Enhanced targeting of invasive glioblastoma cells by peptide-functionalized gold nanorods in hydrogel-based 3D cultures.

Unlabelled: Cancer stem cells (CSCs) are responsible for drug resistance, tumor recurrence, and metastasis in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma Multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed gold nanorods (AuNRs) functionalized with an engineered peptide capable of specific recognition and selective eradication of Nestin positive infiltrating GBM-CSCs.

A defined, controlled culture system for primary bovine chromaffin progenitors reveals novel biomarkers and modulators.

We present a method to efficiently culture primary chromaffin progenitors from the adult bovine adrenal medulla in a defined, serum-free monolayer system. Tissue is dissociated and plated for expansion under support by the mitogen basic fibroblast growth factor (bFGF). The cultures, although not homogenous, contain a subpopulation of cells expressing the neural stem cell marker Hes3 that also propagate.

Hes3 regulates cell number in cultures from glioblastoma multiforme with stem cell characteristics.

Tumors exhibit complex organization and contain a variety of cell populations. The realization that the regenerative properties of a tumor may be largely confined to a cell subpopulation (cancer stem cell) is driving a new era of anti-cancer research. Cancer stem cells from Glioblastoma Multiforme tumors express markers that are also expressed in non-cancerous neural stem cells, including nestin and Sox2.

p53 controls neuronal death in the CA3 region of the newborn mouse hippocampus.

It is important to determine the mechanisms controlling the number of neurons in the nervous system. Previously, we reported that neuronal activity plays a central role in controlling neuron number in the neonatal hippocampus of rodents. Neuronal survival requires sustained activation of the serine-threonine kinase Akt, which is initiated by neurotrophins and continued for several hours by neuronal activity and integrin signaling.

Targeting neural precursors in the adult brain rescues injured dopamine neurons.

In Parkinson's disease, multiple cell types in many brain regions are afflicted. As a consequence, a therapeutic strategy that activates a general neuroprotective response may be valuable. We have previously shown that Notch ligands support neural precursor cells in vitro and in vivo.

Notch signalling regulates stem cell numbers in vitro and in vivo.

The hope of developing new transplantation therapies for degenerative diseases is limited by inefficient stem cell growth and immunological incompatibility with the host. Here we show that Notch receptor activation induces the expression of the specific target genes hairy and enhancer of split 3 (Hes3) and Sonic hedgehog (Shh) through rapid activation of cytoplasmic signals, including the serine/threonine kinase Akt, the transcription factor STAT3 and mammalian target of rapamycin, and thereby promotes the survival of neural stem cells. In both murine somatic and human embryonic stem cells, these positive signals are opposed by a control mechanism that involves the p38 mitogen-activated protein kinase.

A novel role for serum response factor in neuronal survival.

Recent studies indicate that neuroprotection afforded by brain-derived neurotrophic factor (BDNF) is mediated by extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3 kinase (PI3K). However, the mechanisms by which ERK and PI3K exert neuroprotection are not completely understood. Because ERK1/2 and PI3K both stimulate serum response element (SRE)-mediated gene expression, and serum response factor (SRF) is indispensable for SRE-mediated transcription, we investigated whether SRF contributes to ERK1/2 and PI3K neuroprotection.

Developmental expression of PAM (protein associated with MYC) in the rodent brain.

Recently, human protein associated with MYC, PAM, has been cloned and characterized as a large protein that interacts with the transcriptional-activating domain of Myc. The regional expression pattern of PAM in brains has not been yet been defined. Expression patterns of PAM in both rat and mouse brains were examined by using in situ hybridization.