Metabolomic Profiling of Oral Potentially Malignant Disorders and Its Clinical Values.

Oral potentially malignant disorders (OPMD) are a group of lesions carrying the risk of developing into cancer. The gold standard to predict which lesions are more likely to undergo malignant transformation is the presence of dysplasia histologically. However, not all dysplastic lesions progress, and non-dysplastic lesions may also undergo malignant transformation.

A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite the advancement of current treatments, including surgery, chemotherapy, and radiotherapy, the overall survival rate of patients afflicted with HNSCC remains poor. The reasons for these poor outcomes are due to late diagnoses and patient-acquired resistance to treatment.

Dyskeratosis Congenita Links Telomere Attrition to Age-Related Systemic Energetics.

The underlying mechanisms of plasma metabolite signatures of human aging and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, and DKC1) and progressive telomere attrition. We analyzed the effect of telomere attrition on senescence-associated metabolites in fibroblast-conditioned media and DC patient plasma.

Extracellular Prostaglandins E1 and E2 and Inflammatory Cytokines Are Regulated by the Senescence Program in Potentially Premalignant Oral Keratinocytes.

Potentially pre-malignant oral lesions (PPOLs) are composed of keratinocytes that are either mortal (MPPOL) or immortal (IPPOL) in vitro. We report here that MPPOL, but not generally IPPOL, keratinocytes upregulate various extracellular tumor-promoting cytokines (interleukins 6 and 8) and prostaglandins E1 (ePGE1) and E2 (ePGE2) relative to normal oral keratinocytes (NOKs). ePGE upregulation in MPPOL was independent of PGE receptor status and was associated with some but not all markers of cellular senescence.

The Extracellular Metabolome Stratifies Low and High Risk Potentially Premalignant Oral Keratinocytes and Identifies Citrate as a Potential Non-Invasive Marker of Tumour Progression.

Premalignant oral lesions (PPOLs) which bypass senescence (IPPOL) have a much greater probability of progressing to malignancy, but pre-cancerous fields also contain mortal PPOL keratinocytes (MPPOL) that possess tumour-promoting properties. To identify metabolites that could potentially separate IPPOL, MPPOL and normal oral keratinocytes non-invasively in vivo, we conducted an unbiased screen of their conditioned medium. MPPOL keratinocytes showed elevated levels of branch-chain amino acid, lipid, prostaglandin, and glutathione metabolites, some of which could potentially be converted into volatile compounds by oral bacteria and detected in breath analysis.

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications.

Background: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC.

KRT13, FAIM2 and CYP2W1 mRNA expression in oral squamous cell carcinoma patients with risk habits.

Background: Expression of KRT13, FAIM2 and CYP2W1 appears to be influenced by risk habits, thus exploring the associations of these genes in oral squamous cell cancer (OSCC) with risk habits, clinico-pathological parameters and patient survival may be beneficial in identifying relevant biomarkers with different oncogenic pathways.

Materials And Methods: cDNAs from 41 OSCC samples with and without risk habits were included in this study. Quantitative real-time PCR was used to analyze KRT13, FAIM2 and CYP2W1 in OSCC.

Overexpression of MMP13 is associated with clinical outcomes and poor prognosis in oral squamous cell carcinoma.

Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples.

High serum level of retinol and α-tocopherol affords protection against oral cancer in a multiethnic population.

Background: A comparative cross-sectional study involving oral cancer patients and healthy individuals was designed to investigate associations between retinol, α-tocopherol and β-carotene with the risk of oral cancer.

Materials And Methods: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopherol and β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively.

Distinct pattern of chromosomal alterations and pathways in tongue and cheek squamous cell carcinoma.

Background: The purpose of this study was to investigate the cause of behavioral difference between tongue and cheek squamous cell carcinomas (SCCs) by verifying the copy number alterations (CNAs).

Methods: Array comparative genomic hybridization (aCGH) was used to profile unique deletions and amplifications that are involved with tongue and cheek SCC, respectively. This was followed by pathway analysis relating to CNA genes from both sites.

Genetic alterations of chromosome 8 genes in oral cancer.

The clinical relevance of DNA copy number alterations in chromosome 8 were investigated in oral cancers. The copy numbers of 30 selected genes in 33 OSCC patients were detected using the multiplex ligation-dependent probe amplification (MLPA) technique. Amplifications of the EIF3E gene were found in 27.

Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9.

Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH).

Novel MDM2 splice variants identified from oral squamous cell carcinoma.

Introduction: The presence of a variety of MDM2 splice variants has been reported in a range of different tumor types and is associated with poor patient prognosis. Furthermore, several MDM2 variants have been shown to have oncogenic properties. Despite this, MDM2 splice variants have not been comprehensively characterized in oral squamous cell carcinoma (OSCC).

Combined effects of isothiocyanate intake, glutathione S-transferase polymorphisms and risk habits for age of oral squamous cell carcinoma development.

Dietary isothiocyanates (ITCs) found in cruciferous vegetables (Brassica spp.) has been reported to reduce cancer risk by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). This case-control study was aimed at determining associations between dietary ITCs, GSTs polymorphisms and risk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with oral cancer in 115 cases and 116 controls.

MDM2 SNP309 does not confer an increased risk to oral squamous cell carcinoma but may modulate the age of disease onset.

The MDM2 SNP309 has been associated with increased expression of the protein which could suppress p53 function, and has been shown to modulate risk to cancer. We have previously shown that overexpression of MDM2 is a common event in oral cancers. In the present study, we determined the association between the MDM2 SNP309 polymorphism and oral cancer in 207 oral cancer patients and 116 normal subjects.