5-aminolaevulinic Acid Photodynamic Therapy Research Articles

Neoadjuvant Photodynamic Therapy: An Updated Therapeutic Approach for Non-Melanoma Skin Cancers.

Non-melanoma skin cancers (NMSCs) are the most common malignancy and surgical excision is considered treatment of choice for the majority of cases. However, surgery can be very extensive in cases of large, multiple, or cosmetic-sensitive tumors located on areas such as scalp and face or genital region, leading to significant functional and cosmetic deficit. Aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a widely used approach in a variety of skin diseases, demonstrating remarkable efficacy in treatment of actinic keratosis, Bowen disease and basal cell carcinoma. Besides, when employed as a preoperative intervention, ALA-PDT effectively reduces tumor size and minimizes subsequent local surgical morbidity. With its minimally invasive nature and proven effectiveness, ALA-PDT holds significant promise as a neoadjuvant treatment option for NMSCs. In cases where the tumor is large, invasive, multiple, or located in cosmetically and functionally sensitive areas, or when considering patient factors such as age, comorbidity, willingness to undergo surgery, and post-operative quality-of-life, surgical intervention or radiotherapy alone may be impracticable or unacceptable. In such scenarios, neoadjuvant ALA-PDT can offer remarkable outcomes. In order to further ensure the maximum benefit of patients from neoadjuvant PDT, collaboration with multidisciplinary teams and whole-process management may be in need.

ALA-PDT augments intense inflammation in the treatment of acne vulgaris by COX2/TREM1 mediated M1 macrophage polarization

Severe acne vulgaris is a common chronic inflammatory skin disease worldwide. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is effective and safe for severe acne. However, the mechanism is not fully understood. Intense acute inflammatory response at 24 h after ALA-PDT is reported positively correlated to the effectiveness. Inflammation regulation influence the progression or outcome of diseases. ALA-PDT may exert its therapeutic effect by augmenting intense inflammation and break the chronic inflammation. This study was set out to explore the mechanism of ALA-PDT augmenting intense acute inflammation in the treatment of acne. As a result, transcriptome microarrays analysis of severe acne patients showed that ALA-PDT significantly up-regulated expression of various inflammation-related genes, especially TREM1 and PTGS2, which were further confirmed by a C.acnes induced acne-like mouse ear model. The subsequent experiments demonstrated that ALA-PDT could trigger pro-inflammatory M1 polarization of macrophages in vitro and in vivo. Additionally, the crosstalk between keratinocytes and macrophages studied by a transwell co-culture system indicated that PGE2 secreted by ALA-PDT treated HaCaT cells could promote THP-1 macrophages M1 polarization by COX2/PGE2/TLR4/TREM1 axis to augment inflammation. Our study provides a novel insight that ALA-PDT could amplify inflammation by COX2/TREM1 mediated macrophages M1 polarization for the treatment of acne. It is hoped that this research will decipher the mechanism of ALA-PDT for the treatment of acne and provide a theoretical basis for optimizing the clinical ALA-PDT management.

Methyl Aminolaevulinic Acid versus Aminolaevulinic Acid Photodynamic Therapy of Actinic Keratosis with Low Doses of Red-Light LED Illumination: Results of Long-Term Follow-Up.

Photodynamic therapy (PDT) treatment for multiple actinic keratosis (AK) has been found effective when lower doses of red light were used with methyl aminolaevulinic acid (MAL). The aim of this study was to compare the results of lower doses of red light conventional PDT (h-PDT, 16 J/cm2) with MAL and aminolaevulinic acid (ALA) in a long-term follow-up. Patients with more than five symmetrical AK on the scalp who were candidates for PDT were selected and divided randomly between MAL and ALA treatment and patients were followed at 3 and 12 months. The responses were assessed by counting the total AK and the AK per patient. Pain and adverse events were also compiled. A total of 46 patients were treated, 24 with MAL, and 22 with ALA. The two groups were comparable at baseline (p > 0.005). No significant differences were found in the results of both treatments at 12 months, despite ALA exhibiting slightly better results at 3 months. No differences in pain and adverse events were assessed. Both ALA and MAL were effective when lower doses of red light were used in c-PDT. Long term efficacy was also documented. Further studies are necessary to determine the inferior point of red-light illumination without losing efficacy.

Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms.

