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Insertion sequence typing of Mycobacterium tuberculosis: characterization of a widespread subtype with a single copy of IS6110

Fomukong NG, Tang TH, al-Maamary S, Ibrahim WA, Ramayah S, Yates M, et al.

Tuber. Lung Dis., 1994 Dec;75(6):435-40.
PMID: 7718832 DOI: 10.1016/0962-8479(94)90117-1

DNA fingerprinting with the insertion sequence IS6110 (also known as IS986) has become established as a major tool for investigating the spread of tuberculosis. Most strains of Mycobacterium tuberculosis have multiple copies of IS6110, but a small minority carry a single copy only. We have examined selected strains from Malaysia, Tanzania and Oman, in comparison with M. bovis isolates and BCG strains carrying one or two copies of IS6110. The insertion sequence appears to be present in the same position in all these strains, which suggests that in these organisms the element is defective in transposition and that the loss of transposability may have occurred at an early stage in the evolution of the M. tuberculosis complex.
Molecular epidemiology of tuberculosis in Malaysia

Dale JW, Nor RM, Ramayah S, Tang TH, Zainuddin ZF

J Clin Microbiol, 1999 May;37(5):1265-8.
PMID: 10203468

Molecular typing with IS6110 was applied to Mycobacterium tuberculosis isolates from all parts of Malaysia. The degree of clustering increased with patient age, suggesting that reactivation may contribute to clustering. Identical banding patterns were also obtained for isolates from widely separate regions. Therefore, the use of clustering as a measure of recent transmission must be treated with caution. Strains related to the Beijing family were common in Peninsular Malaysia but were less common in Sabah and Sarawak, while a distinct group of strains comprised nearly 40% of isolates from East Malaysia but such strains were rare in Peninsular Malaysia. Single-copy strains, common in South and Southeastern Asia, constituted nearly 20% of isolates from the peninsula but were virtually absent in East Malaysia. The marked geographical difference in the prevailing strains indicates not only a restricted dissemination of M. tuberculosis but also a considerable degree of stability in the banding patterns.
Liquid chromatographic detection of Dowtherm A contamination in oleochemicals and edible oils

Moh FM, Tang TS

J AOAC Int, 1999 8 13;82(4):893-6.
PMID: 10444829

A rapid and direct liquid chromatographic (LC) technique is described for the determination of a eutectic mixture of diphenyl oxide and biphenyl such as Dowtherm A thermal heating fluid (THF) in oleochemicals and palm olein. Analysis is performed with an RP-18 column with fluorescence detection (excitation at 247 nm and emission at 310 nm). The isocratic mobile phase (1.0 mL/min) consists of methanol and water (90 + 10, v/v). A linear calibration model (correlation coefficient = 0.9999) was developed directly from used Dowtherm A THF with the biphenyl peak (4.70 min) as a marker. Average recoveries from spiked glycerin, fatty alcohol mixture, methyl ester mixture, fatty acids, and palm olein were 90.9-108.7%, with a detection limit of 0.1 microgram/mL. The technique requires no prior sample cleanup nor extraction steps and is good for quality assurance purposes.
A direct high-performance liquid chromatographic method for the determination of therminol 66 contamination in commercial glycerin and fatty acids

Moh MH, Tang TS, Tan GH

J Chromatogr Sci, 2001 Dec;39(12):508-12.
PMID: 11767238

A simple and sensitive high-performance liquid chromatographic method for the determination of Therminol 66 thermal heating fluid in glycerin and fatty acids is developed. Sample solutions dissolved in methanol-tetrahydrofuran (50:50, v/v) are injected directly into a reversed-phase C18 column and eluted with a methanol and water mixture (88:12, v/v). The concentration of the thermal heating fluid is monitored by fluorescence detection at 257 nm (excitation) and 320 nm (emission). The calibration graph obtained from various concentrations of the thermal heating fluid in the methanol and tetrahydrofuran mixture is linear (correlation coefficient = 0.999), and the limit of detection is 0.01 microg/mL. Spiked glycerin containing 0.1 to 1.0 microg/g of the thermal heating fluid also gives good linearity with a mean recovery of 95.3%. The mean intra- and interassay precision are 1.80-6.51% and 5.71-9.03%, respectively, at the 0.1-microg/g level. The method is simple and does not require any pretreatment step, thus it is ideal for quality assurance purposes.
Strategies for evaluating B*18 allelic diversity by sequence-based typing applied to studies of a population from Singapore and African-Americans

Hou L, Tu B, Ling G, Tang T, Cao K, Steiner NK, et al.

