Key publications
Diaz A, Hill J, Jenkins R, Kay A, Pye AJ, Morley D, Garavito N (2014). A SWOT Evaluation of University Student-Staff Partnerships in Co-creating Educational Resources, Peer Support and Research Within STEM Subjects. Journal of Scientific Research & Reports, 5(2), 161-170.
Keenan C, Bianco K, Braham J, Bryngfors L, Chapman V, Chilvers L, Croft T, Evans C, Ford N, Frank A, et al (eds)(2014).
Mapping student-led peer learning in the UK., Higher Education Academy (HEA). National Report.
Abstract:
Mapping student-led peer learning in the UK
Abstract.
Campbell SM, Morton CA, Alyahya R, Horton S, Pye A, Curnow A (2008). Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.
Br J Dermatol,
159(2), 387-393.
Abstract:
Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.
BACKGROUND: Photodynamic therapy (PDT) involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in their destruction. Evidence-based guidelines support the efficacy of PDT using topical 5-aminolaevulinic acid (ALA-PDT) in actinic keratoses, Bowen disease and basal cell carcinoma (BCC). Efficacy for nodular BCC appears inferior to that for superficial BCC unless prior debulking or repeat treatments are performed. Objectives the aim of this study was to assess the safety and efficacy of adding a novel iron-chelating agent, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), to topical ALA, to temporarily increase the accumulation of the photosensitizer in the tumour. METHODS: a mixed topical formulation of ALA + increasing concentrations of CP94 was used to carry out PDT on previously biopsied nodular BCC with no prior lesion preparation using standard light delivery. The area was assessed clinically and surgically excised 6 weeks later for histological examination. RESULTS: Enhanced PDT using 40% CP94 resulted in significantly greater clearance rates in nodular BCC than with ALA-PDT alone, in our protocol of single-treatment PDT with no lesion preparation. CONCLUSIONS: the results of this study demonstrate the safe and effective use of an enhanced ALA-PDT protocol for nodular BCC using CP94, with no adverse reactions to this modification. This is the first time this formulation has been used in patients. This formulation is now the focus of further study.
Abstract.
Author URL.
Curnow A, Pye A (2007). Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors. Journal of Environmental Pathology Toxicology and Oncology, 26, 89-103.
Bradfield W, Pye A, Clifford T, Salter L, Gould D, Campbell S, Curnow A (2006). Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet assay study.
J Environ Sci Health a Tox Hazard Subst Environ Eng,
41(2), 143-148.
Abstract:
Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet assay study.
When exposed to UVR, MRC5 fibroblasts incubated with mercuric chloride (0-15 microM) for 1 hour show increased DNA damage (as measured by the comet assay) compared to control cells (UVR irradiated but no mercuric chloride). This demonstrates that mercuric chloride and UVR in combination increase DNA damage in a synergistic manner. This may have implications to those exposed to mercury as it suggests that exposure to mercury in the environment may increase sensitivity to sunlight-induced carcinogenesis.
Abstract.
Author URL.
Publications by category
Journal articles
Curnow A, Pye A (2015). The importance of iron chelation and iron availability during PpIX-induced photodynamic therapy.
Photonics and Lasers in Medicine,
4(1), 39-58.
