Search

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG's role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG’s role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells.

Methyl aminolevulinate (MAL) is a topical compound approved for use with photodynamic therapy (PDT) for the treatment of actinic keratosis (AK) and field cancerization in certain countries. There exists a high burden of disease for patients with AK: repeated treatments are required, there is a known risk of progression to keratinocyte carcinoma, and cosmetic appearance is affected. Delivery of PDT using MAL is a flexible treatment strategy available in many forms; red light, daylight, or artificial daylight can be used for illumination, all of which result in high AK clearance rates and low recurrence. MAL-PDT protocols continue to evolve to further improve adherence and treatment outcomes. Here, we used PubMed to search MEDLINE to identify guidelines, consensus recommendations, and studies describing the use of MAL for the treatment of AK. The aim of this targeted review is to consider various MAL-PDT treatment strategies on the basis of published literature, with a focus on personalizing treatment for the heterogeneous AK population. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review of available literature regarding the use of 5‐aminolevulinic acid (ALA) and ALA derivative photodynamic therapy (PDT) in the treatment of hidradenitis suppurativa (HS) and provide recommendations on its use. Methods: A systematic review was performed of all published studies up to September 1, 2019 from nine databases, including PubMed, that evaluated PDT in the treatment of HS. For each study, quality of evidence and risk of bias was evaluated. Recommendations from the body of evidence were created based on Strength of Recommendation and Taxonomy (SORT) criteria. Results: Eighteen studies met inclusion criteria. The majority of studies had a high risk of bias. Blue light PDT with 20% ALA and red light PDT with 16% methyl aminolevulinate (MAL) demonstrated some benefit based on a small number of poor‐quality studies with a high risk of bias (Grade C, level III evidence). The most promising results were for 1%–5% ALA with intralesional diode, with good to complete response in 78%–94% of anatomic sites treated (Grade B, level II evidence). Limitations: The majority of studies contained high levels of bias, with significant heterogeneity between studies. Conclusions are limited by small samples sizes, lack of randomized controlled trials, and differing protocols. Conclusion: Further studies are needed to determine the clinical efficacy of 20% ALA with blue light and MAL with red light. Intralesional diode PDT shows the most promise and warrants further investigation in larger, randomized controlled trials. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) have unique properties, including size-dependent optical and electronic characteristics, biocompatibility, and ease of functionalization, making them attractive for various diagnostic and therapeutic applications. The goal of this work was to verify the potential application of gold nanoparticles capped with aminolevulinic acid (ALA), methyl aminolevulinate (MALA), and gamma-aminobutyric acid (GABA) in low-energy X-ray diagnostics and therapy of breast cancer. ALA and MALA induce the accumulation of protoporphyrin IX (PpIX) in cancer cells. PpIX, in turn, can be excited by Cherenkov radiation, producing reactive oxygen species after energy or electron transfer from the triplet excited state of PpIX to molecular oxygen, which induces cell death by apoptosis or necrosis. The results indicated that ALA and MALA nanoparticles promoted reduced cell viability by approximately 20 % with X-ray irradiation at an energy level of 35 kV for 5 min. Breast cancer cells possess GABA receptors, allowing for targeted effects by GABANPs, which can enhance contrast and improve diagnostic potential. GABAAuNPs also demonstrated decreased cell viability in ∼10 % following X-ray irradiation, making them a promising material for breast cancer diagnosis and treatment. • ALA and MALA gold nanoparticles enhance PpIX levels in cancer cells. • GABA-coated gold nanoparticles target breast cancer cells through GABA receptors. • Low-kV X-rays and gold nanoparticles diminish breast cancer cell viability. • Cell death mechanism. • The investigated nanoparticles hold promise for theranostic breast cancer management. [ABSTRACT FROM AUTHOR]

Response rates evaluation of photodynamic therapy (PDT) for nodular basal cell carcinoma (BCC) treatment located on high-risk and low-risk areas of the face. Two groups of nodular BCC were selected, debulked, and received 20% methyl aminolevulinate cream. After 3h, the first irradiation was performed (20min, 150J/cm2). Then, the cream was re-applied, and a second irradiation was performed after 1.5h (20min, 150J/cm2). Clearance at 30 days and recurrence-free survival rate were evaluated. The clearance at 30 days after PDT was 89% for the low-risk area group and 87% for the high-risk group. The recurrence-free survival at 60 months was 82% and 85% for the high-risk and low-risk groups, respectively. No significant differences were observed between groups, nor for clearance at 30 days, nor recurrence-free follow-up. These results make the PDT an option for nodular BCC less than 5 mm located in high-risk areas. [ABSTRACT FROM AUTHOR]

