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Thennarasu K.,National Institute of Mental Health and Neuro Sciences | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science
Neuropathology | Year: 2011

Tumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n=73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situ hybridization (FISH). Statistical methods were employed to evaluate the degree of association between 10q23/PTEN deletion status and patient age. Survival analysis was performed using Kaplan-Meier log-rank test and multivariable Cox models to assess the prognostic value of 10q23/PTEN deletion. Interestingly, 10q23/PTEN homozygous deletion was frequent in patients >45 years of age (P=0.034) and the median age of patients harboring PTEN homozygous deletions was significantly higher than those with the retained status (P=0.019). 10q23/PTEN homozygous deletion was associated with shorter survival in the entire cohort as well in patients >45 years (P<0.05), indicating that loss of 10q23/PTEN showed clinical importance in elderly patients. Our study highlights the independent prognostic/predictive value of 10q23/PTEN deletion status as identified by FISH, particularly in glioblastoma patients aged >45 years. © 2010 Japanese Society of Neuropathology.


Kumar D.M.,Indian Institute of Science | Thota B.,National Institute of Mental Health and Neuro Sciences | Shinde S.V.,Indian Institute of Science | Prasanna K.V.,Sri Satya Sai Institute of Higher Medical science | And 5 more authors.
Journal of Proteome Research | Year: 2010

Glioblastoma (GBM; grade IV astrocytoma) is the most malignant and common primary brain tumor in adults. Using combination of 2-DE and MALDI-TOF MS, we analyzed 14 GBM and 6 normal control sera and identified haptoglobin α2 chain as an up-regulated serum protein in GBM patients. GBM-specific up-regulation was confirmed by ELISA based quantitation of haptoglobin (Hp) in the serum of 99 GBM patients as against lower grades (49 grade III/AA; 26 grade II/DA) and 26 normal individuals (p = 0.0001). Further validation using RT-qPCR on an independent set (n = 78) of tumor and normal brain (n = 4) samples and immunohistochemcial staining on a subset (n = 42) of above samples showed increasing levels of transcript and protein with tumor grade and were highest in GBM (p = <0.0001 and <0.0001, respectively). Overexpression of Hp either by stable integration of Hp cDNA or exogenous addition of purified Hp to immortalized astrocytes resulted in increased cell migration. RNAi-mediated silencing of Hp in glioma cells decreased cell migration. Further, we demonstrate that both human glioma and mouse melanoma cells overexpressing Hp showed increased tumor growth. Thus, we have identified haptoglobin as a GBM-specific serum marker with a role on glioma tumor growth and migration. © 2010 American Chemical Society.


Nijaguna M.B.,Indian Institute of Science | Patil V.,Indian Institute of Science | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science | Chandramouli B.A.,National Institute of Mental Health and Neuro Sciences | And 3 more authors.
PLoS ONE | Year: 2015

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 fromnormal healthy individuals (n = 26) and different grades of glioma patients (n = 194).We divided the normal and grade IV glioma/GBMserum samples randomly into equal sized training and test sets. In the training set, the Prediction Analysis forMicroarrays (PAM) identified a panel of 18 cytokines that could discriminate GBM sera fromnormal 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 fromnormal healthy individual sera and also demonstrated the importance of their differential abundance in glioma biology. Copyright: © 2015 Nijaguna et al.


PubMed | Sri Satya Sai Institute of Higher Medical science, National Institute of Mental Health and Neuro Sciences and Indian Institute of Science
Type: | Journal: Scientific reports | Year: 2016

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.


Sham M.E.,Craniomaxillofacial Surgeon | Kiran S.,Sri Satya Sai Institute of Higher Medical science
Open Neurosurgery Journal | Year: 2011

Ultrasonic vibrations have been used to cut tissues for two decades. However, it is only in the last five years that experimental applications have been used routinely for standard clinical applications in many different fields of surgery. Surgically decompressing optic nerve, with the use of conventional drills is associated with greater risk of damage to the optic nerve itself. Developing new & precession bound safer techniques would certainly be beneficial to accomplish this task. Ultrasonic piezo bone surgery is a highly sophisticated device designed specifically for high end precession osseous surgery. In this article we describe our experience in using this device for extradural unroofing of the optic canal. © Sham and Kiran et al.


Dadlani R.,Sri Satya Sai Institute of Higher Medical science | Ghosal N.,Sri Satya Sai Institute of Higher Medical science | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science
Journal of Korean Neurosurgical Society | Year: 2014

Intracranial tumors secondary to radiotherapy are rare. In this group gliomas are the rarest. Only 6 cases of glioblastoma multiforme (GBM) have been reported in patients undergoing radiotherapy (RT) for craniopharyngiomas of which only 4 have been in children less than 18 years of age. In recent years RT has become a mainstay of adjuvant therapy for recurrent or partially excised craniopharyngiomas. We report a child of 12 years who had previously undergone RT for a suprasellar craniopharyngioma and presented 10 years later with a GBM. This is the 5th pediatric case in literature demonstrating a GBM after RT for a craniopharyngioma. The implications of subjecting the pediatric population to RT for a benign lesion versus the outcome of gross total removal and management of RT induced tumors is discussed and the need to avail of safer alternatives such as stereotactic radiosurgery is stressed. © 2014 The Korean Neurosurgical Society.


