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The acute effects of CMF-based chemotherapy on maxillary periodontal microcirculation

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Abstract

Purpose

A high incidence of oral complications is associated with chemotherapy (CT) treatment in cancer patients; however, while knowledge into molecular mechanisms of their pathobiology continue to evolve, the direct physiological effects of CT on oral tissue perfusion remain unexplored. The aim of this investigation was to assess the acute effects of CT on gingival microcirculation perfusion by measuring gingival capillary density.

Methods

Twenty female specific-pathogen free New Zealand White rabbits were randomly divided into four groups receiving four different intravenous dose levels of cyclophosphamide, methotrexate, and fluorouracil (CMF). Noninvasive measurements of gingival capillary density were performed using sidestream dark-field (SDF) imaging prior to and 30 min after CT treatment. Four rabbits receiving saline solution were used as control animals.

Results

Baseline gingival capillary density was 58 ± 11 cpll/mm2, no significant differences in baseline capillary densities between the groups were found. From low to high dose CT, capillary density 30 min after CMF treatment increased in each group by 1 ± 7, 5 ± 7, 13 ± 18 and 20 ± 13 cpll/mm2, respectively. Capillary density increase was significant in the high-dose group. No change in gingival capillary density was found in the control group.

Conclusions

Periodontal microcirculation perfusion had increased 30 min after CT treatment as indicated by a rise in gingival capillary density. Our results support the idea that CT-induced microcirculatory response not only diligently delivers but also saturates peripheral oral tissues with antineoplastic agents by increasing surface area exposure. This functional response of the microcirculation to CT drugs may play a role in contribution to oral complications and the treatment of oral tumors.

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Acknowledgments

We thankfully acknowledge professor Dr. M. A. Pokras from Tufts University for reviewing our drug scaling calculations. We are grateful to Dr. H. A. Griffioen and Dr. W. J. Florijn for their valuable advice on anesthesia in our animals and Mr. K. W. Meyer for biotechnical support. This project was funded by Novartis Pharmaceuticals Inc., Basel, Switzerland.

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Authors and Affiliations

  1. Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Dan M. J. Milstein, Rick Bezemer & Can Ince

  2. Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Dan M. J. Milstein & Jérôme A. H. Lindeboom

  3. Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam, Louwesweg 1, 1066 EA, Amsterdam, The Netherlands

    Dan M. J. Milstein & Jérôme A. H. Lindeboom

Authors
  1. Dan M. J. Milstein
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  2. Rick Bezemer
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  3. Jérôme A. H. Lindeboom
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  4. Can Ince
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Correspondence to Dan M. J. Milstein.

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Milstein, D.M.J., Bezemer, R., Lindeboom, J.A.H. et al. The acute effects of CMF-based chemotherapy on maxillary periodontal microcirculation. Cancer Chemother Pharmacol 64, 1047–1052 (2009). https://doi.org/10.1007/s00280-009-1082-x

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  • DOI: https://doi.org/10.1007/s00280-009-1082-x

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