The Menace of Melanoma: A Photodynamic Approach to Adjunctive Cancer Therapy

Davids, Lester M.; Kleemann, Britta

doi:10.5772/53676

Cited by 7 publications

(1 citation statement)

References 272 publications

(218 reference statements)

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“…As PS used in dermatopathology, only two of them are known to be approved by FDA, namely 5-ALA and MAL, which are prodrugs becoming active upon intracellular metabolization [50], while other PS attempts are currently made with novel (bio) structures related to porphyrin skeleton such as porphycenes [51,52]. Once activated in tumor cell, a PS triggers different pathways depending on intracellular localization of PS, PS's dose and type, light dose, cell genotype, affecting cell fate in terms of death and proliferation.…”

Section: Pathways In Intracellular Events Triggered By Various Photosmentioning

confidence: 99%

Photosensitizers Imprinting Intracellular Signaling Pathways in Dermato-Oncology Therapy

Constantin¹,

Neagu²

2017

Photomedicine - Advances in Clinical Practice

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This chapter describes the main deregulated intracellular pathways at both genetic and proteomic levels that are found in three main skin cancers: basal cell carcinoma, squamous cell carcinoma and melanoma. In basal cell carcinoma, the main intracellular signaling pathways is the Sonic Hedgehog pathway, while in squamous cell carcinoma, it is the p53 pathway. However, in both nonmelanoma skin cancers, these major pathways trigger cross-activation with other important ones. In melanoma, mitogen-activated protein kinase pathway and PI3K/Akt pathways are deeply deregulated, and moreover due to the disease complexity, BRAF, RAS (N/H/K), NF1 and Triple-WT melanoma subtypes need additional molecular stratification. The stage in which photodynamic therapies' clinical application is in the treatment of these diseases is another subject tackled by the chapter. Thus, if basal cell carcinoma and squamous cell carcinoma possess in their therapeutical armamentarium photodynamic therapies approach, melanoma, with its particularities, still needs thorough molecular investigations to adapt this particular therapy. Based on the accumulated knowledge on pathological intracellular pathways, the chapter describes the molecular details that reside in applying photodynamic therapy. In vivo and in vitro models of cutaneous malignancy and photodynamic therapies' molecular events are further detailed.

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Section: Pathways In Intracellular Events Triggered By Various Photosmentioning

confidence: 99%

Photosensitizers Imprinting Intracellular Signaling Pathways in Dermato-Oncology Therapy

Constantin¹,

Neagu²

2017

Photomedicine - Advances in Clinical Practice

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Photosensitized mefloquine induces ROS-mediated DNA damage and apoptosis in keratinocytes under ambient UVB and sunlight exposure

et al. 2014

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The present study illustrates the photosensitizing behavior of mefloquine (MQ) in human skin keratinocytes under ambient doses of UVB and sunlight exposure. Photochemically, MQ generated reactive oxygen species superoxide radical, hydroxyl radical, and singlet oxygen through type I and type II photodynamic reactions, respectively, which caused photooxidative damage to DNA and formed localized DNA lesions cyclobutane pyrimidine dimers. Photosensitized MQ reduced the viability of keratinocytes to 25 %. Significant level of intracellular reactive oxygen species (ROS) generation was estimated through fluorescence probe DCF-H2. Increased apoptotic cells were evident through AO/EB staining and phosphatidyl serine translocation in cell membrane. Single-stranded DNA damage was marked through single-cell gel electrophoresis. Mitochondrial membrane depolarization and lysosomal destabilization were evident. Upregulation of Bax and p21 and downregulation of Bcl-2 genes and corresponding protein levels supported apoptotic cell death of keratinocyte cells. Cyclobutane pyrimidine dimers (CPDs) were confirmed through immunofluorescence. In addition, hallmarks of apoptosis and G2/M phase cell cycle arrest were confirmed through flow cytometry analysis. Our findings suggest that MQ may damage DNA and produce DNA lesions which may induce differential biological responses in the skin on brief exposure to UVB and sunlight.

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The outstanding role of miR-132-3p in carcinogenesis of solid tumors

et al. 2021

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The Menace of Melanoma: A Photodynamic Approach to Adjunctive Cancer Therapy

Abstract: Melanoma accounts for 4% of all dermatologic cancers but remains responsible for 80% of deaths from skin cancer with the average patient diagnosed with disseminated metastases

Cited by 7 publications

References 272 publications

Photosensitizers Imprinting Intracellular Signaling Pathways in Dermato-Oncology Therapy

Photosensitizers Imprinting Intracellular Signaling Pathways in Dermato-Oncology Therapy

Photosensitized mefloquine induces ROS-mediated DNA damage and apoptosis in keratinocytes under ambient UVB and sunlight exposure

The outstanding role of miR-132-3p in carcinogenesis of solid tumors

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