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Chen Y, Guo P, Chen L, He D. 5-aminolevulinic acid induced photodynamic reactions in diagnosis and therapy for female lower genital tract diseases. Front Med (Lausanne) 2024; 11:1370396. [PMID: 39076768 PMCID: PMC11284047 DOI: 10.3389/fmed.2024.1370396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/13/2024] [Indexed: 07/31/2024] Open
Abstract
Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.
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Affiliation(s)
- Yuqing Chen
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, Shaanxi, China
| | - Peng Guo
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, Shaanxi, China
| | - Lihong Chen
- Department of Obstetrics and Gynecology, Shaanxi Provincial People’s Hospital, Xi'an, Shaanxi, China
| | - Dalin He
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, Shaanxi, China
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2
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Han L, Huang X, Zhao B, Zhu H, Wang R, Liu S, Lin H, Feng F, Ma X, Liu F, Xue J, Liu W. TGF-β1 mediates tumor immunosuppression aggravating at the late stage post-high-light-dose photodynamic therapy. Cancer Immunol Immunother 2023; 72:3079-3095. [PMID: 37351605 PMCID: PMC10992786 DOI: 10.1007/s00262-023-03479-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 06/08/2023] [Indexed: 06/24/2023]
Abstract
Photodynamic therapy (PDT) is an emerging clinical treatment that is expected to become an important adjuvant strategy for the immunotherapeutic cancer treatment. Recently, numerous works have reported combination strategies. However, clinical data showed that the anti-tumor immune response of PDT was not lasting though existing. The immune activation effect will eventually turn to immunosuppressive effect and get aggravated at the late stage post-PDT. So far, the mechanism is still unclear, which limits the design of specific correction strategies and further development of PDT. Several lines of evidence suggest a role for TGF-β1 in the immunosuppression associated with PDT. Herein, this study systematically illustrated the dynamic changes of immune states post-PDT within the tumor microenvironment. The results clearly demonstrated that high-light-dose PDT, as a therapeutic dose, induced early immune activation followed by late immunosuppression, which was mediated by the activated TGF-β1 upregulation. Then, the mechanism of PDT-induced TGF-β1 accumulation and immunosuppression was elucidated, including the ROS/TGF-β1/MMP-9 positive feedback loop and CD44-mediated local amplification, which was further confirmed by spatial transcriptomics, as well as by the extensive immune inhibitory effect of local high concentration of TGF-β1. Finally, a TGF-β blockade treatment strategy was presented as a promising combinational strategy to reverse high-light-dose PDT-associated immunosuppression. The results of this study provide new insights for the biology mechanism and smart improvement approaches to enhance tumor photodynamic immunotherapy.
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Affiliation(s)
- Lingfei Han
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, China
| | - Xiaoxian Huang
- Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, China
| | - Bin Zhao
- Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, China
- Tumor Precise Intervention and Translational Medicine Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Hongtan Zhu
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, China
| | - Ruyi Wang
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, China
| | - Shaoxia Liu
- Tumor Precise Intervention and Translational Medicine Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Honglei Lin
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, China
| | - Feng Feng
- Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, China
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Xiao Ma
- Gansu Institute for Drug Control, Gansu, 730000, China
| | - Fulei Liu
- Tumor Precise Intervention and Translational Medicine Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China.
- Pharmaceutical Department, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China.
| | - Jingwei Xue
- Tumor Precise Intervention and Translational Medicine Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China.
| | - Wenyuan Liu
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, China.
- Zhejiang Center for Safety Study of Drug Substances (Industrial Technology Innovation Platform), Hangzhou, 310018, China.
