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Gu R, Fei S, Liu Z, Liu X, Fang X, Wu H, Zhang X, Xu G, Xu F. Effects of photodynamic therapy in patients with infected skin ulcers: A meta-analysis. Int Wound J 2024; 21:e14747. [PMID: 38445778 PMCID: PMC10915826 DOI: 10.1111/iwj.14747] [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: 01/12/2024] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 03/07/2024] Open
Abstract
The purpose of the meta-analysis was to evaluate and compare the photodynamic therapy's effectiveness in treating infected skin wounds. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 6 examinations spanning from 2013 to 2021 were included, encompassing 154 patients with infected skin wounds were the used studies' starting point. Photodynamic therapy had a significantly lower wound ulcer size (MD, -4.42; 95% CI, -7.56--1.28, p = 0.006), better tissue repair (MD, -8.62; 95% CI, -16.76--0.48, p = 0.04) and lower microbial cell viability (OR, 0.13; 95% CI, 0.04-0.42, p < 0.001) compared with red light exposure in subjects with infected skin wounds. The examined data revealed that photodynamic therapy had a significantly lower wound ulcer size, better tissue repair and lower microbial cell viability compared with red light exposure in subjects with infected skin wounds. However, given that all examinations had a small sample size, consideration should be given to their values.
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Affiliation(s)
- Rui Gu
- Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese MedicineBeijingChina
| | - Sha'ni Fei
- Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese MedicineBeijingChina
| | - Zhaoyu Liu
- Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese MedicineBeijingChina
| | - Xiaoqi Liu
- Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese MedicineBeijingChina
| | - Xiaoxiao Fang
- Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese MedicineBeijingChina
| | - Hengjin Wu
- Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese MedicineBeijingChina
| | - Xia Zhang
- Department of NeurologyPeking University Aerospace School of Clinical MedicineBeijingChina
| | - Guomei Xu
- Department of DermatologyBeijing University of Chinese Medicine Third Affiliated HospitalBeijingChina
| | - Fengquan Xu
- Department of PsychosomaticsGuang'anmen Hospital, China Academy of Chinese Medical SciencesBeijingChina
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Lintern N, Smith AM, Jayne DG, Khaled YS. Photodynamic Stromal Depletion in Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:4135. [PMID: 37627163 PMCID: PMC10453210 DOI: 10.3390/cancers15164135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/13/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour-stromal cell interactions. So far, the pre-clinical studies have suggested that PDT can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. However, the complexity of this interplay, including the combined tumour promoting and suppressing effects, poses unknowns for the clinical application of photodynamic stromal depletion in PDAC.
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Affiliation(s)
- Nicole Lintern
- School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - Andrew M. Smith
- Leeds Institute of Medical Research, St James’s University Hospital, Leeds LS9 7TF, UK
| | - David G. Jayne
- Leeds Institute of Medical Research, St James’s University Hospital, Leeds LS9 7TF, UK
| | - Yazan S. Khaled
- Leeds Institute of Medical Research, St James’s University Hospital, Leeds LS9 7TF, UK
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Photodynamic therapy for treating infected skin wounds: A systematic review and meta-analysis from randomized clinical trials. Photodiagnosis Photodyn Ther 2022; 40:103118. [PMID: 36109003 DOI: 10.1016/j.pdpdt.2022.103118] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/16/2022] [Accepted: 09/09/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Infected skin wounds represent a public health problem that effects 20 million people worldwide. Photodynamic therapy (PDT) is a treatment option with excellent results against several infections. OBJECTIVE This study aimed to perform a systematic review and meta-analysis on PDT efficacy for treating infected wounds based on randomized clinical trials (RCTs). METHODS PubMed, Scopus, Web of Science, SciELO, and the Cochrane library were searched. The Delphi List criteria and the Revised Cochrane risk-of-bias (Rob 2) were used for evaluating the quality of clinical trials. Meta-analyses were performed with the random-effect model. The odds ratio was the effect measure for binary outcomes, while the standard mean difference was used for continuous outcomes. The trim-and-fill method was used to detect small-study effects. The quality of evidence was verified for each outcome. RESULTS Only four out of 573 articles were selected for the qualitative and quantitative analyses. The most frequent cause of infected wounds was impaired venous circulation (75%). All studies used red LED light. PDT reduced healing time and improved the healing process and wound oxygenation. Patients treated with PDT showed 15% to 17% (p = 0.0003/ I2=0%) lower microbial cell viability in the wound and a significantly smaller wound size (0.72 cm2/p = 0.0187/I2=0%) than patients treated with placebo or red-light exposure. There was a high level of evidence for each meta-analysis outcome. CONCLUSION PDT can be an excellent alternative treatment for infected skin wounds, though larger trials are needed.
