Application of the adenosine triphosphate sensitivity assay in infantile vascular anomalies

Abstract

Background: The term vascular anomalies include various vascular tumors and vascular malformations, among them infantile hemangiomas and capillary malformations are the most well-known associated diseases in early ages. Multiple drugs have been introduced for intervention, but susceptibility test in vitro were scarcely reported. Objective: To evaluate the inhibition effect of different drugs by adenosine triphosphate sensitivity assay in vitro before the treatment of infantile hemangiomas and capillary malformations. Methods: Specimens were selected from 5 cases of infantile hemangiomas and 11 cases of capillary malformations. Propranolol, rapamycin, sildenafil and itraconazole were tested for their growth inhibition effect by using the adenosine triphosphate sensitivity assay. Results: Propranolol demonstrated inhibitory effects on infantile hemangiomas cells. Rapamycin and itraconazole both showed inhibitory effects on infantile hemangiomas cells and capillary malformations cells. Sildenafil has no growth inhibitory effect on infantile hemangiomas cells or capillary malformations cells. Conclusion: Adenosine triphosphate sensitivity assay is a sensitive and useful testing method before the management of vascular anomalies, and individualized medication suggestions for the choice of therapeutic drugs were offered based on the testing result and together with a comprehensive evaluation of each infant.

Itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of hemangioma endothelial cells by downregulating the hedgehog signaling pathway

“…Itraconazole prevented lung cancer endothelial cells from proliferating and migrating; moreover, it exhibited an antiangiogenic effect via the inhibition of tube formation [ 16 ]. Itraconazole has been proven to be a potential therapeutic for IH in various studies [ 6 , 7 , 11 , 17 ]. Another study reported that itraconazole promoted the regression of IH through the inhibition of platelet-derived growth factor (PDGF) [ 18 ]; however, this finding can only partly explain the inhibitory effect of itraconazole on IH.…”

“…Clinicians found that itraconazole promoted hemangioma regression when used for the treatment of fungal infection of IH [ 6 ]. In addition, itraconazole exerted a significant inhibitory effect on IH cells in vitro [ 7 ]. Furthermore, this drug inhibits endothelial cell proliferation and tube formation by blocking the signaling pathway related to vascular endothelial growth factor receptor 2 (VEGFR2) [ 8 ].…”

Itraconazole therapy for infant hemangioma: Two case reports

“…The liver function and blood test were normal during the treatment, and conditions continued to improve 6 mo after withdrawal of the medicine. Moreover, Li et al [ 13 ] selected specimens of 5 IHs cases and 11 capillary malformations to perform an adenosine triphosphate sensitivity assay to detect the growth inhibition activity of propranolol, rapamycin, sildenafil, and itraconazole[ 13 ]. They found that itraconazole exhibited clear inhibition on the cellular proliferation of both IHs and capillary malformations[ 13 ].…”

“…Moreover, Li et al [ 13 ] selected specimens of 5 IHs cases and 11 capillary malformations to perform an adenosine triphosphate sensitivity assay to detect the growth inhibition activity of propranolol, rapamycin, sildenafil, and itraconazole[ 13 ]. They found that itraconazole exhibited clear inhibition on the cellular proliferation of both IHs and capillary malformations[ 13 ]. Bessar et al [ 14 ] investigated the efficacy of propranolol and itraconazole on IHs by observing the variation of serum angiopoietin-2.…”