Cutaneous Phototoxicity Research Articles

Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort.

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited. Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide. A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment (p < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment. This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.

Triarylboron-Doped Acenethiophenes as Organic Sonosensitizers for Highly Efficient Sonodynamic Therapy with Low Phototoxicity.

The development of efficient organic sonosensitizers is crucial for sonodynamic therapy (SDT) in the field of cancer treatment. Herein, a new strategy for the development of efficient organic sonosensitizers based on triarylboron-doped acenethiophene scaffolds is presented. The attachment of boron to the linear acenethiophenes lowers the lowest unoccupied molecular orbital (LUMO) energy, resulting in redshifted absorptions and emissions. After encapsulation with the amphiphilic polymer DSPE-mPEG2000 , it is found that the nanostructured BAnTh-NPs and BTeTh-NPs (nanoparticles of BAnThand BTeTh) shows efficient hydroxyl radical (• OH) generation under ultrasound (US) irradiation in aqueous solution with almost no phototoxicity, which can overcome the shortcomings of O2 -dependent SDT and avoid the potential cutaneous phototoxicity issue. In vitro and in vivo therapeutic results validate that boron-doped acenethiophenes as sonosensitizers enable high SDT efficiency with low phototoxicity and good biocompatibility, indicating that boron-functionalization of acenes is a promising strategy toward organic sonosensitizers for SDT.

Computational Studies of the Photodegradation Mechanism of the Highly Phototoxic Agent Benoxaprofen.

Computational quantum chemistry within the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) framework is used to investigate the photodegradation mechanism as well as the photochemical and photophysical properties of benoxaprofen (BP), a non steroid anti-inflammatory molecule (2-[2-(4-chlorophenyl)-1,3-benzoxazol-5-yl] propanoic acid). BP is a highly phototoxic agent that causes cutaneous phototoxicity shortly after its administration. On the grounds of concern about serious side effects, especially hepatotoxicity, it was withdrawn from the world market after only 2 years of its release. Our study shows that the drug has the capability to absorb radiation in the UV region, mainly between 300 and 340 nm, and undergoes spontaneous photoinduced decarboxylation from the triplet state. It shows very similar photochemical properties to the highly photolabile non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen, suprofen, and tiaprofenic acid. Like ketoprofen, BP can also decarboxylate from excited singlet states by overcoming low energy barriers. The differences in molecular orbital (highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)) distributions between the neutral and deprotonated BP, their absorption spectra, and the energetics and fate of various photoproducts produced throughout the photodegradation are discussed. Initiation and termination of decarboxylated BP radical species and initiation of propagating lipid peroxidation reactions due to the addition of molecular oxygen giving rise to the corresponding peroxyl radical are also explored in detail.

HSD95 Real-World Treatment Patterns and Healthcare Resource Utilization Among Patients Diagnosed with Erythropoietic Protoporphyria and X-Linked Protoporphyria: Results from a US Electronic Medical Records Study

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare genetic disorders of the heme biosynthetic pathway resulting in severe cutaneous phototoxicity reactions. Symptoms usually present in early childhood and include extremely painful photosensitivity reactions preceded by a “prodrome” of tingling, stinging, and/or burning of sun-exposed skin, with few treatment options. There are limited data regarding how EPP and XLP are managed in real-world settings. This study aims to describe treatment patterns and healthcare resource utilization among patients diagnosed with EPP and/or XLP in the United States.

Sofosbuvir-Velpatasvir (Epclusa)-Associated Photosensitivity in a Hepatitis C Patient: Case Report and Review of Photosensitivity to Hepatitis C Antiviral Agents

Hepatitis C is a ribonucleic acid (RNA) virus, and its presence in individuals was previously considered to be a chronic condition. However, recent therapeutic advances with virus-directed treatment have resulted in a significant increase in cure rates as demonstrated by an absence of virus on repeat testing. Currently, several individual and combination antiviral therapies are available for the treatment of hepatitis C virus infection. However, each of the hepatitis C antiviral agents is associated with potential adverse skin effects whose incidence varies depending on the agent used for treatment. The cutaneous reactions, including photosensitivity, usually resolve once the antiviral treatment is completed. In this report, we discuss the case of a chronic hepatitis C patient who developed sofosbuvir-velpatasvir (Epclusa)-associated toxicity, while receiving the antiviral therapy. The 57-year-old man developed cutaneous phototoxicity when he started treatment with the drug. The adverse skin reaction promptly resolved once the treatment was completed. Clinicians who manage patients being treated with antiviral agents for hepatitis C infection should consider counseling these individuals regarding photoprotection including avoidance of sun exposure, daily sunscreen use, and wearing photoprotective clothing.

