Voltage-dependent K+ channels as oncotargets in malignant gliomas

SCOPUS: no.jinfo:eu-repo/semantics/publishe

How to optimize neurosurgical approach decision in case of inflammatory hidradenitis suppurativa lesions involving the lumbo-sacral area: Report of a clinical case

info:eu-repo/semantics/publishe

Glutamate et gliomes malins, de l'épilepsie l'agressivité biologique: implications thérapeutiques

In this review article, we describe the unrecognized roles of glutamate and glutamate receptors in malignant glioma biology. The neurotransmitter glutamate released from malignant glioma cells in the extracellular matrix is responsible for seizure induction and at higher concentration neuronal cell death. This neuronal cell death will create vacated place for tumor growth. Glutamate also stimulates the growth and the migration of glial tumor cells by means of the activation of glutamate receptors on glioma cells in a paracrine and autocrine manner. The multitude of effects of glutamate in glioma biology supports the rationale for pharmacological targeting of glutamate receptors and transporters in the adjuvant treatment of malignant gliomas in neurology and neuro-oncology. Using the website www.clinicaltrials.gov/ as a reference - a service developed by the National Library of Medicine for the National Health Institute in USA - we have evoked the few clinical trials completed and currently ongoing with therapies targeting the glutamate receptors. © John Libbey Eurotext.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Present and potential future adjuvant issues in high-grade astrocytic glioma treatment.

Despite major advances in the management of malignant gliomas of which glioblastomas represent the ultimate grade of malignancy, they remain characterized by dismal prognoses. Glioblastoma patients have a median survival expectancy of only 14 months on the current standard treatment of surgical resection to the extent feasible, followed by adjuvant radiotherapy plus temozolomide, given concomitantly with and after radiotherapy. Malignant gliomas are associated with such dismal prognoses because glioma cells can actively migrate through the narrow extra-cellular spaces in the brain, often travelling relatively long distances, making them elusive targets for effective surgical management. Clinical and experimental data have demonstrated that invasive malignant glioma cells show a decrease in their proliferation rates and a relative resistance to apoptosis (type I programmed cell death) as compared to the highly cellular centre of the tumor, and this may contribute to their resistance to conventional pro-apoptotic chemotherapy and radiotherapy. Resistance to apoptosis results from changes at the genomic, transcriptional and post-transcriptional level of proteins, protein kinases and their transcriptional factor effectors. The PTEN/ PI3K/Akt/mTOR/NF-kappaB and the Ras/Raf/MEK/ERK signaling cascades play critical roles in the regulation of gene expression and prevention of apoptosis. Components of these pathways are mutated or aberrantly expressed in human cancer, notably glioblastomas. Monoclonal antibodies and low molecular-weight kinase inhibitors of these pathways are the most common classes of agents in targeted cancer treatment. However, most clinical trials of these agents as monotherapies have failed to demonstrate survival benefit. Despite resistance to apoptosis being closely linked to tumorigenesis, tumor cells can still be induced to die by non-apoptotic mechanisms such as necrosis, senescence, autophagy (type II programmed cell death) and mitotic catastrophe. Temozolomide brings significant therapeutic benefits in glioblastoma treatment. Part of temozolomide cytotoxic activity is exerted through pro-autophagic processes and also through the induction of late apoptosis. Autophagy, type II programmed cell death, represents an alternative mechanism to overcome, at least partly, the dramatic resistance of many cancers to pro-apoptotic-related therapies. Another way to potentially overcome apoptosis resistance is to decrease the migration of malignant glioma cells in the brain, which then should restore a level of sensitivity to pro-apoptotic drugs. Recent series of studies have supported the concept that malignant gliomas might be seen as an orchestration of cross-talks between cancer cells, microenvironment, vasculature and cancer stem cells. The present chapter focuses on (i) the major signaling pathways making glioblastomas resistant to apoptosis, (ii) the signaling pathways distinctly activated by pro-autophagic drugs as compared to pro-apoptotic ones, (iii) autophagic cell death as an alternative to combat malignant gliomas, (iv) the major scientific data already obtained by researchers to prove that temozolomide is actually a pro-autophagic and pro-apoptotic drug, (v) the molecular and cellular therapies and local drug delivery which could be used to complement conventional treatments, and a review of some of the currently ongoing clinical trials, (vi) the fact that reducing the levels of malignant glioma cell motility can restore pro-apoptotic drug sensitivity, (vii) the observation that inhibiting the sodium pump activity reduces both glioma cell proliferation and migration, (viii) the brain tumor stem cells as a target to complement conventional treatment.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Traitement des glioblastomes à l'aube de 2010

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Minimally invasive spinal arthrodesis in osteoporotic population using a cannulated and fenestrated augmented screw: Technical description and clinical experience

We describe a percutaneous or minimally invasive approach to apply an augmentation of pedicle fenestrated screws by injection of the PMMA bone cement through the implant and determine the safety and efficiency of this technique in a clinical series of 15 elderly osteoporotic patients. Clinical outcome and the function were assessed using respectively the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI). Peri- and post-operative complications were monitored during a minimum of 2 years of follow-up. Radiographic follow-up was based on plain fluoroscopic control at 3, 6 and 12 months and every year. In this approach, four steps were considered with care: optimal positioning of the screws, correct alignment of the screw heads, waiting time before the injection of cement, fluoroscopic control of the cement injection. Using these precautions, only 2 minor complications occurred. VAS scores and ODI questionnaires showed a statistically significant improvement up to 13.3 months postoperatively. No radiological complications were observed. Based on this experience, PMMA augmentation technique through the novel fenestrated screws provided an effective and long lasting fixation in osteoporotic patients. Applying this procedure through percutaneous or minimally invasive approach under fluoroscopic control seems to be safe. © 2012 Alphonse Lubansu et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Neuropsychiatric disorders revealing primary antiphospholipid syndrome in an elderly patient.

CommentLetterinfo:eu-repo/semantics/publishe

Long-term follow-up survey reveals a high yield, up to 30% of patients presenting newly detected aneurysms more than 10 years after ruptured intracranial aneurysms clipping.

The need to pursue long-term follow-up in patients treated for a ruptured aneurysm remains debated. New aneurysms development is a crucial element to consider but remains scarcely analyzed especially after a mean follow-up longer than 10 years. Our study was designed to provide rates of newly developed aneurysms in patients who have undergone prior clipping who were not followed with serial imaging. Patients were included if they were (1) treated more than 10 years ago by clipping of a ruptured aneurysm, (2) independent at time of discharge, (3) presently younger than 65 years, and if (4) they agreed to undergo a late digital subtraction angiography (DSA) control or to transmit results of a recent one performed elsewhere. Twenty patients were included with a mean delay between aneurysm treatment and late DSA of 18.0 years (10-26.5 years). Out of these patients, six (30%) harbored new aneurysms. Of these six individuals, four (66.6%) presented multiple aneurysms with a total of 15 newly discovered aneurysms. Aneurysm sizes ranged from 1 to 10 mm. One patient suffered from a de novo aneurysm rupture. Multiple aneurysms at the time of the first hemorrhage were a risk factor in developing de novo aneurysm (p=0.0175). In conclusion, based on a 30% rate of new aneurysm formation in patients clipped more than a decade ago, close screening on a very long-term perspective is encouraged. This study suggests aneurysm formation to be a continuous process.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Chronic in vitro temozolomide treatment of human glioblastoma cell lines fails to induce resistance to the drug in vitro or in vivo but modifies gene expression.

info:eu-repo/semantics/nonPublishe