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Chitra Sarkar

Publications and source records attributed to Chitra Sarkar.

54 records · Page 3Linked to original sources
PubMed2004

Increased hMSH2 protein expression in glioblastoma multiforme.

hMSH2 and hMLH1 are the most commonly studied mismatch repair proteins and their absence is associated with microsatellite instability (MSI) especially in hereditary non-polyposis colorectal cancer, and also in some sporadic tumors. However, there are some tumors, namely, urothelial neoplasms and salivary gland tumors, where overexpression of the proteins has been reported, though the implications of these findings are not very clear. There is no report on the expression of these proteins in different grades of human astrocytic tumors. We have studied the expression pattern of hMSH2 and hMLHI in high (Grade IV, glioblastoma multiforme (GBM)) and low (Grade II, astrocytoma (AS)) grade primary human gliomas by immunohistochemistry. We observed that there was a significantly higher expression of hMSH2 protein in 28 GBM (mean 703.07 +/- 236.28) as compared with 27 AS (mean 307.03 +/- 204.71), p = 1.47 x 10(-8) by a two-tailed t-test of unpaired samples. However, for hMLH1 no such difference was observed, mean counts being 543.29 +/- 320.35 for 27 GBM and 505.92 +/- 342.37 for 26 AS, p = 0.67. A small proportion of tumors was observed to be immunonegative for either of the proteins in both high- and low-grade tumors. While MSI has been shown previously to be infrequent in human astrocytic tumors, the implications of the overexpression of hMSH2 in GBM are not clear.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Subependymal giant cell astrocytoma: a clinicopathological study of 23 cases with special emphasis on proliferative markers and expression of p53 and retinoblastoma gene proteins.

AIMS: To gain a better insight into the biological behaviour of subependymal giant cell astrocytoma (SEGA), tumour suppressor gene protein expression and various proliferative indices were studied in these tumours and correlated with histological features and clinical outcome. METHODS: We studied 23 cases of SEGA, 19 from our own Institute and four from the National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore, India. Immunohistochemical staining for various glial and neuronal markers, proliferative markers (MIB-1, Topoisomerase II alpha PCNA) and tumour suppressor gene protein expression of p53 and retinoblastoma (Rb) were performed. RESULTS: Nineteen cases of SEGA were collected over a period of 23 years (January 1978-December 2001), which accounted for 0.16% of all intracranial tumours and 0.51% of all gliomas reported at this centre. Ages ranged from 4 to 37 years (mean 13.2 years) with a male preponderance. Nine of the 23 cases were associated with tuberous sclerosis (TS), six at the time of diagnosis, while three developed TS during the follow-up period. Treatment consisted of surgical resection (total in nine cases and subtotal in 14 cases) followed by radiotherapy in seven cases. Except for two patients who died in the immediate post-operative period of surgical complications, the remaining patients were all alive in the follow-up period (mean 37.1 months). One patient experienced recurrence 22 years after the first surgery and a second patient after 2 years. Necrosis and/or mitoses were observed in five cases. Immunohistochemically, tumours were positive for both glial and neuronal markers. Interspersed inflammatory cells were a mixture of mast cells and lymphocytes of T immunophenotype. The MIB-1 labelling index (LI) ranged from 0 to 8% (mean 3.0%), topoisomerase II alpha (topo II alpha) LI from 0 to 9.5% (mean 2.9%) and PCNA LI from 10 to 59% (mean 32.5%). The difference in the labelling indices of tumours with and without mitoses and/or necrosis was not statistically significant. None of the tumours revealed loss of Rb gene protein expression. p53 immunopositivity was seen in 14 cases (labelling indices ranged from 1 to 7.3% with a mean of 2.4%). The correlation between the MIB-1 LI and topo II alpha LI, and topo II alpha LI and PCNA LI was significant (P<0.05) but not so with other parameters like p53 protein expression, duration of survival and morphological features such as mitoses and necrosis. CONCLUSIONS: SEGAs are rare intraventricular tumours associated with TS and express both neuronal and glial markers. They have a low proliferative potential. Mitoses and necrosis are not associated with a worse prognosis. In view of the low proliferative indices and long survival of these patients without recurrence, the role of post-operative radiotherapy is questionable. These patients should be followed up closely as many of them develop stigmata of tuberous sclerosis at a later stage.

Adolescent↗
PubMed2004

p53 protein alterations in adult astrocytic tumors and oligodendrogliomas.

