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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. Source


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. Source


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. Source


Sreekanthreddy P.,Indian Institute of Science | Srinivasan H.,Indian Institute of Science | Kumar D.M.,Indian Institute of Science | Nijaguna M.B.,Indian Institute of Science | And 10 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM). Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients. Results: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two down-regulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis. Conclusions: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs. Impact: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis. ©2010 AACR. Source


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. Source

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