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Oral Submucous Fibrosis: Review On Mechanisms Of Pathogenesis And Malignant Transformation

R. Ekanayaka, W. Tilakaratne
Published 2013 · Medicine

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Studies focusing on epidemiology, histopathology and molecular biology/pathology on various aspects of oral submucous fibrosis (OSF), especially in the last decade have helped to understand the pathogenesis to a larger extent. In addition research in some aspects of carcinogenesis in the background of fibrosis has also advanced significantly in the recent past allowing us to understand the mechanisms involved in malignant transformation of the most prevalent oral potentially malignant disorder in South Asia. It has been shown that pathogenesis of OSF is directly related to arecoline present in arecanut and most of the alterations in various pathways and molecules leading to accumulation of collagen are mediated as a result of arecoline. Reduction of Matrix metalloproteinases (MMPs) and increased secretion of Tissue inhibitors of matrix metalloproteinases (TIMPs) play the most significant role in collagen accumulation whilst fibrogenic cytokines, mainly TGF-β over expression leads to increased production of collagen. There are various other pathways/molecules contributing to the pathogenesis in varying capacities. Malignant transformation in OSF has also been studied by various groups in the recent past. Role of arecanut as a carcinogen is proven beyond doubt with a large number of animal studies demonstrating its carcinogenicity, mutagenicity and genotoxicity. Studies involved in many molecules implicated in cell cycle regulation, hypoxia, processes leading to DNA double strand breaks, senescence and many other pathways related to carcinogenesis have shown ample evidence for the arecanut induced malignant transformation in OSF. Some of the findings in these studies may be helpful in inventing new treatment strategies for a common disease without an effective treatment up to date. Further, the understanding of mechanisms of malignant transformation may lead to early diagnosis of oral squamous cell carcinoma (OSCC) arising in the background of OSF.
This paper references
10.1177/00220345010800120601
Association between Genetic Polymorphism of Tumor Necrosis Factor-a and Risk of Oral Submucous Fibrosis, a Pre-cancerous Condition of Oral Cancer
C. Chiu (2001)
10.1016/S1368-8375(01)00003-3
Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives.
J. Jeng (2001)
10.1016/J.ORALONCOLOGY.2005.05.006
The upregulation of insulin-like growth factor-1 in oral submucous fibrosis.
C. tSai (2005)
10.1111/J.1600-0714.2005.00339.X
Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization.
Hiroko Utsunomiya (2005)
Characterisation and quantification of mucosal vasculature in oral submucous fibrosis.
R. Rajendran (2005)
10.1111/J.1600-0714.2005.00325.X
Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder.
P. Rajalalitha (2005)
10.1016/J.ORALONCOLOGY.2005.08.005
Oral submucous fibrosis: review on aetiology and pathogenesis.
W. Tilakaratne (2006)
10.1007/s10534-006-9013-3
Effect of areca nut on salivary copper concentration in chronic chewers
K. Raja (2006)
10.1186/1746-160X-2-33
Circulating Immune Complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial
S. Khanna (2006)
10.1016/J.TOX.2005.07.026
Prolonged exposure to arecoline arrested human KB epithelial cell growth: regulatory mechanisms of cell cycle and apoptosis.
Po-Hsuen Lee (2006)
10.1111/J.1601-0825.2006.01313.X
Treatment of oral submucous fibrosis by collagenase: effects on oral opening and eating function.
Lin Hj (2007)
10.4103/0970-9290.33783
Inducible nitric oxide synthase expression is upregulated in oral submucous fibrosis.
R. Rajendran (2007)
10.1016/J.CCA.2007.04.014
The role of epithelial-mesenchymal transition in oral squamous cell carcinoma and oral submucous fibrosis.
Hu Yanjia (2007)
10.1111/J.1601-0825.2006.01349.X
Molecular genetics of premalignant oral lesions.
S. Mithani (2007)
10.1111/J.1600-0714.2006.00491.X
Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: a follow-up study based in a Taiwanese hospital.
Shue-Sang Hsue (2007)
10.3760/J.ISSN:1002-0098.2007.07.012
[Effect of arecoline on the differentiation of myofibroblasts of oral mucosa].
Xia Li (2007)
Treatment of oral submucous fibrosis by collagenase: effects on oral opening and eating function.