Early treatment of oral precancerous lesions is considered as a key strategy for in oral carcinogenesis prevention. Increasing evidence has suggested that the transforming growth factor beta (TGF-β) signaling pathway is tightly involved in the process of oral-carcinogenesis. In this study, we investigated the inhibition effect and potential mechanism of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) in human oral precancerous cells via TGF-β pathway. Here, the dysplastic oral keratinocyte (DOK) cells were incubated with ALA concentration of 1mM/mL for 4h and then irradiated with a Helium-Neon (He-Ne) ion laser at 633nm (200mW/cm2). The control cells were cultured in Dulbecco's modified Eagle's medium (DMEM) medium. We analyzed the differentially expressed genes and correlated pathways in oral precancerous cells following ALA-PDT using Affymetrix microarrays. TGF-β pathway was analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. Bioinformatics analysis was performed to evaluate the expression of TGF-β1 in human oral cancer samples and adjacent normal samples. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and wound healing assay were used to assess the effects of ALA-PDT plus TGF-β receptor inhibitor (LY2109761) in DOK cells. The TGF-β signaling could exert in suppressive effects on DOK cells after ALA-PDT. The cell proliferation and migration rate of DOK cells was significantly reduced and apoptosis and ROS generation induced more effectively by ALA-PDT combined with LY2109761. Furthermore, cell cycle analysis revealed that the combined treatment resulted in G0/G1 phase arrest. ALA-PDT suppresses the growth of oral precancerous cells by regulating the TGF-β signaling pathway, and its suppressive effect was enhanced using LY2109761. These results indicate that it could be a promising alternative treatment against oral precancerous lesions.

A prospective study of adverse reactions of ALA-PDT for acne vulgaris

BackgroundAcne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, the lack of detailed information of adverse reactions limits the promotion of ALA-PDT in clinic. ObjectiveTo systemically investigate the adverse reactions relating to ALA-PDT for acne vulgaris. MethodsA prospective study was performed at the Shanghai Skin Disease Hospital. ResultsIn the prospective study, 35 patients with acne vulgaris completed the trial. The adverse reactions were first divided into acute-phase adverse reactions, including erythema (94.3%), post-treatment pain (91.4%), burning skin (91.4%), dry skin (91.4%), itching (85.7%), pustule (82.9%), edema (20%) and blister (11.4%), or recovery-phase adverse reactions, which included crust (65.6%), exudation (48.6%) and hyperpigmentation (42.7%). Younger patients were more likely to have pustules (P<0.05). Male patients were represented itching more often than female patients (P<0.05). The efficacy of ALA-PDT for severe acne was positively related to the severity of acute-phase adverse reactions. The duration of pain was shortest. Crusting and hyperpigmentation lasted considerably longer. ConclusionIn the present study, we recorded the relative incidence of various adverse reactions following ALA-PDT for acne vulgaris. The severity of adverse reactions tended to decrease with increased patient age, except for itching and hyperpigmentation. Light-to-moderate adverse reactions might be the inflammatory reactions of ALA-PDT, predicting a good efficacy. A form for evaluation of adverse reactions based on the present study could assist dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction.

The effect of 5-Aminolaevulinic Acid Photodynamic Therapy versus CO2 laser in the Treatment of Cervical Low-grade Squamous Intraepithelial Lesions with High-Risk HPV Infection: A non-randomized, controlled pilot study

Background: There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO2 laser therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with high-risk human papillomavirus (HR-HPV), especially for long-term efficacy. Methods: Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4–6 months and 12 months after the treatment. Results: (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO2 laser therapy. (2) 4–6 months after treatment, there was no significant difference between two groups in the complete remission (CR) rates of cervical LSIL and the clearance rate of HR-HPV infection. (3) 12 months after treatment, compared with the CO2 laser group, the CR rates of cervical LSIL in the 5-ALA PDT group was significantly higher than the CO2 laser group. There was no statistical difference in the clearance rate of HR-HPV infection between the two groups. (4) 12 months after treatment, the recurrence rate of cervical lesions and the reinfection rate of HR-HPV infection in 5-ALA PDT group were significantly lower than those in CO2 laser group. Conclusion: The effect of 5-ALA PDT is similar to CO2 laser at 4–6 months. The long-term efficacy of 5-ALA PDT appears better than CO2 laser. As a non-invasive treatment, 5-ALA PDT is a highly effective therapeutic procedure for cervical LSIL with HR-HPV infection.

