Chitra Sarkar

AIIMS Bhopal All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India

Are you Chitra Sarkar?

Claim your profile

Publications (304)594.6 Total impact

  • Source
  • [show abstract] [hide abstract]
    ABSTRACT: Meningeal hemangiopericytomas (HPCs) are aggressive dural-based tumors, for which no prognostic or predictive marker has been identified. Gross total resection is treatment of choice, but not easily achieved; hence, alkylating agents like temozolomide (TMZ) are now being tried. O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation has proven prognostic and predictive value in glioblastomas. This study evaluates MGMT promoter methylation in meningeal HPCs to determine its role in HPC oncogenesis and its association with patient outcome. Meningeal HPCs diagnosed between 2002 and 2011 were retrieved and clinicopathological features reviewed. MGMT promoter methylation status was assessed by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry (IHC) for MGMT protein. HPCs accounted for 1.1% of all CNS tumors. Forty cases were analyzed; the majority were adults (mean age = 41.4 years). Seventy percent were primary and 30% were recurrent tumors; 60% were grade II and 40% were grade III. MGMT promoter methylation was identified in 45% of cases, including Grade II (54.2%) and Grade III (31.3%) (P = 0.203). Promoter methylation was significantly (P = 0.035) more frequent in primary (57.1%) than in recurrent (16.7%) tumors. No correlation was noted between MGMT promoter methylation by MSP and MGMT protein expression by IHC, or with progression-free survival. Thus, a significant proportion of HPCs demonstrate MGMT promoter methylation, suggesting possible susceptibility to TMZ. As promoter methylation is more frequent in primary tumors, TMZ may serve as a therapeutic option in residual primary tumors. Epigenetic inactivation of MGMT in HPCs necessitates the assessment of prognostic and predictive value of MGMT promoter methylation in HPCs in larger clinical trials.
    Neuropathology 02/2014; · 1.91 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Dipeptidyl-peptidase III (DPP III), a cytosolic metallo-aminopeptidase implicated in various physiological and pathological processes. A previous study from our laboratory indicated elevated expression of DPP III in glioblastoma (U87MG) cells. In the present study we investigated the role of IL-6, a pleiotropic cytokine produced by glial tumors in regulation of DPP III expression. Immunohistochemistry, western blotting and qRT-PCR were used for quantitation of DPP III and IL-6 in human glioblastoma cells and tumors. Cell transfections and DPP III promoter reporter assays were performed to study the transcriptional regulation of DPP III by IL-6. Promoter deletion analysis, site directed mutagenesis, Chromatin Immunoprecipitation (ChIP) assays and siRNA technology was employed to elucidate the molecular mechanism of IL-6 mediated regulation of DPP III in glioblastoma cells. Our results for the first time demonstrate a negative correlation(r=0.632, p= 0.01) between DPP III and IL-6 in both human tumors and cultured glioblastoma cells. Treatment of U87MG cells with IL-6 significantly decreased DPP III expression with a concomitant increase in the levels of transcription factor C/EBP-β. Deletion/mutagenesis of C/EBP-β binding motif of DPP III promoter significantly increased its activity and abolished its responsiveness to IL-6. This effect could also be mimicked by C/EBP-β siRNA. In conclusion our study for the first time demonstrates C/EBP-β mediated transcriptional down regulation of DPP III by IL-6. Our results demonstrating negative correlation between IL-6 and DPP III taken together with previously reported prognostic significance of this cytokine in glioblastoma suggests that DPP III may prove useful as a prognostic marker. This article is protected by copyright. All rights reserved.
