Wedelolactone induces apoptosis and pyroptosis in retinoblastoma through promoting ROS generation.

Retinoblastoma is a most frequently occurring primary intraocular tumor in infancy and children, highlighting the requirement to find and develop novel and more effective therapeutic approaches. Wedelolactone (WDL), a nature compound isolated from E. prostrata, exhibits multiple biological activities through regulating various signaling pathways; however, its potential influences on retinoblastoma progression are still unknown, and thus was investigated in our study, as well as the underlying mechanisms. Here, we found that WDL treatments significantly reduced the proliferation of retinoblastoma cells by inducing apoptosis and pyroptosis through increasing Caspase-3, Caspase-1, gasdermin E (GSDME) and gasdermin D (GSDMD) activation. Mitochondrial impairment and reactive oxygen species (ROS) generation were considerably up-regulated in WDL-incubated retinoblastoma cells through a dose-dependent manner. Notably, we found that ROS scavenge significantly abolished the function of WDL to provoke apoptosis and pyroptosis in retinoblastoma cell lines, revealing that ROS was required for WDL to perform its anti-cancer role in retinoblastoma. Moreover, our in vivo experiments indicated that WDL administration significantly reduced the tumor growth in the established retinoblastoma mouse models with undetectable toxicity. Collectively, these findings highlighted the potential of WDL to inhibit the growth and induce cell death of retinoblastoma in vitro and in vivo, and thereby showed promise as a therapeutic agent for the treatment of retinoblastoma.

Clinical efficacy of absolute ethanol combined with n-butyl cyanoacrylate sclerotherapy in the treatment of Puig's classified advanced venous malformation in children.

The aim of the present retrospective study was to investigate the clinical safety and efficacy of absolute ethanol combined with n-butyl cyanoacrylate sclerotherapy in the treatment of Puig's classified advanced venous malformation. Sclerotherapy was performed in 121 children (52 males and 69 females; age range, 5 months to 16 years) with venous malformations under general anesthesia between April 2009 and October 2014 at the Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center, Guangzhou, China. The patients with venous malformations were diagnosed and classified according to the diagnostic criteria of the International Society for the Study of Vascular Anomalies. According to the characteristics of intraoperative percutaneous angiography, 21 patient cases (9 males and 12 females; age range, 6 months to 14 years) were classified as advanced Puig's venous malformation. These 21 patients were treated with absolute ethanol combined with n-butyl cyanoacrylate. The patients were followed-up for 6-24 months (average, 15 months) after treatment. Following treatment with absolute ethanol combined with n-butyl cyanoacrylate, 15 cases were controlled and the total effective rate was 71% (15/21). However, 1 patient developed skin ulcerations, which was classed as a minor complication, 1 patient developed ectopic embolism caused by n-butyl cyanoacrylate reflux, and 1 patient developed transient pulmonary hypertension, the latter two complications were classified as major. Notably, the incidence rate of minor and major complications were 14.3%. To conclude, the present findings indicated that absolute ethanol combined with n-butyl cyanoacrylate sclerotherapy was a safe and effective method with a low complication rate in the treatment of Puig's classified advanced venous malformation in patients.

Efficacy of second-course intra-arterial chemotherapy in children for advanced retinoblastoma recurrence after intra-arterial chemotherapy.

Purpose: The present study determined the efficacy and toxicity of second-course intra-arterial chemotherapy (IAC) in advanced retinoblastoma (RB) recurrence in children following failed initial IAC. Materials and Methods: A total of 24 child patients with unilateral or bilateral intra-ocular advanced RB (IIRC Group D and Group E) undergoing second-course IAC treatment after initial intra-arterial chemotherapy between September 2011 and November 2016 were enrolled. Global salvage, ocular adverse events, and systemic adverse events were assessed. Results: Following second-course IAC, 15 (62.5%) showed complete control at 34 months follow-up, while 8 cases (33.3%) failed the treatment and 1 patient with metastatic disease (4.2%) eventually died of brain metastasis after refusing treatment. Ocular adverse events included eyelid edema (n=12), ptosis (n=5), forehead erythema (n-5), enophthalmos (n=3), and cataract (n=2). None of the patients had systemic adverse events, such as stroke or sepsis. Also, no secondary neoplasms and technical complications were observed. Conclusion: Second-course IAC is a potential alternative to enucleation in children with advanced RB, who fail an initial course of IAC. However, patients with advanced RB should be managed at experienced centers in order to consider all the alternatives before enucleation.

