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PDT
Kinds of PDT Terms modified by PDT Selected AbstractsReduction in the Incidence of Squamous Cell Carcinoma in Solid Organ Transplant Recipients Treated with Cyclic Photodynamic TherapyDERMATOLOGIC SURGERY, Issue 5 2010ANDREA WILLEY MD BACKGROUND AND OBJECTIVES Squamous cell carcinomas (SCCs) produce significant morbidity in solid organ transplant recipients (SOTRs), particularly in patients who develop multiple tumors. Topical photodynamic therapy (PDT) has been shown to decrease the number of keratotic lesions in SOTRs, but the duration of the beneficial effect is limited. The aim of this study was to evaluate the potential benefit of cyclic PDT in the prevention of new SCCs in SOTRs. METHODS Twelve high-risk SOTRs received cyclic PDT treatments at 4- to 8-week intervals for 2 years. The development of new SCCs (invasive and in situ) performed 12 and 24 months after the start of cyclic PDT were compared with the number of SCCs developed during the year before initiation of cyclic PDT. RESULTS The median reduction in the 12- and 24-month post-treatment counts from the 1-month pretreatment counts was 79.0% (73.3,81.8%) and 95.0% (87.5,100.0%), respectively. Treatments were well tolerated. CONCLUSION Cyclic PDT with 5-aminolevulinic acid may reduce the incidence of SCC in SOTRs. Additional studies with larger numbers of patients and optimized protocols are necessary to further explore the potential benefits of cyclic PDT in the prevention of skin cancer in this high-risk patient population. Dr. Lee is member of the Medical Advisory Board of Dusa Pharmaceuticals, Inc. [source] Photodynamic Therapy for the Treatment of Cutaneous Neoplasia, Inflammatory Disorders, and PhotoagingDERMATOLOGIC SURGERY, Issue 5 2009EMILY TIERNEY MD BACKGROUND Photodynamic therapy (PDT) has demonstrated high efficacy, minimal side effects, and improved cosmetic outcome when used for the treatment of actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma, and photoaging. METHODS To review the literature on the use of PDT in dermatologic surgery using MEDLINE. RESULTS Published clinical studies using PDT in the treatment of AKs yield overall efficacy rates ranging from 50% to 71% with one treatment to as high as 88% to 90% with two or more treatments. For superficial BCC, initial clearance rates were 76% to 97%, and for Bowen's disease, initial clearance rates ranged from 72% to 94% overall. The use of PDT for photorejuvenation is a relatively new application of this technology, which has shown promise in improving the appearance of fine lines, pigmentary variation, and telangiectasias. CONCLUSIONS The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy through topical application of aminolevulinic acid and methyl aminolevulinic acid, with outstanding cosmetic results. Although the theory behind the use of chemical photosensitizers and ultraviolet light to treat a wide variety of skin disorders is straightforward, the practical application of this technology is evolving. Additional research into the precise mechanisms of action for specific photosensitizers and optimal light sources will be highly beneficial to the advancement of this technology. [source] Treatment of Inflammatory Facial Acne Vulgaris with Intense Pulsed Light and Short Contact of Topical 5-Aminolevulinic Acid: A Pilot StudyDERMATOLOGIC SURGERY, Issue 8 2006JINDA ROJANAMATIN MD BACKGROUND Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) and red light (550,700 nm) has been introduced for effective treatment of facial acne. Untoward side effects are common, however. OBJECTIVE To evaluate the efficacy and safety of the short contact of topical ALA and intense pulsed light (IPL) in treatment of inflammatory facial acne. METHODS Fourteen patients with inflammatory facial acne were treated with IPL on the left side and combination of IPL and topical ALA on the right side at 3- to 4-week intervals for three sessions. Clinical photographs and lesion counts were obtained for evaluation. RESULTS All patients revealed a reduction in number of acne lesions on both sides. On the ALA-pretreated side, lesion counts decreased 87.7% at 12 weeks after the last treatment (p<.01). Meanwhile, lesion counts on the nonpretreated side decreased 66.8% (p<.01). In addition, a number of lesion counts on the ALA-pretreated side decreased. Mild edema and minimal crust developed on the combined-treatment side. CONCLUSION Short contact of topical ALA and IPL or IPL alone showed some beneficial effect in treatment of inflammatory facial acne; however, degree of improvement was better and remained longer with the combined regimen. Side effects were mild and reversible. [source] Cold Air Analgesia in