Publications by authors named "Ranjan Paul"

55 Publications

Comprehensive Evaluation of PAXgene Fixation on Oral Cancer Tissues Using Routine Histology, Immunohistochemistry, and FTIR Microspectroscopy.

Biomolecules 2021 Jun 15;11(6). Epub 2021 Jun 15.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.

The choice of tissue fixation is critical for preserving the morphology and biochemical information of tissues. Fragile oral tissues with lower tensile strength are challenging to process for histological applications as they are prone to processing damage, such as tissue tear, wrinkling, and tissue fall-off from slides. This leads to loss of morphological information and unnecessary delay in experimentation. In this study, we have characterized the new PAXgene tissue fixation system on oral buccal mucosal tissue of cancerous and normal pathology for routine histological and immunohistochemical applications. We aimed to minimize the processing damage of tissues and improve the quality of histological experiments. We also examined the preservation of biomolecules by PAXgene fixation using FTIR microspectroscopy. Our results demonstrate that the PAXgene-fixed tissues showed significantly less tissue fall-off from slides. Hematoxylin and Eosin staining showed comparable morphology between formalin-fixed and PAXgene-fixed tissues. Good quality and slightly superior immunostaining for cancer-associated proteins p53 and CK5/6 were observed in PAXgene-fixed tissues without antigen retrieval than formalin-fixed tissues. Further, FTIR measurements revealed superior preservation of glycogen, fatty acids, and amide III protein secondary structures in PAXgene-fixed tissues. Overall, we present the first comprehensive evaluation of the PAXgene tissue fixation system in oral tissues. This study concludes that the PAXgene tissue fixation system can be applied to oral tissues to perform diagnostic molecular pathology experiments without compromising the quality of the morphology or biochemistry of biomolecules.
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http://dx.doi.org/10.3390/biom11060889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232633PMC
June 2021

Comparative evaluation of proliferative potential and replicative senescence associated changes in mesenchymal stem cells derived from dental pulp and umbilical cord.

Cell Tissue Bank 2021 Apr 26. Epub 2021 Apr 26.

Department of Oral and Dental Sciences, JIS University, Kolkata, India.

Mesenchymal stem cells (MSC) have been widely studied for tissue regeneration and cell-based therapy. MSC can be isolated from different body tissues while several biological waste sources like dental pulp, umbilical cord, cord derived blood, amniotic fluid or urine have also emerged as potential sources of MSCs. Specifically, isolation of MSCs from such non-conventional sources show promising outcomes due to the non-invasiveness of the extraction process and high proliferation capacity of the isolated MSC. However, these stem cells also exhibit the limitation of replicative senescence in long-term culture condition. Inter-cellular reactive oxygen species is an important contributor for inducing cellular senescence under long-term culture conditions. For translational application, it becomes imperative to compare the stem cells isolated from these sources for their senescence and proliferative properties. In this study, MSC were extracted from two different sources of biological waste materials-dental pulp and umbilical cord, and compared for their proliferation capacity and replicative senescence at different passage numbers (i.e. P2 and P6). Intracellular ROS production was significantly (p < 0.001) less in dental pulp stem cells culture in comparison to umbilical cord-derived stem cells at P6. The β-gal expression also showed significantly (p < 0.001) low expression in DPSC culture compared to that of UCSC at P6. The study indicates the source of stem cells influences the proliferation capacity as well as replicative senescence of MSCs. This study will thus pave the path of future research in selecting appropriate stem cell source for regenerative medicine application.
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http://dx.doi.org/10.1007/s10561-021-09926-8DOI Listing
April 2021

Quantitative in situ imaging and grading of oral precancer with attenuation corrected-optical coherence tomography.

Oral Oncol 2021 Jun 16;117:105216. Epub 2021 Feb 16.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, India.

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http://dx.doi.org/10.1016/j.oraloncology.2021.105216DOI Listing
June 2021

Pathophysiological relationship between hypoxia associated oxidative stress, Epithelial-mesenchymal transition, stemness acquisition and alteration of Shh/ Gli-1 axis during oral sub-mucous fibrosis and oral squamous cell carcinoma.

Eur J Cell Biol 2021 Jan 23;100(1):151146. Epub 2020 Dec 23.

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.

Oral sub-mucous fibrosis (OSF) is a pathophysiological state of oral cavity or oropharynx having a high chance of conversion to oral squamous cell carcinoma (OSCC). It involves fibrotic transformation of sub-epithelial matrix along with epithelial abnormalities. The present work aims to unveil the mechanistic domain regarding OSF to OSCC conversion exploring the scenario of hypoxia associated oxidative stress, epithelial-mesenchymal transition (EMT), metastasis and stemness acquisition. The study involves histopathological analysis of the diseased condition along with the exploration of oxidative stress status, assessment of mitochondrial condition, immunohistochemical analysis of HIF-1α, E-cadherin, vimentin, ERK, ALDH-1, CD133, Shh, Gli-1 and survivin expressions in the oral epithelial region together with the quantitative approach towards collagen deposition in the sub-epithelial matrix. Oxidative stress was found to be associated with type-II EMT in case of OSF attributing the development of sub-epithelial fibrosis and type-III EMT in case of OSCC favoring malignancy associated metastasis. Moreover, the acquisition of stemness during OSCC can also be correlated with EMT. Alteration of Shh and Gli-1 expression pattern revealed the mechanistic association of hypoxia with the phenotypic plasticity and disease manifestation in case of OSF as well as OSCC. Shh/ Gli-1 signaling can also be correlated with survivin mediated cytoprotective phenomenon under oxidative stress. Overall, the study established the correlative network of hypoxia associated oxidative stress, EMT and manifestation of oral pre-cancerous and cancerous condition in a holistic approach that may throw rays of hope in the therapeutic domain of the concerned diseases.
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http://dx.doi.org/10.1016/j.ejcb.2020.151146DOI Listing
January 2021

Epithelial Distribution of E-Cadherin, p63, and Mitotic Figures in ApoTome Images to Determine the Oncogenic Potentiality of Oral Submucous Fibrosis.

Microsc Microanal 2020 12;26(6):1198-1210

Centre for Biomaterials, Cellular and Molecular Theranostics, Vellore Institute of Technology, Room No. 402, ALM Building, Vellore632014, Tamil Nadu, India.

The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann–Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.
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http://dx.doi.org/10.1017/S1431927620024538DOI Listing
December 2020

Multifractal Alterations in Oral Sub-Epithelial Connective Tissue During Progression of Pre-Cancer and Cancer.

IEEE J Biomed Health Inform 2021 01 5;25(1):152-162. Epub 2021 Jan 5.

Bright-field microscopy (BFM) encrypts the optical transillumination profile of the transmitted light attenuated by the complex micro-structural tissue convolutions, manifested by the dense and compact regions of the specimen under examination. The connotations of idiosyncratic tissue interaction dynamics with the onset of pre-cancerous activity are encoded in the BFM acquired oral mucosa histopathological images (OMHI). In the present study, our analysis is focused on the sub-epithelium region of the oral mucosa, which has high clinical significance but sparsely explored in the literature from the textural domain. Histopathology being the gold-standard technique till date, we have used the light microscopic histopathology images for tissue characterization. The tissue-index transmission patches (TITP) from the sub-epithelium region are cropped under the guidance of oral onco-pathologists. After that, the TITPs are characterized for its multi-scale spatial-deformation dynamics, while keeping the intrinsic anisotropic geometry, and local contour connectivity within tolerable limits. With recent studies exhibiting multifractal's potency in diverse biological system analysis, here, we exploit the 2D multifractal detrended fluctuation analysis (2D-MFDFA) on TITPs for exploring a discriminative set of multifractal signatures for healthy, oral potentially malignant disorders and oral cancer tissue sample. The predictive model's competency is validated on an experimentally collected corpus of TITP samples and substantiated via confirmatory data statistics and analysis, showing its inter-class segregation efficacy. Moreover, the 2D-MFDFA analysis evinces the complex multifractal patterns in TITPs, which is due to the presence of composite long-range correlations in the oral mucosa tissue fabric.
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http://dx.doi.org/10.1109/JBHI.2020.2997875DOI Listing
January 2021

Malignant potentiality assessment of oral submucous fibrosis through semi-quantitative approach.

J Oral Maxillofac Pathol 2020 Jan-Apr;24(1):188. Epub 2020 May 8.

Department of Mathematics, Indian Institute of Technology, Kharagpur, West Bengal, India.

Background: In the context of early diagnosis and prevention of oral cancer, precise assessment of malignant potentiality of the oral potentially malignant disorders, particularly oral submucous fibrosis (OSF) is crucial. Till date, the assessment of malignant potentiality suffers from predictive ambiguity due to the lack of precision in the gold standard techniques. This can be addressed by integrating heuristic domain knowledge with quantitative analysis.

Aim: The aim of this study is to propose an index for enhancing accuracy in malignant potentiality evaluation.

Materials And Methods: The present study analyzes important histomorphometric attributes (epithelial thickness, basal cell nuclear size, nuclear-to-cytoplasmic area ratio of basal cells, chromaticity of basal cell nucleus, thickness of basement membrane, ratio of vasculature in juxta-epithelial connective tissue [i.e., area covered by blood vessels/total area], collagen density in the lamina propria) of oral mucosa in dysplastic and nondysplastic OSF in association with relevant oncopathological appreciations (weightage of different features as suggested by oral pathologists) toward proposing a "Malignant Potentiality Index" (MPI).

Results: Analysis of variance and notch box plot analysis depict statistically significant differences ( < 0.0001) in the histopathological features among different study groups (normal oral mucosa, OSF without dysplasia, OSF with dysplasia). Histopathological observation of one OSF patient with calculated MPI is shown.

Conclusion: This newly proposed diagnostic cum prognostic decision-making parameter, the "MPI" may bring a value addition to the conventional diagnostic gold standard.
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http://dx.doi.org/10.4103/jomfp.JOMFP_297_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269314PMC
May 2020

Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour.

Proc Inst Mech Eng H 2020 May 5;234(5):486-495. Epub 2020 Feb 5.

Department of Mechanical Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India.

The extent to which load transfer in a diseased mandible with odontogenic tumour might influence the potential risk of pathological fracture has scarcely been investigated. The study sought to investigate the quantitative deviations in load transfer across healthy and cancer-affected (diseased) mandibles having odontogenic tumours. The effect of size of the tumours (small: 9 mm diameter, large: 19 mm diameter), and variation in bone mechanical (elastic) properties of the mandible on load transfer in cancer-affected mandibles during a mastication cycle have been investigated. Based on patient-specific computed tomography-scan datasets, detailed three-dimensional finite element models of healthy and diseased mandibles were developed. High stresses of 25-30 MPa and strains ∼700 µε were observed in the healthy mandible during the right molar bite. However, marginal deviations were observed in principal stress distributions in the diseased mandibles with small- and large-sized tumours, as compared to the healthy mandible. Maximum principal strains of ∼1474 µε were found in the body region adjacent to the symphysis region for small-sized tumour. Whereas for large-sized tumour, maximum strains of ∼2700 µε were observed in the right buccal regions. Reduction in Young's modulus due to different stages of odontogenic tumours had a localised effect on the principal stress distributions, but triggered an abrupt increase in the principal tensile strains. It appears that there is a potential risk of pathological fracture for large-sized odontogenic tumour, owing to high tensile stresses and strains.
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http://dx.doi.org/10.1177/0954411920904618DOI Listing
May 2020

Cigarette smoking promotes cancer-related transformation of oral epithelial cells through activation of Wnt and MAPK pathway.

