Pharmacologic stimulation of fetal hemoglobin (HbF) expression may be a promising approach for the treatment of ␤-thalassemia. In this study, we have investigated the HbF-inducing activity and molecular mechanisms of specific histone deacetylase (

BACKGROUND:The authors hypothesized that intensified chemotherapy in protocol HIT-GBM-C would increase survival of pediatric patients with high-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG). METHODS: Pediatric patients with newly diagnosed HGG and DIPG were treated with standard fractionated radiation and simultaneous chemotherapy (cisplatin 20 mg/m 2  5 days, etoposide 100 mg/m 2  3 days, and vincristine, and 1 cycle of cisplatin þ etoposide þ ifosfamide 1.5 g/m  5 days [PEI] during the last week of radiation). Subsequent maintenance chemotherapy included further cycles of PEI in Weeks 10, 14, 18, 22, 26, and 30, followed by oral valproic acid. RESULTS: Ninety-seven (pons, 37; nonpons, 60) patients (median age, 10 years; grade IV histology, 35) were treated. Resection was complete in 21 patients, partial in 29, biopsy only in 26, and not performed in 21. Overall survival rates were 91% (standard error of the mean [SE] AE 3%), 56%, and 19% at 6, 12, and 60 months after diagnosis, respectively. When compared with previous protocols, there was no significant benefit for patients with residual tumor, but the 5-year overall survival rate for patients with complete resection treated on HIT-GBM-C was 63% AE 12% SE, compared with 17% AE 10% SE for the historical control group (P ¼ .003, log-rank test). CONCLUSIONS: HIT-GBM-C chemotherapy after complete tumor resection was superior to previous protocols. Cancer 2010;116:705-12.

1 The blood -brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB. 2 We investigated the spatial distribution of intracarotid fluorescein sodium and intravenous lissamine-rhodamine B200 (RB 200) -albumin in the brain of normal and C6 glioma-bearing rats after intracarotid co-administration of 1-O-pentylglycerol (200 mM). To elucidate the mechanisms involved in the alkylglycerol-mediated BBB opening, intraluminal accumulation of fluorescein isothiocyanate (FITC) -dextran 40,000 was studied in freshly isolated rat brain capillaries using confocal microscopy during incubation with different alkylglycerols. Furthermore, 1-O-pentylglycerol-induced increase in delivery of methotrexate (MTX) to the brain was evaluated in nude mice.

Ependymoma with YAP1-MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1-MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1-MAMLD1 fusion was documented by RT-PCR/ Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC Brain Pathology 29 (2019) 205-216

With respect to nephrotoxicity, long-term infusions of cisplatin seem to be preferable over intermittent bolus administration in paediatric patients. The best predictive pharmacokinetic parameters for cisplatin-associated nephrotoxicity in children are peak free Pt concentrations in plasma and urine.