Professor, Department of Oral Pathologyemail@example.com
SGT Dental College Hospital & Research Institute, Gurgaon
Dr. Mohit Sharma, Professor, Dept. of Oral Pathology & Microbiology > 12 years of UG & PG teaching experience. > 38 publications in international & national journals of high repute (https://www.nature.com/articles/s41368-020-00090-5) [23 - Web of Science & 26 - Scopus]. Most of which are in the 1st quartile journal and a co-investigator in a couple of research grants. Scopus h-index-10-306 citations. Article featured in news reports: [pH Gradient Reversal: An Emerging Hallmark of Cancers. 1. https://www.eurekalert.org/news-releases/497464, 2. https://ecancer.org/en/news/8598-a-new-emerging-hallmark-of-cancer, 3. https://www.medindia.net/news/a-new-emerging-hallmark-of-cancer-ph-gradient-reversal-157259-1.htm]. Reviewer: 31 Verified Peer Reviews: https://www.webofscience.com/wos/author/record/L-5739-2019
Membership - IAOMP, ISDR & IDA
BDS, MDS (Oral Pathology)
Interested in research on potentially malignant disorders especially oral submucous fibrosis. Areas of Special Interest are Stem Cell Markers, Epigenetics.
Title:/Research Question: Potential two-way associations b/w oral cancer and cancer pain mediators: An unobserved vicious cycle or Correlation between the tumorigenesis and oral cancer pain: A narrative review Aim: To prove a bidirectional association between cancer and the molecular pain mediators Objective: 1. To identify the molecular markers of pain in lieu of the above 2. To characterize the role of these markers in cancer pathogenesis 3. To Schematically illustrate this relationship
Sachin C. Sarode, Nilesh Kumar Sharma, Gargi Sarode, Mohit Sharma, and Raghu Radhakrishnan
Medical Hypotheses, ISSN: 03069877, eISSN: 15322777, Volume: 165, Published: August 2022 Elsevier BV
Mohit Sharma, Mandana Donoghue, Radhika Pathiyal, and Raghu Radhakrishnan
Medical Hypotheses, ISSN: 03069877, eISSN: 15322777, Volume: 165, Published: August 2022 Elsevier BV
Zoufang Huang, Mohit Sharma, Aparna Dave, Yuqi Yang, Zhe-Sheng Chen and R. Radhakrishnan
Frontiers in Pharmacology, eISSN: 16639812, Published: 4 May 2022
A burning sensation on eating spicy foods purportedly supports the role of capsaicin, an active component of chili peppers, in the etiology of oral submucous fibrosis (OSF). Although the mast cell mediators and activated P2X receptors induce a constant burning sensation through an ATP-dependent mechanism, it is the activation of the transient receptor potential vanilloid 1 (TRPV-1) receptor by capsaicin that aggravates it. The molecular basis for the burning pain in OSF is thus attributable to the activation of TRPV1. There is overwhelming evidence that confirms capsaicin has more of a protective role in attenuating fibrosis and is potentially therapeutic in reversing conditions linked to collagen accumulation. The activation of TRPV-1 by capsaicin increases intracellular calcium ([Ca2+]i), upregulates AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT-1), to enrich endothelium-dependent vasodilation via endothelial nitric oxide synthase (eNOS). The induction of vasodilation induces antifibrotic effects by alleviating hypoxia. The antifibrotic effects of capsaicin are mediated through the upregulation of antioxidant enzymes, downregulation of inflammatory genes and suppression of new collagen fibril formation. Capsaicin also demonstrates an anticarcinogenic effect by upregulating the cytotoxic T cells and downregulating regulatory T cells through the inhibition of angiogenesis and promotion of apoptosis. Judicious administration of capsaicin with an appropriate delivery mechanism may have therapeutic benefits in reducing pain sensation, rendering antifibrotic effects, and preventing the malignant transformation of OSF. This paper provides an overview of the molecular basis of capsaicin and its therapeutic application as an antifibrotic and anticarcinogenic agent for the treatment of OSF. Graphical Abstract
Mohit Sharma, Smitha S. Shetty, and Raghu A. Radhakrishnan
Recent Patents on Anti-Cancer Drug Discovery, ISSN: 15748928, eISSN: 22123970, Pages: 66-79, Published: February 2022 Bentham Science Publishers Ltd.
