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Fulltext Glottic cancer in a non-smoking patient with laryngopharyngeal reflux

Zainuddin N, Mohd Kornain NK

Malays Fam Physician, 2016;11(2-3):35-37.
PMID: 28461858 MyJurnal

The onset of carcinoma of the larynx, especially of the glottis, is heralded mainly by a change of voice. It has a male preponderance and is almost exclusively common to smokers and patients with heavy alcohol consumption. We report a case of glottic carcinoma in a non-smoker female patient. The only possible risk factor for her is a history of laryngopharyngeal reflux.
Fulltext Effects of water-based contrast media on experimentally induced established atherosclerotic plaques in rabbits.

Isa MR, Mohd Noor N, Nawawi H, Kaur M., Rahman T, Mohd Kornain NK, et al.

IIUM Medical Journal Malaysia, 2020;19(2):21-28.
MyJurnal

Imaging techniques involving optical coherence tomography, computed tomography (CT) and high-resolution magnetic resonance imaging (MRI) are used as tools to identify atherosclerotic plaques. However, the effects of water-based contrast media used in Post Mortem Computed Tomography Angiography (PMCTA) on the histopathology of atherosclerotic plaques have not been widely explored. The objective of this study is to determine the effects of water-based contrast media used in PMCTA on the histopathology of atherosclerotic plaques and biomarkers of atherosclerosis in experimentally induced established atherosclerotic rabbits. MATERIALS AND METHODS: Twenty male New Zealand white rabbits were divided into 2 groups. One group was given a high cholesterol diet (HCD) for 12 weeks to establish atherosclerosis and the control group normal diet (ND). Five rabbits from each group were then given intravenous water-based contrast media before being sacrificed. The entire length of aorta was dissected and submitted for histopathological examination and determination of tissue biomarkers α-SMA and MMP-9. RESULTS:Histopathological examination of the aorta including percentage of area covered by plaque and foam cell formation showed no significant difference in atheromatous plaque formation in both groups of HCD rabbits with or without intravenous contrast media injection (plaque: 55±41 vs. 63±15, p=0.731; foam cells: 124±83 vs. 171±55, p=0.325). Similarly, α-SMA and MMP-9 protein expression also showed no significant difference in both groups (α-SMA: 70±20 vs. 67±26, p=0.807; MMP-9: 60±12 vs. 57±17, p=0.785). CONCLUSION:Water-based contrast media used in PMCTA does not affect the morphology or the immunohistochemistry staining of SMA and MMP-9 in atherosclerotic plaques.
Pregnancy outcome and cord blood cotinine level: A cross-sectional comparative study between secondhand smokers and non-secondhand smokers

Abdullah B, Muadz B, Norizal MN, Ismail N, Kornain NK, Kutty M

Eur J Obstet Gynecol Reprod Biol, 2017 Jul;214:86-90.
PMID: 28494268 DOI: 10.1016/j.ejogrb.2017.05.002

OBJECTIVE: To compare the pregnancy outcome and cord blood cotinine levels between secondhand smokers and non-secondhand smokers.
STUDY DESIGN: This was a cross-sectional comparative study in a Malaysian tertiary obstetric hospital involving 200 non-smoking pregnant women at term, of whom 100 were secondhand smokers and 100 were non-secondhand smokers. Those with multiple pregnancies, with a body mass index (BMI) of more than 30kg/m2or who delivered by Caesarean section were excluded. The participants' basic demographic details, delivery details, neonatal outcome and placental weight were recorded. Umbilical cord blood samples were obtained, and cord blood cotinine levels were measured with a Cotinine ELISA kit. The primary outcomes were baby's birth weight, length, and head circumference, Apgar score at 5min and placental weight. The secondary outcome was difference in cord blood cotinine levels between the two groups and the correlation of these differences with the neonatal outcome.
RESULTS: The secondhand smoker group had significantly lower baby weight (2.94±0.31kg vs 3.05±0.40kg), head circumference (30.87±2.35cm vs 37.13±2.36cm), length (46.58±1.95cm vs 51.53±2.05cm) and placental weight (520±73.5g vs 596±61.3g) and significantly higher cord blood cotinine levels (16.35±12.84ng/mL vs 0.56±0.22ng/mL). Cord blood cotinine levels had significant negative correlations with placental weight (r=-0.461), baby's weight (r=-0.297), baby's head circumference (r=-0.501) and baby's length (r=-0.374).
CONCLUSION: Secondhand smoke increases the incidence of adverse pregnancy outcomes (newborns'anthropometric measurements and placental weight) and causes higher cord blood cotinine levels.
Fulltext Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis

Rahman TA, Hassim NF, Zulkafli N, Muid S, Kornain NK, Nawawi H

Food Nutr Res, 2016;60:31525.
PMID: 27799085 DOI: 10.3402/fnr.v60.31525

Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined.
Human Papilloma Virus (HPV) self-sampling: do women accept it?

Abdullah NN, Daud S, Wang SM, Mahmud Z, Mohd Kornain NK, Al-Kubaisy W

J Obstet Gynaecol, 2018 Apr;38(3):402-407.
PMID: 29385850 DOI: 10.1080/01443615.2017.1379061

This study aims to determine the acceptability of Human Papilloma Virus (HPV) self-sampling and the factors associated with willingness to buy HPV self-sampling kit in the future. A total of 164 women aged 28-60 years old from Obstetrics & Gynaecology clinics at a teaching hospital performed HPV self-sampling using the Digene HC2 DNA collection kit. After samples were taken, the participants were given self-administered questionnaires. The majority of the participants were Malay (93.9%), had attained tertiary education (65.2%) and were employed (70.1%). The acceptability was good. More than half of the participants felt that self-sampling was easy. Only 1.2% felt that the procedure was difficult to perform. Most reported no pain at all during the procedure (66.9%). The commonest concern was getting a good sample (90.1%). A number of Pap smears were found to be significantly associated with the willingness to buy the HPV self-sampling kit. HPV self-sampling has the potential to be included in the cervical cancer screening programme. Impact Statement What is already known on this subject: HPV self-sampling is acceptable in some developed and developing countries. It is acceptable because it was easy to perform with very minimal pain or discomfort. Studies on the acceptance of self-screening are needed to plan a policy on self-sampling in the future. What the results of this study add: Our study adds new findings to the body of knowledge on self-sampling in the local population. We found that more women are willing to do the self-sampling at the clinic rather than at home. Although more than 90% expressed willingness to do self-sampling in the future, only 70% of them were willing to purchase the kit. Cost is a potential barrier to women who have the interest to perform the self-sampling. Given the global economic challenges, cost is inevitably an important predictor that we have to consider. What the implications are of these findings for clinical practice and/or further research: Future research should examine women from the rural areas and those who are resilient to Pap smear screening. In clinical practice, clinicians should acknowledge that cost is a potential barrier for women who are willing to do self-sampling. Self-sampling could be an option for women with no financial constraint to buy the kit. However, clinicians should counsel women so that they can make an informed choice in determining their screening method.
Fulltext Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma

Ahmad M, Suhaimi SN, Chu TL, Abdul Aziz N, Mohd Kornain NK, Samiulla DS, et al.

PLoS One, 2018;13(1):e0191295.
PMID: 29329342 DOI: 10.1371/journal.pone.0191295

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.
Fulltext Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort

Chin YM, Tan LP, Abdul Aziz N, Mushiroda T, Kubo M, Mohd Kornain NK, et al.

Int J Cancer, 2016 10 15;139(8):1731-9.
PMID: 27236004 DOI: 10.1002/ijc.30207

Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA = 1.98 × 10(-2) ; pExpr-GSEA = 1.27 × 10(-24) ; pBonf-Combined = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort.
Fulltext Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

Chow YP, Tan LP, Chai SJ, Abdul Aziz N, Choo SW, Lim PV, et al.

Sci Rep, 2017 03 03;7:42980.
PMID: 28256603 DOI: 10.1038/srep42980

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.
Fulltext CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma

Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, et al.

Sci Rep, 2017 09 28;7(1):12372.
PMID: 28959019 DOI: 10.1038/s41598-017-12045-8

Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.