Clinical Practice of Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer.

Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional treatment modalities in clinical practice because of the high frequency of cutaneous phototoxicity and esophageal stricture after the procedure. The second-generation photosensitizer, talaporfin sodium, which features more rapid clearance from the body, was developed to reduce skin phototoxicity, and talaporfin sodium can be excited at longer-wavelength lights comparing with a conventional photosensitizer. Endoscopic PDT using talaporfin sodium was initially developed for the curative treatment of central-type early lung cancer in Japan, and was approved in the early 2000s. After preclinical experiments, PDT using talaporfin sodium was investigated for patients with local failure after chemoradiotherapy, which was the most serious unmet need in the practice of esophageal cancer. According to the favorable results of a multi-institutional clinical trial, PDT using talaporfin sodium was approved as an endoscopic salvage treatment for patients with local failure after chemoradiotherapy for esophageal cancer. While PDT using talaporfin sodium is gradually spreading in clinical practice, further evaluation at the point of clinical benefit is necessary to determine the importance of PDT in the treatment of esophageal cancer.

Porphyria Cutanea Tarda

A 44-year-old man with human immunodeficiency virus infection, untreated hepatitis C virus infection, and active alcohol abuse presented with bilateral blistering on the dorsal hands of 2 months’ duration (Figure 1). The blisters were pruritic and photoexacerbated and resolved spontaneously with scarring. Examination revealed tense bullae limited to the dorsal hands in various stages of healing, including milia and scarring. Biopsy specimens for histopathologic evaluation and direct immunofluorescence revealed pauci-inflammatory subepidermal clefting and homogeneous deposition along the basement membrane and within walls of superficial dermal vessels with multiple conjugates, consistent with porphyria cutanea tarda (PCT; Figure 2). The patient’s baseline ferritin concentration was found to be higher than 800 ng/dL (to convert to pmol/L, multiply by 0.02247). Serum porphyrins demonstrated increased total porphyrins; fractionation showed increased uroporphyrin, confirming PCT.Figure 2A pauci-inflammatory subepidermal blister on histopathologic examination (hematoxylin and eosin, magnification ×200).View Large Image Figure ViewerDownload Hi-res image Download (PPT) PCT, the most common type of porphyria, is caused by inhibition of hepatic uroporphyrinogen decarboxylase (UROD). Pathogenesis involves cutaneous phototoxicity due to deposition of alternative metabolic products from excess hepatic porphyrinogen accumulation. Approximately 20% of cases are associated with familial UROD mutations,1Badenas C. To-Figueras J. Phillips J.D. Warby C.A. Muñoz C. Herrero C. Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives.Clin Genet. 2009; 75: 346-353Crossref PubMed Scopus (28) Google Scholar,2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar whereas 80% of patients present with acquired PCT with absence of UROD mutations. These patients often have liver damage, frequently from alcohol, hepatitis C, human immunodeficiency virus infection, or hemochromatosis.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar, 3Jalil S. Grady J.J. Lee C. Anderson K.E. Associations among behavior-related susceptibility factors in porphyria cutanea tarda.Clin Gastroenterol Hepatol. 2010; 8 (302.e1): 297-302Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 4Gisbert J.P. Garcia-Buey L. Pajares J.M. Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis.J Hepatol. 2003; 39: 620-627Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 5Ellervik C. Birgens H. Tybjærg-Hansen A. Nordestgaard B.G. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls.Hepatology. 2007; 46: 1071-1080Crossref PubMed Scopus (113) Google Scholar Typical presenting features include bullae and dyspigmentation of sun-exposed areas. First-line treatment is therapeutic phlebotomy of 450 mL every 2 weeks until ferritin concentration is less than 20 to 25 ng/dL.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Additional management recommendations include broad-spectrum sun protection, alcohol cessation, and hepatitis C treatment. Hydroxychloroquine can be used when phlebotomy is contraindicated.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Although PCT is readily treated and nonfatal, relapses may follow successful treatment.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Thank you to Dr Scott Tuttle for his contributions to this report.