Abstract:
The importance of iron chelation and iron availability during PpIX-induced photodynamic therapy
Background: Protoporphyrin IX (PpIX)-induced photodynamic therapy (PDT) is being utilised as a topical method of localised ablation of certain non-melanoma skin cancers and precancers. Standardised protocols have been implemented to good effect when the disease remains superficial but improvement is required to treat thicker or acrally located conditions. Concurrent administration of an iron chelator during PpIX-PDT has been demonstrated to increase cellular accumulation of PpIX by reducing its bioconversion to haem (an iron dependent process) thus increasing cell kill on subsequent irradiation. Iron however, can also play a role in reactive oxygen species (ROS) generation and limiting its availability via chemical chelation could theoretically reduce the efficacy of PpIX-PDT, so that a response less than that maximally feasible is produced. Materials and methods: the effects of iron availability and chelation on PpIX-PDT have therefore been investigated via fluorescence quantification of PpIX accumulation, single-cell gel electrophoresis (comet assay) measurement of ROS-induced DNA damage and trypan blue exclusion assessment of cell viability. Cultured human cells were utilised and incubated in standardised iron conditions with the PpIX precursor's aminolaevulinic acid (ALA) or its methyl ester (MAL) in the presence or absence of either of the iron chelating agents desferrioxamine (DFO) or hydroxypyridinone (CP94), or alternatively iron sulphate as a source of iron. Results: ALA or MAL incubation was found to significantly increase cellular PpIX accumulation pre-irradiation as anticipated and this observation correlated with both significantly increased DNA damage and reduced cellular viability following irradiation. Co-incubation with either of the iron chelators investigated (DFO or CP94) significantly increased pre-irradiation PpIX accumulation as well as DNA damage and cell death on irradiation indicating the positive effect of iron chelation on the effectiveness of PpIX-induced PDT. The opposite effects were observed however, when the cells were co-incubated with iron sulphate, with significant reductions in pre-irradiation PpIX accumulation (ALA only) and DNA damage (ALA and MAL) being recorded indicating the negative effects excessive iron can have on PpIX-PDT effectiveness. Some dark toxicity produced by iron sulphate administration in non-irradiated control groups was also observed. Conclusion: Iron chelation and availability have therefore been observed to positively and adversely affect the PpIX-PDT process respectively and it is concluded that the effects of increased PpIX accumulation pre-irradiation produced via iron chelation outweigh any limitations reduced iron availability may have on the ability of iron to catalyse ROS generation/cascades following PpIX-induced PDT. Further investigation of iron chelation within dermatological applications where enhanced PpIX-PDT treatment effects would be beneficial is therefore warranted.
Abstract.
Diaz A, Hill J, Jenkins R, Kay A, Pye AJ, Morley D, Garavito N (2014). A SWOT Evaluation of University Student-Staff Partnerships in Co-creating Educational Resources, Peer Support and Research Within STEM Subjects. Journal of Scientific Research & Reports, 5(2), 161-170.
Campbell SM, Morton CA, Alyahya R, Horton S, Pye A, Curnow A (2008). Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.
Br J Dermatol,
159(2), 387-393.
Abstract:
Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.
BACKGROUND: Photodynamic therapy (PDT) involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in their destruction. Evidence-based guidelines support the efficacy of PDT using topical 5-aminolaevulinic acid (ALA-PDT) in actinic keratoses, Bowen disease and basal cell carcinoma (BCC). Efficacy for nodular BCC appears inferior to that for superficial BCC unless prior debulking or repeat treatments are performed. Objectives the aim of this study was to assess the safety and efficacy of adding a novel iron-chelating agent, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), to topical ALA, to temporarily increase the accumulation of the photosensitizer in the tumour. METHODS: a mixed topical formulation of ALA + increasing concentrations of CP94 was used to carry out PDT on previously biopsied nodular BCC with no prior lesion preparation using standard light delivery. The area was assessed clinically and surgically excised 6 weeks later for histological examination. RESULTS: Enhanced PDT using 40% CP94 resulted in significantly greater clearance rates in nodular BCC than with ALA-PDT alone, in our protocol of single-treatment PDT with no lesion preparation. CONCLUSIONS: the results of this study demonstrate the safe and effective use of an enhanced ALA-PDT protocol for nodular BCC using CP94, with no adverse reactions to this modification. This is the first time this formulation has been used in patients. This formulation is now the focus of further study.
Abstract.
Author URL.
Pye A, Campbell S, Curnow A (2008). Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma.
J Cancer Res Clin Oncol,
134(8), 841-849.
Abstract:
Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma.
PURPOSE: Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. Combining iron chelators with MAL has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This paper investigates this method of enhancement both in vitro and for the first time clinically for the treatment of nodular basal cell carcinoma (BCC). METHODS: Enhancement of MAL-induced PpIX accumulation by the iron chelator CP94 was quantified fluorometrically in human cultured cells (including three dermatological cell types). An open, dose-escalating, pilot study was then conducted in patients with nodular BCC, to determine the safety of this pharmacological modification. RESULTS: Large enhancements in PpIX accumulation were observed in the cultured cells when co-incubated with the iron chelator CP94. Clinically the addition of CP94 was found to be feasible and safe. In addition greater reductions in tumor depth were observed in the CP94 co-incubated tumors. CONCLUSION: Iron chelation by CP94 is an effective enhancer of MAL-induced PpIX accumulation in vitro. This method of enhancement was safely applied to a clinical PDT protocol with no unexpected adverse effects reported. Although the clinical investigation was only intended to be a small pilot to assess safety, enhancements in tumor clearance were observed both clinically and histologically when CP94 was included in the photosensitizing cream.
