Sandra Campbell

The green tea polyphenol (-)-epigallocatechin gallate and green tea can protect human cellular DNA from ultraviolet and visible radiation-induced damage.

Background: Antioxidant compounds in green tea may be able to protect against skin carcinogenesis and it is of interest to investigate the mechanisms involved. A study was therefore conducted to determine whether the isolated green tea polyphenol (−)‐epigallocatechin gallate (EGCG) could prevent ultraviolet radiation (UVR)‐induced DNA damage in cultured human cells. This work was then extended to investigate whether drinking green tea could afford any UVR protection to human peripheral blood cells collected after tea ingestion.

The relationship between protoporphyrin IX photobleaching during real-time dermatological methyl-aminolevulinate photodynamic therapy (MAL-PDT) and subsequent clinical outcome.

The relationship between protoporphyrin IX (PpIX) photobleaching and cellular damage during aminolevulinic (ALA) photodynamic therapy (PDT) has been studied at the cellular level. This study assessed the capability of a non‐invasive fluorescence imaging system (Dyaderm, Biocam, Germany), to monitor changes in PpIX during real time methyl‐aminolevulinate (MAL) PDT in dermatological lesions, and thus to act as a predictive tool in terms of observed clinical outcome post‐treatment.

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.

Photodynamic therapy using meta‐tetrahydroxyphenylchlorin (Foscan®) for the treatment of vulval intraepithelial neoplasia

Background  Photodynamic therapy (PDT) has unique properties which make it suitable for the local treatment of superficial epithelial disorders; it has been suggested as a useful treatment for carcinoma in situ of the vulva.

The effect of air cooling pain relief on protoporphyrin IX photobleaching and clinical efficacy during dermatological photodynamic therapy

Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized to successfully treat licensed indications (e.g. actinic keratosis (AK), superficial basal cell carcinoma (sBCC) and Bowens disease (BD)) in the UK. Air cooling devices (ACD) are commonly utilized as a method of pain relief, however the effect of this on treatment outcome has never been extensively investigated. This non-randomized, retrospective observational controlled study investigated whether the application of the ACD limited photosensitiser (protoporphyrin IX - PpIX) photobleaching during irradiation and/or subsequent clinical outcome. Patients utilizing the ACD throughout treatment were observed to undergo significantly less PpIX photobleaching than the control group (P<0.001) and complete clinical clearances observed at 3 months were also reduced within the ACD group. Separate analysis of the different lesion types indicated that significantly less photobleaching occurred in AK lesions with ACD and all lesion types failed to fully utilize the accumulated PpIX when ACD was employed. The application of the ACD as pain relief during light irradiation therefore resulted in lower PpIX photobleaching which corresponded to a reduction in the efficacy of PDT treatment. Whilst the ACD is an effective method of dermatological PDT analgesia it should be utilized as sparingly as possible to minimize any deleterious effects on treatment outcome.

Using natural dietary sources of antioxidants to protect against ultraviolet and visible radiation-induced DNA damage: an investigation of human green tea ingestion.

Oral ingestion of green tea is a potent dietary source of antioxidant polyphenols. These compounds are of interest as they may be able to provide additional protection to the body to help prevent the deleterious effects of ultraviolet A and visible radiation (UVA/VIS) produced indirectly via reactive oxygen species (ROS) in sunlight exposed skin. A small clinical study was conducted in ten healthy adult volunteers. Samples of whole blood were obtained from each before and 30, 60 and 90 min following ingestion of three breakfast cups of green tea (540 ml in total) prepared in a standardised manner. Peripheral leucocytes were isolated from each blood sample and exposed to increasing periods of UVA/VIS irradiation in the laboratory (0, 9, 12 or 18 min). Alkaline single cell gel electrophoresis (the comet assay) was then conducted to determine the level of DNA damage in each sample from each individual. The findings support those of our previous pilot study and indicate that drinking green tea did significantly reduce the genotoxic effects observed in peripheral blood cells 60 min following ingestion when artificially exposed to 12 min of UVA/VIS irradiation in the laboratory. It is postulated that this protection is afforded by the polyphenol compounds (known to be contained within green tea) via scavenging or quenching of the damaging ROS induced by this form of light exposure. Further investigation should consider whether this dietary-induced protection could be extended to cells of the skin.

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

PurposeMethyl-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).MethodsEnhancement 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.ResultsLarge 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.ConclusionIron 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.

Comparison of protoporphyrin IX accumulation and destruction during methylaminolevulinate photodynamic therapy of skin tumours located at acral and nonacral sites.

Background  Topical photodynamic therapy (PDT) is successful in the treatment of nonmelanoma skin cancers and associated precancers, but efficacy is significantly reduced in actinic keratosis lesions not located on the face or scalp.

Oxygen saturation and perfusion changes during dermatological methylaminolaevulinate photodynamic therapy

Background  Methylaminolaevulinate (MAL)‐photodynamic therapy (PDT) is a successful topical treatment for a number of (pre)cancerous dermatological conditions. In combination, light of the appropriate wavelength, the photosensitizer protoporphyrin IX (PpIX) and tissue oxygen result in the production of singlet oxygen and reactive oxygen species inducing cell death.

Validation of a non-invasive fluorescence imaging system to monitor dermatological PDT

BACKGROUND Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) involves selective accumulation of a photosensitiser, protoporphyrin IX (PpIX), primarily in tumour tissue, which in combination with visible light and tissue oxygen results in reactive oxygen species (ROS) production and thus cellular destruction. METHODS A non-invasive fluorescence imaging system (Dyaderm, Biocam, Germany) has been employed to acquire colour (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. This system had been previously utilised for fluorescence diagnosis, however, here changes in PpIX concentration within the skin lesions and normal tissue were followed after MAL application. Measurements were also recorded from a synthetic PpIX standard. RESULTS Results indicated that imaging distance, imaging angle, position of the region of interest and light conditions all altered the PpIX levels acquired from the synthetic PpIX standard. The imaging system was therefore adapted and a standard operating procedure developed allowing reproducible images of dermatological lesions to be acquired. Different concentrations of synthetic PpIX were analysed with the system and a linear relationship was observed between the PpIX concentration and the mean greyscale value calculated for the images acquired up to 10 microM. CONCLUSIONS The Dyaderm imaging system can now be used reproducibly with confidence to semi-quantify PpIX (within the range of 0-10 microM) within dermatological lesions using the standard operating procedure derived from this work.