Oral Cancer Research Team

Subang Jaya, Malaysia

Oral Cancer Research Team

Subang Jaya, Malaysia
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Saleh A.,Oral Cancer Research Team | Kong Y.H.,Oral Cancer Research Team | Vengu N.,Malaysian Dental | Badrudeen H.,Malaysian Dental | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: Dentists are typically the first professionals who are approached to treat ailments within the oral cavity. Therefore they should be well-equipped in detecting suspicious lesions during routine clinical practice. This study determined the levels of knowledge on early signs and risk factors associated with oral cancer and identified which factors influenced dentist participation in prevention and early detection of oral cancer. Materials and Methods: A survey on dentists' knowledge and their practices in prevention and early detection of oral cancer was conducted using a 26-item self-administered questionnaire. Results and Conclusions: A response rate of 41.7% was achieved. The level of knowledge on early signs and risk habits associated with oral cancer was high and the majority reported to have conducted opportunistic screening and advised patients on risk habit cessation. Factors that influenced the dentist in practising prevention and early detection of oral cancer were continuous education on oral cancer, age, nature of practice and recent graduation. Notably, dentists were receptive to further training in the area of oral cancer detection and cessation of risk habits. Taken together, the study demonstrated that the dental clinic is a good avenue to conduct programs on opportunistic screening, and continuous education in these areas is necessary to adequately equip dentists in running these programs. Further, this study also highlighted knowledge deficits and practice shortcomings which will help in planning and developing programs that further encourage better participation of dentists in prevention and early detection of oral cancer.

Vaithilingam R.D.,University of Malaya | Safii S.H.,University of Malaya | Baharuddin N.A.,University of Malaya | Ng C.C.,University of Malaya | And 5 more authors.
Journal of Periodontal Research | Year: 2014

Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial 'hypothesis-dependent' candidate-gene polymorphism studies did not report valid genetic risk loci. Following a large-scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]), glycosyltransferase 6 domain containing 1 (GLT6D1) and cyclooxygenase 2 (COX2), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of 'hypothesis-free' genome-wide association studies (GWAS). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published - one reported genome-wide association of GLT6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well-designed genetic study with large and sufficiently powered case-control samples of severe phenotypes, are also discussed. © 2014 John Wiley & Sons A/S.

Siow M.Y.,University of Malaya | Karen Ng L.P.,University of Malaya | Vincent Chong V.K.,University of Malaya | Jamaludin M.,University of Malaya | And 7 more authors.
Oral Diseases | Year: 2014

Objectives: To identify differentially expressed miRNA between oral squamous cell carcinoma (OSCC) and non-cancer (NC) and to associate these with clinico-pathological parameters. Materials and methods: miRNA microarray profiling was utilized to obtain the expression profile of miRNAs in four OSCC and four NC samples. The expression of miR-31 and miR-375 was further validated in 26 OSCC and three NC samples using real-time-PCR. The association between miRNA expression and clinico-pathological parameters was tested by univariate and multivariate analyses. Results: Microarray profiling demonstrated that 15 and four miRNAs were up-regulated and down-regulated, respectively, in OSCC as compared with NC. miR-31 and miR-375 were validated as up- and down-regulated miRNAs, respectively. In univariate analyses, expression of miR-31 was significantly elevated in early stage, tumours with no metastatic nodes and those from the buccal mucosa. By contrast, low miR-375 expression was significantly associated with late stage disease, larger tumour size and the non-cohesive type of pattern of invasion in OSCC. The association between miR-31 expression with tumour staging and site and miR-375 with tumour staging remained significant in multivariate analyses. Conclusions: This study has identified 19 miRNAs significantly associated with OSCC, and expressions of miR-31 and miR-375 were significantly related with clinico-pathological parameters suggesting they could be important in driving oral tumourigenesis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Malhotra R.,University of Connecticut | Patel V.,U.S. National Institutes of Health | Chikkaveeraiah B.V.,University of Connecticut | Munge B.S.,Salve Regina University | And 9 more authors.
Analytical Chemistry | Year: 2012

