ABSTRACT
OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.
Subject(s)
Meningeal Neoplasms , Meningioma , Skull Base Neoplasms , Humans , Middle Aged , Meningioma/complications , Meningioma/diagnostic imaging , Meningioma/surgery , Meningeal Neoplasms/complications , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , Treatment Outcome , Sella Turcica/diagnostic imaging , Sella Turcica/surgery , Sella Turcica/pathology , Neurosurgical Procedures/methods , Skull Base Neoplasms/surgery , Retrospective StudiesABSTRACT
Objective: The aim of the study is to explore the characteristics of systolic blood pressure (SBP) and heart rate (HR) changes in patients undergoing percutaneous balloon compression (PBC) for trigeminal neuralgia and analyze the factors that influence the formation of the symbolic pear shape of the balloon, which signifies successful compression. Methods: We retrospectively analyzed the changes in systolic blood pressure (SBP) and heart rate (HR) in 103 consecutive patients with trigeminal neuralgia (TN). Fifty-five patients who underwent operations with intermittent inflating cuff blood pressure (IICBP) monitoring were classified into the IICBP group. The other 48 patients who underwent continuous intra-arterial blood pressure (CIABP) monitoring were classified into the CIABP group. Results: Among all the patients, there were more women than men and the patients in both the groups more commonly had TN on the right side and involving branch III. First, the balloon appeared as "pear-shaped" when the compression was effective, and the SBP increased an average of 59.04% in the CIABP group. CIABP provided us the precise range of the increase. Older patients had higher SBPs, especially patients with hypertension. Second, SBP was more sensitive and lasted much longer than HR in the process of puncturing the foramen ovale and compressing the ganglion. SBP fluctuated much more in the CIABP group than in the IICBP group. Third, the median time taken in the CIABP group was less than the IICBP group, and the prognosis of the CIABP group was better than the IICBP group. Conclusion: Effective ganglion compression significantly increased SBP. CIABP can monitor SBP in real time and can also safeguard the compression process. CIABP is a safe and effective method in the PBC process that is worthy of promotion and application.
Subject(s)
Trigeminal Neuralgia , Arterial Pressure , Catheterization/methods , Female , Humans , Male , Retrospective Studies , Treatment Outcome , Trigeminal Ganglion , Trigeminal Neuralgia/surgerySubject(s)
Meningeal Neoplasms , Meningioma , Plaque, Atherosclerotic , Syringomyelia , Cranial Fossa, Posterior/diagnostic imaging , Humans , Magnetic Resonance Imaging , Meningeal Neoplasms/complications , Meningeal Neoplasms/diagnostic imaging , Meningioma/complications , Meningioma/diagnostic imaging , Plaque, Atherosclerotic/complications , Syringomyelia/complications , Syringomyelia/diagnostic imagingABSTRACT
Craniopharyngiomas (CPs) are benign tumors arising from the sellar region. However, little is known about their clinical features and long-term recurrence due to low morbidity and the lack of large cohort studies. Thus, we aimed to develop nomograms to accurately predict the extent of resection and tumor recurrence using clinical parameters. A total of 545 patients diagnosed with CP between 2009 and 2019 were examined: 381 in the development cohort and 164 in the validation cohort. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed to establish two nomograms. Receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) and Kaplan-Meier (KM) curves were used to evaluate their predictive performance and discriminative power, respectively, in the two cohorts. In addition, the EORTC QLQ-BN20 questionnaire was used to assess neuropsychological status in the follow-up. In the development cohort, the area under the curve (AUC) and C-index were 0.760 and 0.758, respectively, for predicting the extent of resection and 0.78 and 0.75, respectively, for predicting 3-year progression-free survival (PFS) and 5-year PFS. Additionally, the model had a predictive accuracy of 0.785. Both nomograms showed acceptable discrimination in the two cohorts. Moreover, DCA demonstrated excellent clinical benefits from the two nomograms. Finally, participants were classified into two distinct risk groups according to the risk score, and an online calculator was created for convenient clinical use. During long term follow-up, hypothyroidism (77.61%) and hypocortisolism (76.70%) were the most common endocrine dysfunction after surgery and significant deficits were observed concerning visual disorder, motor dysfunction and seizures in the recurrent groups. In particular, better quality of life was associated with gross total resection (GTR), postoperative radiation, anterior interhemispheric (AI) approach and transsphenoidal approach. To our knowledge, these are the first nomograms based on a very large cohort of patients with CP that show potential benefits for guiding treatment decisions and long-term surveillance. The current study demonstrated the online calculator serve as the practical tool for individual strategies based on the patient's baseline characteristics to achieve a better prognosis.