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Sampaio LS, de Annunzio SR, de Freitas LM, Dantas LO, de Boni L, Donatoni MC, de Oliveira KT, Fontana CR. Influence of light intensity and irradiation mode on methylene blue, chlorin-e6 and curcumin-mediated photodynamic therapy against Enterococcus faecalis. Photodiagnosis Photodyn Ther 2020; 31:101925. [DOI: 10.1016/j.pdpdt.2020.101925] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/01/2020] [Accepted: 07/06/2020] [Indexed: 12/11/2022]
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Optimized Cylindrical Diffuser Powers for Interstitial PDT Breast Cancer Treatment Planning: A Simulation Study. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2061509. [PMID: 32280680 PMCID: PMC7125442 DOI: 10.1155/2020/2061509] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 01/31/2020] [Accepted: 03/04/2020] [Indexed: 12/18/2022]
Abstract
Purpose It is well known that interstitial photodynamic therapy (iPDT) of large tumors requires effective planning to ensure efficient delivery of therapeutic dose to the target tumors. This should be achieved in parallel with minimal damage to the nearby intact tissues. To that end, clinical iPDT can be attained using cylindrical diffusing optical fibers (CDFs) as light sources. In this work, we optimize output CDF powers in order to deliver a prescribed light dose to a spherical volume such as a tumor node. Methods Four CDFs are placed vertically inside the tumor node. The fluence rate is calculated using the diffusion equation. Therapeutic target dose is (20-50) J·cm−2. The optical properties (μa = 0.085 cm−1, μs′ = 16 cm−1) of a breast tumor and the treatment time of 150 sec are used to calculate the fluence rate. Results For four CDFs, the therapeutic target dose (20-50) J·cm−2 is delivered to more than 90%. This is the ratio of the total points that receive the target dose in proportion to the total points in the volume of the node of 3 cm in diameter, whereas, in larger nodes, the ratio is decreased to approximately 67%. Five CDFs are required to improve this ratio by more than 10%. Conclusion Optimizing delivered powers enables the distribution of the therapeutic dose uniformly in the medium. In addition, this simulation study represents an essential part of a development dosimetry system for measuring and controlling the optical dose in the breast tumors.
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Haedicke K, Graefe S, Teichgraeber U, Hilger I. Lowering photosensitizer doses and increasing fluences induce apoptosis in tumor bearing mice. BIOMEDICAL OPTICS EXPRESS 2016; 7:2641-9. [PMID: 27446695 PMCID: PMC4948619 DOI: 10.1364/boe.7.002641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 05/19/2016] [Accepted: 05/22/2016] [Indexed: 05/03/2023]
Abstract
The objective of this study was to determine an optimal dose of photodynamic therapy (PDT) for inducing apoptotic tumor cells in vivo. In this context, mice bearing human tongue-squamous epithelium carcinomas were treated with various photosensitizer concentrations and fluences. Tumor apoptosis was imaged after 2 days via a self-designed DY-734-annexin V probe using near-infrared fluorescence (NIRF) optical imaging. Apoptosis was verified ex vivo via TUNEL staining. Apoptotic tumor cells were detected in vivo at a dose of 40 µg photosensitizer and a fluency of 100 J/cm(2). This is the lowest photosensitizer dose reported so far.
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Affiliation(s)
- Katja Haedicke
- Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, Erlanger Allee 101, D-07747 Jena, Germany
| | - Susanna Graefe
- Biolitec Research GmbH, Research & Development, Otto-Schott-Straße 15, D-07745 Jena, Germany
| | - Ulf Teichgraeber
- Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, Erlanger Allee 101, D-07747 Jena, Germany
| | - Ingrid Hilger
- Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, Erlanger Allee 101, D-07747 Jena, Germany
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De Baróid ÁT, McCoy CP, Craig RA, Carson L, Andrews GP, Jones DS, Gorman SP. Optimization of singlet oxygen production from photosensitizer-incorporated, medically relevant hydrogels. J Biomed Mater Res B Appl Biomater 2015; 105:320-326. [PMID: 26505264 PMCID: PMC5244673 DOI: 10.1002/jbm.b.33562] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 10/05/2015] [Accepted: 10/11/2015] [Indexed: 11/12/2022]
Abstract
Photodynamic therapy and photodynamic antimicrobial chemotherapy are widely used, but despite this, the relationships between fluence, wavelength of irradiation and singlet oxygen (1O2) production are poorly understood. To establish the relationships between these factors in medically relevant materials, the effect of fluence on 1O2 production from a tetrakis(4‐N‐methylpyridyl)porphyrin (TMPyP)‐incorporated 2‐hydroxyethyl methacrylate: methyl methacrylate: methacrylic acid (HEMA: MMA:MAA) copolymer, a total energy of 50.48 J/cm2, was applied at varying illumination power, and times. 1O2 production was characterized using anthracene‐9,10‐dipropionic acid, disodium salt (ADPA) using a recently described method. Using two light sources, a white LED array and a white halogen source, the LED array was found to produce less 1O2 than the halogen source when the same power (over 500 − 600 nm) and time conditions were applied. Importantly, it showed that the longest wavelength Q band (590 nm) is primarily responsible for 1O2 generation, and that a linear relationship exists between increasing power and time and the production of singlet oxygen. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 320–326, 2017.
