Displaying publications 1 - 20 of 26 in total

  1. Tan SN, Sim SP
    BMC Med Genomics, 2019 01 15;12(1):9.
    PMID: 30646906 DOI: 10.1186/s12920-018-0465-4
    BACKGROUND: It has been found that chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC). CRS can be caused by gastro-oesophageal reflux (GOR) that may reach nasopharynx. The major component of refluxate, bile acid (BA) has been found to be carcinogenic and genotoxic. BA-induced apoptosis has been associated with various cancers. We have previously demonstrated that BA induced apoptosis and gene cleavages in nasopharyngeal epithelial cells. Chromosomal cleavage occurs at the early stage of both apoptosis and chromosome rearrangement. It was suggested that chromosome breaks tend to cluster in the region containing matrix association region/scaffold attachment region (MAR/SAR). This study hypothesised that BA may cause chromosome breaks at MAR/SAR leading to chromosome aberrations in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is a deletion hotspot in NPC.

    METHODS: Potential MAR/SAR sites were predicted in the AF9 gene by using MAR/SAR prediction tools. Normal nasopharyngeal epithelial cells (NP69) and NPC cells (TWO4) were treated with BA at neutral and acidic pH. Inverse-PCR (IPCR) was used to identify chromosome breaks in SAR region (contains MAR/SAR) and non-SAR region (does not contain MAR/SAR). To map the chromosomal breakpoints within the AF9 SAR and non-SAR regions, DNA sequencing was performed.

    RESULTS: In the AF9 SAR region, the gene cleavage frequencies of BA-treated NP69 and TWO4 cells were significantly higher than those of untreated control. As for the AF9 non-SAR region, no significant difference in cleavage frequency was detected between untreated and BA-treated cells. A few breakpoints detected in the SAR region were mapped within the AF9 region that was previously reported to translocate with the mixed lineage leukaemia (MLL) gene in an acute lymphoblastic leukaemia (ALL) patient.

    CONCLUSIONS: Our findings suggest that MAR/SAR may be involved in defining the positions of chromosomal breakages induced by BA. Our report here, for the first time, unravelled the relation of these BA-induced chromosomal breakages to the AF9 chromatin structure.

  2. Tan SN, Sim SP
    BMC Cancer, 2018 04 12;18(1):409.
    PMID: 29649994 DOI: 10.1186/s12885-018-4327-4
    BACKGROUND: Chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of the major aetiological factors of CRS. Bile acid (BA), the component of gastric duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was suggested to be involved in human malignancies. Cells have the potential and tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase-activated deoxyribonuclease (CAD) has been implicated in mediating translocation in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome breaks mediated by CAD leading to chromosome rearrangement in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is one of the most common deletion sites in NPC.

    METHODS: We tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced.

    RESULTS: BA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute lymphoblastic leukaemia (ALL) patient.

    CONCLUSIONS: These findings suggest a role for BA-induced apoptosis in mediating chromosome rearrangements in NPC. In addition, CAD may be a key player in chromosome cleavages mediated by BA-induced apoptosis. Persistent exposure of sinonasal tract to gastric duodenal refluxate may increase genomic instability in surviving cells.

