Displaying publications 21 - 40 of 92 in total

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  1. Kelly GM, Kong YH, Dobi A, Srivastava S, Sesterhenn IA, Pathmanathan R, et al.
    Molecular and clinical oncology, 2015 Jan;3(1):23-30.
    PMID: 25469265
    Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.
  2. Tan SH, Hindi KW, Chandran PA, Chong AW
    Iran J Otorhinolaryngol, 2015 May;27(80):243-6.
    PMID: 26082908
    INTRODUCTION: A rare case of basaloid squamous cell carcinoma (BSCC) of the larynx, which has not been previously reported, is described.

    CASE REPORT: A 60-year-old man was presented to the Otolaryngology Department with progressive dyspnoea and dysphagia to solids for over a period of 1 week. Direct laryngoscopy revealed a tumour at the laryngeal aspect of the epiglottis, which prolapsed into the laryngeal inlet each time the patient inspired. This resulted in an inspiratory stridor despite adequate glottic opening and normal mobility of the vocal cords.

    CONCLUSION: Therefore, in cases where a ball-valve lesion causes intermittent life-threatening airway obstruction, BSCC of the larynx, though rare, must be considered as a differential diagnosis.

  3. Tan SH
    Disabil Health J, 2015 Jul;8(3):414-23.
    PMID: 25595295 DOI: 10.1016/j.dhjo.2014.11.003
    BACKGROUND: Planning and evaluation of health care services for children with disabilities requires information on their caregivers' needs.
    OBJECTIVE: This paper aims to present the development and psychometric properties of the Caregiver Needs Scale (CNS), a scale assessing the needs of caregivers of children with disabilities aged 0-12 years in Malaysia.
    METHODS: Development of the scale went through a multistage process of literature review, modification of an existing instrument, input from experts and feedback from service users. Literature review identified content domains and response options. An exploratory factor analysis (EFA) was undertaken to identify subscales of caregiver needs. The internal consistency reliability, convergent validity and discriminant validity of the new scale were examined.
    RESULTS: 273 caregivers of children with disabilities completed the fielded questionnaire. EFA revealed 4 subscales of caregiver needs: need for 'Help getting information and services for the child,' 'Help coping with the child,' 'Help getting child care' and 'Help with finances.' Three items with factor loading <0.4 were dropped. Cronbach's alpha coefficients of the subscales ranged from 0.813 to 0.903. Total CNS score correlated with number of child's needs and unmet needs. The score was also higher in families with financial and employment problems.
    CONCLUSION: A new instrument was developed to assess the needs of caregivers of children with disabilities for use in the Malaysian population. The CNS showed satisfactory psychometric properties but further examination is warranted to confirm its validity.
    KEYWORDS: Caregivers; Children with disabilities; Instrument development; Needs assessment; Psychometric properties
  4. Tan SH, Mun KS, Chandran PA, Manuel AM, Prepageran N, Waran V, et al.
    Childs Nerv Syst, 2015 Jul;31(7):1165-9.
    PMID: 25712744 DOI: 10.1007/s00381-015-2667-9
    This paper reports an unusual case of a transsphenoidal encephalocele and discusses our experience with a minimally invasive management. To the best of our knowledge, we present the first case of a combined endoscopic transnasal and transoral approach to a transsphenoidal encephalocele in an infant.
  5. Murugan AC, Karim MR, Yusoff MB, Tan SH, Asras MF, Rashid SS
    Pharm Biol, 2015 Aug;53(8):1087-97.
    PMID: 25630358 DOI: 10.3109/13880209.2014.959615
    CONTEXT: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process.

    OBJECTIVE: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes.

    METHODS: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment.

    RESULTS: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included.

    CONCLUSION: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.

  6. Tan SH, Chong AW, Prepageran N
    Iran J Otorhinolaryngol, 2015 Sep;27(82):391-4.
    PMID: 26568944
    INTRODUCTION: Atypical infratemporal fossa infections are rare and potentially fatal.

