Meerim Park1, Hye Lim Jung2, Ye Jee Shim3, Heung Sik Kim3, Hoi Soo Yoon4, Sang Kyu Park5, Hee Won Cheuh6, Mee Jeong Lee7, Jae Min Lee8, Eun Sil Park9, Jae Hee Lee10, Yeon-Jung Lim11, Young Bae Choi12. 1. Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang, Korea. 2. Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. hl.jung@samsung.com. 3. Department of Pediatrics, Keimyung University School of Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea. 4. Department of Pediatrics, Kyung Hee University College of Medicine, Seoul, Korea. 5. Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea. 6. Department of Pediatrics, Dong-A University College of Medicine, Busan, Korea. 7. Department of Pediatrics, Dankook University College of Medicine, Cheonan, Korea. 8. Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea. 9. Department of Pediatrics, Gyeonsang National University College of Medicine, Jinju, Korea. 10. Department of Pediatrics, Chosun University School of Medicine, Gwangju, Korea. 11. Department of Pediatrics, Chungnam National University College of Medicine, Daejeon, Korea. 12. Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Korea.
Abstract
BACKGROUND: Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment. METHODS: For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter ≥2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays. RESULTS: Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-α, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-α, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. CONCLUSION: MMP-2, VEGF-α, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol. IMPACT: We found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.
BACKGROUND: Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment. METHODS: For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter ≥2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays. RESULTS: Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-α, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-α, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. CONCLUSION:MMP-2, VEGF-α, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol. IMPACT: We found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.
Authors: Rodica Elena Heredea; Eugen Melnic; Laura Elena Cirligeriu; Patricia Lorena Berzava; Maria Corina Stănciulescu; Călin Marius Popoiu; Anca Maria Cimpean Journal: Children (Basel) Date: 2022-06-17