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Affiliation(s)
- Áine T De Baróid
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - Colin P McCoy
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - Rebecca A Craig
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - Louise Carson
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - Gavin P Andrews
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - David S Jones
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - Sean P Gorman
- School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK
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Lou X, Kim G, Yoon HK, Lee YEK, Kopelman R, Yoon E. A high-throughput photodynamic therapy screening platform with on-chip control of multiple microenvironmental factors. LAB ON A CHIP 2014; 14:892-901. [PMID: 24394779 PMCID: PMC3951301 DOI: 10.1039/c3lc51077h] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
We present a novel high-throughput microfluidic platform that enables the evaluation of the anticancer efficacy of photodynamic therapy (PDT) drugs over multiple microenvironmental factors. PDT is uniquely complex, originating from its dependence on three separate but essential elements: drug (also called photosensitizer), oxygen, and light. Thus, obtaining a reliable evaluation of PDT efficacy is highly challenging, requiring considerable effort and time to evaluate all three interdependent parameters. In this paper, we report a high-throughput efficacy screening platform that we implemented by developing microfluidic components that individually control basic PDT elements (photosensitizer concentrations, oxygen levels, and light fluence) and then integrating them into a single triple-layer device. The integrated microfluidic chip consists of an array of small compartments, each corresponding to a specific combination of these three variables. This allows for more than 1000 different conditions being tested in parallel. Cancer cells are cultured within the device, exposed to different PDT conditions, and then monitored for their viability using live/dead fluorescence staining. The entire screening assay takes only 1 hour, and the collected PDT outcomes (cell viability) for combinatorial screening are analysed and reported as traditional dose-response curves or 3D bubble charts using custom software. As a proof of concept, methylene blue is adopted as a photosensitizer and its drug efficacy on C6 glioma cells has been successfully evaluated for a total of 324 PDT conditions using the fabricated chip. This platform can facilitate not only the development of new photosensitizers but also the optimization of current PDT protocols.
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Affiliation(s)
- Xia Lou
- Center for Wireless Integrated Microsystems, Department of EECS, University of Michigan, 1301 Beal Ave, Ann Arbor, MI 48109, USA.
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Bovis MJ, Woodhams JH, Loizidou M, Scheglmann D, Bown SG, Macrobert AJ. Improved in vivo delivery of m-THPC via pegylated liposomes for use in photodynamic therapy. J Control Release 2011; 157:196-205. [PMID: 21982898 DOI: 10.1016/j.jconrel.2011.09.085] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Revised: 09/07/2011] [Accepted: 09/22/2011] [Indexed: 10/17/2022]
Abstract
Pegylated liposomal nanocarriers have been developed with the aim of achieving improved uptake of the clinical PDT photosensitiser, m-THPC, into target tissues through increased circulation time and bioavailability. This study investigates the biodistribution and PDT efficacy of m-THPC in its standard formulation (Foscan®) compared to m-THPC incorporated in liposomes with different degrees of pegylation (FosPEG 2% and FosPEG 8%), following i.v. administration to normal and tumour bearing rats. The plasma pharmacokinetics were described using a three compartmental analysis and gave elimination half lives of 90 h, 99 h and 138 h for Foscan®, FosPEG 2% and 8% respectively. The accumulation of m-THPC in tumour and normal tissues, including skin, showed that maximal tumour to skin ratios were observed at ≤ 24 h with FosPEG 2% and 8%, whilst skin photosensitivity studies showed Foscan® induces more damage compared to the liposomes at drug-light intervals of 96 and 168 h. PDT treatment at 24h post-administration (0.05 mg kg⁻¹) showed higher tumour necrosis using pegylated liposomal formulations in comparison to Foscan®, which is attributed to the higher tumour uptake and blood plasma concentrations. Clinically, this improved selectivity has the potential to reduce not only normal tissue damage, but the drug dose required and cutaneous photosensitivity.
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Affiliation(s)
- Melissa J Bovis
- Division of Surgery and Interventional Science, National Medical Laser Centre, University College London, London, UK.
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10
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Senge MO, Brandt JC. Temoporfin (Foscan®, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin)--a second-generation photosensitizer. Photochem Photobiol 2011; 87:1240-96. [PMID: 21848905 DOI: 10.1111/j.1751-1097.2011.00986.x] [Citation(s) in RCA: 230] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This review traces the development and study of the second-generation photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin through to its acceptance and clinical use in modern photodynamic (cancer) therapy. The literature has been covered up to early 2011.
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Affiliation(s)
- Mathias O Senge
- Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
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11
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Ferraz RCMC, Fontana CR, Ribeiro APD, Trindade FZ, Bartoloni FH, Baader JW, Lins EC, Bagnato VS, Kurachi C. Chemiluminescence as a PDT light source for microbial control. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2011; 103:87-92. [PMID: 21349738 DOI: 10.1016/j.jphotobiol.2011.01.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2010] [Revised: 01/17/2011] [Accepted: 01/18/2011] [Indexed: 10/18/2022]
Abstract
The photodynamic therapy (PDT) is a combination of using a photosensitizer agent, light and oxygen that can cause oxidative cellular damage. This technique is applied in several cases, including for microbial control. The most extensively studied light sources for this purpose are lasers and LED-based systems. Few studies treat alternative light sources based PDT. Sources which present flexibility, portability and economic advantages are of great interest. In this study, we evaluated the in vitro feasibility for the use of chemiluminescence as a PDT light source to induce Staphylococcus aureus reduction. The Photogem® concentration varied from 0 to 75 μg/ml and the illumination time varied from 60 min to 240 min.The long exposure time was necessary due to the low irradiance achieved with chemiluminescence reaction at μW/cm² level. The results demonstrated an effective microbial reduction of around 98% for the highest photosensitizer concentration and light dose. These data suggest the potential use of chemiluminescence as a light source for PDT microbial control, with advantages in terms of flexibility, when compared with conventional sources.