BACKGROUND: p53 is a tumor suppressor gene implicated in the genesis of a variety of malignancies including brain tumors. Overexpression of the p53 protein is often used as a surrogate indicator of alterations in the p53 gene. AIMS: In this study, data is presented on p53 protein expression in adult cases (>15 years of age) of astrocytic (n=152) and oligodendroglial (n=28) tumors of all grades. Of the astrocytic tumors, 86% were supratentorial in location while remaining 14% were located infratentorially - 8 in the the cerebellum and 13 in the brainstem. All the oligodendrogliomas were supratentorial. MATERIALS AND METHODS: p53 protein expression was evaluated on formalin-fixed paraffin-embedded sections using streptavidin biotin immunoperoxidase technique after high temperature antigen retrieval. RESULTS: Overall 52% of supratentorial astrocytic tumors showed p53 immunopositivity with no correlation to the histological grade. Thus, 58.8% of diffuse astrocytomas (WHO Grade II), 53.8% of anaplastic astrocytomas (WHO Grade III) and 50% of glioblastomas (WHO Grade IV) were p53 protein positive. In contrast, all the infratentorial tumors were p53 negative except for one brainstem glioblastoma. Similarly, pilocytic astrocytomas were uniformly p53 negative irrespective of the location. Among oligodendroglial tumors, the overall frequency of p53 immunopositivity was lower (only 28%), though a trend of positive correlation with the tumor grade was noted - 25% in Grade II and 31.5% in grade III (anaplastic oligodendroglioma). Interestingly, p53 labeling index (p53 LI) did not correlate with the histopathological grade in both astrocytic and oligodendroglial tumors. CONCLUSIONS: Thus, this study gives an insight into the genetic and hence biological heterogeneity of gliomas, not only between astrocytic tumors vs. oligodendrogliomas but also within astrocytic tumors with regard to their grade and location. With p53 gene therapy trials in progress, this will possibly have future therapeutic implications.

Adolescent↗
PubMed2004

Sarcoglycanopathies: a clinicopathological study of 13 cases [corrected].

BACKGROUND: Limb girdle muscular dystrophy (LGMD) is a phenotypic expression of a heterogeneous group of diseases and sarcoglycanopathy is one of the causes of LGMD. There is only one study on sarcoglycanopathies in the Indian literature. No data is available from northern India. MATERIALS AND METHODS: All cases of muscular dystrophies, which were diagnosed in our laboratory in the last six years, were reviewed. Immunohistochemistry for various sarcoglycan proteins was done. Clinical features and pathological findings of the cases that were diagnosed as sarcoglycanopathies were reviewed. RESULTS: In the last 6 (1/2) years (1998-June 2004), we received 1435 muscle biopsies, of which 498 cases were of muscular dystrophies, and 13 cases were of sarcoglycanopathies (8 of gamma, 3 of alpha, 1 of both alpha and gamma, and 1 with absence of all four sarcoglycans). Sarcoglycanopathies comprised 2.6% of all muscular dystrophies, 11.8% of LGMD and 0.90% of all muscle diseases diagnosed in our laboratory. The mean age of onset was 7.2 years and the M:F ratio was 1.1:1. Most of them presented with difficulty in getting up, climbing stairs, calf hypertrophy and markedly raised CPK levels. Histological features were like dystrophinopathies. CONCLUSION: Sarcoglycanopathies are a relatively rare cause of LGMD and should be confirmed by immunohistochemistry as it will facilitate counseling and also prognostification. Although rare, in patients with muscle weakness, calves hypertrophy and raised CPK levels this possibility should be considered and needs to be differentiated from dystrophinopathies.

Adolescent↗
PubMed2003

Loss of heterozygosity of a locus in the chromosomal region 17p13.3 is associated with increased cell proliferation in astrocytic tumors.

We had previously reported that loss of heterozygosity (LOH) of the D17S379 locus on 17p13.3 was significantly more frequent in high-grade gliomas (anaplastic astrocytoma, AA; glioblastoma multiforme, GBM) than in those of a low-grade diffuse astrocytoma (DA); however, this was independent of alterations at the TP53 locus, We also showed that LOH of D17S379 was associated with positive staining for p53 protein on immunohistochemistry, but LOH of the TP53 gene had no such association. In this work we show that cell proliferation as determined by MIB-1 labeling index (LI) was significantly higher in tumors with LOH of D17S379 than those with no LOH (NLOH). In accord with our previous results, p53 protein immunopositivity was also associated with increased MIB-1 LI; however, we observed no such association of LI with TP53 LOH. The results further confirm that alteration of one or more putative tumor suppressor loci at 17p13.3 is associated with increased proliferation in astrocytic tumors.

Adult↗
PubMed2003

In vivo and in vitro MR spectroscopic profile of central neurocytomas.