Abstract.
Author URL.
Campbell SM, Pye A, Horton S, Matthew J, Helliwell P, Curnow A (2007). A clinical investigation to determine the effect of pressure injection on the penetration of topical methyl aminolevulinate into nodular basal cell carcinoma of the skin.
J Environ Pathol Toxicol Oncol,
26(4), 295-303.
Abstract:
A clinical investigation to determine the effect of pressure injection on the penetration of topical methyl aminolevulinate into nodular basal cell carcinoma of the skin.
This investigation considered a novel method of enhancing penetration of the topical photosensitizing agent methyl aminolevulinate (MAL) into nodular basal cell carcinomas (BCCs) using an oxygen pressure injection device. Oxygen pressure injection (OPI) is a method to drive compounds into skin using pressured oxygen. The study was an observer-blinded pilot of a single application of MAL to nBCCs, with or without the use of OPI. The BCCs were then excised at different time intervals (0-180 min) and the depth of penetration of the MAL examined using microscopic fluorescence photometry to detect the production of the naturally fluorescent active photosensitiser protoporphyrin IX (PpIX). A highly selective and homogeneous distribution of MAL-induced porphyrin fluorescence was seen in all nBCC tumors studied, and showed a high lesion-to-normal-tissue ratio with very little fluorescence in the surrounding normal tissue. Although it was difficult to compare quantitatively, as individual tumors in each of the different study groups varied, a definite trend of increase in relative tumor concentration of MAL-induced PpIX was observed over time, and this was enhanced when OPI was employed.
Abstract.
Author URL.
Curnow A, Pye A (2007). Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors. Journal of Environmental Pathology Toxicology and Oncology, 26, 89-103.
ACurnow, Pye A (2007). Direct comparison of delta-aminolevulinic acid and methyl-aminolevulinate-derived protoporphyrin IX accumulations potentiated by desferrioxamine or the novel hydroxypyridinone iron chelator CP94 in cultured human cells. Photochemistry and Photobiology, 83(3), 766-773.
Pye A, Curnow A (2007). Direct comparison of delta-aminolevulinic acid and methyl-aminolevulinate-derived protoporphyrin IX accumulations potentiated by desferrioxamine or the novel hydroxypyridinone iron chelator CP94 in cultured human cells.
Photochem Photobiol,
83(3), 766-773.
Abstract:
Direct comparison of delta-aminolevulinic acid and methyl-aminolevulinate-derived protoporphyrin IX accumulations potentiated by desferrioxamine or the novel hydroxypyridinone iron chelator CP94 in cultured human cells.
Aminolevulinic acid photodynamic therapy (ALA-PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. The use of iron chelators in combination with ALA has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This study compares directly for the first time the effects of the novel hydroxypyridinone iron chelating agent CP94 and the more clinically established iron chelator desferrioxamine (DFO) on the enhancement of ALA and methyl-aminolevulinate (MAL)-induced PpIX accumulations in cultured human cells. Cultured human cells were incubated with a combination of ALA, MAL, CP94 and DFO concentrations; the resulting PpIX accumulations being quantified fluorometrically. The use of iron chelators in combination with ALA or MAL was shown to significantly increase the amount of PpIX accumulating in the fetal lung fibroblasts and epidermal carcinoma cells; while minimal enhancement was observed in the normal skin cells investigated (fibroblasts and keratinocytes). Where enhancement was observed CP94 was shown to be significantly superior to DFO in the enhancement of PpIX accumulation.
Abstract.
Author URL.
Bradfield W, Pye A, Clifford T, Salter L, Gould D, Campbell S, Curnow A (2006). Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet assay study.
J Environ Sci Health a Tox Hazard Subst Environ Eng,
41(2), 143-148.
Abstract:
Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet assay study.
When exposed to UVR, MRC5 fibroblasts incubated with mercuric chloride (0-15 microM) for 1 hour show increased DNA damage (as measured by the comet assay) compared to control cells (UVR irradiated but no mercuric chloride). This demonstrates that mercuric chloride and UVR in combination increase DNA damage in a synergistic manner. This may have implications to those exposed to mercury as it suggests that exposure to mercury in the environment may increase sensitivity to sunlight-induced carcinogenesis.
