Displaying publications 1 - 20 of 53 in total

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  1. New Zealand Malayan war veterans' exposure to dibutylphthalate is associated with an increased incidence of cryptorchidism, hypospadias and breast cancer in their children
    Carran M, Shaw IC
    N Z Med J, 2012;125(1358):52-63.
    PMID: 22864157
    It is well known that the endocrine-disrupting chemical (EDC) dibutylphthalate (DBP) inhibits testosterone synthesis and can lead to feminisation in male laboratory animals. Moreover, it has long been speculated that human exposure would result in the similar effects, but this is difficult to study because specific human exposure cohorts are rare. We report increases in the incidences of hypospadias (p<0.05), cryptorchidism (p<0.05) and breast cancer (p<0.05) in the children of New Zealand soldiers who served in Malaya (1948-1960) and were exposed to DBP applied daily to their clothing as an acaricide to prevent tick-transmitted bush typhus. In addition, we modelled absorption of DBP from the soldiers' clothing and using published data for skin absorption, and calculated a large theoretical absorbed dose of 64 mg/kg body weight/day which is similar to DBP's lowest observed adverse effect level (LOAEL) of 50 mg/kg body weight/day and thus indicates a biological effect is possible. This is the first report of a multigenerational developmental effect following DBP exposure in human males.
  2. Fulltext Keeping an eye out for klebsiella endopthalmitis: klebsiella pneumoniae invasive liver abscess syndrome
    Jia Ying S, Ian C, Azlanudin A, Zamri Z, Hairol O
    Journal of Surgical Academia, 2018;8(2):35-38.
    MyJurnal
    Hypervirulent Klebsiella pneumoniae strain is a major cause of liver abscess and this bacteria has metastatic properties. This distinct liver abscess syndrome has been increasingly reported in Asia over the past two decades, but is emerging as a global disease. We described an 81-year-old lady, who presented to the emergency department with 1-week prior duration of fever and right eye swelling. She had been admitted for recurrent liver abscess prior to this. Hence, she was initially treated as sepsis secondary to recurrent liver abscess. Meanwhile, she was managed concurrently by ophthalmology team for endophtalmitis. Despite the initiation of treatment with antibiotics, she did not show any improvement and required right eye evisceration to treat the sepsis. Invasive liver abscess syndrome with metastatic endophthalmitis should be screened in patient with Klebsiella liver abscess. They should be monitored for ocular symptoms as early recognition can prohibit delays in treatment, which has debilitating consequences.
  3. Fulltext The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod
    Patmanathan SN, Yap LF, Murray PG, Paterson IC
    J Cell Mol Med, 2015 Oct;19(10):2329-40.
    PMID: 26171944 DOI: 10.1111/jcmm.12635
    Almost all drugs approved for use in humans possess potentially beneficial 'off-target' effects in addition to their principal activity. In some cases this has allowed for the relatively rapid repurposing of drugs for other indications. In this review we focus on the potential for re-purposing FTY720 (also known as fingolimod, Gilenya(™)), an immunomodulatory drug recently approved for the treatment of multiple sclerosis (MS). The therapeutic benefit of FTY720 in MS is largely attributed to the immunosuppressive effects that result from its modulation of sphingosine 1-phosphate receptor signalling. However, this drug has also been shown to inhibit other cancer-associated signal transduction pathways in part because of its structural similarity to sphingosine, and consequently shows efficacy as an anti-cancer agent both in vitro and in vivo. Here, we review the effects of FTY720 on signal transduction pathways and cancer-related cellular processes, and discuss its potential use as an anti-cancer drug.
  4. Fulltext Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles
    Khoo XH, Paterson IC, Goh BH, Lee WL
    Cancers (Basel), 2019 Aug 14;11(8).