Інтраепітеліальна неоплазія вульви: сучасний погляд на проблему, способи курації (огляд літератури); власний клінічний досвід застосування фотодинамічного методу лікування

Introduction. Vulvar intraepithelial neoplasia is a precancerous pathology of the vulva and is a very important medical and social problem. All the efforts of medical science are aimed at finding and developing the latest organ-preserving methods for the treatment of vulvar intraepithelial neoplasia. One of them is photodynamic therapy-method that allows preserving the anatomical structure of the organ. The aim of the study. The aim of the article is to carry out an analytical review of the literature on modern views on the problem of vulvar intraepithelial neoplasia, methods of its management and to present the results of the own clinical expertise of using a photodynamic method for its treatment. Materials and methods. Content analysis, method of system and comparative analysis, bibliosemantic method of studying the results of current scientific research on modern views on the problem of vulvar intraepithelial neoplasia, methods of its management have been used in the article. Fifty-six literature sources in English have been studied and analyzed. The sources have been taken in the following scientometric medical databases: PubMed-NCBI, Medline, ResearchGate, CochraneLibrary, EMBASE by keywords: intraepithelial neoplasia of the vulva, vulvar intraepithelial neoplasia (VIN), photodynamic therapy (PDT), treatment of vulvar intraepithelial neoplasia; VIN treatment. The results of own clinical expertise of using the photodynamic method for vulvar intraepithelial neoplasia treatment have been described in the article as well. Results. During the PS infusion and the period before the PDT session, the general condition of the patients was satisfactory, and the symptoms of cutaneous phototoxicity, allergic reactions, which were accompanied by severe dysfunctions of vital organs, were absent after it. Despite the premedication carried out before the PDT session, the patients had moderate pain syndrome (I-II degrees) after the session as well as moderately pronounced edema in the area of pathological tissues being under the influence of photoirradiation. Within 1-5 days after treatment, the beginning of the formation of a dark brown or black area of photochemical necrosis was noted. After 3, 6 and 24 months of observation of patients with precancerosis of the vulva, remission of clinical symptoms (pruritus in the vulva) in the treated pathological foci was stated. It should be noted that the insufficient effectiveness of PDT in five cases was due to the use of subtherapeutic doses of PS “Photolon®”. During the follow-up examination at 3, 6 and 24 months in 20 out of 30 patients who received a photosensibilizer session in a subtherapeutic dose followed by photoirradiation of high power (1.0 W), both clinically and morphologically complete regression was noted being justified from both treatment and financial point of view. In the post-procedural period, all patients who were treated with PDT are recommended to: observe the light regime for 3-4 days; adequate pain relief use; hygiene; sexual rest; local treatment. Conclusions. The real advantage of photodynamic therapy associated with vulvar intraepithelial neoplasia is its ability to treat the multifocal disease with minimal tissue destruction, preservation of the vulva anatomy and excellent cosmetic results. These properties confirm the photodynamic therapy to be an effective method in vulvar intraepithelial neoplasia treatment.

Fabrication of Multitargeting and pH-Regulated Nanocomposites for Antitumor Photodynamic Therapy Based on Triphenylphosphine and Graphene Oxide.

Targeted delivery of photosensitizer for antitumor photodynamic therapy has received much attention recently. In this research, a multitargeting graphene oxide (GO) nanosystem (GFFP-TPPa) was fabricated based on the magnetically targeted nano-Fe3O4, active targeted folic acid (FA), and mitochondria-targeted triphenylphosphine, aiming to provide an effective drug delivery system of photosensitizer for improved photodynamic therapy against human tumor. The effective photosensitizer release from GFFP-TPPa under mild acidic pH condition (such as tumor microenvironment) suggested our designed nanosystem could reduce cutaneous phototoxicity of nanoparticles (NPs) in normal cells environment, which was further verified by the observation that the fluorescence of GFFP-TPPa was significantly quenched compared with free PPa. Research of cellular morphological variation, uptaking test, and intracellular single oxygen detection has validated the effectiveness of GFFP-TPPa NPs against tumor cells and potential fluorescence imaging function. Moreover, GFFP-TPPa NPs have excellent superparamagnetic properties and FA-targeted property of NPs, which was verified by the tumor cellular uptake of GFFP-TPPa. Finally, the precise deliver of photosensitizer to mitochondria has been proved by Mito-Tracker Green organelle localization. Our research indicated that the fabricated nanosystem could be applied conveniently for PDT based on multitargetability.