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3
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Oyebanji OA, Brewer C, Bayless S, Schmeusser B, Corbin DA, Sulentic CEW, Sherwin CMT, Chen Y, Rapp CM, Cates EE, Long Y, Travers JB, Rohan CA. Topical Photodynamic Therapy Generates Bioactive Microvesicle Particles: Evidence for a Pathway Involved in Immunosuppressive Effects. J Invest Dermatol 2023; 143:1279-1288.e9. [PMID: 36708950 PMCID: PMC10293022 DOI: 10.1016/j.jid.2022.12.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 01/26/2023]
Abstract
Although effective in treating actinic damage, topical photodynamic therapy (PDT) has been shown to be immunosuppressive through unknown mechanisms, which could potentially limit its effectiveness. Multiple types of environmental stressors, including PDT, can produce the immunosuppressive lipid mediator platelet-activating factor (PAF). Because PAF can produce subcellular microvesicle particles (MVPs), these studies tested whether PDT can generate PAF and MVP release and whether these are involved in PDT-induced immunosuppression. Previously, topical PDT using blue light and 5-aminolevulinic acid was found to be a potent stimulus for PAF production in mice and human skin explants and human patients, and we show that experimental PDT also generates high levels of MVP. PDT-generated MVPs were independent of the PAF receptor but were dependent on the MVP-generating enzyme acid sphingomyelinase. Patients undergoing topical PDT treatment to at least 10% of body surface area showed local and systemic immunosuppression as measured by inhibition of delayed-type hypersensitivity reactions. Finally, using a murine model of contact hypersensitivity, PDT immunosuppression was blocked by genetic and pharmacologic inhibition of acid sphingomyelinase and genetic inhibition of PAF receptor signaling. These studies describe a mechanism involving MVP through which PDT exerts immunomodulatory effects, providing a potential target to improve its effectiveness.
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Affiliation(s)
- Oladayo A Oyebanji
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Chad Brewer
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Sharlo Bayless
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Benjamin Schmeusser
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Danielle A Corbin
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Courtney E W Sulentic
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Catherine M T Sherwin
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA; Department of Pediatrics, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Yanfang Chen
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Christine M Rapp
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Elizabeth E Cates
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
| | - Yuhan Long
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jeffrey B Travers
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA; Department of Dermatology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA; Dayton V.A. Medical Center, Dayton, Ohio, USA.
| | - Craig A Rohan
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA; Department of Dermatology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA; Dayton V.A. Medical Center, Dayton, Ohio, USA
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4
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Howley R, Chandratre S, Chen B. 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy. Bioengineering (Basel) 2023; 10:bioengineering10040496. [PMID: 37106683 PMCID: PMC10136048 DOI: 10.3390/bioengineering10040496] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/17/2023] [Accepted: 04/19/2023] [Indexed: 04/29/2023] Open
Abstract
5-Aminolevulinic acid (ALA) is a naturally occurring amino acid synthesized in all nucleated mammalian cells. As a porphyrin precursor, ALA is metabolized in the heme biosynthetic pathway to produce protoporphyrin IX (PpIX), a fluorophore and photosensitizing agent. ALA administered exogenously bypasses the rate-limit step in the pathway, resulting in PpIX accumulation in tumor tissues. Such tumor-selective PpIX disposition following ALA administration has been exploited for tumor fluorescence diagnosis and photodynamic therapy (PDT) with much success. Five ALA-based drugs have now received worldwide approval and are being used for managing very common human (pre)cancerous diseases such as actinic keratosis and basal cell carcinoma or guiding the surgery of bladder cancer and high-grade gliomas, making it the most successful drug discovery and development endeavor in PDT and photodiagnosis. The potential of ALA-induced PpIX as a fluorescent theranostic agent is, however, yet to be fully fulfilled. In this review, we would like to describe the heme biosynthesis pathway in which PpIX is produced from ALA and its derivatives, summarize current clinical applications of ALA-based drugs, and discuss strategies for enhancing ALA-induced PpIX fluorescence and PDT response. Our goal is two-fold: to highlight the successes of ALA-based drugs in clinical practice, and to stimulate the multidisciplinary collaboration that has brought the current success and will continue to usher in more landmark advances.
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Affiliation(s)
- Richard Howley
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph's University, Philadelphia, PA 19104, USA
| | - Sharayu Chandratre
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph's University, Philadelphia, PA 19104, USA
| | - Bin Chen
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph's University, Philadelphia, PA 19104, USA
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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5
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Uzunbajakava NE, Tobin DJ, Botchkareva NV, Dierickx C, Bjerring P, Town G. Highlighting nuances of blue light phototherapy: Mechanisms and safety considerations. JOURNAL OF BIOPHOTONICS 2023; 16:e202200257. [PMID: 36151769 DOI: 10.1002/jbio.202200257] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/17/2022] [Accepted: 09/21/2022] [Indexed: 06/16/2023]
Abstract
The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were (1) to highlight the nuances behind "colors" of blue light, light propagation in tissue and the plurality of modes of action; and (2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation. We conclude that blue light therapy is safe for human skin. It induces intriguing skin pigmentation, in part mediated by photoreceptor Opsin-3, which might have a photoprotective effect against ultraviolet irradiation. Future research needs to unravel photochemical reactions and the most effective and safe parameters of blue light in dermatology.
