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Physics in Medicine and Biology Dec 2017Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its...
Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its photobleaching. The temporal integral of the product of in vivo photosensitizer concentration and light fluence is called PDT dose, which is an important dosimetry quantity for PDT. However, the detected photosensitizer fluorescence may be distorted by variations in the absorption and scattering of both excitation and fluorescence light in tissue. Therefore, correction of the measured fluorescence for distortion due to variable optical properties is required for absolute quantification of photosensitizer concentration. In this study, we have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and photosensitizer fluorescence data. We measured PDT dose at four sites in the pleural cavity during pleural PDT. We have determined an empirical optical property correction function using Monte Carlo simulations of fluorescence for a range of physiologically relevant tissue optical properties. Parameters of the optical property correction function for Photofrin fluorescence were determined experimentally using tissue-simulating phantoms. In vivo measurements of photosensitizer fluorescence showed negligible photobleaching of Photofrin during the PDT treatment, but large intra- and inter-patient heterogeneities of in vivo Photofrin concentration are observed. PDT doses delivered to 22 sites in the pleural cavity of 8 patients were different by 2.9 times intra-patient and 8.3 times inter-patient.
Topics: Clinical Trials, Phase II as Topic; Dihematoporphyrin Ether; Fluorescence; Humans; Mesothelioma; Monte Carlo Method; Phantoms, Imaging; Photochemotherapy; Photosensitizing Agents; Pleural Neoplasms; Radiometry; Randomized Controlled Trials as Topic; Spectrometry, Fluorescence
PubMed: 29106380
DOI: 10.1088/1361-6560/aa9874 -
Cell Death & Disease Oct 2017Colorectal cancer (CRC) is a most common digestive system malignant tumor. p53 mutation has essential role in cancers and is frequently observed in CRC and presents a...
Colorectal cancer (CRC) is a most common digestive system malignant tumor. p53 mutation has essential role in cancers and is frequently observed in CRC and presents a huge challenge. p53 mutation has been reported to attenuate the inhibitory effect of photofrin-based photodynamic therapy (PDT). p53 mutation-induced gain of function brings up the dysfunction of carcinogenic factors, including miRNAs. Our research found that PDT suppressed CRC cell viability, reduced the tumor size and prolonged the survival time, all of which could be attenuated by p53 mutation or deletion. After p53 mutation or deletion, several miRNA expression levels were downregulated, among which miR-124 was the most strongly downregulated, whereas iASPP expression was upregulated. p53 binds to the promoter of miR-124 to promote its expression and then inhibited iASPP expression, so as to amplify the inhibitory effect of PDT on wild-type p53 cells. In p53-mutant or -deleted cells, this binding no longer worked to promote miR-124 expression, and iASPP expression increased, finally resulted in promoted CRC cell viability upon PDT. The interactive modulation among miR and iASPP in p53-mutant or -deleted cells may serve as a crucial pathway, which mediates therapy resistance when p53 is mutated or deleted, in the process of PDT treatment of CRC.
Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; DNA-Binding Proteins; Dihematoporphyrin Ether; HCT116 Cells; HT29 Cells; Humans; Mice; MicroRNAs; Neoplasm Transplantation; Photochemotherapy; Promoter Regions, Genetic; Transplantation, Heterologous; Tumor Suppressor Protein p53
PubMed: 29022915
DOI: 10.1038/cddis.2017.477 -
Clinical and Experimental Dermatology Jan 2018Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary...
Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary cicatricial alopecia. The role of dysfunctional immune activity and the presence of bacteria, particularly Staphylococcus aureus, appear pivotal. We describe a 26-year-old man with a 4-year history of FD that was recalcitrant to numerous systemic and topical therapies, whose disease was virtually cleared during a follow-up of 25 months following a course of treatment with systemic photodynamic therapy (PDT) using ultraviolet light (100-140 J/cm ) with porfimer sodium 1 mg/kg as monotherapy. This is the first report of the use of systemic PDT as a treatment for FD. Systemic PDT has potent antibacterial effects with little or no resistance. In addition, systemic PDT provides local immunomodulation and improved scar healing. Significant adverse effects following systemic PDT with appropriate aftercare are rare. This case demonstrates that systemic PDT is a useful therapy option in the treatment of recalcitrant FD.