Evaluate a photodynamic therapy (PDT) protocol with less time at the hospital and less painful for low-risk basal cell carcinoma (BCC) treatment. Eight BCCs were selected, debulked, and received 20% methyl aminolevulinate cream. After 3h, the first irradiation was performed at the hospital (20min, 150J/cm2). Then, the cream was re-applied, a portable irradiation prototype was fixed into the lesion. After 1.5h, the patients turned on the prototype for irradiation (2h, 312J/cm2) at home. Disease-free survival rate and pain score during irradiations were evaluated. The clearance at 30 days after PDT was 87.5% by histological analysis. The mean follow-up was 21.5 months and the recurrence-free survival at 22 months was 75%. The pain score was significantly lower at home. A less painful and more comfortable PDT treatment protocol was proved long-term efficient. A randomized clinical trial has been conducted to confirm these results. [ABSTRACT FROM AUTHOR]

Actinic keratoses are a chronic condition in ultraviolet-damaged skin, with a risk of progressing to invasive skin cancer. The aim of this study was to investigate the preventive potential of field-directed repetitive daylight photodynamic therapy for actinic keratoses. A randomized trial was performed, including 58 patients with ≥5 actinic keratoses on photodamaged facial skin, who received either 5 full-face sessions of daylight photodynamic therapy within a period of 2 years or lesion-directed cryosurgery. Primary outcome was the mean cumulative number of new actinic keratoses developed between visits 2 and 6 (visit 6 being a follow-up). This outcome was lower after daylight photo­dynamic therapy (7.7) compared with cryosurgery (10.2), but the difference did not reach significance (–2.5, 95% confidence interval –6.2 to 1.2; p=0.18). Several signs of photoageing (fine lines, pigmentation, roughness, erythema, sebaceous gland hyperplasia) were significantly reduced after daylight photodynamic therapy, but not after cryosurgery. Significantly less pain and fewer side-effects were reported during daylight photodynamic therapy than during cryosurgery. This study found that repetitive daylight photodynamic therapy had photo-rejuvenating effects. However, the prevention of actinic keratoses by this therapy could not be proven in a statistically reliable manner.

Actinic keratoses are a chronic condition in ultravioletdamaged skin, with a risk of progressing to invasive skin cancer. The aim of this study was to investigate the preventive potential of field-directed repetitive daylight photodynamic therapy for actinic keratoses. A randomized trial was performed, including 58 patients with ≥5 actinic keratoses on photodamaged facial skin, who received either 5 full-face sessions of daylight photodynamic therapy within a period of 2 years or lesion-directed cryosurgery. Primary outcome was the mean cumulative number of new actinic keratoses developed between visits 2 and 6 (visit 6 being a follow-up). This outcome was lower after daylight photodynamic therapy (7.7) compared with cryosurgery (10.2), but the difference did not reach significance (-2.5, 95% confidence interval -6.2 to 1.2; p=0.18). Several signs of photoageing (fine lines, pigmentation, roughness, erythema, sebaceous gland hyperplasia) were significantly reduced after daylight photodynamic therapy, but not after cryosurgery. Significantly less pain and fewer side-effects were reported during daylight photodynamic therapy than during cryosurgery. This study found that repetitive daylight photodynamic therapy had photo-rejuvenating effects. However, the prevention of actinic keratoses by this therapy could not be proven in a statistically reliable manner. [ABSTRACT FROM AUTHOR]

Abstract Background The primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization. Methods In a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value