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Affiliation(s)
| | - Desmond J Tobin
- Charles Institute of Dermatology, University College Dublin, Dublin, Ireland
| | - Natalia V Botchkareva
- Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Christine Dierickx
- Skinperium Laser and Cosmetic Dermatology Clinic, Skinperium, Luxembourg City, Luxembourg
| | - Peter Bjerring
- Dermatology Department, Aalborg University Hospital, Aalborg, Denmark
| | - Godfrey Town
- Dermatology Department, Aalborg University Hospital, Aalborg, Denmark
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6
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Yang D, Lei S, Pan K, Chen T, Lin J, Ni G, Liu J, Zeng X, Chen Q, Dan H. Application of photodynamic therapy in immune-related diseases. Photodiagnosis Photodyn Ther 2021; 34:102318. [PMID: 33940209 DOI: 10.1016/j.pdpdt.2021.102318] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 04/09/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023]
Abstract
Photodynamic therapy (PDT) is a therapeutic modality that utilizes photodamage caused by photosensitizers and oxygen after exposure to a specific wavelength of light. Owing to its low toxicity, high selectivity, and minimally invasive properties, PDT has been widely applied to treat various malignant tumors, premalignant lesions, and infectious diseases. Moreover, there is growing evidence of its immunomodulatory effects and potential for the treatment of immune-related diseases. This review mainly focuses on the effect of PDT on immunity and its application in immune-related diseases.
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Affiliation(s)
- Dan Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Shangxue Lei
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Keran Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Ting Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Jiao Lin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Guangcheng Ni
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Jiaxin Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Xin Zeng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Qianming Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Hongxia Dan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China.
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7
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Abstract
Environmental stressors exert a profound effect on humans. Many environmental stressors have in common the ability to induce reactive oxygen species. The goal of this chapter is to present evidence that the potent lipid mediator platelet-activating factor (PAF) is involved in the effects of many stressors ranging from cigarette smoke to ultraviolet B radiation. These environmental stressors can generate PAF enzymatically as well as PAF-like lipids produced by free radical-mediated attack of glycerophosphocholines. Inasmuch as PAF exerts both acute inflammation and delayed immunosuppressive effects, involvement of the PAF system can provide an explanation for many consequences of environmental stressor exposures.
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Affiliation(s)
- Jeffrey B Travers
- Department of Pharmacology and Toxicology, Wright State University, Dayton, OH, USA.
- Dayton Veterans Administration Medical Center, Dayton, OH, USA.
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8
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Gellén E, Fidrus E, Janka E, Kollár S, Paragh G, Emri G, Remenyik É. 5-Aminolevulinic acid photodynamic therapy with and without Er:YAG laser for actinic keratosis: Changes in immune infiltration. Photodiagnosis Photodyn Ther 2019; 26:270-276. [DOI: 10.1016/j.pdpdt.2019.04.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 03/29/2019] [Accepted: 04/10/2019] [Indexed: 12/18/2022]
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9
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Gellén E, Fidrus E, Péter M, Szegedi A, Emri G, Remenyik É. Immunological effects of photodynamic therapy in the treatment of actinic keratosis and squamous cell carcinoma. Photodiagnosis Photodyn Ther 2018; 24:342-348. [DOI: 10.1016/j.pdpdt.2018.10.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Revised: 10/25/2018] [Accepted: 10/26/2018] [Indexed: 01/08/2023]
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10
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Ibbotson S, Wong T, Morton C, Collier N, Haylett A, McKenna K, Mallipeddi R, Moseley H, Rhodes L, Seukeran D, Ward K, Mohd Mustapa M, Exton L. Adverse effects of topical photodynamic therapy: a consensus review and approach to management. Br J Dermatol 2018; 180:715-729. [DOI: 10.1111/bjd.17131] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2018] [Indexed: 12/21/2022]
Affiliation(s)
- S.H. Ibbotson
- Photobiology Unit Department of Dermatology University of Dundee Ninewells Hospital and Medical School Dundee U.K
| | - T.H. Wong
- Stirling Community Hospital StirlingU.K
| | | | - N.J. Collier
- Photobiology Unit Dermatology Centre University of Manchester and Salford Royal NHS Foundation Trust ManchesterU.K
| | - A. Haylett
- Photobiology Unit Dermatology Centre University of Manchester and Salford Royal NHS Foundation Trust ManchesterU.K
| | - K.E. McKenna
- Department of Dermatology Belfast City Hospital BelfastU.K
| | - R. Mallipeddi
- St John's Institute of Dermatology Guy's and St Thomas’ NHS Foundation Trust London U.K
| | - H. Moseley
- Photobiology Unit Department of Dermatology University of Dundee Ninewells Hospital and Medical School Dundee U.K
| | - L.E. Rhodes
- Photobiology Unit Dermatology Centre University of Manchester and Salford Royal NHS Foundation Trust ManchesterU.K
| | | | | | | | - L.S. Exton
- British Association of Dermatologists London U.K
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11
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Early and Late Onset Side Effects of Photodynamic Therapy. Biomedicines 2018; 6:biomedicines6010012. [PMID: 29382133 PMCID: PMC5874669 DOI: 10.3390/biomedicines6010012] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 01/20/2018] [Accepted: 01/25/2018] [Indexed: 01/06/2023] Open
Abstract
Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.
