Introduction: Quality of life (QOL) assessment is increasingly being recognized as an important parameter while evaluating outcomes after endoscopic endonasal transsphenoidal surgery (EETS). There ...has been no study that has evaluated this in the Indian context.
Objectives: We aimed to analyze sinonasal and overall QOL before and after EETS for non-functioning pituitary adenomas (NFPAs), and to evaluate possible correlations between changes in QOL and various clinicoradiological, hormonal, and surgical factors.
Methods: This prospective observational study included 62 patients who underwent EETS for NFPAs. The Anterior Skull Base Nasal Inventory-12 (ASK-12) and Short Form-12 (SF-12) were used to assess QOL. Changes in QOL were recorded at 2 weeks, 3 months, and 1-year follow-up periods.
Results: While the nasal crusting and nasal discharge components of the ASK-12 worsened 2 weeks after EETS, the headache component demonstrated significant improvement (P < 0.05). The overall ASK-12 score (6.69+/−7.98) did not change significantly at follow-up. The SF-12 physical component summary (PCS) score (42.14+/−8.54) improved progressively after surgery, while the SF-12 mental component summary (MCS) score (42.48+/−7.95) improved 1 year later. The SF-12 PCS correlated with visual field improvement at 3-month follow-up (P = 0.04).
Conclusions: EETS affects some components of the ASK-12 without affecting the overall sinonasal QOL in patients with NFPAs. These patients demonstrate progressive postoperative improvement in physical well-being, while their mental functioning improves only a year later. Improvement in physical functioning correlates with visual field improvement at a 3-month follow-up. Hormonal dysfunction and surgical factors do not have any impact on QOL in these patients.
Posterior reversible encephalopathy syndrome (PRES) is an unusual neurological condition known to occur in the setting of various risk factors such as acute hypertension, renal failure, sepsis, ...multiorgan failure, autoimmune disease, and immunosuppression. Twenty cases of PRES have been previously reported in neurosurgical literature, almost all of which were attributed to either hypertension or chemotherapeutic drugs. Herein, we report a case of PRES in a neurosurgical patient in the absence of the commonly described risk factors for the syndrome. The patient was a 9-year-old boy who underwent uneventful transcranial resection of a suprasellar craniopharyngioma. His postoperative clinical course was complicated by hepatic failure and hypothalamic dysfunction, both of which were managed conservatively. Ten days after the onset of these complications, he developed clinical and radiological features suggestive of PRES which eventually resolved at follow-up. We discuss the pathogenesis of this unusual neurological syndrome in our patient in the light of a literature review.
Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct ...classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM. Promoter hypermethylation of ULK2 was confirmed by bisulfite sequencing. GBM and glioma cell lines had low levels of ULK2 transcripts, which could be reversed upon methylation inhibitor treatment. ULK2 promoter methylation and transcript levels showed significant negative correlation. Ectopic overexpression of ULK2-induced autophagy, which further enhanced upon nutrient starvation or temozolomide chemotherapy. ULK2 also inhibited the growth of glioma cells, which required autophagy induction as kinase mutant of ULK2 failed to induce autophagy and inhibit growth. Furthermore, ULK2 induced autophagy and inhibited growth in Ras-transformed immortalized Baby Mouse Kidney (iBMK) ATG5+/+ but not in autophagy-deficient ATG5−/− cells. Growth inhibition due to ULK2 induced high levels of autophagy under starvation or chemotherapy utilized apoptotic cell death but not at low levels of autophagy. Growth inhibition by ULK2 also appears to involve catalase degradation and reactive oxygen species generation. ULK2 overexpression inhibited anchorage independent growth, inhibited astrocyte transformation in vitro and tumor growth in vivo. Of all autophagy genes, we found ULK2 and its homologue ULK1 were only down-regulated in all grades of glioma. Thus these results altogether suggest that inhibition of autophagy by ULK1/2 down-regulation is essential for glioma development.
Intracranial paragangliomas are infrequent and those occurring in the sellar-suprasellar region are rare, with only 31 cases described in literature.
We describe 2 cases of sellar-suprasellar ...paragangliomas in the light of a literature review. The first patient was a 13-year-old boy who presented with an intensely enhancing lesion in the sellar-suprasellar region with multiple flow voids within. Resection of the lesion was limited to a biopsy in view of its hypervascular nature. A second attempt at resection following partial embolization of the lesion was also unsuccessful. The tumor showed progressive reduction in size following radiotherapy. The second case was a 20-year-old man who presented with a similar tumor in the same location. He also had a probable metastatic deposit in the foramen of Magendie. An attempted surgical resection of the suprasellar lesion was abandoned after a biopsy. The patient improved symptomatically after radiotherapy.