Topics: Adult; Alopecia; Anti-Bacterial Agents; Dihematoporphyrin Ether; Folliculitis; Humans; Male; Photochemotherapy; Scalp; Skin; Staphylococcal Infections; Staphylococcus aureus
PubMed: 28940572
DOI: 10.1111/ced.13238 -
Annals of Translational Medicine Apr 2017Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce... (Review)
Review
Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate. Cancer cells consume higher levels of glucose than normal cells and this phenomenon is known as the Warburg effect. Thus, we developed a third-generation PDT, based on the Warburg effect, by synthesizing a novel photosensitizer, sugar-conjugated chlorin, with increased cancer cell-selective accumulation. Glucose-conjugated chlorin (G-chlorin) PDT showed significantly stronger antitumor effects than second-generation talaporfin PDT. We also found that PDT with G-chlorin induced immunogenic cell death which is characterized by the secretion, release, or surface exposure of damage-associated molecular patterns (DAMPs), including calreticulin (CRT) and the high-mobility group box 1 (HMGB1) protein. Mannose-conjugated chlorin (M-chlorin) PDT which targets the mannose receptors on the surface of cancer cells and tumor-associated macrophages (TAMs) in cancer tissue stroma also showed very strong antitumor effects. These novel PDTs using glucose or M-chlorins stand as new candidates for very effective, next-generation PDTs.
PubMed: 28616398
DOI: 10.21037/atm.2017.03.59 -
Journal of Investigative and Clinical... Feb 2018The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and... (Review)
Review
AIM
The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and head and neck squamous cell carcinoma (HNSCC).
METHODS
From 1985 to 2015, PubMed/Medline, Google Scholar, EMBASE, and ISI Web of Knowledge were searched using different combinations of the following key words: PDT, oral precancer, leukoplakia, erythroplakia, erythroleukoplakia, verrucous hyperplasia, oral submucous fibrosis, and HNSCC. Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded.
RESULTS
Twenty-six studies were included in the present study. The number of patients ranged from 2 to 147, with a mean age of 50-67 years. The reported numbers of PMDS and HNSCC ranged between 5 and 225. Photosensitizers used were aminolevulinic acid, meta-tetrahydroxyphenylchlorin, Foscan, hematoporphyrin derivatives, Photofrin, Photosan, and chlorine-e6. Laser wavelength, power density, irradiation duration were 585-652 nm, 50-500 mW/cm , and 1-143 minutes, respectively. Complete, partial, and no response to PDT was found in 22.58%-100%, 4%-66%, and 0%-38.70% of PMDS, respectively, and 16%-100% of complete response in HNSCC patients.
CONCLUSION
PDT is effective in the management of PMDS and HNSCC.
Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Chlorophyllides; Databases, Factual; Dihematoporphyrin Ether; Erythroplasia; Head and Neck Neoplasms; Hematoporphyrins; Humans; Hyperplasia; Indoles; Laser Therapy; Lasers; Leukoplakia; Leukoplakia, Oral; Mesoporphyrins; Oral Submucous Fibrosis; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome
PubMed: 28480637
DOI: 10.1111/jicd.12270 -
Scientific Reports May 2017In Photofrin-mediated photodynamic therapy (PDT), cell fate can be modulated by the subcellular location of Photofrin. PDT triggers oxidative damage to target cells,...
Oxidation of protein-bound methionine in Photofrin-photodynamic therapy-treated human tumor cells explored by methionine-containing peptide enrichment and quantitative proteomics approach.
In Photofrin-mediated photodynamic therapy (PDT), cell fate can be modulated by the subcellular location of Photofrin. PDT triggers oxidative damage to target cells, including the methionine (Met) oxidation of proteins. Here, we developed a new Met-containing peptide enrichment protocol combined with SILAC-based quantitative proteomics, and used this approach to explore the global Met oxidation changes of proteins in PDT-treated epidermoid carcinoma A431 cells preloaded with Photofrin at the plasma membrane, ER/Golgi, or ubiquitously. We identified 431 Met-peptides corresponding to 302 proteins that underwent severe oxidation upon PDT and observed overrepresentation of proteins related to the cell surface, plasma membrane, ER, Golgi, and endosome under all three conditions. The most frequently oxidized Met-peptide sequence was "QAMXXMM-E/G/M-S/G-A/G/F-XG". We also identified several hundred potential Photofrin-binding proteins using affinity purification coupled with LC-MS/MS, and confirmed the bindings of EGFR and cathepsin D with Photofrin. The enzyme activities of both proteins were significantly reduced by Photofrin-PDT. Our results shed light on the global and site-specific changes in Met-peptide oxidation among cells undergoing Photofrin-PDT-mediated oxidative stress originating from distinct subcellular sites, and suggest numerous potential Photofrin-binding proteins. These findings provide new insight into the molecular targets through which Photofrin-PDT has diverse effects on target cells.
Topics: Cell Line, Tumor; Cell Membrane; Dihematoporphyrin Ether; Endoplasmic Reticulum; Endosomes; Golgi Apparatus; Humans; Methionine; Oxidation-Reduction; Oxidative Stress; Peptides; Photochemotherapy; Proteomics
PubMed: 28465586
DOI: 10.1038/s41598-017-01409-9 -
Journal of Biophotonics Dec 2017In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the...