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12
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High Patient Satisfaction with Daylight-Activated Methyl Aminolevulinate Cream in the Treatment of Multiple Actinic Keratoses: Results of an Observational Study in Australia. Dermatol Ther (Heidelb) 2017; 7:525-533. [PMID: 28905294 PMCID: PMC5698198 DOI: 10.1007/s13555-017-0199-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Indexed: 12/26/2022] Open
Abstract
Introduction Actinic keratoses (AK) are treated to reduce the risk of progression to squamous cell carcinoma and for symptomatic and cosmetic benefits. The objective of this observational study was to generate real-life data on the use of daylight photodynamic therapy with methyl aminolevulinate cream (MAL DL-PDT) in treating mild to moderate facial/scalp AK. Methods A multicenter, prospective, observational study was conducted in Australia in patients receiving a single treatment of MAL DL-PDT for mild to moderate AK. Efficacy was assessed 3 months after treatment by investigator-assessed improvement and patient- and physician-completed satisfaction questionnaires. Adverse events were recorded throughout the study. Results Overall, 81 patients were enrolled of mean age 62.7 years, mostly men (76.5%) with skin phototype I (64.2%) or II (35.8%) and a long history of AK (mean duration 16.8 years). Most had multiple lesions (82.7% had >10 lesions) of predominantly grade I (75.3%). At 3 months after treatment, almost half the patients (46.8%) required no further treatment. The proportions of patients and physicians satisfied to very satisfied with the MAL DL-PDT treatment were 79.7% and 83.3%, respectively. After receiving the treatment, 74.1% of patients indicated via the questionnaire that they were not bothered at all by the pain. Related AEs were reported in 48.1% of patients, mainly mild erythema (44.4%). Conclusions In clinical practice in Australia, the use of MAL DL-PDT in treating multiple mild to moderate non-hyperkeratotic AK of the face and/or scalp results in high levels of patient and physician satisfaction reflecting the good efficacy and tolerability of this almost painless, convenient procedure. Trial Registration ClinicalTrials.gov identifier, NCT02674048. Funding Galderma R&D.
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13
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Zverev VV, Makarov OV, Khashukoeva AZ, Svitich OA, Dobrokhotova YE, Markova EA, Labginov PA, Khlinova SA, Shulenina EA, Gankovskaya LV. In vitro studies of the antiherpetic effect of photodynamic therapy. Lasers Med Sci 2016; 31:849-55. [PMID: 27003896 DOI: 10.1007/s10103-016-1912-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 02/10/2016] [Indexed: 11/29/2022]
Abstract
The number of viral infection cases in the Department of Gynecology and Obstetrics has tended to increase over last few years. Viruses form herpesvirus and cytomegalovirus families are associated with an increased risk for recurrent pregnancy loss. Photodynamic therapy (PDT) is a promising new approach to treat viral infections in which viral particles are inactivated. It exhibits great therapeutic potential, particularly among this group of patients. This study examined the use of PDT to treat herpesvirus infection (HVI) using an in vitro model. In this study, we used the Vero сell lineage as a suitable model of HVI, strains of HSV-1 (strain VR-3) and HSV-2 (strain MS) obtained from The National Virus Collection (London, UK), the photosensitizer Fotoditazine (Veta-Grand, Russia), an AFS physiotherapeutic device (Polironic Corporation, Russia). Laser light irradiation and the photosensitizer had different cytotoxic effects on the Vero cell cultures depending on the doses used. The optimal laser light and photosensitizer doses were determined. PDT had an antiviral effect on an in vitro model of HVI in cell culture. PDT has been shown to be effective treatment for HVI in vitro, leading to a reliable decrease of viral titer.