Future Oncol 2019 Oct 31. Epub 2019 Oct 31.

Centre for Healthcare Science & Technology, Indian Institute of Engineering Science & Technology, Shibpur, West Bengal, India.

Study aims to investigate the effect of cigarette smoking on cancer-related transformation in oral epithelial cells of smokers through evaluating the alteration in Wnt/β-catenin and MAPK pathways. Exfoliated oral epithelial cells were collected from 138 subjects and categorized into nonsmokers, smokers and clinically diagnosed precancer and cancer patients. Real-time quantitative PCR was performed to detect the fold changes of related genes. Expressions of biomarkers were assessed using immunofluorescence and western blot. Study shows significant (p < 0.001) alteration in mRNA level of , , , , , and genes under cigarette smoking. Results suggested the progression of oral cancer under cigarette smoking occurs through multiple events and activation of canonical Wnt/MAPK pathways.
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http://dx.doi.org/10.2217/fon-2019-0338DOI Listing
October 2019

Elucidation of Differential Nano-Textural Attributes for Normal Oral Mucosa and Pre-Cancer.

Microsc Microanal 2019 10;25(5):1224-1233

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, West Bengal, India.

Computational analysis on altered micro-nano-textural attributes of the oral mucosa may provide precise diagnostic information about oral potentially malignant disorders (OPMDs) instead of an existing handful of qualitative reports. This study evaluated micro-nano-textural features of oral epithelium from scanning electron microscopic (SEM) images and the sub-epithelial connective tissue from light microscopic (LM) and atomic force microscopic (AFM) images for normal and OPMD (namely oral sub-mucous fibrosis, i.e., OSF). Objective textural descriptors, namely discrete wavelet transform, gray-level co-occurrence matrix (GLCM), and local binary pattern (LBP), were extracted and fed to standard classifiers. Best classification accuracy of 87.28 and 93.21%; sensitivity of 93 and 96%; specificity of 80 and 91% were achieved, respectively, for SEM and AFM. In the study groups, SEM analysis showed a significant (p < 0.01) variation for all the considered textural descriptors, while for AFM, a remarkable alteration (p < 0.01) was only found in GLCM and LBP. Interestingly, sub-epithelial collagen nanoscale and microscale textural information from AFM and LM images, respectively, were complementary, namely microlevel contrast was more in normal (0.251) than OSF (0.193), while nanolevel contrast was more in OSF (0.283) than normal (0.204). This work, thus, illustrated differential micro-nano-textural attributes for oral epithelium and sub-epithelium to distinguish OPMD precisely and may be contributory in early cancer diagnostics.
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http://dx.doi.org/10.1017/S1431927619014867DOI Listing
October 2019

Segmentation and analysis of surface characteristics of oral tissues obtained by scanning electron microscopy to differentiate normal and oral precancerous condition.

Tissue Cell 2019 Aug 16;59:82-87. Epub 2019 Jul 16.

Centre for Biomaterials, Cellular and Molecular Theranostics, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India. Electronic address:

Abnormal epithelial stratification is a sign of oral dysplasia and hence evaluation of surface characteristics of oral epithelial region can help in detection of cancerous progression. Surface characteristics can be better visualised by Scanning Electron Microscopy (SEM) in comparison to light microscopy. In our study we have developed automated image processing algorithms i.e. Gaussian with median filtering and Gradient filtering, using MATLAB 2016b, to segment the surface characteristics i.e. the ridges and pits in the SEM images of oral tissue of normal (13 samples) and Oral Submucous Fibrosis (OSF) (36 samples) subjects. After segmentation, quantitative measurement of the parameters like area, thickness and textural features like entropy, contrast and range filter of ridges as well as area of pit and the ratio of area of ridge vs. area of pit was done. Statistical significant differences were obtained in between normal and OSF study groups for thickness (p=0.0107), entropy (p<0.00001) and contrast of ridge (p<0.00001) for Gaussian with median filtering and for all the parameters except thickness of the ridge(p=1.386), for Gradient filtering. Thus, computer aided image processing by Gradient filter followed by quantitative measurement of the surface characteristics provided precise differentiation between normal and precancerous oral condition.
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http://dx.doi.org/10.1016/j.tice.2019.07.004DOI Listing
August 2019

Fe-exchanged nano-bentonite outperforms FeO nanoparticles in removing nitrate and bicarbonate from wastewater.

J Hazard Mater 2019 08 13;376:141-152. Epub 2019 May 13.

ICAR-Central Soil Salinity Research Institute, Karnal 132001, India.

Nitrate (NO) and bicarbonate (HCO) are harmful for the water quality and can potentially create negative impacts to aquatic organisms, crops and humans. This study deals with the removal of NO and HCO from contaminated wastewater using Fe-exchanged nano-bentonite and FeO nanoparticles. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, surface area measurement and particle size analysis revealed that the adsorbents fall under the nano-scale size range with high specific surface area, and Fe was successfully exchanged in the nano-bentonite clay. The kinetics of adsorption was well defined by pseudo-first order and pseudo-second order kinetic models for both NO and HCO. The Fe-exchanged nano-bentonite was a better performing adsorbent of the oxyanions than FeO nanoparticles. According to the Sips isothermal model, the Fe-exchanged nano-bentonite exhibited the highest NO and HCO adsorption potential of 64.76 mg g and 9.73 meq g, respectively, while the respective values for FeO nanoparticles were 49.90 mg g and 3.07 meq g. Thus, inexpensiveness and easy preparation process of Fe-exchanged nano-bentonite make it attractive for NO and HCO removal from contaminated wastewater with significant environmental and economic benefits.
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http://dx.doi.org/10.1016/j.jhazmat.2019.05.025DOI Listing
August 2019

Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes.