Background: Smokeless Tobacco (SLT) contains 9 times more nicotine than Smoked Tobacco (SMT). The carcinogenic effect of nicotine is intensified by converting nicotine-to-nicotine- derived Nitrosamines (NDNs). Methods: A review of the literature was conducted with a tailored search strategy to unravel the novel pathways and mechanisms of nicotine-induced oral carcinogenesis. Results: Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release. Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance, and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers Ras/Raf-1/MEK1/ERK cascade, promoting anti-apoptosis and pro-proliferative effects. Furthermore, the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear localization of p-EGFR. Conclusion: Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of any carcinogenicity.
Padacherri Vethil Jishnu, Sangeetha U. Shenoy, Mohit Sharma, Aditi Chopra, and Raghu Radhakrishnan
Oral Diseases, ISSN: 1354523X, eISSN: 16010825, Published: 2022 Wiley
OBJECTIVES The objective of the study is to understand the role of experimentally validated miRNA contributing to the acquisition of oncogenic phenotype in oral submucous fibrosis by computation analysis METHODS: A comprehensive review was carried out to corroborate and summarize altered miRNA expression in oral submucous fibrosis by retrieving relevant publications querying MEDLINE, Web of Sciences, Embase, and Scopus. The association between the miRNA-mRNA was performed using miRTarBase 8.0. The visualization of the miRNA-mRNA interaction was plotted using Cytoscape. MIENTURNET was used for the pathway analysis. Enrichment analysis was carried out for elucidating the hierarchical functions of miRNAs related to the acquisition of biological processes involved in the development of cancer. RESULTS Thirteen miRNAs (hsa-miR-499a, hsa-miR-200b, hsa-miR-200c, hsa-miR-1246, hsa-miR-31, hsa-miR-10b, hsa-miR-21, hsa-miR-203, hsa-miR-455, hsa-miR-760, hsa-miR-623, hsa-miR-610, hsa-miR-509-3-5p) were found to be deregulated in OSF. A total of 371 experimentally validated genes were shown to be interacting with the OSF-associated miRNAs. The targets of antifibrotic and profibrotic miRNAs were enriched in the cancer-related pathways. CONCLUSIONS Dysregulated miRNA and its target genes illustrate the physiological role of miRNAs in fibrosis. Understanding the miRNA-mediated fibrotic signaling, and targetting the specific miRNA-target gene interaction might provide relevant cues to ameliorate the fibrotic disease.
Shweta Rehani, Naresh Raj, Prabhakar Jerrgal, Mohit Sharma, KundenduArya Bishen, and Ruchi Nagpal
Journal of Cytology, ISSN: 09709371, eISSN: 09745165, Pages: 225-230, Published: October-December 2021 Medknow
Introduction: Occupational exposure to petrol derivatives possesses an increased risk of various cancers including that of the oral mucosa. Scientific studies have shown the correlation of micronuclei assay (MN) with the cytogenotoxic changes in petrol station attendants. However, very few have reported the use of MN assay as a promising tool for assessing the impact of smoking in these workers. Aim: To explore the cytogenotoxic damage in exfoliated buccal cells obtained from petrol station attendants and control subjects using the MN assay along with additional effects due to smoking. Materials and Methods: The study comprised 60 males who were divided into Group I–IV with each having 15 subjects. These subjects were categorized as exposed smokers, exposed nonsmokers, unexposed smoker group, and unexposed nonsmokers. The MN and additional nuclear abnormalities (karyorrhexis [KH], binucleation [BN], pyknosis [P], and karyolysis [KL]) were calculated in PAP-stained slides. Results: Statistically higher mean frequencies of overall nuclear anomalies were observed in petrol pump workers in comparison with the control group. Petrol pump smokers carry the highest nuclear anomalies followed by non-exposed smokers than exposed non-smokers and the count was the least among unexposed non-smoker workers. Discussion and Conclusion: The present study indicated that the petrol pump workers are under higher cytogenotoxic damage. Also, smoking added to the frequency of damage. Thus, MN and other nuclear anomalies are in-vitro reliable biomarker assays available and should be routinely employed as a screening tool in their periodic medical evaluation.
