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Fulltext Matrix association region/scaffold attachment region (MAR/SAR) sequence: its vital role in mediating chromosome breakages in nasopharyngeal epithelial cells via oxidative stress-induced apoptosis

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.
Fulltext Interleukins, laminin and Epstein - Barr virus latent membrane protein 1 (EBV LMP1) promote metastatic phenotype in nasopharyngeal carcinoma

Chew MM, Gan SY, Khoo AS, Tan EL

BMC Cancer, 2010;10:574.
PMID: 20964870 DOI: 10.1186/1471-2407-10-574

Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated.
Fulltext Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma

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.
Trends in geriatrics-related translational research and funding in the "big 4" medical journals

Ch'ng ASH, Yong KTW, Ng DWH, Heyzer L, Lim WS

J Am Med Dir Assoc, 2017 06 01;18(6):544-545.
PMID: 28431910 DOI: 10.1016/j.jamda.2017.02.018
Fulltext A simple microfluidic chip design for fundamental bioseparation

Chan AS, Danquah MK, Agyei D, Hartley PG, Zhu Y

J Anal Methods Chem, 2014;2014:175457.
PMID: 24527255 DOI: 10.1155/2014/175457

A microchip pressure-driven liquid chromatographic system with a packed column has been designed and fabricated by using poly(dimethylsiloxane) (PDMS). The liquid chromatographic column was packed with mesoporous silica beads of Ia3d space group. Separation of dyes and biopolymers was carried out to verify the performance of the chip. A mixture of dyes (fluorescein and rhodamine B) and a biopolymer mixture (10 kDa Dextran and 66 kDa BSA) were separated and the fluorescence technique was employed to detect the movement of the molecules. Fluorescein molecule was a nonretained species and rhodamine B was attached onto silica surface when dye mixture in deionized water was injected into the microchannel. The retention times for dextran molecule and BSA molecule in biopolymer separation experiment were 45 s and 120 s, respectively. Retention factor was estimated to be 3.3 for dextran and 10.4 for BSA. The selectivity was 3.2 and resolution was 10.7. Good separation of dyes and biopolymers was achieved and the chip design was verified.
Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma

Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, et al.

J Clin Virol, 2012 Sep;55(1):34-9.
PMID: 22739102 DOI: 10.1016/j.jcv.2012.05.017

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia.
Repurposing adult AI radiograph models for neonatal care through continual learning: an international multicentre study

Rao VM, Chen E, Saenz A, Banerjee O, Marklund H, Bijnens L, et al.

Nat Biomed Eng, 2026 Oct 13.
PMID: 42869977 DOI: 10.1038/s41551-026-01812-6

Despite growing clinical adoption of artificial intelligence in radiology, fewer than one in five commercially available models are cleared for paediatric use. Existing systems are trained predominantly on adult data and generalize poorly to neonates, yet efficient strategies for repurposing them without data sharing or large-scale local data curation are lacking. Here we present an international retrospective study of neonatal chest radiographs from 30 neonatal intensive care units across 20 countries and territories, evaluating continual learning as a privacy-preserving approach to adapt a deep learning model for adult endotracheal tube assessment to neonatal care. Each hospital contributed 50 radiographs for sequential model retraining without centralized data pooling. Continual learning achieved lower anatomical landmark localization error (0.67 cm versus 1.29 cm for hospital-specific fine-tuning and 4.30 cm for adult-only models) at 29 of 30 sites, with improved detection of deep intubations at 27 of 30 sites. These findings demonstrate that privacy-preserving collaborative learning can address critical gaps in paediatric AI deployment.