High Hydrostatic Pressure Therapy Annihilates Squamous Cell Carcinoma in a Murine Model.

Toshihito Mitsui,Naoki Morimoto,Atsushi Mahara,Natsuko Kakudo,Sharon Claudia Notodihardjo,Kenji Kusumoto,Tetsuji Yamaoka,Tien Minh Le,Maria Chiara Munisso

doi:10.1155/2020/3074742

Abstract

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. In the treatment of cSCC, it is necessary to remove it completely, and reconstructive surgery, such as a skin graft or a local or free flap, will be required, depending on the size, with donor-site morbidity posing a burden to the patient. The high hydrostatic pressure (HHP) technique has been developed as a physical method of decellularizing various tissues. We previously reported that HHP at 200 MPa for 10 min could inactivate all cells in the giant congenital melanocytic nevus, and we have already started a clinical trial using this technique. In the present study, we explored the critical pressurization condition for annihilating cSCC cells in vitro and confirmed that this condition could also annihilate cSCC in vivo. We prepared 5 pressurization conditions in this study (150, 160, 170, 180, and 190 MPa for 10 min) and confirmed that cSCC cells were killed by pressurization at ≥160 MPa for 10 min. In the in vivo study, the cSCC cells inactivated by HHP at 200 MPa for 10 min were unable to proliferate after injection into the intradermal space of mice, and transplanted cSCC tissues that had been inactivated by HHP showed a decreased weight at 5 weeks after implantation. These results suggested that HHP at 200 MPa for 10 min was able to annihilate SCC, so HHP technology may be a novel treatment of skin cancer.

Highlights

Cutaneous squamous cell carcinoma is one of the most common skin cancers, accounting for 20% of all nonmelanoma skin cancers and posing a deadly threat, due to its ability to metastasize to any organ in the body [1]
We previously reported that high hydrostatic pressure (HHP) at 200 MPa for 10 min was able to inactivate all cells in the giant congenital melanocytic nevus (GCMN), and we have already started a clinical trial
The percentage of Cutaneous squamous cell carcinoma (cSCC) cells stained by the red fluorescence derived from the ethidium homodimer II nucleic acid stain increased with increasing pressure, and the cSCC cells were largely inactivated beyond 190 MPa (Figure 1(f))

Summary

Introduction

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, accounting for 20% of all nonmelanoma skin cancers and posing a deadly threat, due to its ability to metastasize to any organ in the body [1]. Various treatments for cSCC have been developed, such as surgical excision, radiation therapy, chemotherapy, epidermal growth factor receptor inhibitors, and immune checkpoint blockers [2]. In the treatment of the cSCC tumor, it is important to remove cSCC cells completely [3]. Reconstructive surgery, such as a skin graft or a local or free flap, will be required, depending on the defect left after resection [4, 5]. When we reconstruct skin defects after removal surgery, donor-site morbidity is a major issue for patients. A less invasive procedure is desirable in the treatment of cSCC

Methods

Results

Conclusion