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The immunomodulatory effects of photodynamic therapy (PDT) have been reported in several photosensitizers. Pheophorbide a (Pa), a chlorophyll derivative, shows antitumor effects on a number of human...Full Text Available
Full Text Available.The immunomodulatory effects of photodynamic therapy (PDT) have been reported in several photosensitizers. Pheophorbide a (Pa), a chlorophyll derivative, shows antitumor effects on a number of human cancers in a PDT approach (Pa-PDT); however, the potential effect of Pa-PDT on the anticancer immunity has never been studied. In the present work, the underlying action mechanism of Pa-PDT was systemically investigated with a human hepatoma cell line HepG2. We found that Pa-PDT significantly inhibited the growth of HepG2 cells with a half maximal inhibitory concentration/endoplasmic reticulum of 0.35 µM at 24 hours by the induction of apoptosis, as shown by externalization of phosphatidylserine, release of mitochondrial cytochrome c, and activation of the caspases cascade in the treated cells. Interestingly, using two-dimensional polyacrylamide gel electrophoresis analysis, a 57-kDa disulfide-isomerase-like ER resident protein (ERp57) that belongs to the HLA class I-restricted antigen-processing machinery was found to be mediated during the Pa-PDT treatment. This activation of antigen presentation was confirmed by Western blot analysis and immunostaining. Furthermore, a cross-presentation of antigen with HLA class I proteins and 70-kDa heat shock protein was found in Pa-PDT-treated cells, as shown by the confocal microscopic observation and immunoprecipitation assay. Nevertheless, the immunogenicity of HepG2 cells was increased by Pa-PDT treatment that triggered phagocytic capture by human macrophages. Our findings provide the first evidence that Pa-PDT can trigger both apoptosis and cancer immunity in the tumor host.
2001-01-01
Radical tumor resection is the basis for prolonged survival of patients suffering from malignant brain tumors such as glioblastoma multiform. We have carried out a phase II study involving 22 patients with malignant brain tumors to assess the feasibility and the effectiveness of the combination of intraoperative photodynamic diagnosis (PDD) and fluorescence-guided resection (FGR) mediated by the second generation photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). In addition, intraoperative photodynamic therapy (PDT) was performed. Several commercially available fluorescence diagnostic systems were investigated for their applicability for clinical practice. We have adapted and optimized a diagnostic system which includes a surgical microscope, an excitation light source (filtered to 370-440 nm), a video camera detection system, and a ... >>
http://eprints.qut.edu.au/5764/
This paper gives a brief review of methods that assess objectively function in age-related maculopathy (ARM) with emphasis on a newer method, the multifocal electroretinogram (mfERG). In contrast to other electrophysiological tests, such as the full-field and focal electroretinogram (ERG) or the electro-oculogram (EOG), which measure summed responses from various cells from larger areas of the retina, the multifocal electroretinogram maps function locally with a resolution as small as four degrees within the central 30 degrees. By using different paradigms it can measure local cone- and rod-mediated functional impairment at early and late stages of ARM. This improved mapping and higher resolution of the posterior pole compared to other objective methods might lead to earlier detection of ARM. Its usefulness has been demonstrated in documenting the effects of treatment after established laser treatments, such as photodynamic therapy (PDT) and in documenting function after retinal pigment epithelial transplantation, a possible future treatment in late neovascular ARM. Publisher: Optometrists Association Australia Relation: Feigl, Beatrix and Lovie-Kitchin, Jan E. and Brown, Brian (2005) Objective functional assessment of age-related maculopathy: a special application for the multifocal electroretinogram. Clinical and Experimental Optometry, 88(5). pp. 304-312. Format: application/pdf Rights: Copyright 2005 Optometrists Association Australia; The contents of this journal from 1998 to 2005 can be freely accessed online via the journalâs web page (see link).
http://eprints.qut.edu.au/16026/
Age-related maculopathy (ARM) is a central retinal disease with unclear pathogenesis. It is the major cause of permanent vision loss in adults over 50 years and is increasing in prevalence and incidence, faster than the aging population would suggest. Early in the disease process (early ARM) there is little or no vision loss and there are only slight retinal changes with abnormal deposits within Bruch's membrane. As the disease progresses (late ARM or age-related macular degeneration, AMD) vision loss may be quite severe due to atrophy (dry AMD) or the development of chorioretinal neovascularisation (CNV, wet AMD). It is hard to predict from conventional eye examinations and clinical vision tests which cases will progress to the severe, dry or wet forms of the disease. Moreover, most of the conventional clinical tests are based upon subjective vision measures. Objective tests which detect ARM earlier would be a useful aid to diagnosis and to monitoring progression. The multifocal electroretinogram (mfERG) is a relatively new clinical tool which enables the recording of electrical potentials from multiple, small areas of the central retina and thus assesses function from specific retinal locations. It is therefore useful in detecting focal retinal diseases such as hereditary or acquired maculopathies or in monitoring retinal laser or surgical treatment effects. There is cone and rod impairment in ARM and histopathological and psychophysical evidence for a preferential vulnerability of rods compared to cones. This research project investigated if an objective tool such as the mfERG could detect early ARM,its progression and the treatment effects of multiple photodynamic therapies (PDT) on retinal function in late ARM, prior to a battery of subjective vision measures. For comparison purposes a subjective assessment of central retinal function was performed using high and low contrast distance visual acuities (VA), near VA, low luminance VA (SKILL cards), contrast sensitivity (Pelli-Robson, P-R), saturated and desaturated Panel D-15 (sat Panel D-15, desat Panel D-15) and central visual fields (Humphrey 10-2, mean sensitivity, MS and mean defects, MD). As an objective assessment of central retinal function the cone- and rod-mediated multifocal electroretinograms were recorded. Subjective and objective tests of retinal function were compared in early ARM and an age-matched control group (chapter 3). Seventeen eyes of seventeen subjects with early ARM and twenty control subjects with normal vision were measured. For the cone-mediated mfERG responses conventional averaging methods were used and results were correlated with subjective vision tests. The conventional cone-mediated mfERG failed to distinguish between the early ARM and control subjects whereas subjective vision measures such as HC- and LC-VA, desat Panel D-15, MS, P-R were significantly reduced in the ARM group. However, there were significant correlations between the cone-mediated mfERG and the desat Panel D-15 results in the ARM group. This suggests that the mfERG measures similar retinal processes that detect colour vision