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Author Notes:

Syed Faaiz Enam, faaiz.enam@gmail.com

Ravi V. Bellamkonda, ravi@duke.edu

S.F.E. conceived the project. S.F.E., C.Y.K., J.H., C.S.T., and E.I. conducted the in vitro studies and data analysis. S.F.E., B.J.K., and M.I.B. conducted the in vivo studies and histology. R.C. and S.F.E. conducted the computational studies. S.J.B. conducted MRI and analysis. A.F.B. and S.F.E. conducted histological analysis. S.F.E. and S.J.O. designed and fabricated the devices. S.F.E. wrote the manuscript. All authors edited and reviewed the manuscript. S.F.E., J.G.L., and R.V.B. supervised the studies. R.V.B. funded all the studies.

We are grateful to N. Mehta and S. Carroll for providing CAR T cells, the CIVM at Duke University for MRI, the staff (K. Lynn, B. Pickle, J. DeGraff, and F. Orozco) and veterinarians (F. Smith and C. Rouse) at the Duke Vivarium for assistance in setting up and maintaining animal experiments, E. Mallon for advice on setting up a temperature recording system, and S. Ather Enam for neurosurgical insights.

S.F.E., S.J.O., R.C., and R.V.B. are inventors on a patent related to this work filed by Duke University (no. WO2021076962A1, filed on 16 October 2020, published on 22 April 2021) and pending patent filed by Duke University (no. 17/769,985, filed on 18 April 2022). The authors declare no other competing interests.

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Research Funding:

The authors acknowledge that they received no funding in support of this research.

Keywords:

  • Rats
  • Animals
  • Glioblastoma
  • Hypothermia
  • Cytostatic Agents
  • Rats, Sprague-Dawley
  • Hypothermia, Induced

Cytostatic hypothermia and its impact on glioblastoma and survival

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Journal Title:

Science Advances

Volume:

Volume 8, Number 47

Publisher:

, Pages eabq4882-eabq4882

Type of Work:

Article | Final Publisher PDF

Abstract:

Patients with glioblastoma (GBM) have limited options and require novel approaches to treatment. Here, we studied and deployed nonfreezing “cytostatic” hypothermia to stunt GBM growth. This growth-halting method contrasts with ablative, cryogenic hypothermia that kills both neoplastic and infiltrated healthy tissue. We investigated degrees of hypothermia in vitro and identified a cytostatic window of 20° to 25°C. For some lines, 18 hours/day of cytostatic hypothermia was sufficient to halt division in vitro. Next, we fabricated an experimental tool to test local cytostatic hypothermia in two rodent GBM models. Hypothermia more than doubled median survival, and all rats that successfully received cytostatic hypothermia survived their study period. Unlike targeted therapeutics that are successful in preclinical models but fail in clinical trials, cytostatic hypothermia leverages fundamental physics that influences biology broadly. It is a previously unexplored approach that could provide an additional option to patients with GBM by halting tumor growth.

Copyright information:

© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
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