Role of mTOR signaling pathway in the pathogenesis of subependymal giant cell astrocytoma - A study of 28 cases.

Background: Subependymal giant cell astrocytomas (SEGA) are slow-growing benign intraventricular tumors, the pathogenesis of which is debated. Recent studies have shown that tuberous sclerosis complex (TSC) 1 and TSC2 genes are linked to the mammalian target of rapamycin (mTOR) cell signaling pathway. We aimed to analyze TSC1 and TSC2 gene mutation, hamartin and tuberin protein expression, and protein expression of mTOR signaling cascade in a series of SEGA to determine their role in pathogenesis.

Genetic alterations related to BRAF-FGFR genes and dysregulated MAPK/ERK/mTOR signaling in adult pilocytic astrocytoma.

Pilocytic astrocytomas occur rarely in adults and show aggressive tumor behavior. However, their underlying molecular-genetic events are largely uncharacterized. Hence, 59 adult pilocytic astrocytoma (APA) cases of classical histology were studied (MIB-1 LI: 1%-5%).

Effect of Copper on l-Cysteine/l-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson's Disease.

Wilson's disease is a disease of abnormal copper metabolism in which free serum copper level is raised. The objective of the study was to determine, whether in Wilson disease, l-cysteine/l-cystine influx into RBC was decreased or not and the specific amino acid transporter affected by copper in normal human RBC. For l-cysteine/l-cystine influx, ten untreated cases, ten treated cases and ten age and sex matched healthy controls were recruited.

Clinicopathological characteristics, molecular subgrouping, and expression of miR-379/miR-656 cluster (C14MC) in adult medulloblastomas.

Medulloblastoma (MB) is a childhood tumor comprising four molecular subgroups: WNT, SHH, group 3 and group 4, with diagnostic and prognostic connotations. Very few studies are available on molecular subgrouping of adult MBs due to their rarity. Recently, loss of chromosome14q has been reported in SHH MBs, with downregulation of miR-379/miR-656 cluster (C14MC) in pediatric SHH MBs.

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India.

This study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases.

Analysis of Magnaporthe oryzae Genome Reveals a Fungal Effector, Which Is Able to Induce Resistance Response in Transgenic Rice Line Containing Resistance Gene, Pi54.

Rice blast caused by Magnaporthe oryzae is one of the most important diseases of rice. Pi54, a rice gene that imparts resistance to M. oryzae isolates prevalent in India, was already cloned but its avirulent counterpart in the pathogen was not known.

FAT1 is a novel upstream regulator of HIF1α and invasion of high grade glioma.

The hypoxic microenvironment is an important contributor of glioblastoma (GBM) aggressiveness via HIF1α, while tumour inflammation is profoundly influenced by FAT Atypical Cadherin (FAT1). This study was designed to explore the functional interaction and significance of FAT1 and HIF1α under severe hypoxia-mimicking tumour microenvironment in primary human tumours. We first identified a positive correlation of FAT1 with HIF1α and its target genes in GBM tumour specimens, revealing the significance of the FAT1-HIF1α axis in glioma cells.

A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus.

Background & Objectives: Primary central nervous system lymphomas (PCNSLs) are relatively uncommon, accounting for 2-3 per cent of primary brain tumours. Majority of these are diffuse large B cell lymphomas (DLBCL) occurring both in immunocompromised and immunocompetent patients. We undertook this study to classify PCNSL into germinal centre (GC) and non-germinal centre (NGC) type based on Hans classification and to find the role of Epstein-Barr virus (EBV) in pathogenesis both by conventional immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).

Primary Bone Tumors of the Skull: Spectrum of 125 Cases, with Review of Literature.

Aims: Primary skull bone tumors, benign or malignant, are rare, and include a vast repertoire of lesions. These tumors are not reported systematically in the literature, with most studies being on individual entities or as single case reports.

Methods: Primary bone tumors diagnosed over a period of 12 years were retrieved, histological diagnoses reviewed, and clinical parameters noted.

Activation of Dopamine D1 Receptors in Dermal Fibroblasts Restores Vascular Endothelial Growth Factor-A Production by These Cells and Subsequent Angiogenesis in Diabetic Cutaneous Wound Tissues.

In wound beds, fibroblasts are rich sources of vascular endothelial growth factor A, a cytokine necessary for promoting angiogenesis and thereby the healing of wound tissues. However, in diabetes mellitus, these cells are functionally impaired and produce reduced amounts of vascular endothelial growth factor A, resulting in deficient angiogenesis and delayed wound healing. We here for the first time demonstrate that stimulation of D1 dopamine receptors present in dermal fibroblasts restores vascular endothelial growth factor A production by these cells, resulting in adequate angiogenesis and subsequent healing of cutaneous wounds in both type 1 and type 2 diabetic mice.

Intracranial interhemispheric osteochondrolipoma: Diagnostic and surgical challenges in an extremely rare entity.

Intracranial lipomas are rare developmental lesions, predominantly occurring in the interhemispheric location. Osteochondrolipoma is an extremely rare variant of lipoma with osseous and chondroid differentiation. We present a case of interhemispheric osteochondrolipoma, in a 2.

Neuroblastoma-like schwannoma of the skull base: an enigmatic peripheral nerve sheath tumor variant.

