Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy
Background: Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sour...
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| Language: | English |
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Elsevier
2024-02-01
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| Series: | Photodiagnosis and Photodynamic Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1572100023006506 |
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| author | Jane Ng Nico Henriquez Neil Kitchen Norman Williams Marco Novelli Dahmane Oukrif Alexander MacRobert Stephen Bown |
| author_facet | Jane Ng Nico Henriquez Neil Kitchen Norman Williams Marco Novelli Dahmane Oukrif Alexander MacRobert Stephen Bown |
| author_sort | Jane Ng |
| collection | DOAJ |
| description | Background: Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth In vivo, when all components of treatment are administered systemically. Methods: Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the d-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or d-luciferin only. For subcutaneous tumours, size and BLI (light emitted after d-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI. Results: For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) Conclusions: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues. |
| format | Article |
| id | doaj-art-a5674daf4e4b47ac9be8e00ae67d887f |
| institution | Kabale University |
| issn | 1572-1000 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Photodiagnosis and Photodynamic Therapy |
| spelling | doaj-art-a5674daf4e4b47ac9be8e00ae67d887f2024-12-11T05:55:19ZengElsevierPhotodiagnosis and Photodynamic Therapy1572-10002024-02-0145103923Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapyJane Ng0Nico Henriquez1Neil Kitchen2Norman Williams3Marco Novelli4Dahmane Oukrif5Alexander MacRobert6Stephen Bown7UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom; National Medical Laser Centre (now Department of Targeted Intervention, Division of Surgery and Interventional Science), University College London, Charles Bell House 43-45 Foley Street, London W1W 7TS, United KingdomUCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, United KingdomVictor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust, Queen Square, London WC1 3BG, United Kingdom of Great Britain and Northern Ireland, United KingdomDivision of Surgery & Interventional Science, University College London, Charles Bell House, 43-45 Foley Street London W1W 7TS, United KingdomDepartment of Cellular Pathology, University College Hospital, London, 60 Whitfield Street, London W1T 4EU, United KingdomDepartment of Cellular Pathology, University College Hospital, London, 60 Whitfield Street, London W1T 4EU, United KingdomNational Medical Laser Centre (now Department of Targeted Intervention, Division of Surgery and Interventional Science), University College London, Charles Bell House 43-45 Foley Street, London W1W 7TS, United KingdomNational Medical Laser Centre (now Department of Targeted Intervention, Division of Surgery and Interventional Science), University College London, Charles Bell House 43-45 Foley Street, London W1W 7TS, United Kingdom; Corresponding author.Background: Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth In vivo, when all components of treatment are administered systemically. Methods: Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the d-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or d-luciferin only. For subcutaneous tumours, size and BLI (light emitted after d-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI. Results: For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) Conclusions: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues.http://www.sciencedirect.com/science/article/pii/S1572100023006506Grade 4 astrocytoma cellsTransfection of cells with luciferasemTHPCBioluminescence mediated photodynamic therapy (bPDT)Subcutaneous and intracranial tumour growth suppression |
| spellingShingle | Jane Ng Nico Henriquez Neil Kitchen Norman Williams Marco Novelli Dahmane Oukrif Alexander MacRobert Stephen Bown Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy Photodiagnosis and Photodynamic Therapy Grade 4 astrocytoma cells Transfection of cells with luciferase mTHPC Bioluminescence mediated photodynamic therapy (bPDT) Subcutaneous and intracranial tumour growth suppression |
| title | Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy |
| title_full | Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy |
| title_fullStr | Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy |
| title_full_unstemmed | Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy |
| title_short | Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy |
| title_sort | suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated systemic photodynamic therapy |
| topic | Grade 4 astrocytoma cells Transfection of cells with luciferase mTHPC Bioluminescence mediated photodynamic therapy (bPDT) Subcutaneous and intracranial tumour growth suppression |
| url | http://www.sciencedirect.com/science/article/pii/S1572100023006506 |
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