    FEBS Journal 01/2014; · 4.25 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Conventional circumferential stabilization for pathologies causing instability of the thoracic spine requires a 2 or even a 3 staged procedure. The authors present their tertiary care center experience of single staged procedure to establish a circumferential fusion through an extended costo-transversectomy approach. The purpose of this study was to demonstrate [1] neural canal decompression [2] removal of the pathology [3] achieve circumferential fusion and [4] correcting the deformity through a single procedure. Prospective, observational. Forty-six patients with pan thoracic column instability due to various pathologies. Neurological condition was evaluated using ASIA and ECOG grading system. Outcome was evaluated with regard to the decompression of neural canal, correction of deformity, and neurological improvement. All patients were evaluated for neural canal compromise, degree of kyphosis preoperatively, early and late postoperatively. All patients had severe spinal canal compromise (mean, 59% + 9%) and loss of vertebral body height (mean, 55% + 10%). A single stage circumferential fusion was performed (4 level pedicle screw fixation along with a ventral cage fixation following a vertebrectomy or corpectomy) through an extended costo-transversectomy approach. The pathologies included: trauma (21), tuberculosis (18), haemangioma (2), aneurysmal bone cyst (1), recurrent haemangioendothelioma (1), solitary metastasis (1) and solitary plasmacytoma (1) and neurofibromatosis (1). 35/46 patients (76%) demonstrated improvement in the performance status. The major complications included pneumonitis (3), pneumothorax (3) and neurological deterioration (3; improved in 2), deep venous thrombosis (2), recurrent hemoptysis (1). No implant failures were noted on last radiology follow up. There were two mortalities; one due to myocardial infarction and another because of respiratory complications. The following study demonstrated that extended costo-trasversectomy approach is a good option for achieving single staged circumferential fusion for correcting unstable thoracic spine due to both traumatic and non-traumatic pathologies.
    The spine journal: official journal of the North American Spine Society 01/2014; · 2.90 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Background Chordomas are slow-growing tumors and most commonly involve the sacrum and clivus. Multiple recurrences are frequent. Childhood chordomas are rare and often show exceptionally aggressive behavior, resulting in short survival and a high incidence of metastatic spread.Objective This study examined the histologic features and immunohistochemical profile of pediatric chordomas and compared them with their adult counterparts.Methods Nine pediatric and 13 adult cases were included in the study. Childhood chordomas were classified into conventional, atypical, and poorly differentiated types. Immunohistochemistry was performed for cytokeratin, epithelial membrane antigen, vimentin, S100, brachyury, p53, INI1, epidermal growth factor receptor (EGFR), and CD117. Cytogenetic analyses were performed in a subset of tumors for SMARCB1/INI1 locus on 22q chromosome by fluorescent in situ hybridization (FISH) and analysis of the SMARCB1/INI1 gene sequence.ResultsAll tumors showed expression of cytokeratin, epithelial membrane antigen, S100, vimentin, brachyury, and EGFR. Atypical morphology, p53 expression, higher MIB-1 labelling index (LI), and INI1 loss were more frequently seen in pediatric chordomas as compared with adults. None of the tumors showed CD117 expression. No point mutation in the SMARCB1/INI1 gene was noted in the tumors examined; however, 4 pediatric and 1 adult chordoma showed loss of this locus on FISH analysis.ConclusionsA subset of pediatric chordomas with atypical histomorphologic features needs to be identified, as they behave in an aggressive manner and require adjuvant therapy. Pediatric chordomas more frequently show p53 expression, INI1 loss, and higher MIB-1 LI as compared with adults, whereas EGFR expression is common to both.
    Neuro-Oncology 12/2013; · 6.18 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Background. Chordomas are slow-growing tumors and most commonly involve the sacrum and clivus. Multiple recurrences are frequent. at Childhood chordomas are rare and often show exceptionally aggressive behavior, resulting in short survival and a high incidence of meta static spread.
    Neuro-Oncology 12/2013; 2013; 0, 1 – 10, doi:10.1093/neuonc/228. · 6.18 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Ependymomas are relatively rare glial tumours, whose pathogenesis is not well elucidated. They are enigmatic tumours that show site-specific differences in their biological behaviour. Recent studies have hypothesized that ependymoma cancer stem cells (CSC) are derived from radial glia and express stem-cell markers such as nestin, which is associated with a poor prognosis. CSCs reside in 'vascular niches', where endothelial cells and molecular signals like vascular endothelial growth factor (VEGF) play an important role in their survival. Studies analyzing VEGF expression in ependymomas showed that ependymal vascular proliferation is less sensitive to induction by VEGF, questioning the possible beneficial effect of anti-VEGF therapy in ependymomas. We aimed to study nestin and VEGF immunoexpression in ependymomas, correlate them with clinicopathological parameters and reveal a role for VEGF in ependymomas that extends beyond the context of tumour angiogenesis. We analyzed 126 cases of ependymomas of different grades and location for nestin and VEGF immunoexpression. Endothelial cells were labeled with CD34. Vascular patterns and microvascular density was determined. Nestin and VEGF expression in tumour cells were more frequent in supratentorial tumours {89% (33/37) & 65% (24/37) respectively}, and were associated with a significantly poor progression-free survival (PFS). VEGF expression did not reveal any correlation with necrosis or bizarre vascular patterns. Supratentorial location is an independent predictor of a poor PFS. Significant co-expression of nestin and VEGF suggests that latter possibly augments stem cell survival. Thus, anti-VEGF therapy may be a good option in future for nestin immunopositive ependymomas.
