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Journal of Biomedical Optics Aug 2016Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account...
Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates ( ? ). A macroscopic model was adopted to evaluate using calculated reacted singlet oxygen concentration ( [ O 2 1 ] rx ) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma tumors, as singlet oxygen is the primary cytotoxic species responsible for cell death in type II PDT. Using a combination of fluences (50, 135, 200, and 250 ?? J / cm 2 ) and ? (50, 75, and 150 ?? mW / cm 2 ), tumor regrowth rate, k , was determined for each condition. A tumor cure index, CI = 1 ? k / k control , was calculated based on the k between PDT-treated groups and that of the control, Available on the SPIE Digital Library.
Topics: Animals; Dihematoporphyrin Ether; Female; Mice; Mice, Inbred C3H; Models, Biological; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Radiation Dosage; Singlet Oxygen; Xenograft Model Antitumor Assays
PubMed: 27552311
DOI: 10.1117/1.JBO.21.8.088002 -
Photochemistry and Photobiology Mar 2017In prior studies, we have identified the ability of low-level lysosomal photodamage to potentiate the phototoxic effect of subsequent photodamage to mitochondria. The...
In prior studies, we have identified the ability of low-level lysosomal photodamage to potentiate the phototoxic effect of subsequent photodamage to mitochondria. The mechanism involves calpain-mediated cleavage of the autophagy-associated protein ATG5 to form a proapoptotic fragment (tATG5). In this report, we explore the permissible time lag between the two targeting procedures along with the effect of simultaneously targeting both lysosomes and mitochondria. This was found to be as effective as the sequential protocol with no gap between the irradiation steps. Inhibition of calpain reversed the enhanced efficacy of the "simultaneous" protocol. It appears that even a minor level of lysosomal photodamage can have a significant effect on the efficacy of subsequent mitochondrial photodamage. We propose that these results may explain the efficacy of Photofrin, a photosensitizing product that also targets both lysosomes and mitochondria for photodamage.
Topics: Animals; Autophagy-Related Protein 5; Cell Line, Tumor; Dihematoporphyrin Ether; Light; Lysosomes; Mice; Mitochondria; Photochemotherapy; Photosensitizing Agents; Spectrum Analysis
PubMed: 27935055
DOI: 10.1111/php.12692 -
Photochemistry and Photobiology Jan 2019Inflammatory cells, most especially neutrophils, can be a necessary component of the antitumor activity occurring after administration of photodynamic therapy....
Inflammatory cells, most especially neutrophils, can be a necessary component of the antitumor activity occurring after administration of photodynamic therapy. Generation of neutrophil responses has been suggested to be particularly important in instances when the delivered photodynamic therapy (PDT) dose is insufficient. In these cases, the release of neutrophil granules and engagement of antitumor immunity may play an important role in eliminating residual disease. Herein, we utilize in vivo imaging of luminol chemiluminescence to noninvasively monitor neutrophil activation after PDT administration. Studies were performed in the AB12 murine model of mesothelioma, treated with Photofrin-PDT. Luminol-generated chemiluminescence increased transiently 1 h after PDT, followed by a subsequent decrease at 4 h after PDT. The production of luminol signal was not associated with the influx of Ly6G cells, but was related to oxidative burst, as an indicator of neutrophil function. Most importantly, greater levels of luminol chemiluminescence 1 h after PDT were prognostic of a complete response at 90 days after PDT. Taken together, this research supports an important role for early activity by Ly6G cells in the generation of long-term PDT responses in mesothelioma, and it points to luminol chemiluminescence as a potentially useful approach for preclinical monitoring of neutrophil activation by PDT.
Topics: Animals; Biomarkers; Dihematoporphyrin Ether; Luminescence; Luminol; Mesothelioma; Mice; Mice, Inbred BALB C; Neutrophil Activation; Neutrophils; Photochemotherapy; Photosensitizing Agents; Prognosis
PubMed: 30357853
DOI: 10.1111/php.13040 -
Redox Biology Dec 2015Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast,...
Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling.
Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2(.)) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling.
Topics: Animals; Apoptosis; Caspase 8; Catalase; Cell Line; Cell Line, Tumor; Dihematoporphyrin Ether; Enzyme Inhibitors; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Hydrogen Peroxide; Hypochlorous Acid; Light; Metalloporphyrins; Mice; NADPH Oxidases; Nitric Oxide; Peroxynitrous Acid; Photosensitizing Agents; Signal Transduction; Singlet Oxygen; Sulfones; Taurine; fas Receptor
PubMed: 26225731
DOI: 10.1016/j.redox.2015.07.006