Neuroblastoma-like schwannoma is an extremely rare histological variant of schwannoma, which histologically mimics a malignant small round cell tumor. Only 19 cases have been reported in the literature to date. We report a case of this tumor located at the skull base in a 44-year-old woman who presented with symptoms of right-sided earache and hearing loss.

Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma.

Given the involvement of telomerase activation and dysregulated metabolism in glioma progression, the connection between these two critical players was investigated. Pharmacological inhibition of human Telomerase reverse transcriptase (hTERT) by Costunolide induced glioma cell apoptosis in a reactive oxygen species (ROS)-dependent manner. Costunolide induced an ROS-dependent increase in p53 abrogated telomerase activity.

RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS.

Array-based profiling studies have shown implication of aberrant gene expression patterns in epileptogenesis. We have performed transcriptome analysis of hippocampal tissues resected from patients with MTLE-HS using RNAseq approach. Healthy tissues from tumour margins obtained during tumour surgeries were used as non-epileptic controls.

Therapy and progression--induced O6-methylguanine-DNA methyltransferase and mismatch repair alterations in recurrent glioblastoma multiforme.

Despite multimodality treatment protocol including surgical resection, radiotherapy, and chemotherapy in patients with glioblastoma multiforme (GBM), most suffer from treatment failure and tumor recurrence within a few months of initial surgery. The effectiveness of temozolomide (TMZ), the most commonly used chemotherapeutic agent, is largely dependent on the methylation status of the promoter of the gene O6-methylguanine-DNA methyltransferase (MGMT) and the integrity of the mismatch repair (MMR) system. Changes in these regulatory mechanisms at the time of recurrence may influence response to therapy.

HIF-2α mediates a marked increase in migration and stemness characteristics in a subset of glioma cells under hypoxia by activating an Oct-4/Sox-2-Mena (INV) axis.

Hypoxia is a salient feature of most solid tumors and plays a central role in tumor progression owing to its multiple contributions to therapeutic resistance, metastasis, angiogenesis and stemness properties. Reports exist in literature about hypoxia increasing stemness characteristics and invasiveness potential of malignant cells. In order to delineate molecular crosstalk among factors driving glioma progression, we used knockdown and overexpression strategies.

Expression of DNA methyltransferases 1 and 3B correlates with EZH2 and this 3-marker epigenetic signature predicts outcome in glioblastomas.

This study aims to analyze expression of EZH2 and DNA-methyltransferases (DNMT1, 3A and 3B) in astrocytic tumors and investigate their link as well as their correlation with survival, especially in GBMs. Expression of EZH2 and DNMTs (DNMT1, DNMT3A and DNMT3B) in different grades of astrocytomas (n=93) was assessed by qRT-PCR and immunohistochemistry. GBM-U87MG cell line was used for functional studies.

Recurrent rhabdoid meningioma with lymph node, pulmonary and bone metastases: a diagnostic and therapeutic challenge.

Rhabdoid meningioma is a rare meningioma variant, classified as WHO grade III. Although this tumor is known for its aggressive behavior and poor prognosis, extracranial metastasis is rare. We report the rare case of a 31-year-old patient with rhabdoid meningioma which recurred several times despite gross total resection, radiation therapy, and gamma knife radiosurgery, and the last recurrence was associated with metastases to lungs, lymph node and bone.

WNT-activated medulloblastoma with melanotic and myogenic differentiation: Report of a rare case.

Medulloblastoma (MB) with melanotic and myogenic differentiation, previously known as melanotic medullomyoblastoma, is an extremely rare histological variant of MB showing melanocytic as well as skeletal muscle differentiation. Only 10 cases of this rare tumor have been reported in the literature to date. We report this case of a 2-year-old male child who presented with a midline cerebellar mass, which on histopathological examination showed classic MB intermixed with cells containing melanin pigment, along with rhabdomyoblasts, spindle cells and occasional strap cells, which corresponded to WNT subgroup on molecular classification.

A simplified approach for molecular classification of glioblastomas (GBMs): experience from a tertiary care center in India.

This study aims to establish a simplified molecular classification of glioblastomas (GBMs) based on molecular genetic alterations. GBM cases (n-114) were evaluated for IDH-1 and TP53 mutation by Sanger sequencing, PDGFRA and EGFR amplification by FISH, NF1 and YKL40 expression by qRT-PCR. Subsequently they were classified into four subgroups: classical like (CL), proneural like (PN), mesenchymal like (MES) and neural like (NEU).

ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset.

This study aims (1) to evaluate ATRX expression in different grades and subtypes of gliomas and correlate with other hallmark genetic alterations, (2) to identify and characterize mosaic/heterogeneous staining in gliomas in terms of mutation status. One hundred seventy six cases of glioma were assessed for ATRX immunohistochemistry and subdivided into positive, negative and mosaic/heterogeneous staining patterns. Five cases with heterogeneous staining were further subjected to next generation sequencing.

Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors.

Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.

Evaluation of chromosome 1q gain in intracranial ependymomas.

Ependymomas are relatively uncommon gliomas with poor prognosis despite recent advances in neurooncology. Molecular pathogenesis of ependymomas is not extensively studied. Lack of correlation of histological grade with patient outcome has directed attention towards identification of molecular alterations as novel prognostic markers.