Abstract.
Author URL.
Chapters
Pye A, Dogra Y, Tyrrell J, Winyard PG, Curnow A (2009). Photodynamic therapy with aminolevulinic acid and iron chelators: a clinical example of redox signaling. In Jacob C, Winyard PG, Wiley-VCH (Eds.) Redox Signaling and Regulation in Biology and Medicine, Weinheim, Germany: , 351-372.
Conferences
Pye AJ (2016). The UK educational landscape and the potential for establishing PLTLIS partnerships.
Abstract:
The UK educational landscape and the potential for establishing PLTLIS partnerships.
Abstract.
Curnow A, Pye A, Campbell S (2009). Enhancing protoporphyrin IX-induced PDT. Photodynamic Therapy - Back to the Future.
Abstract:
Enhancing protoporphyrin IX-induced PDT
Abstract.
Curnow A, Pye A (2007). Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors.
Abstract:
Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors.
Abstract.
Author URL.
Reports
Keenan C, Bianco K, Braham J, Bryngfors L, Chapman V, Chilvers L, Croft T, Evans C, Ford N, Frank A, et al (eds)(2014).
Mapping student-led peer learning in the UK., Higher Education Academy (HEA). National Report.
Abstract:
Mapping student-led peer learning in the UK
Abstract.
Publications by year
2016
Pye AJ (2016). The UK educational landscape and the potential for establishing PLTLIS partnerships.
Abstract:
The UK educational landscape and the potential for establishing PLTLIS partnerships.
Abstract.
2015
Curnow A, Pye A (2015). The importance of iron chelation and iron availability during PpIX-induced photodynamic therapy.
Photonics and Lasers in Medicine,
4(1), 39-58.
Abstract:
The importance of iron chelation and iron availability during PpIX-induced photodynamic therapy
Background: Protoporphyrin IX (PpIX)-induced photodynamic therapy (PDT) is being utilised as a topical method of localised ablation of certain non-melanoma skin cancers and precancers. Standardised protocols have been implemented to good effect when the disease remains superficial but improvement is required to treat thicker or acrally located conditions. Concurrent administration of an iron chelator during PpIX-PDT has been demonstrated to increase cellular accumulation of PpIX by reducing its bioconversion to haem (an iron dependent process) thus increasing cell kill on subsequent irradiation. Iron however, can also play a role in reactive oxygen species (ROS) generation and limiting its availability via chemical chelation could theoretically reduce the efficacy of PpIX-PDT, so that a response less than that maximally feasible is produced. Materials and methods: the effects of iron availability and chelation on PpIX-PDT have therefore been investigated via fluorescence quantification of PpIX accumulation, single-cell gel electrophoresis (comet assay) measurement of ROS-induced DNA damage and trypan blue exclusion assessment of cell viability. Cultured human cells were utilised and incubated in standardised iron conditions with the PpIX precursor's aminolaevulinic acid (ALA) or its methyl ester (MAL) in the presence or absence of either of the iron chelating agents desferrioxamine (DFO) or hydroxypyridinone (CP94), or alternatively iron sulphate as a source of iron. Results: ALA or MAL incubation was found to significantly increase cellular PpIX accumulation pre-irradiation as anticipated and this observation correlated with both significantly increased DNA damage and reduced cellular viability following irradiation. Co-incubation with either of the iron chelators investigated (DFO or CP94) significantly increased pre-irradiation PpIX accumulation as well as DNA damage and cell death on irradiation indicating the positive effect of iron chelation on the effectiveness of PpIX-induced PDT. The opposite effects were observed however, when the cells were co-incubated with iron sulphate, with significant reductions in pre-irradiation PpIX accumulation (ALA only) and DNA damage (ALA and MAL) being recorded indicating the negative effects excessive iron can have on PpIX-PDT effectiveness. Some dark toxicity produced by iron sulphate administration in non-irradiated control groups was also observed. Conclusion: Iron chelation and availability have therefore been observed to positively and adversely affect the PpIX-PDT process respectively and it is concluded that the effects of increased PpIX accumulation pre-irradiation produced via iron chelation outweigh any limitations reduced iron availability may have on the ability of iron to catalyse ROS generation/cascades following PpIX-induced PDT. Further investigation of iron chelation within dermatological applications where enhanced PpIX-PDT treatment effects would be beneficial is therefore warranted.
