Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.

Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expressed in the neuroectoderm (neural precursor cells) during embryogenesis. New insights are needed to refine tumor classification and to identify therapeutic approaches.

Polio virotherapy targets the malignant glioma myeloid infiltrate with diffuse microglia activation engulfing the CNS.

Background: Malignant gliomas commandeer dense inflammatory infiltrates with glioma-associated macrophages and microglia (GAMM) promoting immune suppression, evasion, and tumor progression. Like all cells in the mononuclear phagocytic system, GAMM constitutively express the poliovirus receptor, CD155. Besides myeloid cells, CD155 is widely upregulated in the neoplastic compartment of malignant gliomas.

Eosinophilic globules in a classic ependymoma: evidence of a possible secretory role.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma.

Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation.

Human mesenchymal stem/stromal cells (hMSCs) are a promising therapy for acute respiratory distress syndrome (ARDS) and other inflammatory conditions. While considerable research has focused on paracrine effects and mitochondrial transfer that improve lung fluid balance, hMSCs are well known to have immunomodulatory properties as well. Some of these immunomodulatory properties have been related to previously reported paracrine effectors such as indoleamine-2,3-dioxygenase (IDO), but these effects cannot fully account for cell-contact dependent immunomodulation.

Management of glioblastoma: State of the art and future directions.

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age.

Frequent Mutations of POT1 Distinguish Pulmonary Sarcomatoid Carcinoma From Other Lung Cancer Histologies.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC) harboring mutations in many canonical NSCLC-driver genes (eg, TP53, KRAS, MET). Protection of telomeres 1 (POT1) mutations are observed in angiosarcoma and chronic lymphocytic leukemia, but their frequency in other solid tumors, including NSCLC subtypes, has not been rigorously explored.

Materials And Methods: We analyzed next-generation sequencing data from 62,368 tumors, including 11,134 NSCLCs and 100 PSCs.

Catastrophic stroke burden in a patient with uncontrolled psoriasis and psoriatic arthritis: a case report.

Background: Psoriasis is the most common chronic inflammatory condition involving the T helper cell system. Population studies have demonstrated that patients with psoriasis and/or psoriatic arthritis have an increased risk of developing vascular risk factors, including diabetes, hypertension, and obesity, and increased risk of adverse vascular events, including myocardial infarction and stroke. Population studies have generally investigated the individual contributions of psoriasis and psoriatic arthritis to development of vascular risk factors; fewer studies have investigated the additive contribution of comorbid inflammatory disorders.

mutation spectrum in tumour types commonly diagnosed among -associated hereditary cancer syndrome families.

Background: The shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline mutations are associated with an autosomal dominant familial cancer syndrome presenting with diverse malignancies, including glioma, angiosarcoma, colorectal cancer and melanoma. Although somatic mutations promote telomere elongation and genome instability in chronic lymphocytic leukaemia, the contribution of mutations to development of other sporadic cancers is largely unexplored.

The genetic landscape of gliomas arising after therapeutic radiation.

Radiotherapy improves survival for common childhood cancers such as medulloblastoma, leukemia, and germ cell tumors. Unfortunately, long-term survivors suffer sequelae that can include secondary neoplasia. Gliomas are common secondary neoplasms after cranial or craniospinal radiation, most often manifesting as high-grade astrocytomas with poor clinical outcomes.

Perilesional edema associated with an intracranial calcifying pseudoneoplasm of the neuraxis in a child: case report and review of imaging features.

Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are rare, nonneoplastic lesions of the CNS. Their radiographic features have been well described, with prominent calcifications seen on CT imaging and generally uniform hypointensity on T1- and T2-weighted MRI sequences, with variable patterns of contrast enhancement. They are not associated with significant perilesional edema.

EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis.

Aberrant activation of EGFR in human cancers promotes tumorigenesis through stimulation of AKT signaling. Here, we determined that the discoidina neuropilin-like membrane protein DCBLD2 is upregulated in clinical specimens of glioblastomas and head and neck cancers (HNCs) and is required for EGFR-stimulated tumorigenesis. In multiple cancer cell lines, EGFR activated phosphorylation of tyrosine 750 (Y750) of DCBLD2, which is located within a recently identified binding motif for TNF receptor-associated factor 6 (TRAF6).

Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas.

Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually associated with a wild-type IDH1 allele (heterozygous) in cancer. Here, we identify 2 gliomas that underwent loss of the wild-type IDH1 allele but retained the mutant IDH1 allele following tumor progression from World Health Organization (WHO) grade III anaplastic astrocytomas to WHO grade IV glioblastomas.

Mutant IDH1 is required for IDH1 mutated tumor cell growth.

Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protein is required for maintaining IDH1 mutated tumor cell growth remains unknown. Here, using a genetically engineered inducible system, we report that selective suppression of endogenous mutant IDH1 expression in HT1080, a fibrosarcoma cell line with a native IDH1(R132C) heterozygous mutation, significantly inhibits cell proliferation and decreases clonogenic potential.

Transcriptional regulation of N-acetylglutamate synthase.

The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways.

Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target.

Purpose Of Review: Isocitrate dehydrogenases, IDH1 and IDH2, decarboxylate isocitrate to α-ketoglutarate (α-KG) and reduce NADP to NADPH. Point mutations of IDH1 and IDH2 have been discovered in gliomas. IDH mutations cause loss of native enzymatic activities and confer novel activity of converting α-KG to 2-hydroxyglutarate (2-HG).

IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain.

Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). IDH1/2 were recently identified as mutated in a large percentage of progressive gliomas. These mutations occur at IDH1(R132) or the homologous IDH2(R172).

Gastrin-releasing peptide, immune responses, and lung disease.

Gastrin-releasing peptide (GRP) is produced by pulmonary neuroendocrine cells (PNECs), with highest numbers of GRP-positive cells present in fetal lung. Normally GRP-positive PNECs are relatively infrequent after birth, but PNEC hyperplasia is frequently associated with chronic lung diseases. To address the hypothesis that GRP mediates chronic lung injury, we present the cumulative evidence implicating GRP in bronchopulmonary dysplasia (BPD), the chronic lung disease of premature infants who survive acute respiratory distress syndrome.

Biochemical properties of recombinant human and mouse N-acetylglutamate synthase.

N-Acetylglutamate synthase (NAGS, EC 2.3.1.