Photodynamic therapy (PDT) has emerged as an interesting alternative option for onychomycosis treatment. The impact of a specific photosensitizer (PS) on the final result is an important factor to consider. We conducted a short‐ and medium‐term controlled trial to compare the effectiveness of PDT in the treatment of mild‐to‐moderate onychomycosis when it is mediated by two different PSs. Twenty patients were randomized to receive nine sessions of PDT distributed over 16 weeks mediated either by methylene blue (MB/PDT group) or methyl aminolevulinate (MAL/PDT group). Onychomycosis severity index (OSI) and nail involvement were checked along the study. Complete cure, treatment success, and clinical improvement were tabulated at 16 and 40‐week follow‐ups. OSI scores decreased significantly along the study, from 12.1 ± 5.4 to 3.6 ± 3.2 (MB/PDT group) and from 14.8 ± 6.0 to 5.4 ± 4.4 (MAL/PDT group). At 16‐week follow‐up, only 20% of the patients in the MB/PDT group reached complete cure and none in the group of MAL/PDT. At 40‐week follow‐up, complete cure rates were 70% and 40% in the MB/PDT group and MAL/PDT group respectively. Both modalities showed good outcomes in treatment of moderate toenail onychomycosis. MB/PDT showed a faster action but with relapse rates slightly higher than MAL/PDT. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) kills target microorganisms via reactive oxygen species (ROS) production. PDT seems to be a good alternative treatment option for onychomycosis. Objective: To compare the efficacy of combined therapies based on oral terbinafine (TN) plus adjunctive PDT mediated by methylene blue (MB) (TN + MB/PDT) or methyl aminolevulinate (MAL) (TN + MAL/PDT) in the treatment of onychomycosis. Methods: Twenty patients affected by severe dermatophyte onychomycosis in the nails of the big toe (>60% disease involvement of target nail) received oral TN for 12 weeks and concomitantly were randomly allocated to receive nine sessions, separated by 2‐week intervals, of urea (40%) plus a PDT protocol mediated by MB (TN + MB/PDT: group I) or mediated by MAL (TN + MAL/PDT: group II). Clinical and mycological efficacy was evaluated at 16‐, 40‐ and 52‐week follow‐up. Results: Both protocols showed a significant decrease in Onychomycosis Severity Index (OSI) scores (P <.05), from 24.2 ± 4.6 to 0.7 ± 0.6 (group I)) and from 18.5 ± 10.1 to 2.1 ± 2.0 (group II). No side effects or complications were reported in any of the combinations used. Mycological cure rates were significantly higher during the last third of the evaluated period of time, reaching 100% and 90% in group I and group II, respectively, at the 52‐week follow‐up. In both modalities, complete cure was achieved in 70% of the patients at the 52‐week follow‐up. Conclusions: TN + MB/PDT and TN + MAL/PDT show similar outcomes in the treatment of toenails with severe onychomycosis. PDT is an effective method to accelerate the TN‐mediated healing process. [ABSTRACT FROM AUTHOR]

This review analyses physical drug delivery enhancement technologies with a focus on improving UV damaged skin, actinic keratoses and non-melanoma skin cancer treatment. In recent years, physical drug delivery enhancement has been shown to enhance cosmeceutical and skin cancer treatment efficacy, but there are pros and cons to each approach which we discuss in detail. Mechanisms of action, clinical efficacy, experimental design, outcomes in academic publications, clinical trial reports and patents are explored to evaluate each technology with a critical, translation focused lens. We conclude that the commercial success of cosmeceutical applications, e.g. microneedles, will drive further innovation in this arena that will impact how actinic keratoses and non-melanoma skin cancers are clinically managed. Unlabelled Image [ABSTRACT FROM AUTHOR]

In order to purposely decrease the time of the photodynamic therapy (PDT) sessions, this study evaluated the effects of PDT using topical and intradermal delivery of two protoporphyrin (PpIX) precursors with intense pulsed light (IPL) as irradiation source. This study was performed on porcine skin model, using an IPL commercial device (Intense Pulse Light, HKS801). IPL effect on different administration methods of two PpIX precursors (ALA and MAL) was investigated: a topical cream application and an intradermal application using a needle-free, high-pressure injection system. Fluorescence investigation showed that PpIX distribution by needle-free injection was more homogeneous than that by cream, suggesting that a shorter drug-light interval in PDT protocols is possible. The damage induced by IPL-PDT assessed by histological analysis mostly shows modifications in collagens fibers and inflammation signals, both expected for PDT. This study suggested an alternative protocol for the PDT treatment, possibility half of the incubation time and with just 3 min of irradiation, making the IPL-PDT, even more, promising for the clinical treatment. [ABSTRACT FROM AUTHOR]

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients. [ABSTRACT FROM AUTHOR]

The article presents the results of the studies on the effectiveness of treatment basal cell carcinoma of the skin with photodynamic therapy with 5-aminolevulinic acid and methyl aminolevulinate. The results of the comparing trials between photodynamic therapy with methyl aminolevulinate and different other treatment modalities are presented.