Mohit Sharma, Keith D. Hunter, Felipe Paiva Fonseca, and Raghu Radhakrishnan
Head and Neck, ISSN: 10433074, eISSN: 10970347, Pages: 3153-3164, Published: October 2021 Wiley
Senescence is a common denominator in wound healing, fibrosis, and cancer. Although, senescence is transiently antifibrotic, when prolonged, promotes fibrosis and malignant transformation. Eligible studies indexed in MEDLINE, Embase and Web of Science were searched to understand the role of cellular senescence in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation. The senescence‐associated secretory phenotype (SASP) components like IL‐1, IL‐6, and GRO‐α induce double‐strand DNA breaks in keratinocytes and drive genetic instability. SASP derived from myofibroblasts induces epithelial–mesenchymal transition in OSF and facilitates cancer progression. The use of senolytics has been shown to eliminate senescent cells from the areas of fibrosis, thereby preventing malignancy. Naturally occurring agents such as apigenin and kaempferol inhibit SASP. Mechanistic insight into the emerging role of senescence in the pathogenesis of OSF and modalities to inhibit senescence‐associated antiapoptotic pathways as a supplementary therapy to prevent malignant transformation of OSF is underlined.
Mohit Sharma, Keith D. Hunter, Felipe Paiva Fonseca, Smitha Sammith Shetty, and Raghu Radhakrishnan
Archives of Oral Biology, ISSN: 00039969, eISSN: 18791506, Volume: 128, Published: August 2021 Elsevier BV
OBJECTIVE(S) The objective of the present manuscript is to elucidate the role of matrix stiffness in the malignant transformation of oral submucous fibrosis. DESIGN The role of matrix stiffness in several cancers including oral cancer was reviewed with a tailored search strategy using relevant keywords as per the Medline format. The role of molecular mediators, Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) was weighed in the context of OSF along two distinct pathways. RESULTS Increased matrix stiffness activates the transcriptional coactivators, YAP and TAZ shuttling between the nucleus and cytoplasm. YAP and TAZ, serve as mechanical transducers in promoting cell migration, invasion and epithelial-mesenchymal transition (EMT). The hypoxic microenvironment in the advanced stage of OSF promotes the migratory phenotype through mechanical memory. CONCLUSIONS Reprogramming of a stiff matrix has the potential to restore the Hippo-YAP/TAZ tumor suppressor pathway and reverse fibrosis-associated tumor development.
Raghu Radhakrishnan, SmithaSammith Shetty, Mohit Sharma, ShamaPrasada Kabekkodu, NV Anil Kumar, and Kapaettu Satyamoorthy
Journal of Carcinogenesis, ISSN: 09746773, eISSN: 14773163, Published: 2021 Medknow
Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a consequence of chronic inflammation and repair in response to injury. Persistent trauma of susceptible oral mucosa due to habitual chewing of betel quid resulting in zealous healing of the mucosal tissue is one plausible explanation for the onset of oral submucous fibrosis (OSF). The irreversibility and resistance of collagen to degradation and its high potential to undergo malignant change are a major reason for morbidity in OSF. Hence, early diagnosis and timely treatment are crucial to prevent the progression of OSF to malignancy. This review focuses on the mechanistic insight into the role of collagen cross-links in advancing fibrosis and possible therapeutic targets that bring about a reversal of fibrosis. These options may be beneficial if attempted as a specific therapeutic modality in OSF as is in organ fibrosis. The upregulation of lysyl oxidase and lysyl hydroxylase has been shown to exhibit the higher levels of the hydroxylysine aldehyde-derived cross-links in fibrosis and tumor stroma promoting the tumor cell survival, resistance, and invasion. The in silico analysis highlights the potential drugs that may target the genes regulating collagen crosslinking.
Mohit Sharma, Felipe Paiva Fonseca, Keith D. Hunter, and Raghu Radhakrishnan
International Journal of Oral Science, ISSN: 16742818, eISSN: 20493169, Published: 1 December 2020 Springer Science and Business Media LLC
Abstract The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.
Smitha Sammith Shetty, Mohit Sharma, Felipe Paiva Fonseca, Pradyumna Jayaram, Ankit Singh Tanwar, Shama Prasada Kabekkodu, Kapaettu Satyamoorthy, and Raghu Radhakrishnan
Japanese Dental Science Review, ISSN: 18827616, eISSN: 22136851, Pages: 97-108, Published: November 2020 Elsevier BV
Summary Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.