Photodynamic Therapy of Basal Cell Carcinomas and Bowen's Disease: An Effective Addition to Treatment: A Pilot StudyDERMATOLOGIC SURGERY, Issue 1 2004FACD, John Pagliaro MB Background. There is considerable interpatient variability in pain tolerance during and after treatment of skin cancer with photodynamic therapy (PDT). Additionally, erythema and edema are common, with mild crusting and healing over 1 to 2 weeks. Objective. To determine whether concurrent cold air analgesia improves the tolerability of PDT. Method. Twenty-six patients with two similar superficial skin cancers were treated with PDT. One lesion was treated with cold air analgesia and the other without. Patients rated their pain during treatment using the Wong Baker Faces Pain Scale and detailed duration of posttreatment pain. At week 2, the inflammatory response was assessed. Result. A statistically significant difference in the analgesia group was shown with respect to the mean duration of pain and the level of erythema after the first treatment as well as pain scores during the second treatment. Conclusion. Patient acceptance of PDT for treatment of nonmelanoma skin cancer is improved with lessened morbidity assessed with concurrent use of cold air analgesia to the treatment field. [source] Photodynamic Therapy of Cutaneous Lymphoma Using 5-Aminolevulinic Acid Topical ApplicationDERMATOLOGIC SURGERY, Issue 8 2000Arie Orenstein MD Background. Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. Objective. We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). Methods. ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580,720 nm) using the VersaLight system. Results. Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10,15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). Conclusion. The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment. [source] The role of surveillance endoscopy and endosonography after endoscopic ablation of high-grade dysplasia and carcinoma of the esophagusDISEASES OF THE ESOPHAGUS, Issue 2 2008A. D. Savoy SUMMARY., Barrett's esophagus (BE) with high-grade dysplasia (HGD) or early carcinoma treated with surgery or photodynamic therapy (PDT) is at risk of recurrence. The efficacy of endoscopic ultrasound (EUS) for surveillance after PDT is unknown. Our objective was to determine if EUS is superior to esophagogastroduodenoscopy (EGD) and/or CT scan for surveillance of BE neoplasia after PDT. The study was designed as a retrospective review with the setting as a tertiary referral center. Consecutive patients with BE with HGD or carcinoma in situ treated with PDT were followed with EUS, CT scan and EGD with jumbo biopsies every 1 cm at 3, 4, or 6-month intervals. Exclusion criteria was < 6 months of follow up and/or < 2 EUS procedures. Main outcome measurements were residual or recurrent disease discovered by any method. Results showed that 67/97 patients met the inclusion criteria (56 men and 11 women). Median follow-up was 16 months. Recurrent or residual adenocarcinoma (ACA) was detected in four patients during follow-up. EGD with random biopsies or targeted nodule biopsies detected three patients. EUS with endoscopic mucosal resection of the nodule confirmed T1 recurrence in one of these three. In the fourth patient, CT scan revealed perigastric lymphadenopathy and EUS-FNA (fine needle aspiration) confirmed adenocarcinoma. There were two deaths, one related to disease progression and one unrelated. The rate of recurrent/persistent ACA after PDT was 4/67 = 6%. EUS did not detect disease when EGD and CT were normal. Limitations of this study include non-blinding of results and preferential status of non-invasive imaging (CT) over EUS. Our experience suggests that EUS has little role in the surveillance of these patients, unless discrete abnormalities are found on EGD or cross-sectional imaging. [source] Photophysical and Photochemical Properties of Fluorinated and Nonfluorinated n -Propanol-Substituted Zinc PhthalocyaninesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 8 2010lke Gürol Abstract The synthesis of symmetrical fluorinated and nonfluorinated zinc(II) phthalocyanine derivatives obtained from 4,5-dichlorophthalonitrile, 4-nitrophthalonitrile and 3-nitrophthalonitrile substituted with 2,2,3,3-tetrafluoro-1-propanol and n -propanol are described. The comparison of the photophysicochemical properties of fluorinated and nonfluorinated substituted zinc(II) phthalocyanines is reported for the first time. The new compounds have been characterized by elemental analysis, IR, 1H NMR and 19F NMR spectroscopy, electronic spectroscopy and mass spectra. The photophysical and photochemical properties of the compounds were studied in dimethyl sulfoxide (DMSO). The complexes