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Journal of Medicinal Chemistry Sep 2014Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me =...
Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2″-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction).
Topics: Cell Line; Cell Survival; Coordination Complexes; Escherichia coli; HeLa Cells; Humans; Light; Microbial Viability; Microscopy, Confocal; Models, Chemical; Molecular Structure; Photochemotherapy; Photosensitizing Agents; Ruthenium; Staphylococcus aureus
PubMed: 25121347
DOI: 10.1021/jm500566f -
Surgical Endoscopy Feb 2020Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy... (Observational Study)
Observational Study
BACKGROUND
Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT).
METHODS
We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled.
RESULTS
A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6]).
CONCLUSIONS
L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Dihematoporphyrin Ether; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retrospective Studies; Salvage Therapy; Treatment Failure
PubMed: 31139985
DOI: 10.1007/s00464-019-06846-3 -
Gastrointestinal Endoscopy Apr 2015
Topics: Bile Duct Neoplasms; Cholangiocarcinoma; Cholangiopancreatography, Endoscopic Retrograde; Dihematoporphyrin Ether; Humans; Male; Middle Aged; Palliative Care; Photochemotherapy; Photosensitizing Agents
PubMed: 25484323
DOI: 10.1016/j.gie.2014.09.060 -
Photodiagnosis and Photodynamic Therapy Jun 2018Photodynamic therapy (PDT) is an office-based treatment for precancerous and early cancerous skin changes. PDT induces cell death through the production of reactive...
Photodynamic therapy (PDT) is an office-based treatment for precancerous and early cancerous skin changes. PDT induces cell death through the production of reactive oxygen species (ROS). Cyclobutane pyrimidine dimers (CPDs) are the most important DNA changes responsible for ultraviolet (UV) carcinogenesis. Recently ROS induced by UVA were shown to generate CPDs via activating melanin. This raised the possibility that PDT induced ROS may also induce CPDs and mutagenesis in melanin containing cells. Previously the effect of PDT on CPDs in melanin containing cells has not been assessed. Our current work aimed to compare the generation of CPDs in melanin containing cells subjected to UVA treatment and porfimer sodium red light PDT. We used ELISA to detect CPDs. After UVA we found a dose dependent increase in CPDs in melanoma cells (B16-F10, MNT-1) with CPD levels peaking hours after discontinuation of UVA treatment. This indicated the generation of UVA induced dark-CPDs in the model. Nevertheless, PDT in biologically relevant doses was unable to induce CPDs. Our work provides evidence for the lack of CPD generation by PDT in melanin containing cells.
Topics: DNA Damage; Dihematoporphyrin Ether; Enzyme-Linked Immunosorbent Assay; Humans; Melanins; Melanocytes; Melanoma; Photochemotherapy; Photosensitizing Agents; Pyrimidine Dimers; Ultraviolet Rays
PubMed: 29702258
DOI: 10.1016/j.pdpdt.2018.04.018 -
Acta Oto-laryngologica Aug 2014Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS)....
CONCLUSION
Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments.
OBJECTIVES
The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer.
METHODS
We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs.
RESULTS
The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice.
Topics: Adult; Aged; Aged, 80 and over; Early Diagnosis; Female; Follow-Up Studies; Humans; Laryngeal Neoplasms; Male; Mesoporphyrins; Middle Aged; Neoplasm Staging; Photochemotherapy; Photosensitizing Agents; Retrospective Studies; Survival Rate; Sweden; Treatment Outcome
PubMed: 24856450
DOI: 10.3109/00016489.2014.906748 -
Lasers in Surgery and Medicine Jul 2018The goal of this study was to compare tumor response to Photofrin photodynamic therapy using intravenous and intratumoral injection of photosensitizer. Systemic skin...
Photofrin photodynamic therapy with intratumor photosensitizer injection provides similar tumor response while reducing systemic skin photosensitivity: Pilot murine study.
OBJECTIVES
The goal of this study was to compare tumor response to Photofrin photodynamic therapy using intravenous and intratumoral injection of photosensitizer. Systemic skin photosensitivity and photosensitizer distribution were also compared between the two delivery methods.
METHODS
SCCVII tumors were initiated in the hind legs of female C3H mice and grown to a volume of ∼1,000 mm . Photofrin was delivered intravenously via the tail vein at a concentration of 2 mg/kg or intratumorally at concentrations ranging from 0.5-2 mg/kg. A 630 nm laser illumination was delivered via interstitial diffuser placement at a fluence rate of 400 mW/cm and fluence of 100 J/cm. Mice were maintained under normal room lighting for 24 hours after treatment, at which point photographs were captured for assessment of skin photosensitivity. Animals were then sacrificed, and their tumors were excised, sectioned, imaged, and stained with hematoxylin and eosin (H&E). H&E slides were imaged to assess necrosis post-PDT, and skin photographs were evaluated by two blinded reviewers for quantification of skin photosensitivity. Whole-body fluorescence imaging was performed before and after photodynamic therapy.
RESULTS
Tumor necrosis was not significantly different based on treatment group (P = 0.33), while skin photosensitivity was significantly reduced in animals that received Photofrin intratumorally (P = 0.0005). Fluorescence imaging revealed similar photosensitizer fluorescence in excised tumors for intratumor and intravenous injection of Photofrin (P = 0.48), although fluorescence decreased significantly with decreasing intratumor injection concentration (P= 0.01).
