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Sarcoma
Volume 2018 (2018), Article ID 3143096, 12 pages
https://doi.org/10.1155/2018/3143096
Research Article

Aerosol Gemcitabine after Amputation Inhibits Osteosarcoma Lung Metastases but Not Wound Healing

1The University of Texas MD Anderson Cancer Center, Division of Pediatrics, 1515 Holcombe Blvd., Unit 0853, Houston, TX 77030, USA
2The University of Texas MD Anderson Cancer Center, Stem Cell Transplantation Research, 1515 Holcombe Blvd., Houston, TX 77030, USA
3Nightlight Urgent Care, 15551 Southwest Freeway, Sugar Land, TX 77478, USA
4Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Children’s Cancer Hospital, 1515 Holcombe Blvd., Unit 1484, Houston, TX 77030, USA
5Department of Orthopedic Surgery, University of West Virginia, P.O. Box 9196, Morgantown, WV 26506-9196, USA
6The University of Texas MD Anderson Cancer Center, Pharmacy Pharmacology Research, 1515 Holcombe Blvd., Unit 0090, Houston, TX 77030, USA
7Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA

Correspondence should be addressed to Eugenie S. Kleinerman

Received 17 August 2017; Accepted 25 October 2017; Published 21 January 2018

Academic Editor: Fritz C. Eilber

Copyright © 2018 Eugenie S. Kleinerman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. In newly diagnosed osteosarcoma (OS) patients, the time between surgery and resumption of chemotherapy is 2–7 weeks. Delays > 16 days are associated with increased risk of relapse and decreased overall survival. Identifying an effective therapy that can be used postoperatively may prevent relapse. We investigated whether aerosol gemcitabine (GCB) initiated after tumor resection inhibited the growth of OS lung metastases without affecting the wound-healing process. Methods. Mice were injected intratibially with OS cells. Amputation was performed when the tumor reached 1.5 cm. Full-thickness excisional wounds were also made on the dorsal skin and tail. Aerosol GCB or PBS was initiated 48 hours after amputation (3 times/week for 3 weeks). Wound sections were evaluated by immunohistochemistry for Ki-67 (proliferation), CD31 (vessels), VEGF, IL-10, bFGF, mast cells, macrophages, and M1/M2 macrophage ratios. The lungs were analyzed for macro- and micrometastases. Results. Aerosol GCB inhibited the growth of the lung metastases but had no effect on the 3 phases of wound healing in the dorsal skin, tail, or bone. Production of cytokines at the wound sites was the same. Conclusion. These data indicate that initiating aerosol GCB postoperatively may kill residual lung metastases thereby preventing relapse and improve survival.