Graduate Thesis Or Dissertation


Prospective Evaluation of the Lymph Node Proteome in Dogs with Multicentric Lymphoma Supplemented with Sulforaphane Public Deposited

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  • Lymphoma (LSA) is one of the most common canine malignancies, and is almost invariably a terminal disease. Epigenetic changes in canine and human lymphomas have been linked to disease progression and poor prognosis, leading to the development of epigenetic-targeted therapies which have shown promise in treating various forms of human LSA. Sulforaphane (SFN), a compound derived from cruciferous vegetables, has recently gained significant interest related to cancer prevention and therapy, in particular due to its effects on the epigenome. However, the use of SFN in tumor-bearing dogs has not been reported. The goal of this study was to examine the impact of SFN supplementation on the lymph node proteome of dogs with multicentric LSA. Seven treatment-naïve dogs with multicentric LSA were prospectively enrolled. Lymph node samples were obtained before and after a week of oral SFN supplementation, analyzed by label-free mass spectrometry and Gene Set Enrichment Analysis followed by validation of the results with Immunoblot analysis. No adverse events directly attributed to SFN supplementation were noted. A total of 915 proteins were detected across all dogs, among which 14 proteins were significantly downregulated, and 10 significantly upregulated post-SFN supplementation. For each individual dog, the expression of several hundred of proteins changed by at least two-fold post-SFN supplementation. Proteome changes post-SFN were not dependent on LSA immunophenotype. Recurrent biological functions for the proteins and gene sets identified included regulation of innate or adaptive immunity, regulation of the transcription machinery, protein transport and ubiquitination, cellular response to oxidative stress, and apoptosis. These results confirm that the impact of SFN in neoplastic cells are manifold, and support further investigation of this compound in canine LSA patients, alone and/or in combination with standard therapies
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