ABSTRACT
Nogo-66 can inhibit neurite outgrowth, while its regulation mechanisms have not been fully elucidated. Recent studies prove that lncRNAs are involved in neurite outgrowth. This study was aimed to investigate whether lncRNA FTX was involved in Nogo-66-induced inhibition of neurite outgrowth and explore the potential mechanism. The expression of relative genes was detected by qRT-PCR and western blot. The function of FTX was determined by overexpression and knockdown techniques. The interaction between FTX and PDK1 was evaluated by RIP and RNA pull-down assays. FTX expression was downregulated by Nogo-66 in PC12 cells. Nogo-66-induced inhibition of neurite outgrowth was relieved by FTX overexpression. FTX bound to PDK1 protein to disturb the interaction between PDK1 and E3 ubiquitin ligase RNF126, thereby blocked the ubiquitination degradation of PDK1 and elevated PDK1 protein level. Mechanically, FTX involved in the Nogo-66-induced inhibition of neurite outgrowth through the PDK1/PKB/GSK-3ß pathway. In SCI rats, FTX knockdown inhibited neurite outgrowth induced by the receptor antagonist of Nogo-66. The present results suggested that FTX took part in Nogo-66-inhibited neurite outgrowth, and FTX exerted its function through regulating PDK1/PKB/GSK-3ß pathway.
Subject(s)
Glycogen Synthase Kinase 3 beta/metabolism , Neuronal Outgrowth/genetics , Nogo Proteins/metabolism , RNA, Long Noncoding/metabolism , Signal Transduction , Animals , Glycogen Synthase Kinase 3 beta/genetics , Male , Neurites/metabolism , Neurons/metabolism , PC12 Cells , Proto-Oncogene Proteins c-akt/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , RNA, Long Noncoding/genetics , RatsABSTRACT
OBJECTIVE: Cortical ependymomas (CEs), supratentorial ependymomas that selectively involve the cerebral cortex, are relatively rare neoplasms that have not been extensively described. The purpose of our study was to identify the clinical features, radiologic characteristics, and treatment of a series of such tumors. METHODS: Thirteen patients with CEs from our hospital were included in this study. Epidemiologic characteristics, clinical features, imaging findings, treatment methods, and clinical outcomes were reviewed retrospectively. RESULTS: The patients consisted of 7 men and 6 women with mean age of 31.1 ± 23.2 years (range, 4-74 years). The most common clinical manifestation was seizure (n = 11; 85%), followed by headache (n = 2; 15%). None of the tumors were incidentally detected. Eight CEs were located in the right hemisphere and 5 in the left side. The 2 most common tumor locations were the frontal (n = 5; 38%) and parietal lobe (n = 5; 38%). All patients underwent surgical resection. Gross total resection was achieved in 12 patients (92%), and subtotal resection was performed in 1 patient (8%). Ten of the 11 patients who presented with seizure are seizure-free after surgery (91% seizure-free rate). According to the World Health Organization classification system, 9 tumors (69%) were Grade II (ependymoma) and 4 (31%) were Grade III (anaplastic ependymoma). The mean follow-up was 52 months (range, 20-88 months). No recurrence was observed in patients with Grade II CEs. Of 4 patients with Grade III CEs, 2 (50%) suffered from tumor recurrence after initial treatment. CONCLUSIONS: CEs are a rare subset of supratentorial ependymomas that selectively involve the cerebral cortex. Most CEs are low grade and present with seizures. Anaplastic CEs show a greater recurrence rate and a relatively poor prognosis. Gross total resection with or without adjuvant radiotherapy is currently the optimal treatment for CEs. CEs seem to have a more favorable prognosis than other supratentorial ependymomas.