Histochem Cell Biol 2018 Jul 23;150(1):61-75. Epub 2018 Apr 23.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, 721 302, India.

Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses indicate that different states of OSF condition may be associated with different forms of competitiveness within epithelial neighbouring cells which might be responsible to shape the present and future of the pre-malignant condition. Analytical findings indicated association of atrophic epithelium with stress-driven competitive environment having low c-Myc, high-p53, and stable HIF-1α (the looser cells) which undergo apoptosis. Whereas, the cells with high c-Myc (winner cells) give rise to hyperplastic epithelium via possible mutation in p53. The epithelial dysplasia plausibly occurs due to clonal expansion of c-Myc and p53 positive supercompetitor cells. Present study proposes quantitative IHC along with neighbourhood analysis which might help us to dig deeper on to the interaction among epithelial cell population to provide a better understanding of field cancerization and malignant transformation of pre-malignancy.
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http://dx.doi.org/10.1007/s00418-018-1671-zDOI Listing
July 2018

Identification of α-enolase as a prognostic and diagnostic precancer biomarker in oral submucous fibrosis.

J Clin Pathol 2018 Mar 18;71(3):228-238. Epub 2017 Aug 18.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.

Aims: Diagnostic ambiguities regarding the malignant potentiality of oral submucous fibrosis (OSF), an oral precancerous condition having dysplastic and non-dysplastic isoforms are the major failure for early intervention of oral squamous cell carcinoma (OSCC) patients. Our goal is to identify proteomic signatures from biopsies that can be used as precancer diagnostic marker for patient suffering from OSF.

Methods: The high throughput techniques adopting de novo peptide sequencing (1D SDS-PAGE coupled nanoLC MALDI tandem mass spectrometry (MS/MS)-based peptide mass fingerprint), immunohistochemistry (IHC), Western blot (WB) and real-time PCR (RT-PCR) analysis are considered for such biomarker identification and multilevel validations.

Results: Alpha-enolase is identified as an overexpressed protein in biopsies of oral submucous fibrosis with dysplasia (OSFWD) compared with oral submucous fibrosis without dysplasia (OSFWT) and normal oral mucosa (NOM). Total proteome analysis of an overexpressed protein band around 47 kDa of OSFWD identifies 334 peptides corresponding to 61 human proteins. Among them α-enolase is identified as a prime protein with highest number of peptides (44 out of 334 peptides) and sequence coverage (66.4%). Furthermore, RT-PCR, WB and IHC analysis also show mRNA and tissue level upregulation of α-enolase in OSFWD validating α-enolase as precancer marker.

Conclusions: This study for the first time identifies and validates α-enolase as a novel biomarker for early diagnosis of malignant potentiality of OSF. Hence, the identified protein marker, α-enolase can help in early therapeutic intervention of OSF patients leading to the reduction of patient's pain, treatment cost and enhancement of patient's quality of life.
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http://dx.doi.org/10.1136/jclinpath-2017-204430DOI Listing
March 2018

Risk prediction for oral potentially malignant disorders using fuzzy analysis of cytomorphological and autofluorescence alterations in habitual smokers.

Future Oncol 2017 Mar 18;13(6):499-511. Epub 2016 Nov 18.

Centre for Healthcare Science & Technology, Indian Institute of Engineering Science and Technology Shibpur, Howrah-711103, India.

Aim: This study aims to develop a novel noninvasive method for early cancer trend diagnosis in habitual smokers by corroborating cytomorphological and autofluorescence alterations.

Materials & Methods: A total of 120 subjects were included and categorized into nonsmoker, smoker and clinically diagnosed oral potentially malignant disorder (OPMD) patients. Oral exfoliative epithelial cells were studied through differential interference contrast and fluorescence microscopy. Fuzzy trend analysis was performed using measured parameters for determining the risk factors among smokers.

Results: The risk assessment in this study showed a positive correlation of smoking duration with early cancer risk factors with a correlation co-efficient of 0.86.

Conclusion: Alterations in cellular morphology and autofluorescence intensities showed positive correlation with OPMD. The present study will benefit to investigate early prediction of OPMD among susceptible individuals.
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http://dx.doi.org/10.2217/fon-2016-0382DOI Listing
March 2017

Genome-wide mitochondrial DNA sequence variations and lower expression of OXPHOS genes predict mitochondrial dysfunction in oral cancer tissue.

Tumour Biol 2016 Sep 7;37(9):11861-11871. Epub 2016 Apr 7.

Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108, India.

Several studies reported that mtDNA mutations may play important roles in carcinogenesis although the mechanism is not clear yet. Most of the studies compared mtDNA sequences in a tumor with those in normal tissues from different individuals ignoring inter-individual variations. In this study, 271 SNPs, 7 novel SNPs (or SNVs), and 15 somatic mutations were detected in mtDNA of 8 oral cancer tissues with respect to reference (rCRS) and adjacent normal tissues, respectively, using Ion PGM next generation sequencing method. Most of the sequence variations (76 SNPs and 1 somatic) are present in D-loop region followed by CyB (36 SNPs), ATP6 (24 SNPs), ND5 (17 SNPs and 5 somatic), ND4 (18 coding and 2 somatic) and other non-coding and coding DNA sequences. A total of 53 and 8 non-synonymous SNPs and somatic mutations, respectively, were detected in tumor tissues and some of these variations may have deleterious effects on the protein function as predicted by bioinformatic analysis. Moreover, significantly low mtDNA contents and expression of several mitochondrial genes in tumor compared to adjacent normal tissues may have also affected mitochondrial functions. Taken together, this study suggests that mtDNA mutations as well as low expression of mtDNA coded genes may play important roles in tumor growth. Although the sample size is low, an important aspect of the study is the use of adjacent control tissues to find out somatic mutations and a change in the expression of mitochondrial genes, to rule out inter-individual and inter-tissue variations which are important issues in the study of mitochondrial genomics.
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http://dx.doi.org/10.1007/s13277-016-5026-xDOI Listing
September 2016

Nanomechanical signatures of oral submucous fibrosis in sub-epithelial connective tissue.

