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Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model.

ABSTRACT: Current treatments for infantile hemangiomas have unpredictable outcomes. The authors' aim was to develop a nanoporphyrin-delivered, high-efficacy treatment for infantile hemangiomas using a mouse hemangioendothelioma model.The authors injected mouse hemangioendothelioma cells intradermally to axillary regions of 5-week-old, female, nude mice (n = 19) to induce hemangioendothelioma growth. They documented nanoporphyrin accumulation in hemangioendotheliomas using positron emission tomography. For the treatment study, the authors randomized hemangioendothelioma-bearing nude mice (n = 9) into three groups (n = 3 each). Group I received only saline injections. Group II received only laser treatment after saline injection, and group III received laser treatment after nanoporphyrin injection through the tail vein. The authors followed up the treatment response with digital caliper measurements.Hemangioendotheliomas started to grow approximately 1 week after inoculation and resembled infantile hemangiomas histologically. Nanoporphyrin uptake in hemangioendotheliomas was 19.7 ± 2.2, 16.7 ± 2.02, 8.4 ± 0.3, and 4.9 ± 0.6 percent injected dose per gram of tissue at 3, 6, 24, and 48 hours after injection, respectively. Nanoporphyrin uptake was significantly higher than in blood at 24 and 48 hours after injection (p < 0.05). Results of ex vivo biodistribution study were consistent with positron emission tomographic imaging. Hemangioendotheliomas in group III started to regress 1 day after the treatment and disappeared totally by day 21. The difference between tumor volumes in group III and other groups was significant on days 17 and 21 (p < 0.05).Nanoporphyrin accumulated in hemangioendotheliomas at high concentrations, enabling a high-efficacy photodynamic therapy. Given the similarities between hemangioendotheliomas and infantile hemangiomas, this treatment potentially can be a high-efficacy treatment for infantile hemangiomas.

SUBMITTER: Orbay H

PROVIDER: S-EPMC5472049 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model.

Orbay Hakan H Li Yuanpei Y Xiao Wenwu W Cherry Simon R SR Lam Kit K Sahar David E DE

Plastic and reconstructive surgery 20160801 2

<h4>Background</h4>Current treatments for infantile hemangiomas have unpredictable outcomes. The authors' aim was to develop a nanoporphyrin-delivered, high-efficacy treatment for infantile hemangiomas using a mouse hemangioendothelioma model.<h4>Methods</h4>The authors injected mouse hemangioendothelioma cells intradermally to axillary regions of 5-week-old, female, nude mice (n = 19) to induce hemangioendothelioma growth. They documented nanoporphyrin accumulation in hemangioendotheliomas usin ...[more]

PMID: 27465164

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Project description:BackgroundInfantile Hemangiomas (IHs) are common benign vascular tumors of infancy that may have serious consequences. The research on diagnostic markers for IHs is scarce.MethodsThe "limma" R package was applied to identify differentially expressed genes (DEGs) in developing IHs. Plugin ClueGO in Cytoscape software performed functional enrichment of DEGs. The Search Tool for Retrieving Interacting Genes (STRING) database was utilized to construct the PPI network. The least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were used to identify diagnostic genes for IHs. The receiver operating characteristic (ROC) curve evaluated diagnostic genes' discriminatory ability. Single-gene based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted by Gene Set Enrichment Analysis (GSEA). The chemicals related to the diagnostic genes were excavated by the Comparative Toxicogenomics Database (CTD). Finally, the online website Network Analyst was used to predict the transcription factors targeting the diagnostic genes.ResultsA total of 205 DEGs were singled out from IHs samples of 6-, 12-, and 24-month-old infants. These genes principally participated in vasculogenesis and development-related, endothelial cell-related biological processes. Then we mined 127 interacting proteins and created a network with 127 nodes and 251 edges. Furthermore, LASSO and SVM-RRF algorithms identified five diagnostic genes, namely, TMEM2, GUCY1A2, ISL1, WARS, and STEAP4. ROC curve analysis results indicated that the diagnostic genes had a powerful ability to distinguish IHs samples from normal samples. Next, the results of GSEA for a single gene illustrated that all five diagnostic genes inhibited the "valine, leucine, and isoleucine degradation" pathway in the development of IHs. WARS, TMEM2, and STEAP4 activated the "blood vessel development" and "vasculature development" in IHs. Subsequently, inhibitors targeting TMEM2, GUCY1A2, ISL1, and STEAP4 were mined. Finally, 14 transcription factors regulating GUCY1A2, 14 transcription factors regulating STEAP4, and 26 transcription factors regulating ISL1 were predicted.ConclusionThis study identified five diagnostic markers for IHs and further explored the mechanisms and targeting drugs, providing a basis for diagnosing and treating IHs.

Project description:BackgroundTo evaluate the efficacy and safety of topical β-blockers in the treatment of superficial infantile hemangiomas (SIH) and mixed infantile hemangiomas (MIH), respectively, and compare the efficacy and safety of topical β-blockers with other interventions.MethodsThe PRISMA guidelines were adhered to. We searched for randomized controlled trials in databases from 2010 to 2018 comparing topical β-blockers with other interventions for infantile hemangiomas. The outcomes evaluated were efficacy and adverse effects. Data analyses were performed using RevMan 5.3. Publication bias was assessed to account for bias in patient selection.ResultsEleven studies, involving 1,235 patients, were subjected to this meta-analysis. Six studies compared topical β-blockers with other interventions (propranolol, placebo, corticosteroids or pulsed dye laser) in treating SIH, and 5 studies evaluated the efficacy and safety of a topical β-blocker when it was combined with another intervention in treating MIH. A topical β-blocker was discovered to be as effective as oral propranolol in treating SIH (risk ratio, RR, 0.96, 95% confidence interval, CI, 0.91-1.02, p = 0.20, I2 = 0%), and topical β-blockers were more beneficial than placebo, corticosteroids or pulsed dye laser in treating SIH (RR 2.25, 95% CI 1.66-3.05, p < 0.00001, I2 = 0%). Topical β-blockers combined with another intervention gave rise to a better clinical response in the treatment of MIH than intervention alone (RR 1.99, 95% CI 1.10-3.60, p = 0.02, I2 = 55%) (standard mean difference 0.80, 95% CI 0.28-1.31, p = 0.002, I2 = 0%). Compared with oral propranolol, topical β-blockers were associated with fewer incidences of adverse effects (RR 0.05, 95% CI 0.01-0.39, p = 0.004, I2 = 0%). No significant difference in adverse effects was found when a topical β-blocker was combined with another intervention in treating MIH (RR 1.01, 95% CI 0.58-1.74, p = 0.98, I2 = 0%).ConclusionsThis meta-analysis provided evidence that topical β-blockers may replace oral propranolol as first-line therapy for SIH and that they are of additive value in treating MIH.

Dataset Information

Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model.

Publications

Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model.

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