MyMedR

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

Vincent-Chong VK, Salahshourifar I, Karen-Ng LP, Siow MY, Kallarakkal TG, Ramanathan A, et al.

ScientificWorldJournal, 2014;2014:897523.

PMID: 25401159 DOI: 10.1155/2014/897523

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. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P = 0.011) and tumor staging (P = 0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P < 0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC.

Evaluation of medicinal interventions for the management of oral submucous fibrosis: a systematic review of the literature

Awan KH, Patil S, Habib SR, Pejcic A, Zain RB

J Contemp Dent Pract, 2014 Nov 1;15(6):812-7.

PMID: 25825114

Oral submucous fibrosis is a chronic, progressive scarring disease associated with both significant morbidity including pain and limited mouth opening and an increased risk for malignancy. This systematic review evaluated the different medicinal (i.e. nonsurgical) interventions available for the management of oral submucous fibrosis. An automated literature searches of online databases from January 1960 to December 2013 were performed and only studies with high level of evidence based on the guidelines of the Oxford Centre for evidence-based medicine were selected. Thirteen studies (3 randomized controlled trials and 10 clinical trials/controlled clinical trials) were included and drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene were used. There is a clear lack of evidence on the available drug treatment for oral submucous fibrosis and further high quality randomized controlled trials are needed to evaluate the different therapeutic agents.

Fulltext Oral lichenoid reactions during antimalarial prophylaxis with sulphadoxine-pyrimethamine combination

Zain RB

Southeast Asian J. Trop. Med. Public Health, 1989 Jun;20(2):253-6.

PMID: 2609215

The prevalence of clinically observed oral lichenoid reaction in 186 Malay army personnel using Fansidar for 9 weeks was found to be 4.8%. The prevalence was found to be 0.5% in 186 army personnel who had stopped using Fansidar for 2 months and 0% in 143 army personnel (control group) who had not used Fansidar for at least 4 months. The lesion showed a higher prevalence for the gingiva. There was no correlation between cigarette smoking and the occurrence of these lesions in each group.

IARC Perspective on Oral Cancer Prevention

Bouvard V, Nethan ST, Singh D, Warnakulasuriya S, Mehrotra R, Chaturvedi AK, et al.

N Engl J Med, 2022 Nov 24;387(21):1999-2005.

PMID: 36378601 DOI: 10.1056/NEJMsr2210097

Proliferating cell nuclear antigen (PCNA) expression in oral squamous cell carcinoma - an aid to conventional histological grading?

Zain RB, Sakamoto F, Shrestha P, Mori M

Malays J Pathol, 1995 Jun;17(1):23-30.

PMID: 8907001

Proliferating cell nuclear antigen (PCNA) is a well known marker for cell proliferation. It tends to accumulate in the late G1 and S-phase of the cell cycle. A monoclonal antibody (MoAb) against PCNA is now available and it can react with paraffin-embedded specimens. In the present study, PCNA immunohistochemical staining of 36 cases of oral cancer specimens obtained from surgery were investigated. The results showed differing nuclear staining patterns for PCNA in normal, hyperplastic and dysplastic epithelium, early cancer and 3 levels of differentiation for squamous cell carcinoma of the oral cavity. It appears that PCNA can be a useful marker in delineating normal epithelium and hyperplastic epithelium from dysplasia in the oral cavity. The use of PCNA staining may further emphasize the conventional histopathological grading of well-differentiated, moderately-differentiated and poorly-differentiated oral squamous cell carcinoma but is still dependent on basic criteria as observed without immunostaining. PCNA expression for all grades of squamous cell carcinoma are present at the deep, infiltrative margins.

Defining a global research and policy agenda for betel quid and areca nut

Mehrtash H, Duncan K, Parascandola M, David A, Gritz ER, Gupta PC, et al.

Lancet Oncol, 2017 12;18(12):e767-e775.

PMID: 29208442 DOI: 10.1016/S1470-2045(17)30460-6

Betel quid and areca nut are known risk factors for many oral and oesophageal cancers, and their use is highly prevalent in the Asia-Pacific region. Additionally, betel quid and areca nut are associated with health effects on the cardiovascular, nervous, gastrointestinal, metabolic, respiratory, and reproductive systems. Unlike tobacco, for which the WHO Framework Convention on Tobacco Control provides evidence-based policies for reducing tobacco use, no global policy exists for the control of betel quid and areca nut use. Multidisciplinary research is needed to address this neglected global public health emergency and to mobilise efforts to control betel quid and areca nut use. In addition, future research is needed to advance our understanding of the basic biology, mechanisms, and epidemiology of betel quid and areca nut use, to advance possible prevention and cessation programmes for betel quid and areca nut users, and to design evidence-based screening and early diagnosis programmes to address the growing burden of cancers that are associated with use.

