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Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron.
Ito, H, Nishio, Y, Hara, T, Sugihara, H, Tanaka, T, Li, XK
European journal of pharmacology. 2018;:25-33
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Heme oxygenase-1 (HO-1) is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance through affecting the differentiation of dendritic cells. The aim of this study is to determine whether the combination of 5-aminolevulinic acid (ALA) and iron induces HO-1 expression in healthy human peripheral blood mononuclear cells (PBMC). The study was an open labeled, non-randomized, non-placebo-controlled trial using healthy male adults and consisted of three parts. Study A aimed to find the peak HO-1 expression at 0, 1, 2, 3, 4, 6, 8, 12, 16, and 24 h after administration. Study B aimed to examine HO-1 dose dependency at 150, 300, and 600 mg of ALA and the need for iron supplementation. Study C aimed to investigate HO-1 changes during a three-day, repetitive administration of ALA and iron. The combination of ALA 600 mg and sodium ferrous citrate (SFC) 942 mg upregulated HO-1 in PBMC at 8 h after administration while sole administration of ALA or SFC was unable to induce HO-1. HO-1 in blood myeloid and plasmacytoid dendritic cells was also upregulated with ALA+SFC. Clear dose dependency of ALA+SFC was not detected, and a slight tendency towards a cumulative effect of HO-1 after three-day, repetitive administration was observed. ALA, which is already approved for use in several countries as a diagnosis agent for cancer, has the potential to become a novel therapeutic drug for diseases stemming from unwanted immune response such as autoimmune diseases and the rejection response following organ transplantation.
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Low light visual function after accelerated corneal Cross-Linking Protocols: 18 mW/cm2 vs. 9 mW/cm2.
Asgari, S, Hashemi, H, Jafarzadehpur, E, Mohamadi, A, Mehravaran, S, Fotouhi, A
Romanian journal of ophthalmology. 2018;(4):270-276
Abstract
Objective. To compare one-year results of vision, corneal aberrometry and contrast sensitivity (CS) in low light conditions between 5- and 10-minute accelerated cross-linking (CXL) protocols. Methods. Thirty eyes were evaluated in each studied group. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity by the SC-2000 Snellen chart, corneal higher order aberrations using the OPD Scan III and CS using MonCv3System was tested under mesopic (20 lux) and scotopic (0.5 lux) light conditions at pre-CXL and 6 and 12 months post-CXL. Results. At 12 months, a mean improvement of 0.06±0.22 (22.2%) and 0.02±0.25 logMAR (7.9%) in mesopic UDVA and 0.01±0.13 (14.3%) and 0.07±0.13 logMAR (87.9%) in mesopic CDVA was observed in the 5- and 10-minute groups, respectively. Mean decline in scotopic UDVA was 0.01±0.16 (1.0%) and 0.03±0.17 logMAR (11.9%) and mean improvement in scotopic CDVA was 0.03±0.10 (35.5%) and 0.02±0.07 logMAR (22.2%), respectively. Inter-group differences in the decrease of corneal aberrations were not statistically significant. Among CS variables, only inter-group changes in corrected CS 0.5 to 2.2 was significantly different (all P<0.050). The linear regression analysis showed that these differences were related to baseline values not CXL protocols; corrected CS 0.5 (Pgroup=0.261 and Pbaseline value<0.001), CS 1.1 (Pgroup=0.250 and Pbaseline value<0.001), and CS 2.2 (Pgroup=0.101 and Pbaseline value=0.054). Conclusions. Changing the intensity of UV in cross-linking from 18mW/ cm2 to 9mW/ cm2 does not affect the visual function under low-light conditions.
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A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer.
Yano, T, Kasai, H, Horimatsu, T, Yoshimura, K, Teramukai, S, Morita, S, Tada, H, Yamamoto, Y, Kataoka, H, Kakushima, N, et al
Oncotarget. 2017;(13):22135-22144
Abstract
Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period. This study aimed to evaluate the safety and efficacy of PDT using second generation photosensitizer, talaporfin sodium for local failure after CRT. This was the multi-institutional non-randomized phase II study. Patients with histologically proven local failure limited within the muscularis propria after 50Gy or more radiotherapy (RT) for esophageal cancer were eligible. We set the primary endpoint as local complete response (L-CR) per patients. And, secondary endpoints were confirmed L-CR, local progression free survival (L-PFS), progression free survival (PFS), overall survival (OS), L-CR per lesions (Lesion L-CR), and confirmed Lesion L-CR. The PDT procedure commenced with intravenous administration of a 40 mg/m2 dose of talaporfin sodium followed by diode laser irradiation at a 664 nm wavelength. 26 eligible patients were enrolled and all were treated with PDT. Twenty three patients with 25 lesions were assessed L-CR after PDT; the L-CR rate per patients was 88.5% (95% CI: 69.8%-97.6%). No skin phototoxicity was observed, and no grade 3 or worse non-hematological toxicities related to PDT were observed. PDT using talaporfin sodium and a diode laser is a safe and curative salvage treatment for local failure after CRT or RT for patients with esophageal cancer.
