CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway.

Hypoxia contributes to the initiation and progression of glioblastoma by regulating a cohort of genes called hypoxia-regulated genes (HRGs) which form a complex molecular interacting network (HRG-MINW). Transcription factors (TFs) often play central roles for MINW. The key TFs for hypoxia induced reactions were explored using proteomic analysis to identify a set of hypoxia-regulated proteins (HRPs) in GBM cells.

Protein-protein interaction network of E. coli K-12 has significant high-dimensional cavities: new insights from algebraic topological studies.

As a model system, Escherichia coli has been used to study various life processes. A dramatic paradigm shift has occurred in recent years, with the study of single proteins moving toward the study of dynamically interacting proteins, especially protein-protein interaction (PPI) networks. However, despite the importance of PPI networks, little is known about the intrinsic nature of the network structure, especially high-dimensional topological properties.

Deep learning identified glioblastoma subtypes based on internal genomic expression ranks.

Background: Glioblastoma (GBM) can be divided into subtypes according to their genomic features, including Proneural (PN), Neural (NE), Classical (CL) and Mesenchymal (ME). However, it is a difficult task to unify various genomic expression profiles which were standardized with various procedures from different studies and to manually classify a given GBM sample into a subtype.

Methods: An algorithm was developed to unify the genomic profiles of GBM samples into a standardized normal distribution (SND), based on their internal expression ranks.

Hypoxia Regulated Gene Network in Glioblastoma Has Special Algebraic Topology Structures and Revealed Communications Involving Warburg Effect and Immune Regulation.

Hypoxia regulated genes (HRGs) formed a complex molecular interaction network (MINW), contributing to many aspects of glioblastoma (GBM) tumor biology. However, little is known about the intrinsic structures of the HRGs-MINW, mainly due to a lack of analysis tools to decipher MINWs. By introducing general hyper-geometric distribution, we obtained a statistically reliable gene set of HRGs (SR-HRGs) from several datasets.

Malignant Intracranial High Grade Glioma and Current Treatment Strategy.

Malignant high-grade glioma (HGG) is the most common and extremely fatal type of primary intracranial tumor. These tumors recurred within 2 to 3 cm of the primary region of tumor resection in the majority of cases. Furthermore, the blood-brain barrier significantly limited the access of many systemically administered chemotherapeutics to the tumor, pointing towards a stringent need for new therapeutic patterns.

Advances in the delivery of antisense oligonucleotides for combating bacterial infectious diseases.

Discovery and development of new antibacterial drugs against multidrug resistant bacterial strains have become more and more urgent. Antisense oligonucleotides (ASOs) show immense potential to control the spread of resistant microbes due to its high specificity of action, little risk to human gene expression, and easy design and synthesis to target any possible gene. However, efficient delivery of ASOs to their action sites with enough concentration remains a major obstacle, which greatly hampers their clinical application.

Hypoxia upregulates HIG2 expression and contributes to bevacizumab resistance in glioblastoma.

Hypoxia contributes to the maintenance of stem-like cells in glioblastoma (GBM), and activates vascular mimicry and tumor resistance to anti-angiogenesis treatments. The present study examined the expression patterns and biological significance of hypoxia-inducible protein 2 (HIG2, also known as HILPDA) in GBM. HIG2 was highly expressed in gliomas and was correlated with tumor grade, and high HIG2 expression independently predicted poor GBM patient prognosis.

The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma.

Glioblastoma (GBM) contains a population of stem-like cells that promote tumor invasion and resistance to therapy. Identifying and targeting stem cell factors in GBM may lead to the development of more effective therapies. High Mobility Group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in normal and cancer stem cells.

Glioblastoma vasculogenic mimicry: signaling pathways progression and potential anti-angiogenesis targets.

Glioblastoma (GBM) is a highly angiogenic malignancy that is resistant to standard therapy; neo-formed vessels of this aggressive malignancy are thought to arise by sprouting of pre-existing brain capillaries. However, the conventional anti-angiogenic therapy, which seemed promising initially, shows transitory and incomplete efficacy. The discovery of vasculogenic mimicry (VM) has offered a new horizon for understanding tumor vascularization.

Overexpression of FRAT1 is associated with malignant phenotype and poor prognosis in human gliomas.

Glioma is the most common malignancy of the central nervous system. Approximately 40 percent of intracranial tumors are diagnosed as gliomas. Difficulties in treatment are associated closely with the malignant phenotype, which is characterized by excessive proliferation, relentless invasion, and angiogenesis.

Disrupting LIN28 in atypical teratoid rhabdoid tumors reveals the importance of the mitogen activated protein kinase pathway as a therapeutic target.

Atypical teratoid rhabdoid tumor (AT/RT) is among the most fatal of all pediatric brain tumors. Aside from loss of function mutations in the SMARCB1 (BAF47/INI1/SNF5) chromatin remodeling gene, little is known of other molecular drivers of AT/RT. LIN28A and LIN28B are stem cell factors that regulate thousands of RNAs and are expressed in aggressive cancers.