Abstract.
2014
Diaz A, Hill J, Jenkins R, Kay A, Pye AJ, Morley D, Garavito N (2014). A SWOT Evaluation of University Student-Staff Partnerships in Co-creating Educational Resources, Peer Support and Research Within STEM Subjects. Journal of Scientific Research & Reports, 5(2), 161-170.
Keenan C, Bianco K, Braham J, Bryngfors L, Chapman V, Chilvers L, Croft T, Evans C, Ford N, Frank A, et al (eds)(2014).
Mapping student-led peer learning in the UK., Higher Education Academy (HEA). National Report.
Abstract:
Mapping student-led peer learning in the UK
Abstract.
2009
Curnow A, Pye A, Campbell S (2009). Enhancing protoporphyrin IX-induced PDT. Photodynamic Therapy - Back to the Future.
Abstract:
Enhancing protoporphyrin IX-induced PDT
Abstract.
Pye A, Dogra Y, Tyrrell J, Winyard PG, Curnow A (2009). Photodynamic therapy with aminolevulinic acid and iron chelators: a clinical example of redox signaling. In Jacob C, Winyard PG, Wiley-VCH (Eds.) Redox Signaling and Regulation in Biology and Medicine, Weinheim, Germany: , 351-372.
2008
Campbell SM, Morton CA, Alyahya R, Horton S, Pye A, Curnow A (2008). Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.
Br J Dermatol,
159(2), 387-393.
Abstract:
Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.
BACKGROUND: Photodynamic therapy (PDT) involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in their destruction. Evidence-based guidelines support the efficacy of PDT using topical 5-aminolaevulinic acid (ALA-PDT) in actinic keratoses, Bowen disease and basal cell carcinoma (BCC). Efficacy for nodular BCC appears inferior to that for superficial BCC unless prior debulking or repeat treatments are performed. Objectives the aim of this study was to assess the safety and efficacy of adding a novel iron-chelating agent, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), to topical ALA, to temporarily increase the accumulation of the photosensitizer in the tumour. METHODS: a mixed topical formulation of ALA + increasing concentrations of CP94 was used to carry out PDT on previously biopsied nodular BCC with no prior lesion preparation using standard light delivery. The area was assessed clinically and surgically excised 6 weeks later for histological examination. RESULTS: Enhanced PDT using 40% CP94 resulted in significantly greater clearance rates in nodular BCC than with ALA-PDT alone, in our protocol of single-treatment PDT with no lesion preparation. CONCLUSIONS: the results of this study demonstrate the safe and effective use of an enhanced ALA-PDT protocol for nodular BCC using CP94, with no adverse reactions to this modification. This is the first time this formulation has been used in patients. This formulation is now the focus of further study.
Abstract.
Author URL.
Pye A, Campbell S, Curnow A (2008). Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma.
J Cancer Res Clin Oncol,
134(8), 841-849.
Abstract:
Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma.
PURPOSE: Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. Combining iron chelators with MAL has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This paper investigates this method of enhancement both in vitro and for the first time clinically for the treatment of nodular basal cell carcinoma (BCC). METHODS: Enhancement of MAL-induced PpIX accumulation by the iron chelator CP94 was quantified fluorometrically in human cultured cells (including three dermatological cell types). An open, dose-escalating, pilot study was then conducted in patients with nodular BCC, to determine the safety of this pharmacological modification. RESULTS: Large enhancements in PpIX accumulation were observed in the cultured cells when co-incubated with the iron chelator CP94. Clinically the addition of CP94 was found to be feasible and safe. In addition greater reductions in tumor depth were observed in the CP94 co-incubated tumors. CONCLUSION: Iron chelation by CP94 is an effective enhancer of MAL-induced PpIX accumulation in vitro. This method of enhancement was safely applied to a clinical PDT protocol with no unexpected adverse effects reported. Although the clinical investigation was only intended to be a small pilot to assess safety, enhancements in tumor clearance were observed both clinically and histologically when CP94 was included in the photosensitizing cream.
Abstract.
Author URL.