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Primary photodynamic therapy with verteporfin for small pigmented posterior pole choroidal melanoma.
Fabian, ID, Stacey, AW, Papastefanou, V, Al Harby, L, Arora, AK, Sagoo, MS, Cohen, VM, ,
Eye (London, England). 2017;(4):519-528
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Abstract
PurposeThe purpose of the study was to investigate the outcomes of primary photodynamic therapy (PDT) for small pigmented posterior pole choroidal melanoma.Patients and methodsProspective interventional consecutive case series of 15 patients with small pigmented posterior pole choroidal melanoma, who were treated with three sessions of PDT and followed-up thereafter. Risk factors for failure were assessed and outcome measures at presentation were compared to those at last follow-up visit.ResultsTumor control was achieved in 12 (80%) patients in a median follow-up time of 15 months (mean 14, range 8-18). Three patients failed treatment, diagnosed in a median time of 5 months (mean 4, range 3-6), after first PDT. In all failed cases, lesions were 100% pigmented; de novo melanoma rather than transformed nevi and showed a radial growth pattern rather than increased thickness. All failed cases were subsequently successfully treated with radiotherapy. In this cohort, subretinal fluid (SRF) was significantly reduced (P<0.001), vision did not deteriorate (P=0.11) and even improved in patients with subfoveal SRF at presentation (P=0.018), tumor height significantly decreased (P=0.037) and no complications were recorded.ConclusionPrimary PDT was found to be a safe and efficient treatment modality for small pigmented posterior pole choroidal melanoma, achieving short-term tumor control in 80% of patients. PDT offers patients the opportunity to preserve vision by avoiding the retinopathy associated with conventional radiation treatments for choroidal melanoma. However, the long-term local control of these tumors remains uncertain.
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Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes.
Caruso, C, Ostacolo, C, Epstein, RL, Barbaro, G, Troisi, S, Capobianco, D
Cornea. 2016;(2):145-50
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PURPOSE To report the clinical outcomes with 24-month follow-up of transepithelial cross-linking using a combination of a D-alpha-tocopheryl polyethylene-glycol 1000 succinate (vitamin E-TPGS)-enhanced riboflavin solution and abbreviated low fluence UV-A treatment. METHODS In a nonrandomized clinical trial, 25 corneas of 19 patients with topographically proven, progressive, mild to moderate keratoconus over the previous 6 months were cross-linked, and all patients were examined at 1, 3, 6, 12, and 24 months. The treatments were performed using a patented solution of riboflavin and vitamin E-TPGS, topically applied for 15 minutes, followed by two 5-minute UV-A treatments with separate doses both at fluence below 3 mW/cm(2) that were based on preoperative central pachymetry. RESULTS During the 6-month pretreatment observation, the average Kmax increased by +1.99 ± 0.29 D (diopter). Postoperatively, the average Kmax decreased, changing by -0.55 ± 0.94 D, by -0.88 ± 1.02 D and by -1.01 ± 1.22 D at 6, 12, and 24 months. Postoperatively, Kmax decreased in 19, 20, and 20 of the 25 eyes at 6 months, 12 months, and 24 months, respectively. Refractive cylinder was decreased by 3 months postoperatively and afterward, changing by -1.35 ± 0.69 D at 24 months. Best spectacle-corrected visual acuity (BSCVA) improved at 6, 12, and 24 months, including an improvement of -0.19 ± 0.13 logarithm of the minimum angle of resolution units at 24 months. There was no reduction in endothelial cell count. No corneal abrasions occurred, and no bandage contact lenses or prescription analgesics were used during postoperative recovery. CONCLUSIONS Transepithelial cross-linking using the riboflavin-vitamin E solution and brief, low-dose, pachymetry-dependent UV-A treatment safely stopped keratoconus progression.
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Morphological and functional correlations in riboflavin UV A corneal collagen cross-linking for keratoconus.
