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Pendharkar N.,National Center for Cell Science | Pendharkar N.,B J Medical College | Gajbhiye A.,National Center for Cell Science | Taunk K.,National Center for Cell Science | And 8 more authors.
Journal of Proteomics | Year: 2016

Worldwide, breast cancer is one of the frequently diagnosed cancers in women with high mortality if not diagnosed at early stage. Although biomarker discoveries through various proteomic approaches have been studied in breast cancer, a limited number of studies have explored the invasive ductal carcinoma with Luminal B HER2 positive (LB) and HER2 enriched (HE) subtypes. The present study employed the complementary quantitative proteomic approaches to find a panel of markers that could discriminate LB and HE subtypes as well as early (ES) and late stages (LS) of these subtypes. A total of 67 and 68 differentially expressed proteins were identified by DIGE for the subtype and stage wise categories, respectively. Multivariate statistical analysis was employed to identify the set of most significant proteins, which could discriminate between these two subtypes and also early and late stages under study. Immunoblotting and MRM based validation in a separate cohort of samples confirmed that panel of biosignatures for LB are APOA1, GELS, HS90B, EF1A1, NHRF1 and PRDX3 and for HE are PRDX1, CATD, CALR, ATPB and CH60. For the diagnosis of early and late stages the potential markers are TPM4, CATD, PRDX3, ANXA3, HSPB1 and CALR, TRFE, GELS, CH60, CAPG, NHRF1, 1433G, GRP78 respectively. © 2015 Elsevier B.V.

Ray S.,Indian Institute of Technology Bombay | Renu D.,Strand Life science Pvt. Ltd | Srivastava R.,Indian Institute of Technology Bombay | Gollapalli K.,Indian Institute of Technology Bombay | And 11 more authors.
PLoS ONE | Year: 2012

This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases. © 2012 2012 Ray et al.

Roy B.,Sanjay Gandhi Post Graduate Institute of Medical Sciences | Verma S.,Indian Institute of Technology Kanpur | Awasthi R.,Sanjay Gandhi Post Graduate Institute of Medical Sciences | Rathore R.K.,Indian Institute of Technology Kanpur | And 5 more authors.
Journal of Magnetic Resonance Imaging | Year: 2011

Purpose: To correlate phase and R2* derived from susceptibility- weighted magnetic resonance imaging (MRI) with computed tomography-Hounsfield (CT-HU) values in calcified neurocysticercosis and to evaluate phase imaging in the assessment of calcified neurocysticercosis. Materials and Methods: Thirty-five patients with 52 calcified lesions underwent both CT and MRI. Phase and R2* were calculated from multi-echo 3D-T2-star-weighted-angiography data. MRI and CT data were coregistered using mutual information. Spearman's correlation was performed between quantitative phase and CT-HU and R2* values. The Mann-Whitney U-test was used to see differences between CT-HU and R2* values from corresponding positive and negative phase regions. Results: The median values of CT-HU and R2* from regions with positive and negative phase were found to be 142.10 (range: 41.89-491.75) and 68.5/sec (range: 20-110/sec) and 137.30 (range: 30.83-458.88) and 69/sec (range: 0-110/sec), respectively. There was a significant correlation of positive phase values with corresponding CT-HU and R2* values. In addition, there was a significant correlation of R2* and CT-HU with negative phase values. Conclusion: We conclude that there is a significant correlation between negative and positive phase with CT-HU and R2* values, suggesting that the CT hyperdense lesion may have both calcium and other minerals, which can be differentiated using phase imaging. Conventional MRI should include phase imaging to detect calcified neurocysticercosis. Copyright © 2011 Wiley Periodicals, Inc.

Kundu M.,Bose Institute of India | Mahata B.,Bose Institute of India | Banerjee A.,Bose Institute of India | Chakraborty S.,Bose Institute of India | And 4 more authors.
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2016

The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor. © 2016 Elsevier B.V.

Dutta M.,Indian Institute of Technology Kharagpur | Subramani E.,Indian Institute of Technology Kharagpur | Taunk K.,National Center for Cell Science | Gajbhiye A.,National Center for Cell Science | And 9 more authors.
Journal of Proteomics | Year: 2015

Endometriosis is a common benign gynecological disease, characterized by proliferation of functional endometrial glands and stroma outside the uterine cavity. The present study involves investigation of alterations in the serum proteome of endometriosis patients compared to healthy controls using 2DE and 2D-DIGE combined with MALDI TOF/TOF-MS. Comparison of serum proteome of endometriosis patients and healthy subjects revealed 25 significant differentially expressed proteins. Gene ontology and network analysis, performed using PANTHER, DAVID, WebGestalt and STRING, revealed that the differentially expressed proteins are majorly involved in response to stimulus, immune system, metabolic, localization and cellular processes. For serum diagnostic marker identification, several robust statistical screening procedures were applied to identify the set of the most significant proteins responsible for successful diagnosis of different endometriosis stages. Partial least squares (PLS) based marker selection tool and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to identify the most significant proteins for disease prediction. Western blotting validation in a separate cohort of patients revealed that haptoglobin (HP), Ig kappa chain C region (IGKC), alpha-1B-glycoprotein (A1BG) can be considered effective serum protein markers for the diagnosis of Stage II, III and IV endometriosis. For diagnosis of Stage I, only IGKC and HP seemed promising. Biological significance: Globally, about 12 in 100 women of reproductive age are diagnosed with endometriosis. The pathogenesis of the disease still remains unclear, leading to non-specific therapeutic approaches for disease management. Moreover, there is a delay of 8-12. years in correct diagnosis after the initial onset of symptoms leading to a considerable impact on the woman's lifestyle. Also, the gold standard for diagnosis of endometriosis, laparoscopy, is an invasive procedure. The value of a noninvasive or semi-invasive diagnostic test for endometriosis with easily accessible fluids such as plasma, serum, urine, and saliva is, therefore, rightfully recognized. The present study is expected to considerably improve the understanding of the disease pathogenesis along with improved diagnostics and therapeutic approaches leading to better management of the disease. © 2014 Elsevier B.V.

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