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  1. Wong SF, Lai LC
    Pathology, 2001 Feb;33(1):85-92.
    PMID: 11280615
    Transforming growth factor beta (TGFbeta) is secreted as a large latent precursor from both normal and transformed cells which needs to be activated for biological activity. The active TGFbeta binds either directly to TbetaR-II or indirectly by binding to beta-glycan which then presents the TGFbeta to TbetaR-II. Formation of the TGFbeta-TbetaR-II complex rapidly leads to phosphorylation of TbetaR-I. TbetaR-I, in turn, phosphorylates receptor-specific Smads and induces their translocation into the nucleus. TGFbeta is able to act as a growth stimulator or inhibitor and elicits a broad spectrum of biological effects on various cell types. However, these cells may lose their sensitivity and responsiveness to TGFbeta. Down-regulation or loss of functional receptors, aberrant signal transduction pathways due to Smad mutations, loss of the cell's ability to activate latent TGFbeta, loss of the peptide itself or functional genes that control the transcription and translation of TGFbeta may contribute to development of cancer.
  2. Mohd Fahmi Z, Lai LL, Loh PS
    Med J Malaysia, 2015 Aug;70(4):243-8.
    PMID: 26358022 MyJurnal
    BACKGROUND: Preoperative anxiety is a significant problem worldwide that may affect patients' surgical outcome. By using a simple and reliable tool such as the Amsterdam Preoperative Anxiety and Information Scale (APAIS), anaesthesiologists would be able to assess preoperative anxiety adequately and accurately.

    OBJECTIVE: The purpose of this study was to develop and validate the Malay version of APAIS (Malay-APAIS), and assess the factors associated with higher anxiety scores.

    METHODS: The authors performed forward and backward translation of APAIS into Malay and then tested on 200 patients in the anaesthetic clinic of University Malaya Medical Centre. Psychometric analysis was performed with factor analysis, internal consistency and correlation with Spielberger's State-Trait Anxiety Inventory (STAI-state).

    RESULTS: A good correlation was shown with STAI-state (r = 0.59). Anxiety and need for information both emerged with high internal consistency (Cronbach's alpha 0.93 and 0.90 respectively). Female gender, surgery with a higher risk and need for information were found to be associated with higher anxiety scores. On the other hand, previous experience with surgery had lower need for information.