Goal. To assess the efficacy of the photodynamic therapy with the external use of methyl aminolevulinate as a photosensitizer with further irradiation with visible red light with the wavelength of 630 nm in the treatment of patients suffering from a surface form of basalioma and actinic keratosis. Materials and methods. The study involved 28 patients diagnosed with the surface form of basalioma and 34 patients diagnosed with actinic keratosis. They underwent treatment by the photodynamic therapy method using a LED lamp radiating visible red light with the wavelength of 630 nm, with the total dose of irradiation equal to 37 J/cm2. All patients also underwent a confocal in vivo laser scanning microscopy of lesions at the baseline and after 7, 30, 90 and 180 days of treatment. Results. Absolute regression of abnormal lesions was observed in 25 (91%) patients diagnosed with the surface form of basalioma and 30 (88.9%) patients diagnosed with actinic keratosis after 30 days of treatment. No signs of the diseases were revealed in these patients after examination by the method of confocal in vivo laser scanning microscopy. Conclusion. The photodynamic therapy with the local administration of methyl aminolevulinate with further irradiation with visible red light with the wavelength of 630 nm is an efficient method of treatment of the surface form of basalioma and actinic keratosis.

Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma. In early stages of the disease, topical therapeutic approaches like steroids, chemotherapy, phototherapy or spot radiation therapy are most commonly used. Photodynamic therapy (PDT) is widely executed in the treatment of actinic keratosis and superficial basal cell carcinoma. The effective use of PDT for early forms of MF has been previously demonstrated in a series of cases. In this instance, the treatment of MF (n = 6, 11 lesions) with methyl alanine PDT (MAL-PDT) in 73% of the treated lesions showed a complete response. Within the timeframe of 25-51 months, no recurrence of the successfully treated lesions was observed, on the contrary some of the patients developed new lesions on different sites. Hence, this case study shows that patients having a single or few MF lesions can be successfully treated by PDT.

The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All mice in four groups of female C3.Cg/TifBomTac hairless immunocompetent mice (N = 100) were irradiated with three standard erythema doses of solar-simulated ultraviolet radiation (UVR) thrice weekly. Three groups received 2 × 2 prophylactic PDT treatments (days 45 + 52 and 90 + 97). The PDT treatments consisted of topical administration of 16% MAL, 20% MB, or 20% RF, and subsequent illumination that matched the photosensitizers’ absorption spectra. Control mice received no PDT. We recorded when the first, second, and third skin tumors developed. The pattern of tumor development after MB-PDT or RF-PDT was similar to that observed in irradiated control mice (p > 0.05). However, the median times until the first, second, and third skin tumors developed in mice given MAL-PDT were significantly delayed, compared with control mice (256, 265, and 272 vs. 215, 222, and 230 days, respectively; p < 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice.

• No data on the efficacy of repeated treatments of MAL DL-PDT for AKs of the face and scalp is available. • We demonstrated that two-treatment schedule of MAL DL-PDT has similar efficacy to the single-treatment for AKs. • The second treatment was associated with higher pain than the first treatment. • Alternative strategies might be recommended to optimize the efficacy of DL-PDT. Efficacy of daylight-photodynamic therapy (DL-PDT) with methyl aminolaevulinate (MAL) has been reported to gradually decrease as the severity of actinic keratosis (AK) lesions increases. Repeated treatments have been suggested to increase the efficacy of DL-PDT. Aim of our pilot study was to evaluate the efficacy and tolerability of a single versus two-treatment schedule of MAL DL-PDT for the treatment of multiple AKs of the face/scalp in a prospective, intra-patient, comparison study. Patients with multiple AKs of the face/scalp received a single treatment of MAL DL-PDT or 2 treatments, 1 week apart, on either half-side. Weather conditions and outdoor temperature were recorded during daylight exposure. Visual analog scale for pain was assessed immediately after each session, and severity of local skin reactions after 2 days. Treatment efficacy was evaluated at 3 months. Thirty-one patients with multiple AKs of the face/scalp were enrolled and completed the study. No significant difference was observed between single and two-treatment schedule in the lesion complete response rate for total AKs (80.7% vs 85.6%, p = 0.28) and for AKs divided by grade (grade I: 88.5% vs 89.2%, p = 0.79; grade II: 67.3% vs 71.0%, p = 0.71; grade III: 50.0% vs 55.6%, p≈1.00). Pain was significantly higher during the second session (p = 0.04). Local skin reactions were generally mild, but more severe after the first treatment (p < 0.01). The two-treatment schedule did not improve significantly the efficacy of MAL DL-PDT for AKs of the face and scalp as compared to the single-treatment. Alternative strategies might be recommended to optimize the efficacy of DL-PDT. [ABSTRACT FROM AUTHOR]