H-J Lin (2007)
10.1016/J.ORALONCOLOGY.2006.08.009
The upregulation of cystatin C in oral submucous fibrosis.
Tsai Chung-Hung (2007)
10.3760/J.ISSN:1002-0098.2007.01.009
[Effects of arecoline and nicotine on the expression of hTERT in oral keratinocytes].
Y. Gao (2007)
2157 - 2518 JCM , an open access journal Oncogenomics of the Head and Neck between lysyl oxidase polymorphisms and oral submucous fibrosis in older male areca chewers
KB Raja (2007)
Oncogenomics of the Head and Neck between lysyl oxidase polymorphisms and oral submucous fibrosis in older male areca chewers
KB Raja (2007)
10.1111/j.1600-0714.2007.00609.x
An altered keratinocyte phenotype in oral submucous fibrosis: correlation of keratin K17 expression with disease severity.
A. Lalli (2008)
10.1016/j.oraloncology.2007.10.006
Polymorphisms of COX-2 -765G>C and p53 codon 72 and risks of oral squamous cell carcinoma in a Taiwan population.
Y. Lin (2008)
10.1111/j.1600-0714.2007.00625.x
Upregulation of HIF-1alpha in malignant transformation of oral submucous fibrosis.
W. Tilakaratne (2008)
10.1016/j.cellbi.2008.01.173
Phosphorylation of survivin Thr34 by p34cdc2 in the carcinogenesis of oral submucous fibrosis
Shang Hui Zhou (2008)
10.3321/J.ISSN:1002-0098.2008.03.012
[Application of bioinformatics tools in analysis of differentially expressed genes in oral submucosal fibrosis].
Yan-jia Hu (2008)
10.1111/j.1600-0714.2007.00633.x
The upregulation of heat shock protein 47 expression in human buccal fibroblasts stimulated with arecoline.
S. Yang (2008)
10.3892/OR_00000005
Gene expression profiling of oral submucous fibrosis using oligonucleotide microarray.
Yanjia Hu (2008)
10.1111/j.1600-0714.2008.00643.x
Fingerprinting genomic instability in oral submucous fibrosis.
M. Teh (2008)
10.1016/j.ijom.2008.01.004
Overexpression of COX-2 gene in oral cancer is independent of stage of disease and degree of differentiation.
M. Pandey (2008)
10.3321/J.ISSN:1002-0098.2008.12.002
[Molecules of G(2)/M phase and the phosphorylation of survivin in the carcinogenesis of oral submucosal fibrosis].
Shang-hui Zhou (2008)
10.1111/j.1600-0714.2008.00649.x
The role of basic fibroblast growth factor in oral submucous fibrosis pathogenesis.
K. Bishen (2008)
10.1016/j.oraloncology.2009.04.004
Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: Modulation by curcumin.
Yi-Ting Deng (2009)
10.1186/1471-2407-10-369
Synergistic effect of stromelysin-1 (matrix metalloproteinase-3) promoter (-1171 5A->6A) polymorphism in oral submucous fibrosis and head and neck lesions
A. Chaudhary (2009)
10.1111/j.1600-0714.2009.00758.x
Arecoline and oral keratinocytes may affect the collagen metabolism of fibroblasts.
L. Xia (2009)
10.1111/j.1600-0765.2008.01176.x
Regulation of oxidative-stress responsive genes by arecoline in human keratinocytes.
G. Thangjam (2009)
[Expression of loricrin and cytochrome P450 3A5 in oral submucous fibrosis and their significance].
N. Li (2009)
10.1177/0022034508329633
Transglutaminase-2 Regulation by Arecoline in Gingival Fibroblasts
G.S. Thangjam (2009)
Association Page 10 of 11 Citation: Ekanayaka RP, Tilakaratne WM (2013) Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation
TM Shieh (2009)
10.1016/j.oraloncology.2010.04.004
Immunohistochemical expression of CD34 for characterization and quantification of mucosal vasculature and its probable role in malignant transformation of atrophic epithelium in oral submucous fibrosis.
R. Desai (2010)
10.3353/OMP.15.21
Relationship of fibrosis and the expression of TGF-β1, MMP-1, and TIMP-1 with epithelial dysplasia in oral submucous fibrosis
R. Illeperuma (2010)
10.4103/0970-9290.70785
Matrix metalloproteinase-1 expression in oral submucous fibrosis: an immunohistochemical study.
