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OBJECTIVEEndothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model.METHODSA CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies.RESULTSThe normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups.CONCLUSIONSThese results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.

Atypical teratoid/rhabdoid tumor (AT/RT) is the most malignant tumor of the central nervous system that generally occurs in young children. Despite the use of intensive multimodal therapy for AT/RT, the prognosis is still poor. The brain tumor initiating cells in AT/RT cells has been suggested as one of the challenges in AT/RT treatment. These cells have high expression of aldehyde dehydrogenase (ALDH). We investigated the combination effect of the ALDH inhibitor, disulfiram and cisplatin in the treatment of AT/RT cells. Isobologram analysis revealed that the combination therapy synergistically increases AT/RT cell death. The enzyme activity of ALDH AT/RT cells was effectively reduced by the combination therapy. We proposed that the synergistic augmentation occurs, at least partially through an increase in cleaved Poly (ADP-ribose) polymerase (PARP)-dependent apoptosis mediated by activating transcription factor 3 (ATF3). In the AT/RT mouse model, the combination therapy decreased tumor volume and prolonged survival. Immunofluorescence assay in mouse brain tissues were consistent with the expression of ATF3 and cleaved PARP. Our study demonstrates enhanced anti-cancer effect of combination therapy of disulfiram and cisplatin. This combination might provide a viable therapeutic strategy for AT/RT patients.

Nonthermal plasma is a promising novel therapy for the alteration of biological and clinical functions of cells and tissues, including apoptosis and inhibition of tumor progression. This therapy generates reactive oxygen and nitrogen species (RONS), which play a major role in anticancer effects. Previous research has verified that plasma jets can selectively induce apoptosis in various cancer cells, suggesting that it could be a potentially effective novel therapy in combination with or as an alternative to conventional therapeutic methods. In this study, we determined the effects of nonthermal air soft plasma jets on a U87 MG brain cancer cell line, including the dose- and time-dependent effects and the physicochemical and biological correlation between the RONS cascade and p38/mitogen-activated protein kinase (MAPK) signaling pathway, which contribute to apoptosis. The results indicated that soft plasma jets efficiently inhibit cell proliferation and induce apoptosis in U87 MG cells but have minimal effects on astrocytes. These findings revealed that soft plasma jets produce a potent cytotoxic effect via the initiation of cell cycle arrest and apoptosis. The production of reactive oxygen species (ROS) in cells was tested, and an intracellular ROS scavenger, N-acetyl cysteine (NAC), was examined. Our results suggested that soft plasma jets could potentially be used as an effective approach for anticancer therapy.