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Photodynamic Therapy in Breast Surgical Oncology: in vitro, in vivo and first human clinical study

Banerjee, Shramana Mitul; (2017) Photodynamic Therapy in Breast Surgical Oncology: in vitro, in vivo and first human clinical study. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Photodynamic therapy (PDT) is a potential novel treatment for primary breast cancer. This thesis presents results obtained from preclinical experimental studies and a Phase I/IIA, open label, non-randomised, single site trial of photodynamic therapy for the treatment of primary breast cancer. The experimental in vitro study investigated the optimum dose required to effect cytotoxicity using liposomal verteporfin-PDT in comparison with the chemotherapeutic and immunomodulatory agent 5- azadeoxycytidine (5ADC) and the effect of the combination of PDT with 5ADC in 4T1 mouse breast cancer cells. PDT treatment resulted in early cytotoxicity while 5ADC treatment elicited delayed cytotoxic effects. Combination treatment was synergistic under certain conditions. Using an orthotopic 4T1 breast cancer mouse model local and distant effects of liposomal verteporfin-PDT were demonstrated in comparison to 5ADC alone and in combination with this agent. Well-demarcated PDT tumour damage with clear margins on histopathology assessment occurred in PDT monotherapy and combination treatment. Flow cytometry and gene expression analysis in PDT treated mice provided evidence for PDT mediated activation of innate immunity. Results of the first human clinical study investigating the effects of PDT in primary breast cancer are presented. The primary aim, namely to identify the light dose required for 12 mm of tumour necrosis (or a plateau of necrosis) assessed by histopathology, was achieved. Post-dose MRI correlated with histopathology findings in treated tumours and in normal breast tissue. 12 patients with median follow-up of 39 months showed PDT was well tolerated, with no adverse effects and comparable outcome to control populations. Tumour necrosis increased with incremental increases in light dose, but some patients showed a poor response even at the highest light dose. Poor response may be predicted by a low intra-tumoural expression of Ki67. Results from these preclinical and clinical studies should determine the direction of future investigations.

Type: Thesis (Doctoral)
Title: Photodynamic Therapy in Breast Surgical Oncology: in vitro, in vivo and first human clinical study
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1574744
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