Aditi Chopra, Raghu Radhakrishnan, and Mohit Sharma
Critical Reviews in Microbiology, ISSN: 1040841X, eISSN: 15497828, Pages: 213-236, Published: 3 March 2020 Informa UK Limited
Abstract Porphyromonas gingivalis (P. gingivalis), a Gram-negative facultative anaerobe of the oral cavity, is associated with the onset of various adverse pregnancy outcomes. P. gingivalis is linked with the development of preeclampsia, preterm labour, spontaneous abortion, gestational diabetes, foetal growth restriction, and misconception. The unique virulence factors, surface adhesions, enzymes of P. gingivalis can directly injure and alter the morphology, microbiome the foetal and maternal tissues. P. gingivalis can even exaggerate the production of cytokines, free radicals and acute-phase proteins in the uterine compartment that increases the risk of myometrial contraction and onset of preterm labour. Although evidence confirms the presence of P. gingivalis in the amniotic fluid and placenta of women with poor pregnancy outcomes, the intricate molecular mechanisms by which P. gingivalis initiates various antenatal and postnatal maternal and foetal complications are not well explained in the literature. Therefore, the present review aims to comprehensively summarise and highlight the recent and unique molecular pathogenic mechanisms of P. gingivalis associated with adverse pregnancy outcomes.
LC. Silva, FP. Fonseca, OP Almeida, BA. Mariz, MA. Lopes, R. Radhakrishnan, M. Sharma, LP. Kowalski, and PA. Vargas
Medicina Oral Patologia Oral y Cirugia Bucal, ISSN: 16984447, eISSN: 16986946, Pages: e49-e55, Published: January 2020 Medicina Oral, S.L.
Background The objective of this study investigated the distribution of immature dendritic cells (DCs), Langerhans cells and plasmacytoid DCs in oral submucous fibrosis (OSMF), OSMF associated with oral squamous cell carcinoma (OSMF-OSCC), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). Material and Methods Fourteen cases of OSMF, 9 of OSMF-OSCC, 8 of OL¸ 45 of OSCC and 8 of normal epithelium were retrospectively retrieved and their diagnoses confirmed. Immunoreactions against CD1a, CD207 e CD303 were performed and the number of positive cells quantified. Results A significant decrease of CD1a+ was found in OSMF (p≤0.05), OSMF-OSCC (p ≤ 0.01), and OSCC (p ≤ 0.001) when compared to normal epithelium. For CD207+ the significance decrease was observed in OSMF-OSCC (p ≤ 0.05), and OSCC (p ≤ 0.01) when compared with normal epithelium, and in OSMF when compared with OL (p ≤ 0.05). There was no significant difference for CD303, but increased in CD303+ was observed in OSCC when compared with normal epithelium. Conclusions The decrease in the number of CD1a+ and CD207+ cells may be associate to the development of oral OSCC, and in OPMDs they might be indicators of malignant transformation. Key words:Premalignant lesions, oral submucous fibrosis, oral squamous cell carcinoma, immune response.
Parul Sah, Pratik Patel, Chetana Chandrashekar, Suganthi Martena, Mamatha Ballal, Manjayya Hegde, Vasudeva Guddattu, Craig Murdoch, Mohit Sharma, and Raghu Radhakrishnan
Journal of Investigative and Clinical Dentistry, ISSN: 20411618, eISSN: 20411626, Published: 1 November 2019 Wiley
AIM The occurrence of oropharyngeal candidiasis (OPC) may be influenced by oral candidal carriage (OCC). Although OPC is strongly associated with low CD4+ cell count (400-700 cells/mm3 ) and a lack of highly active antiretroviral therapy (HAART), the effect of these two parameters on OCC is debatable. We investigated the oral candidal carriage, species diversity, antifungal susceptibility and the association of OCC with CD4+ cell count and HAART. METHODS Oral candidal isolates from 120 HIV+ patients (60 receiving and 60 not receiving HAART) and 60 healthy controls were quantified, and their species determined using standard culture and biochemical methods, followed by antifungal susceptibility testing using the agar dilution method. RESULTS The OCC was significantly higher in HIV+ patients; Candida albicans was the most frequently isolated species in both groups, followed by Candida tropicalis. Candidal density carriage correlated significantly with CD4+ cell count, but not with HIV and HAART status. Among the isolates from HIV+ patients, 35.4% showed reduced susceptibility to fluconazole. CONCLUSION HIV status results in significantly elevated rates of OCC C albicans remains the predominant pathogen, although other species are emerging rapidly. Resistance to fluconazole is on the rise, and more efficient treatment strategies need to be implemented.
