Medical Student Research Fellowship for Summer 2009

Mentor: Sergio Huerta
Department: Surgery
Room number: A568
Mail Code: VA Surgical Services (112)
Phone number: 214 857-1800
E-mail: Sergio.huerta@utsouthwestern.edu
Project title: Mechanisms of resistance in rectal cancer

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic Science

Brief Description of Project:

Our laboratory is interested in factors that lead to resistance to ionizing radiation (IR) in rectal cancer. We have established an in vitro model with a wide range of IR. We have also developed animal models with colorectal cancer xenografts and have submitted these to IR to determine the effects of chemotherapeutic agents in vivo. We have also developed tissue micro-array blocks in patients with rectal cancers who have been treated with IR following surgical resection. We have demonstrated that the p53-p21-p27-axis plays a major role in radioresistance. Our current experimental protocol aims to demonstrate the mechanisms to overcome p53 mediated radioresistance. Our hypothesis will be tested by treating cells with a nitric oxide donor (DETANONOate), an KFkB (Bay-117085) inhibitor, and a peptide mimetic of SMAC (Smac mimetic) to enhance apoptosis. We will then treat cells in xenografts in order to elucidate mechanism that may render a more radiosensitive phenotype.

Previous Research Activities or Publications with Medical Students: (Medical Student in bold]

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References

1. Anguiano-Hernandez YM, Chartier A, Huerta S: Smac/DIABLO and colon cancer. Anticancer Agents Med Chem 2007; 7:467-473.
2. Barleben A, Huerta S, Mendoza R, Patel CV: Left ventricle injury with a normal pericardial window: case report and review of the literature. J Trauma 2007; 63:414-416.
3. Blumetti J, Luu M, Sarosi G, et al.: Surgical site infections after colorectal surgery: do risk factors vary depending on the type of infection considered? Surgery 2007; 142:704-711.
4. Heinzerling JH, Huerta S: Bowel perforation from bevacizumab for the treatment of metastatic colon cancer: incidence, etiology, and management. Curr Surg 2006; 63:334-337.
5. Heinzerling JH, Anthony T, Livingston EH, Huerta S: Predictors of distant metastasis and mortality in patients with stage II colorectal cancer. Am Surg 2007; 73:230-238.
6. Huerta S, Li Z, Li HC, et al.: Feasibility of a partial meal replacement plan for weight loss in low-income patients. Int J Obes Relat Metab Disord 2004; 28:1575-1579.
7. Huerta S, Barleben A, Peck MA, Gordon IL: Meckel's diverticulitis: a rare etiology of an acute abdomen during pregnancy. Curr Surg 2006; 63:290-293.
8. Huerta S, Bui TD, Nguyen TH, et al.: Predictors of mortality and management of patients with traumatic inferior vena cava injuries. Am Surg 2006; 72:290-296.
9. Huerta S, Heinzerling JH, Anguiano-Hernandez YM, et al.: Modification of gene products involved in resistance to apoptosis in metastatic colon cancer cells: roles of Fas, Apaf-1, NFkappaB, IAPs, Smac/DIABLO, and AIF. J Surg Res 2007; 142:184-194.
10. Siddiqui A, Heinzerling J, Livingston EH, Huerta S: Predictors of early mortality in veteran patients with pancreatic cancer. Am J Surg 2007; 194:362-366.