deficiency under desaturated conditions. There was no significant correlation between cone-mediated mfERG measures and funduscopic changes. The conclusion from this study was that the subjective vision tests detected early ARM better than the objective cone-mediated mfERG. Thus the aim of detecting early ARM objectively was not met by the cone-mediated mfERG suggesting the need to develop other objective tests such as a rod-mediated mfERG. Whether the preferential rod vulnerability others have reported in early ARM could be detected by the rod-mediated mfERG was determined in the next study (chapter 4). A protocol for recording rod-mediated mfERG responses was developed by determining the optimal testing luminance to reduce the effect of stray light and elicit maximal rod-mediated responses. Sixteen of the seventeen ARM subjects and seventeen control subjects from the previous study were tested. For analysis, a customized computer template fitting method was developed in MATLAB (Mathworks, Natick, MA, USA). This method has been shown to be useful for low signal-to-noise ratio responses that characterize the rod-mediated mfERG. Significantly delayed rod-mediated mfERG responses were found whereas cone-mediated mfERG responses were within the normal range. This suggested that the effect of ARM on the rod system could be detected objectively with the rod-mediated mfERG before changes in the cone-mediated mfERG. Which of the tests best detected progression of vision loss was investigated in chapter 5. Visual function of 26 (13 ARM and 13 control subjects) of the original 37 subjects (17 ARM and 20 control subjects) had cone- and rod-mediated mfERG and the subjective vision measures repeated after one year. The main purpose was to determine which of the tests best detected progression of vision loss. The mfERG results were analysed by using both averaged and local responses and by using the computer template fitting procedure. On average no significant worsening of either objective or subjective function measures was evident after one year. These results reinforce the slow progression of the disease. With a longer follow-up period progression of ARM may translate into measurable changes in the mfERG and the other visual function tests. The effect of multiple photodynamic therapies (PDT) on cone- and rod-mediated function was assessed with the mfERG in the last study (chapter 6). The cumulative treatment effects of PDT in five subjects with late ARM were determined. Having demonstrated that the rod-mediated mfERG was applicable in early ARM, this study also aimed to investigate how useful it was in late ARM where there is substantially greater rod loss. Cone- and rod-mediated mfERGs, visual acuities, contrast sensitivities and central visual fields were investigated a week before treatment began and then one month after each PDT treatment. The subjects received three treatments each over an average period of five and a half months. In some subjects there were significant transient reductions in cone- and rod-mediated amplitudes possibly reflecting alterations in choroidal hypoperfusion dynamics one month after treatment. Further, b-wave component of the mfERG became increasingly misshapen after each PDT treatment suggesting an ischemic insult mainly targeting post-receptoral sites. However, objective and subjective function was stabilized after multiple PDT treatments in most of the subjects. This pilot study of five cases showed that there was no additional damage to cone- and rod-mediated outer retinal function after three PDT treatments. One of the novel findings of this research was that the rod-mediated function measured with the mfERG was impaired in early ARM. This finding supports histopathological and psychophysical evidence of rod vulnerability in early ARM. The results of these studies also suggest that early ARM affects different aspects of visual function which is reflected by different outcomes from objective and subjective vision tests. A model (chapter 7) based upon the results was developed proposing a hypoxic insult with a preferential alteration of post-receptoral sites in early ARM. The cone-mediated mfERG documented the retinal damage and possible treatment effects on outer retinal function of the multiple PDTs which did not further deteriorate. Thus, this technique might assist in the development of optimal treatment modalities for ARM, especially in retreatment regimes. Greater variability was found for the rod-mediated mfERG and its clinical use in PDT treatment regimes still needs to be investigated. In conclusion, this research has provided a better understanding of the disease process and treatment effects in ARM and might contribute to improvements in diagnosis and treatment of ARM. Publisher: Queensland University of Technology Relation: Feigl, Beatrix Karoline (2005) Age-related Maculopathy: A Multifocal Approach. [QUT Thesis] Format: application/pdf Rights: Copyright Beatrix Karoline Feigl
http://eprints.qut.edu.au/12535/
Aim: To study the cumultative effect of laser treatments with photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) on retinal function in eyes with age–related macular degeneration (AMD). Methods: Seven eyes of seven AMD subjects were investigated before and 4 weeks after each laser treatment during a follow up period of 6 months. Three eyes underwent three PDT treatments and two eyes underwent two PDT treatments. One eye was treated with two TTTs and another eye underwent one PDT and one TTT. We studied subjective macular function by testing visual acuities (VA), central visual fields (VF), contrast sensitivity (Pelli–Robson) and colour vision (sat–D15) as well as cone– and rod–mediated mfERGs (VERIS). The mfERG stimulus for the cones consisted of 103 scaled hexagons and we used the conventional method for deriving the responses. For the rod–mediated mfERG we used a 61 hexagon unscaled stimulus with 3 blank frames, a Wratten 47B filter and reduced the luminance and stray light influence by adding a neutral density filter (1.5 ND) and a surround respectively. For analysis of the mfERG amplitude and implicit time a computer fitting method was applied (Matlab). We compared each of the 103 and 61 local first–order kernel mfERG responses after treatment with those before treatment. Results:Four eyes showed stabilisation in some of the vision measures and three eyes showed impairment in all the psychophysical tests after the second treatment. This was significantly reflected in the cone–mediated mfERG in two eyes (p<0.01). Cone–mediated mfERG function significantly deteriorated in three eyes (p<0.01), improved in one (p<0.01) and remained stable in three eyes after all treatments. Rod–mediated function was significantly impaired in only one eye (p=0.02) and did not show any further deterioration in the other eyes after two treatments. Both eyes treated with TTT showed a significant cone–mediated amplitude reduction greater than 40% which was reflected in reduced subjective function tests in only one eye. Data collection is continuing. Conclusion:Consistent with previous studies with the mfERG after one PDT treatment, subjective and objective function measured by the mfERG appears to be stabilized after multiple PDT treatments. Similarly rod–mediated function seems not to be further compromised. In contrast TTT treated eyes showed greater cone–mediated functional deficits. Publisher: The Association for Research in Vision and Ophthalmology (ARVO) Relation: Feigl, Beatrix and Brown, Brian and Lovie-Kitchin, Jan E. and Swann, Peter G. and Lee, Lawrence (2004) Coneâ and rodâmediated retinal function before and after multiple laser therapies in ageârelated macular degeneration. In: Annual meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, USA. Rights: Copyright 2004 The Association for Research in Vision and Ophthalmology (ARVO)