J Mech Behav Biomed Mater 2017 01 20;65:705-715. Epub 2016 Sep 20.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India.

Oral sub-mucous fibrosis (OSF), a potentially malignant disorder, exhibits extensive remodeling of extra-cellular matrix in the form of sub-epithelial fibrosis which is a possible sequel of assaults from different oral habit related irritants. It has been assumed that micro/nanobio-mechanical imbalance experienced in the oral mucosa due to fibrosis may be deterministic for malignant potential (7-13%) of this pathosis. Present study explores changes in mechanobiological attributes of sub-epithelial connective tissue of OSF and the normal counterpart. The atomic force microscopy was employed to investigate tissue topography at micro/nano levels. It documented the presence of closely packed parallel arrangement of dense collagen fibers with wide variation in bandwidth and loss of D-space in OSF as compared to normal. The AFM based indentation revealed that sub-epithelium of OSF tissue has lost its flexibility with increased Young's modulus, stiffness, adhesiveness and reduced deformation of the juxta-epithealial connective tissue towards the deeper layer. These significant variations in nano-mechanical properties of the connective tissue indicated plausible impacts on patho-physiological microenvironment. Excessive deposition of collagen I and diminished expression of collagen III, fibronectin along with presence of α-SMA positive myofibroblast in OSF depicted its pathological basis and indicated the influence of altered ECM on this pathosis. The mechanobiological changes in OSF were corroborative with change in collagen composition recorded through immunohistochemistry and RT-PCR. The revelation of comparative nanomechanical profiles of normal oral mucosa and OSF in the backdrop of their structural and cardinal molecular attributes thus became pivotal for developing holistic pathobiological insight about possible connects for malignant transformation of this pre-cancer.
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http://dx.doi.org/10.1016/j.jmbbm.2016.09.023DOI Listing
January 2017

Differential Behavior of Normal and Fibrotic Fibroblasts under the Synergistic Influence of Micropillar Topography and the Rigidity of Honey/Silk-Fibroin Substrates.

ACS Biomater Sci Eng 2016 Sep 2;2(9):1528-1539. Epub 2016 Aug 2.

Instability & Soft Patterning Lab, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal -721302, India.

We report differential proliferation behavior of normal and fibrosis associated human oral fibroblasts on micropillar honey embedded silk fibroin substrates (HSF). Oral fibroblasts of different origins manifest differences in proliferation rate, morphology, and the cytoskeletal arrangement on HSF substrates with distinct topography (H, D, and S), stiffness, and honey concentration. It is observed that the proliferation rate is maximized for normal and inhibited for fibrosis associated fibroblasts on a HSF substrate surface with moderate height of ∼8.5 μm and 2% honey concentration. Molecular expression analysis reveals decrease in c-myc and p53 expression in later cells validating the inhibition of their proliferation rate, which is further correlated with the decreased Col I and Col III expression on this substrate. A substrate with enhanced interspacing and intermediate mechanical stiffness (0.57 ± 0.32 μN/nm) favors strong adhesion and stable cell-matrix interaction for normal cells, while exhibiting negative influence on fibrotic fibroblasts with poor adhesion and spreading capability. Decrease in vimentin, fibronectin expression, and cytoskeleton reorganization justify the poor stability of later cells on the optimized substrate, thereby allowing selective modulation of normal and fibrosis associated fibroblasts under the synergistic influence of honey concentration, topography, and rigidity of HSF substrates. The work highlights the possible therapeutic efficacy of honey based micropatterned substrates as smart patches for fast wound healing and in minimizing the chances of recurrence of precancer post oral tumor resection surgeries.
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http://dx.doi.org/10.1021/acsbiomaterials.6b00292DOI Listing
September 2016

Expression deregulation of mir31 and CXCL12 in two types of oral precancers and cancer: importance in progression of precancer and cancer.

Sci Rep 2016 09 6;6:32735. Epub 2016 Sep 6.

Human Genetics Unit, Indian Statistical Institute, Kolkata, India.

Oral cancer generally progresses from precancerous lesions such as leukoplakia (LK), lichen planus (LP) and oral submucous fibrosis (OSMF). Since few of these precancers progress to cancers; it is worth to identify biological molecules that may play important roles in progression. Here, expression deregulation of 7 miRNAs (mir204, mir31, mir31*, mir133a, mir7, mir206 and mir1293) and their possible target genes in 23 cancers, 18 LK, 12 LP, 23 OSMF tissues compared to 20 healthy tissues was determined by qPCR method. Expression of mir7, mir31, mir31* and mir1293 was upregulated and that of mir133a, mir204 and mir206 was downregulated in cancer. Expression of most of these miRNAs was also upregulated in LK and LP tissues but not in OSMF. Expression deregulation of some of the target genes was also determined in cancer, LK and LP tissues. Significant upregulation of mir31 and downregulation of its target gene, CXCL12, in cancer, LK and LP tissues suggest their importance in progression of precancer to cancer. Expression upregulation of mir31 was also validated using GEO data sets. Although sample size is low, novelty of this work lies in studying expression deregulation of miRNAs and target genes in oral cancer and three types of precancerous lesions.
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http://dx.doi.org/10.1038/srep32735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011738PMC
September 2016

MicroRNA and target gene expression based clustering of oral cancer, precancer and normal tissues.