    Neuropathology and Applied Neurobiology 11/2013; · 4.84 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Ependymomas are relatively uncommon tumours of the central nervous system which arise from the ependymal lining of the ventricles and spinal canal. The molecular changes leading to ependymal oncogenesis are not completely understood. We examined chromosome 9q33-34 locus for gain, potential oncogenes at this locus (Notch-1 and Tenascin-C) and Notch pathway target genes (Hes-1, Hey-2 & C-myc) in ependymomas by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, to assess if they have any correlation with clinical characteristics. We analyzed 50 cases of ependymomas by FISH for 9q gain and by IHC for Notch-1 and its target gene proteins (Hes-1, Hey-2 and C-myc) expression. We also performed IHC for Tenascin-C to rule out any correlation with aggressiveness/grade of tumour. FISH study revealed significant chromosome 9q gain in ependymomas of adult onset (age > 18 years) and spinal cord origin. Notch-1 showed significantly more frequent immunohistochemical expression in supratentorial and anaplastic ependymomas. Tenascin-C (TN-C) expression was significant in intracranial, childhood (age ≤ 18 years) and anaplastic ependymomas. Of the three Notch pathway target gene proteins (Hes-1, Hey-2 and C-myc), Hes-1 and C-myc expression showed significant correlation with anaplastic and adult onset ependymomas, respectively. Genetic alterations are independent prognostic markers in ependymomas. A clinicopathological correlation with various molecular signatures may be helpful in the development of new therapeutic targets.
    Journal of Neuro-Oncology 11/2013; · 3.12 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Muscular dystrophies are progressive, genetic disorders of muscle degeneration. The current gold standard for diagnosis is muscle biopsy or genetic studies. Muscle biopsy is an invasive procedure and genetic testing facilities are available only in a few centers. Thus, a diagnostic test that is easily available, simpler, and less invasive is desirable. Over the past 2 decades, skin biopsy has been evolving as a suitable option. Two cases of sarcoglycanopathy are described here, which have been correctly diagnosed by skin biopsy. Muscle biopsy has been used as the gold-standard diagnostic method. Skin biopsy can substitute for muscle biopsy as the preliminary diagnostic tool directing appropriate molecular testing. However, these results require validation in studies with an adequate sample size. This holds promise for the future when repeated biopsies will be required for evaluating protein rescue in trials of novel treatment options in these disorders.
    Journal of child neurology 05/2013; · 1.59 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Dystrophinopathies are diagnosed by genetic studies and muscle biopsy. Most centers have multiplex polymerase chain reaction facilities diagnosing 65% to 70% of dystrophinopathy cases. Muscle biopsy is a time-consuming, invasive procedure whereas skin biopsy is a simple procedure done under local anesthesia. The current study evaluated the diagnostic accuracy of skin biopsy in dystrophinopathy. Overall, 119 confirmed cases of muscular dystrophy (111 males and 8 females) were included in the final analysis, of which 100 (all males) were dystrophinopathy. Skin biopsy diagnosed dystrophinopathy in suspected muscular dystrophy patients with a sensitivity of 98% (92.3%-99.7%), specificity of 99% (93.7%-99.9%), positive predictive value of 94.7% (71.9%-99.7%), and negative predictive value of 90% (66.9%-98.2%). Skin biopsy can be used for screening dystrophinopathy in muscular dystrophy patients (high sensitivity and positive predictive value). It being a simple and minimally invasive procedure, histopathologic and molecular markers of disease progression and response to novel treatment options can be assessed serially.
