Cancer chemoprevention by Metformin Hydrochloride compared to placebo in oral potentially malignant lesions : A randomized clinical trial (part I) / Ahmed Adel Mohamed Abdelazim ; Supervised Fat{u2019}heya Mohamed Zahran , Gihane Gharib Madkor , Heba Ahmed Farrag

Thesis (Ph.D.) - Cairo University - Faculty of Oral and Dental Medicine - Department of Periodontology

Aim: The aim of this study was to compare the effect of metformin hydrochloride on potentially malignant to placebo regarding its efficacy in regression or suppression of the progress into frank cancer. Methodology: This trial was a multicentre, triple{u00AD}blind, placebo{u00AD}controlled, randomized phase II trial. 40 non{u00AD}diabetic adult patients clinically and histologically diagnosed with OPMD were enrolled into the study. Eligible patients were randomly assigned (1:1) to receive oral met{u00AD} formin (500 mg daily) or identical placebo tablets by a stratified computer{u00AD}based randomization method for a duration of 3 months. All patients, clinicians, and outcome assessors were masked to drug allocation until the end of the trial. Recommended standard health and dental care were given to both groups.Clinical data, biopsies, immunohistochemical staining of cyclin D1, and RT{u00AD}qPCR quantification of tissue and salivary miRNA{u00AD}21 were performed for all groups at baseline and at three months point. Results: The current study showed that metformin was effective as a cancer chemopreven{u00AD} tive agent in controlling some of the molecular mechanisms that could lead to the the malignant transformation of OPMDs. Clinical lesion size, nuclear expression of cyclin D1, and tissue and salivary levels of cancer{u00AD}associated miRNA{u00AD}21 showed a statistically significant reduction in the metformin group compared to the placebo group. Cyclin D1 and miRNA{u00AD}21 correlated well to the degree of epithelial dysplasia, while toluidine blue color intensity was of limited value as a prognostic aid in OPMD. miRNA{u00AD}21 demonstrated a positive correlation between tissue and saliva levels, highlighting the emerging role of salivary transcriptomics in the field of OPMDs and oral cancer

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