Multiplexed biomarker protein detection holds unrealized promise for clinical cancer diagnostics due to lack of suitable measurement devices and lack of rigorously validated protein panels. Here we report an ultrasensitive electrochemical microfluidic array optimized to measure a four-protein panel of biomarker proteins, and we validate the protein panel for accurate oral cancer diagnostics. Unprecedented ultralow detection into the 5-50 fg·mL -1 range was achieved for simultaneous measurement of proteins interleukin 6 (IL-6), IL-8, vascular endothelial growth factor (VEGF), and VEGF-C in diluted serum. The immunoarray achieves high sensitivity in 50 min assays by using off-line protein capture by magnetic beads carrying 400 000 enzyme labels and ∼100 000 antibodies. After capture of the proteins and washing to inhibit nonspecific binding, the beads are magnetically separated and injected into the array for selective capture by antibodies on eight nanostructured sensors. Good correlations with enzyme-linked immunosorbent assays (ELISA) for protein determinations in conditioned cancer cell media confirmed the accuracy of this approach. Normalized means of the four protein levels in 78 oral cancer patient serum samples and 49 controls gave clinical sensitivity of 89% and specificity of 98% for oral cancer detection, demonstrating high diagnostic utility. The low-cost, easily fabricated immunoarray provides a rapid serum test for diagnosis and personalized therapy of oral cancer. The device is readily adaptable to clinical diagnostics of other cancers. © 2012 American Chemical Society.

Zanaruddin S.N.S.,Oral Cancer Research Team | Saleh A.,Oral Cancer Research Team | Yang Y.-H.,Kaohsiung Medical University | Hamid S.,Oral Cancer Research Team | And 7 more authors.
Human Pathology | Year: 2013

The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P =.036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC. © 2013 Elsevier Inc.

Dionne K.R.,University of Malaya | Dionne K.R.,Oral Cancer Research Team | Dionne K.R.,University of Colorado at Denver | Warnakulasuriya S.,King's College London | And 3 more authors.
International Journal of Cancer | Year: 2015

Despite commendable progress in the prevention, detection, and treatment of a wide variety of solid tumor types, oral squamous cell carcinoma (OSCC) remains a significant health burden across the globe. OSCC carcinogenesis involves accumulation of genetic alterations that coincide with the multistep malignant transformation of normal oral epithelium. OSCC is often first diagnosed at late stages of the disease (advanced regional disease and/or metastasis). Delayed diagnosis precludes successful treatment and favorable outcomes. In clinical practice, opportunities exist to identify patients with oral potentially malignant disorders (OPMDs), which precede the development of cancer. This review addresses the current status of laboratory and clinical research on OPMDs, with emphasis on leukoplakia and erythroplakia. OSF is also presented, though there is a paucity of published studies on this disorder. We focus on findings that could translate into earlier diagnosis and more efficacious treatment of those lesions with significant malignant potential. We explore how markers of OPMD malignant transformation might be implemented into current diagnostic practice to help clinicians objectively stratify patients into treatment/follow-up groups according to relative risk. We provide an overview of recently concluded and ongoing OPMD chemoprevention trials. We describe laboratory OPMD models that can be used to not only to reveal the genetic and molecular intricacies of oral cancer but also to develop novel screening methods and therapeutic approaches. Finally, we call for targeted screening programs of at-risk populations in order to facilitate diagnosis and treatment of OPMD and early OSCC. © 2014 UICC.

Gan C.P.,Oral Cancer Research Team | Patel V.,Oral Cancer Research Team | Patel V.,U.S. National Institutes of Health | Mikelis C.M.,U.S. National Institutes of Health | And 8 more authors.
Oncotarget | Year: 2014

Oral squamous cell carcinoma (OSCC) has a propensity to spread to the cervical lymph nodes (LN). The presence of cervical LN metastases severely impacts patient survival, whereby the two-year survival for oral cancer patients with involved LN is ~30% compared to over 80% in patients with non-involved LN. Elucidation of key molecular mechanisms underlying OSCC metastasis may afford an opportunity to target specific genes, to prevent the spread of OSCC and to improve patient survival. In this study, we demonstrated that expression of the heterotrimeric G-protein alpha-12 (G'12) is highly up-regulated in primary tumors and LN of OSCC patients, as assessed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). We also found that exogenous expression of the constitutively activated-form of G'12 promoted cell migration and invasion in OSCC cell lines. Correspondingly, inhibition of G'12 expression by shRNA consistently inhibited OSCC cell migration and invasion in vitro. Further, the inhibition of G12 signaling by regulator of G-protein signaling (RGS) inhibited G'12-mediated RhoA activation, which in turn resulted in reduced LN metastases in a tongue-orthotopic xenograft mouse model of oral cancer. This study provides a rationale for future development and evaluation of drug candidates targeting G'12-related pathways for metastasis prevention.