    PMID: 31416147 DOI: 10.3390/cancers11081166
    Drug resistance remains a severe problem in most chemotherapy regimes. Recently, it has been suggested that cancer cell-derived extracellular vesicles (EVs) could mediate drug resistance. In this study, the role of EVs in mediating the response of oral squamous cell carcinoma (OSCC) cells to cisplatin was investigated. We isolated and characterized EVs from OSCC cell lines showing differential sensitivities to cisplatin. Increased EV production was observed in both de novo (H314) and adaptive (H103/cisD2) resistant lines compared to sensitive H103 cells. The protein profiles of these EVs were then analyzed. Differences in the proteome of EVs secreted by H103 and H103/cisD2 indicated that adaptation to cisplatin treatment caused significant changes in the secreted nanovesicles. Intriguingly, both resistant H103/cisD2 and H314 cells shared a highly similar EV protein profile including downregulation of the metal ion transporter, ATP1B3, in the EVs implicating altered drug delivery. ICP-MS analysis revealed that less cisplatin accumulated in the resistant cells, but higher levels were detected in their EVs. Therefore, we inhibited EV secretion from the cells using a proton pump inhibitor and observed an increased drug sensitivity in cisplatin-resistant H314 cells. This finding suggests that control of EV secretion could be a potential strategy to enhance the efficacy of cancer treatment.
  5. Fulltext Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-β1
    Tan ML, Parkinson EK, Yap LF, Paterson IC
    Sci Rep, 2021 01 12;11(1):584.
    PMID: 33436723 DOI: 10.1038/s41598-020-79789-8
    Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
  6. Fulltext Updated parameters and expanded simulation options for a model of the auditory periphery
    Zilany MS, Bruce IC, Carney LH
    J Acoust Soc Am, 2014 Jan;135(1):283-6.
    PMID: 24437768 DOI: 10.1121/1.4837815
    A phenomenological model of the auditory periphery in cats was previously developed by Zilany and colleagues [J. Acoust. Soc. Am. 126, 2390-2412 (2009)] to examine the detailed transformation of acoustic signals into the auditory-nerve representation. In this paper, a few issues arising from the responses of the previous version have been addressed. The parameters of the synapse model have been readjusted to better simulate reported physiological discharge rates at saturation for higher characteristic frequencies [Liberman, J. Acoust. Soc. Am. 63, 442-455 (1978)]. This modification also corrects the responses of higher-characteristic frequency (CF) model fibers to low-frequency tones that were erroneously much higher than the responses of low-CF model fibers in the previous version. In addition, an analytical method has been implemented to compute the mean discharge rate and variance from the model's synapse output that takes into account the effects of absolute refractoriness.
  7. Fulltext Functional Implications of Epstein-Barr Virus Lytic Genes in Carcinogenesis
    Yap LF, Wong AKC, Paterson IC, Young LS
    Cancers (Basel), 2022 Nov 24;14(23).
    PMID: 36497262 DOI: 10.3390/cancers14235780
    Epstein-Barr virus (EBV) is associated with a diverse range of tumors of both lymphoid and epithelial origin. Similar to other herpesviruses, EBV displays a bipartite life cycle consisting of latent and lytic phases. Current dogma indicates that the latent genes are key drivers in the pathogenesis of EBV-associated cancers, while the lytic genes are primarily responsible for viral transmission. In recent years, evidence has emerged to show that the EBV lytic phase also plays an important role in EBV tumorigenesis, and the expression of EBV lytic genes is frequently detected in tumor tissues and cell lines. The advent of next generation sequencing has allowed the comprehensive profiling of EBV gene expression, and this has revealed the consistent expression of several lytic genes across various types of EBV-associated cancers. In this review, we provide an overview of the functional implications of EBV lytic gene expression to the oncogenic process and discuss possible avenues for future investigations.
  8. Development and validation of the osteoporosis patient satisfaction questionnaire (OPSQ)
    Lai PS, Chua SS, Chan SP, Low WY, Wong IC
    Maturitas, 2010 Jan;65(1):55-63.
