MyMedR

A study of two cholera epidemics in the district of Tawau, Sabah (1989-1991)

Khoo A

Southeast Asian J. Trop. Med. Public Health, 1994 Mar;25(1):208-10.

Fulltext Epstein-Barr virus Latent Membrane Protein LMP1 reduces p53 protein levels independent of the PI3K-Akt pathway

Husaini R, Ahmad M, Soo-Beng Khoo A

BMC Res Notes, 2011;4:551.

PMID: 22185663 DOI: 10.1186/1756-0500-4-551

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which commonly occurs in Southern China, Taiwan, North Africa and Southeast Asia. Nasopharyngeal carcinoma is strongly associated with Epstein-Barr virus infection. The p53 tumour suppressor protein is rarely mutated in NPC suggesting that the inactivation of p53 pathway in NPC could be due to the presence of EBV proteins. The aim of this work was to determine the effects of EBV proteins namely LMP1 and LMP2A on the expression levels of p53 protein.

A new BRCA1 germline mutation (E879X) in a Malaysian breast cancer patient of Chinese descent

Khoo AS, Balraj P, Volpi L, Nair S

Hum Mutat, 2000 May;15(5):485.

PMID: 10790221

Fulltext The stethoscope and the transfer of bacteria in the neonatal nursery

Boo NY, Wong YH, Khoo AK

Med J Malaysia, 1989 Mar;44(1):87-8.

PMID: 2696869

Fulltext Measles--an experience in Sandakan Hospital, Sabah, 1990

Khoo A, Ho CK, Ong TK, Khairul A

Singapore Med J, 1994 Dec;35(6):595-8.

PMID: 7761883

A descriptive study of 143 cases of clinically diagnosed measles in patients under the age of 12 years admitted to the Duchess of Kent Hospital, Sandakan, Sabah, during the year 1990 was carried out. The median age of the patients was one year and 13.3% of the cases were between the ages of 6 and 9 months. The male to female ratio was 1.3:1. The majority of the cases (85.3%) were not immunised against measles while 60.0% of the cases were malnourished. Most of the cases (86.0%) had at least one complication with 32.9% of the cases having more than one complications. The main complications were pneumonia (74.1%) and diarrhea (38.5%). Other complications were convulsions, otitis media and corneal ulceration/scarring. A case of pneumonia with mediastinal emphysema and subcutaneous emphysema was noted. The case fatality rate was 1.4% while blindness was the long term morbidity in 1.4% of the cases. Measles remains an important cause of morbidity in children in Sabah.

Mutational characterization of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Malaysia

Balraj P, Lim PG, Sidek H, Wu LL, Khoo AS

J. Endocrinol. Invest., 2013 Jun;36(6):366-74.

PMID: 23027774 DOI: 10.3275/8648

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. Our objective was to identify the 21-hydroxylase active gene, CYP21A2 mutations in Malaysian 21-OHD patients using different techniques.

A novel complex mutation of the OTC (ornithine transcarbamylase) gene in a Malaysian pedigree

Khoo AS, Balraj P, Rachedi A, Chin CN, Volpi L

Hum Mutat, 1999 Nov;14(5):448.

PMID: 10533073

Nested polymerase chain reaction for detection of Plasmodium falciparum infection in Malaysia

Khoo A, Furuta T, Abdullah NR, Bah NA, Kojima S, Wah MJ

Trans R Soc Trop Med Hyg, 1996 1 1;90(1):40-1.

PMID: 8730308

p53 and nasopharyngeal carcinoma: a Malaysian study

Hoe SL, Lee ES, Khoo AS, Peh SC

Pathology, 2009;41(6):561-5.

PMID: 19900105

AIMS: Nasopharyngeal carcinoma (NPC) is a common malignancy among men in Malaysia. To determine the role of p53 in NPC, we screened for p53 mutations and evaluated the protein expression levels in samples from local patients with NPC.

METHODS: Fifty-three formalin-fixed, paraffin-embedded nasopharyngeal carcinoma tissue blocks were chosen for this study. The presence of Epstein-Barr virus (EBV) was determined by in situ hybridisation using an EBER probe. p53 protein expression was detected using immunohistochemistry. Simultaneously, amplifications by PCR were performed for p53 exons 5 to 8, followed by mutation screening via single strand conformation polymorphism (SSCP). Sequencing of all the four exons was performed in five samples with mobility shift. To rule out false negative results by SSCP, 13 samples with p53 overexpression and five samples with low p53 expression were randomly selected and sequenced.