Mohit Sharma and Raghu Radhakrishnan
Oral Oncology, ISSN: 13688375, eISSN: 18790593, Pages: 139-140, Published: October 2019 Elsevier BV
Mohit Sharma and Raghu Radhakrishnan
Oral Oncology, ISSN: 13688375, eISSN: 18790593, Published: May 2019 Elsevier BV
Mohit Sharma, Smitha S. Shetty, and Raghu Radhakrishnan
Recent Patents on Anti-Cancer Drug Discovery, ISSN: 15748928, eISSN: 22123970, Pages: 272-291, Published: 2018 Bentham Science Publishers Ltd.
BACKGROUND Oral submucous fibrosis is an oral potentially malignant disorder with high incidence of malignant transformation and rising global prevalence. However, the genesis of oral submucous fibrosis is still unclear despite superfluity of literature. In the background of ineffective treatment, it is necessary to decode its onset and progression before designing customized treatment regimens. OBJECTIVE The objective of this article is to decipher the pathogenesis of oral submucous fibrosis in order to identify novel drug targets. METHODS A thorough literature review based on oral submucous fibrosis being an overhealing wound was conducted; several related patents were identified and herewith reviewed. Necessary pathways were elaborated and deliberated in the manuscript in the form of schemas, keeping our hypothesis in mind. Several novel molecular targets were identified and discussed in detail. RESULTS Several patents demonstrating inhibition of fibrosis via chemokine ligand mimetics, anticonnexon antibodies, stem cell therapy, fibronectin blocking peptides, HIF inhibitors, recombinant erythropoietin, xanthine oxidase inhibitors, long non-coding RNAs, targeting inflammation, increasing TH-1/TH-2 cytokine ratio, t-box protein 4, chromium containing compositions, Iron-based nanocomposites, Lactate Dehydrogenase-5 inhibitors, Carbonic Anhdrase-9 inhibitors, proton pump inhibitors, liposomal encapsulated glutathione, monocarboxylate-4 inhibitors, autophagy inhibitors, Submucosal anti-IL-6 antibodies, fibrin degradation products for monitoring of malignancy and fibrosis, small molecule antagonists like vorapaxar, tiplaxtinin, and TM-5275, TGF-β signalling inhibitors were identified as future therapeutic avenues. CONCLUSION Considering, oral submucous fibrosis as an overhealing wound explains both pathogenesis and malignant transformation. Certainly, abnormalities in coagulation and fibrinolytic system are a common denominator in the profibrotic milieu and associated malignancy.
Journal of Clinical and Diagnostic Research, ISSN: 2249782X, eISSN: 0973709X, Pages: ZC28-ZC32, Published: 1 September 2017 JCDR Research and Publications
Introduction Micronuclei (MNi) are acentric chromatid or chromosome fragments produced via genetic damage through genotoxic agents contained in tobacco and betel nut. Evidently, the various Oral Potentially Malignant Disorders (OPMDs) like oral lichen Planus, oral leukoplakia and Oral Submucous Fibrosis (OSMF) demonstrate MNi, as a substantiation of genetic damage. As these changes can be easily appreciated in oral exfoliated cells, an exfoliated cell based MNi assay might be utilized as handy and non invasive biomonitoring tool for gauging the genetic damage and hence the propensity for malignant transformation in OPMDs. To this end, MNi are definitely easier to evaluate when compared to chromosome aberrations. Aim To compare the MNi frequency in normal mucosa, in individuals using various tobacco forms without oral leukoplakia, individuals using various tobacco forms with oral leukoplakia, and areca nut chewers with OSMF, using three different stains. Materials and Methods Oral exfoliated cells from 50 cases of normal mucosa (Group I), 50 cases of tobacco chewing people without Oral Leukoplakia (Group II), 50 cases of people with Oral Leukoplakia (Group III) and 50 cases of areca nut chewers with OSMF (Group IV) were taken. MNi frequencies were compared in these groups using three different stains i.e., Papanicolaou (PAP) stain, May Grunwald Giemsa (MGG) stain and Feulgen stain. The data between cases (Group II, III and IV) and control groups (Group I) was analyzed by Kruskal-Wallis Test. The comparison between two independent groups was done by Mann-Whitney U test and interstain comparison between cases and control was done by Wilcoxon Signed Rank Test and the individual p-value was obtained. Results A significant increase in the count was observed during transition of normal mucosa to OPMDs. The best stain for detecting MNi was PAP stain followed by MGG stain and Feulgen stain. Conclusion The higher mean MNi count for PAP stain and MGG stain could be attributed to nonspecific staining. Further study using a larger sample size on quantitative assessment of MNi count in various OPMDs is warranted.