Folate-Targeted Polyethylene Glycol–Modified Photosensitizers for Photodynamic Therapy

Pyropheophorbide a (Pyro) is a promising photosensitizer; however, it has no tumor selectivity and enrichment capability. In our former work, the prepared folic acid (FA)-Pyro conjugates showed considerably improved tumor accumulation and photodynamic therapy (PDT) activity in cell- and animal-based studies. However, the targeting capability, selectivity and water solubility of the conjugate remain problematic. Here, we evaluated the installation of hydrophilic polyethylene glycol chains as the linker between Pyro and FA, by avoiding direct conjugation of Pyro with FA, aiming to improve tumor selectivity and accumulation. However, PEGylation may have negative effects on the PDT activity and cutaneous phototoxicity. Therefore, we chose various lengths of PEGs as linkers to optimize the molecular weight, hydrophilicity, and PDT activity and, thus, to balance the tumor selectivity and biological function of the conjugate. One optimized conjugate, Pyro-PEG1K-FA, exhibited excellent tumor enrichment and was able to eradicate subcutaneous tumors at a considerably reduced dose. We report the synthesis and characterization of these conjugates as well as the evaluation of their tumor accumulation ability and the corresponding PDT efficiency through in vitro and in vivo experiments.

Cutaneous Phototoxicity: Clinical Observations versus Histopathological Findings.

Determination of test material-induced cutaneous phototoxicity for risk assessment has traditionally been based on visually observed skin reactions such as erythema, edema, and flaking. Because of its role in determining a toxic effect, the use of histopathological evaluation in this determination arises from time to time. However, there is little published information regarding the time course and types of histopathologic changes in the skin after test material-induced phototoxic insult nor any regulatory requirement or precedent for its use. This work evaluated both the visual and histopathological time course of the phototoxic response of the skin of the Long-Evans rat after oral administration of the phototoxins sparfloxacin and 8-methoxypsoralen (MOP) followed by a single exposure to solar-simulated ultraviolet radiation. Both sparfloxacin and 8-MOP elicited visual cutaneous reactions and microscopic changes consistent with a phototoxic response. The visually observed cutaneous time course and elicited histopathologic changes differed in response and extent for each phototoxin, but in both instances, microscopic evaluation did not alter the determination of a phototoxic response based on visual observations. These results indicate that, though histopathologic evaluations may have value for investigating mechanisms of phototoxicity, histopathologic evaluation of the skin is not warranted for determination of phototoxic potential in safety assessment intended for regulatory submission.

A sunblock based on bioadhesive nanoparticles.

The majority of commercial sunblock preparations utilize organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO) - a model UV filter - in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water-resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared to a commercial sunscreen formulation.

Retarded photooxidation of cyamemazine in biomimetic microenvironments.

Cyamemazine (CMZ) is a neuroleptic drug that mediates cutaneous phototoxicity in humans. Here, the photobehavior of CMZ has been examined within α1 -acid glycoproteins, β- and γ-cyclodextrins and SDS micelles. In all these microenvironments, CMZ emission was enhanced and blue-shifted, and its lifetime was longer. Irradiation of the entrapped drug at 355 nm, under air; led to the N,S-dioxide. Within glycoproteins or SDS micelles the reaction was clearly slower than in phosphate buffered solution (PBS); protection by cyclodextrins was less marked. Transient absorption spectroscopy in PBS revealed formation of the triplet state ((3)CMZ*) and the radical cation (CMZ(+•)). Upon addition of glycoprotein, the contribution of CMZ(+•) became negligible, whereas (3)CMZ* dominated the spectra; in addition, the triplet lifetime became considerably longer. In cyclodextrins, this occurred to a lower extent. In all microheterogeneous systems, quenching by oxygen was slower than in solution; this was most remarkable inside glycoproteins. The highest protection from photooxidation was achieved inside SDS micelles. The results are consistent with photooxidation of CMZ through photoionization and subsequent trapping of the resulting radical cation by oxygen. This reaction is extremely sensitive to the medium and constitutes an appropriate probe for localization of the drug within a variety of biological compartments.