Tissue Antigens, 2006 Jan;67(1):66-9.
PMID: 16451205

Strategies to resolve B*18 alleles which carry a deletion in intron 1 close to the 5' end of exon 2 relative to other HLA-B alleles or a null allele mutation in exon 1 and to resolve ambiguities among allele combinations including B*18 are described. B*18 allele frequencies from volunteer donors recruited for two hematopoietic stem cell registries show the presence of two alleles, B*180101 and B*1802, in a population from Singapore and only B*180101 in African-Americans.
Reducing by half the percentage of late-stage presentation for breast and cervix cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia

Devi BC, Tang TS, Corbex M

Ann. Oncol., 2007 Jul;18(7):1172-6.
PMID: 17434897 DOI: 10.1093/annonc/mdm105

BACKGROUND:
The registry of the Oncology Departmental in Sarawak General Hospital showed that 79% of nasopharyngeal, 77% of breast and 70% of cervix cancer patients were diagnosed at an advanced stage (stages III and IV) for year 1993. Hence, a low cost Early Cancer Surveillance Program was started in 1994, with the intent of downstaging these three most common cancers in Sarawak.

MATERIALS AND METHODS:
The program consisted of (i) training health staff in hospital and rural clinics to improve their skills in early cancer detection, (ii) raising public awareness through pamphlets, posters and sensitization by health staff.

RESULTS:
Data analysis revealed that the program achieved downstaging in two of the cancers. Breast cancer in stage III and IV was reduced from 60% (1994) to 35% (1998) (P < 0.0001) and cervical cancer in stage III and IV from 60% (1994) to 26% (1998) (P < 0.0001). No reduction was observed for nasopharyngeal cancer at 88% (1994) to 91% (1998).

CONCLUSIONS:
The overall cost of this program was
Fulltext Evaluation of polymerase chain reaction (PCR) method and hybrid capture II (HCII) assay for the detection of human papillomavirus in cervical scrapings

Saini R, Shen TH, Othman NH, Santhanam J, Othman N, Tang TH

Med J Malaysia, 2007 Aug;62(3):206-9.
PMID: 18246908 MyJurnal

In order to investigate the reliability of detecting HPV DNA in cervical smears, we compared the performance of nested MY/GP PCR and FDA approved-Hybrid Capture II (HCII) using clinical cervical scrapings from 40 patients. It was found that PCR was more sensitive (81.8%) in comparison to HCII (36.4%) in detecting HPV although specificity of HCII was much higher (96.6%) than PCR (58.6%). The Negative Predictive Value (NPV) of both the techniques were quite similar but Positive Predictive Value (PPV) of HCII was much higher (80.0%) compared to PCR (42.9%). While the HCII method showed good specificity for HPV detection, its lack of sensitivity as compared to PCR may be a drawback for diagnostic use.
Fulltext Preliminary results from the pilot study on the National Cancer Patient Registry--Cervical Cancer

Devi Beena CR, Tang TS, Gerard LC

Med J Malaysia, 2008 Sep;63 Suppl C:63-5.
PMID: 19230250

Carcinoma of the cervix is the most common malignancy in many developing countries. The purpose of this pilot study on cervical cancer patients treated at selected sites in Malaysia is to examine the achievability of collecting information on patients. The data was collected from the medical records of the patients using case report form. The results reveal that more than 90% of the forms had completed data from all sites. The pilot study has demonstrated that it is feasible to register and collect information on cervical cancer patients using the case report forms. Treatment outcome obtained from this data will form the baseline to establish existing clinical practice and will be useful for treating physicians to monitor the treatment outcome and the late complications and with longer followup to measure the disease free and overall survival. In addition, it is an useful tool as the national indicator.
Fulltext Setting up home-based palliative care in countries with limited resources: a model from Sarawak, Malaysia

Devi BC, Tang TS, Corbex M

Ann Oncol, 2008 Dec;19(12):2061-6.
PMID: 18641007 DOI: 10.1093/annonc/mdn422

The provision of palliative care (PC) and opioids is difficult to ensure in remote areas in low- and middle-income countries. We describe here the set up of a home-care program in Sarawak (the Malaysian part of the Borneo Island), where half the population lives in villages that are difficult to access.
Documenting pain as the fifth vital sign: a feasibility study in an oncology ward in Sarawak, Malaysia