CONCLUSIONS
This pilot study shows that intratumoral administration of Photofrin has the potential to produce similar tumor outcomes, while reducing systemic skin photosensitivity. Further studies are warranted to characterize and optimize intratumor delivery. Lasers Surg. 50:476-482, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Dihematoporphyrin Ether; Disease Models, Animal; Female; Injections, Intralesional; Injections, Intravenous; Mice; Mice, Inbred C3H; Photochemotherapy; Photosensitizing Agents; Skin
PubMed: 29214668
DOI: 10.1002/lsm.22774 -
International Journal of Molecular... Feb 2015Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile...
Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980's. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step.
Topics: Carcinoma; Dihematoporphyrin Ether; Endoscopy, Gastrointestinal; Gastrointestinal Neoplasms; Humans; Japan; Lasers; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 25690028
DOI: 10.3390/ijms16023434 -
Gastrointestinal Endoscopy Jun 2016Photodynamic therapy (PDT) is a less-invasive salvage treatment option for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell...
BACKGROUND AND AIMS
Photodynamic therapy (PDT) is a less-invasive salvage treatment option for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma. The objective of this study was to clarify the long-term outcomes and prognostic factors of salvage PDT.
METHODS
One hundred thirteen consecutive patients treated in our institution with PDT for local failure limited to within T2 without any metastases after definitive CRT performed between 1998 and 2008 were retrospectively enrolled. The complete response rate, adverse events, and survival outcomes were assessed and prognostic factors were investigated using a multivariate analysis.
RESULTS
The complete response rate was 58.4% (95% confidence interval [CI], 49.3%-67.5%). The progression-free survival (PFS) and the overall survival (OS) rates at 5 years after salvage PDT were 22.1% (95% CI, 14.3%-30.0%) and 35.9% (95% CI, 26.7%-45.1%). N0 before CRT was significantly associated with OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91, P = .020), whereas the impact of T1 or T2 before CRT on PFS (HR, 0.63; 95% CI, 0.38-1.04, P = .068) and that of a longer period between CRT and PDT on OS (HR, 0.64; 95% CI, 0.39-1.05, P = .078) were marginal. The treatment-related death rate was 1.8%.
CONCLUSIONS
Salvage PDT was found to have a superior outcome and a satisfactory safety profile. An earlier clinical stage before CRT and a longer interval between CRT and PDT may be associated with a longer survival period.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Dihematoporphyrin Ether; Disease-Free Survival; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Photochemotherapy; Photosensitizing Agents; Proportional Hazards Models; Retrospective Studies; Salvage Therapy; Survival Rate; Treatment Failure; Treatment Outcome
PubMed: 26608125
DOI: 10.1016/j.gie.2015.11.016 -
Photochemistry and Photobiology Jul 2017This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [ O ] , to predict local control rate (LCR) for... (Comparative Study)
Comparative Study
This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [ O ] , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm ) and in-air fluence rates (50-150 mW cm ) at Photofrin dosages of 5 and 15 mg kg and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [ O ] and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [ O ] were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [ O ] ≥ 1.1 mm or PDT dose ≥1200 μm J cm but cannot be predicted with fluence alone. LCR increases with increasing [ O ] and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [ O ] outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.
Topics: Animals; Dihematoporphyrin Ether; Dose-Response Relationship, Drug; Female; Fibrosarcoma; Mice, Inbred C3H; Neoplasms, Radiation-Induced; Photochemotherapy; Photosensitizing Agents; Singlet Oxygen
PubMed: 28083883
DOI: 10.1111/php.12719 -
Photochemistry and Photobiology Mar 2020Explicit dosimetry of treatment light fluence and implicit dosimetry of photosensitizer photobleaching are commonly used methods to guide dose delivery during clinical...
Explicit dosimetry of treatment light fluence and implicit dosimetry of photosensitizer photobleaching are commonly used methods to guide dose delivery during clinical PDT. Tissue oxygen, however, is not routinely monitored intraoperatively even though it is one of the three major components of treatment. Quantitative information about in vivo tissue oxygenation during PDT is desirable, because it enables reactive oxygen species explicit dosimetry (ROSED) for prediction of treatment outcome based on PDT-induced changes in tumor oxygen level. Here, we demonstrate ROSED in a clinical setting, Photofrin-mediated pleural photodynamic therapy, by utilizing tumor blood flow information measured by diffuse correlation spectroscopy (DCS). A DCS contact probe was sutured to the pleural cavity wall after surgical resection of pleural mesothelioma tumor to monitor tissue blood flow (blood flow index) during intraoperative PDT treatment. Isotropic detectors were used to measure treatment light fluence and photosensitizer concentration. Blood-flow-derived tumor oxygen concentration, estimated by applying a preclinically determined conversion factor of 1.5 × 10 μMs cm to the blood flow index, was used in the ROSED model to calculate the total reacted reactive oxygen species [ROS]rx. Seven patients and 12 different pleural sites were assessed and large inter- and intrapatient heterogeneities in [ROS]rx were observed although an identical light dose of 60 J cm was prescribed to all patients.
Topics: Animals; Dihematoporphyrin Ether; Humans; Mice; Photochemotherapy; Photosensitizing Agents; Pleural Neoplasms; Reactive Oxygen Species; Xenograft Model Antitumor Assays
PubMed: 31729774
DOI: 10.1111/php.13176