20% ALA-PDT pretreated by fire needle in patients with dissecting cellulitis of the scalp: An interim analysis

BackgroundDissecting cellulitis of the scalp (DCS) is a rare but distinctive, chronic suppurative condition, and the treatment is a therapeutic challenge. Recently, treatment of DCS with 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) has been considered as a potential option. ObjectiveTo evaluate the efficacy and safety of 20% ALA-PDT pretreated by fire needle in the treatment of DCS. Materials and methodsTopical 20% ALA-PDT with fire needle intervention as a pretreatment, was applied to six patients with DCS. All patients completed three sessions treatment at an interval of ten days. They were assessed for the efficacy at the baseline and on ten days after each treatment. According to the reduction of lesions and the improvements of patients’ symptoms after each session, the objective assessment of therapeutic effect was divided into four grades. The adverse effects were recorded. ResultsA total of six male patients were enrolled in our study. After three sessions of ALA-PDT, among them, three patients recovered, two patients achieved significant improvement and one patient achieved partial response.Patient 4 (Pt.4) relapsed at 6-month follow-up. Pt.1 and Pt.6. maintained complete response after one year follow-up. We also found that the clearance rate of the popular/nodular and cyst/abscess was much higher than sinus. Conclusion20% ALA-PDT pretreated by fire needle could be an effective, minimally-invasive, safe method for DCS patients. Lesion in the early stages have a better response than sinus.

5-Aminolaevulinic acid photodynamic therapy suppresses lipid secretion of primary sebocytes through AMPK/SREBP-1 pathway

BackgroundAcne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, its specific treatment mechanism remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT induced lipid secretion inhibition in acne vulgaris. MethodsPrimary human sebocytes and sebaceous gland of golden hamster were treated with/without ALA-PDT. Cell viability was evaluated by Live/Dead Cell assay. Fluorescence microscope was used to observe lipids secretion in sebocytes after Nile red staining. The expression of SREBP-1 after ALA-PDT was evaluated by qRT-PCR. Regulation of ALA-PDT on AMPK/SREBP-1 was evaluated by western blot. ResultsThe results showed that ALA-PDT suppressed lipid secretion of primary human sebocytes. In addition, ALA-PDT could inhibit the expression of SREBP-1 in vitro. We also found that ALA-PDT activated AMPK pathway, down-regulating the expression of SREBP-1 in sebocytes after ALA-PDT. ConclusionsThese findings elucidate that ALA-PDT suppresses lipid secretion through AMPK/SREBP-1 pathway in treatment of acne vulgaris.

A prospective study of the effect of fire micro-needling plus 5% topical ALA-PDT for the treatment of dissecting cellulitis of the scalp

BackgroundDifferent therapies have been used for dissecting cellulitis of the scalp (DCS) with poor results. Topical 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is effective for many inflammatory skin diseases. ObjectivesTo evaluate the efficacy and safety of fire micro-needling plus 5% ALA-PDT on DCS. MethodsForty-two male DCS patients were enrolled and treated by four sessions of fire micro-needling plus 5% ALA-PDT (occlusion time: 3 h, 100 mW/cm2 for 20–32 min, 633 ± 10 nm LED) with an interval of 1–2 weeks. The reduction of lesions was evaluated at each follow-up visit. The patients` symptoms were evaluated by Dermatology Life Quality Index (DLQI). All of the side effects were recorded. ResultsForty-one DCS patients finished the treatments and the marked effective rate (MER) reached 65.85%. Ten patients (24.39%) were cured and 17 patients (41.46%) achieved excellent improvement. The median of lesion numbers decreased significantly from 25 to 7 (p < 0.001) with DLQI from 13 to 2 (p < 0.001). Although all the ten cured patients had a relapse during the 12-month follow-up, 5/10 patients had a remission of more than 6 months. All the patients tolerated PDT well with mild adverse effects. ConclusionsFire micro-needling plus 5% ALA-PDT is effective for Chinese male DCS patients without the need to take systemic drugs.

5-Aminolaevulinic acid photodynamic therapy amplifies intense inflammatory response in the treatment of acne vulgaris via CXCL8.

