Role of cell proliferation and vascularity in malignant transformation of potentially malignant disorders

Oral potentially malignant disorders are mucosal diseases with a significantly increased risk of squamous carcinoma development – a lethal and deforming disease with rising incidence, especially in young people. Despite the ability to recognise pre-cancer disorders in patients, clinicians remain unable to predict individual mucosal lesion behaviour or quantify the risk of malignant transformation. No clear management guidelines exist and the available scientific literature is unable to answer the fundamental question: does early diagnosis and interventional management treat pre-cancer effectively and prevent malignant transformation?

Download Full-text

TNFα Signaling Is Increased in Progressing Oral Potentially Malignant Disorders and Regulates Malignant Transformation in an Oral Carcinogenesis Model

Frontiers in Oncology ◽

10.3389/fonc.2021.741013 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jeffrey W. Chadwick ◽

Rachel Macdonald ◽

Aiman A. Ali ◽

Michael Glogauer ◽

Marco A. Magalhaes

Keyword(s):

Malignant Transformation ◽

Oncologic Outcomes ◽

Oral Potentially Malignant Disorders ◽

Critical Pathways ◽

Oral Carcinogenesis ◽

Multi Stage ◽

Potentially Malignant Disorders ◽

Potentially Malignant

Oral carcinogenesis represents a multi-stage process which encompasses several genetic and molecular changes that promote the progression of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinomas (OSCCs). A better understanding of critical pathways governing the progression of OMPDs to OSCCs is critical to improve oncologic outcomes in the future. Previous studies have identified an important role of tumor necrosis factor α (TNFα) and TNF receptor 1 (TNFR1) in the invasiveness of oral cancer cell lines. Here, we investigate the expression of TNFα and TNFR1 in human OPMDs that progress to OSCC compared to non-progressing OPMDs utilizing fluorescent immunohistochemistry (FIHC) to show increased TNFα/TNFR1 expression in progressing OPMDs. In order to interrogate the TNFα/TNFR1 signaling pathway, we utilized a 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis to demonstrate that TNFα/TNFR1 expression is upregulated in 4-NQO-induced OSCCs. TNFα neutralization decreased serum cytokines, inhibited the development of invasive lesions and reduced tumor-associated neutrophils in vivo. Combined, this data supports the role of TNFα in oral malignant transformation, suggesting that critical immunoregulatory events occur downstream of TNFR1 leading to malignant transformation. Our results advance the understanding of the mechanisms governing OSCC invasion and may serve as a basis for alternative diagnostic and therapeutic approaches to OPMDs and OSCC management.

Download Full-text

DNA Methylation Patterns in Saliva of Tobacco users with High-Risk Oral Potentially Malignant Disorders

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i32b31754 ◽

2021 ◽

pp. 129-137

Author(s):

Mimansha Patel ◽

Madhuri Nitin Gawande ◽

Minal Shashikant Chaudhary ◽

Alka Harish Hande

Keyword(s):

Dna Methylation ◽

High Risk ◽

Malignant Transformation ◽

Promoter Methylation ◽

Genomic Dna ◽

Premalignant Lesions ◽

Oral Potentially Malignant Disorders ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Methylation Patterns

Background: “Oral Potentially Malignant Disorder (OPMD)” is a well-known symptom that, if untreated, can be carcinogenic. It includes leukoplakia, erythroplakia or erythroleukoplakia. One of the typical premalignant lesions of the oral cavity is “oral leukoplakias (OLs),” which frequently precedes “OSCCs.”OLs with dysplastic characteristics are considered to be at a higher risk of “malignant transformation.” So, early diagnosis of "oral squamous cell carcinomas (OSCCs)" is desperately required to enhance patient prognosis and quality of life (QOL).As a result, we examined the distinctive promoter methylation presence in high-risk OLs. Objectives: To detect, compare & correlate “DNA methylation” patterns in normal individuals, tobacco users without disease and tobacco users with the disease. Methodology: With the participants' full consent, 48 saliva samples were obtained and prepared. DNA isolation, restriction digestion of genomic DNA, extraction of restriction enzyme digested genomic DNA, Polymerase Chain Reaction (PCR), and Agarose Gel Electrophoresis (AGE) were all carried out. Expected results: This study will help us to assess the use of Saliva as an aid to identifying both high and low risk “Oral Potentially Malignant Disorders.” Conclusion: Peculiar promoter methylation of various genes was related to a high possibility of malignant transformation in OLs.

Download Full-text