Photodynamic Therapy: Oncologic Horizons

Photodynamic therapy (PDT) is a light-based intervention with a long and successful clinical track record for both oncology and non-malignancies. In cancer patients, a photosensitizing agent is intravenously, orally or topically applied and allowed time to preferentially accumulate in the tumor region. Light of the appropriate wavelength and intensity to activate the particular photosensitizer employed is then introduced to the tumor bed. The light energy will activate the photosensitizer, which in the presence of oxygen should allow for creation of the toxic photodynamic reaction generating reactive oxygen species. The photodynamic reaction creates a cascading series of events including initiation of apoptotic and necrotic pathways both in tumor and neovasculature, leading to permanent lesion destruction often with upregulation of the immune system. Cutaneous phototoxicity from unintentional sunlight exposure remains the most common morbidity from PDT. This paper will highlight current research and outcomes from the basic science and clinical applications of oncologic PDT and interpret how these findings may lead to enhanced and refined future PDT.

Optical profiles of cathode ray tube and liquid crystal display monitors: implication in cutaneous phototoxicity in photodynamic therapy

Recent clinical reports suggest that overexposure to light emissions generated from cathode ray tube (CRT) and liquid crystal display (LCD) color monitors after topical or systemic administration of a photosensitizer could cause noticeable skin phototoxicity. In this study, we examined the light emission profiles (optical irradiance, spectral irradiance) of CRT and LCD monitors under simulated movie and video game modes. Results suggest that peak emissions and integrated fluence generated from monitors are clinically relevant and therefore prolonged exposure to these light sources at a close distance should be avoided after the administration of a photosensitizer or phototoxic drug.

Photodynamic Therapy Using a Protease-Mediated Theranostic Agent Reduces Cathepsin-B Activity in Mouse Atheromata In Vivo

To investigate whether an intravenously injected cathepsin-B activatable theranostic agent (L-SR15) would be cleaved in and release a fluorescent agent (chlorin-e6) in mouse atheromata, allowing both the diagnostic visualization and therapeutic application of these fluorophores as photosensitizers during photodynamic therapy to attenuate plaque-destabilizing cathepsin-B activity by selectively eliminating macrophages. Thirty-week-old apolipoprotein E knock-out mice (n=15) received intravenous injection of L-SR15 theranostic agent, control agent D-SR16, or saline 3× (D0, D7, D14). Twenty-four hours after each injection, the bilateral carotid arteries were exposed, and Cy5.5 near-infrared fluorescent imaging was performed. Fluorescent signal progressively accumulated in the atheromata of the L-SR15 group animals only, indicating that photosensitizers had been released from the theranostic agent and were accumulating in the plaque. After each imaging session, photodynamic therapy was applied with a continuous-wave diode-laser. Additional near-infrared fluorescent imaging at a longer wavelength (Cy7) with a cathepsin-B-sensing activatable molecular imaging agent showed attenuation of cathepsin-B-related signal in the L-SR15 group. Histological studies demonstrated that L-SR15-based photodynamic therapy decreased macrophage infiltration by inducing apoptosis without significantly affecting plaque size or smooth muscle cell numbers. Toxicity studies (n=24) showed that marked erythematous skin lesion was generated in C57/BL6 mice at 24 hours after intravenous injection of free chlorin-e6 and ultraviolet light irradiation; however, L-SR15 or saline did not cause cutaneous phototoxicity beyond that expected of ultraviolet irradiation alone, neither did we observe systemic toxicity or neurobehavioral changes. This is the first study showing that macrophage-secreted cathepsin-B activity in atheromata could be attenuated by photodynamic therapy using a protease-mediated theranostic agent.

