Clinical efficacy and safety of two different hematoporphyrin monomethyl ether-mediated photodynamic therapy regimen in Chinese children with port-wine stain
Sheng Zhang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorXiuwei Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, Beijing, China
Search for more papers by this authorHongguang Chen
Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Search for more papers by this authorHuina Cao
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorHongli Zhang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorMing Yang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorYun Zhu
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorQin Qin
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorXiaoyan Liu
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorCorresponding Author
Jianhua Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, Beijing, China
Correspondence
Jianhua Wang, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Gaolei Zhang, Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Gaolei Zhang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Correspondence
Jianhua Wang, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Gaolei Zhang, Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Search for more papers by this authorSheng Zhang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorXiuwei Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, Beijing, China
Search for more papers by this authorHongguang Chen
Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Search for more papers by this authorHuina Cao
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorHongli Zhang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorMing Yang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorYun Zhu
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorQin Qin
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorXiaoyan Liu
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Search for more papers by this authorCorresponding Author
Jianhua Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, Beijing, China
Correspondence
Jianhua Wang, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Gaolei Zhang, Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Gaolei Zhang
Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Correspondence
Jianhua Wang, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Gaolei Zhang, Department of Dermatology and Venereology, Capital Institute of Pediatrics, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Ya Bao Street, Chao Yang District, Beijing 100 020, China.
Email: [email protected]
Search for more papers by this authorSheng Zhang, Xiuwei Wang and Hongguang Chen contributed equally to this manuscript.
Abstract
Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has achieved encouraging clinical outcomes in adult port-wine stain (PWS). Optimal treatment option for children with PWS was minimal. To compare whether the clinical effectiveness of HMME-PDT with the 5-min (fast) administration treatment regimen (FATR) was better than the 20-min (slow) administration treatment regimen (SATR) for PWS of children in vivo and in vitro. Thirty-four children with PWS were divided into two groups including FATR and SATR. The two groups received three times HMME-PDT, respectively. Treatment efficacy and safety were evaluated in vivo and in vitro. Erythema index (EI) was used to evaluate the clinical outcomes. Both FATR and SATR were effective and safe in children with PWS after HMME-PDT. There were significance differences between the two groups in reductions of EI after the second treatment (p < 0.001) and the third treatment (p < 0.001) with HMME-PDT. The serum HMME concentration reach the peak level at short time compare with SATR group. A significance increased superoxide levels were observed in FATR group compare to SATR groups in vitro (p < 0.05). Our study suggested that HMME-PDT was effective and safe for children with PWS, the therapy regimen with FATR was better in clinical efficacy than that of the SATR.
CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest to declare.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| exd14834-sup-0001-FigureS1.jpgimage/jpp, 1.7 MB |
Figure S1. Effects of HMME-PDT on the growth of HUVECs. (A)The effectiveness of HMME-PDT on morphologic changes in HUVECs, Bars = 200 μm. (B) Cell viability was detected by MTT assay. HUVECs were cultured in 6-well plates for 36 h, and then subjected to HMME-PDT treatment. A fresh solution of HMME (0, 0.5, 1, 2 and 4 μg/mL) was given to the HUVECs within 5 min (FATR regimen) or 20 min (SATR regimen). The 532 nm green LED light was applied vertically on the HUVECs for 20 min, and MTT assay was performed. Data were presented as mean ± SEM calculated from three repeat tests (n = 3). |
| exd14834-sup-0002-TableS1.docWord document, 32 KB |
Table S1. Pairwise effect comparison of time at each treatment group. |
| exd14834-sup-0003-TableS2.docWord document, 30.5 KB |
Table S2. Comparison of treatment outcome between two groups at each time. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Chen JK, Ghasri P, Aguilar G, et al. An overview of clinical and experimental treatment modalities for port wine stains. J Am Acad Dermatol. 2012; 67(2): 289-304.
- 2Shirley MD, Tang H, Gallione CJ, et al. Sturge–weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013; 368(21): 1971-1979.
- 3Updyke KM, Khachemoune A. Port-wine stains: a focused review on their management. J Drugs Dermatol. 2017; 16(11): 1145-1151.
- 4Hagen SL, Grey KR, Korta DZ, Kelly KM. Quality of life in adults with facial port-wine stains. J Am Acad Dermatol. 2017; 76(4): 695-702.