This study reports in vivo and in vitro magnetic resonance spectroscopic findings in two cases of central neurocytomas (CNC) confirmed by immunohistochemistry. Volume localized in vivo proton magnetic resonance spectroscopy (MRS) was carried out before surgery using a point resolved spectroscopy (PRESS) sequence with a repetition time of six seconds and an echo time of 135 msec. Normal spectrum was obtained from gray matter from a volunteer for comparison. (1)H and (31)P in vitro MRS studies were carried out at 9.4 T on the extracts prepared from the surgically excised tumors. The in vivo spectra showed prominent glycine (Gly) and choline (Cho) and low N-acetyl aspartate compared to the normal. The Gly peak was assigned using the in vitro studies. These studies showed that the major contribution to the Cho peak observed in vivo is from phosphocholine. A combination of the presence of NAA and an increased Gly in the proton MR spectrum could be a characteristic feature of CNCs, which are rare intraventricular tumors of neuronal origin.

Adult↗
PubMed2003

Biochemical characterization of muscle tissue of limb girdle muscular dystrophy: an 1H and 13C NMR study.

The metabolic differences between the muscle biopsies of patients with limb girdle muscular dystrophy (LGMD) and normal controls were characterized using high-resolution 1H and 13C NMR spectroscopy. In all, 44 metabolites were unambiguously assigned in the perchloric acid extracts of skeletal muscle tissue, using 2D double quantum filtered (DQF COSY), total correlation (TOCSY), and 1H/13C heteronuclear multiple quantum coherence (HMQC) spectroscopy. The concentrations of glycolytic substrate, glucose (p=0.03), gluconeogenic amino acids, glutamine (p=0.02) and alanine (p=0.009) together with glycolytic product, lactate (p=0.04), were found to be significantly lowered in LGMD patients as compared with controls. The reduction in the concentration of glucose may be attributed to the decrease in the concentration of gluconeogenic amino acids in the degenerated muscle. Reduction in the rate of anaerobic glycolysis and lowered substrate concentration appear to be the possible reasons for the decrease in the concentration of lactate. A significant reduction in the concentration of choline in LGMD patients was also observed compared with controls. Lower concentration of choline may be the result of decreased rate of membrane turnover in LGMD patients. The data presented here provide an insight into the potentials of in-vitro NMR spectroscopy in the study of muscle metabolism.

Amino Acids↗
PubMed2003

Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma.

Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known. With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry. The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant forms (WHO grade IV giant cell glioblastoma and glioblastoma multiforme) the IR was very weak. These findings suggest that Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit glial proliferation, and thus contribute to progression towards malignancy.

Adolescent↗
PubMed2003

Intramedullary subependymoma of the spinal cord: a case report and review of literature.

A case of cervical spine intramedullary subependymoma in a 52-year-old female is reported. Also, the relevant literature on the 40 cases reported till date is reviewed. Magnetic resonance imaging, even with enhancement, does not show any distinctive features making pre-operative diagnosis often difficult. These tumours are eccentrically located within the spinal cord, thus enabling complete tumour removal in most cases. They are benign with low proliferative potential and hence no post-operative radiotherapy should be administered.

Diagnosis, Differential↗
PubMed2003

Skeletal muscle metabolism in Duchenne muscular dystrophy (DMD): an in-vitro proton NMR spectroscopy study.

The metabolic differences in the skeletal muscle of patients with Duchenne muscular dystrophy (DMD) and normal subjects (controls) were investigated using in-vitro high-resolution proton NMR spectroscopy. In all, 56 metabolites were unambiguously identified in the perchloric acid extract of muscle tissue using one- and two-dimensional NMR. The concentrations of glycolytic substrate glucose (Glc; p < 0.05), gluconeogenic amino acids such as glutamine (Gln; p < 0.05) and alanine (Ala; p < 0.05) and the glycolytic product lactate (Lac; p < 0.05) were statistically significantly lower in DMD patients as compared to controls. A significant reduction in the concentrations of total creatine (TCr; p < 0.05), glycerophosphoryl choline + phosphoryl choline + carnitine (GPC/PC/Car; p < 0.05), choline (Cho; p < 0.05) and acetate (Ace; p < 0.05) was also observed in these patients. Decrease in the level of glucose may be attributed to the reduction in the concentrations of gluconeogenic substrates or membrane abnormalities in degenerated muscle of DMD patients. Lower levels of choline containing compounds indicate membrane abnormalities. Decrease in the concentration of lactate in the muscle of DMD patients may be due to the reduction in anaerobic glycolytic activity or lower substrate concentration. The decrease in the concentration of acetate may reflect reduced transport of fatty acids into mitochondria due to decreased concentration of carnitine in DMD patients. Kreb's cycle intermediate alpha-ketoglutarate was observed only in the diseased muscle, which is suggestive of predominant oxidative metabolism for energy generation.