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Affiliation(s)
- V V Zverev
- Mechnikov Scientific Research Institute of Vaccines and Serums, Maly Kazeynny per., 5A, 105064, Moscow, Russia
| | - O V Makarov
- Department of Obstetrics and Gynecology of Medical Faculty, Pyrogov Russian National Research Medical University, Str. Ostrovityanova, 1, 117997, Moscow, Russia
| | - A Z Khashukoeva
- Department of Obstetrics and Gynecology of Medical Faculty, Pyrogov Russian National Research Medical University, Str. Ostrovityanova, 1, 117997, Moscow, Russia
| | - O A Svitich
- Mechnikov Scientific Research Institute of Vaccines and Serums, Maly Kazeynny per., 5A, 105064, Moscow, Russia
| | - Y E Dobrokhotova
- Department of Obstetrics and Gynecology of Medical Faculty, Pyrogov Russian National Research Medical University, Str. Ostrovityanova, 1, 117997, Moscow, Russia
| | - E A Markova
- Department of Obstetrics and Gynecology of Medical Faculty, Pyrogov Russian National Research Medical University, Str. Ostrovityanova, 1, 117997, Moscow, Russia.
| | - P A Labginov
- Mechnikov Scientific Research Institute of Vaccines and Serums, Maly Kazeynny per., 5A, 105064, Moscow, Russia
| | - S A Khlinova
- Department of Obstetrics and Gynecology of Medical Faculty, Pyrogov Russian National Research Medical University, Str. Ostrovityanova, 1, 117997, Moscow, Russia
| | - E A Shulenina
- Mechnikov Scientific Research Institute of Vaccines and Serums, Maly Kazeynny per., 5A, 105064, Moscow, Russia
| | - L V Gankovskaya
- Department of Immunology, Pyrogov Russian National Research Medical University, Str. Ostrovityanova, 1, 117997, Moscow, Russia
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Reinhard A, Sandborn WJ, Melhem H, Bolotine L, Chamaillard M, Peyrin-Biroulet L. Photodynamic therapy as a new treatment modality for inflammatory and infectious conditions. Expert Rev Clin Immunol 2015; 11:637-57. [DOI: 10.1586/1744666x.2015.1032256] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Effective blue light photodynamic therapy does not affect cutaneous langerhans cell number or oxidatively damage DNA. Dermatol Surg 2014; 40:979-87. [PMID: 25072126 DOI: 10.1097/01.dss.0000452624.01889.8a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin. OBJECTIVE To determine whether broad-area short incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses treated skin. METHODS Patients were evaluated clinically and by standardized facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage. RESULTS Patients had an 81% reduction in AKs and slight improvement in clinical and histologic signs of photoaging after 1 month. The biopsied chronically photodamaged skin without clinically detectable AKs showed no effect of PDT on the LC number, distribution, or morphology; and no oxidative DNA damage, in contrast to the changes reported after customary red light PDT. CONCLUSION Customary blue light BASI-ALA-PDT does not affect the LC number or produce oxidative DNA damage, the sequelae of red light PDT responsible for immunosuppression in treated skin.
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Topical photodynamic therapy induces systemic immunosuppression via generation of platelet-activating factor receptor ligands. J Invest Dermatol 2014; 135:321-323. [PMID: 25050596 PMCID: PMC4268233 DOI: 10.1038/jid.2014.313] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Reginato E, Wolf P, Hamblin MR. Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects. World J Immunol 2014; 4:1-11. [PMID: 25364655 PMCID: PMC4214901 DOI: 10.5411/wji.v4.i1.1] [Citation(s) in RCA: 128] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 12/20/2013] [Accepted: 02/18/2014] [Indexed: 02/05/2023] Open
Abstract
Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment.
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Thanos SM, Halliday GM, Damian DL. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans. Br J Dermatol 2013; 167:631-6. [PMID: 22709272 DOI: 10.1111/j.1365-2133.2012.11109.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. OBJECTIVES To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. METHODS Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. RESULTS High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P < 0·0001); topical and oral nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P < 0·0001). Low irradiance rate PDT was not significantly immunosuppressive in the topical nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045). CONCLUSIONS While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates.
