Background: Long intergenic non-coding RNA, regulator of reprogramming ( LINC-ROR) is a newly identified cytoplasmic long non-coding RNA (lncRNA), which has been found to be dysregulated in different cancers. The present work aimed to quantify LINC-ROR expression profile and assess the tumor proteins p53 and caspase 3 expressions in glioblastoma tissue specimens compared to non-cancer tissues, and to correlate these expression levels with the available clinicopathological and survival data. Methods: LINC-ROR relative expression in 57 glioblastoma cancer tissues and 10 non-cancer tissues was quantified by real-time polymerase chain reaction (qPCR). In addition, methylation-specific PCR of O-6-methylguanine-DNA methyltransferase ( MGMT) promoter and immunohistochemical expression of apoptosis related proteins: p53 and caspase 3 were performed. Results: The up-regulation of LINC-ROR was encountered in 89.5% of patients. The higher expression of LINC-ROR was associated with poor disease progression-free and overall survival as well as a younger age of patients ( P=0.036). p53 protein was expressed only in glioblastoma but not in non-cancer tissues while caspase 3 was weakly expressed in most non-cancer tissues and in varying degrees in glioblastoma (24% weak, 30% moderate, and 16% strong expression). The Kaplan–Meier survival plot illustrated poor survival in glioblastoma patients with over-expressed LINC-ROR ( P=0.010) and down-regulated p53 ( P=0.002). Multivariate analysis showed that glioblastoma patients were clustered into two distinct groups based on LINC-ROR expression profile, p53 staining levels and patients’ overall survival. Conclusions: LINC-ROR up-regulation may have a role in glioblastoma tumorigenesis and could be a potential prognostic marker for this fatal disease.
Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.
Between July 1992, and February 1997, 15 patients with cavernous malformations underwent interactive image-guided resection of their lesions. There were eight women and seven men in the group, ranging in age from 6 years to 62 years (mean 34 years). Clinical presentations included seizures (n = 7), headache (n = 4), and hemorrhage (n = 4). Prior conventional subtotal resection had been performed in one patient, and a history of prior hemorrhage was found for two patients. Diagnosis was made using magnetic resonance imaging and digital substraction angiography. Locations of the lesions were temporal (n = 9), frontal (n = 3), thalamus (n = 1), basal ganglia (n = 1), and pons (n = 1). Size ranged from 9 to 20 mm (mean 12 mm). For those lesions located near or within eloquent areas (n = 7), an awake craniotomy with functional cortical and subcortical mapping was performed. An infrared system was used intraoperatively to confirm the location and the extent of the resection of these lesions in real time. In 1996 we started using a robotic microscope to aid in localization and resection. Clinical follow-up ranged from 2 to 54 months (mean 27 months). In all 15 patients, complete surgical resection was achieved as demonstrated by postoperative magnetic resonance imaging studies. Two patients had postoperative transient neurological deficits (13.3%) that cleared over a 6-month period. One of them had a lesion in the pons, with multiple cranial nerve deficits postoperatively that gradually improved. There was no associated mortality. Histological diagnosis was consistent with cavernous angioma in all cases. Clinical follow-up revealed that 13 patients experienced complete recovery from preoperative symptoms and two patients with seizures showed marked improvement. We conclude that interactive image-guided surgery for deep-seated cavernous malformations represents a very accurate and safe approach.
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