We report 2 cases of paraganglioma occurring in a rare location. Presence of flow voids within tumors in the sellar-suprasellar location should alert the surgeon to this entity. The hypervascular nature of these tumors may limit the extent of resection. In cases of inadequate tumor decompression, or if there is evidence of growth of residual tumor, radiotherapy can help to stabilize the disease.
Glioblastomas (GBM) are the most malignant form of astrocytomas which are difficult to treat and portend a grave clinical course and poor prognosis. In this study, we identified Chromobox homolog 7 ...(Cbx7), a member of Polycomb Repressive Complex 1 (PRC1), as a downregulated gene in GBM owing to its promoter hypermethylation. Bisulphite sequencing and methylation inhibitor treatment established the hypermethylation of Cbx7 in GBM. Exogenous overexpression of Cbx7 induced cell death, inhibited cell proliferation, colony formation and migration/invasion of the glioma cells. GSEA of Cbx7 regulated genes identified Cbx7 as a repressor of transcription co-activators YAP/TAZ, the inhibitory targets of the Hippo signalling pathway. In good correlation, the exogenous expression of Cbx7 repressed the YAP/TAZ-dependent transcription and downregulated CTGF, a bonafide YAP/TAZ target. We also observed reduced levels of phospho-JNK in Cbx7 expressing cells. Additionally, CTGF silencing and pharmacological inhibition of JNK also inhibited glioma cell migration. Further, Cbx7 failed to inhibit cell migration significantly in the presence of exogenously overexpressed CTGF or constitutively active JNK. Thus, our study identifies Cbx7 as an inhibitor of glioma cell migration through its inhibitory effect on YAP/TAZ-CTGF-JNK signalling axis and underscores the importance of epigenetic inactivation of Cbx7 in gliomagenesis.
Glioblastoma (grade IV glioma/GBM) is the most common primary adult malignant brain tumor with poor prognosis. To characterize molecular determinants of tumor-stroma interaction in GBM, we profiled ...48 serum cytokines and identified macrophage colony-stimulating factor (MCSF) as one of the elevated cytokines in sera from GBM patients. Both MCSF transcript and protein were up-regulated in GBM tissue samples through a spleen tyrosine kinase (SYK)-dependent activation of the PI3K-NFκB pathway. Ectopic overexpression and silencing experiments revealed that glioma-secreted MCSF has no role in autocrine functions and M2 polarization of macrophages. In contrast, silencing expression of MCSF in glioma cells prevented tube formation of human umbilical vein endothelial cells elicited by the supernatant from monocytes/microglial cells treated with conditioned medium from glioma cells. Quantitative proteomics based on stable isotope labeling by amino acids in cell culture showed that glioma-derived MCSF induces changes in microglial secretome and identified insulin-like growth factor-binding protein 1 (IGFBP1) as one of the MCSF-regulated proteins secreted by microglia. Silencing IGFBP1 expression in microglial cells or its neutralization by an antibody reduced the ability of supernatants derived from microglial cells treated with glioma cell-conditioned medium to induce angiogenesis. In conclusion, this study shows up-regulation of MCSF in GBM via a SYK-PI3K-NFκB-dependent mechanism and identifies IGFBP1 released by microglial cells as a novel mediator of MCSF-induced angiogenesis, of potential interest for developing targeted therapy to prevent GBM progression.
Background: Glioblastoma is highly aggressive and incurable by current treatment modalities.
Results: MCSF is regulated by the SYK-PI3K-NFκB pathway in glioma and induces secretion of IGFBP1 from microglia to promote angiogenesis.
Conclusion: Microglial IGFBP1 is a key mediator of MCSF-induced angiogenesis.
Significance: IGFBP1 is a potential target for glioblastoma therapy.
Minimally invasive techniques of hematoma evacuation with or without the use of thrombolytic agents to lyse the clots have shown promising outcomes compared to open surgical evacuation. However, ...there is a dearth of literature in developing nations. The objective in this study was to evacuate spontaneous hypertensive basal ganglionic hemorrhages using computed tomography (CT)–guided catheter insertion, hematoma aspiration, and lysis with thrombolytic agents and analyze the efficacy and outcomes.