In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of "death signal", thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide-mediated stress signaling pathways. The work presents the ability of Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture: The survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed) and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density condition.
Topics: Aldehydes; Calcium; Cell Communication; Ceramides; Connexin 26; Connexins; Dihematoporphyrin Ether; Extracellular Space; Gap Junctions; HeLa Cells; Humans; Intracellular Space; Lipid Peroxides; Photochemotherapy
PubMed: 28417552
DOI: 10.1002/jbio.201600255 -
Photodiagnosis and Photodynamic Therapy Jun 2017Iron oxide (FeO) nanoparticles (IO-NP) were recently employed in medical applications as a diagnostic tool and drug carrier. Photofrin (PF) is a photosensitizer that...
BACKGROUND
Iron oxide (FeO) nanoparticles (IO-NP) were recently employed in medical applications as a diagnostic tool and drug carrier. Photofrin (PF) is a photosensitizer that clinically is used in Photodynamic therapy (PDT).
STUDY DESIGN
The photosensitivity of PF and Rose Bengal (RB) mixed with (IO-NP) on red blood cells (RBCs) lysis was investigated. Second, Photohemolysis for post-irradiation (delayed) and during irradiation (continuous) with PF, RB and IO-NP combinations at different concentrations was investigated. Third, the photohemolysis rate, relative lysis steepness and power-concentration dependant parameter were evaluated by modeling and fitting the data using Gompertz function and power law.
METHODS
RBCs were isolated from healthy male human volunteer. Washed cells (7.86×10 cells/mm) were incubated with PF only or with IO-NP for 45min at 37°C then irradiated to a range of temperatures (4-41°C). CPH results were recorded and evaluated using Gompertz function.
RESULTS
The relative steepness of the photohemolysis curves was approximately independent on light dose for delayed irradiation. The presence of IO-NP increases the rupturing time for 50% of the RBCs. Photohemolysis rate for delayed irradiation using the power law, led to 1.7 and 2.3 power dependence, respectively, for PF only and PF mixed with IO-NP. The power dependence of continuous irradiation measurements showed inverse proportionality for different concentrations of IO-NP combined with 2μg/ml PF concentration and 1.5μg/ml for RB concentration.
CONCLUSION
Photosensitization of RBC with PF or RB mixed with IO-NP inhibited rupturing erythrocyte membrane and therefore a consideration should be taken against their combination in clinical applications.
Topics: Adult; Cells, Cultured; Dextrans; Dihematoporphyrin Ether; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Combinations; Erythrocytes; Hemolysis; Humans; Magnetite Nanoparticles; Male; Nanocapsules; Photochemotherapy; Photosensitizing Agents; Rose Bengal
PubMed: 28232076
DOI: 10.1016/j.pdpdt.2017.02.008 -
Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin.ACS Infectious Diseases Apr 2017It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or...
It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or fungi. However, the aPDI activity of PF against Gram-negative bacteria is accepted to be extremely low. Here we report that the nontoxic inorganic salt potassium iodide (KI) at a concentration of 100 mM when added to microbial cells (10/mL) + PF (10 μM hematoporphyrin equivalent) + 415 nm light (10 J/cm) can eradicate (>6 log killing) five different Gram-negative species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii), whereas no killing was obtained without KI. The mechanism of action appears to be the generation of microbicidal molecular iodine (I/I) as shown by comparable bacterial killing when cells were added to the mixture after completion of illumination and light-dependent generation of iodine as detected by the formation of the starch complex. Gram-positive methicillin-resistant Staphylococcus aureus is much more sensitive to aPDI (200-500 nM PF), and in this case potentiation by KI may be mediated mainly by short-lived iodine reactive species. The fungal yeast Candida albicans displayed intermediate sensitivity to PF-aPDI, and killing was also potentiated by KI. The reaction mechanism occurs via singlet oxygen (O). KI quenched O luminescence (1270 nm) at a rate constant of 9.2 × 10 M s. Oxygen consumption was increased when PF was illuminated in the presence of KI. Hydrogen peroxide but not superoxide was generated from illuminated PF in the presence of KI. Sodium azide completely inhibited the killing of E. coli with PF/blue light + KI.
Topics: Anti-Bacterial Agents; Candida albicans; Dihematoporphyrin Ether; Drug Synergism; Gram-Negative Bacteria; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Photosensitizing Agents; Potassium Iodide
PubMed: 28207234
DOI: 10.1021/acsinfecdis.7b00004 -
Photodiagnosis and Photodynamic Therapy Jun 2017
Topics: Aged; Bronchial Neoplasms; Carcinoma, Adenoid Cystic; Dihematoporphyrin Ether; Female; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents
PubMed: 28193565
DOI: 10.1016/j.pdpdt.2017.02.002