Fulltext Betel-quid dependence and oral potentially malignant disorders in six Asian countries

Lee CH, Ko AM, Yen CF, Chu KS, Gao YJ, Warnakulasuriya S, et al.

Br J Psychiatry, 2012 Nov;201(5):383-91.

PMID: 22995631 DOI: 10.1192/bjp.bp.111.107961

Despite gradual understanding of the multidimensional health consequences of betel-quid chewing, information on the effects of dependent use is scant.

Darier disease: a case report

Jalil AA, Zain RB, van der Waal I

Br J Oral Maxillofac Surg, 2005 Aug;43(4):336-8.

PMID: 15993288

The diagnosis of Darier disease of the oral mucosa was made only after biopsying a leukoplakia-like lesion of the palate.

m-Health for Early Detection of Oral Cancer in Low- and Middle-Income Countries

Haron N, Zain RB, Ramanathan A, Abraham MT, Liew CS, Ng KG, et al.

Telemed J E Health, 2020 03;26(3):278-285.

PMID: 31081720 DOI: 10.1089/tmj.2018.0285

Background:
Up to 86% of oral cancer (OC) patients present at the late stage where survival is dismal. Limited access to specialist diagnosis is a significant factor for late presentation. The increasing use of smartphones presents an opportunity to use digital technology to facilitate early detection of OC.
Aim:
To evaluate the feasibility of using Mobile Mouth Screening Anywhere (MeMoSA®) to facilitate early detection of OC.
Methods:
A mobile phone app named MeMoSA was developed and the feasibility of integrating this for documentation of oral lesions, and communication between dentists and specialists for management decisions were evaluated. The experience of dentists and specialists in using MeMoSA was determined using qualitative questionnaires.
Results:
Communication between specialist and dentists using MeMoSA stratified cases and streamlined referral of patients. Twelve of 48 patients were found to have oral lesions or signs suspicious of cancer and 3 required referrals. The patient's compliance for referral was tracked with MeMoSA. All dentists agreed that MeMoSA could facilitate early detection of OC and believed that MeMoSA could assist in the identification of oral mucosal lesions through direct communication with specialists and continuous learning in the recognition of high-risk lesions.
Conclusions:
MeMoSA has the potential to be used to promote equitable health care and streamline patient management that could result in early detection of OC.

Mobile Phone Imaging in Low Resource Settings for Early Detection of Oral Cancer and Concordance with Clinical Oral Examination

Haron N, Zain RB, Nabillah WM, Saleh A, Kallarakkal TG, Ramanathan A, et al.

Telemed J E Health, 2017 03;23(3):192-199.

PMID: 27541205 DOI: 10.1089/tmj.2016.0128

INTRODUCTION: This study examined the concordance in clinical diagnosis of high-risk lesions in the oral cavity and referral decisions between clinical oral examination (COE) and teledentistry.

MATERIALS AND METHODS: Sixteen individuals with a range of oral potentially malignant disorders (OPMD) and normal oral mucosa were included. Five areas of the oral cavity were photographed by three dentists using mobile phone cameras with 5 MP-13 MP resolutions. On the same day, the patients were given COE by two oral medicine specialists (OMS) and 3 weeks later, they reviewed the images taken using the phone, and concordance was examined between the two by Kappa statistics. The sensitivity and specificity of clinical diagnosis using the phone images were also measured. Pre- and post-program questionnaires were answered by both the dentists and the OMS to determine the feasibility of integrating teledentistry in their clinical practice.

RESULTS: The Kappa values in determining the presence of lesion, category of lesion (OPMD or not), and making referral decision were moderate to strong (0.64-1.00). The overall sensitivity was more than 70% and specificity was 100%. The false negative rate decreased as the camera resolution increased. All dentists agreed that the process could facilitate early detection of oral mucosal lesion, and was easy to use in the clinic.

CONCLUSIONS: This study provides evidence that teledentistry can be used for communication between primary care and OMS and could be readily integrated into clinical setting for patient management.

Fulltext The promise of human induced pluripotent stem cells in dental research

Srijaya TC, Pradeep PJ, Zain RB, Musa S, Abu Kasim NH, Govindasamy V

Stem Cells Int, 2012;2012:423868.

PMID: 22654919 DOI: 10.1155/2012/423868

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC lines in vitro from patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.

Bullous pemphigoid--management of a patient with oral and skin lesions

Ali TB, Zain RB, Adam BA

Singapore Dent J, 1994 Jan;19(1):18-21.

PMID: 9582679

A case of bullous pemphigoid with extra-oral and intraoral lesions in a 60-year-old female is reported. Diagnosis is based on histopathology and direct immunofluorescence, and the treatment regime described included oral prescription of prednisolone and topical application of a mixture of fluocinonide ointment and triamcinolone acetonide in Orabase on the oral lesions.