G. Mishra (2010)
10.1016/j.tripleo.2009.10.054
Survivin as a potential early marker in the carcinogenesis of oral submucous fibrosis.
S. Zhou (2010)
10.4103/0970-9290.70815
Transforming growth factor-β-1 polymorphisms are infrequent but exist at selected loci in oral submucous fibrosis.
R. Rajendran (2010)
10.3969/j.issn.1672-7347.2010.06.006
[Expression of FHIT and MDM2 in oral submucous fibrosis and canceration tissues].
X. Yin (2010)
Cytokine expression by the treatment of areca nut extract in cultured fibroblasts: comparision between normal oral fibroblasts and hTERT transfected fibroblasts
Rasika P Illeperuma (2010)
10.3109/1354750X.2011.609602
Role of functional polymorphism of matrix metalloproteinase-2 (-1306 C/T and -168 G/T) and MMP-9 (-1562 C/T) promoter in oral submucous fibrosis and head and neck squamous cell carcinoma in an Indian population
A. Chaudhary (2011)
10.1016/j.etap.2010.09.006
Altered BRCA1 and BRCA2 responses and mutation of BRCA1 gene in mice exposed chronically and transgenerationally to aqueous extract of betel nut (AEBN).
Yashmin Choudhury (2011)
10.1177/1010539511419838
Assessment of Genetic Damage Among Chewers of Mixture Containing Mainly Areca Nut and Tobacco
M. Joshi (2011)
10.1111/j.2041-1626.2011.00055.x
Relationship between thickness of fibrosis and epithelial dysplasia in oral submucous fibrosis.
P. Jayasooriya (2011)
10.1016/j.semcancer.2011.09.001
Cellular senescence: a link between cancer and age-related degenerative disease?
J. Campisi (2011)
10.1021/jf104831n
Arecoline N-oxide: its mutagenicity and possible role as ultimate carcinogen in areca oral carcinogenesis.
Kuo-Hui Lin (2011)
10.1016/j.mehy.2011.07.049
Novel genetic biomarkers for susceptibility to oral submucous fibrosis: cytochrome P450 3A.
N. Li (2011)
10.1016/j.archoralbio.2010.08.012
Cytogenetic alterations in buccal mucosa cells of chewers of areca nut and tobacco.
M. Joshi (2011)
10.4317/MEDORAL.17083
Evaluation of serum copper and iron levels among oral submucous fibrosis patients.
Jyothi Tadakamadla (2011)
10.3109/08977194.2011.582839
Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis
I. Khan (2011)
10.3760/CMA.J.ISSN.1002-0098.2011.08.012
[A retrospective study of oral squamous cell carcinomas originated from oral submucous fibrosis].
F. Guo (2011)
10.4103/0970-9290.80009
Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral submucous fibrosis.
B. Sabarinath (2011)
10.1002/path.2786
Betel‐derived alkaloid up‐regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis
K. Moutasim (2011)
10.1002/path.2839
Senescent mesenchymal cells accumulate in human fibrosis by a telomere‐independent mechanism and ameliorate fibrosis through matrix metalloproteinases
G. Pitiyage (2011)
10.1007/s00784-011-0604-1
Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells
Shuei-Kuen Tseng (2011)
Role of TGF-Î2 and BMP7 in the pathogenesis of oral submucous fibrosis
I Khan (2011)
10.1111/j.1349-7006.2012.02294.x
Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma
Wen-Tsai Ji (2012)
10.1371/journal.pone.0051806
Activation of TGF-β Pathway by Areca Nut Constituents: A Possible Cause of Oral Submucous Fibrosis
I. Khan (2012)
10.4103/0973-1482.98970
Pathogenesis of oral submucous fibrosis.
S. Khan (2012)
10.3760/cma.j.issn.1002-0098.2012.12.012
[Expression of cytochrome P450 related genes in oral submucous fibrosis tissue].
