01064-A: Immunocytochemical Detection and siRNA-Mediated Knockdown of Survivin in Canine Lymphoma

Grant Amount: $12,749

Douglas H Thamm, VMD; Colorado State University

February 1, 2008 - July 31, 2009

Sponsor(s):

Breed(s): -All Dogs

Research Program Area: Oncology

Project Summary

Survivin is a protein found within many cancer cells that can function to prevent cancer cells from being killed by chemotherapy. These researchers recently published data describing methods for measuring survivin in canine lymphoma and found that dogs with low levels of survivin lived longer than those dogs that expressed high levels of survivin. The problem with the previous study is that in order to analyze survivin expression, all dogs needed to undergo a lymph node excision that required anesthesia and surgical removal of a lymph node. One purpose of this study was to determine whether survivin expression could be measured using less invasive techniques such as a fine needle aspirate, which can be done without surgery. The project collected and stained 20 planned samples, and evaluated corresponding tissue blocks, and determined that the smearing technique routinely used for evaluation of fine-needle aspirates was not suitable for the evaluation of survivin levels. The researchers will be evaluating an alternate cell preparation technique in the coming months beyond the scope of the orinal grant, at no additional cost to AKCCHF. The second purpose of this study was to molecularly interfere with survivin levels in canine lymphoma cells that can be grown in the laboratory, in order to test whether these lymphoma cells are more easily killed. Despite numerous attempts to decrease survivin production from the canine lymphoma cells, it was only modestly decreased in either cell line (<50%). This degree of survivin reduction was not able to increase cell death. The researchers are planning to evaluate 2 alternative strategies for survivin inhibition, including a more potent method of gene knockdown, as well as a drug that has been recently shown to inhibit survivin production. These investigations, which are beyond the scope of the original project, will be completed in the coming months, also at no additional cost to AKCCHF.

Publication(s)

Shoeneman, J. K., Ehrhart, E. J., Charles, J. B., & Thamm, D. H. (2014). Survivin inhibition via EZN-3042 in canine lymphoma and osteosarcoma. Veterinary and Comparative Oncology, 14(2), e45–e57. https://doi.org/10.1111/vco.12104

Shoeneman, J. K., Ehrhart, E. J., Eickhoff, J. C., Charles, J. B., Powers, B. E., & Thamm, D. H. (2012). Expression and Function of Survivin in Canine Osteosarcoma. Cancer Research, 72(1), 249–259. https://doi.org/10.1158/0008-5472.CAN-11-2315