- 5Zhao Y, Tu P, Zhou G, et al. Hemoporfin photodynamic therapy for port-wine stain: a randomized controlled trial. PLoS One. 2016; 11(5):e0156219.
- 6Minkis K, Geronemus RG, Hale EK. Port wine stain progression: a potential consequence of delayed and inadequate treatment? Lasers Surg Med. 2009; 41(6): 423-426.
- 7Chapas AM, Eickhorst K, Geronemus RG. Efficacy of early treatment of facial port wine stains in newborns: a review of 49 cases. Lasers Surg Med. 2007; 39(7): 563-568.
- 8Huikeshoven M, Koster PH, de Borgie CA, Beek JF, van Gemert MJ, van der Horst CM. Redarkening of port-wine stains 10 years after pulsed-dye-laser treatment. N Engl J Med. 2007; 356(12): 1235-1240.
- 9Yu W, Zhu J, Wang L, et al. Double pass 595 nm pulsed dye laser does not enhance the efficacy of port wine stains compared with single pass: a randomized comparison with histological examination. Photomed Laser Surg. 2018; 36(6): 305-312.
- 10Savas JA, Ledon JA, Franca K, Chacon A, Nouri K. Pulsed dye laser-resistant port-wine stains: mechanisms of resistance and implications for treatment. Br J Dermatol. 2013; 168(5): 941-953.
- 11van Raath MI, Chohan S, Wolkerstorfer A, van der Horst C, Storm G, Heger M. Port wine stain treatment outcomes have not improved over the past three decades. J Eur Acad Dermatol Venereol. 2019; 33(7): 1369-1377.
- 12Klein A, Baumler W, Landthaler M, Babilas P. Laser and IPL treatment of port-wine stains: therapy options, limitations, and practical aspects. Lasers Med Sci. 2011; 26(6): 845-859.
- 13Li-Qiang G, Hua W, Si-Li N, Chun-Hua T. A clinical study of HMME-PDT therapy in Chinese pediatric patients with port-wine stain. Photodiagnosis Photodyn Ther. 2018; 23: 102-105.
- 14Gao K, Huang Z, Yuan KH, Zhang B, Hu ZQ. Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of port-wine stain birthmarks. Br J Dermatol. 2013; 168(5): 1040-1046.
- 15Zhao Y, Zhou Z, Zhou G, et al. Efficacy and safety of hemoporfin in photodynamic therapy for port-wine stain: a multicenter and open-labeled phase IIa study. Photodermatol Photoimmunol Photomed. 2011; 27(1): 17-23.
- 16Yu W, Ma G, Qiu Y, et al. 18 years long-term results of facial port-wine stain (PWS) after photodynamic therapy (PDT)–a case report. Photodiagnosis Photodyn Ther. 2015; 12(1): 143-145.
- 17Zhao J, Deng H, Xie J, et al. Towards characteristics of photodynamic drugs specifically aimed at microvascular diseases. Mini Rev Med Chem. 2010; 10(4): 332-341.
- 18Wei Y, Kong B, Song K, Qu X, Jin Q, Yang Q. Involvement of mitochondria-caspase pathway in Hemoporfin-mediated cell death. Photochem Photobiol. 2007; 83(6): 1319-1324.
- 19Kessel D, Luo Y, Deng Y, Chang CK. The role of subcellular localization in initiation of apoptosis by photodynamic therapy. Photochem Photobiol. 1997; 65(3): 422-426.
- 20Sun PH, Zhao X, Zhou Y, et al. Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers. Acta Pharmacol Sin. 2011; 32(12): 1549-1554.
- 21Zhang Y, Yang Y, Zhang Z, et al. Clinical study on hemoporfin PDT for infant facial port-wine stains. Photodiagnosis Photodyn Ther. 2019; 25: 106-110.
- 22Wu Q, Tu P, Zhou G, et al. A dose-finding study for hemoporfin in photodynamic therapy for port-wine stain: a multicenter randomized double-blind phase IIb trial. Photodermatol Photoimmunol Photomed. 2018; 34(5): 314-321.
- 23Zhang Y, Zou X, Chen H, Yang Y, Lin H, Guo X. Clinical study on clinical operation and post-treatment reactions of HMME-PDT in treatment of PWS. Photodiagnosis Photodyn Ther. 2017; 20: 253-256.
- 24Pu Y, Chen W, Yu Z. Research progress of Hemoporfin–part one: preclinical study. Photodiagnosis Photodyn Ther. 2012; 9(2): 180-185.