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Affiliation(s)
- Ruy C M C Ferraz
- Institute of Physics of São Carlos, University of São Paulo, USP, São Carlos, Brazil.
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Busch TM, Wang HW, Wileyto EP, Yu G, Bunte RM. Increasing damage to tumor blood vessels during motexafin lutetium-PDT through use of low fluence rate. Radiat Res 2010; 174:331-40. [PMID: 20726728 DOI: 10.1667/rr2075.1] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Photodynamic therapy (PDT) with low light fluence rate has rarely been studied in protocols that use short drug-light intervals and thus deliver illumination while plasma concentrations of photosensitizer are high, creating a prominent vascular response. In this study, the effects of light fluence rate on PDT response were investigated using motexafin lutetium (10 mg/kg) in combination with 730 nm light and a 180-min drug-light interval. At 180 min, the plasma level of photosensitizer was 5.7 ng/microl compared to 3.1 ng/mg in RIF tumor, and PDT-mediated vascular effects were confirmed by a spasmodic decrease in blood flow during illumination. Light delivery at 25 mW/cm(2) significantly improved long-term tumor responses over that at 75 mW/cm(2). This effect could not be attributed to oxygen conservation at low fluence rate, because 25 mW/cm(2) PDT provided little benefit to tumor hemoglobin oxygen saturation. However, 25 mW/cm(2) PDT did prolong the duration of ischemic insult during illumination and was correspondingly associated with greater decreases in perfusion immediately after PDT, followed by smaller increases in total hemoglobin concentration in the hours after PDT. Increases in blood volume suggest blood pooling from suboptimal vascular damage; thus the smaller increases after 25 mW/cm(2) PDT provide evidence of more widespread vascular damage, which was accompanied by greater decreases in clonogenic survival. Further study of low fluence rate as a means to improve responses to PDT under conditions designed to predominantly damage vasculature is warranted.
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Affiliation(s)
- Theresa M Busch
- Department of Radiation Oncology, School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania 19104, USA.
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Bai L, Guo J, Bontempo FA, Eiseman JL. The relationship of phthalocyanine 4 (pc 4) concentrations measured noninvasively to outcome of pc 4 photodynamic therapy in mice. Photochem Photobiol 2009; 85:1011-9. [PMID: 19320848 DOI: 10.1111/j.1751-1097.2009.00542.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The ability to noninvasively measure photosensitizer concentration at target tissues will allow optimization of photodynamic therapy (PDT) and could improve outcome. In this study, we evaluated whether preirradiation tumor phthalocyanine 4 (Pc 4) concentrations, measured noninvasively by the optical pharmacokinetic system (OPS), correlated with tumor response to PDT. Mice bearing human breast cancer xenografts were treated with 2 mg kg(-1) Pc 4 iv only, laser irradiation (150 J cm(-2)) only, Pc 4 followed by fractionated irradiation or Pc 4 followed by continuous irradiation. Laser irradiation treatment was initiated when the tumor to skin ratio of Pc 4 concentration reached a maximum of 2.1 at 48 h after administration. Pc 4 concentrations in tumor, as well as in Intralipid in vitro, decreased monoexponentially with laser fluence. Pc 4-PDT resulted in significant tumor regression, and tumor response was similar in the groups receiving either fractionated or continuous irradiation treatment after Pc 4. Tumor growth delay following Pc 4-PDT correlated with OPS-measured tumor Pc 4 concentrations at 24 h prior to PDT (R2=0.86). In excised tumors, OPS-measured Pc 4 concentrations were similar to the HPLC-measured concentrations. Thus, OPS measurements of photosensitizer concentrations can be used to assist in the scheduling of Pc 4-PDT.