2007
Campbell SM, Pye A, Horton S, Matthew J, Helliwell P, Curnow A (2007). A clinical investigation to determine the effect of pressure injection on the penetration of topical methyl aminolevulinate into nodular basal cell carcinoma of the skin.
J Environ Pathol Toxicol Oncol,
26(4), 295-303.
Abstract:
A clinical investigation to determine the effect of pressure injection on the penetration of topical methyl aminolevulinate into nodular basal cell carcinoma of the skin.
This investigation considered a novel method of enhancing penetration of the topical photosensitizing agent methyl aminolevulinate (MAL) into nodular basal cell carcinomas (BCCs) using an oxygen pressure injection device. Oxygen pressure injection (OPI) is a method to drive compounds into skin using pressured oxygen. The study was an observer-blinded pilot of a single application of MAL to nBCCs, with or without the use of OPI. The BCCs were then excised at different time intervals (0-180 min) and the depth of penetration of the MAL examined using microscopic fluorescence photometry to detect the production of the naturally fluorescent active photosensitiser protoporphyrin IX (PpIX). A highly selective and homogeneous distribution of MAL-induced porphyrin fluorescence was seen in all nBCC tumors studied, and showed a high lesion-to-normal-tissue ratio with very little fluorescence in the surrounding normal tissue. Although it was difficult to compare quantitatively, as individual tumors in each of the different study groups varied, a definite trend of increase in relative tumor concentration of MAL-induced PpIX was observed over time, and this was enhanced when OPI was employed.
Abstract.
Author URL.
Curnow A, Pye A (2007). Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors. Journal of Environmental Pathology Toxicology and Oncology, 26, 89-103.
Curnow A, Pye A (2007). Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors.
Abstract:
Biochemical manipulation via iron chelation to enhance porphyrin production from porphyrin precursors.
Abstract.
Author URL.
ACurnow, Pye A (2007). Direct comparison of delta-aminolevulinic acid and methyl-aminolevulinate-derived protoporphyrin IX accumulations potentiated by desferrioxamine or the novel hydroxypyridinone iron chelator CP94 in cultured human cells. Photochemistry and Photobiology, 83(3), 766-773.
Pye A, Curnow A (2007). Direct comparison of delta-aminolevulinic acid and methyl-aminolevulinate-derived protoporphyrin IX accumulations potentiated by desferrioxamine or the novel hydroxypyridinone iron chelator CP94 in cultured human cells.
Photochem Photobiol,
83(3), 766-773.
Abstract:
Direct comparison of delta-aminolevulinic acid and methyl-aminolevulinate-derived protoporphyrin IX accumulations potentiated by desferrioxamine or the novel hydroxypyridinone iron chelator CP94 in cultured human cells.
Aminolevulinic acid photodynamic therapy (ALA-PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. The use of iron chelators in combination with ALA has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This study compares directly for the first time the effects of the novel hydroxypyridinone iron chelating agent CP94 and the more clinically established iron chelator desferrioxamine (DFO) on the enhancement of ALA and methyl-aminolevulinate (MAL)-induced PpIX accumulations in cultured human cells. Cultured human cells were incubated with a combination of ALA, MAL, CP94 and DFO concentrations; the resulting PpIX accumulations being quantified fluorometrically. The use of iron chelators in combination with ALA or MAL was shown to significantly increase the amount of PpIX accumulating in the fetal lung fibroblasts and epidermal carcinoma cells; while minimal enhancement was observed in the normal skin cells investigated (fibroblasts and keratinocytes). Where enhancement was observed CP94 was shown to be significantly superior to DFO in the enhancement of PpIX accumulation.
Abstract.
Author URL.
2006
Bradfield W, Pye A, Clifford T, Salter L, Gould D, Campbell S, Curnow A (2006). Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet assay study.
J Environ Sci Health a Tox Hazard Subst Environ Eng,
41(2), 143-148.
Abstract:
Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet assay study.
When exposed to UVR, MRC5 fibroblasts incubated with mercuric chloride (0-15 microM) for 1 hour show increased DNA damage (as measured by the comet assay) compared to control cells (UVR irradiated but no mercuric chloride). This demonstrates that mercuric chloride and UVR in combination increase DNA damage in a synergistic manner. This may have implications to those exposed to mercury as it suggests that exposure to mercury in the environment may increase sensitivity to sunlight-induced carcinogenesis.
Abstract.
Author URL.