    PMID: 19962839 DOI: 10.1016/j.maturitas.2009.10.006
    OBJECTIVES: To develop and validate the Osteoporosis Patient Satisfaction Questionnaire (OPSQ) and to assess the opinion of postmenopausal osteoporotic women towards pharmaceutical care.
    METHODS: A 16-item instrument was designed. Each response consists of a five-point Likert-like scale with higher scores indicating greater satisfaction. The face and content validity was established via consultation with an endocrinologist and three pharmacists as well as feedback from participants in a preliminary study. Postmenopausal osteoporotic women taking bisphosphonates were recruited and randomly allocated to the intervention (n=90) and control groups (n=90). Pharmaceutical care was provided at month 2 to the intervention group while the control group received standard pharmacy services. The OPSQ was administered at month 6 (end of the intervention period), to assess patients' satisfaction. Factor analysis was performed using varimax rotation. Internal reliability was established using Cronbach's alpha. Construct validity was performed by using the Mann-Whitney U test.
    RESULTS: The internal reliability of the OPSQ produced a Cronbach's alpha of 0.86. Factor analysis identified one component in the OPSQ, which measured patient satisfaction. The intervention group showed significantly better overall OPSQ score than the control group (91.89+/-7.22% versus 84.32+/-7.48%, p<0.001). This indicates that the OPSQ was able to differentiate between participants who received pharmaceutical care from those who did not.
    CONCLUSIONS: The 16-item OPSQ developed in this study has high internal reliability and is a valid instrument for assessing osteoporotic women's satisfaction with pharmaceutical care service in Malaysia.
  9. Fulltext Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma
    Alabsi AM, Lim KL, Paterson IC, Ali-Saeed R, Muharram BA
    Biomed Res Int, 2016;2016:4904016.
    PMID: 27123447 DOI: 10.1155/2016/4904016
    Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.
  10. Mechanisms of sphingosine 1-phosphate receptor signalling in cancer
    Patmanathan SN, Wang W, Yap LF, Herr DR, Paterson IC
    Cell Signal, 2017 06;34:66-75.
    PMID: 28302566 DOI: 10.1016/j.cellsig.2017.03.002
    S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P1-5. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P. However, cooperativity between the individual S1PRs, functional interactions with receptor tyrosine kinases and the sub-cellular localisation of the S1PRs within tumour cells also appear to play a role in mediating the effects of S1PR signalling during carcinogenesis. Here we review what is known regarding the role of individual S1PRs in cancer and discuss the recent evidence to suggest cross-talk between the S1PRs and other cellular signalling pathways in cancer. We will also discuss the therapeutic potential of targeting the S1PRs and their downstream signalling pathways for the treatment of cancer.
  11. Investigating the binding preferences of small molecule inhibitors of human protein arginine methyltransferase 1 using molecular modelling
    Hong W, Li J, Laughton CA, Yap LF, Paterson IC, Wang H
    J Mol Graph Model, 2014 Jun;51:193-202.
    PMID: 24937176 DOI: 10.1016/j.jmgm.2014.05.010
    Protein arginine methyltransferases (PRMTs) catalyse the methylation of arginine residues of target proteins. PRMTs utilise S-adenosyl methionine (SAM) as the methyl group donor, leading to S-adenosyl homocysteine (SAH) and monomethylarginine (mMA). A combination of homology modelling, molecular docking, Active Site Pressurisation, molecular dynamic simulations and MM-PBSA free energy calculations is used to investigate the binding poses of three PRMT1 inhibitors (ligands 1-3), which target both SAM and substrate arginine binding sites by containing a guanidine group joined by short linkers with the SAM derivative. It was assumed initially that the adenine moieties of the inhibitors would bind in sub-site 1 (PHE44, GLU137, VAL136 and GLU108), the guanidine side chain would occupy sub-site 2 (GLU 161, TYR160, TYR156 and TRP302), with the amino acid side chain occupying sub-site 3 (GLU152, ARG62, GLY86 and ASP84; pose 1). However, the SAH homocysteine moiety does not fully occupy sub-site 3, suggesting another binding pose may exist (pose 2), whereby the adenine moiety binds in sub-site 1, the guanidine side chain occupies sub-site 3, and the amino acid side chain occupies sub-site 2. Our results indicate that ligand 1 (pose 1 or 2), ligand 2 (pose 2) and ligand 3 (pose 1) are the predominant binding poses and we demonstrate for the first time that sub-site 3 contains a large space that could be exploited in the future to develop novel inhibitors with higher binding affinities.
