During the past three years, studies have been in progress to determine and analyze effects of x-rays on normal brain monkey tumors central nervous system man. Although these carried out primarily with 23-mev x-rays, produced by University Illinois betatron, additional comparative utilizing 200 400 kv. also undertaken. Our findings, date, would indicate that both man is more radioresponsive than previously supposed, pathological changes radiations are due a direct effect upon neural...

Abstract Isolation and propagation of neural stem cells derived from human brain tissue uniquely enables the study neurogenesis in vitro . In addition, ex vivo ‐expanded stem/precursor (NPCs) may offer novel therapeutic strategies. We investigated effects extracellular nucleotides on proliferation differentiation mesencephalic (hmNPCs). When combined with mitogens epidermal growth factor fibroblast 2, UTP (1 µ m ) boosted hmNPCs as shown by increased expression marker proliferating cell...

Abstract Members of the miR-125 family are strongly expressed in several tissues, particularly brain, but may be dysregulated cancer including adult and pediatric glioma. In this study, members were downregulated pilocytic astrocytoma (PA) as a group compared to non-neoplastic brain Agilent platform. Nanostring platform, primarily pleomorphic xanthoastrocytomas gangliogliomas. Using CISH for miR-125b, highest levels expression present grade II tumors (11/33, 33% with 3+ 3/70, 4% I tumors) (p...

// Samantha Semenkow 1 , Shen Li 2, 3 Ulf D. Kahlert 4 Eric H. Raabe 1, 5 Jiadi Xu 2 Antje Arnold Miroslaw Janowski 3, 6 Byoung Chol Oh 7 Gerald Brandacher Jeff W.M. Bulte Charles G. Eberhart 8 and Piotr Walczak 9 Department of Pathology, The Johns Hopkins University School Medicine, Baltimore, MD, USA Russel Morgan Radiology Radiological Science, Cellular Imaging Section Vascular Biology Program, Institute for Cell Engineering, Neurosurgery, Heinrich-Heine-University Dusseldorf, Germany...

Here we describe some of the crucial steps to generate induced pluripotent stem cells (iPSCs) using mRNA transfection. Our approach uses a V. virus-derived capping enzyme instead cap-analog, ensuring 100% proper cap orientation for in vitro transcribed mRNA. virus' 2'-O-Methyltransferase creates cap1 structure found higher eukaryotes and has translation efficiency compared other methods. Use polymeric transfection reagent polyethylenimine proved superior The created via this method did not...

Abstract Background Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor. Many patients with unresectable or recurrent/refractory tumors have significant lifelong disability. The majority of pLGG mutations increasing activity Ras/mitogen-activated protein kinase (MAPK) pathway. Activation mammalian target rapamycin (mTOR) also a hallmark pLGG. We therefore hypothesized that dual complexes 1 and 2 (TORC1/2) inhibitor TAK228 would synergize mitogen-activated extracellular...

Pediatric low-grade glioma (pLGG) often initially responds to front-line therapies such as carboplatin, but more than 50% of treated tumors eventually progress and require additional therapy. With the discovery that pLGG contains mammalian target rapamycin (mTOR) activation, new treatment modalities combinations are now possible for patients. The purpose this study was determine if carboplatin is synergistic with mTOR complex 1 inhibitor everolimus in pLGG.We 4 cell lines patient-derived...

The immunological barrier currently precludes the clinical utilization of allogeneic stem cells. Although glial-restricted progenitors have become attractive candidates to treat a wide variety neurological diseases, their survival in immunocompetent recipients is limited. In this study, we adopted short-term, systemically applicable co-stimulation blockade-based strategy using CTLA4-Ig and anti-CD154 antibodies modulate T-cell activation context progenitor transplantation. We found that...

Abstract Purpose: Ductal lavage, a technique used to sample epithelial cells from breast ducts, has potential use in risk assessment and biomarker evaluation among women at increased for cancer. However, little is known about the reliability of procedure. Methods: We evaluated nipple aspirate (NAF) ductal lavage two time points 6 months apart Eligible had 5-year Gail ≥1.66% or lifetime >20%, and/or family history personal All ducts that produced NAF were cannulated. The κ statistic...

The derivation of induced pluripotent stem cells (iPS) from human cell sources using transduction based on viral vectors has been reported by several laboratories. Viral vector-induced integration is a potential cause genetic modification. We have derived iPS foreskin, adult Huntington fibroblasts, and skin fibroblasts healthy donors nonviral nonintegrating procedure mRNA transfer. In vitro transcribed for 5 factors, oct-4, nanog, klf-4, c-myc, sox-2 as well one new factor, hTERT, was used...