    CONCLUSION: The Malay-APAIS is a valid and reliable tool for the assessment of patients' preoperative anxiety and their need for information. By understanding and measuring patient's concerns objectively, the perioperative management will improve to a much higher standard of care.
  3. Nesaretnam K, Jin Lim E, Reimann K, Lai LC
    Toxicology, 2000 Oct 26;151(1-3):117-26.
    PMID: 11074306
    Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.
  4. Ng JH, Nesaretnam K, Reimann K, Lai LC
    Int J Cancer, 2000 Oct 1;88(1):135-8.
    PMID: 10962451
    Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.
  5. Wong SF, Reimann K, Lai LC
    Pathology, 2001 Nov;33(4):454-9.
    PMID: 11827412
    Oestrogens play an important role in the development of breast cancer. Oestrone sulphate (E1S) acts as a huge reservoir of oestrogens in the breast and is converted to oestrone (E1) by oestrone sulphatase (E1STS). E1 is then reversibly converted to the potent oestrogen, oestradiol (E2) by oestradiol-17beta hydroxysteroid dehydrogenase (E2DH). The aim of this study was to assess the effects of transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) on cell growth, E1STS and E2DH activities in the MCF-7 and MDA-MB-231 human breast cancer cell lines. TGFbeta1, IGF-I and IGF-II alone or in combination inhibited cell growth of both cell lines but no additive or synergistic effects were observed. The treatments significantly stimulated E1STS activity in the MCF-7 cell line, except for TGFbeta1 alone and TGFbeta1 and IGF-I in combination, where no effects were seen. Only TGFbeta1 and IGF-II acted synergistically to stimulate E1STS activity in the MCF-7 cells. There was no significant effect on E1STS activity in the MDA-MB-231 cells with any of the treatments. In the MCF-7 cells, TGFbeta1 and IGF-I, IGF-I and IGF-II, and TGFbeta1, IGF-I and IGF-II acted synergistically to stimulate the reductive E2DH activity, while only TGFbeta1, IGF-I and IGF-II synergistically stimulated the oxidative E2DH activity. There were no additive or synergistic effects on both oxidative and reductive E2DH activities in the MDA-MB-231 cells. In conclusion, TGFbeta1, IGF-I and IGF-II may have effects on oestrogen metabolism, especially in the MCF-7 cell line where they stimulated the conversion of E1S to E1 and E1 to E2 and, thus, may have roles to play in the development of breast cancer.
  6. Elsadig RE, Reimann K, Yip CH, Lai LC
    Anticancer Res, 2001 Jul-Aug;21(4A):2693-6.
    PMID: 11724341
    Oestrone sulphate is a major source of active oestrogens in the breast. It is converted to oestrone by oestrone sulphatase. Breast cyst fluid (BCF) is a rich source of sex hormones and growth factors. BCF obtained from British women has been shown to inhibit oestrone sulphatase activity in the MCF-7 oestrogen-receptor-positive breast cancer cell line. The aim of the present study was to assess whether BCF obtained from Malaysian women inhibited oestrone sulphatase activity in the MCF-7 and MDA-MB-231 breast cancer cell lines. The cell lines were grown in supplemented Dulbecco's Modified Eagle Medium for 3 days, following which a 3-day incubation with sterilised BCF was carried out. At the end of the treatment period the cell monolayers were assayed for oestrone sulphatase activity and the number of cell nuclei counted on a Coulter Counter. BCF was also fractionated on a Bio-Sil SEC 125-5 column by HPLC and the effects of the fractions collected on oestrone sulphatase activity in the MDA-MB-231 cell line were assessed. All 18 samples of BCF tested inhibited cell growth in the MDA-MB-231 cell line while 8 out of 10 samples inhibited MCF-7 cell growth; 15 out of 18 BCF samples inhibited oestrone sulphatase activity in the MDA-MB-231 cell line whereas 5 out of 10 samples stimulated oestrone sulphatase activity in the MCF-7 cell line. HPLC fractions corresponding to molecular weights of > 158 kDa and 28 kDa were found to inhibit oestrone sulphatase activity in the MDA-MB-231 cell line. Further work is required to fully characterise these substances as they may have roles to play in the prevention of breast cancer.
  7. Ee YS, Lai LC, Reimann K, Lim PK
    Oncol Rep, 1999 6 22;6(4):843-6.
    PMID: 10373668
    Transforming growth factor-beta (TGF-beta) has been shown to inhibit the growth of mammary epithelial cells and may play a protective role in mammary carcinogenesis. In contrast, oestrogens promote the development of breast cancer. Oestrone sulphate (E1S) is a huge reservoir of active oestrogens in the breast being converted to the weak oestrogen, oestrone (E1), by oestrone sulphatase. E1 is reversibly converted by oestradiol-17beta hydroxysteroid dehydrogenase to the potent oestrogen, oestradiol (E2). The aim of this study was to assess the effect of the TGF-beta1 isoform on growth and oestrogen metabolism in the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines. The results showed that TGF-beta1 significantly inhibited cell growth and stimulated the conversion of E1S to E1 and E1 to E2 in the MCF-7 cell line. In the MDA-MB-231 cell line TGF-beta1 significantly stimulated cell growth and inhibited the interconversions between E1 and E2. In conclusion, the growth inhibitory effect of TGF-beta1 on the MCF-7 cell line would appear to confer a protective effect in breast cancer. However, its ability to increase the amount of E2 would increase the risk of breast cancer. Which of these effects predominates in vivo remains to be explored. The growth stimulatory effect of TGF-beta1 on the MDA-MB-231 cell line probably acts through a mechanism independent of the effect of TGF-beta1 on oestrogen concentrations since this cell line is hormone unresponsive.
  8. Hwa IA, Reimann K, Lim PK, Lai LC
    Int J Mol Med, 1999 Aug;4(2):175-8.
    PMID: 10402485
    Oestrogens play an important role in the development of breast cancer. A very important source of active oestrogens in the breast is oestrone sulphate which is converted to oestrone by oestrone sulphatase. The aim of this study was to assess the effects of IGF-I and IGF-II on oestrone sulphatase activity in, as well as cell growth of, MCF-7 and MDA-MB-231 human breast cancer cell lines. Cells were grown in supplemented DMEM and treated with varying concentrations of IGFs. At the end of the treatment period, intact cell monolayers were washed and assayed for oestrone sulphatase activity and the number of cell nuclei determined on a Coulter Counter. Oestrone sulphatase activity was significantly stimulated by IGF-I and II at concentrations of 100 ng/ml and 200 ng/ml in MCF-7 cells. IGF-I had no effect on oestrone sulphatase activity in MDA-MB-231 cells over the range of concentrations tested. Significant inhibition of oestrone sulphatase was observed in MDA-MB-231 cells at higher concentrations of IGF-II (50 ng/ml, 100 ng/ml and 200 ng/ml). Both IGF-I and IGF-II at higher concentrations (100 ng/ml and 200 ng/ml) significantly inhibited MCF-7 and stimulated MDA-MB-231 cell growth. Since IGF-I and II have effects on cell growth and oestrone sulphatase activity in breast cancer cell lines they may play a role in the development and progression of human breast cancer.
  9. Chua PY, Day AC, Lai KL, Hall N, Tan LL, Khan K, et al.
    Br J Ophthalmol, 2018 Apr;102(4):539-543.
    PMID: 28794074 DOI: 10.1136/bjophthalmol-2017-310725
    PURPOSE: To estimate the incidence, and describe the clinical features and short-term clinical outcomes of acute angle closure (AAC).