  12. Comparative Genome Analysis of Fusobacterium nucleatum
    Ang MY, Dutta A, Wee WY, Dymock D, Paterson IC, Choo SW
    Genome Biol Evol, 2016 10 05;8(9):2928-2938.
    PMID: 27540086
    Fusobacterium nucleatum is considered to be a key oral bacterium in recruiting periodontal pathogens into subgingival dental plaque. Currently F. nucleatum can be subdivided into five subspecies. Our previous genome analysis of F. nucleatum W1481 (referred to hereafter as W1481), isolated from an 8-mm periodontal pocket in a patient with chronic periodontitis, suggested the possibility of a new subspecies. To further investigate the biology and relationships of this possible subspecies with other known subspecies, we performed comparative analysis between W1481 and 35 genome sequences represented by the five known Fusobacterium subspecies. Our analyses suggest that W1481 is most likely a new F. nucleatum subspecies, supported by evidence from phylogenetic analyses and maximal unique match indices (MUMi). Interestingly, we found a horizontally transferred W1481-specific genomic island harboring the tripartite ATP-independent (TRAP)-like transporter genes, suggesting this bacterium might have a high-affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate. Moreover, we found virulence genes in the W1481 genome that may provide a strong defense mechanism which might enable it to colonize and survive within the host by evading immune surveillance. This comparative study provides better understanding of F. nucleatum and the basis for future functional work on this important pathogen.
  13. Fulltext Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis
    Zheng W, Tan MF, Old LA, Paterson IC, Jakubovics NS, Choo SW
    Sci Rep, 2017 06 07;7(1):2949.
    PMID: 28592797 DOI: 10.1038/s41598-017-02399-4
    Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virulence genes. However, we observed subtle differences in genomic islands and prophages between the species. Comparative pathogenomics analysis identified S. sanguinis strains have genes encoding IgA proteases, mitogenic factor deoxyribonucleases, nickel/cobalt uptake and cobalamin biosynthesis. On the contrary, genomic islands of S. gordonii strains contain additional copies of comCDE quorum-sensing system components involved in genetic competence. Two distinct polysaccharide locus architectures were identified, one of which was exclusively present in S. gordonii strains. The first evidence of genes encoding the CylA and CylB system by the α-haemolytic S. gordonii is presented. This study provides new insights into the genetic distinctions between S. gordonii and S. sanguinis, which yields understanding of tooth surfaces colonization and contributions to dental plaque formation, as well as their potential roles in the pathogenesis of IE.
  14. Fulltext The Dynamic Roles of TGF-β Signalling in EBV-Associated Cancers
    Velapasamy S, Dawson CW, Young LS, Paterson IC, Yap LF
    Cancers (Basel), 2018 Jul 27;10(8).
    PMID: 30060514 DOI: 10.3390/cancers10080247
    The transforming growth factor-β (TGF-β) signalling pathway plays a critical role in carcinogenesis. It has a biphasic action by initially suppressing tumorigenesis but promoting tumour progression in the later stages of disease. Consequently, the functional outcome of TGF-β signalling is strongly context-dependent and is influenced by various factors including cell, tissue and cancer type. Disruption of this pathway can be caused by various means, including genetic and environmental factors. A number of human viruses have been shown to modulate TGF-β signalling during tumorigenesis. In this review, we describe how this pathway is perturbed in Epstein-Barr virus (EBV)-associated cancers and how EBV interferes with TGF-β signal transduction. The role of TGF-β in regulating the EBV life cycle in tumour cells is also discussed.
