Emergency Use of Targeted Osmotic Lysis for the Treatment of a Patient with Aggressive Late-Stage Squamous Cell Carcinoma of the Cervix

Abstract

Upregulation of voltage-gated sodium channels (VGSCs) and Na⁺/K⁺-ATPase (sodium pumps) is common across most malignant carcinomas. Targeted osmotic lysis (TOL) is a developing technology in which the concomitant stimulation of VGSCs and pharmacological blockade of sodium pumps causes rapid selective osmotic lysis of carcinoma cells. This treatment of cervical carcinoma is evidence that TOL is a safe, well-tolerated and effective treatment for aggressive advanced carcinomas that has the potential to extend life without compromising its quality. TOL is likely to have broad application for the treatment of advanced-stage carcinomas.

Trial registration: ClinicalTrials.gov NCT01414608.

Keywords: advanced-stage cervical cancer; sodium channels; sodium pumps; targeted osmotic lysis.

Figure 1

The photomicrographs depict the immunohistochemical labeling of voltage-gated sodium channels (VGSCs) (green) in a biopsy of the stage IIB carcinoma of the cervix obtained from the patient prior to treatment with targeted osmotic lysis (TOL). Sections were incubated and then processed with a goat-anti-rabbit 488 Alexa fluorophore secondary antibody, 1:800 dilution. Nuclei were counterstained with DRAQ5 (blue; dilution 1:600). Twelve images taken with a Leica DMi8 confocal microscope at 40× oil magnification were reviewed for evidence of VGSC labeling. Panel (A) depicts a representative portion of the biopsy where many cells, approximately 40% of the total, highly expressed VGSCs. Cellular profiles from three sections were outlined and the mean fluorescence intensity was measured using the ImageJ-FIJI software (imagej.nih.gov; accessed on 19 May 2021) to quantify the sodium channel expression. The histogram (B) presents the average mean fluorescence intensity measured from 50 intensely stained and 50 weakly stained cell profiles compared to the background indicative of the level of VGSC expression in highly expressing tumor cells and minimally expressing neoplastic and stromal cells, respectively. A one-way ANOVA was significant (p < 0.00001); * = p < 0.001 compared to the background; ** = p < 0.001 compared to weakly expressing cells (Student’s t-test with Scheffe’s adjustment). Calibration bar in A = 25 µm.

Figure 2

The photograph depicts the patient in the bore of the custom-built coaxial ring device used to deliver the uniform pulsed electric fields necessary for opening the VGSCs in TOL (The Phantom Laboratory, Salem, NY, USA).

Figure 3

Transverse computed tomographic images of the Stage IIB carcinoma of the cervix obtained from the patient before (A) and 3 (B) and 21 days (C) after treatment with TOL. The images were chosen to depict cuts through the tumor at levels as closely similar as possible. Adjustments of magnifications were made to match the dimensions of bony landmarks of the femoral head and acetabulum. Adjustments of contrast and brightness for optimum clarity of the images were applied equally to all the three images. Note that the size of the tumor increases with each successive image. By contrast-enhanced CT, areas of hypodensity observed within the tumor mass appear larger and much more prominent after treatment with TOL, consistent with the reduction in measured tissue densities from 70 HU pre-treatment (A) to 56 HU (B) by day 3 and 47 HU (C) by day 21 post-treatment. Additional region-of-interest (ROI) reference measurements were made for each scan over the left gluteal musculature revealing values of 127 HU (A), 120 HU (B) and 125 HU (C), respectively. Calibration bar in C = 5 cm.