H. Xie (2012)
10.4103/0971-5851.96966
Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature
S. Muttagi (2012)
10.5301/JBM.2012.9937
Correlation of epigenetic change and identification of risk factors for oral submucous fibrosis
Chun-jiao Xu (2012)
10.4103/1947-2714.93887
Malondialdehyde Levels in Oral Sub Mucous Fibrosis: A Clinicopathological and Biochemical Study
S. Shetty (2012)
10.1111/j.1600-0714.2011.01097.x
Association of XRCC1, XRCC3, and NAT2 polymorphisms with the risk of oral submucous fibrosis among eastern Indian population.
S. Mukherjee (2012)
10.1021/tx300252r
Direct-acting DNA alkylating agents present in aqueous extracts of areca nut and its products.
Chiung-Wen Hu (2012)
10.1007/s12105-012-0341-z
Evaluation of PTEN Immunoexpression in Oral Submucous Fibrosis: Role in Pathogenesis and Malignant Transformation
P. Angadi (2012)
10.1111/j.1600-0714.2012.01129.x
Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 (TIMPs -1 and -2) in fibroblasts are early indicators of oral sub-mucous fibrosis and ageing.
G. Pitiyage (2012)
10.1007/s00784-012-0713-5
EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts
Jenny Zwei-Chieng Chang (2012)
10.1007/s11033-012-1802-x
Association of CYP1A1, GSTM1, and GSTT1 gene polymorphism with risk of oral submucous fibrosis in a section of North Indian population
T. Ghosh (2012)
10.4103/0973-029X.98452
Salivary copper and zinc levels in oral pre-malignant and malignant lesions
B. Ayinampudi (2012)
Activation of TGF-Î2 pathway by areca nut constituents: a possible cause of oral submucous fibrosis
I Khan (2012)
10.1002/hed.23143
Oral squamous cell carcinoma arising in background of oral submucous fibrosis: a clinicopathologically distinct disease
P. Chaturvedi (2013)
10.1016/j.oraloncology.2012.12.004
Progression of precancerous lesions to oral cancer: results based on the Taiwan National Health Insurance Database.
I. Lian (2013)
10.4317/medoral.18226
Expression of transforming growth factor β and its correlation with lipodystrophy in oral submucous fibrosis: An immunohistochemical study
A. Kale (2013)
10.1016/j.gene.2012.10.043
CYP1AI and CYP2E1 gene polymorphisms may increase susceptibility to oral submucous fibrosis among betel quid chewers of eastern India.
S. R. Chaudhuri (2013)
10.1093/carcin/bgt012
Areca nut-induced buccal mucosa fibroblast contraction and its signaling: a potential role in oral submucous fibrosis--a precancer condition.
M. Chang (2013)
Areca nutinduced buccal mucosa fibroblast contraction and its signaling : a potential role in oral submucous fibrosisprecancer condition
MC Chang (2013)
57-69
Y Choudhury (2013)
Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation
R P Ekanayaka (2013)
JCM, an open access journal Oncogenomics of the Head and Neck between lysyl oxidase polymorphisms and oral submucous fibrosis in older male areca chewers
J Carcinogene Mutagene



This paper is referenced by
10.1007/s12105-020-01270-9
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10.1007/978-981-15-5483-4_44
Oral Potentially Malignant Disorders (OPMDs)
W. Tilakaratne (2021)
10.1016/j.oooo.2020.12.020
A clinicobiochemical evaluation of curcumin as gel and as buccal mucoadhesive patches in the management of oral submucous fibrosis.
Aditi Chandrashekar (2020)
10.4103/JMAU.JMAU_23_19
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Sandhya Tamgadge (2020)
Abstract. The molecular mechanism of oral submucous fibrosis (OSF) is yet to be fully elucidated. The identification of reliable signature genes to screen patients with a high risk of OSF and to provide oral cancer surveillance
Prithvi Kumar Singh (2020)
10.4103/ijabmr.IJABMR_222_19
The Stromal Dictators in a Concomitant Case of Oral Submucous Fibrosis - Oral Squamous Cell Carcinoma
Anupama Mukherjee (2020)
10.1016/j.jdsr.2020.07.002
Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma
S. Shetty (2020)
10.1080/01478885.2019.1594543
Expression and distribution pattern of podoplanin in oral submucous fibrosis with varying degrees of dysplasia – an immunohistochemical study
Monika Karunagaran (2019)
10.3329/kyamcj.v10i2.42783
Study On Outcome of Different Combination of Dexamethasone, Hyaluronidase and Placental Extract for Treatment of Oral Submucous Fibrosis
H. Hasan (2019)
10.5005/JP-JOURNALS-10024-2527
Evaluation of Therapeutic Efficacy of Different Treatment Modalities in Oral Submucous Fibrosis: A Comparative Study.