To evaluate a potential relationship between BRAF V600E mutation and PD-L1 expression, we examined the expression of in pediatric high- low-grade glioma cell lines as well cohort patient samples. Half tumors our were V600-wildtype half mutant. All expressed PD-L1. In most tumors, was low (<5%), but some cases over 50% cells positive. Extent immune infiltration independent mutational status. evaluated, including mutant xenograft, Transient transfection with plasmid expressing had minimal...

Abstract Background Diffuse intrinsic pontine glioma (DIPG) is a uniformly lethal brainstem tumor of childhood, driven by histone H3 K27M mutation and resultant epigenetic dysregulation. Epigenomic analyses DIPG have shown global loss repressive chromatin marks accompanied DNA hypomethylation. However, studies providing static view the epigenome do not adequately capture regulatory underpinnings cellular heterogeneity plasticity. Methods To address this, we performed whole-genome bisulfite...

Abstract Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. In orbitofacial neurofibromatosis type 1, NFs may cause progressive, disfiguring tumors lid, brow, temple, face orbit. The purpose this study was identify biological differences between those occurring at other anatomic sites. We used Illumina Methylation EPIC BeadChip DNA methylation ( N = 20) sites 4). Global were...

The mitogen-activated protein kinase pathway is one of the most frequently altered pathways in cancer. It involved control cell proliferation, invasion, and metabolism, can cause resistance to therapy. A number aggressive malignancies, including melanoma, colon cancer, glioma, are driven by a constitutively activating missense mutation (V600E) v-Raf murine sarcoma viral oncogene homolog B (BRAF) component pathway. Mitogen-activated (MEK) inhibition initially effective targeting these...

Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. Orbitofacial NFs, particular, may cause progressive, disfiguring tumors lid, brow, temple, face, orbit, clinical evidence suggests that they increased local aggressiveness compared NFs developing at other sites. The purpose this study was identify biological differences between orbitofacial those occurring anatomic We performed...

Abstract BACKGROUND Diffuse Intrinsic Pontine Glioma (DIPG) is a universally fatal pediatric brain cancer characterized by the histone H3 K27M mutation. The known downstream consequences of this mutation include loss repressive chromatin marks, global DNA hypomethylation, and altered gene expression. METHODS We sought to investigate role epigenetic variability as basis DIPG cellular heterogeneity plasticity using Whole Genome Bisulfite Sequencing (WGBS). Existing methods analysis WGBS are...

1001 Background: Ductal lavage (DL) is a minimally invasive method used to obtain ductal cells for cytological analysis. It currently being as risk assessment tool assist with clinical decision making in women at increased breast cancer. Methods: We evaluated the reproducibility and reliability of DL procedure cytology two time points 6 months apart Eligible had 5 year Gail least 1.66%, and/or personal history cancer, were known BRCA1 or 2 mutation carriers. Ducts that produced nipple...

Abstract Diffuse Midline Glioma, DMG, is one of the worst forms pediatric brain tumors and associated with a 100% mortality rate. unlike other types tumors, exists in hypomethylated epigenetic state. In this study, we investigate contribution Ten Eleven Translocation (TET) enzymes towards unique landscape. The TET which reduce 5methylcytosine (5mC) to 5hydroxymethylcytosine (5hmC) are essential for removing methylation marks genome. our previous studies, saw that there an increased...

Pediatric lower grade glioma (LGG) can cause significant morbidity and mortality in patients. Tumors often initially respond to first line chemotherapies, such as carboplatin, but approximately 50% of the time tumors recur require additional therapy. The discovery that aggressive LGG have MAPK-ERK pathway, well mTOR activation, increases number treatment options available, trametinib, an ERK inhibitor, or everolimus, mTORC1 inhibitor. Using preexisting newly developed models for LGG, our lab...

The mTOR pathway contributes to the tumorigenicity of aggressive pediatric low grade glioma (pLGG) and TORC1 inhibitors have demonstrated efficacy in treating pLGG cell lines. FDA-approved inhibitor, everolimus, is currently clinical trials for patients with recurrent/refractory pLGG. We hypothesized that metabolic alterations downstream inhibition could be targeted synergize everolimus reduce tumorigenicity. identified through unbiased screens stable isotope tracing glutathione was...