- 25Benson L, English T, Conroy DE, Pincus AL, Gerstorf D, Ram N. Age differences in emotion regulation strategy use, variability, and flexibility: an experience sampling approach. Dev Psychol. 2019; 55(9): 1951-1964.
- 26Parsafar P, Fontanilla FL, Davis EL. Emotion regulation strategy flexibility in childhood: when do children switch between different strategies? J Exp Child Psychol. 2019; 183: 1-18.
- 27McRae K, Gross JJ. Emotion regulation. Emotion. 2020; 20(1): 1-9.
- 28Hannivoort LN, Absalom AR, Struys M. The role of pharmacokinetics and pharmacodynamics in clinical anaesthesia practice. Curr Opin Anaesthesiol. 2020; 33(4): 483-489.
- 29Chun-Hua T, Li-Qiang G, Hua W, et al. Efficacy and safety of hemoporfin photodynamic therapy for port-wine stains in paediatric patients: a retrospective study of 439 cases at a single Centre. Photodiagnosis Photodyn Ther. 2021; 36:102568.
- 30Zhao Y, Tao J, Tu P. Quantitative evaluation of efficacy of photodynamic therapy for port-wine stains using erythema index image analysis. Photodiagnosis Photodyn Ther. 2013; 10(2): 96-102.
- 31Yamamoto T, Takiwaki H, Arase S, Ohshima H. Derivation and clinical application of special imaging by means of digital cameras and ImageJ freeware for quantification of erythema and pigmentation. Skin Res Technol. 2008; 14(1): 26-34.
- 32Qiu H, Gu Y, Wang Y, Huang N. Twenty years of clinical experience with a new modality of vascular-targeted photodynamic therapy for port wine stains. Dermatol Surg. 2011; 37(11): 1603-1610.
- 33Zhang B, Zhang TH, Huang Z, Li Q, Yuan KH, Hu ZQ. Comparison of pulsed dye laser (PDL) and photodynamic therapy (PDT) for treatment of facial port-wine stain (PWS) birthmarks in pediatric patients. Photodiagnosis Photodyn Ther. 2014; 11(4): 491-497.
- 34Huang Y, Yang J, Sun L, Zhang L, Bi M. Efficacy of influential factors in hemoporfin-mediated photodynamic therapy for facial port-wine stains. J Dermatol. 2021; 48(11): 1700-1708.
- 35Zhang Y, Jiang S, Chen H, Zou X. Hemoporfin-mediated photodynamic therapy for the treatment of port-wine stain birthmarks in pediatric patients. An Bras Dermatol. 2017; 92(4): 559-561.
- 36Wen L, Zhang Y, Zhang L, et al. Application of different noninvasive diagnostic techniques used in HMME-PDT in the treatment of port wine stains. Photodiagnosis Photodyn Ther. 2019; 25: 369-375.
- 37Gomez-Martin I, Moreno S, Andrades-Lopez E, et al. Histopathologic and immunohistochemical correlates of confocal descriptors in pigmented facial macules on photodamaged skin. JAMA Dermatol. 2017; 153(8): 771-780.
- 38Basaran YK, Gurel MS, Erdemir AT, Turan E, Yurt N, Bagci IS. Evaluation of the response to treatment of psoriasis vulgaris with reflectance confocal microscopy. Skin Res Technol. 2015; 21(1): 18-24.
- 39Fu Z, Huang J, Xiang Y, et al. Characterization of laser-resistant port wine stain blood vessels using In vivo reflectance confocal microscopy. Lasers Surg Med. 2019; 51(10): 841-849.
- 40Barrett CD, Hsu AT, Ellson CD, et al. Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy. Clin Exp Immunol. 2018; 194(1): 103-117.
- 41Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics and pharmacodynamics of isepamicin. Clin Pharmacokinet. 2000; 38(3): 205-223.
- 42Zeng H, Sun M, Zhou C, et al. Hematoporphyrin monomethyl ether-mediated photodynamic therapy selectively kills sarcomas by inducing apoptosis. PLoS One. 2013; 8(10):e77727.
- 43Li B, Chen Z, Liu L, Huang Z, Huang Z, Xie S. Differences in sensitivity to HMME-mediated photodynamic therapy between EBV+ C666–1 and EBV–CNE2 cells. Photodiagnosis Photodyn Ther. 2010; 7(3): 204-209.
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