http://eprints.qut.edu.au/12436/
PURPOSE: To monitor retinal function after multiple laser treatments by photodynamic therapy (PDT) with the multifocal electroretinogram (mfERG) in age-related macular degeneration (AMD). METHODS: Five eyes of five subjects with AMD were investigated before the first and 1 month after each of three PDT treatments. Function was assessed using the cone- and rod-mediated mfERG, high-contrast distance visual acuity, central visual fields and contrast sensitivity. For each subject the local first-order mfERG results before treatment were used as a template and fitted against the local post-treatment results (Matlab, Mathworks). RESULTS: We found transient reduction of the cone- and rod-mediated amplitudes between the first and second treatments but stable or improved mfERG function in four of five eyes for the cone-mediated mfERG and in all eyes for the rod-mediated mfERG after three treatments. Visual acuities and contrast sensitivities remained stable between treatments in four and two eyes respectively, whereas visual fields showed substantially higher mean defects in two subjects after all treatments. CONCLUSION: As found in previous studies of the cone-mediated mfERG after one PDT treatment, objective function was stabilized after multiple treatments in this case report. Similarly, although poor at baseline, rod-mediated function was not further compromised. Transiently reduced amplitudes after 1 month possibly reflected choroidal hypoperfusion. A larger sample size is needed to confirm if additional evaluation using electrophysiological criteria might be helpful in re-treatment decisions during PDT. Publisher: Springer Relation: DOI:10.1007/s10633-005-5319-7; Feigl, Beatrix and Brown, Brian and Lovie-Kitchin, Jan E. and Lee, Lawrence (2005) Dynamics of retinal function after multiple photodynamic therapies in age-related macular degeneration: a report of cases. Documenta Ophthalmologica, 111(3). pp. 135-148. Rights: Copyright 2005 Springer; The original publication is available at SpringerLink http://www.springerlink.com
http://eprints.jcu.edu.au/6661/1/6661_Maharaj_2005.pdf
Melatonin, a naturally occurring chemical mediator, although assigned a diverse range of functions, has attracted interest in recent years because of its ability to function as a free radical scavenger. Because of the implications of singlet oxygen in neurotoxicity, the objective of the study was to investigate the ability of melatonin to quench singlet oxygen generated using laser irradiation or lamp photolysis. The results show that melatonin produces radicals upon laser irradation while the lamp photolysis studies show that melatonin is able to scavenge singlet oxygen produced by naphthalene. While melatonin is a free radical scavenger under biological conditions, it acts as a generator of singlet oxygen and or radicals (as ΦΔ is 1.41) when irradiated with laser light, implying that it has the potential to be used in photodynamic therapy in the destruction of tumors. Publisher: Wiley-Blackwell Format: application/pdf Other identifier: Maharaj, D.S., Molell, H., Antunes, E.M., Maharaj, H., Maree, D.M., Nyokong, T., Glass, B.D., and Daya, S. (2005) Melatonin generates singlet oxygen on laser irradiation but acts as a quencher when irradiated by lamp photolysis. Journal of Pineal Research, 38 (3). pp. 153-156. ISSN 1600-079X
Transperineal in vivo fluence-rate dosimetry in the canine prostate during SnET2-mediated PDT
2004-01-01
Advances in photodynamic therapy (PDT) treatment for prostate cancer can be achieved either by improving selectivity of the photosensitizer towards prostate gland tissue or improving the dosimetry by means of individualized treatment planning using currently available photosensitizers. The latter approach requires the ability to measure, among other parameters, the fluence rate at different positions within the prostate and the ability to derive the tissue optical properties. Here fibre optic probes are presented capable of measuring the fluence rate throughout large tissue volumes and a method to derive the tissue optical properties for different volumes of the prostate. The responsivity of the sensors is sufficient to detect a fluence rate of 0.1 mW cm-2. The effective attenuation coefficient in the canine prostate at 660 nm is higher at the capsule ... >>
The preparation of radiolabelled porphyrins and their use in studies of photodynamic therapy
1987-01-01
The use of radiolabelled HpD and DHE has potential importance in studies of the mechanism of localisation of these compounds in tumours and their mode of action in promoting light-mediated cell damage. A number of methods of preparation of radiolabelled HpD and its components have been investigated. In a novel approach, we have developed methods for producing 14C- or 3H- labelled protoporphyrin from photosynthetic algae. In this way haematoporphyrin and HpD can be produced with much higher specific radioactivity than has hitherto been available. We are using this radiolabelled material in several studies relating to PDT. One application has been the precise determination of the molar absorption coefficient of DHE (and other components of HpD) based on the fact that is specific radioactivity per porphyrin unit must be identical to that of the ... >>
The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances
2008-01-01
Photodynamic therapy (PDT) is a promising modality for the treatment of both pre-malignant and malignant lesions. The mechanism of action converges mainly on the generation of reactive oxygen species which damage cancer cells directly as well as indirectly acting on tumor vasculature. The exact mechanism of PDT action is not fully understood, which is a formidable barrier to its successful clinical application. Elucidation of the mechanisms of cancer cell elimination by PDT might help in establishing highly specific, non-genotoxic anti-cancer treatment of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor p53 protein recognized as the guardian of the genome. Together with its family members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress stimuli. The wild-type and mutant p53-targeting chemotherapeutics are ... >>
1990-07-01
The effect on normal skin of combined modality treatment with 300 kV X-rays and photodynamic therapy (PDT) using the photosensitising drug meso-tetra (sulphonatophenyl) porphine (TPPS) was studied using the mouse tail necrosis assay. Prior treatment with a tolerance dose of PDT produced a significant increase in the probability of necrosis following graded doses of ionising radiation. A tolerance dose of X-rays administered prior to graded doses of PDT also produced a significant rise in the necrosis rate. TPPS appeared to have a radiosensitising effect but, as the animals were kept in subdued light, the low dose of PDT they therefore received may provide an alternative explanation. The effect of prolonging the interval between the modalities on the necrosis rate did not appear to be related to the time course of either the changes in blood flow produced by each modality, measured by zenon clearance studies or the development of the skin reaction following X-ray irradiation. (author).