  15. Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage
    Wang H, Chen M, Sang X, You X, Wang Y, Paterson IC, et al.
    Eur J Med Chem, 2020 Apr 01;191:112154.
    PMID: 32092587 DOI: 10.1016/j.ejmech.2020.112154
    Transforming growth factor-β (TGF-β) is a member of a superfamily of pleiotropic proteins that regulate multiple cellular processes such as growth, development and differentiation. Following binding to type I and II TGF-β serine/threonine kinase receptors, TGF-β activates downstream signaling cascades involving both SMAD-dependent and -independent pathways. Aberrant TGF-β signaling is associated with a variety of diseases, such as fibrosis, cardiovascular disease and cancer. Hence, the TGF-β signaling pathway is recognized as a potential drug target. Various organic molecules have been designed and developed as TGF-β signaling pathway inhibitors and they function by either down-regulating the expression of TGF-β or by inhibiting the kinase activities of the TGF-β receptors. In this review, we discuss the current status of research regarding organic molecules as TGF-β inhibitors, focusing on the biological functions and the binding poses of compounds that are in the market or in the clinical or pre-clinical phases of development.
  16. Risk factors associated with adverse drug reactions in hospitalised children: international multicentre study
    Rashed AN, Wong IC, Cranswick N, Tomlin S, Rascher W, Neubert A
    Eur J Clin Pharmacol, 2012 May;68(5):801-10.
    PMID: 22166934 DOI: 10.1007/s00228-011-1183-4
    BACKGROUND: Understanding the epidemiology and risk factors of adverse drug reactions (ADRs) is important in order to develop appropriate prevention strategies. This study aimed to identify risk factors associated with ADRs in hospitalised children and recommend strategies to minimise ADRs.

    METHODS: A prospective multicentre cohort study was conducted on paediatric general medical wards in five European and non-European hospitals. ADRs were identified by intensive chart review. Multivariable logistic regression was used to investigate risk factors associated with ADRs. For the risk factor analysis, prescribed drugs were divided into high-risk and low-risk drug groups. Analgesics, anti-epileptics, antibacterials and antimycotics for systemic use, corticosteroids for systemic use and immunosuppressant agents were considered as high-risk groups whereas the remaining drug classes were defined as low-risk drug groups.

    RESULTS: A total of 1,253 paediatric patients were identified [Australia (n = 145), Germany (n = 372), Hong Kong (n = 138), Malaysia (n = 291), UK (n = 307)]. A total of 328 ADRs were observed in 16.7% of patients (186/1,115). Use of five or more low-risk drugs per patient or three or more high-risk drugs was a strong predictor for ADRs (OR 4.7, 95% CI 2.4-9.3; OR 6.5, 95% CI 2.7-16.0 respectively; p < 0.001). Older children were more likely to experience ADRs; gender was not significantly associated.

    CONCLUSION: To reduce the risk of ADRs in children, clinicians and pharmacists should aim to minimise polypharmacy and be aware of higher ADR risks associated with some drug groups.

  17. Fulltext Drug Utilisation Patterns in Children Admitted to a Paediatric General Medical Ward in Five Countries
    Rashed AN, Wong IC, Wilton L, Tomlin S, Neubert A
    Drugs Real World Outcomes, 2015 11 18;2(4):397-410.
    PMID: 26690854 DOI: 10.1007/s40801-015-0049-y
    OBJECTIVE: To investigate and compare drug prescription patterns in children admitted to a paediatric general medical ward in five countries.

