Displaying publications 1 - 20 of 87 in total

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  1. Wong MM, Aziz NA, Ch'ng ES, Armon S, Chook JB, Bong JJ, et al.
    J Mol Histol, 2024 Apr 17.
    PMID: 38630414 DOI: 10.1007/s10735-024-10191-8
    BACKGROUND: Autophagy plays multifaceted roles in regulating hepatocellular carcinoma (HCC) and the mechanisms involved are under-explored. Regulatory microRNAs (miRNAs) have been reported to target autophagy proteins but their roles in HCC is not well studied. Using HCC patient tissues, this study aims to investigate the association of autophagy with several clinicopathological parameters as well as identifying the autophagy-related miRNAs and the possible pathways.

    METHODS AND RESULTS: Autophagy level in the HCC patient-derived cancer and non-cancer tissues was determined by immunohistochemistry (IHC) targeting SQSTM1, LC3A and LC3B proteins. Significance tests of clinicopathological variables were tested using the Fisher's exact or Chi-square tests. Gene and miRNA expression assays were carried out and analyzed using Nanostring platform and software followed by validation of other online bioinformatics tools, namely String and miRabel. Autophagy expression was significantly higher in cancerous tissues compared to adjacent non-cancer tissues. High LC3B expression was associated with advanced tumor histology grade and tumor location. Nanostring gene expression analysis revealed that SQSTM1, PARP1 and ATG9A genes were upregulated in HCC tissues compared to non-cancer tissues while SIRT1 gene was downregulated. These genes are closely related to an autophagy pathway in HCC. Further, using miRabel tool, three downregulated miRNAs (hsa-miR-16b-5p, hsa-miR-34a-5p, and hsa-miR-660-5p) and one upregulated miRNA (hsa-miR-539-5p) were found to closely interact with the abovementioned autophagy-related genes. We then mapped out the possible pathway involving the genes and miRNAs in HCC tissues.

    CONCLUSIONS: We conclude that autophagy events are more active in HCC tissues compared to the adjacent non-cancer tissues. We also reported the possible role of several miRNAs in regulating autophagy-related genes in the autophagy pathway in HCC. This may contribute to the development of potential therapeutic targets for improving HCC therapy. Future investigations are warranted to validate the target genes reported in this study using a larger sample size and more targeted molecular technique.

  2. Pang SW, Armon S, Chook JB, Chew J, Peh KB, Lim WW, et al.
    Mol Biol Rep, 2024 Jan 16;51(1):124.
    PMID: 38227097 DOI: 10.1007/s11033-023-09150-5
    BACKGROUND: Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients.

    METHODS: We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted.

    RESULTS: FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046).

    CONCLUSIONS: FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.

  3. Bradley DA, Essa RZ, Peh SC, Teow SY, Chew MT, Zubair HT, et al.
    Appl Radiat Isot, 2023 Aug;198:110875.
    PMID: 37257265 DOI: 10.1016/j.apradiso.2023.110875
    Review is provided of a number of low-dose, low dose rate situations that in study require advances in the development of dosimetric facilities. Using a clinical linac set up to provide doses down to the few mGy level, the performance of a real-time radioluminescence system has then been illustrated, accommodating pulsed as well as continuous dose delivery. The system gate times provide for tracking of the pattern of dose delivery, allowing detailed account of dose and dose-rate variations. The system has been tested in both x-ray and electron mode dose delivery.
  4. Low WF, Ngeow YF, Chook JB, Tee KK, Ong SK, Peh SC, et al.
    Expert Rev Mol Med, 2022 Nov 16;25:e11.
    PMID: 36380484 DOI: 10.1017/erm.2022.38
    Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.
  5. Chan NN, Ong KW, Siau CS, Lee KW, Peh SC, Yacob S, et al.
    BMC Public Health, 2022 02 14;22(1):296.
    PMID: 35164734 DOI: 10.1186/s12889-022-12632-z
    BACKGROUND: The COVID-19 pandemic has resulted in a global health emergency and lock-down measures to curb the uncontrolled transmission chain. Vaccination is an effective measure against COVID-19 infections. In Malaysia amidst the national immunisation programme (NIP) which started in February 2021, there were rising concerns regarding the prevalence of vaccine hesitancy and refusal, and therefore, vaccine uptake among Malaysians. Although there are many quantitative studies on COVID-19 vaccination, the subjective experience of individuals was understudied. This study aims to explore the lived experiences of Malaysians regarding vaccine hesitancy and refusal, and facilitating factors that could enhance vaccine acceptance and uptake.