  3. Tan SN, Gendeh HS, Sani A, Mat-Baki M
    Int J Surg Case Rep, 2016;21:99-103.
    PMID: 26957189 DOI: 10.1016/j.ijscr.2016.02.012
    Myeloid Sarcoma (MS) or Granulocytic Sarcoma is an uncommon laryngeal malignancy. It may arise from myelodysplastic syndromes, malignancy or de novo. Presentation in the larynx is rare and some may present with Acute Myeloid Leukaemia (AML) whereby the later may be asymptomatic.
  4. Tan SN, Tee CS, Wong HL
    Plant Biotechnol (Tokyo), 2018 Dec 25;35(4):325-334.
    PMID: 31892819 DOI: 10.5511/plantbiotechnology.18.0711a
    Pongamia pinnata is a legume plant which has great potential to be used as a biofuel feedstock. Conventional propagation of P. pinnata was found to be inefficient for mass propagation. Employing plant tissue culture techniques for micropropagation and further plant improvement of P. pinnata will be the right path to fulfill future challenges in biofuel production. This study aimed to establish a plant regeneration system for potential micropropagation and genetic manipulation of P. pinnata in future. In vitro nodal explants were used and Woody Plant Medium (WPM) containing 30 µM 6-benzylaminopurine (BAP) and 1 mM phloroglucinol (PG) was able to induce higher frequency of multiple shoot buds compared to other media investigated in this study. For shoot regeneration study, WPM containing 15 µM of zeatin and 1 mM PG was able to induce longer shoots while rooting of the regenerated shoots was enhanced by WPM supplemented with indole-3-butyric acid (IBA) in combination with silver thiosulphate (STS). A simple and effective acclimatisation protocol was established with very high survival frequency of regenerated plantlets. Root nodulation of the successfully acclimatised plants was also observed. In short, multiple shoot buds were successfully induced, regenerated and rooted in vitro. The rooted plantlets were successfully acclimatised and grown healthily. It was concluded that a successful plant regeneration protocol of P. pinnata was achieved for potential application in micropropagation and genetic manipulation.
  5. Tan SN, Sim SP, Khoo AS
    Cell Biosci, 2016;6:35.
    PMID: 27231526 DOI: 10.1186/s13578-016-0103-9
    Genetic aberrations have been identified in nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains elusive. There are increasing evidences that the apoptotic nuclease caspase-activated deoxyribonuclease (CAD) is one of the players leading to translocation in leukemia. Oxidative stress, which has been strongly implicated in carcinogenesis, is a potent apoptotic inducer. Most of the NPC etiological factors are known to induce oxidative stress. Although apoptosis is a cell death process, cells possess the potential to survive apoptosis upon DNA repair. Eventually, the surviving cells may carry rearranged chromosomes. We hypothesized that oxidative stress-induced apoptosis may cause chromosomal breaks mediated by CAD. Upon erroneous DNA repair, cells that survive apoptosis may harbor chromosomal rearrangements contributing to NPC pathogenesis. This study focused on the AF9 gene at 9p22, a common deletion region in NPC. We aimed to propose a possible model for molecular mechanism underlying the chromosomal rearrangements in NPC.
  6. Arunathan R, Ariffin AHZ, Khor KG, Tan SN
    Pediatric investigation, 2019 Sep;3(3):191-193.
    PMID: 32851317 DOI: 10.1002/ped4.12148
    Introduction: Congenital tracheal stenosis (CTS) is a serious and rare condition. In most cases, CTS is associated with cardiopulmonary abnormalities; however, isolated CTS is present in 10%-30% of patients. The severity of the disorder is dependent on the symptoms, which correlate with the CTS classification.

    Case presentation: We discuss our findings in an infant who presented with severe respiratory compromise where incidental intra-operative findings revealed CTS with no cardiopulmonary abnormalities. Because of a lack of resources in the emergency department, we created a tracheostoma and inserted an endotracheal tube.

    Conclusion: The main aim in treating CTS is to secure the airway and provide sufficient oxygen.

  7. Mohamad Ishak LA, Khor KG, Tan SN
    Pediatric investigation, 2019 Sep;3(3):188-190.
    PMID: 32851316 DOI: 10.1002/ped4.12149
    Introduction: The incidence of foreign body ingestion in the upper gastrointestinal tract accounts for 75%-85% of foreign body ingestions in pediatric patients.

    Case presentation: An 8-month old boy presented with vomiting and was referred to the otorhinolaryngology team based on his mother's suspicion that her child might have ingested a foreign body. Flexible laryngoscopy revealed a phone screen protector at the vallecular region. The foreign body was removed in the operating theatre.

    Conclusion: Foreign body ingestion should always be suspected in young patients. Consideration of the patient's symptoms, level of lodgement, and type of foreign body will determine whether immediate intervention or a conservative approach is warranted.

  8. Mariana A, Santhana Raj AS, Tan SN, Ho TM
    Trop Biomed, 2007 Dec;24(2):29-37.
    PMID: 18209705
    Many finer taxonomic characters of Blomia tropicalis are not distinctly visible under conventional light microscopy. Scanning electron micrographs of this mite are therefore presented in this paper for better appreciation of the inconspicuous features of the morphology of the species. The differences in morphology of male and female B. tropicalis are also briefly discussed.
  9. Mariana A, Santana Raj AS, Ho TM, Tan SN, Zuhaizam H
    Trop Biomed, 2008 Dec;25(3):217-24.
    PMID: 19287360
    Scanning electron microscope (SEM) images of two dust mites, Sturnophagoides brasiliensis and Sturnophagoides halterophilus, are presented to provide an improved visualization of the taxonomic characters of these mites. Sturnophagoides halterophilus can be differentiated from S. brasiliensis by their expanded genu and femur of leg I. The differences in morphology of male and female S. brasiliensis are also discussed.
  10. Tan SN, Sim SP, Khoo ASB
    BMC Mol. Biol., 2018 12 04;19(1):15.
    PMID: 30514321 DOI: 10.1186/s12867-018-0116-5
    BACKGROUND: Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that oxidative stress-induced apoptosis could be a potential mechanism mediating chromosome breakages in nasopharyngeal epithelial cells. Additionally, caspase-activated DNase (CAD) may be the vital player in mediating the chromosomal breakages during oxidative stress-induced apoptosis. Chromosomal breakage occurs during apoptosis and chromosome rearrangement. Chromosomal breakages tend to cluster in certain regions, such as matrix association region/scaffold attachment region (MAR/SAR). We hypothesised that oxidative stress-induced apoptosis may result in chromosome breaks preferentially at the MAR/SAR sites. The AF9 gene at 9p22 was targeted in this study because 9p22 is a deletion site commonly found in NPC.