Adolescent↗
PubMed2003

Transforming growth factor beta in hepatitis C virus infection: in vivo and in vitro findings.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of chronic liver disease (CLD) worldwide. The chronicity is a result of viral persistence and the ability of the virus to escape from the immune mechanisms of the host. Transforming growth factor (TGF)-beta is a cytokine thought to be responsible for viral persistence and liver fibrogenesis. METHODS: The present study examined the levels of TGF-beta messenger (m)RNA by reverse transcription polymerase chain reaction (RT-PCR) in 35 liver biopsies and HCV-transfected HepG2 cells. RESULTS: Transforming growth factor-beta mRNA was detected in nine liver biopsies from patients with chronic HCV infection, but was not detected in patients with non-HCV-related CLD or controls. On quantitation by semiquantitative PCR, TGF-beta mRNA levels ranged from 10-4.75 to 10-12.8 amol (10-7.46 +/- 3.771) in liver biopsies of HCV-related CLD. No significant difference in TGF-beta receptor levels was observed by RT-PCR in HCV- or non-HCV-related CLD by immunohistochemistry. To correlate these findings with in vitro experiments, levels of TGF-beta mRNA and its receptors were determined by RT-PCR in HepG2 cells transfected with HCV and hepatitis B virus (HBV) constructs, using mock-transfected cells as control. The TGF-beta protein levels were quantitated in these cell supernatants by enzyme immunoassay. The TGF-beta mRNA and protein levels were two logs and approximately 30 times higher in HCV-transfected HepG2 cells than in HBV- and mock-transfected cells, respectively. The TGF-beta receptors in HepG2 cells were also downregulated in HCV-transfected cells as compared with mock-transfected cells. CONCLUSION: These observations suggest upregulation of TGF-beta in HCV infection and a probable role for TGF-beta in the pathogenesis of HCV-related CLD.

Adult↗
PubMed2003

Preoperative diagnosis of allergic fungal sinusitis.

OBJECTIVES/HYPOTHESIS: Although the diagnosis of allergic fungal sinusitis is mainly based on characteristic histopathological findings, certain preoperative diagnostic criteria have been proposed. However, their usefulness in differentiating allergic fungal sinusitis from other sinus diseases is unknown. The objective of the study was to identify accurate preoperative diagnostic parameters for allergic fungal sinusitis. STUDY DESIGN: Prospective, comparative study. METHODS: Twenty consecutive cases of allergic fungal sinusitis were evaluated prospectively and compared with 16 cases of ethmoidal polyposis and 5 cases of invasive sinus aspergillosis, with regard to various clinical, radiological, and immunological parameters. All patients were categorized based on histopathological findings. RESULTS: Nasal polyps were seen in all 20 cases of allergic fungal sinusitis, all 16 cases of ethmoidal polyposis, and 2 of 5 cases of invasive sinus aspergillosis. Computed tomography (CT) scan hyper-attenuation was seen in all 20 cases of allergic fungal sinusitis but also in 2 (13%) cases of ethmoidal polyposis and 2 (40%) cases of invasive sinus aspergillosis. Serum levels of specific anti-Aspergillus immunoglobulin E were elevated in 14 (70%) cases of allergic fungal sinusitis, 2 (13%) cases of ethmoidal polyposis, and 3 (60%) cases of invasive sinus aspergillosis. The combination of all three (ie, nasal polyps, CT scan hyper-attenuation, and elevated titers of anti-Aspergillus immunoglobulin) was not found in any case of ethmoidal polyposis or invasive sinus aspergillosis. This triad demonstrated a sensitivity of 70% and a specificity of 100% for the preoperative diagnosis of allergic fungal sinusitis. CONCLUSIONS: Nasal polyps, CT scan, and specific immunoglobulin E titers, when considered in combination, have a high preoperative diagnostic value in allergic fungal sinusitis. However, they should not be considered in isolation because considerable overlap occurs with invasive sinus aspergillosis and ethmoidal polyposis.

Adolescent↗
PubMed2002

Absence of simian virus 40 in human brain tumors from northern India.