Gene 2016 Nov 8;593(1):58-63. Epub 2016 Aug 8.

Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata 700108, India. Electronic address:

Purpose: Development of oral cancer is usually preceded by precancerous lesion. Despite histopathological diagnosis, development of disease specific biomarkers continues to be a promising field of study. Expression of miRNAs and their target genes was studied in oral cancer and two types of precancer lesions to look for disease specific gene expression patterns.

Methods: Expression of miR-26a, miR-29a, miR-34b and miR-423 and their 11 target genes were determined in 20 oral leukoplakia, 20 lichen planus and 20 cancer tissues with respect to 20 normal tissues using qPCR assay. Expression data were, then, used for cluster analysis of normal as well as disease tissues.

Results: Expression of miR-26a and miR-29a was significantly down regulated in leukoplakia and cancer tissues but up regulated in lichen planus tissues. Expression of target genes such as, ADAMTS7, ATP1B1, COL4A2, CPEB3, CDK6, DNMT3a and PI3KR1 was significantly down regulated in at least two of three disease types with respect to normal tissues. Negative correlations between expression levels of miRNAs and their targets were observed in normal tissues but not in disease tissues implying altered miRNA-target interaction in disease state. Specific expression profile of miRNAs and target genes formed separate clusters of normal, lichen planus and cancer tissues.

Conclusion: Our results suggest that alterations in expression of selected miRNAs and target genes may play important roles in development of precancer to cancer. Expression profiles of miRNA and target genes may be useful to differentiate cancer and lichen planus from normal tissues, thereby bolstering their role in diagnostics.
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http://dx.doi.org/10.1016/j.gene.2016.08.011DOI Listing
November 2016

Fourier-transform-infrared-spectroscopy based spectral-biomarker selection towards optimum diagnostic differentiation of oral leukoplakia and cancer.

Anal Bioanal Chem 2015 Oct 5;407(26):7935-43. Epub 2015 Sep 5.

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, 721302, India.

In search of specific label-free biomarkers for differentiation of two oral lesions, namely oral leukoplakia (OLK) and oral squamous-cell carcinoma (OSCC), Fourier-transform infrared (FTIR) spectroscopy was performed on paraffin-embedded tissue sections from 47 human subjects (eight normal (NOM), 16 OLK, and 23 OSCC). Difference between mean spectra (DBMS), Mann-Whitney's U test, and forward feature selection (FFS) techniques were used for optimising spectral-marker selection. Classification of diseases was performed with linear and quadratic support vector machine (SVM) at 10-fold cross-validation, using different combinations of spectral features. It was observed that six features obtained through FFS enabled differentiation of NOM and OSCC tissue (1782, 1713, 1665, 1545, 1409, and 1161 cm(-1)) and were most significant, able to classify OLK and OSCC with 81.3 % sensitivity, 95.7 % specificity, and 89.7 % overall accuracy. The 43 spectral markers extracted through Mann-Whitney's U Test were the least significant when quadratic SVM was used. Considering the high sensitivity and specificity of the FFS technique, extracting only six spectral biomarkers was thus most useful for diagnosis of OLK and OSCC, and to overcome inter and intra-observer variability experienced in diagnostic best-practice histopathological procedure. By considering the biochemical assignment of these six spectral signatures, this work also revealed altered glycogen and keratin content in histological sections which could able to discriminate OLK and OSCC. The method was validated through spectral selection by the DBMS technique. Thus this method has potential for diagnostic cost minimisation for oral lesions by label-free biomarker identification.
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http://dx.doi.org/10.1007/s00216-015-8960-3DOI Listing
October 2015

Connecting cyto-nano-architectural attributes and epithelial molecular expression in oral submucous fibrosis progression to cancer.

J Clin Pathol 2015 Aug 2;68(8):605-13. Epub 2015 Jun 2.

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.

Objective: Problems in pre-cancer diagnosis complicate cancer theragnosis as well as life expectancy. There is uncertainty regarding malignant transformation of oral submucous fibrosis (OSF), an oral pre-cancer with dysplastic (OSFWD) and non-dysplastic (OSFWT) subtypes. Understanding the structural, molecular and physical aspects of epithelial homeostasis may be useful.

Materials And Methods: Histopathological grading of biopsy sections was performed using H&E staining. Alterations in epithelial surface architecture in different groups was evaluated using scanning electron microscopy (SEM). The expression of crucial epithelial genes (p63, CK-5/6, CK-10, E-cadherin and β-catenin) was studied by immunohistochemistry, Western blot and RT-PCR analysis.

Results: SEM observations revealed that the surface epithelial ridge pattern became thick and dense, and pit pattern gradually decreased in OSFWD and oral squamous cell carcinoma (OSCC). p63, ΔNp63 and CK-5/6 were up-regulated in OSFWD and OSCC but down-regulated in OSFWT. CK-10 was down-regulated in OSFWD compared to OSFWT. Cytoplasmic expression of E-cadherin and β-catenin was elevated in dysplastic and cancerous conditions. Moreover, statistical correlation between SEM features (ridges and pits) and molecular attributes demonstrated a significant positive relationship between the ridge-to-pit ratio and p63 population density (r=0.85) and the ridge-to-pit ratio and CK-5/6 intensity (r=0.63).

Conclusions: Molecular changes related to epithelial progressive maturation and cellular proliferation are correlated with concomitant alteration of epithelial surface architecture which helps to predict the malignant potentiality of OSF.
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http://dx.doi.org/10.1136/jclinpath-2014-202791DOI Listing
August 2015

NMR ((1)H and (13)C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect.

Biochem Biophys Res Commun 2015 Apr 11;459(4):574-8. Epub 2015 Mar 11.