Acne vulgaris is a chronic inflammatory cutaneous disease. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is a novel and effective approach for severe acne vulgaris treatment. However, its specific treatment mechanism still remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT regulated intense inflammatory response in acne vulgaris. It appeared that ALA-PDT suppresses proliferation and lipid secretion of primary human sebocytes. Besides, ALA-PDT could up-regulate the expression of CXCL8 in vivo and in vitro, amplifying the inflammatory response by recruiting T cells, B cells, neutrophils and macrophages. We also found that ALA-PDT elevated the expression of CXCL8 via p38 pathway. SB203580, a p38 pathway inhibitor, decreased the expression of CXCL8 in sebocytes after ALA-PDT. These findings indicate that ALA-PDT amplifies the intense inflammatory response in the treatment of acne vulgaris via CXCL8. Our data decipher the mechanism of intense inflammatory response after ALA-PDT for acne vulgaris.

The place of 5-aminolaevulinic acid-photodynamic therapy in the treatment landscape of urethral warts: A systematic review.

Human papilloma virus (HPV) infection is the most common sexually transmitted disease worldwide and the main cause of genital warts. Clear recommendations for the management of urethral warts, which are often hard to detect and difficult to treat, are still lacking. To summarize all available data describing treatment modalities of urethral warts, compare their efficacy and side effects, and provide physicians a treatment strategy outline. Till June 2020, we conducted a systematic review of articles studying the different treatment modalities of urethral condylomas. A chi-square test was used to compare the recurrence rates between treatment modalities, the complete clearance rates at first follow-up and the rates of adverse events. A total of 26 articles with 1730 patients were included in our review. 61 % of patients were deemed completely cured on the first follow-up while 21 % recurred. 5-aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) was the most common treatment and yielded the lowest recurrence rate (7.5 %) followed by laser therapy (24 %) and topical therapy (31 %) (p < 0.01). ALA-PDT resulted in a higher rate of clearance on follow up (96 %) compared to laser therapy (69 %) and topical therapy (14 %) (p < 0.01). Adverse events were more frequent in the ALA-PDT group (69 %) compared to laser therapy (28 %) and topical treatment (30 %) (p < 0.01). ALA-PDT appears to be the most effective treatment of urethral condylomas in term of clearance and recurrence rate, but with a higher risk of adverse events. Management should be tailored to the type of lesion found at presentation.

Skin field cancerisation: A systematic review of the literature regarding its treatment.

Skin neoplasms are the most frequent malignant lesions, increasing patient's morbidity when associated with skin field cancerisation. There is a need to understand the current therapies, both clinical and surgical. A systematic review was performed according to the PRISMA guideline, registered in PROSPERO: CRD42018114826, including studies from 2012 to 2019. Seven hundred and eighty-two studies were found, of which 21 were included. Of these, 8 primary studies were randomised controlled trials: fractional CO2 laser-assisted photodynamic therapy (PDT) vs. PDT (no significance), daylight PDT vs. PDT (no significance, daylight PDT had less adverse effects), trichloroacetic acid peel vs. 5-aminolaevulinic acid PDT (clinical improvement of aminolaevulinic acid PDT), 5-Fluorouracil 0.5%/Salicylic Acid 10% vs. vehicle (clinical improvement of 5-Fluorouracil 0.5%/Salicylic Acid 10%), photolyase vs. sun filters (no significance), sunscreens vs. sunscreens plus DNA repair enzymes (DNA Repair Enzymes was more effective in reducing field cancerisation). Only one systematic review was included in which there was effectiveness of daylight PDT in the treatment of actinic keratoses. The other 12 included studies had a lower level of evidence including surgical studies. Clinical studies are more relevant in the treatment of the field cancerisation. There is a lack of surgical studies.

Assessment of 5-Aminolaevulinic Acid Photodynamic Therapy (ALA-PDT) in Chinese patients with actinic keratosis: Correlation of dermoscopic features with histopathology.