A potent and selective antimicrobial poly(amidoamine) dendrimer conjugate with LED209 targeting QseC receptor to inhibit the virulence genes of gram negative bacteria.

Unlabelled: The pandemic of multidrug-resistant Gram negative bacteria (GNB) is a worldwide healthcare concern, and very few antibiotics are being explored to match the clinical challenge. Recently, amino-terminated poly(amidoamine) (PAMAM) dendrimers have shown potential to function as broad antimicrobial agents. However, PAMAM displays a generation dependent cytotoxicity to mammalian cells and low selectivity on bacterial cells, which limits PAMAM to be developed as an antibacterial agent for systemic administration.

LGR5/GPR49 is implicated in motor neuron specification in nervous system.

The biological roles of stem cell marker LGR5, the receptor for the Wnt-agonistic R-spondins, for nervous system are poorly known. Bioinformatics analysis in normal human brain tissues revealed that LGR5 is closely related with neuron development and functions. Interestingly, LGR5 and its ligands R-spondins (RSPO2 and RSPO3) are specifically highly expressed in projection motor neurons in the spinal cord, brain stem and cerebral.

LIN28A facilitates the transformation of human neural stem cells and promotes glioblastoma tumorigenesis through a pro-invasive genetic program.

The cellular reprogramming factor LIN28A promotes tumorigenicity in cancers arising outside the central nervous system, but its role in brain tumors is unknown. We detected LIN28A protein in a subset of human gliomas observed higher expression in glioblastoma (GBM) than in lower grade tumors. Knockdown of LIN28A using lentiviral shRNA in GBM cell lines inhibited their invasion, growth and clonogenicity.

LGR5 is a proneural factor and is regulated by OLIG2 in glioma stem-like cells.

The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs.

CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia.

Background: A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified.

Methods: The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated.

Promoting effects of chemical permeation enhancers on insulin permeation across TR146 cell model of buccal epithelium in vitro.

To find potential enhancers for facilitating the buccal delivery of insulin, a TR146 cell-culture model of buccal epithelium, cultured on commercially available insert plates, was used to evaluate the permeability-enhancing effects of several traditional and new types of chemical enhancers, including N-acetyl-L-cysteine (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan-2-one (Azone), and soybean lecithin (SPC) (50 and 10 μg/mL respectively). Permeability studies were performed to determine the enhancing effects of these compounds on insulin permeation across the cell-culture model. The enhancing effects of the enhancers were assessed by calculating the apparent permeability coefficients and enhancement ratio.

BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model.

Purpose: BRAF is frequently activated by gene fusion or point mutation in pilocytic astrocytoma, the most common pediatric brain tumor. We investigated the functional effect of constitutive BRAF activation in normal human neural stem and progenitor cells to determine its role in tumor induction in the brain.

Experimental Design: The constitutively active BRAF(V600E) allele was introduced into human neurospheres, and its effects on MAPK (mitogen-activated protein kinase) signaling, proliferation, soft agarose colony formation, stem cell phenotype, and induction of cellular senescence were assayed.

Overexpression of ZNF217 in glioblastoma contributes to the maintenance of glioma stem cells regulated by hypoxia-inducible factors.

Glioblastoma multiforme (GBM) is the most aggressive and common kind of primary brain tumor in adults, and is thought to be driven by a subpopulation of glioma stem cells (GSCs). GSCs reside in a specialized hypoxic niche, which can regulate the tumorigenic capacity of GSCs primarily through the hypoxia-inducible factors (HIFs), HIF1α and HIF2α. ZNF217 is an oncogene frequently amplified in many kinds of tumors.

Maintenance of critical properties of brain tumor stem-like cells after cryopreservation.

It would be very useful to be able to classify brain tumor stem cells (BTSCs) by certain criteria to afford the design of specific or individualized treatment. Here, we studied two BTSC lines with differing biological and molecular features and whose respective features were well preserved after cryopreservation as single cells in SFM or 90% serum with 10% DMSO, a method not previously reported. The resuscitated BTSCs shared properties indistinguishable from their respective parental cells, including tumor sphere forming potentials, growth and differentiation properties, and tumorigenesis in vivo.

Brain Tumor Stem-Like Cells Identified by Neural Stem Cell Marker CD15.

In recent years, a small number of cells that have stem cell properties were identified in human gliomas called brain tumor stem cells (BTSCs), which were thought to mainly contribute to the initiation and development of gliomas and could be identified by the surface marker CD133. However, recent studies indicated that the expression of CD133 might be regulated by environmental conditions such as hypoxia and that there might be CD133(-) BTSCs. Genetic mouse models demonstrated that some gliomas originated from transformed neural stem cells (NSCs).

Progress on potential strategies to target brain tumor stem cells.

The identification of brain tumor stem cells (BTSCs) leads to promising progress on brain tumor treatment. For some brain tumors, BTSCs are the driving force of tumor growth and the culprits that make tumor revive and resistant to radiotherapy and chemotherapy. Therefore, it is specifically significant to eliminate BTSCs for treatment of brain tumors.