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Fulltext 14C-urea breath test: a useful non-invasive test in the diagnosis of Helicobacter pylori infection

Goh KL, Parasakthi N, Peh SC, Ong KK

Med J Malaysia, 1995 Sep;50(3):208-11.
PMID: 8926896

Sixty-three breath samples were collected from patients who underwent a 14C-urea breath test. Following ingestion of a radiolabelled 14C-labelled urea solution, breath samples containing 14C-labelled carbon dioxide were trapped in a solution containing hyamine hydroxide. Samples were then counted in a liquid scintillation counter. Breath samples were collected at 2, 15, 20, 25 and 30 minutes following ingestion of the urea solution. The presence or absence of Helicobacter pylori (HP) infection was determined on the basis of endoscopic biopsy tests which included culture, histological examination, rapid urease test and a gram stain of a fresh tissue smear. Thirty-two HP positive and 31 HP negative samples were collected. The mean counts at 15, 20, 12 and 30 minutes time points were: 4413, 4458, 4109 and 3795 dpm respectively for the positive samples and 1275, 877, 690 and 565 dpm respectively for the negative samples. Based on a cutoff value (mean of the negative samples + 3 standard deviations) for every time point, HP positive and negative samples could be clearly differentiated giving a sensitivity and specificity of 100%. The 14C-urea breath test is a reliable and convenient diagnostic test for H. pylori.
18q21 Rearrangement and trisomy 3 in extranodal B-cell lymphomas: a study using a fluorescent in situ hybridisation technique

Tai YC, Tan JA, Peh SC

Virchows Arch., 2004 Nov;445(5):506-14.
PMID: 15365830

t(11;18)(q21;q21) Translocation and trisomy 3 are the most common chromosomal aberrations reported in low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. The current study aims to investigate the frequency of these chromosomal aberrations in a series of 52 extranodal B-cell lymphomas. The tumours were categorised into three histological grades: grade 1 (low-grade lymphoma of MALT type), grade 2 [diffuse large B-cell lymphoma (DLBCL) with MALT component] and grade 3 (DLBCL without MALT component). Fluorescence in situ hybridisation analyses on paraffin tissue sections were performed using a locus-specific probe for the 18q21 region and a centromeric probe for chromosome 3. The 18q21 rearrangement was detected in 9 of 40 (23%) cases, including 7 of 23 (30%) grade-1 and 2 of 11 (18%) grade-3 tumours. Amplification of the 18q21 region was detected in 10 of 40 (25%) cases, and trisomy 3 was detected in 9 of 34 (26%) cases. Amplification of the 18q21 region may be an important alternative pathogenetic pathway in MALT lymphoma and was found almost exclusively in tumours without 18q21 rearrangement. Our study showed that tumours with 18q21 rearrangement and 18q21 amplification develop along two distinct pathways, and the latter was more likely to transform into high-grade tumours upon acquisition of additional genetic alterations, such as trisomy 3. Trisomy 3 was more frequently found in coexistence with 18q21 abnormalities, suggesting that it was more likely to be a secondary aberration.
A unilateral mesenchymal disorder of the head

Raman R, Kumar V, Arianayagam S, Peh SC

J Craniomaxillofac Surg, 1989 Apr;17(3):143-5.
PMID: 2708537

A hitherto undescribed group of lesions consisting of cystic bony lesions, exostosis, fibromatous lesion, unilateral tonsillar hypertrophy, epidermoid cyst (cholesteatoma) and hyperplasia of the mandible confined to the left side of the face is reported. The case may represent a variant of the Proteus syndrome.
Alpha-fetoprotein in hepatocellular carcinoma: a serological and histochemical study in Malaysian patients

Yap SF, Peh SC

Malays J Pathol, 1991 Dec;13(2):115-8.
PMID: 1726642

Serum alpha-fetoprotein (AFP) levels and its expression in liver tissue was studied in 50 cases of histologically confirmed hepatocellular carcinoma (HCC). Serum AFP levels were elevated (greater than 20iu/ml) in 35/50 (70%) of the cases, 28 of whom had levels greater than 500 iu/ml, which is highly suggestive of HCC. These results indicate that serum AFP, by itself, is a relatively insensitive diagnostic test for HCC. Although elevated levels in high risk patients provide a specific clue, a negative result does not exclude the diagnosis of HCC. Expression of AFP by tumour cells paralleled that of serum in the majority of cases. However, tissue AFP was negative in 7 patients who had markedly elevated serum AFP. This observation may be a reflection of preferential excretion of the tumour antigen or differential expression of the antigen by the tumour cells. None of the patients with normal serum AFP demonstrated a reaction for tissue AFP. There was no correlation between AFP production and tumour differentiation.
Fulltext An immunohistochemical and molecular study of gastrointestinal stromal tumours