    METHODS: A prospective cohort study conducted on paediatric medical wards in the UK, Germany, Australia, Hong Kong (HK) and Malaysia. Data were collected over 3 months in each country except in Australia (1 month). All medications prescribed were classified according to the WHO Anatomical Therapeutic Chemical (ATC) classification. For each drug, frequency of prescriptions and patient exposures were calculated for ATC anatomical and therapeutic levels overall and by country.

    RESULTS: One thousand two hundred and seventy-eight patients were included (Australia 146, Germany 376, UK 313, HK 143 and Malaysia 300); 89.2 % of patients (1140) received medications, median 3 (interquartile range 2-5) drugs per patient. 5367 drugs were prescribed. The most frequently prescribed therapeutic groups in all countries were: systemic antibacterials (1355; 25.2 %), analgesics/non-steroidal anti-inflammatory drugs (NSAIDs) (1173; 21.8 %) and drugs for obstructive airway diseases (472; 8.8 %). Overall, 65.1 % (742) of patients received at least one systemic antibacterial, 63.7 % (726) received one or more analgesic/NSAIDs, and 23.6 % (269) received 'drugs for obstructive airway diseases'. The number of patients exposed to these groups differed significantly between countries (p 
  18. Fulltext Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
    Lau CC, Aminuddin A, Chan KM, Paterson IC, Law LM, Ng PY
    Life (Basel), 2021 Nov 02;11(11).
    PMID: 34833046 DOI: 10.3390/life11111170
    Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell lines and the potential mechanisms involved. Through GEPIA dataset analysis, high expression levels of mRNA encoding P2Y receptors, the ATP-induced G protein-coupled receptors, were associated with better overall patient survival in head and neck squamous cell carcinoma. qPCR analysis showed that the poorly differentiated OSCC SAS cell line, had higher P2RY1 expression level compared to the well-differentiated H103 and H376 cell lines. Western blotting and flow cytometry analyses revealed that ATP phosphorylated ERK and elevated intracellular calcium signaling in all tested cell lines. A significant S-phase cell cycle arrest was observed in SAS, and preincubation with the MEK inhibitor PD0325901 reversed the ATP-induced S-phase arrest. We further demonstrated that ATP induced a slight reduction in cell count and colony formation yet significant apoptosis in SAS. Overall, we postulate that the ATP-induced S-phase arrest effect in SAS cells may be regulated through P2Y receptor-mediated ERK signaling, thus suggesting a potential antitumor effect of ATP via interaction with its distinct profile of P2Y receptors.
  19. Fulltext Genome Sequence of Parvimonas micra Strain A293, Isolated from an Abdominal Abscess from a Patient in the United Kingdom
    Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.
    Genome Announc, 2013;1(6).
    PMID: 24309744 DOI: 10.1128/genomeA.01025-13
    Parvimonas micra is an important oral microbe that has the ability to grow and proliferate within oral biofilms and is involved in periodontal disease, leading to gingival bleeding, gingival recession, alveolar bone loss, and tooth mobility. However, occasionally these normally oral pathogens can cause infections at other sites in the body. We present the genome sequence of Parvimonas micra strain A293, a smooth Parvimonas micra strain isolated from an abdominal abscess from a patient at Barts Hospital, London, United Kingdom.
  20. Fulltext Genome Sequence of Fusobacterium nucleatum Strain W1481, a Possible New Subspecies Isolated from a Periodontal Pocket
    Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.
    Genome Announc, 2014;2(1).
    PMID: 24526626 DOI: 10.1128/genomeA.00009-14
    Fusobacterium nucleatum is a bacterial species commonly detected in dental plaque within the human oral cavity, with some strains associated with periodontal disease, one of the most common clinical bacterial infections in the human body. The exact mechanisms of its pathogenesis are still not completely understood. In this study, we present the genome sequence and annotation of F. nucleatum strain W1481, isolated from a periodontal pocket of a dental patient at the University of Bristol, United Kingdom, the 16S rRNA gene sequencing of which showed it to be markedly different from the five previously named subspecies.
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