were quenched with benzoquinone (BQ), and their fluorescence-quenching properties were investigated in the same solvent. The effects of the number of the substitution and the position on the photophysical and photochemical parameters of the zinc(II) phthalocyanines 1a,7a are also reported. Photophysical and photochemical properties of phthalocyanine complexes are very useful for photodynamic therapy (PDT) of cancer applications. In particular, high singlet-oxygen quantum yields are very important for Type II mechanisms. These complexes have good singlet-oxygen quantum yields and show potential as Type-II photosensitizers. [source] Dimensions of Mothers' and Fathers' Differential Treatment of Siblings: Links With Adolescents' Sex-Typed Personal Qualities,FAMILY RELATIONS, Issue 1 2003Corinna Jenkins Tucker We explored mothers' and fathers' differential treatment (PDT) of their adolescent offspring in five domains (privileges, chores, affection, discipline, and temporal involvement) and examined how siblings' personal qualities were associated with PDT. Participants were 188 families with first- and secondborn adolescents. Equal treatment was the modal parental style except for privileges and discipline. Even where equal treatment was normative a substantial proportion of parents reported differential treatment. Further, the similarity of the nature of parents' differential treatment varied by domain. Sex was associated with parents' differential temporal involvement. Sex-typed personal qualities were related to parents' differential discipline. Both sex and sex-typed personal characteristics were linked to differential affection. Privileges and chores were associated with age and birth order. [source] Anticancer effect of photodynamic therapy with hexenyl ester of 5-aminolevulinic acid in oral squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2010Yeon-Hee Moon MS Abstract Background. Five-aminolaevulinic acid (ALA) and its derivatives act as precursors of the photosensitizer protoporphyrin IX (PpIX). In this study, the effect of photodynamic therapy (PDT) with hexenyl ester of ALA (ALA-hx) was examined in a human oral squamous cell carcinoma, YD10B cells. Methods. PpIX accumulation and mRNA expression of coproporphyrinogen oxidase (CPO) by ALA and ALA-hx was examined. Cell viability was examined by MTT assay and the molecular mechanism was investigated. Results. The PpIX synthesis and mRNA expression of CPO was much higher in the cells treated with ALA-hx than ALA. At the concentration that PDT with ALA did not affect cell growth, ALA-hx PDT effectively produced reactive oxygen species (ROS) and suppressed cell growth. Growth inhibition by ALA-hx PDT was due to mitochondrial-dependent apoptosis. Conclusion. Our results suggest that ALA-hx PDT effectively induced apoptosis of YD-10B cells and can be considered as a therapeutic alternative for oral cancer. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Synthesis and Photochemical Evaluation of Iodinated Squarylium Cyanine DyesHELVETICA CHIMICA ACTA, Issue 5 2005Paulo Several (multiply) iodinated squarylium cyanine dyes of type 1 and 8 (see Scheme and Table), derived from 1,3-benzothiazole and 6-iodo-1,3-benzothiazole, were synthesized as potential new photosensitizers, with absorptions in the 700-nm region. Their ability to generate singlet oxygen (1O2) was assessed by luminescence-decay measurement in the near-IR. Some of these new dyes show interesting photophysical properties, and may be potentially used in photodynamic therapy (PDT). [source] In vitro Studies of Functionalized Mesoporous Silica Nanoparticles for Photodynamic TherapyADVANCED MATERIALS, Issue 2 2009Hsiung-Lin Tu A versatile platform for photodynamic therapy (PDT), mesoporous silica nanoparticles functionalized with protoporphyrin IX (PpIX-MSNs), has been developed. In vitro studies on HeLa cells show high uptake efficiency. Phototoxicity results give both irradiation time- and dosage-dependent cell death events. Because of the ease of incorporating other biomedical functional groups, we believe MSNs would be an ideal platform for biomedical applications. [source] Disparity between prostate tumor interior versus peripheral vasculature in response to verteporfin-mediated vascular-targeting therapyINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Bin Chen Abstract Photodynamic therapy (PDT) is a light-based cancer treatment modality. Here we employed both in vivo and ex vivo fluorescence imaging to visualize vascular response and tumor cell survival after verteporfin-mediated PDT designed to target tumor vasculature. EGFP-MatLyLu prostate tumor cells, transduced with EGFP using lentivirus vectors, were implanted in athymic nude mice. Immediately