title: A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy.
abstract: OBJECTIVE
  The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice.
  
  
  METHODS
  SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy.
  
  
  RESULTS
  Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice.
  
  
  CONCLUSIONS
  Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy.
authors.affiliation: a Department of Immunology .|b Department of Radiation Medicine , and.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Winslow
authors.affiliation: a Department of Immunology .
authors.forename: Annu
authors.initials: A
authors.lastname: Eranki
authors.affiliation: a Department of Immunology .
authors.forename: Soumya
authors.initials: S
authors.lastname: Ullas
authors.affiliation: b Department of Radiation Medicine , and.
authors.forename: Anurag K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: a Department of Immunology .
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Repasky
authors.affiliation: c Department of Cell Stress Biology , Roswell Park Cancer Institute , Buffalo , NY , USA.
authors.forename: Arindam
authors.initials: A
authors.lastname: Sen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D045604:Extracellular Fluid; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D006801:Humans; D006979:Hyperthermia, Induced; D000860:Hypoxia / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D008081:Liposomes; D016513:Mice, SCID; D010865:Pilot Projects; D011312:Pressure; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: D005456:Fluorescent Dyes; D008081:Liposomes
keywords: Human head and neck cancer; hypoxia; interstitial fluid pressure; radiation therapy; tumour perfusion