Ten patients with spontaneous basal ganglionic hemorrhage underwent CT-guided clot catheter insertion, followed by aspiration of hematoma and clot lysis using 25,000 IU urokinase instilled every 12 hours. Details including symptoms, clinical and radiologic findings, efficacy of the technique, functional outcomes during follow-up, length of stay, and cost were recorded. Relevant details for 12 age- and sex-matched conservatively treated patients were compared.
Functional outcome in the catheter group at 6 months was better than the medically managed group, with improved mean Glasgow Outcome Scale score (0.4 vs. 0.08), reduced modified Rankin scale score (−0.8 vs. −0.25), and reduced National Institutes of Health Stroke Scale score (−6.8 vs. −1.5 points). However, it was not statistically significant. Average hematoma volume reduction in the catheter group was 83.14%. In the medically managed group, 2 of 12 patients (16.6%) had hematoma expansion, 6 patients (50%) developed hydrocephalus, and 2 patients (16.6%) died. In the catheter group, 4 of 10 patients (40%) developed mild pneumocephalus that resolved.
The evacuation of hypertensive basal ganglionic hematomas is feasible with basic neurosurgical instruments and existing resources (e.g., CT scan) with improved functional outcome compared with conservative treatment alone.
Glioblastomas (GBM) are largely incurable as they diffusely infiltrate adjacent brain tissues and are difficult to diagnose at early stages. Biomarkers derived from serum, which can be obtained by ...minimally invasive procedures, may help in early diagnosis, prognosis and treatment monitoring. To develop a serum cytokine signature, we profiled 48 cytokines in sera derived from normal healthy individuals (n = 26) and different grades of glioma patients (n = 194). We divided the normal and grade IV glioma/GBM serum samples randomly into equal sized training and test sets. In the training set, the Prediction Analysis for Microarrays (PAM) identified a panel of 18 cytokines that could discriminate GBM sera from normal sera with maximum accuracy (95.40%) and minimum error (4.60%). The 18-cytokine signature obtained in the training set discriminated GBM sera from normal sera in the test set as well (accuracy 96.55%; error 3.45%). Interestingly, the 18-cytokine signature also differentiated grade II/Diffuse Astrocytoma (DA) and grade III/Anaplastic Astrocytoma (AA) sera from normal sera very efficiently (DA vs. normal-accuracy 96.00%, error 4.00%; AA vs. normal-accuracy 95.83%, error 4.17%). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using 18 cytokines resulted in the enrichment of two pathways, cytokine-cytokine receptor interaction and JAK-STAT pathways with high significance. Thus our study identified an 18-cytokine signature for distinguishing glioma sera from normal healthy individual sera and also demonstrated the importance of their differential abundance in glioma biology.
Glioblastomas (GBM) continue to remain one of the most dreaded tumours that are highly infiltrative in nature and easily preclude comprehensive surgical resection. GBMs pose an intricate etiology as ...they are being associated with a plethora of genetic and epigenetic lesions. Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated pathways and genes have been comprehensively studied, its impact on the miRNome is yet to be explored. The objective of this study was to elucidate the PI3 kinase pathway regulated miRNAs in GBM.
miRNA expression profiling was conducted to monitor the differentially regulated miRNAs upon PI3 kinase pathway abrogation. qRT-PCR was used to measure the abundance of miR-326 and its host gene encoded transcript. Proliferation assay, colony suppression assay and wound healing assay were carried out in pre-miR transfected cells to investigate its role in malignant transformation. Potential targets of miR-326 were identified by transcriptome analysis of miR-326 overexpressing cells by whole RNA sequencing and selected targets were validated. Several publically available data sets were used for various investigations described above.
We identified several miRNA that were regulated by PI3 kinase pathway. miR-326, a GBM downregulated miRNA, was validated as one of the miRNAs whose expression was alleviated upon abrogation of the PI3 kinase pathway. Overexpression of miR-326 resulted in reduced proliferation, colony suppression and hindered the migration capacity of glioma cells. Arrestin, Beta 1 (ARRB1), the host gene of miR-326, was also downregulated in GBM and interestingly, the expression of ARRB1 was also alleviated upon inhibition of the PI3 kinase pathway, indicating similar regulation pattern. More importantly, miR-326 exhibited a significant positive correlation with ARRB1 in terms of its expression. Transcriptome analysis upon miR-326 overexpression coupled with integrative bioinformatics approach identified several putative targets of miR-326. Selected targets were validated and interestingly found to be upregulated in GBM.
Taken together, our study uncovered the PI3 kinase regulated miRNome in GBM. miR-326, a PI3 kinase pathway inhibited miRNA, was demonstrated as a tumour suppressor miRNA in GBM.
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