• A new protocol consisting of 3 MA L/PDT sessions with 4 weeks in between was tested. • This protocol was effective, safe with excellent cosmesis. • No recurrence was observed at 12-month follow-up. Although surgical removal is the treatment of choice in Bowen's disease (BD), there are cases in which by age, comorbidities, use of anticoagulants, location, cosmetic result, or size, it is preferable to use other treatments such as cryotherapy, 5-fluorouracil cream, imiquimod 5% cream or photodynamic therapy (PDT). Efficacy of PDT in BD is supported by substantial research and clinical data. This study aimed to evaluate the long term effectiveness of methyl aminolevulinate-PDT (MAL/PDT) on a wide range of Bowen lesions in different locations and sizes. Patients diagnosed with BD were treated in 3 sessions with a 4-week interval in between with MAL/PDT between January 2016 and January 2017 in a private clinic. Clinical response and relevant patient and tumour characteristics were analyzed during the first year after start of the PDT sessions. In total, 21 BD lesions in 18 patients were included in the study. Complete regression (CR) after 3rd PDT session was 87.5% and 100% at the 6-month follow-up. Treatment was well tolerated and local adverse reactions were very scarce. No recurrence was observed at 12-month follow-up. Cosmetic outcome at 12 months was good or excellent in 100% of patients. MAL/PDT is an effective, non invasive and safe treatment modality for BD with excellent cosmesis. [ABSTRACT FROM AUTHOR]

Background: Oral cancer is a common cancer with a high mortality rate. While surgery is the most effective treatment for oral cancer, it frequently causes deformity and dysfunction in the orofacial region. In this study, methyl aminolevulinate photodynamic therapy (MAL‐PDT) as a prevention tool against progression of precancerous lesion to oral cancer was explored. Methods: For in vitro studies, we evaluated the effects of MAL‐PDT on viability of DOK oral precancerous cells by XTT, cell morphology by TEM, and intracellular signaling pathways by flow cytometry, Western blotting, and immunofluorescence. For in vivo study, DMBA was used to induce oral precancerous lesions in hamsters followed by MAL‐PDT treatment. We measured tumor size and body weight weekly. After sacrifice, buccal pouch lesions were processed for H&E stain and immunohistochemistry analysis. Results: MAL‐PDT induced autophagic cell death in DOK oral precancerous cells. The autophagy‐related markers LC3II and p62/SQSTM1 and autophagosome formation in DOK cells were increased after MAL‐PDT treatment. In vivo, Metvix®‐PDT treatment decreased tumor growth and enhanced LC3II expression in hamster buccal pouch tumors induced by DMBA. Conclusions: Our in vitro and in vivo results suggest that MAL‐PDT may provide an effective therapy for oral precancerous lesions through induction of autophagic cell death. [ABSTRACT FROM AUTHOR]

Background: Topical methyl aminolevulinate photodynamic therapy (MAL-PDT) is highly effective for the treatment of superficial basal cell carcinoma (sBCC). Current European treatment protocol requires two hospital visits, which is costly and unpractical. The aim of this study was to evaluate the efficacy of fractionated MAL-PDT, using two light fractions at 3 and 4 h compared to illumination at 3 and 5 h after MAL-application. Methods: Thirty patients were randomized into two groups. The first group received illumination at 3 and 4 h (20 + 55 J/cm2) after MAL-application (3/4 group). In the other group, two light fractions were performed at 3 and 5 h (20 + 55 J/cm2) after MAL-application (3/5 group). The lesion response was evaluated at 3 and 12 months posttreatment. Results: In the 3/5 group, 70.0% showed a complete response (CR) at 3 months compared to 63.6% in the other group. At 12 months, 100% showed a CR in the 3/5 group compared to 80.0% in the other group. However, most failures/recurrences were eventually due to the presence of a more aggressive BCC subtype, mostly caused by sampling error of the primary punch biopsy. Conclusion: Single day protocol for MAL-PDT for sBCC is feasible and this study shows promising results. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.