Porphyrie érythropoïétique congénitale traitée par allogreffe de cellules souches hématopoïétiques

Congenital erythropoietic porphyria (CEP) is a genodermatosis associated uroporphyrinogen III synthase deficit that results in porphyrin accumulation in various organs, particularly the skin. It is the most severe form of porphyria associated with haemolytic anaemia and cutaneous phototoxicity. We report a severe case of CEP treated by allogeneic bone marrow transplantation. A one-year-old child presented erythrodontia and scarring on exposed areas. The diagnosis of CEP was confirmed by the decline of uroporphyrinogen III synthase activity. Demonstration of p.Cys73Arg mutation confirmed the severity of the disease. Allogeneic bone marrow transplantation resulted in persistent resolution of clinical signs 25months after grafting. Symptomatic treatment is ineffective in this serious disease associated with early mortality. 11of the 13patients treated by allogeneic hematopoietic stem cell graft, including our patient, continued to be asymptomatic an average of seven years after transplantation. This new case confirms the role of allogeneic hematopoietic stem cell grafting in the treatment of congenital erythropoietic porphyria.

ChemInform Abstract: A New Benzoangelicin with Strong Photobiological Activity.

Benzoangelicins 4-6 were synthesized in good yields from 7-hydroxy-5-methoxy-4-methylcoumarin (1). In the absence of UVA radiation, compounds 5 and 6 were only weakly active against HL60 and HeLa tumour cells; in its presence, compound 6 was 10 times more active than the reference compound 8-methoxypsoralen. None of 4-6 exhibited cutaneous phototoxicity.

Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: A literature review

Some porphyrias are associated with cutaneous phototoxicity due to photoactivation of porphyrins, but whether ionizing radiation can have an additive effect is not clear. We report a case of severe radiation therapy-related toxicity in a patient with porphyria cutanea tarda and review the literature. A 50-year-old man with porphyria cutanea was treated for lower lip squamous cell carcinoma with definitive radiation therapy. During radiation therapy, acute toxicity was of an expected onset and severity. Six months after treatment completion, he developed skin hypopigmentation, soft tissue fibrosis, and areas of painful denuded skin and crusting within the previous treatment field. Reports of 7 patients with porphyria receiving radiation therapy to at least 9 separate sites were reviewed, with only 1 previous report suggestive of increased radiation therapy-related toxicity. Based on this and 1 other report, caution is warranted when considering radiation therapy in patients with active porphyria.

5-ALA Photodynamic Therapy Eliminates Resistant Barrettʼs Cells

Purpose: Photodynamic therapy (PDT) with sodium porfimer has been shown to decrease both high grade dysplasia and cancer formation in Barretts esophagus. However, we have previously shown that sodium porfimer mediated PDT is not as effective in patients who are p16 deficient which is important in cell cycle regulation. p16 was associated with a substantial risk of treatment failure defined as persistence of high-grade dysplasia or advancement to cancer. Recently, 5-amino levulinic acid (ALA) has become available for use in the United States. It is important to determine if ALA mediated PDT has advantages over sodium porfimer mediated PDT other than shorter duration of cutaneous phototoxicity and decreased stricture formation. Our aim was to determine if ALA mediated PDT cell killing was independent of p16 status. Methods: A Barretts epithelial cell line immortalized with H-Tert (human telomerase) was provided to us (RF Souza, Texas Southwester) which has been described as having normal cell functions other than an absence of p16 expression. We used an adenovirus-mediated p16 to infect and re-introduce p16 expression to this cell line. We then compared the effect of PDT with ALA in cells with and with p16. After the cells were estabished in culture, ALA was provided in concentrations of 0, 2.5, 5, 10, 25, 50, 100, and 250 ug/ml and incubated for 6 hours prior to photoradiation with a broadband xenon light source for a total of 20 J/square cm. Cells were then observed for 4 days after which cell death was assessed with propidium iodide. Results: 5-ALA mediated cell death was similar in both p16+ and p16- Barretts epithelial cells (P > 0.05). There was no significant difference in cell death at any concentration of ALA. Control cells had less than 5% cell death while those that were treated with 50 ug/ml of 5-ALA had about 20% cell death. Treatment with either 100 or 250 ug/ml of 5-ALA produced 90% cell death. The LD50 for 5-ALA was 68 ug/ml. Conclusion: 5-ALA mediated PDT appears to kill Barretts cells resistant to sodium porfimer mediated PDT. 5-ALA may be able to eliminate Barretts epithelium in those 20% of patients with high grade dysplasia who have failed sodium porfimer.