Teong YT, Teo ST, Tan LP, Wu BQ, Peh SC

Med J Malaysia, 2006 Dec;61(5):526-33.
PMID: 17623951 MyJurnal

Gastrointestinal stromal tumour (GIST) is a rare but most common mesenchymal tumour in the gastrointestinal tract. Although GIST research has been carried out extensively worldwide, it has yet to be studied in Malaysia. To establish the immunohistochemical expression pattern of CD117 (c-KIT), CD34, S-100 and Desmin, the incidence of c-KIT and PDGFRA genes mutation in GISTs, and correlate it with clinicopathological parameters. Eleven clinically diagnosed GISTs were stained for CD117, CD34, Desmin and S-100 protein by immunohistochemical technique, and c-KITand PDGFRA gene mutations were studied by PCR-CSGE-DNA sequencing method. All GISTs (7 cases) stain positive for CD117, and co-expressed CD34. None of these cases express Desmin, and only one expressed S-100 protein focally. Fifty-seven percent (4/7 cases) of GIST harboured mutations at exon 11 of c-KIT gene, and they were all high risk and malignant cases. No mutation was detected at exons 9, 13 and 17 of KIT gene, and exons 12 and 18 of PDGFRA gene. Immunohistochemistry using a panel of antibodies shows consistent pattern of CD117 and CD34 expression in GIST, and mutational study may be a useful prognostic marker for kinase inhibitor treatment of GIST.
Analyses of Epstein-Barr virus latent membrane protein-1 in Malaysian nasopharyngeal carcinoma: high prevalence of 30-bp deletion, Xho1 polymorphism and evidence of dual infections

Tan EL, Peh SC, Sam CK

J Med Virol, 2003 Feb;69(2):251-7.
PMID: 12683415

Nasopharyngeal carcinoma, a malignancy associated closely with Epstein-Barr virus (EBV), is prevalent among Chinese of Southern China origin. Epidemiological studies indicate a high prevalence of EBV in Asia with viral isolates having typical characteristics of the putative viral oncogene, latent membrane protein 1 (LMP-1), such as the loss of the Xho1 restriction site in Exon 1 and the 30-bp deletion in Exon 3. The EBV LMP-1 gene from throat washings of 120 nasopharyngeal carcinoma patients and 14 healthy individuals were analyzed. Similar analyses were also carried out on 30 and 12 postnasal space biopsies from nasopharyngeal carcinoma patients and healthy individuals, respectively. The 30-bp deletion was detected in 20% of nasopharyngeal carcinoma throat washes and in 100% of nasopharyngeal carcinoma postnasal space biopsies. Interestingly, 16% of the nasopharyngeal carcinoma biopsies possessed both the deleted and the undeleted variants, suggestive of dual infections. The notion of dual infections in nasopharyngeal carcinoma was further supported by the coexistence of both "F" and "f" (BamH1F region) EBV variants in 11% of the nasopharyngeal carcinoma biopsies. All of the throat washes and biopsies from the healthy controls showed the undeleted variant. The loss of the Xho1 restriction site was found with higher frequency both in throat washes and biopsies from patients with nasopharyngeal carcinoma. The discrepancy in the frequency of the 30-bp deletion between throat washes (20%) and postnasal space biopsies (100%) was an indication that this deletion is specific for viral isolates from primary tumour sites.
Angiomyolipoma of the vagina--an uncommon tumour. Case report

Peh SC, Sivanesaratnam V

Br J Obstet Gynaecol, 1988 Aug;95(8):820-3.
PMID: 3166957
Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

Teow SY, Liew K, Ali SA, Khoo AS, Peh SC

J Trop Med, 2016;2016:2853045.
PMID: 27956904

Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family) or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus). As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived from plant is believed to have profound medicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by the multidrug-resistant strains, have emerged as a global health issue and urgent action is needed. This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent.
Association between autophagy and KRAS mutation with clinicopathological variables in colorectal cancer patients

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.
Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients

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.
Fulltext Bactericidal Properties of Plants-Derived Metal and Metal Oxide Nanoparticles (NPs)

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.
Fulltext Bone marrow and peripheral blood changes in non-Hodgkin's lymphoma

Lim EJ, Peh SC

Singapore Med J, 2000 Jun;41(6):279-85.
PMID: 11109344

47 patients with non-Hodgkin's lymphoma (NHL) were studied retrospectively to determine their marrow and blood changes at diagnosis.
Fulltext C-MYC, BCL2 and BCL6 Translocation in B-cell Non-Hodgkin Lymphoma Cases

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.
Fulltext CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma

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.
Campylobacter pylori infection: experience in a multiracial population

Goh KL, Peh SC, Wong NW, Parasakthi N, Puthucheary SD

J Gastroenterol Hepatol, 1990 5 1;5(3):277-80.
PMID: 2103410

Over a 15-month period, 399 patients with dyspepsia were investigated for the presence of Campylobacter pylori infection. Half of the patients (50.6%) had Campylobacter organisms in the antrum of the stomach. C. pylori was found in 96.1% of patients with histological changes of chronic active gastritis in the antrum. Of patients with duodenal and gastric ulcers, 87.8% and 87.5%, respectively, had Campylobacter organisms, as did 39.3% of patients with non-ulcer dyspepsia. C. pylori infection was most commonly found in Chinese and Indians. Although the prevalence of infection appeared to increase with age, there was an equal distribution amongst the sexes.
Fulltext Cerebrospinal fluid rhinorrhoea secondary to amyloidosis of the sphenoid sinus