1990-01-01
The effect on normal skin of combined modality treatment with 300 kV X-rays and photodynamic therapy (PDT) using the photosensitising drug meso-tetra (sulphonatophenyl) porphine (TPPS) was studied using the mouse tail necrosis assay. Prior treatment with a tolerance dose of PDT produced a significant increase in the probability of necrosis following graded doses of ionising radiation. A tolerance dose of X-rays administered prior to graded doses of PDT also produced a significant rise in the necrosis rate. TPPS appeared to have a radiosensitising effect but, as the animals were kept in subdued light, the low dose of PDT they therefore received may provide an alternative explanation. The effect of prolonging the interval between the modalities on the necrosis rate did not appear to be related to the time course of either the changes in blood flow produced by each modality, ... >>
Full Text Available.BackgroundPhotodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period.ResultsOur results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux.ConclusionThe combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors.
BackgroundPhotodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength...Full Text Available
1998-02-01
The Medical Applications and Biophysical Research Division of the Office of Biological and Environmental Research supports and manages research in several distinct areas of science and technology. The projects described in this book are grouped by the main budgetary areas: General Life Sciences (structural molecular biology), Medical Applications (primarily nuclear medicine) and Measurement Science (analytical chemistry instrumentation), Environmental Management Science Program, and the Small Business Innovation Research Program. The research funded by this division complements that of the other two divisions in the Office of Biological and Environmental Research (OBER): Health Effects and Life Sciences Research, and Environmental Sciences. Most of the OBER programs are planned and administered jointly by the staff of two or all three of the divisions. This summary book provides information on research supported in these program areas during Fiscal Years 1996 and 1997.
Simultaneous two-photon excitation of photodynamic therapy agents
1998-01-01
The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type 1 and type 2 photodynamic therapy (PDT) agents are examined.
Preparation of radiolabelled porphyrins and their use in studies of photodynamic therapy
1987-11-01
The use of radiolabelled HpD and DHE has potential importance in studies of the mechanism of localisation of these compounds in tumours and their mode of action in promoting light-mediated cell damage. A number of methods of preparation of radiolabelled HpD and its components have been investigated. In a novel approach, we have developed methods for producing /sup 14/C- or /sup 3/H- labelled protoporphyrin from photosynthetic algae. In this way haematoporphyrin and HpD can be produced with much higher specific radioactivity than has hitherto been available. We are using this radiolabelled material in several studies relating to PDT. One application has been the precise determination of the molar absorption coefficient of DHE (and other components of HpD) based on the fact that is specific radioactivity per porphyrin unit must be identical to that of the porphyrin from which it was prepared.
Porphyrin-based Photocatalytic Nanolithography
2009-06-08
Nanoarray fabrication is a multidisciplinary endeavor encompassing materials science, chemical engineering and biology. We form nanoarrays via a new technique, porphyrin-based photocatalytic nanolithography (PCNL). The nanoarrays, with controlled features as small as 200 nm, exhibit regularly ordered patterns and may be appropriate for (a) rapid and parallel proteomic screening of immobilized biomolecules, (b) protein-protein interactions and/or (c) biophysical and molecular biology studies involving spatially dictated ligand placement. We demonstrate protein immobilization utilizing nanoarrays fabricated via PCNL on silicon substrates, where the immobilized proteins are surrounded by a non-fouling polymer background.
2006-01-01
We have developed a series of novel photosensitizers which have potential for anticancer photodynamic therapy (PDT). Photosensitizers include zinc phthalocyanine tetra-sulphonic acid and a family of derivatives with amino acid substituents of varying alkyl chain length and degree of branching. Subcellular localization of these photosensitizers at the phototoxic IC5 concentration in human cervical carcinoma cells (SiHa Cells) was similar to that of the lysosomal dye Lucifer Yellow. Subsequent nuclear relocalization was observed following irradiation with 665 nm laser light. The PDT response was characterized using the Sulforhodamine B cytotoxicity assay. Flow cytometry was used for both DNA cell cycle and dual Annexin V-FITC/propidium iodide analysis. Phototoxicity of the derivatives was of the same order of magnitude as for tetrasulphonated ... >>
1987-01-01
Volume I of this book contains: Basics of Photochemistry; Molecular and Cellular Photobiology; Acute Cutaneous Effects of Light; The Homology of UV-Mediated Cutaneous Carcinogenic and Aging Processes; Effects of Sunlight on the Eye; Photoimmunology; Photosensitivity to Drugs; and Porphyrias. Volume II contains: The Idiopathic Photodermatoses; Xeroderma Pigmentosum; Beta-Carotene Therapy for Erythropoietic Protoporphyria and Other Photosensitivity Diseases; Photochemotherapy of Psoriasis Using the Furocoumrains; Photochemotherapy of Various Skin Disorders; Photodynamic Therapy of Cancer; and Photoimmunotherapy. Volume III of this book contains: The Phthalocyanines: Sensitizers with Potential for Photodynamic Therapy of Cancer; Lasers in Surgery and Medicine; Lasers in Opthalmology; The Carbon Dioxide Laser in Orthopedic Surgery. Diagnostic Uses of Light; Sources and Measurements of Optical Radiation for Medical Applications; and Safety Measures in Optical Radiation Treatment.
