Characterising the effects of 1,4,5-Oxathiazinane-4,4-dioxide (OTD) on non-neoplastic cells and primary and metastatic melanoma cells in vitro
type: CreativeWork
description: Melanoma is an aggressive form of skin cancer, responsible for the largest proportion of skin cancer related deaths in Ireland (69.4%) despite only accounting for 9% of all skin cancers leading to the development of several adjuvant therapies aiming to reduce mortality. Tissue damage inflicted by surgical excision of tumours, can induce an exaggerated sterile proinflammatory immune response followed by immunosuppression, providing an optimal environment for residual tumour cells to differentiate, proliferate and propagate into surrounding and distant tissues resulting in cancer recurrence. Surgical adjuvants have the potential to induce cytotoxicity in residual tumour cells and reduce excessive inflammation, possibly preventing subsequent immunosuppression. The synthesised compound 1,4,5-oxathiazinane-4,4-dioxide (OTD) is a structural analogue of Taurultam derived from anti-inflammatory Taurolidine. OTD demonstrates anti-neoplastic actions against several cancers, however, its effects on inflammation and wound healing remain undetermined. The overall aim of this study was to assess the potential of OTD as an adjuvant treatment following melanoma excision by investigating its effects on cells involved in wound healing (Human Dermal Fibroblast (HDF) cells), tumourigenesis (primary and metastatic melanoma cells) and the adaptive immune system (CD8+ T lymphocytes). The physiological and pathological functions of these cell types were assessed in vitro with five concentrations of OTD (0.25mM, 0.5mM, 0.75mM, 1mM and 1.25mM). Given the critical role of wound healing in the post-operative period, this thesis initially assessed the effects of OTD on the wound healing capacity of HDF cells. At concentrations up to 0.75mM of OTD this study demonstrated that OTD, does not significantly impair HDF migratory function in a wound healing assay (n=3, p>0.05). Additionally, OTD effectively suppressed the release of pro-inflammatory cytokines, IL-6 and IL-8, in IL-1α stimulated HDF ce…
abstract: Melanoma is an aggressive form of skin cancer, responsible for the largest proportion of skin cancer related deaths in Ireland (69.4%) despite only accounting for 9% of all skin cancers leading to the development of several adjuvant therapies aiming to reduce mortality. Tissue damage inflicted by surgical excision of tumours, can induce an exaggerated sterile proinflammatory immune response followed by immunosuppression, providing an optimal environment for residual tumour cells to differentiate, proliferate and propagate into surrounding and distant tissues resulting in cancer recurrence. Surgical adjuvants have the potential to induce cytotoxicity in residual tumour cells and reduce excessive inflammation, possibly preventing subsequent immunosuppression. The synthesised compound 1,4,5-oxathiazinane-4,4-dioxide (OTD) is a structural analogue of Taurultam derived from anti-inflammatory Taurolidine. OTD demonstrates anti-neoplastic actions against several cancers, however, its effects on inflammation and wound healing remain undetermined. The overall aim of this study was to assess the potential of OTD as an adjuvant treatment following melanoma excision by investigating its effects on cells involved in wound healing (Human Dermal Fibroblast (HDF) cells), tumourigenesis (primary and metastatic melanoma cells) and the adaptive immune system (CD8+ T lymphocytes). The physiological and pathological functions of these cell types were assessed in vitro with five concentrations of OTD (0.25mM, 0.5mM, 0.75mM, 1mM and 1.25mM). Given the critical role of wound healing in the post-operative period, this thesis initially assessed the effects of OTD on the wound healing capacity of HDF cells. At concentrations up to 0.75mM of OTD this study demonstrated that OTD, does not significantly impair HDF migratory function in a wound healing assay (n=3, p>0.05). Additionally, OTD effectively suppressed the release of pro-inflammatory cytokines, IL-6 and IL-8, in IL-1α stimulated HDF ce…
author: O'Callaghan, Stephanie
language: en
keywords: Melanoma, OTD, Postoperative inflammation, Immunosuppression, Wound healing, Surgical adjuvant
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
date published: 2024
date modified: 2026-07-24T01:47:31Z
provider: University College Cork
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University College Cork

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10468/18431