    CASE REPORT: A case of an aspergillosis localized in the infratemporal fossa and another case of tuberculosis of the infratemporal fossa originating from the maxillary sinus, is described. The first patient was immunocompromised and showed symptoms of facial numbness; whereas the other was an immunocompetent man who complained of trigeminal neuralgia type pain. It was difficult to differentiate between infection and tumour despite the utilization of computed tomography scans and magnetic resonance imaging.

    CONCLUSION: These cases illustrate the need for a high index of suspicion; in addition to endoscopic confirmation and histopathology to establish precise diagnosis and early intervention.

  7. Tan SH, Prepageran N
    J Laryngol Otol, 2015 Sep;129(9):928-31.
    PMID: 26193981 DOI: 10.1017/S0022215115001838
    This case report presents our experience of endoscopic transnasal management of medial intra- and extraconal lesions.
  8. Soo JS, Ng CH, Tan SH, Malik RA, Teh YC, Tan BS, et al.
    Apoptosis, 2015 Oct;20(10):1373-87.
    PMID: 26276035 DOI: 10.1007/s10495-015-1158-5
    Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers.
  9. Tan SH
    Asia Pac J Public Health, 2015 Nov;27(8 Suppl):41S-51S.
    PMID: 26122314 DOI: 10.1177/1010539515592461
    Information on unmet health care needs reveal problems that are related to unavailability and inaccessibility of services. The study objectives were to determine the prevalence, and the reasons for unmet service needs among children with disabilities in the state of Penang, Malaysia. Caregivers of children with disabilities aged 0 to 12 years registered with the Penang Social Welfare Department in 2012 answered a self-administered mailed questionnaire. A total of 305 questionnaires were available for analysis (response rate 37.9%). Services that were very much needed and yet highly unmet were dental services (49.6% needed, 59.9% unmet), dietary advice (30.9% needed, 63.3% unmet), speech therapy (56.9% needed, 56.8% unmet), psychology services (25.5% needed, 63.3% unmet), and communication aids (33.0% needed, 79.2% unmet). Access problems were mainly due to logistic issues and caregivers not knowing where to obtain services. Findings from this study can be used to inform strategies for service delivery and advocacy for children with disabilities in Penang, Malaysia.
  10. Tan SH, Ganesan D, Rusydi WZ, Chandran H, Prepageran N, Waran V
    Eur Spine J, 2015 Dec;24(12):2776-80.
    PMID: 26210311 DOI: 10.1007/s00586-015-4153-1
    PURPOSE: Osteoradionecrosis (ORN) is a rare yet well-recognized complication following radiotherapy to the head and neck. We illustrate the only case of a spontaneous extrusion of the sequestered C1 arch through the oral cavity and discuss our experience with a combined endoscopic transnasal and transoral approach for cervical ORN.

    METHODS: A 56-year-old female presented with a 3-month history of blood-stained nasal discharge. She had been treated with radiotherapy for nasopharyngeal carcinoma 25 years earlier. Flexible nasal endoscopy demonstrated an exposed bone with an edematous posterior nasopharyngeal mass. Computed tomography showed a pre-vertebral mass with destruction of C1 and C2. She underwent occipito-cervical fusion followed by a combined transnasal and transoral endoscopic debridement of non-viable bone in the same perioperative setting. Healing of the raw mucosa was by secondary intention and reconstruction was not performed.

    RESULTS: Histopathological examination reported ulcerated inflamed granulation tissue with no evidence of malignancy. During follow-up, she remained neurologically intact with no recurrence.

    CONCLUSION: Using both nasal and oral spaces allows placement of the endoscope in the nasal cavity and surgical instruments in the oral cavity without splitting the palate. Hence, the endoscopic transnasal and transoral approach has vast potential to be effective in carefully selected cases of cervical ORN.

