• alexandrite laser
• color Doppler ultrasound
• hybrid infantile hemangioma
• pulsed dye laser
• treatment

• Hemangiol
• infantile haemangioma
• oral propranolol
• safety

• Infantile hemangioma
• Neonate
• PHACE
• Propranolol
• Timolol

• IFNAR1/2
• JAK-STAT
• apoptosis
• immunogenic cell death
• necroptosis

Infantile hemangiomas (IHs) are the most common benign vascular tumor of infancy. They occur more frequently in female infants. The cause of hemangioma is currently unknown; however, current studies suggested the importance of estrogen (E2) signaling in hemangioma proliferation.

Hemangioma-derived stem cells (HemSCs) were cultured with estrogen for 48–72 h; the cell viability and proliferation were evaluated with the messenger RNA (mRNA) and protein expression levels of fibroblast growth factor 2 (FGF2), vascular endothelial growth factor-A (VEGF-A) and estrogen receptor-α (ER-α), by application of several in vitro assays, such as methyl thiazolyl tetrazolium (MTT), reverse transcriptase–polymerase chain reaction (RT-PCR), real-time PCR, enzyme-linked immunosorbent assay (ELISA) and Western blotting. Also, the cell population’s response to external estrogen was investigated by in vivo experiments. HemSCs and human umbilical vein endothelial cells (HUVECs) were mixed and injected subcutaneously into 20 flank of BALB/c-nu mice, which were randomly divided into 5 groups based on different E2 treatment doses (0, 0.01, 0.1 and 1 mg, respectively), 0.1 mg dimethyl sulfoxide (DMSO) as control. Each group of mice were treated intramuscularly every week, then 2 and 4 weeks later, the subcutaneous implants were harvested and evaluated the tumor tissues with microvessel density (MVD) assay and immunohistochemistry.

The study demonstrated that application of E2 increased the expression of FGF2, VEGF-A, and ER-α in HemSCs with the optimal concentration from 10⁻⁹ to 10⁻⁵ M. Two-week treatment of E2 promoted expression of VEGF-A and FGF2 in HemSCs culture. Morphological, histological and immunohistological improvements were observed in vivo using murine IH model in which HemSCs and HUVECs were implanted into BALB/c-nu mice that were post-injected with E2. In the grafts, mean MVD was markedly increased.

The results suggested that E2 promotes angiogenesis via combination with ER-α to up-regulate the expression of VEGF-A in HemSCs, promoting proliferation of IHs. These findings provide critical insight into the potential mechanisms of E2 action on IHs.

• estrogen
• estrogen receptor-α
• hemangioma-derived stem cells
• infantile hemangioma
• vascular endothelial growth factor-A

• Infantile hemangiomas
• acrodermatitis enteropathica
• atopic dermatitis
• biotin and vitamin B6 deficiency
• candidiasis
• diaper dermatitis
• erythema toxicum neonatorum
• erythroderma
• fasciitis
• herpes simplex virus
• impetigo
• napkin disease
• omphalitis
• psoriasis
• pyodermitis
• seborrhoeic dermatitis
• varicella zoster virus

• Hemangioma
• PEDF
• Proliferation
• Regression
• VEGF

• Adolescent
• Antigens, CD34/biosynthesis
• Antigens, CD34/genetics
• Cell Proliferation
• Child
• Child, Preschool
• Eye Proteins/biosynthesis
• Eye Proteins/genetics
• Fluorescent Antibody Technique
• Hemangioma/pathology
• Humans
• Infant
• Ki-67 Antigen/biosynthesis
• Ki-67 Antigen/genetics
• Nerve Growth Factors/biosynthesis
• Nerve Growth Factors/genetics
• RNA, Messenger/biosynthesis
• Serpins/biosynthesis
• Serpins/genetics
• Vascular Endothelial Growth Factor A/biosynthesis
• Vascular Endothelial Growth Factor A/genetics

• Administration, Topical
• Adrenergic beta-Antagonists/therapeutic use
• Eyelid Neoplasms/drug therapy
• Hemangioma, Capillary/drug therapy
• Humans
• Infant
• Skin Neoplasms/drug therapy

Infantile hemangioma (IH) is the most common benign tumor seen in infancy. This review provides up-to-date information on the pathophysiology, variations in clinical presentation, and natural history of IH, elaborating on associated anomalies, such as PHACE(S) syndrome and LUMBAR syndrome. Because of the benign and self-limiting characteristics seen in more than 90% of cases of IH, a conservative approach is usually chosen. However, some circumstances, such as ulceration, vision loss, breathing difficulties, or potential disfigurement, will require treatment during the proliferative phase. For decades, treatment of IH has primarily consisted of corticosteroids or surgery. Since 2008, propranolol has become the treatment of first choice. In this article, we bring to light the crucial changes in the treatment of IH over the past years. To date, there is still a lack of data on the possible long-term effects of propranolol treatment in young infants. A theoretical probability of the central nervous system being affected (that is, impairment of short- and long-term memory, psychomotor function, sleep quality, and mood) has recently been suggested. This review highlights research topics concerning these long-term adverse effects. Finally, information is provided on the potential instruments to measure IH severity and activity in clinical trials and/or in clinical practice and the recently developed and first-validated IH-specific quality-of-life questionnaire.

• Infantile hemangioma
• Propranolol
• Beta-blocker
• Adverse effect
• Development