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Affiliation(s)
- Lihua Bai
- Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Mannino S, Molinari A, Sabatino G, Ciafrè SA, Colone M, Maira G, Anile C, Arancia G, Mangiola A. Intratumoral vs systemic administration of meta-tetrahydroxyphenylchlorin for photodynamic therapy of malignant gliomas: assessment of uptake and spatial distribution in C6 rat glioma model. Int J Immunopathol Pharmacol 2008; 21:227-31. [PMID: 18336750 DOI: 10.1177/039463200802100126] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Malignant gliomas, with an incidence of 5 cases per 100,000 population per year, represent the most common primary brain tumour. They have an overall survival length of less than 2 years. Many different adjuvant therapies have been developed. Among them, Photodynamic Therapy (PDT), that is based on photochemical reactions between light and tumoral tissue selectively labelled with exogenous photosensitizing agents. Among photosensitizers, m-THPC (Temoporfin), seems to be the most promising one for the treatment of brain tumors, but, unfortunately, it causes problems of high skin photosensitivity. To by-pass this problem, we devised an intratumoral route of administration of this photosensitizer. The aim of this study is to investigate and compare the uptake of m-THPC in brain tumor and normal tissue after systemic and intratumoral administration of the drug. 30 female Wistar rats received m-THPC 12 days after C6 tumor implantation. Temoporfin was administered intratumorally in 24 rats at two different concentrations. 6 rats constituted the control group and received m-THPC by means of an intraperitoneal injection. The brains were extracted at 4 h, 24 h and 96 h after Temoporfin injection. The samples were examined with a confocal laser scanning microscope. All samples showed high fluorescence emission exclusively in the tumour area, without appreciable differences between the samples taken at the different times of sacrifice and the two routes of administration. No fluorescence whatsoever was detected among normal brain tissue surrounding the tumour. The intratumoral route appears to give comparable results to the systemic one, regarding intracellular uptake efficiency and tumour--normal tissue ratio, with the advantage of a much shorter time needed to reach optimal intratumoural concentration--that is just four hours from m-THPC injection.
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Affiliation(s)
- S Mannino
- Institute of Neurosurgery, Catholic University of the Sacred Heart, Rome, Italy.
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Mackenzie GD, Jamieson NF, Novelli MR, Mosse CA, Clark BR, Thorpe SM, Bown SG, Lovat LB. How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of high-grade dysplasia in Barrett's esophagus. Lasers Med Sci 2007; 23:203-10. [PMID: 17610005 DOI: 10.1007/s10103-007-0473-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2006] [Accepted: 05/03/2007] [Indexed: 12/21/2022]
Abstract
Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is a novel treatment for high-grade dysplasia (HGD) in Barrett's esophagus (BE). Our aim was to evaluate the effectiveness of differing light doses. Patients with HGD in BE received oral ALA (60 mg/kg) activated by low (500 J/cm), medium (750 J/cm), high (1,000 J/cm), or highest (1,000 J/cm x2) light dose at 635 nm. Follow-up was by regular endoscopy with quadrantic biopsies. Twenty-four patients were treated. Successful eradication of HGD was significantly correlated with light dose (log rank, p < 0.01). Six of eight patients (75%) treated with the highest light dose, one of two treated with high dose (50%), two of nine (22%) receiving medium light dose, and zero of five receiving low light dose had successful eradication of HGD (median follow-up 45 months, range 1-78 months). No skin photosensitivity or esophageal strictures occurred. The efficacy of ALA-PDT for eradication of HGD in BE is closely related to the light dose used. With a drug dose of 60 mg/kg and light at 635 nm, we recommend a minimum light dose of 1,000 J/cm of esophagus. This dose appears safe.
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Affiliation(s)
- Gary D Mackenzie
- National Medical Laser Centre, Department of Surgery, Royal Free and University College Medical School, University College London, UK
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Kunz L, MacRobert AJ. Intracellular Photobleaching of 5,10,15,20-Tetrakis(m-hydroxyphenyl) chlorin (Foscan®) Exhibits a Complex Dependence on Oxygen Level and Fluence Rate¶. Photochem Photobiol 2007. [DOI: 10.1562/0031-8655(2002)0750028ipotmh2.0.co2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Oberdanner CB, Plaetzer K, Kiesslich T, Krammer B. Photodynamic Treatment with Fractionated Light Decreases Production of Reactive Oxygen Species and Cytotoxicity In Vitro via Regeneration of Glutathione¶. Photochem Photobiol 2007. [DOI: 10.1111/j.1751-1097.2005.tb00233.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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18
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Kato H, Usuda J, Okunaka T, Furukawa K, Honda H, Sakaniwa N, Suga Y, Hirata T, Ohtani K, Inoue T, Maehara S, Kubota M, Yamada K, Tsuitsui H. Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital. Lasers Surg Med 2007; 38:371-5. [PMID: 16788919 DOI: 10.1002/lsm.20346] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND AND OBJECTIVES We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years. STUDY DESIGN/MATERIALS AND METHODS PDT for 264 centrally located early-stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition. RESULTS Recent results of interstitial PDT for peripheral-type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter. CONCLUSIONS In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT.
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Affiliation(s)
- H Kato
- Department of Thoracic Surgery, Tokyo Medical University Hospital, Tokyo 160-0023, Japan
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Influence of treatment-induced changes in tissue absorption on treatment volume during interstitial photodynamic therapy. ACTA ACUST UNITED AC 2006. [DOI: 10.1016/j.mla.2006.08.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Curnow A, MacRobert AJ, Bown SG. Comparing and combining light dose fractionation and iron chelation to enhance experimental photodynamic therapy with aminolevulinic acid. Lasers Surg Med 2006; 38:325-31. [PMID: 16596660 DOI: 10.1002/lsm.20328] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES Enhancement of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been demonstrated experimentally using light dose fractionation or CP94 iron chelation. This study extends this research. STUDY DESIGN/MATERIALS AND METHODS In normal rat colon, CP94 administration and light dose fractionation were independently and concurrently employed to enhance ALA-PDT. In colonic rat tumors, the most successful enhancement regimes were employed separately. RESULTS Independent use of light dose fractionation and iron chelation produced similar results in normal colon (2.4- and 2.9-fold more necrosis than controls, respectively). Using both techniques simultaneously produced fivefold enhancement. In the colonic tumors, light dose fractionation and iron chelation (using different parameters) produced two and five times the volume of necrosis, respectively. CONCLUSIONS Both techniques significantly enhanced ALA-PDT in the normal and neoplastic tissues investigated and produced similar levels of enhancement when comparable parameters were employed. Concurrent use of light dose fractionation and iron chelation in normal colon produced considerably more enhancement than either technique could achieve independently.
