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Angiotensin-(1–7) synergizes with colony-stimulating factors in hematopoietic recovery

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Angiotensin (1–7) [A(1–7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1–7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and the recovery of circulating formed elements following chemotherapy.

Methods

Mice were injected with gemcitabine followed 2 days later with A(1–7). Circulating blood cells and bone marrow progenitors were measured over time.

Results

Combination of A(1–7) with Neupogen (the latter given only 3 days starting at the white blood cell nadir) decreased the amount of Neupogen needed for optimal recovery by 10-fold. The progenitors measured include CFU-GEMM, CFU-GM, CFU-Meg and BFU-E. A(1–7) increased recovery of all progenitors when given alone or in combination with Neupogen above that with Neupogen alone. Combination of A(1–7) with Epogen slightly increased (not significantly) red blood cell concentrations above those achieved by Epogen alone. However, in this model, A(1–7) or A(1–7) in combination with Epogen increased all erythroid progenitors with the largest effect on early erythroid progenitors (immature BFU-E).

Conclusions

Neupogen and Epogen acted synergistically with A(1–7) to increase the concentration of myeloid, megakaryocytic and erythroid progenitor cells in the bone marrow following chemotherapy suggesting that A(1–7)’s multilineage effect on early progenitors in the marrow facilitates proliferation in response to lineage-specific growth factors.

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Acknowledgments

Financial support for this research was provided by Tarix Inc. The authors would like to thank Melissa Donald for assistance in manuscript preparation and submission.

Conflict of interest

Only Dr. Rodgers and Dr. diZerega have conflicts. They are inventors on patents covering the activities of A(1–7) in bone marrow recovery.

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Authors and Affiliations

  1. Titus Family Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Room 530, Los Angeles, CA, 90089, USA

    Kathleen E. Rodgers, Theresa B. Espinoza, Norma Roda & Christopher J. Meeks

  2. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Gere S. diZerega

Authors
  1. Kathleen E. Rodgers
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  2. Theresa B. Espinoza
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  3. Norma Roda
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  4. Christopher J. Meeks
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  5. Gere S. diZerega
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Corresponding author

Correspondence to Kathleen E. Rodgers.

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Rodgers, K.E., Espinoza, T.B., Roda, N. et al. Angiotensin-(1–7) synergizes with colony-stimulating factors in hematopoietic recovery. Cancer Chemother Pharmacol 72, 1235–1245 (2013). https://doi.org/10.1007/s00280-013-2312-9

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  • DOI: https://doi.org/10.1007/s00280-013-2312-9

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