Genetic Variants Influence the Severity of Oral Mucositis in Pediatric Osteosarcoma Patients.

Background: The variability in patients' risk of oral mucositis (OM) has been, in part, attributed to differences in host genomics. The aim better define the role of genomics as an OM risk by investigating the association between genetic variants and the presence and severity of OM in pediatric patients with osteosarcoma (OS) undergoing chemotherapy (CT).

Methods: A longitudinal observational retrospective study was conducted.

High Expression of GABA Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma.

Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the γ-aminobutyric acid (GABA) type A (GABA) receptor, which is a ligand-gated ion channel. GABA receptor activation via GABA binding allows for an intracellular influx of Cl ions, thus inducing cellular hyperpolarization. Each GABA receptor consists of a combination of five subunits, and several subunits have been proposed as biomarkers and therapeutic targets in cancer.

Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma.

Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle.

Histone Methyltransferases G9a/ and GLP/ Are Associated with Cell Viability and Poorer Prognosis in Neuroblastoma and Ewing Sarcoma.

Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the () gene, as well as its related protein GLP, which is encoded by the / gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types.

The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.

Neuropilins are transmembrane glycoproteins that regulate developmental processes in the nervous system and other tissues. Overexpression of neuropilin-1 (NRP1) occurs in many solid tumor types and, in several instances, may predict patient outcome in terms of overall survival. Experimental inhibition of NRP1 activity can display antitumor effects in different cancer models.

Modulation of Viability, Proliferation, and Stemness by Rosmarinic Acid in Medulloblastoma Cells: Involvement of HDACs and EGFR.

Medulloblastoma (MB) is a heterogeneous group of malignant pediatric brain tumors, divided into molecular groups with distinct biological features and prognoses. Currently available therapy often results in poor long-term quality of life for patients, which will be afflicted by neurological, neuropsychiatric, and emotional sequelae. Identifying novel therapeutic agents capable of targeting the tumors without jeopardizing patients' quality of life is imperative.

Low Expression of the Gene Is Associated with Shorter Overall Survival in Patients with Sonic Hedgehog and Group 3 Medulloblastoma.

Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor. Neuropilin-1 (NRP1), encoded by the NRP1 gene, is a transmembrane glycoprotein overexpressed in several types of cancer. Previous studies indicate that NRP1 inhibition displays antitumor effects in MB models and higher NRP1 levels are associated with poorer prognosis in MB patients.

Targeting the epigenome of cancer stem cells in pediatric nervous system tumors.

Medulloblastoma, neuroblastoma, and pediatric glioma account for almost 30% of all cases of pediatric cancers. Recent evidence indicates that pediatric nervous system tumors originate from stem or progenitor cells and present a subpopulation of cells with highly tumorigenic and stem cell-like features. These cancer stem cells play a role in initiation, progression, and resistance to treatment of pediatric nervous system tumors.

Avoiding vascular complications in insular glioma surgery - A microsurgical anatomy study and critical reflections regarding intraoperative findings.

Introduction: Vascular lesions in insular glioma surgery can severely impact patients' quality of life. This study aims to present the results of our dissections and authors' reflections on the insular vascular anatomy.

Matherials And Methods: The insular vascularization was examined using ×3 to ×40 magnification in 20 cadaveric cerebral hemispheres in which the arteries and veins had been perfused with colored silicone.

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials.

The serine/threonine kinase Akt is a major player in the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and its modulation impacts multiple cellular processes such as growth, proliferation, and survival. Several abnormalities in this pathway have been documented over the years, and these alterations were shown to have great implications in tumorigenesis and resistance to chemotherapy. Thus, multiple Akt inhibitors have been developed and tested in adult tumors, and some of them are currently undergoing phase I, II, and III clinical trials for distinct cancers that arise during adulthood.

Cancer Stem Cells and Chemoresistance in Ewing Sarcoma.

Resistance to chemotherapy poses a major challenge for cancer treatment. Reactivating a stem cell program resembling that seen in embryonic development can lead cancer cells to acquire a stem-cell phenotype characterized by expression of stemness genes, pluripotency, high self-renewal ability, and tumor-initiating capability. These cancer stem cells (CSCs) are usually resistant to anticancer drugs and are likely involved in treatment failure in many cancer types.

ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma.

Medulloblastoma (MB) is a malignant brain tumor that afflicts mostly children and adolescents and presents four distinct molecular subgroups, known as WNT, SHH, Group 3, and Group 4. ZEB1 is a transcription factor that promotes the expression of mesenchymal markers while restraining expression of epithelial and polarity genes. Because of ZEB1 involvement in cerebellum development, here we investigated the role of ZEB1 in MB.

High P2X6 receptor expression in human bladder cancer predicts good survival prognosis.

As alterations in purinergic signaling have been observed in bladder diseases, we aimed to assess the potential prognostic role of purinergic receptors in bladder cancer in a translational approach based on clinical databases and in vitro data. The prognostic role of purinergic receptors in the survival of patients with bladder cancer and the expression profile of the altered P2 receptors in normal and in tumor samples were determined using The Cancer Genome Atlas databank. In T24 and RT4 human bladder cancer cell lines, the P2 purinergic receptors were characterized by RT-PCR and RT-qPCR analysis including radiotherapy exposure as treatment.

The Entorhinal Cortex as a Gateway for Amygdala Influences on Memory Consolidation.

The amygdala, specifically its basolateral nucleus (BLA), is a critical site integrating neuromodulatory influences on memory consolidation in other brain areas. Almost 20 years ago, we reported the first direct evidence that BLA activity is required for modulatory interventions in the entorhinal cortex (EC) to affect memory consolidation (Roesler, Roozendaal, and McGaugh, 2002). Since then, significant advances have been made in our understanding of how the EC participates in memory.

G9a/EHMT2 is a Potential Prognostic Biomarker and Molecular Target in SHH Medulloblastoma.

Changes in epigenetic programming are associated with cancer development during childhood. Components of the epigenetic machinery involved in normal embryonic development and hijacked by pediatric cancers include enzymes mediating post-translational modifications of DNA and histones that regulate chromatin structure, such as histone methyltransferases (HMTs). Overexpression of the HMT G9a (euchromatic histone lysine methyltransferase 2, EHMT2) has been described in several cancer types.

Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma.

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets.

EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents.

Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state.

Tuberous sclerosis complex (TSC) is an autosomal dominant cancer predisposition disorder caused by heterozygous mutations in TSC1 or TSC2 genes and characterized by mTORC1 hyperactivation. TSC-associated tumors develop after loss of heterozygosity mutations and their treatment involves the use of mTORC1 inhibitors. We aimed to evaluate cellular processes regulated by mTORC1 in TSC cells with different mutations before tumor development.

Neuroinflammation and immunoregulation in glioblastoma and brain metastases: Recent developments in imaging approaches.

Brain tumors and brain metastases induce changes in brain tissue remodeling that lead to immunosuppression and trigger an inflammatory response within the tumor microenvironment. These immune and inflammatory changes can influence invasion and metastasis. Other neuroinflammatory and necrotic lesions may occur in patients with brain cancer or brain metastases as sequelae from treatment with radiotherapy.

The G protein-coupled estrogen receptor (GPER) regulates recognition and aversively-motivated memory in male rats.

Estrogens, particularly 17β-estradiol (estradiol, E), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERβ, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce.