Promoter hypermethylation-mediated down-regulation of RUNX3 gene in human brain tumors.

BACKGROUND: The Runx family proteins, including RUNX3, are tissue-restricted transcription factors and play role in neuronal development and tumorigenesis. RUNX3 has an important role in glioblastoma (GBM) tumorigenesis because of its promoter hypermethylation. AIM: We aimed to evaluate the methylation-mediated expression regulation of RUNX3 gene in brain tumors. PATIENTS AND METHODS: Cases of meningiomas WHO grade III (3), anaplastic astrocytomas (3), diffuse astrocytoma (3), and GBM (12) were recruited into this study. Real-time quantitative PCR was performed for analyses of DNA promoter methylation and analyses of methylation-mediated expression status of RUNX3 gene was performed by real-time quantitative RT-PCR. RESULTS: There was no significant difference between methylated and unmethylated quantitative ratio of RUNX3 gene promoter region and also no significant difference in relative ratio of RUNX3 gene expression in brain tumor groups. Methylated and unmethylated ratio in anaplastic astrocytoma, diffuse astrocytoma, GBM, meningioma (WHO grade III) and in all groups were; 1.44, 1.09, 1.51, 1.52 and 1.43, respectively. One allele was found methylated necessarily. No methylation was detected in one case of GBM group and one case of anaplastic astrocytoma group. There was no unmethylated promoter in one of the GBM cases. There were significant differences between relative ratio of RUNX3 gene expression and methylated/unmethylated ratio rates for all cases (p = 0.001) and GBM groups (p = 0.041). CONCLUSION: This study overemphasized the RUNX3 gene importance in brain tumors, due to the existence of at least one methylated allele.

Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study.

Cancer vaccine therapy represents a promising therapeutical option. Consistently, with these new treatment strategies, the use of dendritic cell vaccines is becoming increasingly widespread and currently in the forefront for cancer treatment. The purpose of this study was to evaluate the feasibility and safety of tumor lysate-pulsed dendritic cell (DC) vaccine in patients with advanced cancers. For this purpose, eighteen patients with relapsed or refractory cancer were vaccinated with peripheral monocyte-derived DCs generated with GM-CSF and IL-4, and pulsed consequently with 100 microg/ml of tumor lysate before maturation in culture in the presence of IL-1beta, PGE2 and TNF alpha for two days. The first two vaccinations were given intradermally every two weeks while further injections were given monthly. Tumor lysate-pulsed dendritic cell injections were well-tolerated in all patients with no more than grade 1 injection-related toxicity. Local inflammatory response was mainly erythematous which subsided in 48 hrs time. No end organ toxicity or autoimmune toxicity was identified. Clinical responses observed in our study were satisfactory for a phase I clinical study. We observed 4 (22%) objective clinical responses. These responses are significantly correlated with delayed type hypersensitivity testing (DTH) (p < 0.01). The results showed that this active immunotherapy is feasible, safe, and may be capable of eliciting immune responses against cancer.

Cerebral cortical and deep venous thrombosis without sinus thrombosis: clinical MRI correlates.

BACKGROUND: Cortical and/or deep vein thrombosis (CDVT) without dural sinus involvement is uncommon and presents diagnostic difficulty for many reasons. Our aim is to determine the relationship between magnetic resonance imaging (MRI) findings and clinical findings in patients with CDVT. METHODS: Forty-six patients with venous stroke proved on MRI included in our Registry, corresponding to 0.1% of 4650 patients with stroke, were studied. Magnetic resonance angiography (MRA) was performed in all patients, and 18 of them had follow-up MRA. Outcome was evaluated by using the Glasgow Outcome Scale at the time of discharge and during follow-up. RESULTS: Thirty-two patients presented cortical venous stroke; 21 of them had involvement of the dorsomedial venous system, six had a defect in the posteroinferior venous group, and five had a defect in the anteroinferior venous group. Thirteen patients presented simultaneous involvement of the superficial and deep venous system; seven with a defect in the parietal and internal cerebral veins (three with involvement of vein of Gallen), four with a defect in the temporooccipital (vein of Labbé) and basal vein of Rosenthal, two with a deficit in the anterior frontotemporal and uncal-pterygoid venous system. One patient had deep venous thrombosis primarily localized to the thalami bilaterally and the basal ganglia on the right because of occlusion of the thalamostriate veins. The main presenting symptoms of CDVT were headache, focal neurologic signs, partial complex or secondary generalized seizures, and consciousness disturbances in those with deep venous thrombosis, presented alone or in combination at onset. CDVT was more than twofold more frequent in women than in men. Pregnancy, puerperium, oral contraceptive use, and infections were the most common predisposing factors. CONCLUSION: Computerized tomography, conventional MRI and diffusion-weighted imaging showing ischemic and/or hemorrhagic lesion that does not follow the boundary of classical arterial boundaries without signs of sinus thrombosis, and partial or generalized seizures followed by focal neurologic signs may predict CDVT. The outcome of patients with cortical venous stroke was good, but not in those with cortical plus deep venous infarction.

Posttraumatic intradural internal carotid artery-cavernous sinus fistula associated with ipsilateral carotid dissection. Transarterial embolization with detachable coils.

SUMMARY: We describe a relatively unusual case of traumatic direct carotid-cavernous fistula in association with a giant intradural venous pouch and ipsilateral carotid dissection, related to carotid artery fistula located in the supraclinoid segment just below the origin of posterior communicating artery. Endovascular therapy could be accomplished by use of detachable coils transarterially. Awareness of an unusual intradural origin of a carotid-cavernous sinus fistula and the possibility of an embolization should be kept in mind.

Failure to detect Chlamydia pneumoniae DNA in cerebral aneurysmal sac tissue with two different polymerase chain reaction methods.

OBJECTIVE: Chlamydia pneumoniae (C pneumoniae) is a common cause of a usually mild, community acquired pneumonia. This organism, however, can spread from the respiratory tract into other parts of the body and has been detected in up to 70% of atheromatous lesions in blood vessels. Although the exact mechanism of the C Pneumoniae contribution to the pathogenesis of atherosclerosis remains unknown, prophylactic antibiotic trials are planned for people at high risk for coronary disease. METHOD: In this study the authors aimed to investigate C pneumoniae DNA content in the cerebral aneurysmal sac tissue with the aid of polymerase chain reaction (PCR) method. C pneumoniae DNA was searched in 15 surgically clipped and removed aneurysmal sac tissue and in two tumour (an ependymoma of the fourth ventricle and a craniofaringoma) samples by touchdown enzyme time release PCR (TETR PCR) targeting 16S rRNA gene and by nested PCR targeting ompA gene. RESULTS: Both PCR methods were sensitive to detect in C pneumoniae 4x10(-2) genomes. C pneumoniae DNA was not detected in any of the 17 sample tissues of these patients. CONCLUSION: The contribution of C pneumoniae in the development of intracranial aneurysms cannot be excluded despite the results of this study. Further studies on the possible role of C pneumoniae or any other micro-organisms in the pathogenesis of aneurysms should be performed.

Efficacy of controlled-release papaverine pellets in preventing symptomatic cerebral vasospasm.

OBJECT: Vasospasm as a complication of subarachnoid hemorrhage is a major concern in clinical practice. The systemic drugs in current use are of limited value. Topical, intrathecal, or intraarterial papaverine administered during surgical or angiographic procedures is a potent vasodilating drug; however, hypotension limits its systemic application. Local application of papaverine in a biodegradable controlled- or sustained-release matrix is proposed for vasospasm prophylaxis to be used in patients scheduled for aneurysm surgery. METHODS: Controlled-release papaverine (PapaCR) drug pellets were prepared using the biodegradable aliphatic polyester poly(DL-lactide-co-glycolide) as the carrier matrix. In vitro tests were performed to determine drug kinetics. One hundred seventeen patients, 73 assigned to the control group and 44 assigned to the PapaCR-treated group, participated in this study. Patients who were deemed to be at high risk for the development of vasospasm were selected to participate in the study. During aneurysm surgery, drug pellets were placed in cisterns over arterial segments. In two patients, cerebrospinal fluid was sampled every 6 hours for the first 5 days through a lumbar catheter that had been inserted at the beginning of aneurysm surgery. The incidence of clinical vasospasm and Glasgow Outcome Scale scores in the patients were evaluated statistically. The results of in vitro studies showed that effective local concentrations of papaverine could be maintained for more than 10 days. The first-degree drug-release profile was demonstrated using this design. In clinical studies no adverse effects due to the drug were seen. The PapaCR effectively prevented development of clinical vasospasm. and outcome scores were significantly better in patients in the treated group. CONCLUSIONS: Local application of controlled- or sustained-release papaverine can be safely used in preventing vasospasm.