Devi BCR, Tang TS

Oncology, 2008;74 Suppl 1:35-9.
PMID: 18758195 DOI: 10.1159/000143216

BACKGROUND: Monitoring acute postoperative pain as the fifth vital sign is currently practiced in many developed countries. In Sarawak, pain is an important symptom as 70% of cancer patients present with advanced disease. As the existing validated pain assessment tools were found to be difficult to use, we studied the feasibility of modifying the use of a pain assessment tool, consisting of the short form of the Brief Pain Inventory and the Wong-Baker Faces Scale.
METHOD: This tool was used to document pain in all 169 patients who were admitted for pain control to the oncology ward between July 2000 and June 2001. Nurses were trained in the use of the modified scale before the start of the study.
RESULTS: The method was easy to use, and the mean number of days to reduce pain was found to be 3.1 days (SD: 2.9; median: 2 days; range: 1-31 days). At discharge, none in the group with initially mild pain had pain, and the severity of pain for 98% of patients with moderate pain and 61% with severe pain was downgraded to mild pain.
CONCLUSION: The staff found that the tool allowed continuous pain assessment in an objective manner.
Fulltext Draft Genome Sequence of a Clinical Isolate of Mycobacterium tuberculosis Strain PR05

Ismail A, Teh LK, Ngeow YF, Norazmi MN, Zainul ZF, Tang TH, et al.

Genome Announc, 2013;1(3).
PMID: 23788553 DOI: 10.1128/genomeA.00397-13

We report the annotated genome sequence of a clinical isolate, Mycobacterium tuberculosis strain PR05, which was isolated from the human cerebrospinal fluid of a patient diagnosed with tuberculosis.
Fulltext Differentiating Schistosoma haematobium from Schistosoma magrebowiei and other closely related schistosomes by polymerase chain reaction amplification of a species specific mitochondrial gene

Akinwale OP, Hock TT, Chia-Kwung F, Zheng Q, Haimo S, Ezeh C, et al.

Trop Parasitol, 2014 Jan;4(1):38-42.
PMID: 24754026 DOI: 10.4103/2229-5070.129163

Schistosoma haematobium infection afflicts about 150 million people in 53 countries in Africa and the Middle East. In many endemic areas, S. haematobium is sympatric with Schistosoma bovis, Schistosoma mattheei, Schistosoma curassoni, Schistosoma intercalatum and Schistosoma magrebowiei, its closely related species. In addition, they also develop in the same intermediate snail hosts. Since these schistosome species often infect snails inhabiting the same bodies of water, examining cercariae or infected snails for estimating transmission of S. haematobium is always confounded by the need to differentially identify S. haematobium from these other species. Recently, differentiating S. haematobium by polymerase chain reaction (PCR) from S. bovis, S. mattheei, S. curassoni and S. intercalatum, but not from S. magrebowiei was reported. However, to be able to evaluate residual S. haematobium transmission after control interventions in areas where S. haematobium may be sympatric with S. magrebowiei, a differential tool for accurate monitoring of infected snails is needed.
Fulltext Metabolomics for characterization of gender differences in patients infected with dengue virus

Shahfiza N, Osman H, Hock TT, Shaari K, Abdel-Hamid AH

Asian Pac J Trop Med, 2015 Jun;8(6):451-6.
PMID: 26194829 DOI: 10.1016/j.apjtm.2015.05.012

OBJECTIVE: To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of (1)H NMR-spectrometry.
METHODS: The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with (1)H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database, Chenomx Profiler.
RESULTS: The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions; infected with dengue. Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle.
CONCLUSIONS: The (1)H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures, gave an evidence for the existence of distinct metabolic differentiation of individuals, according to their gender, modulates with the infection risk.
Fulltext JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

Nairismägi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, et al.

Leukemia, 2016 06;30(6):1311-9.
PMID: 26854024 DOI: 10.1038/leu.2016.13

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Fulltext Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study

Li Z, Xia Y, Feng LN, Chen JR, Li HM, Cui J, et al.

Lancet Oncol, 2016 Sep;17(9):1240-7.
PMID: 27470079 DOI: 10.1016/S1470-2045(16)30148-6

BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL.
METHODS: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset.
FINDINGS: Associations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection.
INTERPRETATION: To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.
FUNDING: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).
Letter to Editor re: 'Mechanochemical endovenous ablation of saphenous veins using the ClariVein: A systematic review' - MOCA data reporting needs to be tighter and standardized!

Saravana K, Tang TY

Phlebology, 2017 12;32(10):679-681.
PMID: 28764596 DOI: 10.1177/0268355517724618
Interleukin-28 Polymorphism: Ethnic variations and the response to chronic hepatitis C treatment in Malaysia

Hoe CH, Suan MAM, Hoe CH, Tang TH, Kiew KK, Hassan MRA, et al.

