Displaying publications 41 - 60 of 87 in total

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  1. 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.
  2. 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.

  3. Tai YC, Kim LH, Peh SC
    Pathol. Int., 2004 Mar;54(3):158-66.
    PMID: 14989738
    Natural killer (NK)/T-cell lymphomas are frequently associated with Epstein-Barr virus (EBV), and usually lack TCR gene rearrangement. Studies from Asia have reported frequent deletion in the LMP-1 gene in EBV-associated nasopharyngeal carcinoma (NPC). The present study aims to investigate LMP-1 and TCRgamma gene status in upper aerodigestive tract lymphomas. A total of 43 cases were classified into T-, B-, and NK/T-cell tumors based on the phenotype expressions of CD3(+)/CD20(-)/CD56(-), CD3(-)/CD20(+)/CD56(-), and CD3(+)/CD20(-)/CD56(+), respectively. The presence of EBV in the tumor was confirmed by EBV early RNA-in situ hybridization. LMP-1 gene deletion and TCR gamma gene rearrangement were analyzed by polymerase chain reaction on paraffin-embedded tissues. There were 20 NK/T-, eight T-, and 15 B-cell phenotype lymphomas in the present series, and EBV was detected in 19 (95%), two (25%), and three (20%) cases in the respective groups. All EBV+ cases carried 30-bp deletion in the LMP-1 gene, and two of the NK/T-cell cases were infected by both the wild type and deleted strains. Five (25%) of the NK/T-cell phenotype lymphomas showed rearranged TCR gamma gene. The present study revealed a high frequency of EBV association, and a high frequency of 30-bp deletion in the LMP-1 gene in the virus in the present series of lymphoma. The NK/T-phenotype lymphomas are comprised of both NK-cell and cytotoxic T-lymphocyte-derived tumors.
  4. Shia AK, Gan GG, Jairaman S, Peh SC
    J Clin Pathol, 2005 Sep;58(9):962-7.
    PMID: 16126878
    Recent reports have divided diffuse large B cell lymphoma (DLBCL) into germinal centre B cell-like and activated B cell-like subgroups with implicated differences in prognosis.
  5. Tai YC, Tan JA, Peh SC
    Pathol. Int., 2004 Nov;54(11):811-8.
    PMID: 15533223
    p53 gene mutation is not a frequent event in the tumorigenesis of lymphomas and the expression of p53 protein is independent of p53 gene mutations. The present study aimed to investigate mutations in the p53 gene in a series of extranodal B-cell lymphomas, and its association with p53 protein expression. A total of 52 cases were graded histologically into Grade 1, Grade 2 and Grade 3 tumors and p53 protein expression was detected using immunohistochemistry. Mutations in the p53 gene were analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and mobility shifts were confirmed by direct sequencing. The tumors comprised 26 (50%) Grade 1, 9 (17%) Grade 2 and 15 (29%) Grade 3. A high proportion of Grade 2 (25%) tumors expressed p53 protein (P = 0.051) and carried p53 gene mutation (33%) (P = 0.218). However, p53 protein expression was not associated with p53 gene mutations (P = 0.057). Transversion mutations (88%) were more frequently detected than transition mutations (12%). The present study revealed that p53 gene mutations and p53 protein expression occurred in higher frequencies in Grade 2 tumors, which may be of pathogenetic importance. The high frequency of transversion mutations may reflect the influence of an etiological agent in the tumorigenesis of mucosa-associated lymphoid tissue (MALT lymphoma).
  6. Peh SC
    Histopathology, 2001 May;38(5):458-65.
    PMID: 11422484
    AIMS: The pattern of malignant lymphoma is known to vary in different populations. This study aims to elucidate the effect of ethnicity on subtype frequency of non-Hodgkin's lymphoma and EBV association rate.

