Investigation of the physiological response of radiation-induced cystitis patients using hyperbaric oxygen

Abstract

Introduction: In this pilot study we have taken a novel functional approach to assess whether differences exist in the activity of key genes involved in the response to radiation and oxidative stress between patients with radiation cystitis.

Materials and methods: Arm 1 consisted of patients who had previously been treated for prostate cancer and who had received definitive radiation treatment and had subsequently developed cystitis and/or proctitis and were being treated by hyperbaric oxygen (HBO). Arm 2 consisted of patients who had never been treated by radiation but who were scheduled for HBO treatment for another pathology. The genes chosen for the study were HMOX1, NOS2, SOD2, TNFα, IL-6 and TGFβ. Blood and urine was collected pre and post HBO treatment.

Results: Gene expression showed a significant difference in NOS2 (p = 0.0178) and TNFα (p = 0.037) between the control and cystitis patients. The plasma levels of VEGF-A were significantly elevated in cystitis patients and there was a strong trend for significant overexpression in urine. Comparing pre and post-dive samples showed little difference in both groups of patients except for VEGF-A which was reduced after the dive in plasma from cystitis patients.

Conclusions: This study uncovered some physiological differences in patients with radiation-induced cystitis using HBO treatment as a stimulus to induce mild oxidative stress. Further research is ongoing to assess whether the acute exposure to HBO might be a physiological screening tool to identify patients susceptible to chronic radiation toxicity.

Keywords: Biomarkers; Hyperbaric oxygen; Prostate cancer; Radiation cystitis.

Fig. 1

Pathway analysis to select genes of interest highlighted by the black arrows.

Fig. 2

Changes in gene expression pre-and post-dive. The data is presented as the relative quantitation for each gene as a ratio of change of the post-divevalues compared to the pre-dive values for patients with (black) and without (grey) radiation-induced cystitis.

Fig. 3

Protein expression in plasma (A) and urine (B) samples from cystitis and control patients prior to the HBO dive.

Fig. 4

Protein expression in plasma and urine samples pre- and post-dive specimens for control (gray symbol) and cystitis patients (black symbol). The dashed line in each graph represents the line of unity.