The role of basic fibroblast growth factor in oral submucous fibrosis pathogenesis

Bishen, Kundendu Arya; Radhakrishnan, Raghu; Satyamoorthy, Kapaettu

doi:10.1111/j.1600-0714.2008.00649.x

Cited by 41 publications

(41 citation statements)

References 24 publications

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“…This suggests that arecoline induces TGF β in epithelial cells and furthermore this is observed only in epithelial cells but not in human gingival fibroblast cells, indicating that epithelial cells could be the source of TGF β in OSF. We have confirmed the above finding with one of our studies, that OSF is a epithelial driven disease as the early signals are given to epithelial cells to secrete TGF β through αvβ 6 integrin and the expression of TGF β disappears when the drug tropicamide blocks αvβ6 integrin [28]. Phosphorylation of SMAD-2 was observed following treatment of epithelial cells by catechin, tannin and alkaloids, hence the authors state that arecanut mediated activation of p-SMAD-2 involves upregulation and activation of TGF β [27].…”

Section: Growth Factors and Inflammatory Cytokinessupporting

confidence: 88%

“…Nuclear positivity for phosphorylated SMAD 2 was found in lesional keratinocytes as well, suggesting the role of TGF-β 1 in inhibiting the epithelial growth and thereby causing pronounced epithelial atrophy in OSF. Analyzing the findings of the entire study we concluded that the pathogenesis of OSF may be epithelial-driven and involve arecoline-dependent up-regulation of αvβ 6 integrin [28]. αvβ 6 integrin is discussed in more detail later in the review under malignant transformation.…”

Section: Growth Factors and Inflammatory Cytokinesmentioning

confidence: 92%

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Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation

Ekanayaka¹,

Tilakaratne²

2013

J Carcinog Mutagen

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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.

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Section: Growth Factors and Inflammatory Cytokinessupporting

confidence: 88%

Section: Growth Factors and Inflammatory Cytokinesmentioning

confidence: 92%

Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation

Ekanayaka¹,

Tilakaratne²

2013

J Carcinog Mutagen

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“…Consistent with the above finding overexpression of p53 in the nuclei of epithelial cells of PHT induced GO tissues have been observed (Saito, 1999). Both the overexpression of mitogenic factors and p53 has been observed in oral dysplastic and precancerous lesions, and has been frequently associated with the development of a wide range of carcinomas including OSCCs (Haque, 1998;Wakulich, 2002;Abbas, 2007;Angiero, 2008;Bishen, 2008;Pai, 2009;). Incidentally, cyclosporine-an immunosuppressant and nifedepine-a calcium channel blocker induce GO and OSCCs have been reported to arise from these tissues as well (Varga, 1991;Pahor, 1996).…”

Section: Introductionsupporting

confidence: 69%

Lack of Mutation in p53 and H-ras Genes in Phenytoin Induced Gingival Overgrowth Suggests its Non Cancerous Nature

Jayaraman¹,

Valiathan²,

Jayakumar³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: There have been case reports of oral squamous cell carcinoma arising from gingival overgrowth induced by phenytoin -an antiepileptic drug. However, a detailed analysis for the presence of mutations in p53 and ras genes, which are the two most frequently mutated genes in cancers, in phenytoin induced gingival overgrowth tissues has hitherto not been performed. Methods: Cellular DNA isolated from twenty gingival overgrowth tissues collected from patients undergoing phenytoin therapy were amplified using primers for p53 (exons 5-8) and H-ras (exons 1-2) genes. The PCR amplicons were then gel purified and subjected to direct sequencing analysis to screen for mutations. Results: Direct sequencing of twenty samples of phenytoin induced gingival growth did not identify mutations in any of the exons of p53 and H-ras genes that were analyzed. Conclusion: Our result indicates that mutational alteration of p53 and H-ras genes is infrequent in phenytoin induced gingival growth, which thus suggests a non malignant nature of this pathology. The findings in the present study are clinically significant as a large number of epileptic patients are treated with phenytoin.

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“…50 In the present study, we suggest that the folic acid deficiency is probably due to poor or insufficient intake of folic acid-containing diet because OSF patients usually have functional impairment in food intake and chewing. Further studies are necessary to explore the real causes resulting in vitamin B 12 and folic acid deficiencies in OSF patients.…”

Section: Discussionmentioning

confidence: 98%

High frequencies of vitamin B12 and folic acid deficiencies and gastric parietal cell antibody positivity in oral submucous fibrosis patients

Wang

Cheng

et al. 2015

Journal of the Formosan Medical Association

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The role of basic fibroblast growth factor in oral submucous fibrosis pathogenesis

Cited by 41 publications

References 24 publications

Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation

Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation

Lack of Mutation in p53 and H-ras Genes in Phenytoin Induced Gingival Overgrowth Suggests its Non Cancerous Nature

High frequencies of vitamin B12 and folic acid deficiencies and gastric parietal cell antibody positivity in oral submucous fibrosis patients

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