Intradural Aneurysm Caused by Arterial Injury during Surgery: Treatment with Coil Embolization.

SUMMARY: We described a patient with subarachnoid hemorrhage due to a ruptured intradural aneurysm caused by arterial injury during surgery and severe symptomatic vasospasm. The iatrogenic posttraumatic aneurysm was occluded by using GDC with preservation of parent artery followed by intraarterial infusion of papaverine to treat vasospasm as an one-stage procedure. This resulted in significant angiographic resolution of the vasospasm and the patient's clinical outcome was excellent. Endovascular approach to posttraumatic intracranial aneurysms and endosaccular GDC embolization of aneurysm with concomitant intraarterial papaverine infusion to treat vasospasm are discussed.

Multielectrode array for simultaneous recording of glucose, oxygen and electrocorticography from cerebral cortex in experimental focal epilepsy.

Delineating epileptic tissue before and during surgery is still a major problem. Electroencephalography (EEG), electrocorticography (ECoG), and magnetoencephalography (MEG) evaluations may not always correlate with outcome. Metabolic mapping, i.e. positron emission tomography (PET) or single photon emission tomography (SPECT), is not practical or not sensitive--both spatial and temporal--enough for use in neurosurgery. Amperometric electrochemical electrodes for recording oxygen and glucose from nervous tissue are developed and tested in rat experimental focal penicillin epilepsy model. With a three-by-three array of glucose electrodes, epileptic focus is mapped. Simultaneous recordings of ECoG, oxygen and glucose levels performed. During seizure, extracellular glucose level showed a biphasic response pattern while oxygen level decreased slightly. It has been concluded that such a combined subdural grid recording might help before and during surgery. This method can be used in ischemia and such experimental metabolic studies.

Effect of surface boundary on neuronal magnetic stimulation.

The effect of the surface boundary between free space and a conducting medium on the excitation properties of neurons by magnetic fields are analyzed. The electric field and the spatial derivative of the induced field generated by a coil mounted both parallel and perpendicular to the surface of a semi-infinite conducting medium were calculated using the method of images. An imaginary axon is located in the same relative position from the coil in both configurations and the excitation properties are compared. The calculations are expressed in terms of the activating function for the electrical stimulation of axons. The calculations indicate that the activating function for magnetic stimulation is biphasic as opposed to triphasic for electrical stimulation. The large spatial extent of the magnetically induced electric field compared to the electric field generated by point source electrode suggests a different mode of excitation for neuronal structures in the CNS. The field distribution have been verified experimentally and are important for the understanding of the mechanisms of magnetic stimulation of neural tissue.

Effects of methyl prednisolone, dimethyl sulphoxide and naloxone in experimental spinal cord injuries in rats.

The effects of methyl prednisolone (MPD), dimethyl sulphoxide (DMSO), and naloxone were examined in 38 albino rats after making an impact spinal cord injury on the midthoracic segments with a modified Allen's weight dropping trauma method. Somatosensorial evoked potentials (SEPs) were recorded before and 12 h and 14 d after the injury from epidurally inserted electrodes on the parietal cortex with sciatic nerve stimulations. Lower extremity motor functions of the animals were also examined. It may be concluded that in this study model, DMSO has a moderate effect which can be demonstrated clinically and through SEPs. Naloxone has no effect on the clinical outcome but causes reasonable improvement electrophysiologically.