Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma.

Background: Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies.

Functional analysis of human Na(+)/K(+)-ATPase familial or sporadic hemiplegic migraine mutations expressed in Xenopus oocytes.

Aim: Functional characterization of ATP1A2 mutations that are related to familial or sporadic hemiplegic migraine (FHM2, SHM).

Methods: cRNA of human Na(+)/K(+)-ATPase α2- and β1-subunits were injected in Xenopus laevis oocytes. FHM2 or SHM mutations of residues located in putative α/β interaction sites or in the α2-subunit's C-terminal region were investigated.

Functional characterization of a novel C-terminal ATP1A2 mutation causing hemiplegic migraine and epilepsy.

Background: We describe a four-generation Italian family with familial hemiplegic migraine (FHM) and epilepsy due to a novel ATP1A2 missense mutation (R1007W).

Case Results: Mutational analysis revealed a heterozygous nucleotide substitution c.3019C>T resulting in the missense substitution p.

Measuring cation transport by Na,K- and H,K-ATPase in Xenopus oocytes by atomic absorption spectrophotometry: an alternative to radioisotope assays.

Whereas cation transport by the electrogenic membrane transporter Na(+),K(+)-ATPase can be measured by electrophysiology, the electroneutrally operating gastric H(+),K(+)-ATPase is more difficult to investigate. Many transport assays utilize radioisotopes to achieve a sufficient signal-to-noise ratio, however, the necessary security measures impose severe restrictions regarding human exposure or assay design. Furthermore, ion transport across cell membranes is critically influenced by the membrane potential, which is not straightforwardly controlled in cell culture or in proteoliposome preparations.

Treatment of children with glioblastoma with conformal radiation, temozolomide, and bevacizumab as adjuncts to surgical resection.

Prognosis for children with glioblastoma is unacceptably poor. Modest improvements in progression-free survival were seen in adults with glioblastoma by combining temozolomide and bevacizumab with conformal radiation. We retrospectively reviewed 3 cases of glioblastoma in children treated using upfront bevacizumab and temozolomide during radiation, followed by 12 cycles of maintenance therapy.

Inhibition of nuclear factor kappa-B signaling reduces growth in medulloblastoma in vivo.

Background: Medulloblastoma is a highly malignant pediatric brain tumor that requires surgery, whole brain and spine irradiation, and intense chemotherapy for treatment. A more sophisticated understanding of the pathophysiology of medulloblastoma is needed to successfully reduce the intensity of treatment and improve outcomes. Nuclear factor kappa-B (NFκB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer.

Biophysical properties of human medulloblastoma cells.

Medulloblastoma is a pediatric high-grade cerebellar malignancy derived from neuronal precursors. Although electrophysiologic characteristics of cerebellar granule neurons at all stages of cell development have been well described, such characterization has not been reported for medulloblastoma. In this study we attempt to characterize important electrophysiologic features of medulloblastoma that may distinguish it from the surrounding cerebellum.

A second conserved GAF domain cysteine is required for the blue/green photoreversibility of cyanobacteriochrome Tlr0924 from Thermosynechococcus elongatus.

Phytochromes are widely occurring red/far-red photoreceptors that utilize a linear tetrapyrrole (bilin) chromophore covalently bound within a knotted PAS-GAF domain pair. Cyanobacteria also contain more distant relatives of phytochromes that lack this knot, such as the phytochrome-related cyanobacteriochromes implicated to function as blue/green switchable photoreceptors. In this study, we characterize the cyanobacteriochrome Tlr0924 from the thermophilic cyanobacterium Thermosynechococcus elongatus.

Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA).

Purpose: Current medulloblastoma therapy, surgery, radiation, and chemotherapy, is unacceptably toxic. However, 13-cis retinoic acid (RA) and SAHA, a histone deacetylase inhibitor, have each been shown to induce apoptosis in medulloblastoma cultures and mouse models. Both drugs cross the blood brain barrier, have been given safely to children, and achieve brain concentrations that are at or near therapeutic levels.

Suberoylanilide hydroxamic acid is effective in preclinical studies of medulloblastoma.

Purpose: Suberoylanilide hydroxamic acid (SAHA) has been studied in adult solid and hematologic malignancies. However, little information has been reported on the effects of SAHA on central nervous system (CNS) tumors including medulloblastoma, the most common malignant brain tumor in children. We investigated SAHA in preclinical medulloblastoma models to determine its anti-cancer efficacy as well as its ability to affect intracranial lesions when administered systemically.

Metastatic malignant melanoma presenting as pancytopenia in a three-year-old boy.

Malignant melanoma is rare in childhood and has never been reported to cause pancytopenia due to bone marrow metastases in a child. We report a 3-year-old boy with a large congenital melanocytic nevus who presented with bone pain and pancytopenia due to diffuse bone and bone marrow infiltration with metastatic melanoma without an identifiable primary site. Despite treatment with imatinib mesylate there was no response and the patient died with progressive disease.