Photodynamic Therapy for Head and Neck Cancer Xenografts in Athymic Mice

1986 ◽  
Vol 95 (5) ◽  
pp. 602-606 ◽  
Author(s):  
James H. Hill ◽  
Randall L. Plant ◽  
David M. Harris ◽  
Randal C. Paniello

This study examines efficacy and optimal treatment variables of photodynamic therapy (PDT) for human head and neck squamous cancer (HNSC) xenografts in athymic mice. Two and four days after injection of hematoporphyrin derivative (HPD), tumors were illuminated with red light from an argon-dye laser. Sixty-three tumors were treated. With HPD dose and light intensity constant at 7.5 mg/kg and 100 mW/cm2, respectively, the extent of tumor necrosis was strongly dependent on duration of light exposure. There was no substantial difference in results for 30- and 60-minute treatment durations between animals injected with HPD 2 and 4 days before treatment. After 30 minutes treatment time, responses were seen in 8 of 10 mice (2 days post-HPD) and 11 of 12 mice (4 days post-HPD). After 60 minutes treatment time, toxicity was high. We conclude that, in this model, PDT is effective in selective killing of HNSC. For future comparison studies in this model, if the indicated HPD dose and light intensity are used we recommend a 2-day delay after HPD injection and a light exposure duration of 30 minutes

2012 ◽  
Vol 288 (1) ◽  
pp. 677-686 ◽  
Author(s):  
Hsin-I Hung ◽  
Justin M. Schwartz ◽  
Eduardo N. Maldonado ◽  
John J. Lemasters ◽  
Anna-Liisa Nieminen

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Stefania Romeo ◽  
Daniela Di Camillo ◽  
Alessandra Splendiani ◽  
Marta Capannolo ◽  
Cristina Rocchi ◽  
...  

Recent data indicates that prolonged bright light exposure of rats induces production of neuromelanin and reduction of tyrosine hydroxylase positive neurons in thesubstantia nigra. This effect was the result of direct light reaching thesubstantia nigraand not due to alteration of circadian rhythms. Here, we measured the spectrum of light reaching thesubstantia nigrain rats and analysed the pathway that light may take to reach this deep brain structure in humans. Wavelength range and light intensity, emitted from a fluorescent tube, were measured, using a stereotaxically implanted optical fibre in the rat mesencephalon. The hypothetical path of environmental light from the eye to thesubstantia nigrain humans was investigated by computed tomography and magnetic resonance imaging. Light with wavelengths greater than 600 nm reached the ratsubstantia nigra, with a peak at 709 nm. Eyes appear to be the gateway for light to the mesencephalon since covering the eyes with aluminum foil reduced light intensity by half. Using computed tomography and magnetic resonance imaging of a human head, we identified the eye and the superior orbital fissure as possible gateways for environmental light to reach the mesencephalon.


1988 ◽  
Vol 99 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Sherman A. Sprik ◽  
Michael J. Sullivan ◽  
Thomas E. Carey

In vitro experiments were performed to evaluate the direct cytotoxic and photosensitizing effects of dihematoporphyrin-ether (DHE) on the head and neck squamous cancer cell line, UM-SCC-38. Normal fibroblasts, normal cultured keratinocytes, and the UM-MEL-1 pigmented malignant melanoma cell line were used as controls. The parameters of duration of light exposure, drug concentration, and incubation periods were studied. Uptake of DHE by squamous cancer cells, as assessed microscopically by intensity of fluorescence, was rapid and reached a dose-dependent maximum intensity within 10 minutes. Cells were irradiated with polychromatic light with an energy of one milliwatt/cm2 at a distance of 1.5 ft. Cells growing in plastic dishes were incubated in the dark for 1 to 4 hours with DHE in concentrations that ranged from 1.25 to 50 μg/ml. The cell monolayers were washed and irradiated for periods of time ranging from 15 to 120 min. Dose-dependent loss of cell viability could be detected by trypan blue dye uptake as early as 1 hour after radiation and continued to increase until 4 hours after light exposure. No further loss of cell viability was observed over the next 10 hours. There was no phototoxicity in the absence of DHE. UM-SCC-38 cells were more sensitive to the photosensitizing effects of DHE than were either normal fibroblasts or malignant melanoma cells. Recovery from the photosensitizing effects of DHE was observed if the DHE-containing medium was removed and the cells were incubated in the dark for periods that ranged from 1 to 14 hours before light exposure. UM-SCC-38 cells recovered more rapidly than normal fibroblasts, normal keratinocytes, or UM-MEL-1 cells.


2009 ◽  
Vol 53 (9) ◽  
pp. 3929-3934 ◽  
Author(s):  
Tianhong Dai ◽  
George P. Tegos ◽  
Zongshun Lu ◽  
Liyi Huang ◽  
Timur Zhiyentayev ◽  
...  

ABSTRACT Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.


2001 ◽  
Vol 5 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Faten Gad ◽  
Gilles Viau ◽  
Michele Bousbira ◽  
Richard Bertrand ◽  
Robert Bissonnette

Background: Preliminary studies have suggested that photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) can improve psoriasis and mycosis fungoides, two diseases where normal or malignant T cells play a central role. Objectives: To determine if ALA-PDT induces apoptosis and caspase activation in Jurkat cells, a malignant T-cell line. Methods: Jurkat cells were incubated with ALA in the presence of [14C]-thymidine followed by red light exposure. DNA fragmentation was measured 24 hours later with a DNA elution assay. The influence on DNA fragmentation of ALA concentration, time between ALA addition and light exposure, as well as light fluence were studied. The occurrence of oligonucleosome-sized DNA fragmentation was also studied with DNA electrophoresis. Caspase-3-like activity was monitored by measuring Ac-DEVD-AMC hydrolysis. Results: DNA fragmentation as high as 88% was observed 24 hours after ALA-PDT. The percentage of DNA fragmentation increased with increasing doses of ALA, red light fluence, as well as longer incubation time with ALA. DNA fragmentation was observed as early as 3 hours after ALA-PDT. The presence of apoptosis after ALA-PDT was confirmed by DNA electrophoresis. An increase in caspase-3-like activities was detected following ALA-PDT. Conclusion: ALA-PDT induces apoptosis and caspase-3-like activation in Jurkat cells.


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