Beenakumary Tp (2019)
10.4103/jcrt.JCRT_522_17
Oral submucous fibrosis: An enigmatic morpho-insight
Alka Hande (2019)
10.4103/jomfp.JOMFP_239_18
Estimation of serum sialic acid in oral submucous fibrosis and oral squamous cell carcinoma
Samatha Chittemsetti (2019)
10.4103/ijdr.IJDR_186_17
Role of angiogenesis in oral submucous fibrosis using vascular endothelial growth factor and CD34: An immunohistochemical study
Ettishree Sharma (2019)
10.1111/jicd.12473
Immunoexpression of alpha smooth muscle actin correlates with serum transforming growth factor-β1 levels in oral submucous fibrosis.
I. Singh (2019)
10.4103/ams.ams_280_18
Carcinoma Arising in the Background of Oral Submucous Fibrosis
S. Rangaswamy (2019)
10.1007/s12253-019-00700-6
Expression of hTERT in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma – an Immunohistochemical Analysis
Lizbeth Raju K (2019)
10.1016/j.archoralbio.2018.10.016
Delineating metabolic dysfunction in cellular metabolism of oral submucous fibrosis using 1H nuclear magnetic resonance spectroscopy.
Vertika Rai (2019)
10.4103/jomfp.JOMFP_275_17
A retrospective study of clinicopathological features of oral squamous cell carcinoma with and without oral submucous fibrosis
S. Acharya (2019)
10.1155/2018/4154165
An Evaluation of Clinical and Histopathological Aspects of Patients with Oral Submucous Fibrosis in the Background of Oral Squamous Cell Carcinoma
B. S. M. S. Siriwardena (2018)
Effects of Ganoderma Lucidum on Palliative Cares In Oral Squamous Cell Carcinoma ( Oscc ) Patients : An Evidence of Excellent Postoperative Support for Cancer Patients *
Masud Hossain (2018)
10.31254/DENTISTRY.2018.3108
Assessment of utility of Tulsi and Turmeric in treatment of oral submucous fibrosis: A clinical study
Deepa Virani (2018)
10.15713/ins.mmj.26
Current state of research, diagnosis, staging and outcome of oral submucosal fibrosis
P. Patil (2018)
10.1016/j.jormas.2017.12.006
Thioctic acid in oral submucous fibrosis (India's disease) - A better tomorrow.
Gowri P Bhandarkar (2018)
10.3126/jngmc.v14i2.21542
Comparative Study of Intralesional Dexamethasone Plus Hyaluronidase & Oral Colchicine in Patients with Oral Submucous Fibrosis
G. Neupane (2018)
Histomorphometric Analysis of Epithelial Thickness and Mucosal Vasculature in Oral Submucous Fibrosis
D. S. Paul (2018)
10.26717/bjstr.2018.03.000924
An Insight into Oral Submucous Fibrosis
S. Kanneppady (2018)
10.1016/J.MGENE.2018.04.001
Role of matrix metalloproteinase-9 polymorphisms in basement membrane degradation and pathogenesis of oral submucous fibrosis
Atul Katarkar (2018)
10.4172/2157-2518.1000311
Assessment of Serum and Salivary Progranulin Levels in Oral Submucous Fibrosis
R. Swarnalakshmi (2018)
10.1007/978-3-319-14911-0_8
Oral Submucous Fibrosis
S. Warnakulasuriya (2017)
10.1016/j.oraloncology.2017.10.023
Evaluation of the diagnostic efficacy and spectrum of autofluorescence of benign, dysplastic and malignant lesions of the oral cavity using VELscope.
R. S. Ganga (2017)
CURCUMIN ORABASE IN THE MANAGEMENT OF ORAL SUBMUCOUS FIBROSIS: A NOVEL APPROACH.
R. Devaraju (2017)
10.5005/JP-JOURNALS-10054-0026
Effect of Areca Nut Consumption on Hypoxia-inducible Factor-1 Alfa Expression in Patients with Oral Squamous Cell Carcinoma
J. Prasad (2017)
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