    RESULTS: By using MAR/SAR recognition signature (MRS), potential MAR/SAR sites were predicted in the AF9 gene. The predicted MAR/SAR sites precisely match to the experimentally determined MAR/SARs. Hydrogen peroxide (H2O2) was used to induce apoptosis in normal nasopharyngeal epithelial cells (NP69) and NPC cells (HK1). Nested inverse polymerase chain reaction was employed to identify the AF9 gene cleavages. In the SAR region, the gene cleavage frequency of H2O2-treated cells was significantly higher than that of the non-treated cells. A few chromosomal breakages were detected within the AF9 region which was previously found to be involved in the mixed lineage leukaemia (MLL)-AF9 translocation in an acute lymphoblastic leukaemia patient. As for the non-SAR region, no significant difference in the gene cleavage frequency was found between the untreated control and H2O2-treated cells. Furthermore, H2O2-induced cleavages within the SAR region were reduced by caspase-3 inhibitor, which indirectly inhibits CAD.

    CONCLUSIONS: These results reaffirm our previous findings that oxidative stress-induced apoptosis could be one of the potential mechanisms underlying chromosome breakages in nasopharyngeal epithelial cells. MAR/SAR may play a vital role in defining the location of chromosomal breakages mediated by oxidative stress-induced apoptosis, where CAD is the major nuclease.

  11. Tan SN, Gendeh HS, Gendeh BS, Ramzisham AR
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1683-1686.
    PMID: 31763224 DOI: 10.1007/s12070-015-0918-4
    Hemangioma is a disease of head and neck commonly, but its presence in the nasal cavity or sinus is rare. It is a form of benign tumour of vascular origin consisting of predominantly blood vessels. It can be categorized into capillary, cavernous and mixed type in accordance to its histopathology features. Retrospectively, we reviewed five cases of nasal hemangioma presenting at University Kebangsaan Malaysia Medical Center (UKMMC) between September 2007 and May 2015. Information on the patients age, gender, ethnicity, clinical symptoms, imaging findings (if available), treatment modalities were collected retrospectively for analysis. Five patients were analysed. Females were more affected than male with ratio of 4:1. All patients presented with unilateral lobular capillary hemangioma of the nasal cavity with 60 % (3/5) of the lesions on the right side and 40 % (2/5) on the left side. The common symptoms at presentation were epitaxis and nasal obstruction (5/5, 100 %), followed by rhinorrhea (3/5, 60 %) and facial pain (1/5, 20 %). All the patients underwent a surgical excision of the hemangioma. The five patients had no recurrence on subsequent follow ups. Computed tomography of paranasal sinuses can be performed to exclude bony erosions. Endoscopic sinus haemangioma excision provide good visualisation and better outcomes. In conclusion, nasal hemangioma should always be differential diagnosis for nasal lesions and surgical excision is still the preferred first line treatment.
  12. Tan SN, Sim SP, Khoo AS
    Hum Genomics, 2018 06 18;12(1):29.
    PMID: 29914565 DOI: 10.1186/s40246-018-0160-8
    BACKGROUND: The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a potent apoptotic inducer. During apoptosis, chromatin cleavage and DNA fragmentation occur. However, cells may undergo DNA repair and survive apoptosis. Non-homologous end joining (NHEJ) pathway has been known as the primary DNA repair system in human cells. The NHEJ process may repair DNA ends without any homology, although region of microhomology (a few nucleotides) is usually utilised by this DNA repair system. Cells that evade apoptosis via erroneous DNA repair may carry chromosomal aberration. Apoptotic nuclease was found to be associated with nuclear matrix during apoptosis. Matrix association region/scaffold attachment region (MAR/SAR) is the binding site of the chromosomal DNA loop structure to the nuclear matrix. When apoptotic nuclease is associated with nuclear matrix during apoptosis, it potentially cleaves at MAR/SAR. Cells that survive apoptosis via compromised DNA repair may carry chromosome rearrangement contributing to NPC tumourigenesis. The Abelson murine leukaemia (ABL) gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. This study aimed to identify the chromosome breakages and/or rearrangements in the ABL gene in cells undergoing oxidative stress-induced apoptosis.