Subject(s)
Ependymoma/pathology , Supratentorial Neoplasms/pathology , Adolescent , Adult , Aged , Child , Child, Preschool , Ependymoma/complications , Ependymoma/therapy , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methods , Radiotherapy, Adjuvant , Retrospective Studies , Seizures/etiology , Supratentorial Neoplasms/complications , Supratentorial Neoplasms/therapyABSTRACT
OBJECTIVE: Supratentorial extraventricular ependymomas are relatively rare. Long-term outcomes and prognostic factor for this rare tumor have not been well established. The purpose of this study was to demonstrateprogression-freesurvival(PFS),overallsurvival(OS), and prognostic factors of such tumor. PATIENTS AND METHODS: Fifty-five patients with supratentorial extraventricular ependymomas from our hospital were included in this study. Epidemiological characteristics, clinical features, treatment,long-term outcomes, and prognostic factors for PFS and OS were reviewed retrospectively. RESULTS: The patients consisted of 30 males and 25 females with mean age of 30.0⯱â¯23.6â¯years (range, 1-74 years). Twenty-nine tumors were located in the right hemisphere, and 26 in the left side. The 2 most common tumor locations were the frontal (nâ¯=â¯19; 35%) and parietal lobe (nâ¯=â¯11; 20%). All patients underwent surgical resection. Gross-total resection (GTR) was achieved in 42 cases (76%) and subtotal resection (STR) was performed in 13 patients (24%). According to the WHO classification system, 38 tumors (69%) were Grade III (anaplastic ependymoma), and 17 (31%) were Grade II (ependymoma). Three-,5-, and 10â¯year PFS rates were 60%, 49%, and 36%, respectively. Three-,5-, and 10â¯year OS rates were 79%, 64%, and 49%, respectively. EOR and tumor grade were identified as prognostic factors for PFS and OS on univariate analysis, multivariate analysis, and Kaplan-Meierlog-rank testing. Subtotal resection (STR) predicted a worse PFS (HRâ¯=â¯4.808; 95%, 1.942-11.905; Pâ¯=â¯.001) and OS (HRâ¯=â¯5.650; 95%, 2.114-15.152; Pâ¯=â¯.001). WHO Grade III tumors also had worse PFS (HRâ¯=â¯3.922; 95%, 1.429-18.182; Pâ¯=â¯.012) and OS (HRâ¯=â¯6.329; 95%, 1.328-30.303; Pâ¯=â¯0.021). For patients with tumor recurrence, reoperation was significant prognostic factors for OS (HRâ¯=â¯2.091; 95%, 0.939-4.654; pâ¯=â¯.000). Age, sex, tumor side, and postoperativeradiotherapy were not prognostic factors for PFS and OS. CONCLUSIONS: Most supratentorial extraventricular ependymomas are WHO grade III tumors. STRandWHO Grade III pathology predicted worse PFS and OS. Gross-total resection remains the optimal treatment for patients with supratentorial extraventricular ependymoma. Reoperation should be considered first in cases of recurrence. The role of postoperative radiotherapy as an adjuvant treatment for supratentorial extraventricular ependymoma needs further investigation.
Subject(s)
Brain Neoplasms/surgery , Ependymoma/surgery , Neoplasm Recurrence, Local/surgery , Adolescent , Adult , Aged , Brain Neoplasms/diagnosis , Child , Child, Preschool , Ependymoma/diagnosis , Female , Humans , Infant , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neurosurgical Procedures , Prognosis , Retrospective Studies , Supratentorial Neoplasms/diagnosis , Time , Young AdultABSTRACT
BACKGROUND: Aberrant DNA methylation is associated with tumor onset and progression. Study has verified that the DNA methylation of miR-152 was mediated in many tumors, but whether it involved in glioblastomas was still unclear. METHODS: This study enrolled 20 patients with glioma to analyze the expression pattern of miR-152. Real-time PCR and western blot were used to detect the mRNA or protein expression level, respectively. The relationship between miR-152 and runx2 was detected by Luciferase reporter assay. The methylation level of miR-152 was determined by methylation-specific PCR. Cell proliferation and apoptosis were detected by MTT and Annexin-FITC/PI assay. RESULTS: The expression of miR-152 was down-regulated while the expression of DNMT1 was up-regulated in both glioma tissue and cell lines. MiR-152 was hypermethylated and its expression was negatively correlated with DNMT in glioma cell lines. DNMT1 knockdown promoted the expression of miR-152, however, DNMT1 overexpression suppressed the expression of miR-152. MiR-152 overexpression promoted glioma cell apoptosis while miR-152 knockdown promoted cell proliferation. MiR-152 targets Runx2 to regulate its expression, Runx2 overexpression abolished the effects of miR-152 overexpression. CONCLUSION: MiR-152 regulated cell proliferation and apoptosis of glioma mediated by Runx2, while the mechanism of down regulated miR-152 in glioma tissues and cells was its hypermethylation.