    METHODS: This qualitative study employed the hermeneutic phenomenological study design. Purposive sampling strategies were used to recruit Malaysians that had direct experiences with friends, family members and their community who were hesitating or refusing to accept the COVID-19 vaccines. A semi-structured interview guide was developed based on the expert knowledge of the investigators and existing literature on the topic. A series of focus group interviews (FGIs) was conducted online facilitated by a multidisciplinary team of experts. The group interviews were transcribed verbatim and analysed.

    RESULTS: Fifty-nine participants took part in seven FGIs. We found that "incongruence" was the overall thematic meaning that connected all the 3 main themes. These themes comprise firstly, the incongruence between the aims and implementation of the National Immunization Program which highlighted the gap between realities and needs on the ground. Secondly, the incongruence between Trust and Mistrust revealed a trust deficit in the government, COVID-19 news, and younger people's preference to follow the examples of local vaccination "heroes". Thirdly, the incongruence in communication showed the populace's mixed views regarding official media and local social media.

    CONCLUSIONS: This study provided rich details on the complex picture of the COVID-19 immunization program in Malaysia and its impact on vaccine hesitancy and refusal. The inter-related and incongruent factors explained the operational difficulty and complexity of the NIP and the design of an effective health communication campaign. Identified gaps such as logistical implementation and communication strategies should be noted by policymakers in implementing mitigation plans.

  6. Latif AA, Lee KW, Phang K, Rashid AA, Chan NN, Peh SC, et al.
    Tzu Chi Med J, 2022;34(4):473-484.
    PMID: 36578649 DOI: 10.4103/tcmj.tcmj_212_21
    OBJECTIVES: This systematic review aims to identify influencing factors of medication adherence behavior in patients with end-stage renal disease (ESRD), with a special interest in patient-related factors based on the World Health Organization adherence model.

    MATERIALS AND METHODS: Primary electronic databases comprising PubMed, Scopus, Web of Science, Embase and Cochrane Library, as well as ProQuest (Health and Medical), ProQuest (Psychology), and EBSCOHost (APA PsychARTICLES) were used to search for literature on patient-related factors in medication adherence, from inception till August 31, 2021.

    RESULTS: 479 articles were identified and six articles meeting eligibility criteria were reviewed and remained in this systematic review. The present review found that despite different tools being used to measure ESRD's perception of medication's necessity and beliefs, there was a profound association between perception and beliefs with medication adherence behavior. There is a positive relationship between knowledge, belief, educational level, ethnicity, female, and medication adherence behavior. Mixed finding was reported between perception, age, and medication adherence behavior. However, there were no studies on patients' attitudes and medication adherence behavior as suggested in the WHO adherence model.

    CONCLUSION: Only a limited number of patient-related factors were available for evaluation in the current systematic review. Additional research is needed to advance the understanding of medication adherence behavior affected by patient-related factors on the medication and illness. However, the findings must be taken with caution because of the limited studies included in this review.

