TY - THES

T1 - Investigating the thermosensitivity of cancer cell division dynamics

T2 - Toward cancer thermotherapies?

AU - Steel, Christopher

PY - 2021

Y1 - 2021

N2 - The application of heat to treat disease can be dated back over 5000 years. Ancient Egyptian papyrus records describe heated instruments being used to cauterise breast tumours. In recent times, hyperthermia range temperatures are increasingly routinely used to treat cancer. Heating tumours alongside conventional therapies and pre-heating aqueous drug suspensions prior to administration are both commonplace in oncology clinics. Despite this, the mechanisms which underpin the efficacy of hyperthermia therapy in cancer treatment remain poorly understood. In particular, the impact of temperature on cancer cell cycle dynamics is under explored. We set out to investigate these mechanisms. We employed time lapse confocal microscopy and fluorescence ubiquitin-based cell cycle indicator expressing cancer cell lines to interrogate the effects of temperature on the cell cycle. To complement our investigation, we utilised the open source cancer genomics platforms cBioPortal and XenaBrowser to explore potential molecular determinants of cancer thermosensitivity. Through tracking the breast cancer cell line MCF-7 we observed hyperthermia to result in increased instances of endoreplication and mitotic catastrophe induced cell death. We also highlight components of the T complex protein ring complex as playing a potential role in testicular cancer. These findings will guide design of future cancer thermosensitivity study and may contribute towards novel adjuvant therapeutic cancer strategies.

AB - The application of heat to treat disease can be dated back over 5000 years. Ancient Egyptian papyrus records describe heated instruments being used to cauterise breast tumours. In recent times, hyperthermia range temperatures are increasingly routinely used to treat cancer. Heating tumours alongside conventional therapies and pre-heating aqueous drug suspensions prior to administration are both commonplace in oncology clinics. Despite this, the mechanisms which underpin the efficacy of hyperthermia therapy in cancer treatment remain poorly understood. In particular, the impact of temperature on cancer cell cycle dynamics is under explored. We set out to investigate these mechanisms. We employed time lapse confocal microscopy and fluorescence ubiquitin-based cell cycle indicator expressing cancer cell lines to interrogate the effects of temperature on the cell cycle. To complement our investigation, we utilised the open source cancer genomics platforms cBioPortal and XenaBrowser to explore potential molecular determinants of cancer thermosensitivity. Through tracking the breast cancer cell line MCF-7 we observed hyperthermia to result in increased instances of endoreplication and mitotic catastrophe induced cell death. We also highlight components of the T complex protein ring complex as playing a potential role in testicular cancer. These findings will guide design of future cancer thermosensitivity study and may contribute towards novel adjuvant therapeutic cancer strategies.

U2 - 10.17635/lancaster/thesis/1192

DO - 10.17635/lancaster/thesis/1192

M3 - Master's Thesis

PB - Lancaster University

ER -