Keywords: allergic contact dermatitis; case report; exposure; methyl aminolevulinate; Metvix; occupational; photodynamic therapy EN allergic contact dermatitis case report exposure methyl aminolevulinate Metvix occupational photodynamic therapy 50 52 3 06/19/20 20200701 NES 200701 Photodynamic therapy (PDT) is widely used for treatment of different types of nonmelanoma skin cancers. In conclusion, we would like to point out that sensitization to MAL and resulting allergic contact dermatitis is not only an important adverse event in patients receiving repetitive PDT treatment but also in individuals with occupational exposure. 2007; 23 (1): 35 - 36. 4 Hohwy T, Andersen KE, Solvsten H, Sommerlund M. Allergic contact dermatitis to methyl aminolevulinate after photodynamic therapy in 9 patients. [Extracted from the article]

Actinic (solar) keratoses are premalignant lesions caused by prolonged exposure to ultraviolet radiation, with the potential to progress into squamous cell carcinoma. Hence, use of appropriate therapies is critical for effective treatment. Daylight-mediated photodynamic therapy with methyl aminolevulinate cream is a convenient new option for the safe and effective treatment of actinic (solar) keratosis lesions, offering similar efficacy to conventional photodynamic therapy, nearly painless treatment, and reduced in-clinic times. Use of appropriate therapies and optimization of clinical practice are critical for safe and effective treatment. Nurses play a key role in ensuring best clinical practice and effective treatment. This article explains the practicalities and principles of daylight-mediated photodynamic therapy to ensure best practice by treating nurses. [ABSTRACT FROM AUTHOR]

Abstract: Acne vulgaris is one of the most common dermatological problems, and its therapeutic options include topical and systemic retinoids and antibiotics. However, increase in problems associated with acne treatment, such as side‐effects from conventional agents and bacterial resistance to antibiotics, has led to greater use of photodynamic therapy. The purpose of this study was to compare the bactericidal effects of indocyanine green‐ and methyl aminolevulinate‐based photodynamic therapy on Propionibacterium acnes. P. acnes were cultured under anaerobic conditions; then they were divided into three groups (control, treated with indocyanine green and treated with methyl aminolevulinate) and illuminated with different lights (630‐nm light‐emitting diode, 805‐nm diode laser and 830‐nm light‐emitting diode). The bactericidal effects were evaluated by comparing each group's colony‐forming units. The cultured P. acnes were killed with an 805‐nm diode laser and 830‐nm light‐emitting diode in the indocyanine green group. No bactericidal effects of methyl aminolevulinate‐based photodynamic therapy were identified. The clinical efficacy of indocyanine green‐based photodynamic therapy in 21 patients was retrospectively analyzed. The Korean Acne Grading System was used to evaluate treatment efficacy, which was significantly decreased after treatment. The difference in the efficacy of the 805‐nm diode laser and 830‐nm light‐emitting diode was not statistically significant. Although the methyl aminolevulinate‐based photodynamic therapy showed no bactericidal effect, the indocyanine green‐based photodynamic therapy has bactericidal effect and clinical efficacy. [ABSTRACT FROM AUTHOR]

Background: Research has shown daylight-mediated photodynamic therapy (PDT) for the treatment of actinic keratosis (AK) to be effective, tolerable, and convenient, with excellent patient satisfaction and cosmesis. Although success has been demonstrated in areas with similar latitudes to Switzerland and Scandinavia, this treatment has not been studied in a Canadian population. Objectives: The purpose of this study is to investigate the effectiveness, safety, and patient satisfaction of daylight-mediated methyl 5-aminolevulinate (MAL)–PDT to make recommendations for its use in Canadian practice. Methods: A retrospective chart review of patients who received treatment of daylight-mediated MAL-PDT for the indication of AK at the Institute of Cosmetic and Laser Surgery in Oakville, Ontario, between 2009 and 2016. Results: A total of 112 patients were included, consisting of 94 males and 18 females with a mean age of 63.79 years. A total of 177 sites were treated among all patients, mostly consisting of the face (n = 92) and scalp (n = 55). A total of 13.4% of patients experienced side effects, the most common being redness (n = 4) and scabbing (n = 4). Of the 42 patients who expressed their level of satisfaction, 83.3% reported being happy with the treatment, χ2(1) = 18.67, P ≤ .05; 6.3% of patients were noted to be completely clear, 86.6% had a good response, 0.9% had a mild response, and 0% had no response, χ2(1) = 101.04, P ≤ .05. Conclusions: Daylight-mediated MAL-PDT is a suitable treatment option for AK lesions in a Canadian population due to the demonstrated efficacy, patient satisfaction, tolerability, and convenience. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of actinic keratosis (AK) continues to increase worldwide. Currently available options for the treatment of AK include topical 5-fluorouracil (5-FU) and daylight- mediated photodynamic therapy (DLPDT). This split-face pilot study compared DLPDT using 16% methyl aminolevulinate (MAL) cream versus 5-FU cream in patients with AK on the face/scalp. Methods: Five male subjects (mean age 70 years) with grade I–III AK on the face/scalp were enrolled. Subjects received a single session of DL-PDT with 16% MAL on one side and topical 5% 5-FU for 21 days on the other side. Evaluations of efficacy, safety, and subject satisfaction were conducted 48 h, 7 days, 14 days, 1 month, and 3 months after treatment. Results: At 3 months, the lesion complete response rate was 80% and 93% for DL-PDT and 5-FU, respectively. Lesion partial response was 20% and 7%, respectively. Fewer treatment-related adverse events (AEs) were reported with DL-PDT than with 5-FU, and they resolved spontaneously in 5–7 and 27–30 days, respectively. Subjects preferred DL-PDT because of the lower incidence of AEs and rapid recovery compared with 5-FU. Conclusion: DL-PDT is a convenient alternative to 5-FU with good efficacy and a favorable safety profile, allowing patients to effectively treat their AK without compromising their social life. [ABSTRACT FROM AUTHOR]

