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BackgroundTotal annual cancer rates have decreased due to improved treatment and prevention. However, the incidence of melanoma is rising, and not all patients respond to immune and targeted approaches. Therefore, we sought to determine the efficacy of red light (RL) phototherapy in preclinical models of melanoma.MethodsMelanoma cells (A375, B16F10, MNT-1) were irradiated with RL. Melanoma proliferation, apoptosis, oxidative stress, and p53 phosphorylation were measured in vitro. In C57BL/6 mice, phototherapy safety, B16F10 tumor growth, and immunocyte infiltration were assessed following RL.ResultsIn vitro, 640 J/cm2 RL decreased cellular proliferation without increasing apoptosis, while 1280 J/cm2 increased apoptosis. RL increased intracellular reactive oxygen species generation and p53 phosphorylation. In animal models, 2560 J/cm2 RL significantly prevented melanoma growth and increased the expression of CD103+ dendritic cells. 1280 and 1920 J/cm2 RL decreased tumor volume, but not significantly. RL did not cause skin inflammation or erythema in normal skin.ConclusionRL represents a potentially safe and effective melanoma therapeutic. RL prevented tumor growth and increased the expression of immune markers, such as CD103, that are associated with favorable melanoma outcomes. Further research is needed to determine the optimal clinical treatment regimen for melanoma using RL.

Fibrosis occurs when collagen deposition and fibroblast proliferation replace healthy tissue. Red light (RL) may improve skin fibrosis via photobiomodulation, the process by which photosensitive chromophores in cells absorb visible or near-infrared light and undergo photophysical reactions. Our previous research demonstrated that high fluence RL reduces fibroblast proliferation, collagen deposition, and migration. Despite the identification of several cellular mechanisms underpinning RL phototherapy, little is known about the transcriptional changes that lead to anti-fibrotic cellular responses. Herein, RNA sequencing was performed on human dermal fibroblasts treated with RL phototherapy. Pathway enrichment and transcription factor analysis revealed regulation of extracellular matrices, proliferation, and cellular responses to oxygen-containing compounds following RL phototherapy. Specifically, RL phototherapy increased the expression of MMP1, which codes for matrix metalloproteinase-1 (MMP-1) and is responsible for remodeling extracellular collagen. Differential regulation of MMP1 was confirmed with RT-qPCR and ELISA. Additionally, RL upregulated PRSS35, which has not been previously associated with skin activity, but has known anti-fibrotic functions. Our results suggest that RL may benefit patients by altering fibrotic gene expression.

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.

BackgroundVisible light (400 to 700 nm) is common in our environment, comprising 44% of total solar radiation and a large component of environmental light exposure. The effects of visible light on skin remain undefined. The red light portion of the visible spectrum (600 to 700 nm) may be used to treat skin diseases as a monotherapeutic modality or in combination with other agents. Light-emitting diode-red light (LED-RL) phototherapy may represent an important advance in light-based treatment modalities because it is non-invasive, inexpensive, portable, and easily combinable with other therapies. We previously determined the maximum tolerated dose (MTD) of high-fluence LED-RL (HF-LED-RL) in skin of color individuals to be 320 J/cm2. To the best of our knowledge, no clinical trials have been performed to determine the safety of higher doses of HF-LED-RL in Caucasian non-Hispanic individuals. The aim of this study is to investigate the safety of HF-LED-RL at doses of 480 and 640 J/cm2 in healthy Caucasian non-Hispanic individuals.MethodsThis is a single-blind, dose-escalation, randomized, controlled, phase I trial titled Safety Trial Assessing Red-light on Skin (STARS) 2. Healthy subjects will be randomly assigned to groups of five (three subjects randomly assigned to HF-LED-RL phototherapy and two subjects randomly assigned to mock therapy). Subjects in group 1 will receive HF-LED-RL or mock irradiation at the starting dose of 480 J/cm2, and the dose will be escalated in the subsequent group (group 2) to 640 J/cm2. The MTD is defined as the dose level below the dose at which two or more subjects (>20% of the cohort) experience a dose-limiting toxicity (DLT). After either the MTD is established or the study endpoint of 640 J/cm2 is achieved, additional HF-LED-RL phototherapy subjects and mock therapy subjects will be enrolled at that fluence (group 3) for a total number of up to 60 subjects. Each subject will receive a total of nine irradiation sessions, three times per week for three consecutive weeks.DiscussionThis follow-up study aims to provide important knowledge about safety and cutaneous effects of HF-LED-RL phototherapy of 480 and 640 J/cm2 in Caucasian non-Hispanic subjects. The importance of this clinical trial is that it may establish new treatment paradigms and a safety profile for LED-RL based on race and ethnicity.Trial registrationClinicalTrials.gov Identifier: NCT03433222 . Registered on February 1, 2018 - Retrospectively registered. Protocol date and version: January 12, 2018; version 1.