  7. Awi NJ, Yap HY, Armon S, Low JSH, Peh KB, Peh SC, et al.
    Malays J Pathol, 2021 Aug;43(2):269-279.
    PMID: 34448791
    Autophagy is a host defensive mechanism responsible for eliminating harmful cellular components through lysosomal degradation. Autophagy has been known to either promote or suppress various cancers including colorectal cancer (CRC). KRAS mutation serves as an important predictive marker for epidermal growth factor receptor (EGFR)-targeted therapies in CRC. However, the relationship between autophagy and KRAS mutation in CRC is not well-studied. In this single-centre study, 92 formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients (42 Malaysian Chinese and 50 Indonesian) were collected and KRAS mutational status was determined by quantitative PCR (qPCR) (n=92) while the expression of autophagy effector (p62, LC3A and LC3B) was examined by immunohistochemistry (IHC) (n=48). The outcomes of each were then associated with the clinicopathological variables (n=48). Our findings demonstrated that the female CRC patients have a higher tendency in developing KRAS mutation in the Malaysian Chinese population (p<0.05). Expression of autophagy effector LC3A was highly associated with the tumour grade in CRC (p<0.001) but not with other clinicopathological parameters. Lastly, the survival analysis did not yield a statistically significant outcome. Overall, this small cohort study concluded that KRAS mutation and autophagy effectors are not good prognostic markers for CRC patients.
  8. Wong MM, Chan HY, Aziz NA, Ramasamy TS, Bong JJ, Ch'ng ES, et al.
    Mol Biol Rep, 2021 Apr;48(4):3695-3717.
    PMID: 33893928 DOI: 10.1007/s11033-021-06334-9
    Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths in the world. The most common type of liver cancers is hepatocellular carcinoma (HCC). Autophagy is the cellular digestion of harmful components by sequestering the waste products into autophagosomes followed by lysosomal degradation for the maintenance of cellular homeostasis. The impairment of autophagy is highly associated with the development and progression of HCC although autophagy may be involved in tumour-suppressing cellular events. In regards to its protecting role, autophagy also shelters the cells from anoikis- a programmed cell death in anchorage-dependent cells detached from the surrounding extracellular matrix which facilitates metastasis in HCC. Liver cancer stem cells (LCSCs) have the ability for self-renewal and differentiation and are associated with the development and progression of HCC by regulating stemness, resistance and angiogenesis. Interestingly, autophagy is also known to regulate normal stem cells by promoting cellular survival and differentiation and maintaining cellular homeostasis. In this review, we discuss the basal autophagic mechanisms and double-faceted roles of autophagy as both tumour suppressor and tumour promoter in HCC, as well as its association with and contribution to self-renewal and differentiation of LCSCs.
  9. Teh JKL, Bradley DA, Chook JB, Lai KH, Ang WT, Teo KL, et al.
    PLoS One, 2021;16(5):e0252273.
    PMID: 34048477 DOI: 10.1371/journal.pone.0252273
    BACKGROUND: The aim of the study was to visualize the global spread of the COVID-19 pandemic over the first 90 days, through the principal component analysis approach of dimensionality reduction.

    METHODS: This study used data from the Global COVID-19 Index provided by PEMANDU Associates. The sample, representing 161 countries, comprised the number of confirmed cases, deaths, stringency indices, population density and GNI per capita (USD). Correlation matrices were computed to reveal the association between the variables at three time points: day-30, day-60 and day-90. Three separate principal component analyses were computed for similar time points, and several standardized plots were produced.

    RESULTS: Confirmed cases and deaths due to COVID-19 showed positive but weak correlation with stringency and GNI per capita. Through principal component analysis, the first two principal components captured close to 70% of the variance of the data. The first component can be viewed as the severity of the COVID-19 surge in countries, whereas the second component largely corresponded to population density, followed by GNI per capita of countries. Multivariate visualization of the two dominating principal components provided a standardized comparison of the situation in the161 countries, performed on day-30, day-60 and day-90 since the first confirmed cases in countries worldwide.

    CONCLUSION: Visualization of the global spread of COVID-19 showed the unequal severity of the pandemic across continents and over time. Distinct patterns in clusters of countries, which separated many European countries from those in Africa, suggested a contrast in terms of stringency measures and wealth of a country. The African continent appeared to fare better in terms of the COVID-19 pandemic and the burden of mortality in the first 90 days. A noticeable worsening trend was observed in several countries in the same relative time frame of the disease's first 90 days, especially in the United States of America.

  10. Awi NJ, Armon S, Peh KB, Peh SC, Teow SY
    Malays J Pathol, 2020 Apr;42(1):85-90.
    PMID: 32342935
    INTRODUCTION: Autophagy is a mechanism that degrades large damaged organelles and misfolded proteins to maintain the homeostasis in all cells. It plays double-faceted roles in tumourigenesis and prevention of various cancers. In our side observation of investigating the prognostic value of autophagy in colorectal cancer (CRC), we found high expression of autophagy proteins (LC3A, LC3B, and p62/SQSTM1) in the colonic ganglion cells. To our best understanding, this is the first paper reporting such finding.

    MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) CRC tissues blocks were retrieved and confirmed by haematoxylin & eosin (H&E) staining. Immunohistochemistry (IHC) targeting autophagy proteins (LC3A, LC3B, and p62/SQSTM1) was then performed followed by pathological examination.

    RESULTS: All three autophagy proteins were present in both normal and tumour tissues of CRC patients. Interestingly, high expression of autophagy proteins in colonic ganglion cells was consistently seen regardless of tissue type (normal or cancer) or tumour site (caecum, ascending, transverse, descending, sigmoid colon and rectum).

    CONCLUSIONS: This work highlights the high autophagic activities in human colonic ganglion cells.

  11. Loke YL, Chew MT, Ngeow YF, Lim WWD, Peh SC
    PMID: 33364203 DOI: 10.3389/fcimb.2020.603086
    Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.
  12. Salam DSDA, Thit EE, Teoh SH, Tan SY, Peh SC, Cheah SC
    J Cancer, 2020;11(1):190-198.
    PMID: 31892985 DOI: 10.7150/jca.36954
    C-MYC, BCL2 and BCL6 genes are the most commonly oncogenes involved in B-Cell lymphomas. Translocations of these oncogenes are associated with an aggressive clinical course. This study aims to elucidate the patterns of BCL6, BCL2 and C-MYC gene aberrations among Malaysian B-cell Non-Hodgkin Lymphoma (NHL) using fluorescence in situ hybridization (FISH). Eighty-one B-cell NHL tissue blocks were retrieved between the year 2011 to 2015 and investigated using immunohistochemistry and interphase FISH dual colour break-apart probes of BCL2, BCL6, C-MYC and IgH. A significant difference was detected between the nodal and extranodal sites in all the BCL2 (p=0.01), C-MYC (p=0.03) and IgH (p=0.006) cases except for BCL6 (p=0.2). Our study showed that BCL6 had the highest gene translocation while BCL2/BCL6 had the most mixed aberrations of gain copies and translocation, however no mixed aberrations of gain copies and translocation was found in C-MYC. None of the mixed gain copies and translocation was found in any of the germinal centre B-cell (GCB) subtype of Diffuse Large B-cell Lymphoma, however, five were found in BCL6 and IgH gene in the non-GCB subtype; while mixed gain copies and translocation cases of BCL2 gene was found in the Follicular Lymphoma cases only. The study found interesting findings of BCL2, C-MYC and IgH gene aberrations between nodal and extranodal sites. This information might benefit future study in predicting prognosis and determine effective therapeutic strategies in the multi-ethnic populations of Malaysia as well as the Asian population.
  13. Teoh SH, Khoo JJ, Abdul Salam DSD, Peh SC, Cheah SC
    Malays J Pathol, 2019 Dec;41(3):273-281.
    PMID: 31901912
    INTRODUCTION: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin's lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway.

    MATERIALS AND METHODS: 51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement.

    RESULTS: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression.

    CONCLUSION: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.