Oral pyogenic granuloma (excluding pregnancy tumour)--a clinical analysis of 304 cases

Zain RB, Khoo SP, Yeo JF

Singapore Dent J, 1995 Jul;20(1):8-10.

PMID: 9582682

A clinical analysis of 304 cases of pyogenic granuloma (excluding pregnancy tumour) were obtained from the clinical evaluations submitted by clinicians while sending specimens for biopsy. The average age of the patients with pyogenic granuloma was 28.9 years with a peak age incidence in the second decade. More female patients were affected and the lesions present mainly in the Chinese. The majority of the lesions were ulcerated and pedunculated. The lesions had a mean diameter of 10.8 mm with a mean lesion duration of 6.0 months. The gingiva was the prevalent site for these lesions with a greater number being located in the maxilla. The recurrence rate was found to be 14.1%.

Radiographic features of periapical cysts and granulomas

Zain RB, Roswati N, Ismail K

Singapore Dent J, 1989 Dec;14(1):29-32.

PMID: 2487471

Many studies have been reported on radiographic lesion sizes of periapical lesions. However no studies have been reported on prevalences of subjective radiographic features in these lesions except for the early assumption that a periapical cyst usually exhibit a radiopaque cortex. This study is conducted to evaluate the prevalences of several subjective radiographic features of periapical cysts and granulomas in the hope to identify features that maybe suggestive of either diagnosis. The results showed that a regular (circular or semi-circular) radiographic outline is likely to be a periapical cyst while an irregular radiographic outline is not indicative of either a cyst or a granuloma. The association between the regular/irregular radiographic outline and the type of periapical lesion was found to be statistically significant (p less than 0.001). The associations of two other radiographic features and the type of periapical lesion were found to be just statistically significant (p less than 0.01). These features are the symmetry/asymmetry of the radiolucency in relation to the apex and the funnel-shaped/angular-shaped extension of the radiolucency. The widely accepted criteria that the possession of a radiopaque cortex surrounding the radiolucency can discriminate between a periapical cyst and granuloma cannot be statistically supported in this study.

The cracked tooth syndrome--crown root vertical fracture

Majid ZA, Zain RB

Singapore Dent J, 1988 Dec;13(1):44-6.

PMID: 3155005

A case of an incomplete tooth fracture followed by a complete fracture was presented. The difficulty of diagnosing this condition was discussed as well as the possible histological explanation of the symptoms experienced by the patient. It once again points out to practising dentists, that whilst deep pockets can give rise to severe periodontal pain, intense and excruciating pain should be investigated with the cracked tooth in mind.

Fulltext Healthcare Professional in the Loop (HPIL): Classification of Standard and Oral Cancer-Causing Anomalous Regions of Oral Cavity Using Textural Analysis Technique in Autofluorescence Imaging

Awais M, Ghayvat H, Krishnan Pandarathodiyil A, Nabillah Ghani WM, Ramanathan A, Pandya S, et al.

Sensors (Basel), 2020 Oct 12;20(20).

PMID: 33053886 DOI: 10.3390/s20205780

Oral mucosal lesions (OML) and oral potentially malignant disorders (OPMDs) have been identified as having the potential to transform into oral squamous cell carcinoma (OSCC). This research focuses on the human-in-the-loop-system named Healthcare Professionals in the Loop (HPIL) to support diagnosis through an advanced machine learning procedure. HPIL is a novel system approach based on the textural pattern of OML and OPMDs (anomalous regions) to differentiate them from standard regions of the oral cavity by using autofluorescence imaging. An innovative method based on pre-processing, e.g., the Deriche-Canny edge detector and circular Hough transform (CHT); a post-processing textural analysis approach using the gray-level co-occurrence matrix (GLCM); and a feature selection algorithm (linear discriminant analysis (LDA)), followed by k-nearest neighbor (KNN) to classify OPMDs and the standard region, is proposed in this paper. The accuracy, sensitivity, and specificity in differentiating between standard and anomalous regions of the oral cavity are 83%, 85%, and 84%, respectively. The performance evaluation was plotted through the receiver operating characteristics of periodontist diagnosis with the HPIL system and without the system. This method of classifying OML and OPMD areas may help the dental specialist to identify anomalous regions for performing their biopsies more efficiently to predict the histological diagnosis of epithelial dysplasia.

Fulltext Genetic alterations of chromosome 8 genes in oral cancer

Yong ZW, Zaini ZM, Kallarakkal TG, Karen-Ng LP, Rahman ZA, Ismail SM, et al.

Sci Rep, 2014;4:6073.