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Affiliation(s)
- Alison Curnow
- Cornwall Dermatology Research, Peninsula Medical School, Truro, Cornwall TR1 3HD, UK.
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21
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van Veen RLP, Nyst H, Rai Indrasari S, Adham Yudharto M, Robinson DJ, Tan IB, Meewis C, Peters R, Spaniol S, Stewart FA, Levendag PC, Sterenborg HJCM. In vivo fluence rate measurements during Foscan-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator. JOURNAL OF BIOMEDICAL OPTICS 2006; 11:041107. [PMID: 16965135 DOI: 10.1117/1.2338009] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan absorption.
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Affiliation(s)
- R L P van Veen
- Erasmus Medical Center, Center of Optical Diagnosis and Therapy, Rotterdam, The Netherlands
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22
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Woodhams JH, MacRobert AJ, Novelli M, Bown SG. Photodynamic therapy with WST09 (Tookad): quantitative studies in normal colon and transplanted tumours. Int J Cancer 2006; 118:477-82. [PMID: 16052532 DOI: 10.1002/ijc.21335] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Photodynamic therapy (PDT) is attracting increasing interest for the safe destruction of localised tumours in a range of organs. However, most photosensitising drugs require a delay of hours to days between drug administration and light activation with skin photosensitivity that may last for weeks. WST09 (Tookad) is a new faster acting photosensitiser that clears within a few hours. In normal rat colon, after sensitisation with an intravenous bolus of WST09, light was delivered to a single point on the mucosa and the extent of PDT necrosis measured 3 days later. The lesion diameter was greatest with the highest dose of drug and light and the shortest drug light interval (DLI), falling rapidly with a DLI more than 5 min. In tumours transplanted subcutaneously or into the colon, the extent of necrosis only started falling with a DLI greater than 15 min, suggesting a possible window for tumour selectivity. Histological changes 3 days after PDT were essentially the same as those seen with longer acting photosensitisers. The lesion dimensions were comparable to the largest ones seen with other photosensitisers under similar experimental conditions. We conclude that WST09 is a powerful photosensitiser that produces PDT effects similar to those seen with longer acting drugs, but with the major advantages of a short DLI and rapid clearance.
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Affiliation(s)
- Josephine H Woodhams
- National Medical Laser Centre, Academic Division of Surgical Specialities, Royal Free and University College Medical School, University College London, London, United Kingdom
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Abstract
The photodynamic therapy technique involving pulsed oxygen depletion (POD) in tissue by long high-energy pulses of light was studied theoretically. The possibility of creating a uniform distribution of a therapeutic dose throughout a tumor using both surface and interstitial irradiation is shown. Possible thickness of the treated tissue layer is estimated. The comparison with other methods of nonlinear photodynamic therapy is made.
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Affiliation(s)
- Boris Ya Kogan
- Organic Intermediates and Dyes Institute, B. Sadovaya str. 1/4, 123995 Moscow, Russia.
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Lovat LB, Jamieson NF, Novelli MR, Mosse CA, Selvasekar C, Mackenzie GD, Thorpe SM, Bown SG. Photodynamic therapy with m-tetrahydroxyphenyl chlorin for high-grade dysplasia and early cancer in Barrett's columnar lined esophagus. Gastrointest Endosc 2005; 62:617-23. [PMID: 16185985 DOI: 10.1016/j.gie.2005.04.043] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2005] [Accepted: 04/20/2005] [Indexed: 02/08/2023]
Abstract
BACKGROUND Many patients with high-grade dysplasia and localized adenocarcinoma in Barrett's esophagus have localized disease but are either unfit for major surgery or decline esophagectomy. Photodynamic therapy with the powerful photosensitizer m-tetrahydroxyphenyl chlorin may be a nonsurgical therapeutic option. METHODS This is a pilot study to evaluate the efficacy and complications of m-tetrahydroxyphenyl chlorin photodynamic therapy. The design is a case series of 19 consecutive patients at a tertiary referral unit with a special interest in photodynamic therapy. The study included 7 patients with high-grade dysplasia and 12 with early esophageal cancer, who had refused or were unfit for esophagectomy. Three days after photosensitization with 0.15 mg/kg m-tetrahydroxyphenyl chlorin, red or green light was delivered endoscopically when using either a bare fiber or a diffuser device. Results were assessed by endoscopic surveillance. RESULTS By using red light via the diffuser, 4/6 patients with cancer and 3/4 with high-grade dysplasia were successfully treated with photodynamic therapy alone. When using the bare-tipped fiber, there was one procedure-related death and only 1/5 patients with cancers were successfully treated. Two others were downgraded to high-grade dysplasia. With green light delivered via a diffuser, 0/3 patients with high-grade dysplasia are in long-term remission. Two serious complications arose (including one death) from taking multiple biopsy specimens too soon after therapy. Two esophageal strictures occurred. CONCLUSIONS Photodynamic therapy with m-tetrahydroxyphenyl chlorin is, potentially, a valuable therapeutic option for localized esophageal neoplasia. Red light via a diffuser device appears to be the most effective light-delivery technique. Biopsy specimens should not be taken for at least 2 months after treatment.