Med J Malaysia, 2018 08;73(4):260.
PMID: 30121693

No abstract provided.
Fulltext In-vitro evaluation of apoptotic effect of Germacrone on human melanoma, cervical and gastric adenocarcinoma

Tang, T. F., Loh, C. Y., Khaing, S. L., Looi, C. Y., Wong, Won Fen

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):24-24.
MyJurnal

Introduction: Germacrone is a natural product isolated from Rhizoma curcuma with anti-tumor, anti-inflammatory, and anti-bacterial properties. Previous studies have demonstrated that Germacrone exhibits anti-tumor effect in breast and hepatoma cancer cell lines but the studies of its molecular mechanisms and anti-tumor properties in other cancers are not well studied. This study aims to investigate the anti-tumor effect of Germacrone on human skin, cervix, and gastric cancer cell lines and the molecular mechanism underlying the anti-tumor effect of Germacrone. Methods: A375 (skin malignant melanoma), AGS (gastric adenocarcinoma), and HeLa 229 (cervix adenocarcinoma) cell lines were employed for this research. Treatment of the cell lines with Germacrone has inhibited the cell proliferation in a dose-dependent manner as assessed by MTT assay. The cell lines were incubated with Germacrone for 24 hours followed by detection of the expression of BAX, BAK, p53, BCL2, MCL1, and BCL-XL using Real-time PCR. Results: Results from Real-time PCR has showed that pro-apoptotic gene BAK was highly expressed in all the human cell lines after the treatment with Germacrone. Furthermore, the expression of pro-apoptotic gene p53 were elevated in both A375 and HeLa 229 cell lines but not inAGS cell lines. The expression level of pro-survival genes BCL2 and MCL1 were found to be decreased in both AGS and A375 cell lines. Conclusion: In conclusion, Germacrone might be a potent anti-tumor drug candidate for Human Melanoma, Cervix Adenocarcinoma, and Gastric Adenocarcinoma by increasing the expression level of pro-apoptotic proteins BAK. Future studies will focus on studying the cytotoxicity effect of combination of Germacrone with standard chemotherapy drugs on Human Melanoma, Cervix Adenocarcinoma, and Gastric Adenocarcinoma.
Fulltext The role of Hedgehog signalling pathway in human cancers development

Loh C. Y., Tang, T. F., Wong, W. F., Looi, Chung Yeng

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):22-22.
MyJurnal

Introduction: The Hedgehog (Hh) pathway serves as a major regulator in organ development, stem cell maintenance, cell proliferation, and cell differentiation. This pathway is highly regulated and aberrant activation will promote tumorigenesis. Hh pathway notably Sonic Hedgehog pathway was reported to be upregulated and promote tumorigenesis in various human malignancies including colorectal, gastric, lung, prostate, and breast. This review was aimed to discuss the current understanding of Hh pathway activation in different types of human cancers and discuss the development of the therapeutic applications targeting Hh pathway. Methods: A systematic review was conducted using the electronic research database PubMed Central (PMC) from 2014-2019. The search was limited to studies that are relevant to both Hh signalling pathway and human cancers. A total of 50 articles were selected and their references cited were searched and reviewed. Results: The results regarding the role of Hh signalling in pancreatic cancer and colorectal cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive activity. Besides, results from other studies suggesting that Hh signalling pathway plays an oncogenic role by inducing tumor cells proliferation, promoting metastasis and maintaining cancer stem cells in human cancers such as lung, stomach, and breast. To date, Glasdegib (PF-04449913) is the only Hh targeting small molecule inhibitor being studied at FDA Phase 3 clinical trial. Identification of the right tumors and minimization of the side effects remain as the main obstacles in the development of Hh signalling inhibitors. Conclusion: In conclusion, advancement in our understanding of Hh pathway has provided us opportunity to develop novel therapeutic strategies to fight human cancers with activated Hh pathway but more studies need to be conducted to solve the controversial regarding the role of Hh pathway in certain cancers.
Fulltext Physicochemical and sensory analyses of high fibre bread incorporated with corncob powder

Lee, C. M., Gan, Y. L., Chan, Y. L., Yap, K. L., Tang, T. K., Tan, C. P., et al.

International Food Research Journal, 2019;26(5):1609-1616.
MyJurnal

The primary objectives of the present work were to produce corncob powder (CCP) from
corncobs and incorporate the CCP into bread formulation in order to develop high fibre bread,
and to investigate the physicochemical and sensory properties of the produced high fibre
bread (HFB). The corncobs were collected and washed before they underwent the grinding
and drying processes. The obtained CCP was incorporated into the bread formulation in three
different proportions (5, 10 and 20%) to partially substitute bread flour in the formulation. All
three bread samples and the control (0% CCP in the formulation) were analysed to obtain their
physicochemical and sensory properties. The incorporation of CCP significantly affected the
texture, colour and volume attributes of the produced breads. Increasing the content of CCP
in the formulation was found to be responsible for firmer, smaller and darker bread loaves as
compared to the composite bread samples. The bread formulation incorporated with 10% CCP
had the highest mean scores (7.00) of overall acceptability among all the other formulations,
and it was comparable to the commercial breads in the current market.

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