1987-01-01
Volume I of this book contains: Basics of Photochemistry. Molecular and Cellular Photobiology. Acute Cutaneous Effects of Light. The Homology of UV-Mediated Cutaneous Carcinogenic and Aging Processes. Effects of Sunlight on the Eye. Photoimmunology. Photosensitivity to Drugs. And Porphyrias. Volume II contains: The Idiopathic Photodermatoses. Xeroderma Pigmentosum. Beta-Carotene Therapy for Erythropoietic Protoporphyria and Other Photosensitivity Diseases. Photochemotherapy of Psoriasis Using the Furocoumrains. Photochemotherapy of Various Skin Disorders. Photodynamic Therapy of Cancer. And Photoimmunotherapy. Volume III of this book contains: The Phthalocyanines: Sensitizers with Potential for Photodynamic Therapy of Cancer. Lasers in Surgery and Medicine. Lasers in Opthalmology. The Carbon Dioxide Laser in Orthopedic Surgery. Diagnostic Uses ... >>
Neutrons in Biology. A satellite meeting of the IUPAB/EBSA biophysics congress
2005-07-01
This meeting focussed on the study of the structure and dynamics of biological molecules, with particular emphasis on neutron and complementary methods as well as related enabling technologies. The program covered biological problems that are being addressed by neutron scattering and those where there is the potential to do so in the future. This document provides the abstracts of the different presentations. (A.L.B.)
Modulation of MHC class-I molecules on melanoma cells after photodynamic treatment
2003-01-01
Full text: Endogenous antigenic peptides are presented in the context of MHC class-I molecules on the cell surface for recognition by CD8+ T lymphocytes. Down-regulation of MHC molecules is a frequently observed strategy of tumor cells to escape immune attack. E.g., B16 melanoma is characterized by extremely low MHC-I surface expression and high tumorigenicity in syngeneic mice. Generally, the efficiency of photodynamic therapy is low for melanotic tumors. On the other hand, PDT has been shown capable of inducing anti-tumoral immunity. Therefore, we investigated the effect of PDT treatment in vitro on the MHC class-I surface expression of surviving B16 cells. When sensitized with 50 ng/mL hypericin and then irradiated the viability of the cells gradually decreased with increasing light dose. However, with 4 J/cm2 50 % of cells were still viable after 24 hours. ... >>
Medical applications of ultra-short pulse lasers
1999-06-08
The medical applications for ultra short pulse lasers (USPLs) and their associated commercial potential are reviewed. Short pulse lasers offer the surgeon the possibility of precision cutting or disruption of tissue with virtually no thermal or mechanical damage to the surrounding areas. Therefore the USPL offers potential improvement to numerous existing medical procedures. Secondly, when USPLs are combined with advanced tissue diagnostics, there are possibilities for tissue-selective precision ablation that may allow for new surgeries that cannot at present be performed. Here we briefly review the advantages of short pulse lasers, examine the potential markets both from an investment community perspective, and from the view. of the technology provider. Finally nominal performance and cost requirements for the lasers, delivery systems and diagnostics and the present state of development will be addressed.
Magnetofullerenosome mediated near-infrared laser therapy of hamster tongue carcinoma
2004-01-01
This study was performed to demonstrate the usefulness of magnetofullerenosomes- a lipidic nanostructures with incorporated fullerenes C60 in their lipid bilayers and co-encapsulated photosensitizer naphthalocyanate and magnetite nanoparticles for the oral cancer combined hyperthermia and photodynamic therapy. Tumors were induced in golden hamster tongue by 9,10-dimethyl 1-1,2- benzanthracene application. Magnetofullerenosome suspension was locally injected into the tumorbearing tongue and the tongues were irradiated with near-infrared laser light leading to tumor heating, and photosensitzer release combined with its activation. The inhibition of the growth of tongue carcinoma group was significantly greater than in the control group. These results strongly suggest the usefulness of this novel multifunctional approach to the cancer ... >>
1983-01-01
Liposomes have been employed as membrane models applicable to photosensitization in phototherapy procedures. The results with 8-methoxypsoralen, the sensitizer in PUVA therapy of psoriasis, show that singlet oxygen generated by near-uv (uv-A) irradiation induces membrane damage leading to lysis. A similar role of singlet oxygen has been shown for photosensitization of liposomes by methylene blue, with the new observation that hydrodynamic forces promote the lytic action initiated by singlet oxygen attack on an unsaturated site of phosphatidylcholine. Liposome photosensitization by hematoporphyrin follows a Type II mechanism mediated by singlet oxygen for low sensitizer concentrations, and a Type I, anoxic, mechanism when the hematoporphyrin is aggregated. Similar concentration effects obtain with hematoporphyrin derivative (hpd), the photosensitizer in photoradiation therapy of malignant tumors. Studies on the components of hpd separated by gel chromatography show that the putative biological active fraction can photosensitize membrane damage under oxic and anoxic conditions. The oxic pathway was suppressed by binding to human serum albumin, as involved in serum transport of hpd prior to localization in tumor tissue. A study on hematoporphyrin photosensitization of targets other than membranes has shown that singlet oxygen is responsible for the photosensitized inactivation of subtilisin BPN' and photooxidation of tryptophan in human and bovine serum albumin. In the case of the serum proteins, the singlet oxygen is generated by the sensitizer-protein complex and it may react with all protein in the system. 11 references.
