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Metrics details. The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons.

All cell cultures have the potential to carry as yet unidentified adventitious agents. It is the responsibility of the end user to ensure that their facilities comply with biosafety regulations for their own country. The Culture Collections represent deposits of cultures from world-wide sources. While every effort is made to ensure details distributed by Culture Collections are accurate, Culture Collections cannot be held responsible for any inaccuracies in the data supplied. References where quoted are mainly attributed to the establishment of the cell culture and not for any specific property of the cell line, therefore further references should be obtained regarding cell culture characteristics. Passage numbers where given act only as a guide and Culture Collections does not guarantee the passage number stated will be the passage number received by the customer.

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Federal government websites often end in. The site is secure. Primary data not included in the primary or Supplemental Material are available upon request. Glioblastoma is a rapidly progressing brain cancer that is very difficult to treat. Given that many aspects of cell and tissue behavior are controlled by electric signaling, we sought to test whether drugs that target ion channel proteins might be effective at controlling the spread and functionality of glioblastoma cells in culture. Testing aspects of cell growth and physiology, we show that several novel combinations of ion channel drugs, which are already approved in human patients for other purposes, are highly effective against two types of glioblastoma cells. This facilitates the development of new strategies to address cancer by repurposing the large class of ion channel drugs against cancer. Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials and an acidic intertumoral extracellular pH have been associated with a proliferative state and drug resistance, suggesting that forced hyperpolarization and disruption of proton pumps in the plasma membrane could be a successful strategy for targeting glioblastoma overgrowth. A subset of these were tested in the U87 human glioblastoma cell line. A FUCCI cell cycle reporter was stably integrated into both cell lines to monitor proliferation and cell cycle response. Immunocytochemistry, electrophysiology, and a panel of physiological dyes reporting voltage, calcium, and pH were used to characterize responses.

Received : 22 August

The differentiated type of neuroblastomaxglioma hybrid cell line, NG, has widely been used in in vitro studies instead of primary-cultured neurons. Here we examined whether NG cells can be used as a model for studying the neuronal differentiation process. We compared the expression of neuronal proteins neurofilament NF , phosphorylated-NF p-NF , microtubule associated protein 2, synaptophysin, syntaxin 1, choline acetyltransferase, and acetylcholinesterase AChE and a glial protein vimentin between undifferentiated and differentiated NG cells by immunocytochemistry and immunoblot analysis. The expression of all neuronal proteins, with the exception of NF and p-NF, was positive in differentiated cells, but almost negative in undifferentiated cells. On the other hand, cytoskeletal intermediate filaments NF and p-NF for neurons and that vimentin for glia were present in both undifferentiated and differentiated cells. Our results showed that even though the expression of cytoskeletal filaments does not change during differentiation of NG cells, these cells during differentiation can serve as an appropriate tool for investigating and understanding the mechanisms involved in neuronal development and differentiation.

Federal government websites often end in. The site is secure. Primary data not included in the primary or Supplemental Material are available upon request. Glioblastoma is a rapidly progressing brain cancer that is very difficult to treat. Given that many aspects of cell and tissue behavior are controlled by electric signaling, we sought to test whether drugs that target ion channel proteins might be effective at controlling the spread and functionality of glioblastoma cells in culture. Testing aspects of cell growth and physiology, we show that several novel combinations of ion channel drugs, which are already approved in human patients for other purposes, are highly effective against two types of glioblastoma cells. This facilitates the development of new strategies to address cancer by repurposing the large class of ion channel drugs against cancer. Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials and an acidic intertumoral extracellular pH have been associated with a proliferative state and drug resistance, suggesting that forced hyperpolarization and disruption of proton pumps in the plasma membrane could be a successful strategy for targeting glioblastoma overgrowth. A subset of these were tested in the U87 human glioblastoma cell line.

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In the fundamental process of neuronal path-finding, a growth cone at the tip of every neurite detects and follows multiple guidance cues regulating outgrowth and initiating directional changes. Using fluorescence time lapse microscopy we could identify two distinct modes of growth cone collapse leading either to neurite retraction or to a controlled halt of neurite extension. In the latter case, lateral movement and folding of actin bundles filopodia confine microtubule extension and limit microtubule-based expansion processes without the necessity of a constantly engaged actin turnover machinery. We term this previously unreported second type fold collapse and suggest that it marks an intermediate-term mode of growth regulation closing the gap between full retraction and small scale fluctuations. Neuronal development during embryogenesis as well as regeneration after injury is a highly complex process that requires robust mechanisms on the single-cell level to produce reliable results. Therefore, a multitude of interacting and overlapping signaling and guidance mechanisms is necessary to regulate neuronal growth and steer neuronal processes towards their respective target areas. For this purpose, the highly complex and motile growth cone develops at the tip of outgrowing axons and, to a lesser extent, of dendrites. Footnote 1 This hand-shaped entity contains mostly filaments of actin and microtubules MTs as dynamic and stabilizing structures. The typical structure of a growth cone is shown and described in Fig. We also recommend the review by Lowery and Van Vactor for more detailed information.

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Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation. Fan X. The effect of locally delivered cisplatin is dependent on an intact immune function in an experimental glioma model. Unified theory on the basic mechanism of normal mitotic control and oncogenesis. Figure 5. As shown in Figure 4 , the protein level of Na v 1. No staining was seen when PBS was used instead of the primary antibody in the above procedure. This approach has already been used for the design of interventions to repair birth defects of the brain [ , ]. More importantly, the level of Na v 1. TMZ treatment alone only showed a slight increase in proliferation after treatment was removed, and NS alone showed a high increase in proliferation.

Federal government websites often end in. The site is secure. Liposomes are concentric lipid vesicles that allow a sustained release of entrapped substances.

Juarez M. Culture and characteristics of hormone-responsive neuroblastoma X glioma hybrid cells. Interestingly, that same study showed that pantoprazole interfered with proteasome function, which might explain why it worked so well as a combinatorial treatment. Thus, due to the location and importance of these channels in cancer cell proliferation, migration, and metastasis, ion channels provide an optimal target for the development of new GBM treatments. J Neurosci. Jen Q. Anti-Cancer Drug Discov. In mammalian models, several recent studies have shown that ion channelopathies that affect resting membrane potential are present in many cancers and play a key role in cell proliferation, progression through the cell cycle, and metastasis [ 25 , 29 , 31 , 36 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Kang T. Bender R. Importantly, in vivo experiments in Xenopus tadpoles showed that co-expression of hyperpolarizing ion channels, or optogenetic activation of channels with human oncogenes, can prevent the tumors induced by oncogene expression alone [ 34 , 38 , 47 , 48 ].