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  1. Saleh A, Kong YH, Vengu N, Badrudeen H, Zain RB, Cheong SC
    Asian Pac J Cancer Prev, 2014;15(1):229-37.
    PMID: 24528031
    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.

  2. Saleh A, Kong YH, Haron N, Aripin SF, Vadiveloo M, Hussaini H, et al.
    Community Dent Oral Epidemiol, 2017 04;45(2):112-119.
    PMID: 27805279 DOI: 10.1111/cdoe.12266
    OBJECTIVES: 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.

    METHODS: 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.

    RESULTS: 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.

    CONCLUSIONS: 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.

  3. Loo TH, Arvinder-Singh HS, Ang YC, Kong YH, Vikram Suarn S, Rakesh S
    Med J Malaysia, 2022 Nov;77(6):643-649.
    PMID: 36448379
    INTRODUCTION: Psychological distress had been documented since the beginning of the COVID-19 outbreak in 2019. The aim of the study is to describe the psychological impact among those who were hospitalized for COVID-19 infection within 6 months after being discharged from the hospital. The psychological impact in this study is defined as depression, anxiety, and stress.

    MATERIALS AND METHODS: This was a cross-sectional study conducted from July 2020 till August 2021 in a regional state hospital, north of Malaysia. All patients requiring hospitalization for COVID-19 were approached within the first 2 weeks after admission to administer the Depression, Anxiety and Stress Scale - 21 Items (DASS-21) scale. Follow-up phone calls were made within 3 months of discharged to enquire about the DASS-21 items as well as the Impact of Event Scale-Revised (IES-R) scale items. Participants above the age of 18 and technology savvy to answer an online questionnaire were recruited for the study. We excluded participants with a known history of psychotic disorder from the study. We utilised the DASS-21 to screen for depression, anxiety, and stress, as well as the IES-R to identify symptoms of post-traumatic stress disorder. Participants could answer the questionnaires in either English or Bahasa Malaysia. For comparison of two categorical data, a chi-square was applied. A univariate analysis was first conducted and all variables with a p ≤0.3 was then entered into the multivariate analysis for the final output. Other than the univariate analysis, all other p values <0.05 were considered to be statistically significant. All data collected were tabulated and analysed in the SPSS v21.0 system.

    RESULTS: A total of 306 out of 696 COVID-19 patients responded. The mean age for the participants was 31.69 (SD:11.19) years old. From the total, 54.2% were ladies, 78.8% were Malay, 50.7% were unmarried, 55.2% had higher education, and 67.6% were employed at the time of the survey. We found 20.5% of the participants were depressed, 38.9% had moderate anxiety, and 17.3% were stressed. From the total, 31.7% of the participants were deemed to have had some symptoms of post-traumatic stress disorder (PTSD) ranging from mild to severe. From the final multivariate analysis, it was found that depression (p=0.02) had a 2.78 times likeliness of having PTSD, anxiety (p<0.001) had a 3.35 times likeliness of having PTSD and stressed patients (p=0.02) 2.86 times likeliness of having PTSD when compared to those without PTSD.

    CONCLUSION: Patients reported to suffer from symptoms of PTSD and might benefit from psychological interventions to mitigate the impact in the long run.

  4. Soon CF, Thong KT, Tee KS, Ismail AB, Denyer M, Ahmad MK, et al.
    Biotech Histochem, 2016 May;91(4):283-95.
    PMID: 27008034 DOI: 10.3109/10520295.2016.1158865
    We describe a new scaffold-free three-dimensional (3D) cell culture model using cholesteryl ester based lyotropic liquid crystal (LC) substrates. Keratinocytes were deposited randomly on the LC surface where they self-assembled into 3D microtissues or keratinospheroids. The cell density required to form spheroids was optimized. We investigated cell viability using dead/live cell assays. The adhesion characteristics of cells within the microtissues were determined using histological sectioning and immunofluorescence staining. Fourier transform infrared spectroscopy (FTIR) was used to characterize the biochemistry of the keratinospheroids. We found that both cells and microtissues could migrate on the LC surface. The viability study indicated approximately 80% viability of cells in the microtissues up to 20 days of culture. Strong intercellular adhesion was observed in the stratification of the multi-layered microspheroids using field emission-scanning electron microscopy (FE-SEM) and histochemical staining. The cytoskeleton and vinculins of the cells in the microtissues were expressed diffusely, but the microtissues were enriched with lipids and nucleic acids, which indicates close resemblance to the conditions in vivo. The basic 3D culture model based on LC may be used for cell and microtissue migration studies in response to cytochemical treatment.
  5. Kelly GM, Kong YH, Dobi A, Srivastava S, Sesterhenn IA, Pathmanathan R, et al.
    Mol Clin Oncol, 2015 Jan;3(1):23-30.
    PMID: 25469265
    Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.
  6. Kong YH, Syed Zanaruddin SN, Lau SH, Ramanathan A, Kallarakkal TG, Vincent-Chong VK, et al.
    PLoS One, 2015;10(7):e0134045.
    PMID: 26214683 DOI: 10.1371/journal.pone.0134045
    Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer's aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT) is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1 and LAMC2) at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated with Broder's grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management.
  7. Zanaruddin SN, Yee PS, Hor SY, Kong YH, Ghani WM, Mustafa WM, et al.
    PLoS One, 2013;8(11):e80229.
    PMID: 24224046 DOI: 10.1371/journal.pone.0080229
    OBJECTIVES: The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC).

    MATERIALS AND METHODS: The OncoCarta(™) panel v1.0 assay was used to characterize oncogenic mutations. In addition, exons 4-11 of the TP53 gene were sequenced. Statistical analyses were conducted to identify associations between mutations and selected clinico-pathological characteristics and risk habits.

    RESULTS: Oncogenic mutations were detected in PIK3CA (5.7%) and HRAS (2.4%). Mutations in TP53 were observed in 27.7% (31/112) of the OSCC specimens. Oncogenic mutations were found more frequently in non-smokers (p = 0.049) and TP53 truncating mutations were more common in patients with no risk habits (p = 0.019). Patients with mutations had worse overall survival compared to those with absence of mutations; and patients who harbored DNA binding domain (DBD) and L2/L3/LSH mutations showed a worse survival probability compared to those patients with wild type TP53. The majority of the oncogenic and TP53 mutations were G:C > A:T and A:T > G:C base transitions, regardless of the different risk habits.

    CONCLUSION: Hotspot oncogenic mutations which are frequently present in common solid tumors are exceedingly rare in OSCC. Despite differences in risk habit exposure, the mutation frequency of PIK3CA and HRAS in Asian OSCC were similar to that reported in OSCC among Caucasians, whereas TP53 mutations rates were significantly lower. The lack of actionable hotspot mutations argue strongly for the need to comprehensively characterize gene mutations associated with OSCC for the development of new diagnostic and therapeutic tools.

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