The study examines the changes in dermoscopic features of actinic keratosis (AK) after photodynamic therapy, and delineates the association between AK dermoscopic and histopathological findings. A total of 21 patients (23 lesions) with pathologically confirmed actinic keratosis who received 5-aminolaevulinic acid (ALA) photodynamic therapy (ALA-PDT) were enrolled. The numbers of PDT treatments were: 1, n=1; 2, n=2; 3, n=10; 4, n=6; 5, n=2; 6, n=2). The dermoscopic features before and after the PDT were compared. There were statistically significant decreases in the positive rates of dermoscopic features including scales (P<0.001), follicular plugs with whitish halo (P=0.013), and red pseudonetwork (P=0.022) among patients treated with ALA-PDT. Dermoscopic feature was significantly associated with pathological grade (P<0.001). Histopathological hyperkeratosis was significantly associated with dermoscopic red pseudonetwork (P=0.034) and wavy vessel (P=0.005). Parakeratosis was associated with wavy vessels (P=0.001). For vascular hyperplasia in dermal papillae, the significant correlates included scales (P=0.011), follicular plugs with whitish halo (P=0.011), red pseudonetwork (P<0.001); coiled vessels (P=0.003) and rosette sign (P=0.004). Wavy vessels was the only feature correlating keratosis pilaris (P=0.003). The findings of the present study support dermoscopy as having potential to be useful for diagnosing and monitoring of actinic keratosis.

Advanced application of holmium: YAG laser combined ALA-PDT for the treatment of refractory condylomata acuminata in anal canal.

Anal canal condylomata acuminata is a disease caused by the human papilloma virus. Conventional cauterizing laser treatment cannot achieve a satisfactory result owing to a high recurrence rate, and the application of 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) also has limitations in the anal canal. Holmium yttrium aluminum garnet (Ho: YAG) laser with fiber is found to be effective at removing canal lesions, and may create suitable conditions for ALA-PDT. We aim to investigate the feasibility of Ho: YAG laser combined with ALA-PDT and to explore a more optimal therapy in refractory anal canal condylomata. Data of 37 patients with anal canal condylomata (number of warts≥ 10 lesions) from May 2017 to March 2019 were reviewed. In total 17 cases were treated with Ho: YAG laser plus ALA-PDT, and 20 patients treated with CO2 laser plus ALA-PDT were selected as control. Wart clearance and recurrence rates were evaluated as well as laser complications. Most warts (88.23 %) were removed after a session of Ho: YAG laser pretreatment. The average number of laser sessions required to clear all warts was 1.94 in the Ho: YAG laser plus ALA-PDT group. Meanwhile, no wound infections or defecation disfunctions were found. Ho: YAG laser with ALA-PDT could significantly reduce wart recurrence rates (17.6 %) in comparison with CO2 laser with ALA-PDT (55 %). Ho: YAG laser combined with ALA-PDT raised the cure rate of refractory anal canal condylomata and has important guidance implications for clinical application.

Treatment of dissecting cellulitis of the scalp with 10% ALA‐PDT

Dissecting cellulitis of the scalp (DCS) is difficult to be treated and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is considered to be a potential treatment for inflammatory skin diseases. To analyze the efficacy and safety of ALA-PDT on DCS. The treatment areas of DCS patients were incubated with freshly prepared 10% ALA for 3 hours. The 633 ± 10 nm light with the intensity of 80-100 mw/cm2 was used as the irradiation source of ALA-PDT, and the irradiation time was 20-30 minutes. Three sessions were applied at an interval of 10-15 days. According to the reduction of lesions and the improvements of patients' symptoms after each session, the objective assessment of therapeutic effect was divided into four grades. The adverse effects were recorded. Seven male DCS patients finished the treatments and assessments. One month after three sessions of treatment, one patient recovered, three patients received significant improvement, and one patients received medium improvement. At the 3-month follow-up, two patients recovered, four patients received significant improvement, and one patients received medium improvement. The patients tolerated well to the therapy without any severe adverse effects. 10% ALA-PDT is effective and safe on male DCS patients. As a localized and less invasive treatment, it provides a preferable choice for DCS patients. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Dermoscopic Monitoring for Treatment and Follow-Up of Actinic Keratosis With 5-Aminolaevulinic Acid Photodynamic Therapy

Objectives:To assess the usefulness of dermoscopy in monitoring the treatment response and recurrence of actinic keratosis treated with 5-aminolaevulinic acid photodynamic therapy.Methods:In total, 35 patients with 75 actinic keratosis lesions were treated with 5-aminolaevulinic acid photodynamic therapy. The patients were divided randomly into 2 groups, dermoscopic group and the control group. Sixteen patients with 35 actinic keratosis lesions were treated with dermoscopic monitoring to determine the end point of the treatment. The remaining 19 patients with 40 skin lesions served as control and treated without dermoscopic monitoring and observed with naked eyes. At 1-year follow-up, patients were examined to look for the recurrence rate of the disease.Results:In the dermoscopic group, 1 (2.85%) of 35 actinic keratosis lesions showed recurrence of disease after 6 months of treatment. The recurrence was noted with red pseudo-network and scales at the treated site, whereas in the control group, 5 (12.5%) of 40 lesions showed recurrence.Conclusions:Dermoscopy can be a useful tool for monitoring the skin lesions in patients with actinic keratosis during photodynamic therapy and follow-up.