  14. Izadiyan Z, Shameli K, Miyake M, Teow SY, Peh SC, Mohamad SE, et al.
    PMID: 30606561 DOI: 10.1016/j.msec.2018.11.008
    Core-shell Fe3O4/Au nanostructures were constructed using an advanced method of two-step synthesis from Juglans regia (walnut) green husk extract. Several complementary methods were applied to investigate structural and magnetic properties of the samples. X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), electron diffraction, optical, thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM) were used for nanoparticle characterizations. As shown by HR-TEM, the mean diameter of core-shell Fe3O4/Au nanoparticles synthesized using co-precipitation method was 6.08 ± 1.06 nm. This study shows that the physical and structural properties of core-shell Fe3O4/Au nanoparticles possess intrinsic properties of gold and magnetite. VSM revealed that the core-shell Fe3O4/Au have high saturation magnetization and low coercivity due to the magnetic properties. The core-shell nanoparticles show the inhibitory concentration (IC)50 of 235 μg/ml against a colorectal cancer cell line, HT-29. When tested against non-cancer cells, IC50 was not achieved even up to 500 μg/ml. This study highlights the magnetic properties and anticancer action of core-shell Fe3O4/Au nanoparticles. This compound can be ideal candidate for cancer treatment and other biomedical applications.
  15. Yap HY, Tee SZ, Wong MM, Chow SK, Peh SC, Teow SY
    Cells, 2018 Oct 09;7(10).
    PMID: 30304822 DOI: 10.3390/cells7100161
    Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient's response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.
  16. Teow SY, Wong MM, Yap HY, Peh SC, Shameli K
    Molecules, 2018 06 06;23(6).
    PMID: 29882775 DOI: 10.3390/molecules23061366
    Nanoparticles (NPs) are nano-sized particles (generally 1⁻100 nm) that can be synthesized through various methods. The wide range of physicochemical characteristics of NPs permit them to have diverse biological functions. These particles are versatile and can be adopted into various applications, particularly in biomedical field. In the past five years, NPs’ roles in biomedical applications have drawn considerable attentions, and novel NPs with improved functions and reduced toxicity are continuously increasing. Extensive studies have been carried out in evaluating antibacterial potentials of NPs. The promising antibacterial effects exhibited by NPs highlight the potential of developing them into future generation of antimicrobial agents. There are various methods to synthesize NPs, and each of the method has significant implication on the biological action of NPs. Among all synthetic methods, green technology is the least toxic biological route, which is particularly suitable for biomedical applications. This mini-review provides current update on the antibacterial effects of NPs synthesized by green technology using plants. Underlying challenges in developing NPs into future antibacterials in clinics are also discussed at the present review.
  17. Abdelrahim LM, Peh SC, Kallarakkal TG
    Malays J Pathol, 2018 Apr;40(1):49-56.
    PMID: 29704384
    INTRODUCTION: Epstein-Barr virus (EBV) might be an aetiological agent involved in the pathogenesis of certain Non-Hodgkin's Lymphomas (NHLs). EBV infection has been diagnosed by serologic testing within the tumour biopsies of patients with NHL. However, the association between EBV and NHL is inconsistent with a preference for certain anatomic sites, histologic subtypes and immunosuppressed patients. The objective of this study was to characterise the B-cell NHLs of the oral cavity and maxillofacial region using histological and immunophenotypical techniques and to determine its association with EBV infection.

    MATERIALS AND METHODS: This was a descriptive cross-sectional study that included 14 cases of B-cell NHLs of the oral cavity and maxillofacial region. The haematopoietic and lymphoid tissue tumours classification of WHO was used to categorize the cases. In-situ hybridisation for EBV-encoded RNA was performed to confirm the EBV infection.

    RESULTS: The average age of the patients included in the study was found to be 48.8 ± 23 years with a higher female to male ratio (1.3:1). Our study suggested that diffuse large B-cell lymphomas (DLBCLs) and Burkitt's lymphomas (BLs) constitute the predominant subtypes of lymphomas affecting the oral cavity and maxillofacial regions.

    CONCLUSION: The findings from our study support the view that at least a relatively smaller proportion of B-cell NHLs that occur in the oral cavity and maxillofacial region do not have a pathogenic association with EBV.

  18. Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, et al.
    Sci Rep, 2017 09 28;7(1):12372.
    PMID: 28959019 DOI: 10.1038/s41598-017-12045-8
    Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.
  19. Teow SY, Yap HY, Peh SC
    J Pathog, 2017;2017:7349268.
    PMID: 29464124 DOI: 10.1155/2017/7349268
    Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets B-lymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt's lymphoma (BL), and Hodgkin's lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development as well as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside.
  20. Chook JB, Ngeow YF, Tee KK, Peh SC, Mohamed R
    J Pathog, 2017;2017:1231204.
    PMID: 29410920 DOI: 10.1155/2017/1231204
    Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%), K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%). We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.
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