after PDT with different doses of verteporfin, tumor-bearing animals were injected with a fluorochrome-labeled albumin. The extravasation of fluorescent albumin along with tumor EGFP fluorescence was monitored noninvasively with a whole-body fluorescence imaging system. Ex vivo fluorescence microscopy was performed on frozen sections of tumor tissues taken at different times after treatment. Both in vivo and ex vivo imaging demonstrated that vascular-targeting PDT with verteporfin significantly increased the extravasation of fluorochrome-labeled albumin in the tumor tissue, especially in the tumor periphery. Although PDT induced substantial vascular shutdown in interior blood vessels, some peripheral tumor vessels were able to maintain perfusion function up to 24 hr after treatment. As a result, viable tumor cells were typically detected in the tumor periphery in spite of extensive tumor cell death. Our results demonstrate that vascular-targeting PDT with verteporfin causes a dose- and time-dependent increase in vascular permeability and decrease in blood perfusion. However, compared to the interior blood vessels, peripheral tumor blood vessels were found less sensitive to PDT-induced vascular shutdown, which was associated with subsequent tumor recurrence in the tumor periphery. © 2008 Wiley-Liss, Inc. [source] Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor lociINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Mariska Hage Abstract Barrett's esophagus (BE) is a major predisposing factor for the development of esophageal adenocarcinoma. Current strategies for treatment of BE, both dysplastic and nondysplastic, include photodynamic therapy (PDT) and argon plasma coagulation (APC). However, the effect of ablative therapy at the genetic level is unclear. We performed loss of heterozygosity (LOH) analysis of BE in baseline and follow-up biopsy specimens from 21 patients with BE (17 male, 4 female) treated with PDT and/or APC. At baseline, 14 patients had intestinal metaplasia without dysplasia (MET), 4 low-grade dysplasia (LGD) and 3 high-grade dysplasia (HGD). LOH was assessed using a panel of 9 polymorphic markers for evaluation of the P53 gene on 17p, P16 on 9p, DCC and SMAD4 on 18q and the APC gene on 5q. The tissue specimens obtained at baseline (t = 0) were analysed, as well as the first (t = 1; mean interval: 4 months) and last (t = 2; mean interval: 8 months) available biopsy with residual or recurrent BE after ablation. At t = 0, allelic loss was detected of 5q in 27%, 9p in 56%, 17p in 31% and 18q in 6% of informative cases. At t = 1 (18 patients with persistent MET and 3 with LGD) and at t = 2 (8 MET, 2 LGD), the LOH patterns were not statistically different from t = 0. Further, multiple genetic lineages before and after therapy were detected in 15 cases illustrating the multiclonal nature of BE. We conclude that recurrent and/or persistent BE after ablative therapy still contains genetic alterations associated with malignant progression to cancer. Therefore, the goal of treatment should be the complete elimination of Barrett's mucosa. © 2005 Wiley-Liss, Inc. [source] mTHPC-mediated photodynamic therapy for early oral squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Colin Hopper Abstract Surgery and radiotherapy are standard treatments for early oral squamous cell carcinoma, both resulting in good tumour control. However, neither of these modalities is without consequent functional or cosmetic impairment, and there are patients in whom both are contraindicated. Furthermore, there is a significant risk of metachronous tumours developing in the oral cavity, and salvage or retreatment with either surgery or radiotherapy poses difficulties. Photodynamic therapy (PDT) offers the potential for improved functional and cosmetic outcomes, while achieving comparable tumour control. We conducted an open-label, multicentre study to assess the efficacy and safety of meta-tetrahydroxyphenylchlorin (mTHPC) in patients with early oral cancer. One hundred twenty-one patients received intravenously administered mTHPC, followed 96 hr later by illumination of the tumour surface with 652 nm laser light. Of these patients, 114 were protocol compliant. A complete tumour response was achieved in 85% of protocol-compliant patients (97 of 114 patients). A complete response was maintained in 85% of responders at 1 year and in 77% at 2 years. One- and 2-year actuarial survival rates were 89% and 75%, respectively. In the opinion of the investigators, tumour clearance was accompanied by excellent cosmetic and functional results, without impact on the patients' performance status. Mild-to-moderate pain at the treatment site, a recognised side effect of PDT in the oral cavity, was