Repository logo
 

Chemotherapeutic responses in canine lymphoma models after treatment with the CHOP protocol

Date

2016

Authors

Ramirez, Dominique, author
Wittenburg, Luke, author

Journal Title

Journal ISSN

Volume Title

Abstract

In both human and veterinary oncology, multi-drug resistance is a phenomenon where a cancer gains a cyto-protective effect against chemotherapeutics. Resistance is often witnessed when remitted cancers relapse and become untreatable. As an example, canine lymphomas are notorious for relapsing after treatment with the multi-drug CHOP protocol. While canonical drug efflux transporters have been implicated with the chemo-resistance phenotype, there are other transporters which might also contribute. Recent research has demonstrated that exposure to chemotherapeutics results in epigenetic changes to transporter gene expression; this could be a possible route for acquiring the resistance phenotype. What is still unknown, however, is a mechanistic understanding of the chemotherapy-transporter expression relationship. To address this void, we are focusing our research on three questions: 1) What are the temporal fluctuations in transporter expression following exposure to multi-drug regimens? 2) What patterns of epigenetic markers on transporter genes promote altered expression? 3) How does transporter expression correlate to protein levels in chemo-resistant lymphomas? We will address each of these questions using a panel of four chemo-sensitive canine lymphomas as our models, and the CHOP protocol as our drug regimen. We will expose the lymphomas to combinations of the CHOP protocol to mimic short- and long-term treatments, and monitor transporter expression via QT-PCR, and epigenetic changes via ChIP-assays. Additionally, protein levels will be monitored with LC-MS/MS methods to correlate expression with translation. We hypothesize that changes in transporter expression exhibit temporal and drug-dependent patterns.

Description

Includes bibliographical references.

Rights Access

Subject

chemoresistance
CHOP protocol
SLC transporters
SLC expression
canine clinical lymphoma

Citation

Associated Publications

Collections