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Kevin F Staveley-O'Carroll, MD, PhD
Professor of Surgery
College of Medicine
MUSC

Email: staveley@musc.edu
 
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Kevin F Staveley-O'Carroll, MD, PhD

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Research Interest:

As a physician-scientist, one goal has been to translate my basic research into clinical practice.  My studies assessing the effects of opioid growth factor on the growth of hepatocellular cancer have led directly to an investigator-initiated Phase I clinical trial that is nearing completion. My studies of ceramide nanoliposomes’ in vivo inhibition of hepatocellular cancer (Gut, 2010, IF-10.6, featured in Nature Reviews) will be assessed in Phase I clinical trial pending FDA approval of the IND application. I also have clinical protocols assessing the changes in the immune-response to HCC antigens, AFP and GPC-3, which occur with radiofrequency ablation or chemoembolization in patients with hepatocellular cancer. My current project has been conceived with similar translational goals in mind and was funded by the NIH to elucidate the cellular and molecular mechanisms by which the chemotherapeutic agent sunitinib prevents immunotolerance and enhances T-cell mediated immunotherapy of hepatocellular cancer. I have established a unique murine model with the typical fibrosis/cirrhosis and hepatocellular cancer features seen in human hepatocellular cancer. My team has now demonstrated that tumor antigen-specific CD8 T-cell tolerance is prevented by the administration of sunitinib, an FDA approved inhibitor of multiple receptor tyrosine kinases. Moreover, we made the critical observation that sunitinib combined with adoptive transfer of CD8 T-cells leads to durable long term regression of established hepatocellular cancer tumors. These results suggest that sunitinib blocks the development of an immunosuppressive state within the liver, allowing effective immunotherapy. This study will advance our knowledge of the sunitinib-mediated mechanisms of action on distinct immune cell subsets in the setting of hepatocellular cancer. The knowledge gained will lay the foundation for translational approaches in human hepatocellular cancer that combines this chemotherapeutic drug with new or existing immunotherapies.

Honors:
Alice Ruth Reeves Folk Endowed Chair of Clinical Oncology

Positions:
Chief, Section of Surgical Oncology, Department of Surgery, Medical University of South Carolina
Medical Director, Hollings Cancer Center Clinical Service Line, Medical University of South Carolina
Director, Cell Evaluation & Therapy Shared Resource, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Yoo L, Oluyemi A, Dye C, Staveley-O'Carroll K, Mathew A. Removal of a partially prolapsing intraductal ampullar adenoma. Gastrointest Endosc. .79(3):377, 2014.
View in: PubMed

2.Nikfarjam M, Weinberg L, Fink MA, Muralidharan V, Starkey G, Jones R, Staveley-O'Carroll K, Christophi C. Pressurized pulse irrigation with saline reduces surgical-site infections following major hepatobiliary and pancreatic surgery: randomized controlled trial. World J Surg. .38(2):447-55, 2014.
View in: PubMed

3.Bhayani NH, Enomoto LM, James BC, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Multivisceral and extended resections during pancreatoduodenectomy increase morbidity and mortality. Surgery. .155(3):567-74, 2013.
View in: PubMed

4.Kline CL, Schiccitano A, Zhu J, Beachler C, Sheikh H, Harvey HA, Mackley HB, McKenna K, Staveley-O'Carroll K, Poritz L, Messaris E, Stewart D, Sivik J, El-Deiry WS. Personalized Dosing via Pharmacokinetic Monitoring of 5-Fluorouracil Might Reduce Toxicity in Early- or Late-Stage Colorectal Cancer Patients Treated With Infusional 5-Fluorouracil-Based Chemotherapy Regimens. Clin Colorectal Cancer. ., 2013.
View in: PubMed

5.Bhayani NH, Miller JL, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Perioperative outcomes of pancreaticoduodenectomy compared to total pancreatectomy for neoplasia. J Gastrointest Surg. .18(3):549-54, 2013.
View in: PubMed

6.Kaifi JT, Kunkel M, Zhu J, Dicker DT, Gusani NJ, Yang Z, Sarwani NE, Li G, Kimchi ET, Staveley-O'Carroll KF, El-Deiry WS. Circulating tumor cells are associated with diffuse spread in stage IV colorectal cancer patients. Cancer Biol Ther. .14(12), 2013. PMCID: PMC3912041
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7.Bhayani NH, Enomoto LM, Miller JL, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Morbidity of total pancreatectomy with islet cell auto-transplantation compared to total pancreatectomy alone. HPB (Oxford). ., 2013.
View in: PubMed

8.Kulaylat AN, Sahajwani S, Staveley-O'Carroll KF, Kaifi JT. Reconstructive options for gastroesophageal junction adenocarcinoma after Roux-en-Y gastric bypass. J Thorac Cardiovasc Surg. .146(5):1296-8, 2013.
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9.Bhayani NH, Hamed OH, Gupta A, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Do patients' outcomes suffer when surgical fellows are involved in hepatic resection? Surgery. .154(5):1024-30, 2013.
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10.Lim B, Scicchitano A, Beachler C, Gusani N, Sarwani N, Yang Z, Staveley-O'Carroll K, Ashkenazi A, Portera C, El-Deiry WS. FOLFIRI plus dulanermin (rhApo2L/TRAIL) in a patient with BRAF-mutant metastatic colon cancer. Cancer Biol Ther. .14(8):711-9, 2013. PMCID: PMC3841210
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11.Kavuturu S, Sarwani NE, Ruggeiro FM, Deshaies I, Kimchi ET, Kaifi JT, Staveley-O'Carroll KF, Gusani NJ. Lymphoepithelial cysts of the pancreas. Can preoperative imaging distinguish this benign lesion from malignant or pre-malignant cystic pancreatic lesions? JOP. .14(3):250-5, 2013.
View in: PubMed

