for colon cancer, are also studied. Anadditional clinical trial with laboratory correlative studies, originally designed and written by a menteehematology-oncology fellow of Dr. Holcombe's involves the treatment of patients with gastric cancer.Mentoring activity over the past 5 years and mentoring plans for the next 5 years are described. Theaccomplishments of mentees are outlined as are their current activities, espeicially as related to ongoingparticipation in patient-oriented research. Ongoing mentoring plans include formal coursework,basic/translational research experiences, instruction in the development and implementation of clinicalresearch trials, and hands-on experiences in clinical research. The original goals and objectives of thecurrent award are reviewed and the extent to which these have been achieved is delineated. Documentationof institutional support and justification of the need for continued support through the K24 mechanism isprovided.
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