School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal, India. Electronic address:

At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using (1)H and (13)C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but d-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect.
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http://dx.doi.org/10.1016/j.bbrc.2015.02.149DOI Listing
April 2015

Computer-aided molecular pathology interpretation in exploring prospective markers for oral submucous fibrosis progression.

Head Neck 2016 May 29;38(5):653-69. Epub 2015 Jun 29.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India.

Background: Evaluation of molecular pathology markers using a computer-aided quantitative assessment framework would help to assess the altered states of cellular proliferation, hypoxia, and neoangiogenesis in oral submucous fibrosis and could improve diagnostic interpretation in gauging its malignant potentiality.

Methods: Immunohistochemical (IHC) expression of c-Myc, hypoxia-inducible factor-1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), VEGFRII, and CD105 were evaluated in 58 biopsies of oral submucous fibrosis using computer-aided quantification. After digital stain separation of original chromogenic IHC images, quantification of the diaminobenzidine (DAB) reaction pattern was performed based on intensity and extent of cytoplasmic, nuclear, and stromal expression.

Results: Assessment of molecular expression proposed that c-Myc and HIF-1α may be used as strong screening markers, VEGF for risk-stratification and VEGFRII and CD105 for prognosis of precancer into oral cancer.

Conclusion: Our analysis indicated that the proposed method can help in establishing IHC as an effective quantitative immunoassay for molecular pathology and alleviate diagnostic ambiguities in the clinical decision process.
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http://dx.doi.org/10.1002/hed.23962DOI Listing
May 2016

A quest for miRNA bio-marker: a track back approach from gingivo buccal cancer to two different types of precancers.

PLoS One 2014 15;9(8):e104839. Epub 2014 Aug 15.

Human Genetics Unit, Indian Statistical Institute, Kolkata, India.

Deregulation of miRNA expression may contribute to tumorigenesis and other patho-physiology associated with cancer. Using TLDA, expression of 762 miRNAs was checked in 18 pairs of gingivo buccal cancer-adjacent control tissues. Expression of significantly deregulated miRNAs was further validated in cancer and examined in two types of precancer (leukoplakia and lichen planus) tissues by primer-specific TaqMan assays. Biological implications of these miRNAs were assessed bioinformatically. Expression of hsa-miR-1293, hsa-miR-31, hsa-miR-31* and hsa-miR-7 were significantly up-regulated and those of hsa-miR-206, hsa-miR-204 and hsa-miR-133a were significantly down-regulated in all cancer samples. Expression of only hsa-miR-31 was significantly up-regulated in leukoplakia but none in lichen planus samples. Analysis of expression heterogeneity divided 18 cancer samples into clusters of 13 and 5 samples and revealed that expression of 30 miRNAs (including the above-mentioned 7 miRNAs), was significantly deregulated in the cluster of 13 samples. From database mining and pathway analysis it was observed that these miRNAs can significantly target many of the genes present in different cancer related pathways such as "proteoglycans in cancer", PI3K-AKT etc. which play important roles in expression of different molecular features of cancer. Expression of hsa-miR-31 was significantly up-regulated in both cancer and leukoplakia tissues and, thus, may be one of the molecular markers of leukoplakia which may progress to gingivo-buccal cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104839PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134240PMC
December 2015

Correlated analysis of semi-quantitative immunohistochemical features of E-cadherin, VEGF and CD105 in assessing malignant potentiality of oral submucous fibrosis.

Pathol Res Pract 2014 Dec 24;210(12):1054-63. Epub 2014 Jun 24.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India.

Oral submucous fibrosis, a potentially premalignant condition for oral squamous cell carcinoma, manifests both non-dysplastic and dysplastic grades. Early and specific identification of its malignant potentiality suffers from diagnostic limitations that may be addressed by correlated molecular pathology attributes having histopathological backdrop. Present study correlates expressional alteration in prime epithelial marker E-cadherin, with neo-angiogenic molecules viz. VEGF and CD105 for elucidation of malignant potentiality in different stages of oral submucous fibrosis. Sixty-eight incision biopsies from normal oral mucosa (n = 10), non-dysplastic (n = 18) and different dysplastic grades (n = 40) of oral submucous fibrosis were semi-quantitatively analyzed for immunohistochemical expressions of E-cadherin (membranous and cytoplasmic), VEGF and CD105 which were further statistically correlated. The loss of membranous E-cadherin with increase in cytoplasmic accumulation in differentiative layers of epithelium through the progression of dysplasia was noted along with up-regulation in VEGF expressions. The number of CD105(+) blood vessels and their major axis also showed significant increase from non-dysplasia toward higher grades of dysplasia. The positive correlation between deregulated expression of epithelial cell-cell adhesion molecule and increase in neo-angiogenic attributes of oral submucous fibrosis with increase in dysplastic grades indicated elucidatory potential of molecular expression features in assessment of malignant potentiality in oral submucous fibrosis.
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http://dx.doi.org/10.1016/j.prp.2014.06.009DOI Listing
December 2014

Association between risk of oral precancer and genetic variations in microRNA and related processing genes.

J Biomed Sci 2014 May 17;21:48. Epub 2014 May 17.

Human Genetics Unit, Indian Statistical Institute, 203, B,T, Road, Kolkata 700108, India.

Background: MicroRNAs have been implicated in cancer but studies on their role in precancer, such as leukoplakia, are limited. Sequence variations at eight miRNA and four miRNA processing genes were studied in 452 healthy controls and 299 leukoplakia patients to estimate risk of disease.