    Journal of child neurology 04/2013; · 1.59 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Uterus-like mass is an extremely rare choristoma of müllerian origin arising in association with neural tube defects. In this article, we describe the case of a 9-year-old girl with spina bifida, a mass lesion within the conus, and a subcutaneous lipoma in the lumbosacral region. Histopathological examination of the conus lesion revealed a uterus-like structure comprising of endometrial glands and stroma surrounded by fascicles of smooth muscle. This case differs from the few previously described cases in absence of neurological symptoms and early age at diagnosis. Thorough histopathological examination of resected tissue is therefore recommended for the diagnosis of this rare entity, as it may not have a typical presentation in all instances.
    Pediatric Neurosurgery 04/2013; · 0.42 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Background Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas.Materials and methodsFifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations.ResultsConcordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells.ConclusionsIHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.
    Neuro-Oncology 03/2013; · 6.18 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: AIM: To mark out objectively, abnormal areas of MRI, PET and ECoG using neuronavigation so as to [1] enhance the accuracy of margins of the epileptogenic zone [2] understand the relationship of all the 3 modalities to each other. METHODS: Prospective study: 37 patients with intractable epilepsy due to lesional, neocortical pathologies from non-eloquent areas. Prior to surgery, fusion and transfer of MRI and PET images on to a neuronavigation system was performed. At surgery, this was correlated to intra-operative ECoG using the electrode as referential points. An objective score was created for every electrode point which was correlated with MRI, PET abnormality at the point. The extent of surgical resection mapped out using this data. RESULTS: From a total of the data recorded from 1280 electrode points, 23.5% were located over lesion. Over the lesions, 93% of PET and 66% of ECoG points were abnormal. Over the perilesional areas, 43% of PET and 45% of ECoG points were abnormal. Using this data for surgery, both lesional and peri-leisonal areas were resected; 33/37 patients had good outcome (25 Engel I, 8 Engel II) (mean follow up: 23.6 + 3.2 months; range: 18-31 months). CONCLUSION: Multimodal imaging and ECoG using this method seems to provide a better objective localization of the epileptogenic foci.
    World Neurosurgery 02/2013; · 1.77 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: OBJECTIVE: To describe management and outcome in a large cohort of patients with spinal tuberculosis METHODS: 212 patients of spinal tuberculosis treated between Jan 1999-June 2011 of which, 179 patients were included (> 6 months follow-up, mean age- 34.8 years; age range 10-75 years). The cohort was divided into 2 groups (n = 89 and 90 respectively), Group I :1999-2003 and Group II: 2004-2011. RESULTS: There were 93 males. Mean age was 34.8 + 7.2 years (range: 10-75 years). Mean duration of symptoms was 2.4 months. Sensory-motor deficits were present in 167 (93.5%; 74 patients were paraplegic), 156 (87%) had pain, 127 (71.7%) had bladder involvement and extra spinal tuberculosis was present in 36 patients (22.3%). 92% were on prior chemotherapy, 1/5(th) of the total on second-line chemotherapy. Thoracic spine was commonest (n= 86, 57%), followed by cervical (n=50, 29%), craniovertebral junction (22, 15%) and lumbo-sacral spine (n= 20, 10.5%). 146 patients underwent surgery, 68% instrumented fusions and 16% circumferential fusions. Mean follow-up: 20.2 months (range 6-60 months). 89% improved in motor/sensory deficits, 71% improved in pain, 88% improved in bladder symptoms, paraplegia improved in 77%. Group II had higher incidence of cord compression (p<0.01), severe vertebral body (p<0.001) collapse and paraplegia (p<0.001). Group II underwent more instrumented surgeries (p<0.01), especially circumferential fusions (p<0.001). The improvement of paraplegia was better after 2004 (Group II). Bladder symptoms correlated with the timing of surgery (p<0.1) CONCLUSION: Medical treatment is the main stay, however radical, instrumented surgeries should be offered when indicated. Presence of paraplegia should not preclude surgery. A practical management paradigm is also suggested.