A Thennavan, M Sharma, C Chandrashekar, K Hunter, and R Radhakrishnan
Oral Diseases, ISSN: 1354523X, eISSN: 16010825, Pages: 737-748, Published: September 2017 Wiley
Laser capture microdissection (LCM) is a high-end research and diagnostic technology that helps in obtaining pure cell populations for the purpose of cell- or lesion-specific genomic and proteomic analysis. Literature search on the application of LCM in oral tissues was made through PubMed. There is ample evidence to substantiate the utility of LCM in understanding the underlying molecular mechanism involving an array of oral physiological and pathological processes, including odontogenesis, taste perception, eruptive tooth movement, oral microbes, and cancers of the mouth and jaw tumors. This review is aimed at exploring the potential application of LCM in oral tissues as a high-throughput tool for integrated oral sciences. The indispensable application of LCM in the construction of lesion-specific genomic libraries with emphasis on some of the novel molecular markers thus discovered is also highlighted.
Mohit Sharma and Raghu Radhakrishnan
Journal of Oral Pathology and Medicine, ISSN: 09042512, eISSN: 16000714, Pages: 424-430, Published: July 2017 Wiley
Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch-mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia-mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)-mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF-1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored.
Mohit Sharma and Raghu Radhakrishnan
Oral Oncology, ISSN: 13688375, eISSN: 18790593, Pages: e10-e11, Published: May 2016 Elsevier BV
Mohit Sharma and Raghu Radhakrishnan
Oral Oncology, ISSN: 13688375, eISSN: 18790593, Pages: e1-e3, Published: 2016 Elsevier BV
Mohit Sharma, Madhusudan Astekar, Sonal Soi, Bhari Manjunatha, Devi Shetty, and Raghu Radhakrishnan
Recent Patents on Anti-Cancer Drug Discovery, ISSN: 15748928, eISSN: 22123970, Pages: 244-258, Published: 1 October 2015 Bentham Science Publishers Ltd.
Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer "pH gradient reversal". Normalizing pH gradient reversal through inhibition of various proton transporters such as Na(+)-H(+) exchanger (NHE), Vacuolar-type H(+)-ATPase (V-ATPase), H(+)/K(+)-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.
Mohit Sharma, Madhusudan Astekar, Sonal Soi, Bhari Manjunatha, and Devi Shetty
Recent Patents on Biomarkers, ISSN: 22103090, eISSN: 22103104, Pages: 25-34, Published: 1 June 2015 Bentham Science Publishers Ltd.
Raghu Radhakrishnan, Mohit Sharma, Parul Sah, and SonalSoi Sharma
Journal of Oral and Maxillofacial Pathology, ISSN: 0973029X, eISSN: 1998393X, Pages: 240-247, Published: May 2013 Medknow
Treatment planning for oral squamous cell carcinoma (OSCC) is based on the clinical TNM (Tumor, Node and Metastasis) classification. This system operates on the assumption that small tumours without clinical spread have a better prognosis than larger tumours with metastases. However, it is a well-known fact that some tumours with the same clinical staging show different growth patterns and clinical behaviour. This makes the prognosis for patients with OSCC difficult to predict on the basis of clinical staging alone. Although many histopathological characteristics of OSCC have been identified as prognostic factors, none is believed to be completely infallible. Therefore, a great need exists for more reliable prognostic markers, which will assist in treatment decisions. It is now well documented that several molecular events of significance for tumour spread, such as gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour–host interface or invasive front, where the deepest and presumably most aggressive cells reside. This review describes the various molecular events and interactions, which take place in the invasive front of the OSCC, and elucidates their role as prognostic markers.