1983-01-01
Liposomes have been employed as membrane models applicable to photosensitization in phototherapy procedures. The results with 8-methoxypsoralen, the sensitizer in PUVA therapy of psoriasis, show that singlet oxygen generated by near-uv (uv-A) irradiation induces membrane damage leading to lysis. A similar role of singlet oxygen has been shown for photosensitization of liposomes by methylene blue, with the new observation that hydrodynamic forces promote the lytic action initiated by singlet oxygen attack on an unsaturated site of phosphatidylcholine. Liposome photosensitization by hematoporphyrin follows a Type II mechanism mediated by singlet oxygen for low sensitizer concentrations, and a Type I, anoxic, mechanism when the hematoporphyrin is aggregated. Similar concentration effects obtain with hematoporphyrin derivative (hpd), the photosensitizer in ... >>
1988-01-01
Laser light-induced, dye-mediated photolysis of leukemic cells was tested in an in vitro model for its efficacy in eliminating occult tumor cells for ex vivo autologous bone marrow purging. Merocyanine 540 (MC540) was mixed with acute promyelocytic leukemia (HL-60) cells in the presence of human albumin. This cell-dye mixture was irradiated with 514 nm argon laser light. Results show that in the presence of 0.1%, 0.25% and 0.5% albumin, laser light doses of 62.4 J/cm/sup 2/, 93.6 J/cm/sup 2/ and 109.2 J/cm/sup 2/, respectively, were required for a 5 log reduction in the survival of leukemic cells. Under identical conditions, 80% to 84% of the normal bone marrow cells and 41% of the granulocyte-macrophage colony forming cells survived. The number of surviving stromal cells was reduced (1+) compared to the untreated control (4+). Mixing of irradiated bone marrow cells with equal number of HL-60 cells did not interfere with the killing of HL-60 cells treated with MC540 and laser light. The non-specific cytotoxicity of laser light alone was less than 6% for normal bone marrow cells. These results suggest that the concentration of human albumin plays an important role in laser light-induced phototoxicity. This laser light-induced selective photolysis of leukemic cells can be used in ex vivo purging of tumor cell-contaminated bone marrow grafts to achieve very high survival rates of normal bone marrow cells and granulocyte-macrophage colony forming cells.
INEL BNCT research program publications, 1993
1994-05-01
This document is a collection of the published reports describing research supporting the Idaho National Engineering Laboratory Boron Neutron Capture Therapy Research Program for calendar year 1993. Contributions from the principal investigators are included, covering chemistry (pituitary tumor studies, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, ICP-AES analysis of biological samples), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (tissue and efficacy studies of small and large animal models). These reports have previously appeared in the book: Advances in Neutron Capture Therapy, edited by A. H. Soloway, R. F. Barth, D. E. Carpenter, Plenum Press, 1993. Reports have also appeared in three journals: Angewandte Chemie, Strahlentherapie und Onkologie, and Nuclear Science and Engineering. This individual papers have been indexed separately elsewhere.
2006-01-01
The present study demonstrates the in vitro effect of hypericin-mediated photodynamic therapy with fractionated light delivery. Cells were photosensitized with unequal light fractions separated by dark intervals (1 h, 6 h). The changes in survival, apoptosis and cell cycle were compared on HT-29 cells irradiated with a single light dose (12 J/cm2) to the fractionated light delivery (1+11 J/cm2) 24 h and 48 h after photodynamic treatment. It was found that a fractionated light regime with a longer dark period resulted in a decrease of hypericin photo-cytotoxicity. Cell survival was 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 G1 phase of ... >>
1986-11-01
The effects of various scavengers of reactive oxygen and/or radical species on cell survival in vitro of EMT6 and CHO cells following photodynamic therapy (PDT) or gamma irradiation were compared. None of the agents used exhibited major direct cytotoxicity. Likewise, none interfered with cellular porphyrin uptake, and none except tryptophan altered singlet oxygen production during porphyrin illumination. The radioprotector cysteamine (MEA) was equally effective in reducing cell damage in both modalities. In part, this protection seems to have been induced by oxygen consumption in the system due to MEA autoxidation under formation of H/sub 2/O/sub 2/. The addition of catalase, which prevents H/sub 2/O/sub 2/ buildup, reduced the effect of MEA to the same extent in both treatments. Whether the remaining protection was due to MEA's radical-reducing action or some remaining oxygen limitation is unclear. The protective action of MEA was not mediated by a doubling of cellular glutathione levels, since addition of buthionine sulfoximine, which prevented glutathione increase, did not diminish the observed MEA protection. The hydroxyl radical scavenger mannitol also afforded protection in both, but it was approximately twice as effective in gamma irradiation as in PDT. This is consistent with the predominant role of OH radicals in ionizing radiation damage and their presumed minor involvement in PDT damage. Superoxide dismutase, a scavenger of O/sub 2/, acted as a radiation protector but was not significantly effective in PDT. Catalase, which scavenges H/sub 2/O/sub 2/, was ineffective in both modalities. Tryptophan, an efficient singlet oxygen scavenger, reduced cell death through PDT by several orders of magnitude while being totally ineffective in gamma irradiation. These data reaffirm the predominant role of 1O2 in the photodynamic cell killing but also indicate some involvement of free radical species.
