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Ito D, Childress M, Mason N, et al. A double blinded, placebo-controlled pilot study to examine reduction of CD34 . F1000Res. 2015;4:42doi: 10.12688/f1000research.6055.2.
Ito, D., Childress, M., Mason, N., Winter, A., O'Brien, T., Henson, M., Borgatti, A., Lewellen, M., Krick, E., Stewart, J., Lahrman, S., Rajwa, B., Scott, M. C., Seelig, D., Koopmeiners, J., Ruetz, S., & Modiano, J. (2015). A double blinded, placebo-controlled pilot study to examine reduction of CD34 . F1000Research, 442. https://doi.org/10.12688/f1000research.6055.2
Ito, Daisuke, et al. "A double blinded, placebo-controlled pilot study to examine reduction of CD34 ." F1000Research vol. 4 (2015): 42. doi: https://doi.org/10.12688/f1000research.6055.2
Ito D, Childress M, Mason N, Winter A, O'Brien T, Henson M, Borgatti A, Lewellen M, Krick E, Stewart J, Lahrman S, Rajwa B, Scott MC, Seelig D, Koopmeiners J, Ruetz S, Modiano J. A double blinded, placebo-controlled pilot study to examine reduction of CD34 . F1000Res. 2015 Feb 11;4:42. doi: 10.12688/f1000research.6055.2. eCollection 2015. PMID: 28357033; PMCID: PMC5357040.
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F1000Res. 2015 Feb 11;4:42. doi: 10.12688/f1000research.6055.2. eCollection 2015.

A double blinded, placebo-controlled pilot study to examine reduction of CD34 .

F1000Research

Daisuke Ito, Michael Childress, Nicola Mason, Amber Winter, Timothy O'Brien, Michael Henson, Antonella Borgatti, Mitzi Lewellen, Erika Krick, Jane Stewart, Sarah Lahrman, Bartek Rajwa, Milcah C Scott, Davis Seelig, Joseph Koopmeiners, Stephan Ruetz, Jaime Modiano

Affiliations

  1. Animal Cancer Care and Research Program, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
  2. Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN, 47907, USA.
  3. Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19104, USA; Department of Pathology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19104, USA.
  4. Animal Cancer Care and Research Program, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Clinical Investigation Center, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA.
  5. Animal Cancer Care and Research Program, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA; Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA.
  6. Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19104, USA.
  7. Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN, 47907, USA.
  8. Animal Cancer Care and Research Program, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA.
  9. Novartis Pharma AG, Basel, 4056, Switzerland.
  10. Animal Cancer Care and Research Program, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA.

PMID: 28357033 PMCID: PMC5357040 DOI: 10.12688/f1000research.6055.2

Abstract

We previously described a population of lymphoid progenitor cells (LPCs) in canine B-cell lymphoma defined by retention of the early progenitor markers CD34 and CD117 and "slow proliferation" molecular signatures that persist in the xenotransplantation setting. We examined whether valspodar, a selective inhibitor of the ATP binding cassette B1 transporter (ABCB1, a.k.a., p-glycoprotein/multidrug resistance protein-1) used in the neoadjuvant setting would sensitize LPCs to doxorubicin and extend the length of remission in dogs with therapy naïve large B-cell lymphoma. Twenty dogs were enrolled into a double-blinded, placebo controlled study where experimental and control groups received oral valspodar (7.5 mg/kg) or placebo, respectively, twice daily for five days followed by five treatments with doxorubicin 21 days apart with a reduction in the first dose to mitigate the potential side effects of ABCB1 inhibition. Lymph node and blood LPCs were quantified at diagnosis, on the fourth day of neoadjuvant period, and 1-week after the first chemotherapy dose. Valspodar therapy was well tolerated. There were no differences between groups in total LPCs in lymph nodes or peripheral blood, nor in event-free survival or overall survival. Overall, we conclude that valspodar can be administered safely in the neoadjuvant setting for canine B-cell lymphoma; however, its use to attenuate ABCB1

Keywords: ABCB1/P-glycoprotein; canine; cells; lymphoma; non-Hodgkin; progenitor; valspodar

Conflict of interest statement

Competing interests: Dr. Stephan Ruetz is employed by Novartis Pharma AG. All other authors have no competing interest to declare.

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