    METHODS AND RESULTS: A total of 232 reconfirmed lymphoma cases in Malaysian patients were retrieved from the archives in the Department of Pathology, University Hospital, Kuala Lumpur. There were 24 (10%) Hodgkin's and 208 (90%) non-Hodgkin's lymphomas, 173 of the latter were in adult group (aged > or = 15 years). The ethnic composition were 41 Malays, 107 Chinese, 21 Indians and four none of the above. A male : female ratio of 2.4 : 1 was observed. Complete immunohistochemical studies in 158 cases revealed 36 (23%) T-cell, 121 (76%) B-cell and one (1%) null-cell phenotype. Seventy-five percent of the T-cell lymphomas were peripheral T/NK-cell types. Among the classifiable lesions, low-grade/indolent lymphomas constituted 17%: 2% were the lymphocytic subtype and 10% were follicular lymphomas. Approximately one-third of the follicular lymphomas occurred in Indian patients. The largest group of high-grade lymphoma was diffuse large B-cell type (46%), followed by peripheral T/NK-cell (18%). A predominance of NK/T-cell lymphomas occurred in Chinese (5/7), and all were EBV associated. Burkitt's lymphoma accounted for 5% (eight cases), all were Chinese males, with a 38% EBV-association rate. The frequency of EBV-associated B-cell lymphoma is three times more common in Chinese than Malays. The EBV positivity rate among lymphomas in ethnic Malay, Chinese and Indian patients was 5%, 15% and 22%, respectively, and in T- and B-cell lymphomas was 36% and 7%, respectively.

    CONCLUSIONS: This Malaysian series reveals differences in the subtype frequencies of non-Hodgkin's lymphomas and EBV association rate amongst patients of various ethnic groups residing in the same environment.

  7. Sandvej K, Peh SC, Andresen BS, Pallesen G
    Blood, 1994 Dec 15;84(12):4053-60.
    PMID: 7994023
    In this study, we have sequenced the C-terminal part of the Epstein-Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV-positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T-cell lymphomas (PTLs) and from tonsils of Danish infectious mononucleosis (IM). Our study showed that some of the 7 single-base mutations and the 30-bp deletion previously detected between codons of amino acid 322 and 366 in the BNLF-1 gene of the nasopharyngeal carcinoma cell line CAO were present in all Malaysian PTLs and in 60% of the Danish PTLs. In HD and the IM cases, the mutations were present in about 30%. The 30-bp deletion and the single base mutations occurred independently, and mutations were detectable in the majority of EBV type B-positive cases. These findings suggest that the 30-bp deletion and the 7 single-base mutations in the C-terminal part of the CAO-BNLF-1 gene do not characterize a new EBV type A substrain. Rather, some of the positions of single base mutations and the 30-bp deletion are hot spots that may have mutated independently through the evolution of EBV strains.
  8. Shaminie J, Peh SC, Tan MJ
    Pathology, 2003 Oct;35(5):414-21.
    PMID: 14555386
    AIMS: PCR has been the primary method used for the detection of t(14;18) translocation in formalin-fixed, paraffin-embedded tissues. This technique mainly targets the well-characterised breakpoint regions in chromosomes 14 and 18. FISH is now applicable on paraffin tissue sections and has been suggested to be capable of detecting essentially 100% of t(14;18) translocated cases. In this study, we described the application of both PCR and FISH for the detection of t(14;18) translocation.

    METHODS: Fifty follicular lymphoma cases were retrieved from the files of the Department of Pathology, University of Malaya Medical Centre (UMMC). Nested PCR amplification of MBR/JH and mcr/JH was performed in these cases, and those cases that did not demonstrate the translocation were subjected to FISH analysis.

    RESULTS: Thirty cases (60%) had t(14;18) translocation detected by PCR, 25 (50%) had breakpoint with MBR and five (10%) involved mcr. Twenty cases without detectable t(14;18) translocation by PCR were analysed by FISH. Eleven cases were successfully probed, and four of them showed positive translocation signal.

    CONCLUSIONS: The combination of PCR and FISH analysis on paraffin tissue sections for the detection of t(14;18) translocation increases the sensitivity of detection from 60 to 68%. Problems encountered in our FISH analysis on tissue sections impose certain limitations in using this technique for retrospective screening of large number of samples. Therefore, we suggested the application of PCR as the first screening tool on retrospective archival materials, followed by FISH on those PCR-negative cases.