This split-face design study evaluated the effect of pretreatment with calcipotriol prior to daylight-mediated photodynamic therapy (DL-PDT) in patients with actinic keratosis (AK). The study included 11 subjects with grade I–III AK (mean age: 55 years). Subjects used once-daily calcipotriol 50 mcg/g ointment on half the face/scalp for 15 days prior to DL-PDT. Evaluations of efficacy, safety and subject satisfaction were conducted 48 h and 7 days after treatment, and at 1- and 3-month follow-ups. Three months after treatment with calcipotriol/DL-PDT and DL-PDT alone, the complete response rate was 85% and 70%, respectively. The partial response rate was 12% and 25%, respectively. During calcipotriol pretreatment, 6 subjects reported erythema and moderate desquamation. In 7 subjects, calcipotriol/DL-PDT was associated with more marked erythema than that observed with DL-PDT alone. Eight subjects reported they preferred DL-PDT alone due to the inconvenience caused by the daily application of calcipotriol and the related erythema and desquamation. Although calcipotriol improved the efficacy of DL-PDT, it may not be applicable to all patients. DL-PDT is a simpler, safer and more convenient option than conventional-PDT. Therefore, the use of additional agents prolonging the course of treatment and increasing cost may diminish the advantages currently offered by DL-PDT. [ABSTRACT FROM AUTHOR]

Background Pretreatment of skin to remove scales/crusts and roughen the surface is essential to enhance the penetration of topically applied methyl aminolevulinate (MAL) prior to photodynamic therapy and to permit daylight to access all parts of the skin lesions. Numerous procedures of skin preparation are currently available. This study compared the in vitro penetration of MAL into ex vivo human skin pretreated with skin preparation pad abrasion or a microneedling device, and evaluated the effectiveness of an iontophoretic device in delivering MAL into ex vivo human skin. Methods Human skin samples, obtained from aesthetic surgeries, were used in this study. The thickness of the skin samples ranged between 1.44–2.87 mm. Pretreatment of samples was performed with 10 passages of the Ambu ® Unilect™ 2121 M (Ambu A/S, Denmark) skin preparation pad, 8 rolling repetitions using the microneedling device Dermaroller ® HC 902 (Dermaroller GmbH, Germany), or by an iontophoresis device (Feeligreen SA, France) for 1.5 h. The effect of these pretreatment procedures on the penetration of MAL into the skin was assessed. Results Penetration in the total skin, liquid receptor and total penetration was most increased by skin preparation pad treatment, followed by microneedling and iontophoresis. Overall, MAL total penetration was increased up to 103-fold by skin preparation pad treatment, 4-fold by microneedling and 1.8-fold by iontophoresis. Conclusions Abrasion with skin preparation pad was shown to be superior to microneedling and iontophoresis for increasing MAL penetration in ex vivo human skin. [ABSTRACT FROM AUTHOR]

(1) Background: Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, followed by South-Central Asia and South America. According to the Brazilian National Institute of Cancer (INCA), 16,370 new cases of cervical cancer were estimated for each year of the biennium of 2018−2019. About 90% of cervical cancers originate from the malignant progression of cervical intraepithelial neoplasia (CIN) which is classified based on cytohistological characteristics (low- and high-grade lesions). The present study reports the long-term effectiveness of topical photodynamic therapy (PDT) for CIN grades 1 and 2/3 with up to two years of follow up. (2) Methods: A total of 56 patients with CIN 1, ten with CIN 2, and 14 patients for the placebo group were enrolled in this study. (3) Results: 75% (n = 42) of CIN 1 patients presented a complete response to PDT and only 23.2% (n = 13) of recurrence, progression, and/or lesions remaining two years after PDT. For CIN 2/3 patients, 90% were observed to be cured after one and two years of follow up. (4) Conclusions: PDT presented best results two years after a non-invasive, fast, and low-cost procedure and in comparison with the placebo group, preventing the progression of cervical intraepithelial neoplasia and preserving the cervix.