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Affiliation(s)
- S M Thanos
- Discipline of Dermatology, Bosch Institute, The University of Sydney at Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
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Wlodek C, Ali FR, Lear JT. Use of photodynamic therapy for treatment of actinic keratoses in organ transplant recipients. BIOMED RESEARCH INTERNATIONAL 2012; 2013:349526. [PMID: 23509711 PMCID: PMC3591189 DOI: 10.1155/2013/349526] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Accepted: 09/05/2012] [Indexed: 12/25/2022]
Abstract
Solid organ transplant recipients are predisposed to actinic keratoses (AK) and nonmelanoma skin cancers, owing to the lifelong immunosuppression required. Today, increasing numbers of organ transplants are being performed and organ transplant recipients (OTRs) are surviving much longer. Photodynamic therapy (PDT) is proving a highly effective treatment modality for AK amongst this susceptible group of patients. Following an overview of the pathogenesis of AK amongst OTRs, the authors review current safety and efficacy data and how this relates to the role of PDT for the treatment of AK in OTRs.
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Affiliation(s)
- Christina Wlodek
- St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK
| | - Faisal R. Ali
- The Dermatology Centre, Manchester Academic Health Science Centre, University of Manchester, Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK
| | - John T. Lear
- The Dermatology Centre, Manchester Academic Health Science Centre, University of Manchester, Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK
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20
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Huang YY, Tanaka M, Vecchio D, Garcia-Diaz M, Chang J, Morimoto Y, Hamblin MR. Photodynamic therapy induces an immune response against a bacterial pathogen. Expert Rev Clin Immunol 2012; 8:479-94. [PMID: 22882222 DOI: 10.1586/eci.12.37] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin(®). PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease.
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Affiliation(s)
- Ying-Ying Huang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
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21
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Milla Sanabria L, Rodríguez ME, Cogno IS, Rumie Vittar NB, Pansa MF, Lamberti MJ, Rivarola VA. Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment. Biochim Biophys Acta Rev Cancer 2012; 1835:36-45. [PMID: 23046998 DOI: 10.1016/j.bbcan.2012.10.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Revised: 09/28/2012] [Accepted: 10/01/2012] [Indexed: 12/31/2022]
Abstract
Photodynamic therapy (PDT) is a novel cancer treatment. It involves the activation of a photosensitizer (PS) with light of specific wavelength, which interacts with molecular oxygen to generate singlet oxygen and other reactive oxygen species (ROS) that lead to tumor cell death. When a tumor is treated with PDT, in addition to affect cancer cells, the extracellular matrix and the other cellular components of the microenvironment are altered and finally this had effects on the tumor cells survival. Furthermore, the heterogeneity in the availability of nutrients and oxygen in the different regions of a tridimensional tumor has a strong impact on the sensitivity of cells to PDT. In this review, we summarize how PDT affects indirectly to the tumor cells, by the alterations on the extracellular matrix, the cell adhesion and the effects over the immune response. Also, we describe direct PDT effects on cancer cells, considering the intratumoral role that autophagy mediated by hypoxia-inducible factor 1 (HIF-1) has on the efficiency of the treatment.
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Affiliation(s)
- Laura Milla Sanabria
- Department of Molecular Biology, National University of Río Cuarto, Río Cuarto (5800), Córdoba, Argentina
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Ibbotson S. Photodynamic therapy and immunosuppression. Br J Dermatol 2012; 167:465-7. [DOI: 10.1111/j.1365-2133.2012.11189.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Differential cytotoxic response in keloid fibroblasts exposed to photodynamic therapy is dependent on photosensitiser precursor, fluence and location of fibroblasts within the lesion. Arch Dermatol Res 2012; 304:549-62. [DOI: 10.1007/s00403-012-1264-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Revised: 06/25/2012] [Accepted: 07/05/2012] [Indexed: 11/25/2022]
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Choi DH, Lee KH, Kim JH, Kim MY, Lim JH, Lee J. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult. Biochem Biophys Res Commun 2012; 422:274-9. [PMID: 22580279 DOI: 10.1016/j.bbrc.2012.04.147] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Accepted: 04/26/2012] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. MATERIALS & METHODS Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm(2) and 50 mW/cm(2)) were given once to four times within 8h at 2h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. RESULTS Images captured after MAP2 immunocytochemistry showed significant (p<0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p<0.05). CONCLUSION Our data suggest that LED treatment may promote synaptogenesis through MAPK activation and subsequently protect cell death in the in vitro stroke model.
