Publications by authors named "Stephen Bown"

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.

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Significance: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed.

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Background: . Grade 4 astrocytoma is incurable due to the diffusely infiltrative nature of the disease. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is not feasible when cancer cells infiltrate unknown areas of normal brain.

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Background: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery.

Methods: 30 patients with TNM buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps.

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Significance: India has one of the highest rates of oral cancer incidence in the world, accounting for 30% of reported cancers. In rural areas, a lack of adequate medical infrastructure contributes to unchecked disease progression and dismal mortality rates. Photodynamic therapy (PDT) has emerged as an effective modality with potential for treating early stage disease in resource-limited settings, while photosensitizer fluorescence can be leveraged for treatment guidance.

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Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment.

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Sentinel lymph node biopsy is a standard diagnosis procedure to determine whether breast cancer has spread to the lymph glands in the armpit (the axillary nodes). The metastatic status of the sentinel node (the first node in the axillary chain that drains the affected breast) is the determining factor in surgery between conservative lumpectomy and more radical mastectomy including axillary node excision. The traditional assessment of the node requires sample preparation and pathologist interpretation.

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Objective: Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options for the treatment of Barrett's esophagus (BE) associated neoplasia. Development of subsquamous intestinal metaplasia after successful PDT and/or RFA is a recognized phenomenon; however, the occurrence of neoplasia arising from buried glands is a rare complication.

Methods: This is a prospective case series of patients treated with PDT and/or RFA from 1999 to 2014 at University College London Hospital for neoplasia associated with BE, whose outcomes were analyzed retrospectively.

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The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment.

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Photodynamic therapy for photochemists.

Philos Trans A Math Phys Eng Sci

July 2013

Photodynamic therapy (PDT) is an evolving technique for localized control of diseased tissue with light after prior administration of a photosensitizing agent and in the presence of oxygen. The biological effect is quite different from surgery, radiotherapy and chemotherapy. With no temperature change during treatment, connective tissues like collagen are largely unaffected, so maintaining the mechanical integrity of hollow organs.

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This study investigated the photophysical and photobiological properties of a new amphiphilic chlorin photosensitiser, disulfonated tetraphenylchlorin (TPCS(2a)), for photochemical internalisation (PCI). The absorption and fluorescence spectra of TPCS(2a) were examined in a range of solvents together with fluorescence lifetime measurements. The fluorescence lifetime of TPCS(2a) was found to be 8.

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Although photodynamic therapy (PDT) has been used successfully to treat an assortment of different types of cancer, it has yet to reach the level of mainstream medicine on either side of the Atlantic. Unsubstantiated claims of PDT's efficacy in the past may be part of the reason for this. However, perhaps the main obstacle to PDT's endorsement by conventional medicine is the limited number of high-quality randomized controlled trials (RCTs) comparing it with relevant comparators for all meaningful outcomes, including effectiveness, safety, adverse events, quality of life, survival, and cost.

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Since the first report of the use of photodynamic therapy (PDT) for prostate cancer in 1990 it has been investigated as a primary and a salvage treatment, using either whole gland or focal approaches. Since 1990 advances in the transperineal approach to the prostate, coupled with photosensitizers which have a short drug-light interval and minimal skin phototoxicity, have resulted in major advances in the field. This review will look at the work done to date, and the ongoing studies which help to define the place of PDT as a useful treatment modality for organ-confined prostate cancer.

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Article Synopsis
  • Pegylated liposomal nanocarriers have been created to enhance the delivery of m-THPC, a clinical photosensitiser, by increasing its circulation time and bioavailability for better targeting of tumors.
  • The study compares the biodistribution and effectiveness of standard m-THPC (Foscan®) with m-THPC in pegylated liposomes (FosPEG 2% and 8%) in normal and tumor-bearing rats, revealing longer elimination half-lives with pegylation and better tumor accumulation.
  • Results show that pegylated formulations lead to greater tumor necrosis and less damage to surrounding healthy tissue compared to the standard formulation, suggesting potential clinical benefits like reduced drug dose and lower photosensitivity.
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Photochemical internalisation (PCI) is a site-specific technique for improving cellular delivery of macromolecular drugs. In this study, a cell penetrating peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a porphyrin photosensitiser has been shown to be effective for PCI. Herein we report an investigation of the photophysical and photobiological properties of a water soluble bioconjugate of the cationic Tat peptide with a hydrophobic tetraphenylporphyrin derivative.

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Aortoesophageal fistulas are a rare but commonly fatal complication of esophageal cancer. Reports of successfully managed cases are few, with high mortality and morbidity usually resulting from failure to control the initial massive haemodynamic insult. We report the case of a 47-year-old Caucasian man with recently diagnosed advanced esophageal cancer who suffered an episode of massive haematemesis.

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Photodynamic therapy (PDT) is being investigated as a treatment for localized prostate cancer. Photodynamic therapy uses a photosensitizing drug which is activated by a specific wavelength of light, in the presence of oxygen. The activated drug reacts with tissue oxygen to produce reactive oxygen species which are responsible for localized tissue necrosis.

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A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes.

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Photochemical internalisation (PCI) is a delivery technology that employs a sub-lethal form of photodynamic therapy (PDT) in which a photosensitiser is activated by light to break down intracellular membranes and release macromolecules into the cytosol where they can be biologically active. Although PCI does enhance the PDT killing of transplanted tumours in mice after local injection of the cytotoxic agent, gelonin, the redistribution of gelonin from intracellular organelles into the cytosol has only previously been demonstrated in vitro. This study is designed to understand the factors controlling the efficacy of PCI in vivo and to document the mechanism of action.

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Elastic scattering spectroscopy (ESS) may be used to detect high-grade dysplasia (HGD) or cancer in Barrett's esophagus (BE). When spectra are measured in vivo by a hand-held optical probe, variability among replicated spectra from the same site can hinder the development of a diagnostic model for cancer risk. An experiment was carried out on excised tissue to investigate how two potential sources of this variability, pressure and angle, influence spectral variability, and the results were compared with the variations observed in spectra collected in vivo from patients with Barrett's esophagus.

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Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA-PDT) is an attractive alternative to PDT with porfimer sodium for the treatment of high-grade dysplasia (HGD) in Barrett's oesophagus (BO) because of the shorter duration of light photosensitivity and low risk of oesophageal stricture formation. Published results, however, show marked variation in its efficacy, and optimum treatment parameters have not been defined. This study investigated how the dose of ALA and the colour of the illuminating light influenced the biological effect.

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Understanding of the biology of photodynamic therapy (PDT) has expanded tremendously over the past few years. However, in the clinical situation, it is still a challenge to match the extent of PDT effects to the extent of the disease process being treated. PDT requires drug, light and oxygen, any of which can be the limiting factor in determining efficacy at each point in a target organ.

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Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is a novel treatment for high-grade dysplasia (HGD) in Barrett's esophagus (BE). Our aim was to evaluate the effectiveness of differing light doses. Patients with HGD in BE received oral ALA (60 mg/kg) activated by low (500 J/cm), medium (750 J/cm), high (1,000 J/cm), or highest (1,000 J/cm x2) light dose at 635 nm.

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Objectives: The palliation of patients with malignant bile duct obstruction using metal or plastic biliary stents may be limited by stent occlusion. The aim of this study was to determine the safety and efficacy of endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy in the treatment of irresectable malignant biliary strictures and recurrent stent occlusion.

Methods: Thirteen patients with malignant biliary obstruction owing to carcinoma of the biliary tract (n=9), pancreas (n=3) or stomach (n=1), were studied.

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