reported by 82% of patients but was manageable with appropriate analgesia. Mild-to-moderate skin photosensitivity reactions were reported for 13% of patients. mTHPC offers an effective alternative treatment for early oral squamous cell carcinoma. It is associated with excellent functional and cosmetic results and can be used in conjunction with other standard therapies. © 2004 Wiley-Liss, Inc. [source] Perceptions of Deservedness of Social Aid as a Function of Prenatal Diagnostic Testing,JOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 1 2003Karen L. Lawson This study examined whether judgments of deservedness of social aid subsequent to the birth of a disabled child vary as a function of prenatal diagnostic testing (PDT) use as predicted by the attribution-affect-action model (Weiner, 1980). A sample of family physicians/obstetricians (n= 341) and a university employee sample (n= 281) made attribution ratings in 3 scenarios in which an at-risk pregnant woman gave birth to a disabled child. The findings indicate that women who chose not to use PDT or who chose to continue the pregnancy following a diagnosis were judged more responsible, more to blame, and less deserving of both sympathy and social aid subsequent to giving birth to a disabled child than were women to whom testing was not made available. [source] Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Ho-Kee Koon Abstract Epidermal growth factor receptor (EGFR), a receptor often expressed in nasopharyngeal carcinoma (NPC) cells, is one of the recently identified molecular targets in cancer treatment. In the present study, the effects of combined treatment of Zn-BC-AM PDT with an EGFR inhibitor AG1478 were investigated. Well-differentiated NPC HK-1 cells were subjected to PDT with 1,µM of Zn-BC-AM and were irradiated at a light dose of 1,J/cm2 in the presence or absence of EGFR inhibitor AG1478. Specific protein kinase inhibitors of downstream EGFR targets were also used in the investigation. EGFR, Akt, and ERK were found constitutively activated in HK-1 cells and the activities could be inhibited by the EGFR inhibitor AG1478. A sub-lethal concentration of AG1478 was found to further enhance the irreversible cell damage induced by Zn-BC-AM PDT in HK-1 cells. Pre-incubation of the cells with specific inhibitors of EGFR (AG1478), PI3k/Akt (LY294002), or MEK/ERK (PD98059) before light irradiation were found to enhance Zn-BC-AM PDT-induced formation of apoptotic cells. The efficacy of Zn-BC-AM PDT can be increased through the inhibition of EGFR/PI3K/Akt and EGFR/MEK/ERK signaling pathways in NPC cells. Combination therapy with Zn-BC-AM PDT and EGFR inhibitors may further be developed for the treatment of advanced NPC. J. Cell. Biochem. 108: 1356,1363, 2009. © 2009 Wiley-Liss, Inc. [source] Methylene blue-mediated photodynamic therapy induces mitochondria-dependent apoptosis in HeLa CellJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Yan Lu Abstract Methylene blue (MB), a widely studied reagent, is investigated in this work for its usage in photodynamic therapy (PDT). PDT has been proved to be highly effective in the treatment of different types of cancers. Previous studies showed MB has both high affinity for mitochondria and high photodynamic efficiency. To elucidate the effects of MB in PDT, we analyzed PDT-induced apoptosis in HeLa cells by introducing different doses of MB into the culture media. Our data showed that MB-mediated PDT triggered intense apoptotic cell death through a series of steps, beginning with photochemical generation of reactive oxygen species. The release of cytochrome c and activation of caspase-3 indicated that MB-PDT-mediated apoptosis in HeLa cells was executed by the mitochondria-dependent apoptotic pathway. Importantly, proteomic studies confirmed that expression levels of several mitochondrial proteins were altered in MB-PDT-induced apoptosis, including TRAP1, mitochondrial elongation factor Tu and peroxiredoxin 3 isoform b. Western blot data showed that phosphorylation of ERK1/2 and PKA were reduced in MB-PDT treated cells, indicating several signal molecules participating in this apoptotic cascade. Moreover, MB-PDT induced an increase in the strength of interaction between Bcl-xL and dephosphorylated Bad. This led to loss of the pro-survival function of Bcl-xL and resulted in mitochondria-mediated apoptosis. This study provides solid evidence of a strong induction by MB-PDT of a mitochondria-dependent apoptosis cascade in HeLa cells. J. Cell. Biochem. 