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Affiliation(s)
- Laurence B Lovat
- National Medical Laser Centre, Department of Surgery, Royal Free and University College Medical School, London, United Kingdom
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Harada M, Woodhams J, MacRobert AJ, Feneley MR, Kato H, Bown SG. The vascular response to photodynamic therapy with ATX-S10Na(II) in the normal rat colon. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2005; 79:223-30. [PMID: 15896649 DOI: 10.1016/j.jphotobiol.2004.08.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2004] [Revised: 08/12/2004] [Accepted: 08/30/2004] [Indexed: 11/15/2022]
Abstract
The mechanism of tissue damage from photodynamic therapy (PDT) may be cellular, vascular or both, depending on the photosensitising agent and the treatment conditions. Well established photosensitisers like porfimer sodium have an optimum drug light interval of two days and may cause skin photosensitivity lasting several weeks. ATX-S10Na(II) is a new photosensitiser that remains largely in the vasculature after systemic administration and clears from the body within a few hours. The present study looks at the factors controlling the extent of PDT necrosis using ATX-S10Na(II) and correlates these with changes in the circulation after PDT. Normal Wistar rats were sensitised with ATX-S10Na(II), 2 mg/kg. At laparotomy, a laser fibre was positioned just touching the colonic mucosa and 50 J light at 670 nm delivered varying the drug light interval (0.5-24 h) and light delivery regime (100 mW continuous, 20 mW continuous or 100 mW in five fractions). Some animals were killed at three days to document the area of necrosis, others received fluorescein shortly prior to death (from a few minutes to three days after PDT) to outline the zone of PDT induced vascular shutdown. Maximum necrosis was seen with the shortest drug light interval (0.5 h), with no effect by 6 h. Fractionating the light or lowering the power did not increase the necrosis. The area of fluorescein exclusion increased over the first 2 h after PDT (in contrast to the re-perfusion seen with other photosensitisers) and correlated with the area of necrosis. PDT with ATX-S10Na(II) is most effective with a drug light interval of less than one hour. It induces irreversible vascular shutdown that extends after completion of light delivery and which is largely independent of the light delivery regime.
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Affiliation(s)
- Masahiko Harada
- National Medical Laser Centre, Academic Division of Surgical Specialties, Royal Free and University College Medical School, 1st Floor, Charles Bell House, 67-73 Riding House Street, London W1W 7EJ, UK
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Wei HJ, Xing D, Lu JJ, Gu HM, Wu GY, Jin Y. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques. World J Gastroenterol 2005; 11:2413-9. [PMID: 15832410 PMCID: PMC4305627 DOI: 10.3748/wjg.v11.i16.2413] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.
METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integrating-sphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.
RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength, and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength. There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa, and there were also large differences in these value ranges between both colon muscle layer/chorion. There are the same orders of magnitude in the absorption coefficients for four kinds of colon tissues. The scattering coefficients of these tissues exceed the absorption coefficients by at least two orders of magnitude.
CONCLUSION: There were large differences in the three optical parameters between normal and adenomatous human colon mucosa/submucosa at the same laser wavelength, and there were also large differences in these parameters between both colon muscle layer/chorion at the same laser wavelength. Large differences in optical parameters indicate that there were large differences in compositions and structures between both colon mucosa/submucosa, and between both colon muscle layer/chorion. Optical parameters for four kinds of colon tissues are wavelength dependent, and these differences would be useful and helpful in clinical applications of laser and tumors photodynamic therapy (PDT).
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Affiliation(s)
- Hua-Jiang Wei
- Institute of Laser Life Science, South China Normal University, Guangzhou 510631, Guangdong Province, China
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Sacková V, Kuliková L, Mikes J, Kleban J, Fedorocko P. Hypericin-mediated Photocytotoxic Effect on HT-29 Adenocarcinoma Cells Is Reduced by Light Fractionation with Longer Dark Pause Between Two Unequal Light Doses. Photochem Photobiol 2005; 81:1411-6. [PMID: 16354114 DOI: 10.1562/2005-05-05-ra-514] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The present study demonstrates the in vitro effect of hypericin-mediated PDT with fractionated light delivery. Cells were photosensitized with unequal light fractions separated by dark intervals (1 or 6 h). We compared the changes in viability, cell number, survival, apoptosis and cell cycle on HT-29 cells irradiated with a single light dose (12 J/cm(2)) to the fractionated light delivery (1 + 11 J/cm(2)) 24 and 48 h after photodynamic treatment. We found that a fractionated light regime with a longer dark period resulted in a decrease of hypericin cytotoxicity. Both cell number and survival were higher after light sensitization with a 6-h dark interval. DNA fragmentation occurred after a single light-dose application, but in contrast no apoptotic DNA formation was detected with a 6-h dark pause. After fractionation the percentage of cells in the G1 phase of the cell cycle was increased, while the proportion of cells in the G2 phase decreased as compared to a single light-dose application, i.e. both percentage of cells in the G1 and G2 phase of the cell cycle were near control levels. We presume that the longer dark interval after the irradiation of cells by first light dose makes them resistant to the effect of the second illumination. These findings confirm that the light application scheme together with other photodynamic protocol components is crucial for the photocytotoxicity of hypericin.