Furtado S.V.,Sri Satya Sai Institute of Higher Medical science | Ghosal N.,Sri Satya Sai Institute of Higher Medical science | Venkatesh P.K.,Sri Satya Sai Institute of Higher Medical science | Gupta K.,Sri Satya Sai Institute of Higher Medical science | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science
Journal of Clinical Neuroscience | Year: 2010

Pituicytoma is a rare, indolent, benign tumor of the sellar and suprasellar region arising from pituicytes of the neurohypophysis. It is most often diagnosed pre-operatively as a pituitary adenoma. We report two patients with pituicytoma operated on at our Institute over 8 years. Imaging of one patient showed a parasellar and medial temporal extension, which has not been reported to our knowledge. The radiological features that help distinguish this low-grade tumor from other sellar and parasellar tumors are discussed along with its distinct histological findings. The authors also review the literature on its clinical presentation, diagnosis, surgical management and outcome. © 2010 Elsevier Ltd. All rights reserved.


Furtado S.V.,Sri Satya Sai Institute of Higher Medical science | Thakre D.J.,Sri Satya Sai Institute of Higher Medical science | Venkatesh P.K.,Sri Satya Sai Institute of Higher Medical science | Reddy K.,Sri Satya Sai Institute of Higher Medical science | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science
Acta Neurochirurgica | Year: 2010

Purpose: Foramen magnum dimensions and intracranial volume in Chiari I malformations in children were studied, and the statistical relationship between patient demographics, radiological features and foramen magnum morphometry was investigated. Methods: Linear measurements were used to calculate the intracranial volume using preoperative magnetic resonance images and computed tomogram images. The area of the foramen magnum was obtained independently using computer imaging software and a regression formula. The result of 21 pediatric patients was compared with a matched control group. Results: The area of the foramen magnum was within the range of the expected value deduced using a formula based on the intracranial volume. There was no statistical difference in the area and linear dimensions of the foramen magnum in the study and control groups. Six patients (28%) had a foramen magnum in close proximity to a spherical shape. Conclusion: The authors provide a simple, accurate and reproducible method of estimating foramen magnum area in the pediatric Chiari I group. The irregular shape of the foramen magnum is accentuated by developmental bony and soft tissue anomalies at the cranio-vertebral junction in Chiari malformation. Consequently, an individualized cross-sectional assessment of the foramen magnum in relation to the hindbrain tissue in the same plane is required to study the initiation and propagation of the Chiari I symptomatology. © 2009 Springer-Verlag.


Furtado S.V.,Sri Satya Sai Institute of Higher Medical science | Saikiran N.A.,Sri Satya Sai Institute of Higher Medical science | Ghosal N.,Sri Satya Sai Institute of Higher Medical science | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science
Pediatric Neurology | Year: 2010

Pituitary adenomas are extremely rare in prepubescent children. Most of these tumors are functioning adenomas, but can also present with vision disturbances and changes in body morphology. We discuss the presentation, management, and outcome of a giant, solid, invasive prolactinoma in a 7-year-old boy who presented with visual disturbances and gynecomastia. The child demonstrated significant improvement in vision and a reduction in size of the tumor after subtotal tumor decompression and treatment with oral bromocriptine for 4 months. Tumor decompression and oral dopamine agonist therapy comprise the accepted treatment for pediatric prolactinomas. To our knowledge, only two previous reports described a giant prolactinoma in a prepubescent child. The relevant literature on pediatric pituitary tumours and prolactinoma is reviewed. © 2010 Elsevier Inc. All rights reserved.


Dadlani R.,Sri Satya Sai Institute of Higher Medical science | Ghosal N.,Sri Satya Sai Institute of Higher Medical science | Hegde A.S.,Sri Satya Sai Institute of Higher Medical science
Journal of Neurosciences in Rural Practice | Year: 2012

Intracranial metastasis of a uterine cervical carcinoma is a very rare occurrence. These metastases are characteristically multiple, supra-tentorial, associated with multiple systemic dissemination, usually occur relatively late in the course of the disease, and are most often seen in squamous carcinomas. We present an unusual case which defied these characteristics. This patient was in long-term remission (11 years), presented with a solitary cerebellous metastases, had no evidence of other systemic spread, and the pathology was an adenocarcinoma. We present this rare case with interesting clinical ramifications. This is probably the longest duration of remission prior to the metastasis in the published literature.

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