Ali EA, Philip R, Prepageran N, Peh SC

Med J Malaysia, 2008 Oct;63(4):341-2.
PMID: 19385501 MyJurnal

Amyloidosis of the skull base is a rare entity. A patient with localized amyloidosis of the sphenoid sinus presented at our institution with cerebrospinal fluid rhinorrhoea. Endoscopic excision of the lesion and multilayered obliteration of the sphenoid sinus resolved the symptoms.
Chronic pyelonephritis: the significance of renal renin and the vascular changes in the human kidney

Peh SC, Lindop GB

J Pathol, 1991 Apr;163(4):343-9.
PMID: 2033493

Hypertension complicates chronic pyelonephritis. Since arterial narrowing is common in the damaged kidney, activation of the renin-angiotensin system due to renal ischaemia has been suggested as a pathogenetic mechanism. We used an antiserum to human renin and an immunoperoxidase technique to study the anatomy of renin-containing cells (RCC) in 18 kidneys removed for pyeloneophritis. We independently assessed the degree of arterial narrowing and correlated these variables with the clinical findings. There was histological evidence of hyperplasia of RCC in 5 of the 6 hypertensive patients and in 7 of the 12 non-hypertensive cases. There was no difference in the apparent number or distribution of RCC between the hypertensive and the non-hypertensive cases. Also, the degree of arterial narrowing did not correlate with either the hyperplasia of RCC or the blood pressure of the patients. Our results do not support the hypothesis that narrowing of the intrarenal arteries is important in the pathogenesis of hypertension in pyelonephritis. In our cases, the renal veins were more severely damaged than the arteries and their lumina were often obliterated by organized thrombus. We suggest that such widespread obliteration of the renal venous tree could impair blood flow and contribute to the tissue damage in the pyelonephritic kidney.
Clinical relevance of CD10, BCL-6 and multiple myeloma-1 expression in diffuse large B-cell lymphomas in Malaysia

Peh SC, Gan GG, Lee LK, Eow GI

Pathol. Int., 2008 Sep;58(9):572-9.
PMID: 18801072 DOI: 10.1111/j.1440-1827.2008.02273.x

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and it is recognized to constitute a heterogenous group of neoplasms. It can be divided into germinal center B-cell-like (GCB) and non-GCB subgroups. The aim of the present study was to evaluate the utility of immunophenotype subgrouping of DLBCL in a cohort of multi-ethnic Asian patients. A total of 84 reconfirmed de novo DLBCL were immunostained for the expression of CD10, BCL-2, BCL-6 and multiple myeloma-1. Thirty-three (39.3%) had the GCB phenotype, and the remainder (60.7%), the non-GCB phenotype. The results concur with most reports using a similar method of stratification. Forty-five patients had complete demographic and phenotype studies and 42 patients did not have rituximab treatment and had sufficient data for survival rate analysis. Similar to other studies, patients with combined low and low-intermediate International Prognostic Index score had better overall survival (P = 0.006). But patients with GCB phenotype did not have better prognosis, and BCL-2 expression was not associated with better prognosis. The expression of BCL-6 was associated with lower overall survival rate (P = 0.038). No apparent difference in overall and disease-free survival was noted between patients with GCB and non-GCB disease. BCL-6 expression by tumor cells appears to be associated with poorer prognosis.
Fulltext Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota

Loke YL, Chew MT, Ngeow YF, Lim WWD, Peh SC

Front Cell Infect Microbiol, 2020;10:603086.
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.
Common ALK gene rearrangement in Asian CD30+ anaplastic large cell lymphoma: an immunohistochemical and fluorescence in situ hybridisation (FISH) study on paraffin-embedded tissue

Tai YC, Kim LH, Peh SC

Pathology, 2003 Oct;35(5):436-43.
PMID: 14555389

AIMS: The most common recurrent genetic aberration in anaplastic large cell lymphoma (ALCL) is translocation involving the ALK gene that results in ectopic expression of ALK protein in lymphoid tissue. This study aims to investigate the frequency of ALK gene rearrangement in a series of Asian ALCL.
METHODS: ALK gene rearrangement was detected by immunostaining of ALK protein and fluorescence in situ hybridisation (FISH) targeting at the 2p23 region.
RESULTS: The expression of ALK protein was detected in 24/34 (71%) of the cases, and it was significantly higher in childhood cases (100%) when compared to adult cases (47%). The analyses by FISH were consistent with the results from immunostaining of ALK protein, but the analyses were only successful in 15/34 (44%) cases. FISH analyses detected extra copies of ALK gene in three cases, including one case that expressed ALK protein and showed 2p23 rearrangement.
CONCLUSIONS: The current series revealed a high frequency of ALK gene rearrangement, especially in the children. Immunostaining of ALK protein is a reliable indication of ALK gene rearrangement, and is superior to FISH. However, FISH analysis is useful in detecting other genetic aberrations that are not related to ALK gene rearrangement.

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