RESULTS: There was no mutation found in exons 5 to 8 in all the samples despite 46 (87%) of them having high p53 levels. EBV was detected in 51 (96%) out of 53 samples. There was no statistically significant association between p53 expression level and EBV presence.

CONCLUSIONS: High-intensity staining for p53 by immunohistochemistry was common in our series of NPC tissue samples but was not associated with 'hot spot' mutations of exons 5-8 of the gene. We did not find a significant relationship between the expression level of p53 and presence of EBV. Our study confirms that mutation of the DNA-binding domain of p53 is rare in NPC.

Fulltext Mutation analysis of the BRCA1 gene in Malaysian breast cancer patients

Balraj P, Khoo AS, Volpi L, Tan JA, Nair S, Abdullah H

Singapore Med J, 2002 Apr;43(4):194-7.

PMID: 12188064

Thirty patients with early onset breast cancer or familial breast cancer from Malaysia were analysed for germline mutation in the early onset breast cancer I gene (BRCA1). Direct sequencing of the entire coding region of BRCA1 identified a frameshift mutation, c.5447-5448insC (insC5447) (codon 1776 of exon 21) in a patient aged 32 of the Malay ethnic origin, who had no family history of breast and/or ovarian cancer. Eight polymorphisms (2201C > T, 2430T > C, P871L, E1038G, K1183R, 4427T > C, S1613G and IVS8-57delT) were identified in the samples tested.

Fulltext Nasopharyngeal Carcinoma Database

Pua KC, Khoo AS, Yap YY, Subramaniam SK, Ong CA, Gopala Krishnan G, et al.

Med J Malaysia, 2008 Sep;63 Suppl C:59-62.

PMID: 19230249

Nasopharyngeal carcinoma (NPC) is a cancer which is common in Asia. We report the establishment and early results of a multi-institutional prospective study of nasopharyngeal carcinoma, which seeks to systematically collect data as well as blood and tumour tissue samples from patients diagnosed with nasopharyngeal cancer at six centres in Malaysia. A total of 484 confirmed NPC cases were reported from the six participating centres between 1st July 2007 and 29th February 2008. Of these, 225 were newly diagnosed cases, 53 were recurrent cases and 206 were in remission at the time of reporting. Amongst the newly diagnosed cases, the most common presenting symptom was the presence of neck lumps (42%). Ophthalmo-neurologic symptoms were the presenting symptoms of 11% of the new cases. The majority of cases (75%) presented at stage III/IV.

Fulltext Acute dengue in a neonate secondary to perinatal transmission

Chin PS, Khoo AP, Asmah Hani AW, Chem YK, Norizah I, Chua KB

Med J Malaysia, 2008 Aug;63(3):265-6.

PMID: 19248708 MyJurnal

We report a newborn baby girl with acute dengue due to vertical transmission. A 31 year old factory worker of 38+ week gestation, gravida 5 para 3+1, developed acute dengue fever two days prior to delivery. She delivered a normal term baby girl by spontaneous vaginal delivery and recovered uneventfully without peripartum haemorrhage despite the presence of thrombocytopenia. The baby girl developed low grade fever on day four of post-natal life and except for the transient thrombocytopenia, also recovered uneventfully following three days of mild illness. The clinical diagnosis of acute dengue virus infection was confirmed by laboratory tests.

Fulltext The occurrence of dihydrofolate reductase (DHFR) point mutation (SER-108-->ASN-108) in Malaysian isolates of Plasmodium falciparum

Lim PK, Tan SK, Khoo AS, Noor Rain A, Nagappan S, Mak JW

Southeast Asian J. Trop. Med. Public Health, 1998 Mar;29(1):27-30.

PMID: 9740263

Dielectrophoretic deformation of breast cancer cells for lab on a chip applications

Chan JY, Ahmad Kayani AB, Md Ali MA, Kok CK, Ramdzan Buyong M, Hoe SLL, et al.

Electrophoresis, 2019 10;40(20):2728-2735.

PMID: 31219180 DOI: 10.1002/elps.201800442

This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA-MB-231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA-MB-231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA-MB-231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 Vpp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.

Parallel genome-wide RNAi screens identify lymphocyte-specific protein tyrosine kinase (LCK) as a targetable vulnerability of cell proliferation and chemoresistance in nasopharyngeal carcinoma

Liew K, Yu GQS, Wei Pua LJ, Wong LZ, Tham SY, Hii LW, et al.

Cancer Lett, 2021 Apr 28;504:81-90.

PMID: 33587980 DOI: 10.1016/j.canlet.2021.02.006

Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.

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