105: 1451,1460, 2008. © 2008 Wiley-Liss, Inc. [source] Diffusion-weighted MRI for monitoring tumor response to photodynamic therapyJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2010Hesheng Wang MS Abstract Purpose: To examine diffusion-weighted MRI (DW-MRI) for assessing the early tumor response to photodynamic therapy (PDT). Materials and Methods: Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second-generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high-field (9.4 Tesla) small animal MR scanner was used to acquire diffusion-weighted MR images pre-PDT and 24 h after the treatment. DW-MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect. Results: Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre-PDT. The average ADC was 0.511 ± 0.119 × 10,3 mm2/s pre-PDT and 0.754 ± 0.181 × 10,3 mm2/s 24 h after the PDT. There is no significant difference in ADC values pre-PDT and 24 h after PDT in the control tumors (P = 0.20). Conclusion: The change of tumor ADC values measured by DW-MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4-PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409,417. © 2010 Wiley-Liss, Inc. [source] Hyalgan® has a dose-dependent differential effect on macrophage proliferation and cell deathJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003Kyle M. Sheehan Abstract The intra-articular injection of high molecular weight hyaluronic acid (HA) has been reported to be an effective treatment for pain of osteoarthritis of the knee. However, the mechanism by which HA exerts its effect is unknown. To explore HA's influence on the growth of U937 human macrophages, cells were incubated for 168 h with three concentrations, 1, 0.1 and 0.01 mg/mL, of Hyalgan®, a high molecular weight HA preparation. At 24-h increments, the cells were examined for proliferation, cell cycle distribution as well as the number of apoptotic and dead cells. Exposing macrophages to 1 mg/mL Hyalgan® significantly reduced the rate of cellular proliferation and altered the cell cycle distribution to yield decreased proportions of G0/G1 cells but increased S and G2/M cells. Concomitantly, a 10-fold increase in apoptotic cells and a 12-fold increase in dead cells were observed. The population doubling time (PDT) for cells treated with 1.0 mg/mL Hyalgan® increased from 23.6 to 52.9 h. By contrast, the two lower Hyalgan® concentrations significantly promoted macrophage proliferation in a dose-dependent manner. They also increased the proportion of G2/M cells, but had no effect on the number of apoptotic or dead cells. The PDTs of 21.5 and 22.2 h were less than the control time of 23.6 h. These results demonstrate that Hyalgan® concentrations have a differential effect on macrophage growth dynamics and suggest an anti-inflammatory effect at high HA concentrations. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Lethal photosensitization of periodontal pathogens by a red-filtered Xenon lamp in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2003Donco Matevski Background:, The ability of Helium,Neon (He,Ne) laser irradiation of a photosensitizer to induce localized phototoxic effects that kill periodontal pathogens is well documented and is termed photodynamic therapy (PDT). Objectives:, We investigated the potential of a conventional light source (red-filtered Xenon lamp) to activate toluidine blue O (TBO) in vitro and determined in vitro model parameters that may be used in future in vivo trials. Materials and methods:,Porphyromonas gingivalis 381 was used as the primary test bacterium. Results:, Treatment with a 2.2 J/cm2 light dose and 50 µg/ml TBO concentration resulted in a bacterial kill of 2.43 ± 0.39 logs with the He,Ne laser control and 3.34 ± 0.24 logs with the lamp, a near 10-fold increase (p = 0.028). Increases in light intensity produced significantly higher killing (p = 0.012) that plateaued at 25 mW/cm2. There was a linear relationship between light dose and bacterial killing (r2 = 0.916); as light dose was increased bacterial survival decreased. No such relationship was found for the drug concentrations tested. Addition of serum or blood at 50% v/v to the P. gingivalis suspension prior to irradiation diminished killing from approximately 5 logs to 3 logs at 10 J/cm2. When serum was washed off, killing returned to 5 logs for all species tested except Bacteroides forsythus (3.92 ± 0.68 logs kill). Conclusions:, The data indicate that PDT utilizing a conventional light source is at least as effective as laser-induced treatment in vitro. Furthermore, PDT achieves significant bactericidal activity in the presence of serum and blood when used with the set parameters of 10 J/cm2, 100 mW/cm2 and 12.5 µg/ml TBO. [source] Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical applicationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2005Paul A. McCarron Abstract Aminolevulinic acid (ALA) stability within topical formulations intended for photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5-dipropionic acid (PY). Most strategies to improve stability use low pH vehicles, which can cause cutaneous irritancy. To overcome this problem, a novel approach is investigated that uses a non-aqueous vehicle to retard proton-induced charge separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell below pharmaceutically acceptable levels after 6 months, with bioadhesive patches stored at 5°C demonstrating the best stability by maintaining 86.2% of their original loading. Glycerol-based gels maintained 40.2% in similar conditions. However, ALA loss did not correspond to expected increases in PY, indicating the presence of another degradative process that prevented dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in respect of the mechanism observed in the patch system, but showed clearly that an esterification reaction involving ALA and both glycerol and poly(ethyleneglycol) was occurring. This was especially marked in the glycerol gels, where only 2.21% of the total expected PY was detected after 204 days at 5°C. Non-specific esterase hydrolysis demonstrated that ALA was recoverable from the gel systems, further supporting esterified binding within the gel matrices. It is conceivable that skin esterases could duplicate this finding upon topical application of the gel and convert these derivatives back to ALA in situ, provided skin penetration is not affected adversely. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1756,1771, 2005 [source] A new limb salvage surgery in cases of high-grade soft tissue sarcoma using photodynamic surgery, followed by photo- and radiodynamic therapy with acridine orangeJOURNAL OF SURGICAL ONCOLOGY, Issue 6 2008Tomoki Nakamura MD Abstract Background To maintain excellent limb function after tumor resection in patients with high-grade malignant sarcomas, we developed and established a new surgical adjuvant therapy using acridine orange (AO) after intra-lesional or marginal resection while sparing normal tissues of major nerves, vessels or bones adjacent to the tumor. Method Our AO therapy procedure was combined with photodynamic surgery (PDS), photodynamic therapy (PDT) and radiodynamic therapy (RDT). In this study, 26 patients with primary high-grade soft tissue sarcomas were treated with AO therapy. Result Results showed a low local recurrence rate (7.7%) and good local recurrence-free rate (88%) after AO therapy. Limb function of all patients was maintained at 100% of ISOLS criteria. Conclusion Based on these results, we concluded that AO therapy is useful for local control after margin-positive tumor resection and for preserving excellent limb function in patients with high-grade soft tissue sarcomas. J. Surg. Oncol. 2008;97:523,528. © 2008 Wiley-Liss, Inc. [source] Guidelines for practical use of MAL-PDT in non-melanoma skin cancerJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2010E Christensen Abstract Methyl aminolaevulinate photodynamic therapy is increasingly practiced in the treatment of actinic keratoses, Bowen's disease and basal cell carcinomas. This method is particularly suitable for treating multiple lesions, field cancerization and lesions in areas where a good cosmetic outcome is of importance. Good treatment routines will contribute to a favourable result. The Norwegian photodynamic therapy (PDT) group consists of medical specialists with long and extensive PDT experience. With support in the literature, this group presents guidelines for the practical use of topical PDT in non-melanoma skin cancer. [source] Intraindividual, right,left comparison of topical 5-aminolevulinic acid photodynamic therapy vs.JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 9 20095% imiquimod cream for actinic keratoses on the upper extremities Abstract Backround, Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is important. Objective, To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms. Methods, Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients' preference 6 months after treatment. Efficacy end point included the individual AK lesion clearance rate. Results, Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ). Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT. Conclusions, Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes. Conflicts of interest None declared. [source] Liposomes in dermatology todayJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2009J De Leeuw Abstract Liposomes are vesicles consisting of spherical phospholipid bi-layers with specific properties making them useful for topical application of drugs. Liposome research has expanded considerably over the last 30 years and nowadays, it is possible to construct a wide range of liposomes varying in size, phospholipids composition and surface characteristics to suit the specific application for which they are intended. In dermatology, the topical application of liposomes has proven to be of therapeutic value. Liposomes can be used as carriers for hydrophilic as well as lipophilic therapeutic agents because of their amphipathic character. They may improve stabilization of instable drugs by encapsulating them and serve as penetration enhancers facilitating the transport of compounds that otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation by sustaining the release of drugs and by hydration of the epidermis. They also have the potential to target drugs into the pilosebaceous structures and hence they have an additional advantage for treatment of hair follicle-associated disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and optimizes the results of Photodynamic Therapy (PDT). Conflicts of interest None declared [source] A review of photodynamic therapy in cutaneous leishmaniasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2008EM Van Der Snoek Summary We present a review of six clinical studies investigating the use of photodynamic therapy (PDT) using porphyrin precursors for the treatment of Old World cutaneous leishmaniasis (CL). Thirty-nine patients with a total of 77 lesions received PDT using a range of treatment schedules following topical application of aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL). The tissue response to PDT is accompanied by a mild burning sensation, erythema and reversible hypo- and hyperpigmentation. Few mechanistic studies have addressed the principles underlying the use of PDT for CL. All six reviewed papers suggest that PDT with porphyrin precursors is relatively effective in treating CL. Data are still limited, and PDT cannot at this point be recommended in routine clinical practice. The mechanism of action of this promising therapeutic modality needs to investigated further and additional controlled trials need to be performed. [source] Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgarisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2008M Hædersdal Abstract Background, There is a considerable need for effective and safe treatment for acne vulgaris. Objective, In a systematic review with an evidence-based approach to assess the effects of optical treatments for acne vulgaris. Methods, Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library. Results, A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short-term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl-aminolevulinic acid (MAL) and red light]. IPL-assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side-effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL. Conclusion, Evidence from controlled clinical trials indicates a short-term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments. [source] Photodynamic therapy: update 2006 Part 1: Photochemistry and photobiologyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2007PG Calzavara-Pinton Abstract Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new ,second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT. [source] Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis.JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2006A randomized, double-blind phase I/II study Abstract Background, Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. Objective, A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. Methods, In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm2 and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). Results, The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. Conclusion, Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile. [source] Photodynamic therapy with violet light and topical ,-aminolaevulinic acid in the treatment of actinic keratosis, Bowen's disease and basal cell carcinomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2001AT Dijkstra Abstract Background Most clinical studies using photodynamic therapy (PDT) with topical application of ,-aminolaevulinic acid (,-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of ,-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. Aim To study the efficacy of violet light in combination with topical ,-ALA PDT in the treatment of premalignant and malignant skin lesions. Methods Eight hours after 20%,-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400,450 nm). Lesions received 10,20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. Results Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90,100% of the solitary lesions of Bowen's disease. Conclusions ,-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin. [source] | |||||||||||||||||||||||||||||||||||||