Comparison between absolute ethanol and bleomycin for the treatment of venous malformation in children.

The aim of this study was to investigate the therapeutic efficacies and treatment effects of absolute ethanol and bleomycin for the treatment of venous malformation (VM) in children. A total of 138 children with VM were randomly divided into two groups; 75 patients were treated with absolute ethanol, while a further 63 were treated with bleomycin under general anesthesia between February 2009 and February 2012. The treatment outcome and complications were observed in the two groups and the treatment efficacy was classified as one of four categories: cured, markedly effective, effective and ineffective. The curative effect was analyzed 6-24 months after treatment, with a mean of 15 months. Absolute ethanol was effective (cured, markedly effective or effective) in 71 cases and bleomycin was effective in 41 cases, and the difference between the effective rates was considered to be statistically significant (χ2=19.6, P<0.05). In the absolute ethanol group there were 14 cases with skin necrosis, 17 patients had serious localized swelling which required additional treatment, three patients developed muscle fibrosis and one patient suffered a brain embolism. In the bleomycin group there were five cases with skin necrosis and the difference in the incidence of adverse reactions was considered to be statistically significant (χ2=18.8, P<0.05). The curative effect of sclerotherapy for VM is clear, and absolute ethanol is the most effective sclerosing agent, but has a greater incidence of adverse side-effects than bleomycin. The major side-effect is skin necrosis. The choice of sclerotherapy depends on the classification of VM in children.

An effective approach for treating unresectable hepatoblastoma in infants and children: Pre-operative transcatheter arterial chemoembolization.

The objective of the present study was to investigate the feasibility and efficacy of pre-operative transcatheter arterial chemoembolization (TACE) for unresectable hepatoblastoma in infants and children. A total of 24 patients (14 males and 10 females) with unresectable hepatoblastoma, aged between 26 days and 41 months, were treated with pre-operative TACE between March 2007 and March 2011. All cases were confirmed by computed tomography (CT) and liver tumor biopsy prior to TACE. Arteriography was performed and the chemoembolization mixture (pirarubicin and cisplatin emulsified in lipiodol) was injected, followed by polyvinyl alcohol (PVA). The procedure was performed one to four times depending on the patient's response. There was a significant reduction in tumor volume associated with decreased α-fetoprotein (AFP) levels following TACE. Tumor volumes decreased by between 46.1 and 90.2%, with a mean value of 72%. The AFP levels fell by between 63.8 and 99.9%, with a mean value of 95.7%. A total of 22 cases underwent subsequent safe complete surgical resection and the remaining two patients accepted a partial resection. To evaluate the toxicity of TACE, the alanine aminotransferase (ALT), serum creatinine (Cr) and creatine kinase (CK) levels of the patients were measured to assess liver, renal and cardiac function, respectively. The results showed that no marked chemotherapeutic agent-induced toxicity occurred during TACE. It may be concluded that TACE is an effective and feasible pre-operative therapeutic approach for treating unresectable hepatoblastoma and that it may improve the resectability of bulky liver tumors.

Folate-functionalized polymeric micelles based on biodegradable PEG-PDLLA as a hepatic carcinoma-targeting delivery system.

Targeted delivery of anti-cancer drugs is a highly desirable strategy to improve therapeutic outcome because of the combination of enhanced efficacy and reduced toxicity. In this study, the anti-cancer drug doxorubicin (DOX) was accommodated in the cores of polymeric micelles self-assembled from amphiphilic block copolymers of poly(ethylene glycol)(PEGs) and poly(D,L-lactide) (PDLLA) with a targeting ligand (folate) attached to the distal ends of the PEG (Folate-PEG-PDLLA). In vitro tumor cell targeting efficacy was evaluated upon observing cellular uptake of these micelles by human hepatic carcinoma cells (Bel 7402 cells) overexpressing surface receptors for folate. In control release tests, DOX behavior of controlled release in folate receptor-mediated micellar folate-PEG-PDLLA-DOX-micelles was obvious, with pH sensitivity. Bel 7402 cells showed micelles to have low toxicity and suggested potential therapeustic application as a multifunctional platform for tumor management.