ABSTRACT
AIMS: The present study aimed to investigate the effects of laser irradiation on the growth factors and cell apoptosis of in vitro cultured infant hemangioma endothelial cells. MAIN METHODS: Endothelial cells of infant hemangioma were cultured in vitro and irradiated using a variable pulse width 1064â¯nm Nd:YAG laser and intense pulsed light (IPL), the expression of VEGF, VEGFR-2, bFGF and their mRNAs before and after irradiation were measured by ELISA, western blot, RT-PCR and flow cytometry, and changes in the apoptotic rate of endothelial cells in hemangioma were monitored. KEY FINDINGS: The mRNA and protein expressions of VEGF, VEGFR-2, bFGF in hemangioma endothelial cells were inhibited by both Nd:YAG laser and ILP compared to the control cells. The apoptotic rates of hemangioma endothelial cells were also decreased after both laser irradiation treatments in comparison to the blank group. The differences were statistically significant. SIGNIFICANCE: Laser irradiation treats hemangioma not only through a selective photothermal mechanism, but also through cytokine signaling pathways.
Subject(s)
Apoptosis/radiation effects , Endothelial Cells/radiation effects , Gene Expression Regulation, Neoplastic/radiation effects , Hemangioma/metabolism , Hemangioma/pathology , Laser Therapy/methods , Cell Proliferation , Cytokines/genetics , Cytokines/metabolism , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Hemangioma/radiotherapy , Humans , In Vitro Techniques , Infant , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
Infantile hemangioma (IH) is a benign tumor that is formed by aberrant angiogenesis and that undergoes spontaneous regression over time. Propranolol, the first-line therapy for IH, inhibits angiogenesis by downregulating activation of the vascular endothelial growth factor (VEGF) pathway, which is hyperactivated in IH. However, this treatment is reportedly ineffective for 10% of tumors, and 19% of patients relapse after propranolol treatment. Both pro-angiogenic and anti-angiogenic factors regulate angiogenesis, and pigment epithelium-derived factor (PEDF) is the most effective endogenous anti-angiogenic factor. PEDF/VEGF ratio controls many angiogenic processes, but its role in IH and the relationship between this ratio and propranolol remain unknown. Results of the present study showed that the PEDF/VEGF ratio increased during the involuting phase of IH compared with the proliferating phase. Similarly, in hemangioma-derived endothelial cells (HemEC), which were isolated with magnetic beads, increasing the PEDF/VEGF ratio inhibited proliferation, migration, and tube formation and promoted apoptosis. Mechanistically, the VEGF receptors (VEGFR1 and VEGFR2) and PEDF receptor (laminin receptor, LR) were highly expressed in both IH tissues and HemEC, and PEDF inhibited HemEC function by binding to LR. Interestingly, we found that propranolol increased the PEDF/VEGF ratio but did so by lowering VEGF expression rather than by upregulating PEDF as expected. Furthermore, the combination of PEDF and propranolol had a more suppressive effect on HemEC. Consequently, our results suggested that the PEDF/VEGF ratio played a pivotal role in the spontaneous regression of IH and that the combination of PEDF and propranolol might be a promising treatment strategy for propranolol-resistant IH.
Subject(s)
Eye Proteins/metabolism , Hemangioma/drug therapy , Nerve Growth Factors/metabolism , Propranolol/therapeutic use , Serpins/metabolism , Vascular Endothelial Growth Factor A/metabolism , Apoptosis/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Eye Proteins/genetics , Eye Proteins/pharmacology , Hemangioma/blood supply , Hemangioma/metabolism , Humans , Infant , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/prevention & control , Nerve Growth Factors/genetics , Nerve Growth Factors/pharmacology , Receptors, Laminin/genetics , Receptors, Laminin/metabolism , Remission, Spontaneous , Serpins/genetics , Serpins/pharmacology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vasodilator Agents/therapeutic useABSTRACT
Los hemangiomas infantiles subglóticos (HIS) son poco frecuentes y potencialmente mortales. Muchos tratamientos se han descrito para los HIS. El propranolol es una nueva alternativa terapéutica, con resultados exitosos en hemangiomas infantiles de piel y de vía áerea. Caso clínico: Se reporta el manejo de un lactante con HIS que presentaba una obstrucción del 90 por ciento de su vía aérea, que debió ser traqueostomizado, luego se inicio propranolol oral, presentando una muy buena respuesta al mes de tratamiento, con 10 por ciento de obstrucción, retirando traqueostomía precozmente. Conclusión: El descubrimiento del efecto del propranolol en los HIS ha revolucionado su manejo, desplazando a los corticoides y a la cirugía como primera línea de tratamiento. En el presente reporte se discute el manejo actual de los HIS.
Infantile Subglottic Hemangiomas (ISH) are rare and potentially fatal. Many treatments have been described for this condition. Propranolol is a new therapeutic alternative, with successful results in skin and airway infantile hemangiomas. Case study: The case of an infant with ISH and 90 percent blockage of his airway is presented. The patient underwent a tracheostomy procedure and then treated with oral propranolol, showing a good response after a month of treatment, presenting 10 percent obstruction and consequently, ending the tracheostomy early. Conclusion: The discovery of the effect of propranolol in the ISH has revolutionized the management of this condition, displacing steroids and surgery as first-line treatments. This study discusses the current ISH management.
Subject(s)
Humans , Female , Infant , Glottis , Hemangioma/drug therapy , Laryngeal Neoplasms/drug therapy , Propranolol/therapeutic use , Hemangioma/diagnosis , Laryngoscopy , Laryngeal Neoplasms/diagnosis , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Los hemangiomas en la infancia representan el tumor benigno más común. Un porcentaje significativo de estas lesiones es asociado con morbilidad sustancial en la infancia y la niñez. Se realiza una revisión bibliográfica con el fin de profundizar y ampliar los conocimientos sobre el diagnóstico y el tratamiento actualizado del hemangioma infantil. El diagnóstico de los hemangiomas es fundamentalmente clínico. Su cuadro es raramente confundible con otras lesiones. Sin embargo, en ocasiones los hemangiomas profundos pueden presentar problemas de diagnóstico diferencial con otras tumoraciones azuladas en esta localización. Los ß-bloqueantes constituyen el tratamiento de elección de los HI. Aunque se han descrito efectos secundarios aislados, se puede afirmar que es un tratamiento seguro en la edad pediátrica
The hemangiomas in infancy represent the commonnest benign tumor. A significant percentage of these injuries is associated with substantial morbility in infancy and childhood. A bibliographic revision with the aim of deepening and increasing the knowledge on the diagnosis and the treatment updated of the infant hemangioma comes true. The hemangiomas's diagnosis is fundamentally clinical. Your picture is rarely easily confused with another one injuries. However, at times the deep hemangiomas can present problems of differential diagnosis with another one tubercles blued at this location. Them ß-bloqueantes constitute the HI's treatment of choice Although they have described isolated side effects, it can be affirmed that it is a safe treatment in the pediatric age