    RESULTS: In the present study, in silico prediction of MAR/SAR was performed in the ABL gene. More than 80% of the predicted MAR/SAR sites are closely associated with previously reported patient breakpoint cluster regions (BCR). By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H2O2)-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that contains a MAR/SAR. Intriguingly, we detected two translocations in H2O2-treated cells. Region of microhomology was found at the translocation junctions. This observation is consistent with the operation of microhomology-mediated NHEJ.

    CONCLUSIONS: Our findings suggested that oxidative stress-induced apoptosis may participate in chromosome rearrangements of NPC. A revised model for oxidative stress-induced apoptosis mediating chromosome rearrangement in NPC is proposed.

  13. Teng ST, Tan SN, Lim HC, Dao VH, Bates SS, Leaw CP
    J Phycol, 2016 12;52(6):973-989.
    PMID: 27403749 DOI: 10.1111/jpy.12448
    Forty-eight isolates of Pseudo-nitzschia species were established from the Miri coast of Sarawak (Malaysian Borneo) and underwent TEM observation and molecular characterization. Ten species were found: P. abrensis, P. batesiana, P. fukuyoi, P. kodamae, P. lundholmiae, P. multistriata, P. pungens, P. subfraudulenta, as well as two additional new morphotypes, herein designated as P. bipertita sp. nov. and P. limii sp. nov. This is the first report of P. abrensis, P. batesiana, P. kodamae, P. fukuyoi, and P. lundholmiae in coastal waters of Malaysian Borneo. Pseudo-nitzschia bipertita differs from its congeners by the number of sectors that divide the poroids, densities of band striae, and its cingular band structure. Pseudo-nitzschia limii, a pseudo-cryptic species in the P. pseudodelicatissima complex sensu lato, is distinct by having wider proximal and distal mantles, a higher number of striae, and greater poroid height in the striae of the valvocopula. The species were further supported by the phylogenetic reconstructions of the nuclear-encoded large subunit ribosomal gene and the second internal transcribed spacer. Phylogenetically, P. bipertita clustered with its sister taxa (P. subpacifica + P. heimii); P. limii appears as a sister taxon to P. kodamae and P. hasleana in the ITS2 tree. Pairwise comparison of ITS2 transcripts with its closest relatives revealed the presence of both hemi- and compensatory base changes. Toxicity analysis showed detectable levels of domoic acid in P. abrensis, P. batesiana, P. lundholmiae, and P. subfraudulenta, but both new species tested below the detection limit.
  14. Tan SN, Teng ST, Lim HC, Kotaki Y, Bates SS, Leaw CP, et al.
    Harmful Algae, 2016 12;60:139-149.
    PMID: 28073557 DOI: 10.1016/j.hal.2016.11.003
    The distribution of the toxic pennate diatom Nitzschia was investigated at four mangrove areas along the coastal brackish waters of Peninsular Malaysia. Eighty-two strains of N. navis-varingica were isolated and established, and their identity confirmed morphologically and molecularly. Frustule morphological characteristics of the strains examined are identical to previously identified N. navis-varingica, but with a sightly higher density of the number of areolae per 1μm (4-7 areolae). Both LSU and ITS rDNAs phylogenetic trees clustered all strains in the N. navis-varingica clade, with high sequence homogeneity in the LSU rDNA (0-0.3%), while the intraspecific divergences in the ITS2 data set reached up to 7.4%. Domoic acid (DA) and its geometrical isomers, isodomoic A (IA) and isodomoic B (IB), were detected in cultures of N. navis-varingica by FMOC-LC-FLD, and subsequently confirmed by LC-MS/MS, with selected ion monitoring (SIM) and multiple reaction monitoring (MRM) runs. DA contents ranged between 0.37 and 11.06pgcell-1. This study demonstrated that the toxigenic euryhaline diatom N. navis-varingica is widely distributed in Malaysian mangrove swamps, suggesting the risk of amnesic shellfish poisoning and the possibility of DA contamination in the mangrove-related fisheries products.
  15. Tan SN, Sani D, Lim CW, Ideris A, Stanslas J, Lim CTS
    PMID: 32051689 DOI: 10.1155/2020/8068797
