Search

Aims Schwann cells myelinate axons of the peripheral nervous system. This process of myelination is regulated by various transcription factors. c- Jun and Sox-2 are negative regulators of myelination and control Schwann cell differentiation and plasticity. Schwannoma cells within tumours no longer express myelin markers, and show increased proliferation and decreased apoptosis. We have shown previously that several signalling pathways are activated in schwannoma cells in situ, in particular the c- Jun N-terminal kinase ( JNK) pathway. Both in vitro and in vivo we have demonstrated that c- Jun and Sox-2 are co-regulated in Schwann cells and evidence shows that both these proteins regulate myelination negatively. In this study, we aimed to characterize the expression of c- Jun and Sox-2 in schwannoma and traumatic neuroma. Methods and results Immunohistochemistry using antibodies to c- Jun and Sox-2 was applied to six schwannomas, and the results were compared with those seen in traumatic neuroma and normal nerve. Increased expression of c- Jun and Sox-2 was seen in schwannoma. Conclusions We have demonstrated increased expression of c- Jun and Sox-2 in schwannoma compared to traumatic neuroma. There was no expression of c- Jun and Sox-2 in a histologically normal peripheral nerve. [ABSTRACT FROM AUTHOR]

Aims: Schwannomas are common tumours that may be multiple in neurofibromatosis type 2, when they may be difficult to treat without significant morbidity using surgery and radiosurgery. Previous in vitro work has suggested that merlin loss is associated with activation of the JNK/JUN, PI3K/AKT and MEK/ERK pathways and that these pathways may be susceptible to pharmacological inhibition. The aim was to investigate the expression of proteins involved in these pathways in human schwannomas in situ. Methods and results: Immunohistochemistry using antibodies to AKT, pAKT, MEK, pMEK, ERK, pERK, JUN and pJUN was applied to 16 schwannomas (sporadic and NF2), and the results were compared with those seen in traumatic neuromas. Increased expression of pMEK, pERK and pJUN was seen in the schwannomas samples and of pAKT in schwannomas and controls. Conclusions: These findings provide further direct evidence for activation of the JNK/JUN, PI3K/AKT and MEK/ERK signalling pathways in schwannomas and support the development of therapeutic agents directed against these pathways for the treatment of this group of tumours. [ABSTRACT FROM AUTHOR]

Neurofibromatosis 2 (NF2) is a hereditary tumor disease characterized by bilateral vestibular schwannomas. Polyneuropathy seems to occur quite frequently in NF2 and in most cases, the etiology of this neuropathy is unclear, especially when the neuropathy is symmetric. NF2 is believed to follow the two-hit hypothesis. According to this, one allele is mutated in the germline, and the second hit is somatic and results in tumor formation. The second hit most frequently is a loss of the NF2 locus, often the entire chromosome 22. We set out to investigate the underlying genetics in peripheral nerve of NF2 patients with polyneuropathy. We identified NF2 patients with polyneuropathy in which we could detect the germline mutation and analyzed NF2 gene dosage in archived nerve biopsies from these patients using a newly developed method. We observed merlin haploinsufficiency in peripheral nerves of two different patients with NF2-related polyneuropathy. This finding was further supported by showing that approximately 50% merlin expression in a cell line using shRNA results in altered gene expression as previously shown in schwannomas. Thus, we suggest that reduced merlin gene dosage is relevant in NF2-associated polyneuropathy. [ABSTRACT FROM AUTHOR]

Several LnSr2Ta2Li7O12 compounds are prepared as ordered tetragonal garnet phase along with a small amount of cubic garnet by firing stoichiometric amounts of the metal oxides and a 20% excess of Li2CO3 (pre-reacted pellets on ZrO2 in Al2O3 crucible, 850 °C, 14 h). [ABSTRACT FROM AUTHOR]