Displaying publications 41 - 54 of 54 in total

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  1. Rajandram R, Yap NY, Ong TA, Mun KS, Mohamad Wali HA, Hasan MS, et al.
    Malays J Pathol, 2017 Apr;39(1):47-53.
    PMID: 28413205 MyJurnal
    INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to cause urinary tract damage. However, there is little information on the pathological effects of ketamine from oral administration. We aimed to study the effects of oral ketamine on the urinary tract and the reversibility of these changes after cessation of ketamine intake.

    METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder.

    RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys.

    CONCLUSION: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.

  2. Mun KS, Pailoor J, Reddy SC
    Malays J Pathol, 2005 Dec;27(2):113-5.
    PMID: 17191394
    A 62-year-old lady presented with a six-month history of swelling of the left upper eyelid, resulting in mild mechanical ptosis. Clinical assessment suggested a provisional diagnosis of dermoid cyst. The lesion was excised and histology revealed nodular deposits of amorphous eosinophilic material surrounded by lymphocytes and plasma cells. Special histochemistry and immunoperoxidase stain results showed deposition of amyloid, non-AA type. The lesion recurred 6 months later.
  3. Mun KS, Cheah PL, Baharudin NB, Looi LM
    Malays J Pathol, 2006 Dec;28(2):73-7.
    PMID: 18376794 MyJurnal
    Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes.
  4. Kanmalar M, Abdul Sani SF, Kamri NINB, Said NABM, Jamil AHBA, Kuppusamy S, et al.
    Cell Mol Biol Lett, 2022 Jan 29;27(1):9.
    PMID: 35093030 DOI: 10.1186/s11658-022-00307-x
    Bladder cancer is the fourth most common malignancy in males. It can present across the whole continuum of severity, from mild through well-differentiated disease to extremely malignant tumours with poor survival rates. As with other vital organ malignancies, proper clinical management involves accurate diagnosis and staging. Chemotherapy consisting of a cisplatin-based regimen is the mainstay in the management of muscle-invasive bladder cancers. Control via cisplatin-based chemotherapy is threatened by the development of chemoresistance. Intracellular cholesterol biosynthesis in bladder cancer cells is considered a contributory factor in determining the chemotherapy response. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1), one of the main regulatory components in cholesterol biosynthesis, may play a role in determining sensitivity towards chemotherapy compounds in bladder cancer. FDFT1-associated molecular identification might serve as an alternative or appendage strategy for early prediction of potentially chemoresistant muscle-invasive bladder cancer tissues. This can be accomplished using Raman spectroscopy. Developments in the instrumentation have led to it becoming one of the most convenient forms of analysis, and there is a highly realistic chance that it will become an effective tool in the pathology lab. Chemosensitive bladder cancer tissues tend to have a higher lipid content, more protein genes and more cholesterol metabolites. These are believed to be associated with resistance towards bladder cancer chemotherapy. Herein, Raman peak assignments have been tabulated as an aid to indicating metabolic changes in bladder cancer tissues that are potentially correlated with FDFT1 expression.
  5. Ho CC, Mun KS, Naidu R
    Malays J Pathol, 2013 Jun;35(1):33-43.
    PMID: 23817393 MyJurnal
    Breast cancer is the most common malignancy in women worldwide. The incidence of breast cancer in Malaysia is lower compared to international statistics, with peak occurrence in the age group between 50 to 59 years of age and mortality rates of 18.6%. Despite current diagnostic and prognostic methods, the outcome for individual subjects remain poor. This is in part due to breast cancers' wide genetic heterogeneity. Various platforms for genetics studies are now employed to determine the identity of these genetic abnormalities, including microarray methods like high density single-nucleotide-polymorphism (SNP) oligonucleotide arrays which combine the power of chromosomal comparative genomic hybridization (cCGH) and loss of heterozygosity (LOH) in the offering of higher-resolution mappings. These platforms and their applications in highlighting the genomic alteration frameworks manifested in breast carcinoma will be discussed.
  6. Cheah PL, Li J, Looi LM, Koh CC, Lau TP, Chang SW, et al.
    Malays J Pathol, 2019 Aug;41(2):91-100.
    PMID: 31427545
    Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreement between detection of loss of DNA mismatch repair using immunohistochemistry and the detection of downstream microsatellite instability using PCR. After consideration of advantages and shortcomings of both methods, it is our opinion that the choice of preferred technique for MSI analysis would depend on the type of laboratory carrying out the testing.
  7. Murty OP, Mun KS, Hussin H
    J Forensic Leg Med, 2008 Jan;15(1):37-41.
    PMID: 18309549
    This is a case report of 16-year-old adolescent school boy who died due to unusual calcification of coronary arteries. He died while cycling with his friends. While cycling fast he fell. He was brought dead to hospital. At times unsuspected cardiac lesions cause sudden death during extraneous physical activities in healthy persons. Sudden death in adolescents is not very common. It is an unusual case as apparently healthy adolescent boy actively participating in sports had stony hard coronary arteries. The coronaries showed advanced calcification and early bone formation. The myocardial septum had extensive fibrosis. The pathogenesis and other possible similar conditions are also discussed in the report.
  8. Chew YK, Cheong JP, Brito-Mutunayagam S, Khir A, Prepageran N, Mun KS
    Med J Malaysia, 2011 Mar;66(1):62-3.
    PMID: 23765147
    Olfactory neuroblastoma is a rare, slow growing, malignant tumour of neuroectodermal origin that begins in neuroepithelial cells of the olfactory membrane. A metastatic rate of 20% to 60% is reported with the most common site being the cervical lymph node. Other sites include the parotid glands, skin, lungs, bone, liver, orbit, spinal cord and spinal canal. We describe a case of olfactory neuroblastoma presented to us with scalp metastasis.
  9. Yee PS, Zainal NS, Gan CP, Lee BKB, Mun KS, Abraham MT, et al.
    Target Oncol, 2019 04;14(2):223-235.
    PMID: 30806895 DOI: 10.1007/s11523-019-00626-8
    BACKGROUND: Given that aberrant activation of epidermal growth factor receptor family receptors (ErbB) is a common event in oral squamous cell carcinoma, and that high expression of these receptor proteins is often associated with poor prognosis, this rationalizes the approach of targeting ErbB signaling pathways to improve the survival of patients with oral squamous cell carcinoma. However, monotherapy with the ErbB blocker afatinib has shown limited survival benefits.

    OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.

    METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.

    RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.

    CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.

  10. Paramanantham Y, B M Said NA, Mun KS
    Malays J Pathol, 2023 Apr;45(1):19-29.
    PMID: 37119243
    INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients.

    MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53.

    RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case.

    CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.

  11. Ng CH, Pathy NB, Taib NA, Mun KS, Rhodes A, Yip CH
    Asian Pac J Cancer Prev, 2012;13(4):1111-3.
    PMID: 22799290
    The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.
  12. Cheah PL, Looi LM, Lee GE, Teoh KH, Mun KS, Nazarina AR
    Diagn Pathol, 2011;6:56.
    PMID: 21699710 DOI: 10.1186/1746-1596-6-56
    Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urothelium's expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion.
  13. Cheah PL, Looi LM, Teoh KH, Mun KS, Nazarina AR
    Asian Pac J Cancer Prev, 2012;13(2):469-72.
    PMID: 22524808
    The present study was conducted to assess utility of p16(INK4a) immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for p16(INK4a) (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were p16(INK4a) immunopositive. All normal squamous epithelium did not express p16(INK4). p16(INK4a) expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC.The increased p16(INK4a) immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.
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