    Edible bird's nest (EBN) which is solidified swiftlet's saliva contains high nutritional value. It is widely consumed in countries like Malaysia, Indonesia, and Thailand. However, previous proximate analysis of Malaysia EBN was not representative of all the regions in Malaysia. In recent years, safety issues such as high nitrate and nitrite contents, presence of heavy metal, adulteration, fungal infection, and cancer cell stimulation were associated with EBN. Hence, this study aimed to determine the proximate analysis, safety profile during normal weather and hazy periods, and its effect on cancer cells stimulation in Malaysia-farmed EBN. Seven raw cleaned EBN samples were sourced from 6 different regions in Malaysia. Proximate analysis and safety profile were performed using official AOCA methods and Malaysian Standard. High protein (53.03-56.37%) and carbohydrate content (27.97-31.68%) with an acceptable level of moisture (10.8-14.04%) and ash (2.22-3.38%) were reported. A good safety profile was obtained with low nitrite and nitrate levels, with undetectable heavy metals and no significant growth of pathogenic microorganism except mould. Epidermal growth factor was detected but below the quantification level with the chicken EGF ELISA kit. The microculture tetrazolium (MTT) assay was performed for growth stimulation assessment comparing human EGF and EBN. There was no significant cell growth observed in cancer cells after EBN treatment. In conclusion, EBN Malaysia has a good nutritional profile, free of heavy metals, and an acceptable level of nitrate, nitrite, and microorganism profile except for mould contents. Furthermore, the in vitro study indicated that EBN was not associated with cancer cell growth.
  16. Tan SB, Lee YL, Tan SN, Ng TY, Teo YT, Lim PK, et al.
    J Hosp Palliat Nurs, 2020 10;22(5):407-414.
    PMID: 32898385 DOI: 10.1097/NJH.0000000000000678
    Palliative care providers find meaning in their work, even though stress, burnout, and compassion fatigue can be a concern. In this study, we aimed to explore the experiences of well-being of palliative care providers in Malaysia. Data collected using semistructured interviews were thematically analyzed. Eighteen palliative care providers participated: 9 doctors and 9 nurses. Five subthemes were generated: (1) values and strengths, (2) coping and work-life balance, (3) social support and spirituality, (4) passion and satisfaction, and (5) learning, growth, and transformation. These subthemes were further categorized into 2 themes: resilience and reward. The results may inform the development of interventions in the promotion and sustenance of well-being of palliative care providers.
  17. Phan CL, Tan SN, Tan SM, Kadir SSSA, Ramli NLM, Lim TO, et al.
    Cancer Genet, 2021 01;250-251:20-24.
    PMID: 33220656 DOI: 10.1016/j.cancergen.2020.11.003
    Acute lymphoblastic leukemia (ALL) cases with e13a3 fusion transcripts are extremely rare. We report a 24-year-old male with Ph-positive (Ph+) ALL with an aberrant e13a3 fusion transcript treated with CD19-specific chimeric antigen receptor T-cell (CAR-T) therapy. He developed refractory disease post-chemotherapy induction, andreceived allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage with imatinib in combination with chemotherapy regimen. Unfortunately, the patient relapsed after +90 days post-transplant. He was consented to CAR-T therapy trial and achieved complete remission, highlighting the efficacy of CAR-T treatment in relapsed-refractory B-ALL irrespective of the underlying genetic drivers in leukemia cells .
  18. Teng ST, Abdullah N, Hanifah AH, Tan SN, Gao C, Law IK, et al.
    Toxicon, 2021 Sep 30;202:132-141.
    PMID: 34600910 DOI: 10.1016/j.toxicon.2021.09.018
    In March 2018, an algal bloom of Pseudo-nitzschia was detected, for the first time, in a semi-enclosed lagoon in Miri, Sarawak, Malaysia Borneo. The plankton samples were collected for cell enumeration and species identification by electron microscopy and molecular characterization. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to detect and quantify the neurotoxin domoic acid (DA) in both the plankton and shellfish samples. The abundance of Pseudo-nitzschia cells ranged from 5.6 × 105 to 3.5 × 106 cell L-1 during the bloom event. Morphological observation of the cells by transmission electron microscopy showed that the plankton samples comprised a single Pseudo-nitzschia morphotype resembling P. cuspidata. The ITS2 sequence-structure phylogenetic inference further supported the species identity as Pseudo-nitzschia cuspidata. Low levels of DA were detected in the plankton samples, with cellular DA, particulate DA, and dissolved DA of 257-504 fg DA cell-1, 676 ng L-1, and 15 ng L-1, respectively. The amount of DA, 8 μg g-1 tissue, was found present in the shellfish sample (Magallana sp.) which is below the regulatory limit of 20 μg DA g-1 tissue. The study documented, for the first time, DA contamination in shellfish that associated with bloom of P. cuspidata in the Western Pacific region.
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