PMID: 25123227 DOI: 10.1038/srep06073

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 27.3% of the patients, MYC in 18.2%, RECQL4 in 15.2% and MYBL1 in 12.1% of patients. The most frequent gene losses found were the GATA4 gene (24.2%), FGFR1 gene (24.2%), MSRA (21.2) and CSGALNACT1 (12.1%). The co-amplification of EIF3E and RECQL4 was found in 9% of patients and showed significant association with alcohol drinkers. There was a significant association between the amplification of EIF3E gene with non-betel quid chewers and the negative lymph node status. EIF3E amplifications did not show prognostic significance on survival. Our results suggest that EIF3E may have a role in the carcinogenesis of OSCC in non-betel quid chewers.

Fulltext Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins

Karsani SA, Saihen NA, Zain RB, Cheong SC, Abdul Rahman M

Proteome Sci, 2014;12(1):3.

PMID: 24422745 DOI: 10.1186/1477-5956-12-3

A limiting factor in performing proteomics analysis on cancerous cells is the difficulty in obtaining sufficient amounts of starting material. Cell lines can be used as a simplified model system for studying changes that accompany tumorigenesis. This study used two-dimensional gel electrophoresis (2DE) to compare the whole cell proteome of oral cancer cell lines vs normal cells in an attempt to identify cancer associated proteins.

Fulltext Identification of host-immune response protein candidates in the sera of human oral squamous cell carcinoma patients

Chen Y, Azman SN, Kerishnan JP, Zain RB, Chen YN, Wong YL, et al.

PLoS One, 2014;9(10):e109012.

PMID: 25272005 DOI: 10.1371/journal.pone.0109012

One of the most common cancers worldwide is oral squamous cell carcinoma (OSCC), which is associated with a significant death rate and has been linked to several risk factors. Notably, failure to detect these neoplasms at an early stage represents a fundamental barrier to improving the survival and quality of life of OSCC patients. In the present study, serum samples from OSCC patients (n = 25) and healthy controls (n = 25) were subjected to two-dimensional gel electrophoresis (2-DE) and silver staining in order to identify biomarkers that might allow early diagnosis. In this regard, 2-DE spots corresponding to various up- and down-regulated proteins were sequenced via high-resolution MALDI-TOF mass spectrometry and analyzed using the MASCOT database. We identified the following differentially expressed host-specific proteins within sera from OSCC patients: leucine-rich α2-glycoprotein (LRG), alpha-1-B-glycoprotein (ABG), clusterin (CLU), PRO2044, haptoglobin (HAP), complement C3c (C3), proapolipoprotein A1 (proapo-A1), and retinol-binding protein 4 precursor (RBP4). Moreover, five non-host factors were detected, including bacterial antigens from Acinetobacter lwoffii, Burkholderia multivorans, Myxococcus xanthus, Laribacter hongkongensis, and Streptococcus salivarius. Subsequently, we analyzed the immunogenicity of these proteins using pooled sera from OSCC patients. In this regard, five of these candidate biomarkers were found to be immunoreactive: CLU, HAP, C3, proapo-A1 and RBP4. Taken together, our immunoproteomics approach has identified various serum biomarkers that could facilitate the development of early diagnostic tools for OSCC.

Fulltext CD4+CD25hiCD127low regulatory T cells are increased in oral squamous cell carcinoma patients

Lim KP, Chun NA, Ismail SM, Abraham MT, Yusoff MN, Zain RB, et al.

PLoS One, 2014;9(8):e103975.

PMID: 25153698 DOI: 10.1371/journal.pone.0103975

Regulatory T cells (Tregs), a subset of CD4+ T cells plays a pivotal role in regulating the immune system. An increase in Treg numbers enables cancer progression by dampening the immune system and allowing tumor cells to evade immune detection and destruction. An increase in Treg numbers and expression of inhibitory cytokines including TGF-β and IL-10 are mechanisms by which Tregs exert their immune suppressive function. However, the presence of Tregs and inhibitory cytokines in oral cancer patients is still unclear. In this study, the presence of circulating Tregs in 39 oral cancer patients and 24 healthy donors was examined by studying the presence of the CD4+CD25hiCD127low cell population in their peripheral blood mononuclear cells using flow cytometry. Serum levels of TGF-β and IL-10 were measured by ELISA. T cell subsets of OSCC patients were found to differ significantly from healthy donors where a decrease in CD8+ cytotoxic T cells and an increase in Tregs (CD4+CD25hiCD127low) were observed. Further, the ratio of CD8+ T cells/Tregs was also decreased in patients compared to healthy donors. The presence of Tregs was accompanied by a decrease in IL-10 but not TGF-β secretion in OSCC patients when compared to donors; in addition, the analysis also revealed that an increased presence of Tregs was accompanied by better patient survival. Amongst OSCC patients, smokers had significantly higher levels of TGF-β. It is apparent that the immune system is compromised in OSCC patients and the characterization of the Treg subpopulation could form a basis for improving our understanding of the perturbations in the immune system that occur during OSCC tumorigenesis.

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