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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Dermatologic Surgery Vol. 40, No. 5 ( 2014-05), p. 589-
    In: Dermatologic Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 5 ( 2014-05), p. 589-
    Type of Medium: Online Resource
    ISSN: 1076-0512
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 2020062-6
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  • 2
    In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 86, No. 3 ( 2008-08-15), p. 423-429
    Type of Medium: Online Resource
    ISSN: 0041-1337
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 2035395-9
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  • 3
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 10 ( 2021-09-26), p. 1558-
    Abstract: Extracorporeal photopheresis (ECP), an immunomodulatory therapy for the treatment of chronic graft-versus-host disease (cGvHD), exposes isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light to induce the apoptosis of T-cells and, hence, to modulate immune responses. However, 8-MOP-ECP kills diseased and healthy cells with no selectivity and has limited efficacy in many cases. The use of 5-aminolevulinic acid (ALA) and light (ALA-based photodynamic therapy) may be an alternative, as ex vivo investigations show that ALA-ECP kills T-cells from cGvHD patients more selectively and efficiently than those treated with 8-MOP-ECP. The purpose of this phase I-(II) study was to evaluate the safety and tolerability of ALA-ECP in cGvHD patients. The study included 82 treatments in five patients. One patient was discharged due to the progression of the haematological disease. No significant persistent changes in vital signs or laboratory values were detected. In total, 62 adverse events were reported. Two events were severe, 17 were moderate, and 43 were mild symptoms. None of the adverse events evaluated by the internal safety review committee were considered to be likely related to the study medication. The results indicate that ALA-ECP is safe and is mainly tolerated well by cGvHD patients.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 4
    In: Journal of Skin Cancer, Hindawi Limited, Vol. 2011 ( 2011), p. 1-6
    Abstract: Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0–4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage ( P ≤ 0.001 ) . Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.
    Type of Medium: Online Resource
    ISSN: 2090-2905 , 2090-2913
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2011
    detail.hit.zdb_id: 2581531-3
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  • 5
    In: Journal of Skin Cancer, Hindawi Limited, Vol. 2016 ( 2016), p. 1-5
    Abstract: Basal cell carcinoma (BCC) is an invasive epithelial skin tumour. The thickness of the outermost epidermal layer of the skin, the stratum corneum (SC), influences drug uptake and penetration into tumour and may thereby affect the response of BCC to topical treatment. The aim was to investigate a possible relationship between the thickness of the SC and that of the viable part of BCC. Histopathological evaluations of the corresponding SC and viable tumour thickness measurements of individual BCCs of different subtypes were explored. A total of 53 BCCs from 46 patients were studied. The median tumour thickness was 1.7 mm (0.8–3.0 mm), with a significant difference between subtypes ( p 〈 0.001 ). The SC had a median thickness of 0.3 mm (0.2–0.4 mm), with no difference between tumour subtypes ( p = 0.415 ). Additionally, no significant association between the thickness of the SC and that of the viable part of the tumour was demonstrated ( p = 0.381 ). In conclusion our results indicate that SC thickness is relatively constant in BCC.
    Type of Medium: Online Resource
    ISSN: 2090-2905 , 2090-2913
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2581531-3
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  • 6
    In: Cancers, MDPI AG, Vol. 12, No. 2 ( 2020-02-06), p. 377-
    Abstract: Extracorporeal photopheresis (ECP), a modality that exposes isolated leukocytes to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light, is used to treat conditions such as cutaneous T-cell lymphoma and graft-versus-host disease. However, the current procedure of ECP has limited selectivity and efficiency; and produces only partial response in the majority of treated patients. Additionally, the treatment is expensive and time-consuming, so the improvement for this modality is needed. In this study, we used the concept of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor of an endogenously synthesized photosensitizer protoporphyrin IX (PpIX) in combination with blue light to explore the possibility of targeting activated human blood T cells ex vivo. With various T-cell activation protocols, a high ALA-induced PpIX production took place in activated CD3+, CD4+CD25+, and CD8+ T cell populations with their subsequent killing after blue light exposure. By contrast, resting T cells were much less damaged by the treatment. The selective and effective killing effect on the activated cells was also seen after co-cultivating activated and resting T cells. Under our clinically relevant experimental conditions, ALA-PDT killed activated T cells more selectively and efficiently than 8-MOP/UV-A. Monocyte-derived dendritic cells (DCs) were not affected by the treatment. Incubation of ALA-PDT damaged T cells with autologous DCs induced a downregulation of the co-stimulatory molecules CD80/CD86 and also upregulation of interleukin 10 (IL-10) and indoleamine 2,3-dioxygenase expression, two immunosuppressive factors that may account for the generation of tolerogenic DCs. Overall, the data support the potential use of ALA-PDT strategy for improving ECP by selective and effective killing of activated T cells and induction of immune tolerance.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 7
    In: Biomedicines, MDPI AG, Vol. 10, No. 2 ( 2022-01-21), p. 232-