    World Neurosurgery 01/2013; · 1.77 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Cell cycle regulator genes are major target of mutation in many human malignancies including glioblastomas (GBMs). CDKN2A is one such tumor suppressor gene which encodes p16INK4a protein and serves as an inhibitor of cell cycle progression. Very few studies are available regarding the association of CDKN2A deletion with p16 protein expression in GBMs. There is limited data on the frequency of CDKN2A deletion in different age groups. The aim of the present study was to analyze the frequency of CDKN2A gene deletions in GBM and correlate CDKN2A deletional status with (i) age of the patient (ii) p16 protein expression and (iii) other genetic alterations, namely EGFR amplification and TP53 mutation. A combined retrospective and prospective study was conducted. Sixty seven cases were included. The patients were grouped into pediatric (≤18 years), young adults (19-40 years) and older adults (>40 years). CDKN2A and EGFR status were assessed by Fluorescence in situ Hybridization.TP53 mutation was analyzed by PCR based method. p16 expression was assessed using immunohistochemistry. CDKN2A deletion was noted in 40.3% cases of GBM with majority being homozygous deletion (74%). It was commoner in primary GBMs (65.8%) and cases with EGFR amplification (50%). A variable frequency of CDKN2A was observed in older adults (42.3%), young adults (44%), and pediatric patients (31.25%). The difference however was not statistically significant. There was statistically significant association between CDKN2A deletion and p16 immunonegativity with a high negative predictive value of immunohistochemistry.
    Neuropathology 01/2013; · 1.91 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Mantle cell lymphoma (MCL) is a distinct non-Hodgkin's lymphoma type that commonly affects extra nodal sites. The most often affected sites are bone marrow, gastrointestinal tract and Waldeyer's ring, being the skin rarely involved. We report a case of 56 year-old man with MCL, exhibiting multiple large maculopapular skin rashes and skin ulcers. Histopathological examination had not shown direct infiltration by any atypical cells. He had significant improvement of skin lesions with combination chemotherapy and debridement. Awareness of skin manifestations of MCL is crucial for dermatologists and haematologists to establish the early diagnosis and timely administration of appropriate treatment.
    Mediterranean Journal of Hematology and Infectious Diseases 01/2013; 5(1):e2013020.
  • [show abstract] [hide abstract]
    ABSTRACT: We retrospectively reviewed the outcomes of 195 patients with intramedullary tumors who underwent surgery between January 2001 and December 2010 at a single institution. The symptomatology, neurological and neuroradiological findings, operative details, perioperative and postoperative complications, histopathological data and follow-up examinations of the 137 (70.2%) males and 58 (29.7%) females were studied and analyzed. Epidermoid was the most common intramedullary tumour in children (23%), whereas in adults, ependymomas were more common (46%). Ependymomas were more amenable to resection (total excision in 57.7% and near-total excision in 39.4%) as compared to astrocytomas (total excision in 29%; near total excision in 60.5%). At the final clinical follow-up, 24 patients (16.4%) had improved in McCormick grade, 112 patients (76.7%) remained unchanged and 11 patients (7.5%) had worsened. Complete removal of the lesion is the primary goal of surgery. We conclude that the strongest predictor of functional outcome was the preoperative neurological condition, beyond the histological differentiation of the intramedullary tumor.
    Journal of Clinical Neuroscience 12/2012; · 1.25 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Object Bone marrow-derived stem cells enhance the rate of regeneration of neuronal cells leading to clinical improvement in nerve injury, spinal cord injury, and brain infarction. Recent experiments in the local application of bone marrow-derived mononuclear cells (BM-MNCs) in models of sciatic nerve transection in rats have suggested their beneficial role in nerve regeneration, although the effects of variable doses of stem cells on peripheral nerve regeneration have never been specifically evaluated in the literature. In this paper, the authors evaluated the dose-dependent role of BM-MNCs in peripheral nerve regeneration in a model of sciatic nerve transection in rats. Methods The right sciatic nerve of 60 adult female Wistar rats (randomized into 2 test groups and 1 control group, 20 rats in each group) underwent transection under an operating microscope. The cut ends of the nerve were approximated using 2 epineural microsutures. The gap was filled with low-dose (5 million BM-MNCs/100 μl phosphate-buffered saline [PBS]) rat BM-MNCs in one group, high-dose (10 million BM-MNCs/100 μl PBS) rat BM-MNCs in another group, and only PBS in the control group, and the approximated nerve ends were sealed using fibrin glue. Histological assessment was performed after 30 days by using semiquantitative and morphometric analyses and was done to assess axonal regeneration, percentage of myelinated fibers, axonal diameter, fiber diameter, and myelin thickness at distal-most sites (10 mm from site of repair), intermediate distal sites (5 mm distal to the repair site), and site of repair. Results The recovery of nerve cell architecture after nerve anastomosis was far better in the high-dose BM-MNC group than in the low-dose BM-MNC and control groups, and it was most evident (p < 0.02 in the majority of the parameters [3 of 4]) at the distal-most site. Overall, the improvement in myelin thickness was most significant with incremental dosage of BM-MNCs, and was evident at the repair, intermediate distal, and distal-most sites (p = 0.001). Conclusions This study emphasizes the role of BM-MNCs, which can be isolated easily from bone marrow aspirates, in peripheral nerve injury and highlights their dose-dependent facilitation of nerve regeneration.