  9. 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.
  10. Hoe SL, Lee ES, Khoo AS, Peh SC
    Malays J Pathol, 2009 Jun;31(1):53-6.
    PMID: 19694314 MyJurnal
    The retinoblastoma-related gene Rb2/p130 has been reported to be mutated in several malignancies such as lung cancer and Burkitt's lymphoma. Nasopharyngeal carcinoma (NPC) is a common cancer in Malaysia especially amongst the ethnic Chinese. We screened for Rb2/p130 gene (exons 19 to 21) mutations in 53 archival NPC samples via PCR-SSCP-direct sequencing approach. Only one sample had a base change which involved a serine to glycine substitution at codon 995 (S995G). We conclude that Rb2/p130 genetic alterations are infrequent in NPC and may not be essential for the pathogenesis of the disease.
  11. 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.
  12. Peh SC, Looi LM, Lam KL, Teh BH
    Malays J Pathol, 1987 Aug;9:73-8.
    PMID: 3452712
    In the 12-year period between 1974 and 1985, 19 children aged between 8 and 12 years with systemic lupus erythematosus (SLE) were seen in the Department of Paediatrics, University Hospital, Kuala Lumpur. A preponderance of females (M:F = 1:2.8) and ethnic Chinese was evident. Renal biopsies revealed a wide Iange of renal morphology, including minimal change glomerulonephritis, focal proliferative glomerulonephritis, diffuse proliferative glomerulonephritis with varying degrees of severity and membranous glomerulonephritis. The majority (15) of patients had clinical SLE at the time of renal biopsy, of whom 4 were also grossly nephrotic. In the remaining 4 patients a diagnosis of SLE was made after further investigation for nephrotic syndrome (2) and acute nephritis (2). The pattern of renal pathology in childhood lupus nephritis appears not to differ significantly from adults.
    Key words: Systemic lupus erythematosus, glomerulonephritis
  13. 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.