    Abstract: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment. We report from the first study on the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). The treatment reduced the cytokines and exosomes studied, although there was variation among individual PBMC samples. This reduction is consistent with PDT-mediated survivals of subsets of PBMCs. More specifically, the ALA-PDT treatment apparently decreased all pro-inflammatory cytokines included, suggesting that this treatment may provide a strong anti-inflammatory effect. In addition, the treatment has decreased the levels of different types of exosomes, the HLA-DRDPDQ exosome in particular, which plays an important role in the rejection of organ transplantation as well as autoimmune diseases. These results may suggest future therapeutic strategies of ALA-PDT.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 8
    In: Journal of Histochemistry & Cytochemistry, SAGE Publications, Vol. 71, No. 3 ( 2023-03), p. 111-120
    Abstract: Photodynamic therapy (PDT) is an effective and cosmetically beneficial treatment of low-risk basal cell carcinomas (BCCs). To optimize PDT response, it is important to correctly select tumors. We sought to find markers that could identify such tumors beyond contributions from clinical and histological examination. Studies have shown that β-catenin, E-cadherin, and α-smooth muscle actin (SMA) expression can indicate BCC aggressiveness/BCC invasiveness. We wanted to use these markers in an explorative study to investigate whether they were differently expressed among non-recurring compared with recurring BCCs, to evaluate their ability of predicting PDT outcome. Fifty-two BCCs were stained with antibodies against β-catenin, E-cadherin, and α-SMA, and evaluated using immunoreactive score (IRS), subcellular localization, and stromal protein expression. Results showed that IRS of E-cadherin was significantly different among recurring compared with non-recurring BCCs and with area under a receiver operating characteristic curve of 0.71 (95% confidence interval: 0.56–0.86, p=0.025). Stromal β-catenin expression significantly increased among recurring BCCs. Some recurring BCCs had intense expression in the deep invading tumor edge. In conclusion, E-cadherin, and stromal and deep edge β-catenin expression were most prominent in BCCs that recurred post-PDT, suggesting they could potentially predict PDT outcome. Further studies are needed to investigate whether these results are of clinical value:
    Type of Medium: Online Resource
    ISSN: 0022-1554 , 1551-5044
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 1421306-0
    SSG: 12
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  • 9
    In: Lasers in Surgery and Medicine, Wiley, Vol. 50, No. 5 ( 2018-07), p. 469-475
    Abstract: Extracorporeal photopheresis (ECP), an established modality for cutaneous T‐cell lymphoma (CTCL) and graft‐versus‐host disease, involves ex vivo treatment of isolated leukocytes of a patient with the photosensitizing drug 8‐methoxypsoralen (8‐MOP) and ultraviolet‐A (UV‐A) exposure before reinfusion back to the patient. However, 8‐MOP binds to both diseased and normal cells and thus kills both types of the cells after UV‐A illumination with little selectivity. Clinically, this modality gives only partial response in the majority of treated patients. 5‐Aminolevulinic acid (5‐ALA), a precursor of the potent photosensitizer protoporphyrin IX (PpIX), has been shown to selectively induce PpIX in activated T lymphocytes (T cells) and could be an alternative for 8‐MOP. The objectives of this study were to investigate ex vivo 5‐ALA dark toxicity, 5‐ALA‐induced PpIX production, and photodynamic effect on T cells obtained from clinical ECP patients after the treatment of 5‐ALA or 8‐MOP plus a built‐in certified UV‐A source in the commercial Therakos™ Photopheresis System. Materials and Methods Flow cytometry was used to study dark cytotoxic effects of 5‐ALA on human leukocytes, to measure the production of 5‐ALA‐induced PpIX in CD25 + activated T cells from both diluted mononuclear cells and undiluted buffy coat samples of ECP patients and to compare photodynamic effects on CD4 + and CD8 + T cells with 5‐ALA/UV‐A or 8‐MOP/UV‐A. Results No dark toxicity of 5‐ALA on the leukocytes of ECP patients was seen at concentrations up to 10 mM for an incubation of up to 20 hours. 5‐ALA‐induced PpIX was produced more in CD25 + activated T cells than resting T cells in both diluted mononuclear cells and undiluted buffy coat samples, although there was a huge variation of samples from different individual patients. The CD4 + and CD8 + T cells treated with 5‐ALA/UV‐A were killed more than those treated with 8‐MOP/UV‐A. Conclusion These results suggest that 5‐ALA/UV‐A may have the potential for improving the efficacy of ECP. Lasers Surg. Med. 50:469–475, 2018. © 2018 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0196-8092 , 1096-9101
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1475539-7
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  • 10
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 5 ( 2023-02-25), p. 4554-
    Abstract: Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) which is the precursor of the photosensitizer protoporphyrin IX (PpIX) is an available treatment for several diseases. ALA-PDT induces the apoptosis and necrosis of target lesions. We have recently reported the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). This study has investigated the ALA-PDT-mediated effects on PBMC subsets from patients with active Crohn’s disease (CD). No effects on lymphocyte survival after ALA-PDT were observed, although the survival of CD3−/CD19+ B-cells seemed slightly reduced in some samples. Interestingly, ALA-PDT clearly killed monocytes. The subcellular levels of cytokines and exosomes associated with inflammation were widely downregulated, which is consistent with our previous findings in PBMCs from healthy human subjects. These results suggest that ALA-PDT may be a potential treatment candidate for CD and other immune-mediated diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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