Results: Genotyping by TaqMan assay followed by statistical analyses showed that variant genotypes at Gemin3 and mir-34b reduced risk of disease [OR = 0.5(0.3-0.9) and OR = 0.7(0.5-0.9) respectively] in overall patients as well as in smokers [OR = 0.58(0.3-1) and OR = 0.68(0.5-0.9) respectively]. Among chewers, only mir29a significantly increased risk of disease [OR = 1.8(1-3)]. Gene-environment interactions using MDR-pt program revealed that mir29a, mir34b, mir423 and Xpo5 modulated risk of disease (p < 0.002) which may be related to change in expression of these genes as observed by Real-Time PCR assays. But association between polymorphisms and gene expressions was not found in our sample set as well as in larger datasets from open access platforms like Genevar and 1000 Genome database.

Conclusion: Variations in microRNAs and their processing genes modulated risk of precancer but further in-depth study is needed to understand mechanism of disease process.
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http://dx.doi.org/10.1186/1423-0127-21-48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035900PMC
May 2014

Computational analysis of p63(+) nuclei distribution pattern by graph theoretic approach in an oral pre-cancer (sub-mucous fibrosis).

J Pathol Inform 2013 31;4:35. Epub 2013 Dec 31.

School of Medical Science and Technology, Kharagpur, India.

Background: Oral submucous fibrosis (OSF) is a pre-cancerous condition with features of chronic, inflammatory and progressive sub-epithelial fibrotic disorder of the buccal mucosa. In this study, malignant potentiality of OSF has been assessed by quantification of immunohistochemical expression of epithelial prime regulator-p63 molecule in correlation to its malignant (oral squamous cell carcinoma [OSCC] and normal counterpart [normal oral mucosa [NOM]). Attributes of spatial extent and distribution of p63(+) expression in the epithelium have been investigated. Further, a correlated assessment of histopathological attributes inferred from H&E staining and their mathematical counterparts (molecular pathology of p63) have been proposed. The suggested analytical framework envisaged standardization of the immunohistochemistry evaluation procedure for the molecular marker, using computer-aided image analysis, toward enhancing its prognostic value.

Subjects And Methods: In histopathologically confirmed OSF, OSCC and NOM tissue sections, p63(+) nuclei were localized and segmented by identifying regional maxima in plateau-like intensity spatial profiles of nuclei. The clustered nuclei were localized and segmented by identifying concave points in the morphometry and by marker-controlled watersheds. Voronoi tessellations were constructed around nuclei centroids and mean values of spatial-relation metrics such as tessellation area, tessellation perimeter, roundness factor and disorder of the area were extracted. Morphology and extent of expression are characterized by area, diameter, perimeter, compactness, eccentricity and density, fraction of p63(+) expression and expression distance of p63(+) nuclei.

Results: Correlative framework between histopathological features characterizing malignant potentiality and their quantitative p63 counterparts was developed. Statistical analyses of mathematical trends were evaluated between different biologically relevant combinations: (i) NOM to oral submucous fibrosis without dysplasia (OSFWT) (ii) NOM to oral submucous fibrosis with dysplasia (OSFWD) (iii) OSFWT-OSFWD (iv) OSFWD-OSCC. Significant histopathogical correlates and their corroborative mathematical features, inferred from p63 staining, were also investigated into.

Conclusion: Quantitative assessment and correlative analysis identified mathematical features related to hyperplasia, cellular stratification, differentiation and maturation, shape and size, nuclear crowding and nucleocytoplasmic ratio. It is envisaged that this approach for analyzing the p63 expression and its distribution pattern may help to establish it as a quantitative bio-marker to predict the malignant potentiality and progression. The proposed work would be a value addition to the gold standard by incorporating an observer-independent framework for the associated molecular pathology.
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http://dx.doi.org/10.4103/2153-3539.124006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908487PMC
February 2014

An unusual presentation of medullary thyroid carcinoma.

Indian J Otolaryngol Head Neck Surg 2013 Jul 21;65(Suppl 1):195-8. Epub 2013 Feb 21.

Department of Otorhinolaryngology, Institute of Postgraduate Medical Education & Research (IPGME&R), 244B, Acharya J. C. Bose Road, Kolkata, 700020 India.

Medullary thyroid carcinoma (MTC) is extremely uncommon having varied presentations & their prognosis is not exactly known; but as MTC is an aggressive tumor hence it needs to be documented in literature to help to know the behaviour of this variant. We report a rare presentation of medullary carcinoma of thyroid in a 48 years old man who presented with huge swelling at left side of neck extending from parotid to supraclavicular region with normal-sized thyroid gland of long duration. FNAC & incision HPE of this swelling was inconclusive so we had operated this swelling. Immunohistochemistry reported it as metastatic Medullary carcinoma of thyroid; tumor cells express Cytokeratin, Calcitonin, EMA, Synaptophysin, Chromogranin-A. The stroma shows deposits of Amyloid, which have been confirmed by Congo red staining. Post-operatively FNAC from thyroid gland supported the diagnosis of Medullary carcinoma. Post-operatively the residual mass was regressed with chemotherapy & radiotherapy. The calcitonin level also decreased following this treatment. There was no recurrence at 11 months but ultimately patient died with metastasis.
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http://dx.doi.org/10.1007/s12070-013-0624-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718962PMC
July 2013

Minimyringoplasty: repair of small central perforation of tympanic membrane by fat graft: a prospective study.

Indian J Otolaryngol Head Neck Surg 2013 Dec 25;65(4):302-4. Epub 2012 Feb 25.

Department of ENT, IPGMER, Kolkata, 700 020 India.

Ear lobule fat was used as graft material for the closure of small size central perforation of tympanic membrane. We describe this procedure as minimyringoplasty. This study was done over a period of 2 year on fifty properly selected cases. Closure of perforation was found in 92% of cases within 2-3 months of surgery. Hearing gain was 7 dB on an average and morbidity was insignificant in successful cases.
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http://dx.doi.org/10.1007/s12070-011-0379-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851509PMC
December 2013
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