12.Hamed O, Kimchi ET, Sehmbey M, Gusani NJ, Kaifi JT, Staveley-O'Carroll K. Impact of genetic targets on cancer therapy: hepatocellular cancer. Adv Exp Med Biol. .779:67-90, 2013.
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13.Hamed OH, Bhayani NH, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Simultaneous colorectal and hepatic procedures for colorectal cancer result in increased morbidity but equivalent mortality compared with colorectal or hepatic procedures alone: outcomes from the National Surgical Quality Improvement Program. HPB (Oxford). .15(9):695-702, 2012.
View in: PubMed

14.Kaifi JT, Kibbe MR, Lemaire SA, Staveley-O'Carroll KF, Kao LS, Sosa JA, Kimchi ET, Pawlik TM, Gusani NJ. Scientific impact of Association for Academic Surgery and Society of University Surgeons plenary session abstracts increases in the era of the Academic Surgical Congress from 2006 to 2010. J Surg Res. .182(1):6-10, 2012.
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15.Avella DM, Li G, Schell TD, Liu D, Zhang SS, Lou X, Berg A, Kimchi ET, Tagaram HR, Yang Q, Shereef S, Garcia LS, Kester M, Isom HC, Rountree CB, Staveley-O'Carroll KF. Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model. Hepatology. .55(1):141-52, 2012. PMCID: PMC3243781
View in: PubMed

16.Krishnegowda G, Prakasha Gowda AS, Tagaram HR, Carroll KF, Irby RB, Sharma AK, Amin S. Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway. Bioorg Med Chem. .19(20):6006-14, 2011. PMCID: PMC3235409
View in: PubMed

17.Kaifi JT, Gusani NJ, Jiang Y, Mackley HB, Dye CE, Mathew A, Kimchi ET, Reed MF, Staveley-O'Carroll KF. Multidisciplinary management of early and locally advanced esophageal cancer. J Clin Gastroenterol. .45(5):391-9, 2011.
View in: PubMed

18.Tagaram HR, Divittore NA, Barth BM, Kaiser JM, Avella D, Kimchi ET, Jiang Y, Isom HC, Kester M, Staveley-O'Carroll KF. Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. Gut. .60(5):695-701, 2010.
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19.Nikfarjam M, Kimchi ET, Gusani NJ, Staveley-O'Carroll KF. Complete surgical resection of giant mucinous hepatic cystadenomas. Am Surg. .76(5):E17-9, 2010.
View in: PubMed

20.Avella DM, Kimchi ET, Donahue RN, Tagaram HR, McLaughlin PJ, Zagon IS, Staveley-O'Carroll KF. The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer. Am J Physiol Regul Integr Comp Physiol. .298(2):R459-66, 2009. PMCID: PMC2828179
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21.Kimchi ET, Nikfarjam M, Gusani NJ, Avella DM, Staveley-O'Carroll KF. Combined pancreaticoduodenectomy and extended right hemicolectomy: outcomes and indications. HPB (Oxford). .11(7):559-64, 2009. PMCID: PMC2785950
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22.Gusani NJ, Jiang Y, Kimchi ET, Staveley-O'Carroll KF, Cheng H, Ajani JA. New pharmacological developments in the treatment of hepatocellular cancer. Drugs. .69(18):2533-40, 2009.
View in: PubMed

23.Nikfarjam M, Shereef S, Kimchi ET, Gusani NJ, Jiang Y, Avella DM, Mahraj RP, Staveley-O'Carroll KF. Survival outcomes of patients with colorectal liver metastases following hepatic resection or ablation in the era of effective chemotherapy. Ann Surg Oncol. .16(7):1860-7, 2008.
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24.Ryan CM, Staveley-O'Carroll K, Schell TD. Combined anti-CD40 conditioning and well-timed immunization prolongs CD8+ T cell accumulation and control of established brain tumors. J Immunother. .31(9):906-20, 2008. PMCID: PMC2923041
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25.Tagaram HR, Watson AM, Lemonnier FA, Staveley-O'Carroll K, Tevethia SS, Schell TD. An SV40 VP1-derived epitope recognized by CD8+ T cells is naturally processed and presented by HLA-A*0201 and cross-reactive with human polyomavirus determinants. Virology. .376(1):183-90, 2008. PMCID: PMC2464359
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26.Staveley-O'Carroll K, Schell TD, Jimenez M, Mylin LM, Tevethia MJ, Schoenberger SP, Tevethia SS. In vivo ligation of CD40 enhances priming against the endogenous tumor antigen and promotes CD8+ T cell effector function in SV40 T antigen transgenic mice. J Immunol. .171(2):697-707, 2003.
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27.Sotomayor EM, Borrello I, Rattis FM, Cuenca AG, Abrams J, Staveley-O'Carroll K, Levitsky HI. Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood. .98(4):1070-7, 2001.
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28.Staveley-O'Carroll K, Sotomayor E, Montgomery J, Borrello I, Hwang L, Fein S, Pardoll D, Levitsky H. Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acad Sci U S A. .95(3):1178-83, 1998. PMCID: PMC18712
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