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Affiliation(s)
- Dong-Hee Choi
- Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Republic of Korea
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Evangelou G, Farrar M, Cotterell L, Andrew S, Tosca A, Watson R, Rhodes L. Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma. Br J Dermatol 2012; 166:1112-5. [DOI: 10.1111/j.1365-2133.2012.10823.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- G. Evangelou
- Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester M6 6HD, U.K
| | - M.D. Farrar
- Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester M6 6HD, U.K
| | - L. Cotterell
- Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester M6 6HD, U.K
| | - S. Andrew
- Department of Cellular Pathology, Salford Royal NHS Foundation Hospital, Manchester, U.K
| | - A.D. Tosca
- University Hospital of Crete, Heraklion, Crete, Greece
| | - R.E.B. Watson
- Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester M6 6HD, U.K
| | - L.E. Rhodes
- Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester M6 6HD, U.K
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Rakvit P, Kerr AC, Ibbotson SH. Localized bullous pemphigoid induced by photodynamic therapy. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2012; 27:251-3. [PMID: 21950630 DOI: 10.1111/j.1600-0781.2011.00609.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Topical photodynamic therapy (PDT) causes localized phototoxicity and has been shown both in vitro and in humans to have immunomodulatory and immunosuppressive effects. We report a case of localized bullous pemphigoid (BP) developing after PDT. Although BP has been reported to develop following cutaneous insults such as surgery, radiotherapy, psoralen ultraviolet A (PUVA) and ultraviolet B phototherapy, PDT has not previously been reported as a trigger. Possible mechanisms include direct mechanical injury to the basement membrane and subsequent autoantibody formation, an indirect immunomodulatory effect of PDT, or most likely, precipitation of BP in individuals with pre-existing low titres of epidermal autoantibodies (so-called subclinical BP). PDT should be added to the list of possible exogenous triggers for BP and this condition should be considered if blistering develops following PDT.
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Affiliation(s)
- Pariyawan Rakvit
- Department of Dermatology, Photobiology Unit, Ninewells Hospital and Medical School, Dundee, UK.
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27
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Basset-Seguin N, Baumann Conzett K, Gerritsen M, Gonzalez H, Haedersdal M, Hofbauer G, Aguado L, Kerob D, Lear J, Piaserico S, Ulrich C. Photodynamic therapy for actinic keratosis in organ transplant patients. J Eur Acad Dermatol Venereol 2011; 27:57-66. [DOI: 10.1111/j.1468-3083.2011.04356.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Evangelou G, Farrar M, White R, Sorefan N, Wright K, McLean K, Andrew S, Watson R, Rhodes L. Topical aminolaevulinic acid-photodynamic therapy produces an inflammatory infiltrate but reduces Langerhans cells in healthy human skin in vivo. Br J Dermatol 2011; 165:513-9. [DOI: 10.1111/j.1365-2133.2011.10433.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Ishizuka M, Abe F, Sano Y, Takahashi K, Inoue K, Nakajima M, Kohda T, Komatsu N, Ogura SI, Tanaka T. Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy. Int Immunopharmacol 2011; 11:358-65. [PMID: 21144919 DOI: 10.1016/j.intimp.2010.11.029] [Citation(s) in RCA: 181] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2010] [Revised: 11/21/2010] [Accepted: 11/22/2010] [Indexed: 12/13/2022]
Abstract
Early detection and intervention are needed for optimal outcomes in cancer therapy. Improvements in diagnostic technology, including endoscopy, photodynamic diagnosis (PDD), and photodynamic therapy (PDT), have allowed substantial progress in the treatment of cancer. 5-Aminolevulinic acid (ALA) is a natural, delta amino acid biosynthesized by animal and plant mitochondria. ALA is a precursor of porphyrin, heme, and bile pigments, and it is metabolized into protoporphyrin IX (PpIX) in the course of heme synthesis. PpIX preferentially accumulates in tumor cells resulting in a red fluorescence following irradiation with violet light and the formation of singlet oxygen. This reaction, utilized to diagnose and treat cancer, is termed ALA-induced PDD and PDT. In this review, the biological significance of heme metabolites, the mechanism of PpIX accumulation in tumor cells, and the therapeutic potential of ALA-induced PDT alone and combined with hyperthermia and immunotherapy are discussed.
