Nuclear phosphorylated Y142 ß-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion.

Glioblastoma multiforme (GBM) is a fast growing brain tumor characterized by extensive infiltration into the surrounding tissue and one of the most aggressive cancers. GBM is the most common glioma (originating from glial-derived cells) that either evolves from a low grade astrocytoma or appears de novo. Wnt/ß-catenin and Hepatocyte Growth Factor (HGF)/c-Met signaling are hyperactive in human gliomas, where they regulate cell proliferation, migration and stem cell behavior. We previously demonstrated that ß-catenin is phosphorylated at Y142 by recombinant c-Met kinase and downstream of HGF signaling in neurons. Here we studied phosphoY142 (PY142) ß-catenin and dephospho S/T ß-catenin (a classical Wnt transducer) in glioma biopsies, GBM cell lines and biopsy-derived glioma cell cultures. We found that PY142 ß-catenin mainly localizes in the nucleus and signals through transcriptional activation in GBM cells. Tissue microarray analysis confirmed strong nuclear PY142 ß-catenin immunostaining in astrocytoma and GBM biopsies. By contrast, active ß-catenin showed nuclear localization only in GBM samples. Western blot analysis of tumor biopsies further indicated that PY142 and active ß-catenin accumulate independently, correlating with the expression of Snail/Slug (an epithelial-mesenchymal transition marker) and Cyclin-D1 (a regulator of cell cycle progression), respectively, in high grade astrocytomas and GBMs. Moreover, GBM cells stimulated with HGF showed increasing levels of PY142 ß-catenin and Snail/Slug. Importantly, the expression of mutant Y142F ß-catenin decreased cell detachment and invasion induced by HGF in GBM cell lines and biopsy-derived cell cultures. Our results identify PY142 ß-catenin as a nuclear ß-catenin signaling form that downregulates adhesion and promotes GBM cell invasion.

Primary bone non-Hodgkin lymphoma of the cervical spine: case report and review.

Primary bone lymphomas (PBL) account for approximately 3% of all malignant tumors and are commonly found in the femur or pelvis. Only 1.7% of the PBLs are found in the spine. We report the case of a 73-year-old male complaining of cervical pain with progressive loss of strength and frequent falls. The MRI showed invasion of the fourth cervical vertebra and an infiltrating prevertebral mass. A C4 corpectomy was performed. The pathology exam revealed a diffuse large B-cell lymphoma. Due to the previous condition of the patient only radiotherapy treatment was applied. PBL arising from the cervical spine is an exceptional event. The low incidence of this condition and its unspecific radiological features make the diagnosis challenging for the clinician. When neurological deficit appears, early surgery for decompression is indicated, followed by local radiotherapy and systemic chemotherapy.

Bilateral traumatic facial paralysis. Case report.

Although traumatic injury of the facial nerve is a relatively common condition in neurosurgical practice, bilateral lesions related to fracture of temporal bones are seldom seen. We report the case of a 38-year-old patient admitted to Intensive Care Unit after severe head trauma requiring ventilatory support (Glasgow Coma Scale of 7 on admission). A computed tomography (CT) scan confirmed a longitudinal fracture of the right temporal bone and a transversal fracture of the left. After successful weaning from respirator, bilateral facial paralysis was observed. The possible aetiologies for facial diplegia differ from those of unilateral injury. Due to the lack of facial asymmetry, it can be easily missed in critically ill patients, and both the high resolution CT scan and electromyographic studies can be helpful for correct diagnosis.

[Normal pressure hydrocephalus: prognostic value of height in patients treated with an identical shunt system]. / Hidrocefalia crónica del adulto: valor pronóstico de la estatura en pacientes manejados con un mismo sistema derivativo valvular.

INTRODUCTION: Normal pressure hydrocephalus (NPH) is a clinical entity frequently managed by means of a cerebrospinal fluid shunt. Hydrodynamic hypotheses consider hydrostatic pressure (as well as height) a very important variable for shunt system function. However, we did not find empirical studies supporting the influence of height on clinical response in the literature. Our objective was to study the prognostic value of height, as a variable related to hydrostatic pressure, when an identical shunt system is used. MATERIAL AND METHOD: A prospective series of 61 idiopathic NPH cases was analyzed. All cases were shunted by means of a ventricle-peritoneal system with a 100mmH2O opening pressure valve. Anthropometric, clinical, radiological and pressure variables were registered, as well as delay for treatment, improvement and complications. RESULTS: 78.7% of cases improved after shunting. This group of patients was significantly taller (P=.005) than the group without response (median value 165cm versus 152cm). There was also a significant correlation between height and ventricular size decrease after the shunt. CONCLUSIONS: In our series opening valve pressure was a constant (100mmHg) and we could consequently focus on the effect of hydrostatic pressure (height). Moreover, we found a positive predictive value for taller patients, probably because we had selected an opening pressure especially suitable for them. Current gravitational valve shunt systems also recommend considering patient height when customising the system. Our study empirically supports this idea.

ß-Catenin Signalling in Glioblastoma Multiforme and Glioma-Initiating Cells.

Glioblastoma multiforme (GBM) is a commonly occurring brain tumor with a poor prognosis. GBM can develop both "de novo" or evolve from a previous astrocytoma and is characterized by high proliferation and infiltration into the surrounding tissue. Following treatment (surgery, radiotherapy, and chemotherapy), tumors often reappear. Glioma-initiating cells (GICs) have been identified in GBM and are thought to be responsible for tumors initiation, their continued growth, and recurrence. ß-catenin, a component of the cell-cell adhesion complex and of the canonical Wnt pathway, regulates proliferation, adhesion, and migration in different cell types. ß-catenin and components of the Wnt canonical pathway are commonly overexpressed in GBM. Here, we review previous work on the role of Wnt/ß-catenin signalling in glioma initiation, proliferation, and invasion. Understanding the molecular mechanisms regulating GIC biology and glioma progression may help in identifying novel therapeutic targets for GBM treatment.

Second malignancies in pediatric patients: imaging findings and differential diagnosis.

Therapeutic advances in the treatment of pediatric neoplasms have improved the prognosis but have also increased the risk of developing rare second malignant neoplasms (SMNs). Primary neoplasms that are often associated with SMNs include lymphoma, retinoblastoma, medulloblastoma, neuroblastoma, and leukemia. The most common SMNs are central nervous system (CNS) tumors, sarcomas, thyroid and parotid gland carcinomas, and leukemia, particularly acute myeloblastic leukemia. Genetic predisposition, chemotherapy, and especially radiation therapy are implicated as pathogenic factors in SMN. All survivors of childhood cancer should have lifelong follow-up, preferably with magnetic resonance imaging, which does not require ionizing radiation and provides greater anatomic detail and resolution in the head and neck region and the CNS. A new or progressive lesion may represent recurrence of the primitive neoplastic process, late radiation injury, or, more infrequently, an SMN. Differential diagnosis can be very difficult, and outcome is often fatal. Treatment protocols should be modified to reduce the risk for SMN without compromising the effectiveness of initial therapy. Clinicians should individualize treatment for patients who are genetically predisposed to SMN. In addition, radiologists should be familiar with the long-term consequences of antineoplastic therapy to facilitate diagnosis and anticipate adverse outcomes.