5‐Aminolevulinic acid (5‐ALA) photodynamic therapy (PDT) is a treatment for actinic keratosis (AK) and has been studied as a treatment for noninvasive cutaneous squamous cell carcinoma (cSCC). PDT induces apoptosis and necrosis in AKs and cSCC. 5‐ALA blue light PDT may modulate gene expression and pathways in surviving cells. In this study, differential gene expression and pathway analysis of cSCC and human dermal fibroblasts were compared before and after 5‐ALA blue light PDT using RNA sequencing. No genes were differentially expressed after correcting for multiple testing (false discovery rate < 0.05). As a result, transcription factor, gene enrichment, and pathway analysis were performed with genes identified before multiple testing (p < 0.05). Pathways associated with proliferation and carcinogenesis were downregulated. These findings using 5‐ALA blue light PDT are similar to previously published studies using methyl‐aminolevulinic and red light protocols, indicating that surviving residual cells may undergo changes consistent with a less aggressive cancerous phenotype. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) can be used to treat a range of conditions in dermatology. PBM refers to the changes induced by red (RL, 620–700 nm) and near‐infrared (NIR, 700–1440 nm) light. Light radiation‐induced DNA damage is a major contributor to aging and skin cancer. It is crucial to study the effects of PBM on DNA to ensure safety. Our lab previously demonstrated that RL (633 ± 6 nm) did not result in human dermal fibroblasts (HDFs) DNA damage. This study employed similar methods to investigate NIR effects. Commercially available LED‐NIR (830 ± 5 nm) panels (66, 132, and 264 J/cm2) did not result in DNA damage measured by cyclobutane pyrimidine dimers and pyrimidine‐6,4‐pyrimidone photoproducts in HDFs compared to temperature‐matched controls immediately, 3 h, and 24 h following irradiation and compared to positive and negative controls. This demonstrates that LED‐NIR does not damage DNA in HDFs in vitro. [ABSTRACT FROM AUTHOR]

This article discusses the use of network pharmacology as a platform for drug discovery for hypertrophic scars. Hypertrophic scars are a type of abnormal wound healing that can cause disfigurement and impair functionality. Current treatment options are often ineffective, so novel approaches are needed. The study utilized network pharmacology to identify scar-associated genes and signaling pathways, and identified crizotinib as a promising treatment. The study also highlights the potential of computational modeling and experimental validation to identify new drugs and repurpose existing drugs. However, the study focused exclusively on hypertrophic scars and not keloids, which are often more severe and treatment resistant. Further research and clinical trials are needed to establish the safety and efficacy of new treatments for scars. [Extracted from the article]

Skin fibrosis is a debilitating feature of several systemic and dermatologic diseases. While current treatment options carry significant risk of side effects and recurrence, high‐fluence light emitting diode‐generated red light (LED‐RL) is an alternative therapeutic that is safe, non‐invasive, and accessible. We previously demonstrated LED‐RL decreases fibroblast proliferation, a key pathogenic component of fibrosis. However, the cellular mechanism by which high fluence LED‐RL modulates fibroblast proliferation is unclear. Herein, we explored the effects of high fluence LED‐RL on human dermal fibroblast cell cycle progression. We demonstrate that LED‐RL at 640 J/cm2 induced significant arrest of cells in G0/G1 compared to temperature‐matched control. This was accompanied by a corresponding increase in expression of checkpoint regulator p53 in irradiated cells. These data demonstrate high fluence LED‐RL may exert its anti‐proliferative effect on fibroblasts by inducing G0/G1 arrest. Further, this study provides insight into the molecular mechanism underlying LED‐RL as an anti‐fibrotic therapeutic. [ABSTRACT FROM AUTHOR]