    METHODS: Patients with newly diagnosed AAC were identified prospectively over a 12-month period (November 2011 to October 2012) by active surveillance through the Scottish Ophthalmic Surveillance Unit reporting system. Data were collected at case identification and at 6 months follow-up.

    RESULTS: There were 114 cases (108 patients) reported, giving an annual incidence of 2.2 cases (95% CI 1.8 to 2.6) or 2 patients (95% CI 1.7 to 2.4) per 1 00 000 in the whole population in Scotland. Precipitating factors were identified in 40% of cases. Almost one in five cases was associated with topical dilating drops. Best-corrected visual acuity (BCVA) at presentation ranged from 6/6 to perception of light. The mean presenting intraocular pressure (IOP) was 52 mm Hg (SD 11). Almost 30% cases had a delayed presentation of 3 or more days. At 6 months follow-up, 75% had BCVA of 6/12 or better and 30% were found to have glaucoma at follow-up. Delayed presentation (≥3 days) was associated with higher rate of glaucoma at follow-up (22.6% vs 60.8%, p<0.001), worse VA (0.34 vs 0.74 LogMAR, p<0.0001) and need for more topical medication (0.52 vs 1.2, p=0.003) to control IOP.

    CONCLUSION: The incidence of AAC in Scotland is relatively low compared with the Far East countries, but in line with previous European data. Almost one in five cases were associated with pupil dilation for retinal examination.

  10. Sarojini S, Faridah A, Lim CM, Sameerah SA, Lim TO, Lai LS, et al.
    Med J Malaysia, 2008 Aug;63(3):203-6.
    PMID: 19248690 MyJurnal
    The National Medicines Use Survey (NMUS) which started in 2004 and is still ongoing was conducted with the intent to continuously and systematically collect data on the use of medicines, to provide an overview on the use of medicines in Malaysia. The objective of the NMUS is therefore to quantify the present state and time trends of medicines utilization at various levels of our health care system whether national, regional, local or institutional. From the data available, for the Year 2005, the most commonly used medicine in Malaysia were anti-diabetic medications, of which glibenclamide is the most common followed by metformin, were the top 2 of the list of drugs utilized in DDD/1000 population/day. Collectively, however, taking into account the various antihypertensives by therapeutic groups, anti-hypertensive medicines were more commonly used than anti-diabetics. Hypertension and diabetes mellitus are the two most prevalent chronic disorders in the country and thus, such high medicines utilization rates for these conditions are to be expected. From the general practice prescription data, it was estimated that a patient with hypertension was prescribed a median of only one (1) anti-hypertensive medication. This means, the vast majority of patients (81%) were on monotherapy, which is hardly sufficient to achieve treatment target. Clearly then, given the prevalence of hypertension, many patients were not on drug treatment at all, and of those treated, their drug treatment are likely to be inadequate.
  11. Yeap SS, Asarudin SI, Chow SK, Chua CT, Lai LC
    Med J Malaysia, 2002 Sep;57(3):311-8.
    PMID: 12440271
    The best therapeutic choice in the treatment of lupus nephritis remains open to debate. In addition, there have been little data on the treatment of lupus nephritis in Asian patients. The objective of this study was to look at the response rate and complications of treatment given for lupus nephritis in a group of South East Asian patients with systemic lupus erythematosus (SLE). This was a retrospective, cross-sectional study of 103 patients with lupus nephritis. Detailed analysis was done on 58 patients with Class IV disease. The median time to remission was 12.1 months for azathioprine (AZA), 15.01 months for oral cyclophosphamide (CPM) and 15.25 months for intravenous (i.v.) CPM. The percentage of patients achieving remission after the first course of treatment was 42.9% with AZA, 83.3% with oral CPM and 90.9% with i.v. CPM. Overall, 41/58 (70.7%) of patients went into remission following the first course of treatment. Seventeen (41.5%) subsequently relapsed, requiring a second course of treatment. Fifty-two (50.5%) of all patients had drug-related complications from their treatment. The most frequent complication for the group was amenorrhoea (23.3% of all patients, 40% of those who had CPM previously), which was significantly more frequent in patients given CPM. In conclusion, more patients achieve remission when treated with CPM compared with AZA alone but this is associated with a higher complication rate, especially amenorrhoea.
  12. Sthaneshwar P, Lai LC, Raja Azzidin RE, Mohd Hussain B, Anas SS, Supremaniam S, et al.
    Malays J Pathol, 2021 Apr;43(1):41-48.
    PMID: 33903304
    INTRODUCTION: The Malaysian Association of Clinical Biochemists (MACB) established a Task Force for Chronic Kidney Disease. A survey was undertaken by the Task Force on the reporting of estimated glomerular filtration rate (eGFR) and urine albumin by hospital laboratories in Malaysia in both the government and private sectors.

