CXCL12 alone is insufficient for gliomagenesis in Nf1 mutant mice.
ABSTRACT Tumorigenesis requires interactions between tumor progenitors and their microenvironment. We found that low cAMP levels were sufficient for tumorigenesis in a mouse model of Neurofibromatosis-1 (NF1)-associated optic pathway glioma (OPG). We hypothesized that the distinct pattern of glioma in NF1 reflected spatiotemporal differences in CXCL12 effects on cAMP levels. Thus, we sought to alter the pattern of gliomagenesis through manipulation of CXCL12-CXCR4 pathway activation in Nf1 OPG mice. Forced CXCL12 expression induced glioma at a low frequency. Further, treatment of Nf1 OPG mice with AMD3100, a CXCR4 antagonist, did not attenuate glioma growth. Thus, it appears, CXCL12 alone cannot promote gliomagenesis in NF1 mice.
SourceAvailable from: Frank Pajonk[Show abstract] [Hide abstract]
ABSTRACT: To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation. Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription-polymerase chain reaction to study the Notch pathway in response to radiation. We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose-dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells. Additionally, radiation activated the Notch pathway. Treatment with a γ-secretase inhibitor prevented radiation-induced Notch family gene expression and led to a significant reduction in the size of the breast cancer stem cell pool. Our results indicate that, if combined with radiation, γ-secretase inhibitors may prevent up-regulation of Notch receptor and ligand family members and thus reduce the number of surviving breast cancer stem cells.International journal of radiation oncology, biology, physics 08/2013; DOI:10.1016/j.ijrobp.2013.06.2064 · 4.18 Impact Factor
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ABSTRACT: Neurofibromatosis type 1 (NF1) is the most common monogenic disorder in which individuals manifest CNS abnormalities. Affected individuals develop glial neoplasms (optic gliomas, malignant astrocytomas) and neuronal dysfunction (learning disabilities, attention deficits). Nf1 genetically engineered mouse models have revealed the molecular and cellular underpinnings of gliomagenesis, attention deficit, and learning problems with relevance to basic neurobiology. Using NF1 as a model system, these studies have revealed critical roles for the NF1 gene in non-neoplastic cells in the tumor microenvironment, the importance of brain region heterogeneity, novel mechanisms of glial growth regulation, the neurochemical bases for attention deficit and learning abnormalities, and new insights into neural stem cell function. Here we review recent studies, presented at a symposium at the 2012 Society for Neuroscience annual meeting, that highlight unexpected cell biology insights into RAS and cAMP pathway effects on neural progenitor signaling, neuronal function, and oligodendrocyte lineage differentiation.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2012; 32(41):14087-93. DOI:10.1523/JNEUROSCI.3242-12.2012 · 6.75 Impact Factor
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ABSTRACT: This paper presents a theoretical study on thermohydrodynamic lubrication of liquid seals with a notched rotor face. The 3D numerical modelisation used in this work has been previously developed for smooth rotor face. Henceforth, the numerical program integrates the modelisation of deep rotor face seal. The finite difference method is used and some hypotheses have been made in order to determine the pressure and the temperature in the notch. The effects of the presence of notches on rotor face seal are analysed and discussed.