Farzadi A.,University of Malaya | Waran V.,University of Malaya | Solati-Hashjin M.,University of Malaya | Rahman Z.A.A.,Oral Cancer Research Team | And 2 more authors.
Ceramics International | Year: 2015

Recent advancements in computational design and additive manufacturing have enabled the fabrication of 3D prototypes with controlled architecture resembling the natural bone. Powder-based three-dimensional printing (3DP) is a versatile method for production of synthetic scaffolds using sequential layering process. The quality of 3D printed products by this method is controlled by the optimal build parameters. In this study, Calcium Sulfate based powders were used for porous scaffolds fabrication. The X-direction printed scaffolds with a pore size of 0.8 mm and a layer thickness of 0.1125 mm were subjected to the depowdering step. The effects of four layer printing delays of 50, 100, 300 and 500 ms on the physical and mechanical properties of printed scaffolds were investigated. The compressive strength, toughness and tangent modulus of samples printed with a delay of 300 ms were observed to be higher than other samples. Furthermore, the results of SEM and μCT analyses showed that samples printed with a delay of 300 ms have higher dimensional accuracy and are significantly closer to CAD software based designs with predefined 0.8 mm macro-pore and 0.6 mm strut size. © 2015 The Authors.

Gan C.P.,Oral Cancer Research Team | Gan C.P.,University of Malaya | Hamid S.,Oral Cancer Research Team | Hor S.Y.,Oral Cancer Research Team | And 7 more authors.
Head and Neck | Year: 2012

Background There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC. Methods Growth inhibition effects of VPA alone or in combination with 5-aza- 2′deoxycytidine (5-aza-dC) or all-trans retinoic acid (ATRA) was evaluated with MTT and clonogenic assays on 5 HNSCC cell lines. The mechanism of growth inhibition was investigated by looking at markers of terminal differentiation and senescence. Results Growth inhibition profiles of HNSCC cell lines varied in response to VPA. Inhibition of clonogenic survival in response to VPA was associated with an upregulation of p21, expression of terminal differentiation markers, and cellular senescence. Notably, a combination treatment of 5-Aza-dC-VPA-ATRA enhanced growth inhibition in cells resistant to VPA. Conclusion VPA is a potent inhibitor of proliferation in some HNSCC cell lines, and may be used to treat HNSCC. Copyright © 2011 Wiley Periodicals, Inc.

PubMed | University of Otago, Malaysian Private Dental Practitioners Association MPDPA, Oral Cancer Research Team, University of Malaya and Outreach
Type: | Journal: Community dentistry and oral epidemiology | Year: 2016

Private dental practitioners constitute approximately 40% of all registered dentists in Malaysia, and this group affords an avenue for prevention and early detection of oral cancer. However, such activities are still limited. This study investigated the feasibility of incorporating opportunistic screening of oral cancer in the private dental setting.Dentists were recruited through two main dental associations in Malaysia and attended a 1-day training session on recognizing abnormalities within the oral cavity. Following the training, the dentists conducted screening and provided risk habits cessation advice at their respective clinics for 6 months. The impact of the program was evaluated by determining the number of patients who were screened and/or provided with risk habits cessation advice.Twenty-six dentists took part in the program and conducted opportunistic screening on a total of 2603 individuals. On average, they screened about 23.0% of their patients and 5.1% were given risk habits cessation advice. Notably, dentists who had lower patient load were more likely to conduct opportunistic screening.While the participating private dentists state that they have a role in performing opportunistic screening and providing risk habits cessation advice, these activities are still not a priority area in the private clinics, strongly suggesting that strategies to motivate dentists in this setting are urgently needed.

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