Simian virus 40 (SV40), a monkey polyomavirus, was a contaminant of early poliovirus vaccines administered to millions of individuals in the 1950s and early 1960s. SV40 causes brain tumors in laboratory animals, and SV40 DNA sequences have been variably identified in human choroid plexus tumors and ependymomas. We studied the possible association between SV40 and human brain tumors in northern India, where humans have frequent contact with SV40-infected rhesus macaques. DNA from pathologic specimens from 33 ependymomas, 14 choroid plexus tumors and 18 control brain tissues (contused brain, brain metastases) was extracted and analyzed under masked conditions. We used real-time PCR to detect and quantify SV40 (T antigen) and human (GAPDH) DNA sequences. The SV40 PCR assay detected as few as 10 copies of SV40 DNA and had a linear range from 1 x 10(2) to 1 x 10(6) copies. SV40 DNA was detected in 1 specimen (an ependymoma). However, few SV40 DNA copies were detected in this sample (<10 copies, equivalent to <1 copy/350 cells, based on simultaneous GAPDH quantification), and SV40 was not detected when this sample was retested. Our findings do not support a role for SV40 in choroid plexus tumors or ependymomas from northern India.

Adolescent↗
PubMed2002

Microfilariae of Wuchereria bancrofti in cyst fluid of tumors of the brain: a report of three cases.

Microfilariae of various nematodes, including Loa loa, Dirofilariae, and Onchocerca volvulus, have been identified in the central nervous system (CNS). The CNS, however, is a rare site for the isolation of microfilariae of Wuchereria bancrofti. To the best of our knowledge, the presence of microfilariae of W. bancrofti in tumor cyst fluids or cerebrospinal fluid has not been reported to date. We report three cases in which microfilariae were identified in the cyst fluid of tumors of the brain. Cyst fluid aspirated from space-occupying lesions in the thalamus and C6-D1 spinal segments in a 46-yr-old man and a 35-yr-old man, respectively, showed numerous microfilariae of W. bancrofti, along with fragments of tumor suggestive of glioma. In the third case, in a 12-yr-old boy, the fluid from the space-occupying lesion in the third ventricle showed microfilariae in a necrotic dirty background with a few squames and cholesteral crystals. Histopathologic examination of the tumor showed an anaplastic astrocytoma and a low-grade astrocytoma in the first two cases, respectively, and a craniopharyngioma in the third case. No microfilariae were identified on the histology sections.

Adult↗
PubMed2002

Epithelioid sarcoma of the sciatic nerve perineural sheath: a mimic of nerve sheath tumor.

We report herein a rare case of epithelioid sarcoma, in a 39-year old lady involving the sciatic nerve. Clinically and radiologically it stimulated a nerve sheath tumor. Involvement of a nerve by an epithelioid sarcoma is extremely uncommon. To the best of our knowledge, this is the first case of an epithelioid sarcoma involving the sciatic nerve and needs documentation.

Adult↗
PubMed2002

Are childhood and adult medulloblastomas different? A comparative study of clinicopathological features, proliferation index and apoptotic index.

Childhood medulloblastomas have been suspected to be biologically different from adult tumors, though comparative studies are sparse in the literature. The present study aims to establish any differences or nexus in the biological characteristics between childhood and adult medulloblastomas. A total of 181 medulloblastomas were studied with respect to clinical and histological characteristics, MIB-1 labeling index (MIB-1 LI), apoptotic index (AI), ratio of apoptotic to LI, p53 and Bcl-2 protein expressions. Two-thirds (112) of the 181 medulloblastomas occurred in children (< or = 15 years) and 69 in adults (> 15 years). Childhood tumors were more commonly of classical histology and midline location while the desmoplastic variant and lateral location occurred more frequently in adults. Adult medulloblastomas were biologically less aggressive, having lower growth rate parameters (mean MIB-1 LI 19.1 +/- 15.7; AI 3.73 +/- 2.71 and AI:LI 0.207 +/- 0.162) as compared to childhood tumors (mean MIB-1 LI 28.3 +/- 20.4; AI 2.86 +/- 2.14 and AI:LI 0.108 +/- 0.111). p53 and Bcl-2 protein expressions were infrequent in all groups of tumors. No difference was noted in any of the parameters when classical and desmoplastic medulloblastomas were compared as a whole. But when compared between the age groups, an interesting observation (hitherto unreported in English literature) was that both classical and desmoplastic variants of childhood medulloblastomas had higher LI, lower AI and lower AI:LI ratio than their counterparts in adults, indicating that differences in growth rates cannot be attributed to differences in the frequency of occurrence of the histological variants in the two age groups. Thus, this study conclusively shows that there is a biological difference between childhood and adult medulloblastomas which is independent of standard histology and appeared to be associated more with age-related factors. This also warrants less-aggressive therapy for adult medulloblastoma.

Adolescent↗