    MATERIALS AND METHODS: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria.

    RESULTS: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was <60 ml/min/1.73m2. The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units.

    CONCLUSION: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.

  13. Steinberg AG, Lai LYC, Vos GH, Singh RB, Lim TW
    Am J Hum Genet, 1961 Dec;13:355-71.
    PMID: 13916666
    The ABO, MN and Rh blood types, and the Hp, Tf, and Gm [Gm (a), Gm (x), Gm(b), and Gm-like] factors were determined for 128 unrelated Indians (parents of families, 63 with two parents tested and two with one parent tested), and 90 unrelated Chinese (parents of 46 families, 44 with two parents tested and two with one parent tested), and for the offspring from these families. The frequencies of the several blood types are presented. They were done primarily to aid in paternity testing. They compare favorably with the findings of previous studies. The allele Hp1 is rare in the Indian population (.09) and relatively infrequent in the Chinese (.29). Unfortunately, the data shed no light on the problem of the inheritance of the phenotype Hp O. Only Tf C was found among the Indians. About four per cent of the Chinese were heterozygous for Tf CD,, all other were Tf CC. The Indians have a high frequency of Gm(a) and of Gm (x), and a low frequency of Gm (b). They appear to have alleles Gma, Gmax, and Gmb in the following frequencies: .535, .234(5), and .230(5), respectively. Three families appear to have a GMxb allele, providing the offspring are not extra-marital. The Chinese appear to have the alleles Gm^ab, Gm^a, and Gm^ax in the following frequencies: .741, .231, and .028, respectively.
  14. Kavsak PA, Lai L, Langman L, Jones PM, Hammett-Stabler CA
    Clin Biochem, 2015 Dec;48(18):1211-2.
    PMID: 26601569 DOI: 10.1016/j.clinbiochem.2015.11.013
  15. Lai LC, Cheong SK, Goh KL, Leong CF, Loh CS, Lopez JB, et al.
    Malays J Pathol, 2003 Dec;25(2):83-105.
    PMID: 16196365
    Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.
  16. Sthaneshwar P, Thambiah SC, Mat Salleh MJ, Nasuruddin DN, Ahmad Zabidi NF, Jelani AM, et al.
    Malays J Pathol, 2021 Aug;43(2):281-290.
    PMID: 34448792
    INTRODUCTION: Serum protein electrophoresis (SPE) is a well-established laboratory technique. However, reporting of results varies considerably between laboratories. The variation in reporting can cause confusion to the clinician with a potential of adversely impacting patient care. The purpose of the survey was to find out the variation in reporting and to prepare recommendations to the Malaysian laboratories based on the survey to reduce both the variation in reporting between laboratories and the risk of misinterpretation of reports.

    MATERIALS AND METHODS: To determine the extent of variation in reporting of protein electrophoresis results questionnaires were distributed to the pathologists of various laboratories in Malaysia regarding the method, quantification of paraprotein concentrations and immunoglobulin assays, and information regarding current laboratory electrophoresis practices.

    RESULTS: Variation was found in the following reporting practices: (a) screening protocol; (b) reporting of serum albumin; (c) numerical reporting of protein fractions and paraprotein; (d) co-migration of a paraprotein with a normal serum protein; (e) reporting of multiple paraprotein bands (f) appearance of small abnormal band and oligoclonal bands and (g) communication about of interferences.

    CONCLUSION: The pathologists of the country made recommendations on the reporting of protein electrophoresis. Harmonised reporting will reduce inconsistency, variation in reporting, improve the quality of the report and most importantly improve patient care.

  17. Yeo JG, Wasser M, Kumar P, Pan L, Poh SL, Ally F, et al.
    Nat Biotechnol, 2020 06;38(6):757.
    PMID: 32467644 DOI: 10.1038/s41587-020-0574-4
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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