Subject(s)
Apoptosis/physiology , Cell Proliferation/physiology , Core Binding Factor Alpha 1 Subunit/biosynthesis , DNA (Cytosine-5-)-Methyltransferase 1/biosynthesis , Glioma/metabolism , MicroRNAs/physiology , Cell Line, Tumor , Core Binding Factor Alpha 1 Subunit/genetics , DNA (Cytosine-5-)-Methyltransferase 1/genetics , Glioma/genetics , HumansABSTRACT
Nogo-66 plays a central role in the myelin-mediated inhibition of neurite outgrowth. Tau is a microtubule-associated protein involved in microtubule assembly and stabilization. It remains unverified whether tau interacts directly with growth factor receptors, or engages in cross-talk with regeneration inhibitors like Nogo-66. Here, we report that plasmid overexpression of tau significantly elevated the protein levels of total tau, phosphorylated tau, and microtubule-affinity regulating kinase (MARK). Nogo-66 transiently elevated the total tau protein level and persistently reduced the level of p-S262 tau (tau phosphorylated at serine 262), whereas it had little influence on the level of p-T205 tau (tau phosphorylated at threonine 205). Nogo-66 significantly decreased the protein level of MARK. Hymenialdisine, an inhibitor of MARK, significantly reduced the level of p-S262 tau. Overexpression of tau rescued the Nogo-66-induced inhibition of neurite outgrowth in neuroblastoma 2a (N2a) cells and primary cortical neurons. However, concomitant inhibition of MARK abolished the rescue of neurite outgrowth by tau in N2a cells. We conclude that dephosphorylation of tau at S262 is able to regulate Nogo-66 signaling, and that overexpression of tau can rescue the Nogo-66-induced inhibition of neurite outgrowth in vitro.
Subject(s)
Neurites/drug effects , Neurons/cytology , Neurons/drug effects , Nogo Proteins/pharmacology , tau Proteins/metabolism , Analysis of Variance , Animals , Azepines/pharmacology , Cells, Cultured , Cerebral Cortex/cytology , Embryo, Mammalian , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation/drug effects , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Mice , Neuroblastoma/pathology , Protein Serine-Threonine Kinases/metabolism , Pyrroles/pharmacology , Rats , Rats, Sprague-Dawley , Time Factors , Transfection , tau Proteins/geneticsABSTRACT
Evidence suggested that glycogen synthase kinase-3ß (GSK-3ß) is involved in Nogo-66 inhibiting axonal regeneration in vitro, but its effect in vivo was poorly understood. We showed that stereotactic injection of shRNA GSK-3ß-adeno associated virus (GSK-3ß-AAV) diminished syringomyelia and promoted axonal regeneration after spinal cord injury (SCI), using stereotactic injection of shRNA GSK-3ß-AAV (tested with Western blotting and RT-PCR) into the sensorimotor cortex of rats with SCI and by the detection of biotin dextran amine (BDA)-labeled axonal regeneration. We also determined the right position to inject into the sensorimotor cortex. Our findings consolidate the hypothesis that downregulation of GSK-3ß promotes axonal regeneration after SCI.
Subject(s)
Glycogen Synthase Kinase 3 beta/genetics , Nerve Regeneration/genetics , Spinal Cord Injuries/genetics , Syringomyelia/genetics , Animals , Axons/drug effects , Axons/metabolism , Dependovirus/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Humans , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Rats , Sensorimotor Cortex/drug effects , Sensorimotor Cortex/pathology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/therapy , Syringomyelia/pathology , Syringomyelia/therapyABSTRACT
The ability of neurons in the adult mammalian central nervous system (CNS) to regenerate after injury is limited by inhibitors in CNS myelin. Nogo-66 is the most important myelin inhibitor but the mechanisms of Nogo-66 inhibition of neurite outgrowth remain poorly understood. Particularly, the relationship between Nogo-66 and microtubule-affinity regulating kinase 2 (MARK2) has not been examined. This study investigated the role of MARK2 in Nogo-66 inhibition and the function of MARK2 in neurite elongation in neurons in vitro. MARK2 and phosphorylated MARK2 at Ser212 (p-Ser212) alterations in Neuro 2a cells were assessed at different Nogo-66 exposure times; the relationships between MARK2 and microtubule-associated proteins (MAPs) were determined via the overexpression or interference of MARK2. Our study reports that Nogo-66 inhibited the expression of total MARK2 but also reduced Ser212 phosphorylation of MARK2, whereas levels of MAP1-b and tau varied depending on MARK2 overexpression or reduced expression. Furthermore, MARK2 increased the proportion of tyrosinated α-tubulin, thereby disrupting the stability of tubulin, most likely affecting axonal growth. In line with these results, overexpression of MARK2 promoted neurite elongation and therefore is able to rescue the inhibitory effect of Nogo-66 on neurite growth. In conclusion, the intracellular PKB/MARK2/MAPs/α-tubulin pathway appears to be essential for neurite elongation in neurons in vitro. These results suggest a critical role for MARK2 in overcoming Nogo-66-induced inhibition of axon outgrowth in neurons. Pharmacological activators of MARK2 may be applicable to promote successful axonal outgrowth following many types of CNS injuries.