1986-01-01
The effects of various scavengers of reactive oxygen and/or radical species on cell survival in vitro of EMT6 and CHO cells following photodynamic therapy (PDT) or gamma irradiation were compared. None of the agents used exhibited major direct cytotoxicity. Likewise, none interfered with cellular porphyrin uptake, and none except tryptophan altered singlet oxygen production during porphyrin illumination. The radioprotector cysteamine (MEA) was equally effective in reducing cell damage in both modalities. In part, this protection seems to have been induced by oxygen consumption in the system due to MEA autoxidation under formation of H2O2. The addition of catalase, which prevents H2O2 buildup, reduced the effect of MEA to the same extent in both treatments. Whether the remaining protection was due to MEA's ... >>
1989-05-01
The effects of photosensitizers chloroaluminum sulfonated phthalocyanine (ClAlSPc) and hematoporphyrin derivative (HpD) on the functional activities of macrophages and natural killer (NK) cells, have been investigated. Murine peritoneal macrophages treated in vivo with ClAlSPc or HpD at 10 mg/kg body weight showed no impairment of Fc-mediated phagocytic capacity and only minor disturbances of in vitro tumoricidal/tumoristatic function. The NK cell activity of splenocytes obtained from photosensitizer-treated mice, assayed 24 or 48 h after i.v. injection of ClAlSPc or HpD at 10 mg/kg was unaffected compared to controls. However significant inhibition of NK activity was observed when splenocytes obtained from mice with or without subcutaneous Colo 26 tumors, treated with ClAlSPc plus laser therapy (675 nm) were used as effector cells. The results show that impairment of some anti-tumor activity can be observed in phthalocyanine treated or phthalocyanine + laser-treated animals but this relatively minor impairment may augur well for the use of systemic phthalocyanine administration in photodynamic therapy. (author).
1989-01-01
The effects of photosensitizers chloroaluminum sulfonated phthalocyanine (ClAlSPc) and hematoporphyrin derivative (HpD) on the functional activities of macrophages and natural killer (NK) cells, have been investigated. Murine peritoneal macrophages treated in vivo with ClAlSPc or HpD at 10 mg/kg body weight showed no impairment of Fc-mediated phagocytic capacity and only minor disturbances of in vitro tumoricidal/tumoristatic function. The NK cell activity of splenocytes obtained from photosensitizer-treated mice, assayed 24 or 48 h after i.v. injection of ClAlSPc or HpD at 10 mg/kg was unaffected compared to controls. However significant inhibition of NK activity was observed when splenocytes obtained from mice with or without subcutaneous Colo 26 tumors, treated with ClAlSPc plus laser therapy (675 nm) were used as effector cells. The results show that ... >>
Division of Biological and Medical Research annual report 1978
1978-01-01
The research during 1978 in the Division of Biological and Medical Research, Argonne National Laboratory, is summarized. Studies related to nuclear energy include responses of beagles to continuous low-level /sup 60/Co gamma radiation, and development of leukemic indicators; comparison of lifetime effects in mice of low-level neutron and /sup 60/Co gamma radiation; genetic effects of high LET radiations; and metabolic and therapeutic studies of heavy metals. Studies of nonnuclear energy sources deal with characterization and toxicological evaluation of effluents of fluidized bed combustion and coal gasification; electrical storage systems; electric fields associated with energy transmission; and development of population projection models and assessment of human risk. Basic research studies include fundamental structural and biophysical investigations; circadian rhythms; mutagenesis in bacteria and mammalian cells; cell killing, damage, and repair in mammalian cells; carcinogenesis and cocarcinogenesis; the use of liposomes as biological carriers; and studies of environmental influences on life-span, physiological performance, and circadian cycles. In the area of medical development, proteins in urine and tissues of normal and diseased humans are analyzed, and advanced analytical procedures for use of stable isotopes in clinical research and diagnosis are developed and applied. The final sections of the report cover support facilities, educational activities, the seminar program, staff talks, and staff publications.
Combined treatment of endoscopic laser irradiation and radiotherapy for lung cancer
1989-04-01
Sixty-six patients with lung cancer were treated with endoscopic laser irradiation. In this study, photodynamic laser therapy (PDT) was performed on 28 patients with early lung cancer and 38 patients with advanced lung cancer having 69 biopsy-proven malignant lesions of the trachea and bronchus. The patients were administered HpD (2.5 mg/kg of their weight) injected intravenously three days prior to HpD-mediated laser phototherapy. These patients have completed at least one course of this therapy which was carried out by flexible bronchofiberscope. The laser beam was delivered through an optical fiber connected to the output of a dye laser (630+-3 nm). The optical fiber was passed through the large inside channel of the flexible bronchofiberscope. Among the 69 malignant lesions of the trachea and bronchus, complete responses were obtained in 9 malignant lesions, partial responses in 44 cases, regressions in 13 cases, and the remaining 3 cases had progressions. Of the 66 patients, 19 patients are alive with no recurrence or metastasis, while the remaining 47 patients died after photodynamic laser therapy. The patients treated with photodynamic laser therapy (PDT) had unresectable lung cancer which was observable by bronchofiberscopy but not suitable for radical treatment either by chemotherapy or radiation therapy. We studied a selection of patients with unresectable lung cancer for application of a treatment combining endoscopic laser irradiation and radiotherapy. (author).