Effect of light polarization on the efficiency of photodynamic therapy of basal cell carcinomas: an in vitro cellular study.

In an in vitro study, the effect of light polarization on the efficiency of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) of basal cell carcinoma (BCC) was investigated. Three states of light polarization (non-polarized, linearly polarized, and circularly polarized) were considered. Cells were exposed to green (532 pm 20 nm) irradiation from light emitting diodes. Cell survival was measured by the colorimetric assay (WST-1) and Trypan blue staining. The colorimetric assay showed a pronounced decrease in the cell viability (up to 30%) using polarized light compared to the non-polarized one in the wavelength region used. Similar results were obtained by the cell counting method (20-30% increase in cell death). The observed effect was dependent on the concentration of photosensitizer. The effect is more expressed in the case of linearly polarized light compared to the circularly polarized one. Results show that the use of polarized light increases the efficiency of in vitro ALA-PDT of BCC. Utilizing polarized light, it is possible to obtain the same effect from PDT by lower concentrations of photosensitizer. Additionally, the concentration dependency of PDT response and photo-bleaching is also reduced.

Light therapies for acne: abridged Cochrane systematic review including GRADE assessments.

We undertook a Cochrane review of randomized controlled trials (RCTs) evaluating the effects of light-based interventions for acne vulgaris. We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and grey literature sources (September 2015). We used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach to assess the quality of evidence (QoE). We included 71 RCTs (4211 participants, median sample size 31). Results from a single study (n = 266, low QoE) showed little or no difference in effectiveness on participants' assessment of improvement between 20% aminolaevulinic acid (ALA) photodynamic therapy (PDT), activated by blue light, vs. vehicle plus blue light, whereas another study (n = 180) comparing ALA-PDT (red light) concentrations showed that 20% ALA-PDT was no more effective than 15% ALA-PDT but better than 10% and 5% ALA-PDT. Pooled data from three studies (n = 360, moderate QoE) showed that methyl aminolaevulinate PDT, activated by red light, had a similar effect on changes in lesion counts vs. placebo cream with red light. Several studies compared yellow light with placebo or no treatment, infrared light with no treatment, gold microparticle suspension with vehicle and clindamycin/benzoyl peroxide (C/BPO) combined with pulsed dye laser with C/BPO alone. None of these showed any clinically significant effects. Most studies reported adverse effects, but inadequately, with scarring reported as absent, and blistering only in studies on intense pulsed light, infrared light and PDT (very low QoE). Carefully planned studies, using standardized outcome measures and common acne treatments as comparators, are needed.

Peptide-targeted prodrugs for aminolaevulinic acid photodynamic therapy

Peptide-targeted prodrugs for aminolaevulinic acid photodynamic therapy

Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts.

Actinic keratoses (AKs) are generally accepted as common precursor lesions to invasive squamous cell carcinoma. Photodynamic therapy (PDT) is a common, in-office, field therapy modality used in the treatment of AKs. Clinical and laboratory observations have demonstrated that temperature modulation can affect PDT efficacy. To demonstrate thermal PDT increases apoptotic cell death, and to investigate the mechanistic role of reactive oxygen species (ROS) free radicals in an in vitro human skin fibroblast model. This study was completed using commercially available primary human skin fibroblasts treated with aminolaevulinic acid (ALA) at specific concentrations and controlled temperatures. Cell death, apoptosis and superoxide ROS levels were quantified. We found that thermal PDT with 0·5 mmol L(-1) ALA resulted in significant temperature-dependent increases in total apoptosis and superoxide ROS generation between 33 °C and 42 °C. Our results indicate that thermal PDT significantly increases apoptotic cell death through increased generation of superoxide ROS in a temperature-dependent manner.