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Affiliation(s)
- Veronika Sacková
- Institute of Biology and Ecology, Faculty of Sciences, P. J. Safárik University, Kosice, Slovakia
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Oberdanner CB, Plaetzer K, Kiesslich T, Krammer B. Photodynamic Treatment with Fractionated Light Decreases Production of Reactive Oxygen Species and Cytotoxicity In Vitro via Regeneration of Glutathione¶. Photochem Photobiol 2005. [DOI: 10.1562/2004-08-23-rn-284.1] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Woodhams JH, Kunz L, Bown SG, MacRobert AJ. Correlation of real-time haemoglobin oxygen saturation monitoring during photodynamic therapy with microvascular effects and tissue necrosis in normal rat liver. Br J Cancer 2004; 91:788-94. [PMID: 15266317 PMCID: PMC2364783 DOI: 10.1038/sj.bjc.6602036] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Photodynamic therapy (PDT) requires a photosensitising drug, light and oxygen. While it is known that the haemoglobin oxygen saturation (HbSat) can be altered by PDT, little has been done to correlate this with microvascular changes and the final biological effect. This report describes such studies on the normal liver of rats sensitised with aluminium disulphonated phthalocyanine. In total, 50 J of light at 670 nm, continuous or fractionated at 25 or 100 mW, was applied with a single laser fibre touching the liver surface. HbSat was monitored continuously 1.5-5.0 mm from the laser fibre using visible light reflectance spectroscopy (VLRS). Vascular shutdown was assessed by fluorescein angiography 2-40 min after light delivery. Necrosis was measured at post mortem 3 days after PDT. In all treatment groups at a 1.5 mm separation, HbSat fell to zero with little recovery after light delivery. At 2.5 mm, HbSat also decreased during light delivery, except with fractionated light, but then recovered. The greatest recovery of fluorescein perfusion after PDT was seen using 25 mW, suggesting an ischaemia/reperfusion injury. Necrosis was more extensive after low power and fractionated light than with 100 mW, continuous illumination. We conclude that VLRS is a useful technique for monitoring HbSat, although the correlation between HbSat, fluorescein exclusion and necrosis varied markedly with the light delivery regimen used.
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Affiliation(s)
- J H Woodhams
- National Medical Laser Centre, Academic Division of Surgical Specialities, Royal Free and University College Medical School, University College London, Charles Bell House, 67-73 Riding House Street, London W1W 7EJ, UK.
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Babilas P, Schacht V, Liebsch G, Wolfbeis OS, Landthaler M, Szeimies RM, Abels C. Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo. Br J Cancer 2003; 88:1462-9. [PMID: 12778078 PMCID: PMC2741044 DOI: 10.1038/sj.bjc.6600910] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
To improve efficacy of photodynamic therapy (PDT) with intravenously administered 5-aminolaevulinic acid (ALA) fractionating the light dose or reducing the light intensity may be a possibility. Therefore, Syrian Golden hamsters were fitted with dorsal skinfold chambers containing an amelanotic melanoma (n=26). PDT was performed (100 mW cm(-2), 100 J cm(-2), continuously or fractionated, and 25 mW cm(-2), 100 J cm(-2); continuously or fractionated) using an incoherent light source following i.v. application of ALA. Following fractionated irradiation, the light was paused after 20 J cm(-2) for 15 min. Prior to and up to 24 h after PDT tissue, pO(2) was measured using luminescence lifetime imaging. The efficacy was evaluated by measuring the tumour volume of amelanotic melanoma cells grown subcutaneously in the back of Syrian Golden hamsters (n=36). Only high-dose PDT resulted in a significant decrease of pO(2). Irrespective of the mode of irradiation only high-dose PDT induced complete remission of all tumours (13 out of 13). It could be shown that low-dose PDT failed to induce a significant decrease of pO(2). No significant effect of fractionated irradiation was shown regarding the therapeutic efficacy 28 days after PDT. Thus performing a fractionated PDT with ALA or reducing the light intensity seems not to be successful in clinical PDT according to the present data.
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Affiliation(s)
- P Babilas
- Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
| | - V Schacht
- Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
| | - G Liebsch
- Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
| | - O S Wolfbeis
- Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
| | - M Landthaler
- Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
| | - R-M Szeimies
- Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
| | - C Abels
- Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
- Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. E-mail:
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