THOMAS SEYFRIED

..The view of metastasis as a macrophage metabolic disease can provide novel insight for therapeutic management...

..Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer...

..Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter...

..Activated AMPK acts as either an inducer or suppressor of apoptosis depending on the severity of energy stress and the presence or absence of certain functional tumor suppressor genes...

..It is also unclear how these biomarker changes in calorically restricted mice relate to those observed previously in calorically restricted humans...

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..Such cells would naturally embody the capacity to express the multiple behaviors of metastatic cells. The view of metastasis as a myeloid/macrophage disease will impact future cancer research and anti-metastatic therapies...

..Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (OL) and the Arg tRNA...

..Also discussed are implications of these concepts for the diagnosis and therapy of human brain tumors...

..1Bird) or the Mecp2 (308/y) RS mice...

..The goal here was to determine if low doses of 2-DG could act synergistically with the KD-R to better manage growth of the CT-2A malignant mouse astrocytoma...

..The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms...

..A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention...

..Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies...

..Issues of implementation and use protocols are presented for the metabolic management of brain cancer...

..CONCLUSIONS: We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders...

..Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers...

..We conclude that N B-DNJ may inhibit tumour growth through an effect on ganglioside biosynthesis and may be useful as a new chemotherapy for brain tumours...

..The findings are relevant to the basic mechanisms of epilepsy and to theories of genetic recombination and gene mapping...

..Although an association was observed previously between Ca(2+)-ATPase activity and susceptibility to audiogenic seizures (AGS), no significant association was observed for the expression of Ntp and AGS susceptibility...

..The genetic dissection of convulsive behavior in EL and AGS susceptible mice could help identify candidate genes for human multifactorial epilepsies...

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..6, respectively) or GABA (23.5 +/- 0.7, 19.5 +/- 3.2, and 21.8 +/- 3.2, respectively). Thus, enhanced aspartate release precedes the onset of EL seizures and may be related to the cause rather than to the effects of seizure activity...

..This tumour will be a useful natural model for evaluating the role of gangliosides and other glycolipids in tumour cell invasion and metastasis...

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..These data suggest that gene-linked changes in ganglioside composition influence the growth and angiogenic properties of the CT-2A astrocytoma...

..These findings suggest that substrate reduction therapy using NB-DGJ may be an effective early intervention for GM1 gangliosidosis and possibly other GSL lysosomal storage diseases...

..CONCLUSIONS: These findings indicate that oxygenation prevents sudden death in seizure-prone mice and suggest that oxygenation may protect some seizure-prone humans at risk for SUDEP...

..Because extensive angiogenesis and resistance to apoptosis are hallmarks of gliomas, this study provides new insight into the molecular basis of the DR-induced inhibition of brain tumor growth...

..A better understanding of the compensatory genetic and neurochemical networks of brain energy metabolism may produce novel antiepileptic therapies that are more effective and biologically friendly than those currently available...

..We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms...

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..The new VM tumor model will be useful for defining the biological processes of cancer metastasis and for evaluating potential therapies for tumor management...

..NS and Syn mitochondrial lipidomic heterogeneity could influence energy metabolism, which may contribute to metabolic compartmentation of the brain...

..Moreover, the CT-2A cells also express a series of interferon-induced signature proteins that may be specific to this tumor. These data highlight the utility of LC-MS/MS for the identification of brain tumor membrane biomarkers...

..The EL mouse can be a useful model for evaluating neuron-glia interactions related to idiopathic epilepsy...

..Our findings present a model system for assessing retinal pathobiology and therapies for the gangliosidoses...

..These results suggest that the reduced brain beta-gal activity alone cannot account for the elevation of total brain gangliosides and GM1 in the D2 mice...

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..Our results show that NB-DGJ is effective in reducing total brain ganglioside and GM2 content at early neonatal ages...

..The proposed studies will provide essential information on combinatorial therapies for the ganglioside storage diseases and will have translational benefit to the clinic. ..

..The proposed research will better define the relationship between gangliosides and tumor angiogenesis and can lead to new experimental strategies for managing brain tumors. ..

..Since there are no effective treatments for human ganglioside storages disease, the proposed research could offer a novel therapy for the early intervention of these neurodegenerative disorders. ..

..The proposed studies will provide essential information on combinatorial therapies for the ganglioside storage diseases and will have translational benefit to the clinic. ..