Combined treatment of endoscopic laser irradiation and radiotherapy for lung cancer
1989-01-01
Sixty-six patients with lung cancer were treated with endoscopic laser irradiation. In this study, photodynamic laser therapy (PDT) was performed on 28 patients with early lung cancer and 38 patients with advanced lung cancer having 69 biopsy-proven malignant lesions of the trachea and bronchus. The patients were administered HpD (2.5 mg/kg of their weight) injected intravenously three days prior to HpD-mediated laser phototherapy. These patients have completed at least one course of this therapy which was carried out by flexible bronchofiberscope. The laser beam was delivered through an optical fiber connected to the output of a dye laser (630+-3 nm). The optical fiber was passed through the large inside channel of the flexible bronchofiberscope. Among the 69 malignant lesions of the trachea and bronchus, complete responses were obtained in 9 malignant ... >>
2003-01-01
Full text: Photodynamic therapy (PDT) can result in apoptosis and/or necrosis. Several steps in the apoptotic program depend on ATP and the intracellular ATP level is one determinant in the decision between apoptosis and necrosis. Therefore, photochemical damage of cellular targets involved in energy supply might play a crucial role for the mode of cell death being executed. The present study aimed at the characterization of changes in cellular energy supply and the associated cell death modes in response to PDT. Using the human epidermoid carcinoma cell line A431 and aluminum (III) phthalocyanine tetrasulfonate (2.5 muM) as a photosensitizer, we studied the changes in mitochondrial function and intracellular ATP-level after irradiation with different light doses. Employing assays for caspase-3 activation and nuclear fragmentation, 50 % of the cells were ... >>
2005-06-07
A singlet oxygen dose model is developed for PDT with Photofrin. The model is based on photosensitizer photobleaching kinetics, and incorporates both singlet oxygen and non-singlet oxygen mediated bleaching mechanisms. To test our model, in vitro experiments were performed in which MatLyLu (MLL) cells were incubated in Photofrin and then irradiated with 532 nm light. Photofrin fluorescence was monitored during treatment and, at selected fluence levels, cell viability was determined using a colony formation assay. Cell survival correlated well to calculated singlet oxygen dose, independent of initial Photofrin concentration or oxygenation. About 2 x 10{sup 8} molecules of singlet oxygen per cell were required to reduce the surviving fraction by 1/e. Analysis of the photobleaching kinetics suggests that the lifetime of singlet oxygen in cells is 0.048 {+-} 0.005 {mu}s. The generation of fluorescent photoproducts was not a result of singlet oxygen reactions exclusively, and therefore did not yield additional information to aid in quantifying singlet oxygen dose.
2005-01-01
A singlet oxygen dose model is developed for PDT with Photofrin. The model is based on photosensitizer photobleaching kinetics, and incorporates both singlet oxygen and non-singlet oxygen mediated bleaching mechanisms. To test our model, in vitro experiments were performed in which MatLyLu (MLL) cells were incubated in Photofrin and then irradiated with 532 nm light. Photofrin fluorescence was monitored during treatment and, at selected fluence levels, cell viability was determined using a colony formation assay. Cell survival correlated well to calculated singlet oxygen dose, independent of initial Photofrin concentration or oxygenation. About 2 x 108 molecules of singlet oxygen per cell were required to reduce the surviving fraction by 1/e. Analysis of the photobleaching kinetics suggests that the lifetime of singlet oxygen in cells is 0.048 ... >>
Application of spectral hole burning to the study of in vitro cellular systems
1999-11-08
Chapter 1 of this thesis describes the various stages of tumor development and a multitude of diagnostic techniques used to detect cancer. Chapter 2 gives an overview of the aspects of hole burning spectroscopy important for its application to the study of cellular systems. Chapter 3 gives general descriptions of cellular organelles, structures, and physical properties that can serve as possible markers for the differentiation of normal and cancerous cells. Also described in Chapter 3 are the principles of cryobiology important for low temperature spectroscopy of cells, characterization of MCF-10F (normal) and MCF-7 (cancer) cells lines which will serve as model systems, and cellular characteristics of aluminum phthalocyanine tetrasulfonate (APT), which was used as the test probe. Chapters 4 and 5 are previously published papers by the author pertaining to the results obtained from the application of hole burning to the study of cellular systems. Chapter 4 presents the first results obtained by spectral hole burning of cellular systems and Chapter 5 gives results for the differentiation of MCF-10F and MCF-7 cells stained with APT by an external applied electric (Stark) field. A general conclusion is presented in Chapter 6. Appendices A and B provide additional characterization of the cell/probe model systems. Appendix A describes the uptake and subcellular distribution of APT in MCF-10F and MCF-7 cells and Appendix B compares the hole burning characteristics of APT in cells when the cells are in suspension and when they are examined while adhering to a glass coverslip. Appendix C presents preliminary results for a novel probe molecule, referred to as a molecular thumbtack, designed by the authors for use in future hole burning applications to cellular systems.
2003-01-01
Full text: The effect of photodynamic therapy (PDT) on anti-tumoral immune reactions is still discussed controversially. Several studies have demonstrated that PDT is able to activate immune reactions against tumor antigens. However, there is also evidence that PDT exerts immunosuppressive effects. Dendritic cells (DC) are professional antigen presenting cells and play an important role in, both, the induction of immune reactions as well as the induction and maintenance of immunologic tolerance. Therefore, we investigated the effect of hypericin-mediated PDT on the capability of bone marrow-derived DC for antigen uptake, processing and presentation to CD4+ T lymphocytes. Using beta-galactosidase as model antigens we found that, under sublethal PDT conditions, antigen is still incorporated and degraded by surviving DC. PDT-treated DC, in the presence of ... >>
APPLICATIONS OF THE JEFFERSON LAB FREE ELECTRON LASER FOR PHOTOBIOLOGY.
2000-02-15
No abstract prepared.
A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy
2007-01-01
We have developed a comprehensive theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O2) consumption and transport and microscopic photodynamic dose deposition during photodynamic therapy (PDT) in vivo. Previously published models have been improved by considering perfused vessels as a time-dependent 3O2 source and linking the 3O2 concentration in the vessel to that within the tissue through the Hill equation. The time-dependent photochemical 3O2 consumption rate incorporates sensitizer photobleaching effects and an experimentally determined initially nonuniform photosensitizer distribution. The axial transport of 3O2 is provided for in the capillaries and in the surrounding tissue. A ... >>
A center of excellence for the medical application of lasers: Progress report
1994-04-01
This progress report presents six areas where lasers are used in diagnostic or therapeutic uses. They are: oncology; pulmonary/thoracic surgery; dermatology/plastic surgery; obstetrics and gynecology; ophthalmology; and dentistry. Within each area research findings and all publications resulting from the research are summarized.
2006-07-01
This document gathers the posters that were presented during the poster session of this workshop. These posters highlight the results obtained by ESRF'users in different fields such as surface structure, Compton scattering studies, localized vibrational modes in thermoelectric materials, Ni-Ti thin films, residual stresses in superconducting wires, and changes in crystal and magnetic structure of NdFeO{sub 3}.
Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy
2003-01-01
Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy ... >>
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