Background: Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated.Methods/design: In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale. Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6. Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events).Discussion: This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760).Trial Registration: ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014-005121-13. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy ( PDT) has been reported as an effective alternative treatment for patients with acne. Purpose To evaluate the efficacy and safety of DL- PDT in moderate to severe acne and to compare outcomes with those of laser-assisted daylight photodynamic therapy. Methods Patients were randomly assigned to either a DL- PDT group (D group) or a fractional laser-assisted DL- PDT group (F group). The outcomes were assessed by measuring acne lesion counts and severity grade at 4, 8, 12, and 16 weeks after therapy commenced. Results Twenty-eight subjects completed the study. Compared with baseline, the mean inflammatory lesion counts significantly decreased by 36.0% in the D group and 51.8% in the F group at 8 weeks ( P<.001). The mean acne severity grades in both groups significantly decreased starting at 4 weeks ( P=.012), and the beneficial effects lasted 16 weeks. Conclusion DL- PDT with MAL shows clinically good responses to inflammatory lesions and is well tolerated in patients with moderate to severe acne. [ABSTRACT FROM AUTHOR]

Background:Actinic keratoses (AKs) are a consequence of chronic exposure to ultraviolet radiation. Treatment of chronically photo-damaged skin and AKs is driven by risk of progression to squamous cell carcinoma, as well as for symptomatic relief. Conventional photodynamic therapy (c-PDT) is indicated when AKs are multiple or confluent and if patients respond poorly or are unable to tolerate other therapies. c-PDT is limited by the field size that can be treated in single sessions and can cause significant discomfort. Objective:Recent studies investigated daylight illumination to activate protoporphyrin IX and daylight-PDT (d-PDT) is now licensed in the UK for face and scalp AKs. A group of experts met to discuss application of d-PDT with methyl aminolevulinate (MAL) and develop a UK consensus statement, specific to UK weather conditions. Methods:The UK consensus recommendations were reached among eight experts, who reviewed recent studies on d-PDT, assessed UK meteorological data and discussed personal experiences of d-PDT for AKs. Results:Recommendations from these discussions provide guidance on d-PDT use, specifically regarding patient selection, therapeutic indications, when to treat, skin preparation, MAL application and daylight exposure for patients with AKs. Conclusions:This UK expert consensus provides practical guidance for UK application of d-PDT. [ABSTRACT FROM PUBLISHER]

Background Photodynamic therapy (PDT) is a successful treatment for non-melanoma skin cancers. Methyl-aminolevulinate (MAL) is metabolized to protoporphyrin IX (PpIX) which accumulates in the skin lesion and which generates a painful photochemical toxic reaction upon red light exposure. PDT using daylight (DL) exposure is now used to reduce pain and subjects are advised to protect the areas with sunscreen. This work investigated the effect of sunscreen on MAL penetration and PpIX photoactivation in ex vivo human skin. Methods To measure skin penetration of MAL, particle-free sunscreens were applied on ex vivo human skin samples mounted on diffusion cells before application of Metvix cream containing [ 14 C]-MAL for 2.5 h. To circumvent the absence of skin penetration of PpIX, skin samples were first treated with microneedles and mounted on diffusion cells before the application of PpIX solution for 1 h followed by sunscreens. Skin samples were then exposed to solar simulator for 1 h. Concentrations of [ 14 C]-MAL or PpIX were measured in both total skin and receptor liquid. Results and conclusions The results showed that the in vitro skin penetration of MAL and the PpIX photoactivation on ex vivo human skin samples are not modified by pretreatments of ex vivo human skin with sunscreens. This study demonstrates that neither in vitro skin penetration of MAL nor PpIX photoactivation were modified by pretreatments with Cetaphil SPF 30 Dermacontrol and Actinica ® Lotion SPF 50+. This supports the efficacy and safety of MAL DL-PDT in the clinical situation. [ABSTRACT FROM AUTHOR]