Mazzotta, C, Caporossi, T, Denaro, R, Bovone, C, Sparano, C, Paradiso, A, Baiocchi, S, Caporossi, A
Acta ophthalmologica. 2012;(3):259-65
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PURPOSE To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross-linking (CXL) for the stabilization of progressive keratoconus. METHODS Forty-four eyes with progressive keratoconus were enrolled in the Siena Eye Cross Study (prospective nonrandomized phase II open trial). All eyes underwent Riboflavin UV A CXL. Preoperative and postoperative evaluation comprised: UCVA, BSCVA, optical pachymetry (Visante OCT, Zeiss, Germany), corneal topography (CSO, Florence, Italy) and tomography (Orbscan IIz; B&L, Rochester, NY, USA) and in vivo confocal microscopy (Heidelberg Retina Tomograph II; Rostock, Heidelberg Gmbh, Germany). Examinations were performed preoperatively 6 months and one day before treatment and at 1, 3, 6 and 12 months of follow-up. RESULTS In vivo corneal confocal microscopy showed time-dependent postoperative epithelial and stromal modifications after cross-linking. Epithelial thinning associated with stromal oedema and keratocytes apoptosis explained initial tendency towards slightly reduced VA and more glare one month postoperatively in 70% of eyes. Furthermore, a statistically not significant early worsening of topographic mean K values was observed. Orbscan II analysis significantly underestimated pachymetric values after treatment. Pachymetric underestimation was rectified by high-resolution optical pachymetry provided by the Visante OCT system. After the third post-CXL month, epithelial thickening, disappearance of oedema and new collagen compaction recorded by in vivo corneal confocal microscopy explained the improvements in visual performance during the follow-up. Changes in stromal reflectivity and collagen compaction observed by in vivo confocal microscopy were associated with corneal flattening and reduction in anterior elevation values recorded by differential topographic analysis. CONCLUSION Corneal structural changes assessed by in vivo corneal confocal microscopy demonstrated significant correlations with visual function (UCVA and BSCVA) and morphological (corneal topography, pachymetry, elevation analysis) findings recorded after riboflavin-UV A-induced CXL.
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A European multicentre photopatch test study.
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The British journal of dermatology. 2012;(5):1002-9
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BACKGROUND The two most common agent groups currently responsible for photoallergic contact dermatitis (PACD) are organic ultraviolet (UV) absorbers in sunscreens and topical nonsteroidal anti-inflammatory drugs (NSAIDs). However, availability of information on the photoallergenic potential of these agents is scarce. OBJECTIVES To obtain current information on the frequency of PACD to 19 organic UV absorbers and five topical NSAIDs, including newer agents, in common usage in Europe. METHODS A prospective, multicentre photopatch test study was conducted with 1031 patients attending for investigation of suspected PACD in 30 centres across 12 European countries. RESULTS A total of 346 PACD reactions in 200 (19·4%) subjects occurred. PACD was most commonly caused by the topical NSAIDs, ketoprofen (128 subjects) and etofenamate (59 subjects). Of the organic UV absorbers, octocrylene, benzophenone-3 and butyl methoxydibenzoylmethane most frequently elicited PACD. The 'newer' organic sunscreen absorbers rarely led to PACD. There appeared to be an association between the agents ketoprofen, octocrylene and benzophenone-3, with several subjects developing PACD to two or all three agents concomitantly. Allergic contact dermatitis (ACD) was less commonly observed than PACD, comprising 55 reactions in 47 (5%) subjects. Irritant reactions and photoaugmentation and photoinhibition of ACD occurred infrequently. CONCLUSIONS The European multicentre photopatch test study has provided current information on the relative frequency of PACD to common photoallergens. Such data will be of value when deciding on which agents to include in a future European 'baseline' photopatch test series.
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Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer.
Yano, T, Muto, M, Yoshimura, K, Niimi, M, Ezoe, Y, Yoda, Y, Yamamoto, Y, Nishisaki, H, Higashino, K, Iishi, H
Radiation oncology (London, England). 2012;:113
Abstract
BACKGROUND Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer. METHODS This phase I, laser dose escalation study used a fixed dose (40 mg/m²) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm², with an escalation plan to 75 J/cm² and 100 J/cm². RESULTS 9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT. CONCLUSIONS PDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm².
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A multicenter Phase I safety study of intratumoral photoactivation of talaporfin sodium in patients with refractory solid tumors.
Lustig, RA, Vogl, TJ, Fromm, D, Cuenca, R, Alex Hsi, R, D'Cruz, AK, Krajina, Z, Turić, M, Singhal, A, Chen, JC
Cancer. 2003;(8):1767-71
Abstract
BACKGROUND Photodynamic therapy (PDT) currently is approved for the palliative treatment of malignancies of the aerodigestive tract using laser-activated porfimer sodium. A new approach has been developed, based on intratumoral placement of a nonlaser light device that activates talaporfin sodium, that may expand the use of PDT to include a broader range of treatment-resistant malignancies. The safety of this approach was assessed in a Phase I study in patients with locally advanced, refractory tumors. METHODS Twenty-one patients with radiation-resistant or chemotherapy-resistant or inoperable malignancies were enrolled in four cohorts representing four light doses. Patients were treated with a single intratumoral light device and a fixed photosensitizer dose. Safety assessments were based on review of adverse events (AEs) and serious adverse events (SAEs), and independent evaluation of computed tomography (CT) images. RESULTS The observed occurrence of treatment-related AEs and SAEs was minimal. No cutaneous phototoxicity was observed in any patient. The overall observed tumor response rate was 33%. CONCLUSIONS Photoactivation of talaporfin sodium using intratumoral nonlaser light was found to be safe in the patient population of the current study at all light dose levels tested.