Laboratory of John F. Renz, MD, PhD
Principal Investigator
John F. Renz MD, PhD
- Residency: University of California San Francisco
- Fellowship: University of California Los Angeles Graduate: Thomas Jefferson University (Biochemistry and Molecular Biology)
Background for Research Project
Hepatocellular carcinoma (HCC) is a highly prevalent cancer with an annual world incidence of 1.2 million. Since the introduction of liver transplantation (LTX), HCC has been an indication for the procedure; however, the overall results of LTX for HCC remain poor. While a surgical resident, I obtained data that demonstrate a survival advantage for patients with known HCC who received arterial embolization (AE) immediately prior to LTX versus recipients with incidentally discovered HCC at LTX.
The rationale of pre-LTX AE is founded upon the concept of tumor cell dissemination at the time of surgery. Evidence supporting tumor cell dissemination at LTX include: the liver as the most common site of HCC recurrence post-LTX, and the isolation of viable tumor cells from the central venous blood of patients undergoing hepatic resection for HCC.
My hypothesis is acute ischemic injury, resulting from AE, alters the biology of HCC through the expression of heat shock proteins (Hsp) that elicit an enhanced anti-tumor response. Hsp are a family of cytosolic proteins expressed by hepatocytes and other cells during periods of metabolic stress. Expression of Hsp by tumor cell lines from breast, colon, lung, and gliomas have resulted in increased tumor immunogenicity and tumor killing by non-apoptotic mechanisms. Hsp participate in T cell- mediated immunity through their ability to bind and deliver tumor antigens to professional antigen presenting cells, a function termed “antigen chaperones”. Hsp-tumor antigen complexes may “break” a patient’s tolerance of specific tumors and mediate antigen presentation, immune cell recruitment, or activation. Furthermore, the immunity conferred by Hsp-tumor antigen complexes is specific for the tumor and mediated through an increased frequency of tumor-specific T cells in animals and humans.
Thus, the induction of Hsp by AE, prior to the unavoidable tumor cell dissemination that occurs during the performance of LTX, generates HCC cells with a lower malignant potential, yielding the observed clinical results.
Main Focus of the Laboratory:
The specific aims of the laboratory are:
- Develop a reliable animal model of Hsp inducible HCC to perform in vitro and in vivo studies.
- Investigate Hsp induction and expression within human HCC treated by AE.
- Determine the effect of Hsp expression, upon human HCC replication, differentiation, and immunogenicity in vitro and in vivo.
Current Projects:
- Creation of a rodent model to evaluate the effect of Hsp expression upon the immunogenicity of HCC.
- Evaluation of human liver explant specimens to determine Hsp expression within normal and cirrhotic liver as well as HCC.
Recent Publications:
Renz, J.F., McDiarmid, S.V., Edelstein, S., Yersiz, H., Hisatake, G.M., Gordon, S., Saggi, B.H., Busuttil, R.W., Farmer, D.G. Application of combined liver-intestinal transplantation as a staged procedure, Transplantation Proceedings, 2004;36(2):314-315.
Renz, J.F., Emond, J.C., Yersiz, H., Ascher, N.L., Busuttil, R.W. Split-Liver Transplantation in the United States: Outcomes of a National Survey, Annals of Surgery, 2004;239(2):172-181
Renz, J.F., Yersiz, H., Hisatake, G.M., Reichert, P.R., Emond, J.C., Busuttil, R.W. Split-Liver Transplantation: A Review, American Journal of Transplantation, 2003;3(11):1323-1335.
Yersiz, H., Renz, J.F., Farmer, D.G., Ghobrial, R.M., Hisatake, G.M., McDiarmid, S.V., Busuttil, R.W. One-Hundred In Situ Split-Liver Transplantations: A Single Center Experience, Annals of Surgery, 2003;238(4):496-505.
Yersiz, H., Renz, J.F., Hisatake, G.M., Gordon, S., Saggi, B.H., Feduska, N.J., Jr., Busuttil, R.W., Farmer, D.G. Multivisceral and Isolated Intestinal Procurement Techniques, Liver Transplantation 2003;9(8):881-886.
Renz, J.F., Yersiz, H., Farmer, D.G., Hisatake, G.M., Ghobrial, R.M., Busuttil, R.W. Changing Faces of Liver Transplantation: Partial-Liver Grafts for Adults, Journal of Hepatobiliary Pancreatic Surgery, 2003;10(1):31-44.
Emond, J.C., Freeman, R.B., Renz, J.F., Yersiz, H., Rogiers, X., Busuttil, R.W. Optimizing the Use of Donated Cadaver Livers: Analysis and Policy Development to Increase the Application of Split-Liver Transplantation, 2002;8(10):863-872.
Diaz, G.C., Renz, J.F., Mudge, C., Roberts, J.P., Ascher, N.L., Emond J.C., Rosenthal P. Donor Health Assessment Following Living-Donor Liver Transplantation, Annals of Surgery, 2002;236(1):120-126.
Renz, J.F., Ascher, N.L. Liver Transplantation for Non-Viral, Non-Malignant Diseases: The Problem of Recurrence, World Journal of Surgery, 2002;26(2):247-256.
Reichert, P.R., Renz, J.F., D’ Albuquerque, L.A.C., Rosenthal, P., Lim, R.C., Roberts, J.P., Ascher, N.L., Emond, J.C. Surgical Anantomy of the Left Lateral Segment as Applied to Living-Donor and Split-Liver Transplantation: A Clinico- Pathologic Study, Annals of Surgery, 2000;232:658-664.
Recent (last 5 years) Surgery Residents (Columbia and outside):
Charles Yoon MD Resident University of California Los Angeles
Cindy Kin Student College of Physicians and Surgeons of Columbia University
Geraldine Diaz DO Resident University of California Los Angeles
Paulo Reichert MD Resident University de Passo Fundo, Brazil
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