| 268 | Valerie Sampson, Ph.D. | <p>Assistant Research Scientist II </p> | (302) 651-4832 | (302) 651-4827 | valerie.sampson@nemours.org | Cancer Therapeutics Laboratory A.I. duPont Hospital for Children Rockland Center I 1701, Rockland Road Wilmington, DE. 19803 | | | <ul>
<li><strong>B.S.</strong> - University of the West Indies (Trinidad)
</li><li><strong>Ph.D.</strong> - University of the West Indies (Trinidad)
</li><li><strong>Postdoctoral -</strong> New York Medical College, NY </li></ul> | | <p>The Cancer Therapeutics Laboratory (CTL) conducts basic and preclinical research to understand the biology of pediatric bone tumors and to test novel approaches to identify the path toward improving outcomes for patients with these diseases. One longstanding area of focus has been targeted therapies that have been studied in pediatric patients with osteosarcoma and Ewing sarcoma. Unfortunately, acquired drug resistance is a major hurdle to the successful treatment of these diseases. In general, tumors can develop one or more complex mechanisms of drug resistance that maintain tumor cell survival and can render targeted therapies ineffective in most patients. Our laboratory focuses on understanding the mechanism(s) of action of new and existing anticancer drugs to identify potential molecular targets for diagnostic, prognostic and therapeutic strategies in pediatric sarcomas.</p>
<p>The development of reliable preclinical testing data for drug candidates can be used to support the development of future clinical trials in pediatric patients.</p> | <ul>
<li><strong>Receptor tyrosine kinase (RTK) inhibition. </strong>Signaling through RTKs promotes proliferation and survival in sarcoma. Selective inhibition of the Type 1 insulin-like growth factor receptor (IGF-1R) and other RTKs has demonstrated poor clinical responses in pediatric patients with solid tumors. The lack of clinical benefits in patients to this treatment approach is not fully understood and there is general concern with the development of resistance and relapse to the strategy of tyrosine kinase inhibition. In this study, we examine dual inhibition of anaplastic lymphoma receptor (ALK) and IGF-1R tyrosine kinase inhibitors in osteosarcoma cell lines and patient-derived osteosarcoma xenograft tumors. We are investigating the effects of targeted inhibition on key signaling transduction pathways that are involved in cell proliferation and survival.
</li><li><strong>Microtubule inhibition. </strong>We are also interested in the activity of microtubule inhibitors in sarcoma. Microtubules are cylindrical and dynamic polymers that consist of the protein tubulin. The biological function of the microtubule cytoskeleton relies on the precise arrangement of microtubules in the cell. Agents that disrupt microtubule structures can successfully eliminate cancer cells. We aim to characterize these mechanisms of drug action and use this insight to investigate how agents that target the microtubule cytoskeleton can be developed for safe and effective treatment strategies against pediatric osteosarcoma.
</li><li><strong>microRNAs (miRNAs). </strong>We are also exploring the role of miRNAs in pediatric sarcoma. These are small RNA molecules of approximately 20 to 22 nucleotides that reduce expression of proteins through mRNA degradation and/or translational silencing. Each known miRNA has a large number of predicted targets and has been shown to regulate critical cellular process and functions in cancer. Our current work identifies miRNAs that are either overexpressed (oncogenes) or lost (tumor suppressors) in osteosarcoma and Ewing sarcoma. The small size of these molecules along with the ability to be detected in patient blood samples, make miRNAs interesting molecules that may be developed for potential diagnostic and prognostic targets. </li></ul> | <ul>
<li>Andy Kolb, MD - Lab Head/Director, Nemours Center for Cancer and Blood Disorders
</li><li>Nancy Vetter, BS - Research Assistant I
</li><li>Renee Gresh, MD - Fellow </li></ul> | <ol>
<li><strong>Sampson VB</strong>, Vetter NS, Kamara DF, Collier AB, Gresh RC, Kolb EA. Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways. PLoS One. 2015 Nov 16;10(11).
</li><li><strong>Sampson VB</strong>, Yoo S, Kumar A, Vetter NS, Kolb EA. MicroRNAs and Potential Targets in Osteosarcoma: Review. Front Pediatr. 2015 Aug 24;3:69.
</li><li>Kolb EA, Sampson V, Stabley D, Walter A, Sol-Church K, Cripe T, Hingorani P, Ahern CH, Weigel BJ, Zwiebel J, Blaney SM. A phase I trial and viral clearance study of reovirus (Reolysin) in children with relapsed or refractory extra-cranial solid tumors: A Children's Oncology Group Phase I Consortium report. Pediatr Blood Cancer. 2015 May;62(5):751-8.
</li><li><strong>Sampson VB</strong>, David JM, Puig I, Patil PU, de Herreros AG, Thomas GV, Rajasekaran AK. (2014) Wilms’ Tumor Protein Induces an Epithelial-Mesenchymal Hybrid Differentiation State in Clear Cell Renal Cell Carcinoma. PLoS One. 2014 Jul 15;9(7).
</li><li>Hingorani P, <strong>Sampson, VB</strong>, Lettieri CK, Kolb EA. (2014) Oncolytic Viruses for Potential Osteosarcoma Therapy. Current Advances in Osteosarcoma. Adv Exp Med Biol. 2014;804:259-83.
</li><li><strong>Sampson VB</strong>, Kamara D, Kolb EA. (2013). Xenograft and Genetically engineered mouse model systems of Osteosarcoma and Ewing Sarcoma: Tumor models for cancer drug discovery. Expert Opin. Drug Discov. Oct;8(10):1181-9.
</li><li><strong>Sampson VB</strong>, Gorlick R, Kamara D, Anders Kolb E. (2013). A review of targeted therapies evaluated by the pediatric preclinical testing program for osteosarcoma. Front Oncol. 2013 May 31;3:132.
</li><li>Huynh TP, Mah V, <strong>Sampson VB</strong>, Chia D, Fishbein MC, Horvath S, Alavi M, Wu DC, Harper J, Sarafian T, Dubinett SM, Langhans SA, Goodglick L, Rajasekaran AK. (2012) Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer. Am J Physiol Lung Cell Mol Physiol. 302(11):L1150-8.
</li><li>Alleyne T, <strong>Sampson VB</strong>. (2009) Early electron transfer in cytochrome c oxidase occurs by a chymotrypsin type relay. West Indian Med J. Dec 58(6): 499-505.
</li><li>Tummala R, Wolle D, Barwe SP, <strong>Sampson VB</strong>, Rajasekaran AK, Pendyala L. (2009) Expression of Na,K-ATPase-beta(1) subunit increases uptake and sensitizes carcinoma cells to oxaliplatin. Cancer Chemother. Pharmacol. Nov;64(6):1187-94.
</li><li><strong>Sampson VB</strong>, Ashe D, Alleyne T. (2009) Probing the specifics of Substrate Binding for Cytochrome c Oxidase: A Computer Assisted Approach. West Indian Med. J. 58(1):54-60.
</li><li><strong>Sampson VB</strong>, Dunn SP, Rymeski B, Malatack J, Rong NH, Flynn L, Krueger LJ. (2008) Failure of immunosuppressive drug levels to predict T-cell reactivity in pediatric transplant patients. J. Ped. Res. J. Pediatr Surg Jun; 43(6):1134-41.
</li><li><strong>Sampson VB</strong>, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, Petrelli NJ, Dunn SP, Krueger LJ. (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 67(20):9762-70.
</li><li>Gupte RS, <strong>Sampson V</strong>, Tragonos F, Darzynkiewicz Z, Lee MY. (2006) Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7 cells. Exp Cell Res. 312(6): 796-806. </li></ol> | | | | |