    Journal of Neurosurgery 10/2012; · 3.15 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Glioblastoma multiforme (GBM) is the most aggressive and the commonest primary brain tumor with a tendency for local invasiveness. The pathways of neoplasia, invasion and inflammation are inextricably linked in cancer and aberrations in several regulatory pathways for these processes have been identified. Here we have studied the FAT1 (Homo sapiens FAT tumor-suppressor homolog 1 (Drosophila)) gene to identify its role in the tumorigenecity of the gliomas. The expression of FAT1 was found to be high in grade IV glioma cell lines (U87MG, A172, U373MG and T98G) but low in grade III glioma cell lines (GOS3 and SW1088). Two cell lines (U87MG and A172) with high FAT1 expression were chosen for in vitro FAT1-knockdown studies. FAT1 knockdown by small interfering RNA resulted in decreased migration and invasion of both the cell lines along with increased expression of the tumor-suppressor gene programmed cell death 4 (PDCD4). Increased PDCD4 expression led to the attenuation of activator protein-1 (AP-1) transcription by inhibiting c-Jun phosphorylation and resulted in concomitant decrease in the expression of AP-1-target genes like MMP3, VEGF-C and PLAU, the pro-inflammatory regulator COX-2 and cytokines IL1β and IL-6. Conversely, simultaneous silencing of PDCD4 and FAT1 in these cells significantly enhanced AP-1 activity and expression of its target genes, resulting in increase in mediators of inflammation and in enhanced migratory and invasive properties of the cells. We also observed a negative correlation between the expression of FAT1 and PDCD4 (P=0.0145), a positive correlation between the expression of FAT1 and COX-2 (P=0.048) and a similar positive trend between FAT1 and IL-6 expression in 35 primary human GBM samples studied. Taken together, this study identifies a novel signaling mechanism mediated by FAT1 in regulating the activity of PDCD4 and thereby the key transcription factor AP-1, which then affects known mediators of neoplasia and inflammation.Oncogene advance online publication, 17 September 2012; doi:10.1038/onc.2012.393.
    Oncogene 09/2012; · 7.36 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Alveolar soft part sarcoma (ASPS) is a relatively rare tumor that mostly presents as a slow growing mass in the deep soft tissue of the extremities. A substantial number of cases in children occur in the head and neck region; however, in any age group, it is very rarely reported in the sinonasal region. We report a case of ASPS of the paranasal sinuses with sellar extension in a 25-year-old man that masqueraded as a giant invasive pituitary adenoma. This is only the fifth case of sinonasal ASPS in literature. The clinical and radiological diagnoses were misleading, but an extensive pathology workup including electron microscopy helped reach an accurate diagnosis in this unusual case.
    Annals of diagnostic pathology 08/2012;

Publication Stats

2k Citations
329 Downloads
594.60 Total Impact Points

Institutions

  • 2005–2014
    • AIIMS Bhopal All India Institute of Medical Sciences
      Bhopal, Madhya Pradesh, India
  • 1987–2013
    • All India Institute of Medical Sciences
      • • Department of Pathology
      • • Department of Biochemistry
      • • Department of Neurosurgery
      • • Department of Neurology
      New Delhi, NCT, India
  • 2004
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France