  14. Peh SC, Danielle Quen QW
    Med J Malaysia, 2003 Jun;58(2):196-204.
    PMID: 14569739
    Epstein-Barr virus (EBV) is believed to have a pathogenic role in lymphomas of the upper-aerodigestive tract. This study aims to elucidate the virus association pattern in nasal and nasal-type NK/T-cell lymphomas, and in sequential biopsies of these tumours. A total of 31 cases of previously diagnosed as lethal midline granuloma. Stewart's granuloma, nasal T-cell non-Hodgkin's lymphoma (T-NHL) and NK/T-cell lymphomas from all anatomical sites were retrieved from the files for the study. Reviews of these cases confirm 8 nasal T-NHL, 19 nasal and 4 extranasal lymphomas of NK/T-cell phenotype from 10 Malays, 18 Chinese, 2 Indian and 1 Kadazan. The male: female ratio was 2.4: 1. All T- and NK/T-cell lymphomas strongly expressed TIA-1 and 63% expressed CD2. The majority of NK/T-cell lymphoma occurred in Chinese (13/23), of which 12/13 (92%) of these cases were associated with EBV. Of the 15 nasal and 9 tonsillar B-cell lymphomas included for a comparison study, only 3 (20%) of the nasal cases were associated with EBV (1 male Chinese, 1 female Chinese and 1 male of other ethnic group). Eight cases of NK/T-cell tumours with sequential biopsies show persistence of EBV, irrespective of the interval and sites of subsequent presentations. This study confirms the cytotoxic nature of NK/T-cell tumour and that EBV is strongly associated with the disease regardless of the anatomical site of presentation and ethnicity. However, nasal and paranasal lymphomas of all phenotypes appear to show higher predilection of EBV association in the ethnic Chinese when compared to non-Chinese.
  15. Tan LP, Ng BK, Balraj P, Lim PK, Peh SC
    Pathology, 2007 Apr;39(2):228-34.
    PMID: 17454753
    BACKGROUND AND AIMS: Colorectal cancers of different subtypes involve different pathogenic pathways like the Wnt and the mutator pathways. In this study, we screened 73 colorectal cancer cases from a multi-racial group for genetic and expression profile defects with the aim of correlating these with patients' clinicopathological characteristics.
    METHODS: Mutation screening of the entire coding region of APC and exon 3 of CTNNB1, loss of heterozygosity (LOH) of APC, and microsatellite instability (MSI) status were assessed for 44 patients with available paired frozen normal and tumour tissues. In addition, 29 cases with available paraffin embedded tumour blocks were screened for mutation in exon 3 of CTNNB1, the APC mutation cluster region (codon 1286-1513), and hMLH1, hMSH2, hMSH6 protein expressions by immunohistochemistry method.
    RESULTS: In our study, 15/73 cases showed APC mutations (20.5%), 1/73 cases had CTNNB1 mutation (1.4%), 5/32 cases had APC LOH (15.6%), and 16/70 (22.9%) cases revealed at least some form of mismatch repair (MMR) defect. Tumour grade (poor differentiation) was found to correlate significantly with right-sided tumour and mucinous histology (p = 0.01879 and 0.00320, respectively). Patients of younger age (below 45 years) more often had tumours of mucinous histology (p = 0.00014), while patients of older age (above 75 years) more often had tumours on the right side of the colon (p = 0.02448). Tumours of the mucinous histology subtype often had MMR defects (p = 0.02686). There was no difference in the occurrence of APC and CTNNB1 mutations and MMR defects found within our multi-racial colorectal cancer patient cohort.
    CONCLUSION: Our findings support the notion that racial factor may not be related to the occurrence of MMR defects and APC and CTNNB1 mutations in our multi-racial patient cohort.
  16. 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.
  17. Goh KL, Peh SC, Parasakthi N, Wong NW, Tan KK, Lo YL
    Am J Gastroenterol, 1994 Oct;89(10):1789-92.
    PMID: 7942668
    OBJECTIVES: Our objectives were to determine the effect of dual therapy with omeprazole and amoxicillin and of triple therapy with omeprazole, amoxicillin, and metronidazole in the eradication of Helicobacter pylori (HP) and to study the long-term results of eradication in these patients.
    METHODS: A prospective, randomized, controlled trial was performed. Patients who were recruited had unequivocal evidence of HP infection based on culture, histology, rapid urease test, and Gram's stain of a tissue smear. Eradication was defined as the absence of bacteria in all tests performed on both corpus and antral biopsies.
    RESULTS: The infection was eradicated in 15 of 19 (78.9%) patients randomized to receive dual therapy and in 19 of 22 (86.4%) patients who received triple therapy. We followed the course of 30 patients in whom HP had been eradicated for a prolonged term (up to 12 months). All remained clear of HP. Twenty-five of 28 patients (89.3%) with duodenal ulcers in whom HP was successfully eradicated remained healed at 12 months. Fewer side effects were reported among patients who received the dual therapy.
    CONCLUSIONS: Combination therapy with omeprazole and amoxicillin with or without metronidazole is effective in the eradication of HP. In particular, the dual therapy regimen with amoxicillin is not only effective but is also well tolerated by patients.
  18. Goh KSK, Ong TA, Peh SC, Yuen HL, Naicker M
    Med J Malaysia, 2004 Oct;59(4):515-21.
    PMID: 15779585
    Loss of P53 function is regarded as one of the critical steps in colorectal carcinogenesis. This study determines the P53 expression pattern of colorectal carcinoma in a cohort of 116 local patients. There was no significant relationship between overexpression of P53 with tumour stage (p=-0.209, chi square test) and grade (p=0.877, chi square test). Survival analysis using Kaplan-Meier procedure did not show significant relationship between P53 positivity with overall recurrence-free and survival outcome (p=0.3322 and 0.921 respectively; log rank test). Long-term follow-up may give a better evaluation on the prognostic value of P53 overexpression in colorectal carcinoma.
  19. Ong TA, Peh SC, Goh KSK, Naicker MS, Khan AF, Chua BC, et al.
    Asian J Surg, 2003 Jan;26(1):31-6.
    PMID: 12527492 DOI: 10.1016/S1015-9584(09)60212-8
    To study the incidence of p53 oncoprotein overexpression and its relationship to tumour grade, stage and clinical prognosis in a cohort of local Malaysian patients.
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