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Affiliation(s)
- Masahiro Ishizuka
- SBI ALApromo Co, LTD Roppongi 1-6-1, Minato-ku, Tokyo 106-6019, Japan
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31
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Ibbotson SH. Adverse effects of topical photodynamic therapy. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2011; 27:116-30. [DOI: 10.1111/j.1600-0781.2010.00560.x] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Mroz P, Hamblin MR. The immunosuppressive side of PDT. Photochem Photobiol Sci 2011; 10:751-8. [PMID: 21437314 PMCID: PMC3441049 DOI: 10.1039/c0pp00345j] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2010] [Accepted: 02/25/2011] [Indexed: 12/29/2022]
Abstract
Photodynamic therapy (PDT) is a promising novel therapeutic procedure for the management of a variety of solid tumors and many non-malignant diseases. PDT has been described as having a significant effect on the immune system, which may be either immunostimulatory or, in some circumstances, immunosuppressive. The immunosuppressive effects of PDT have nearly all been concerned with the suppression of the contact hypersensitivity reaction in mice. Here, we review the immunosuppressive aspects of PDT treatment and discuss some additional mechanisms that may be involved.
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Affiliation(s)
- Pawel Mroz
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
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Nobbe S, Trüeb RM, French LE, Hofbauer GFL. Herpes simplex virus reactivation as a complication of photodynamic therapy. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2011; 27:51-2. [PMID: 21198884 DOI: 10.1111/j.1600-0781.2010.00552.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
We report the case of an 81-year-old male patient who developed a reactivation of herpes simplex virus localized to the right forehead, where photodynamic therapy (PDT) for actinic keratosis was performed. Considering the wide use of PDT, herpes virus infection or reactivation as well as other infections seem to be a very rare but potentially serious complication that has to be distinguished from common inflammatory reactions after PDT. Further applications of PDT under antiviral prophylaxis were well tolerated by our patient, with no further herpetic reactivation and successful treatment of actinic keratoses.
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Affiliation(s)
- Stephan Nobbe
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
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Brackett CM, Gollnick SO. Photodynamic therapy enhancement of anti-tumor immunity. Photochem Photobiol Sci 2011; 10:649-52. [PMID: 21253659 DOI: 10.1039/c0pp00354a] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Photodynamic therapy (PDT) is an FDA-approved modality for the treatment of early-stage disease and palliation of late-stage disease. Pre-clinical studies using mouse models and clinical studies in patients have demonstrated that PDT is capable of influencing the immune system. The effect of PDT on the generation of anti-tumor immunity is regimen-dependent and is tightly linked to the degree and nature of inflammation induced by PDT. However, the precise mechanism underlying PDT-regulated adaptive anti-tumor immunity remains unclear. This review will focus on the current knowledge of immune regulation by PDT.
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Affiliation(s)
- Craig M Brackett
- Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
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Photodynamic therapy-induced immunosuppression in humans is prevented by reducing the rate of light delivery. J Invest Dermatol 2011; 131:962-8. [PMID: 21248771 DOI: 10.1038/jid.2010.429] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Photodynamic therapy (PDT) of non-melanoma skin cancers currently carries failure rates of 10-40%. The optimal irradiation protocol is as yet unclear. Previous studies showed profound immunosuppression after PDT, which may compromise immune-mediated clearance of these antigenic tumors. Slower irradiation prevents immunosuppression in mice, and may be at least as effective as high-fluence-rate PDT in preliminary clinical trials. The photosensitizers 5-aminolaevulinic acid and/or methyl aminolaevulinate were applied to discrete areas on the backs of healthy Mantoux-positive volunteers, followed by narrowband red light irradiation (632 nm) at varied doses and fluence rates. Delayed type hypersensitivity (Mantoux) reactions were elicited at test sites and control sites to determine immunosuppression. Human ex vivo skin received low- and high-fluence-rate PDT and was stained for oxidative DNA photolesions. PDT caused significant, dose-responsive immunosuppression at high (75 mW cm(-2)) but not low (15 or 45 mW cm(-2)) fluence rates. DNA photolesions, which may be a trigger for immunosuppression, were observed after high-fluence-rate PDT but not when light was delivered more slowly. This study demonstrates that the current clinical PDT protocol (75 mW cm(-2)) is highly immunosuppressive. Simply reducing the rate of irradiation, while maintaining the same light dose, prevented immunosuppression and genetic damage and may have the potential to improve skin cancer outcomes.
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