  11. Tan SH, Brand Y, Prepageran N, Waran V
    Neurol India, 2015 Sep-Oct;63(5):673-80.
    PMID: 26448224 DOI: 10.4103/0028-3886.166539
    We present our experience in managing pathologies involving the anterior and middle cranial base using an endoscopic transnasal approach, highlighting the surgical technique, indications, and complications. The different types of endoscopic approaches used include the transtuberculum/transplanum, transcribiform, transsellar, and cavernous sinus approaches. The common indications include repair of cerebrospinal fluid leaks (both spontaneous and post traumatic) and excision of pituitary adenomas, meningiomas, craniopharyngiomas, esthesioneuroblastomas, and other malignancies of the anterior cranial base. Careful reconstruction is performed with the multilayer technique utilizing fat, fascia lata, and fibrin sealant. The endoscopic transnasal approach, coupled with the present-day sophisticated neuronavigation systems, allows access to lesions in the midline extending from the cribriform plate to the craniovertebral junction. However, preoperative planning and careful selection of cases with evaluation of each case on an individual basis with regard to the lateral extension of the lesion are imperative.
  12. Liu L, Mo Z, Liang Z, Zhang Y, Li R, Ong KC, et al.
    BMC Med, 2015;13:226.
    PMID: 26381232 DOI: 10.1186/s12916-015-0448-7
    To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy.
  13. Woo SP, Yasin Z, Tan SH, Kajihara H, Fujita T
    Zookeys, 2015.
    PMID: 26798290 DOI: 10.3897/zookeys.545.6415
    Five sea cucumber species including one new species of the genus Stichopus are reported from the shallow coral reefs of Straits of Malacca. The new species Stichopus fusiformiossa has unusual fusiform spicules in the tentacles, which are not found in the other species of the genus. Pseudo-tables and large perforated plates are newly recorded for Stichopus hermanni Semper, 1868 and Stichopus vastus Sluiter, 1887, respectively.
  14. Tan BS, Tiong KH, Choo HL, Chung FF, Hii LW, Tan SH, et al.
    Cell Death Dis, 2015;6:e1826.
    PMID: 26181206 DOI: 10.1038/cddis.2015.191
    p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers.
  15. Tan SH, Ong KC, Perera D, Wong KT
    Antiviral Res, 2016 Aug;132:196-203.
    PMID: 27340013 DOI: 10.1016/j.antiviral.2016.04.015
    BACKGROUND: Enterovirus A71 (EV-A71) encephalomyelitis is an often fatal disease for which there is no specific treatment available. Passive immunization with a specific monoclonal antibody to EV-A71 was used on a murine model of EV-A71 encephalomyelitis to evaluate its therapeutic effectiveness before and after established central nervous system (CNS) infection.

    METHODS: Mice were intraperitoneally-infected with a mouse-adapted EV-A71 strain and treated with a dose of monoclonal antibody (MAb) daily for 3 days on day 1, 2 and 3 post-infection or for 3 days on 3, 4 and 5 post-infection. Treatment effectiveness was evaluated by signs of infection and survival rate. Histopathology and qPCR analyses were performed on mice sacrificed a day after completing treatment.

    RESULTS: In mock-treated mice, CNS infection was established from day 3 post-infection. All mice treated before established CNS infection, survived and recovered completely without CNS infection. All mice treated after established CNS infection survived with mild paralysis, and viral load and antigens/RNA at day 6 post-infection were significantly reduced.

    CONCLUSIONS: Passive immunization with our MAb could prevent CNS infection in mice if given early before the establishment of CNS infection. It could also ameliorate established CNS infection if optimal and repeated doses were given.

  16. Tiong KH, Tan BS, Choo HL, Chung FF, Hii LW, Tan SH, et al.
    Oncotarget, 2016 Sep 06;7(36):57633-57650.
    PMID: 27192118 DOI: 10.18632/oncotarget.9328
    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.
  17. Tan SH, Normi YM, Leow AT, Salleh AB, Murad AM, Mahadi NM, et al.
    J. Biochem., 2017 02 01;161(2):167-186.
    PMID: 28175318 DOI: 10.1093/jb/mvw058
    The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetical protein (HP) termed Bleg1_2437 from the genome of alkaliphilic Bacillus lehensis G1 which exhibited MBL-like properties of B3 subclass; but evolutionary divergent from other circulating B3 MBLs. Domain and sequence analysis of HP Bleg1_2437 revealed that it contains highly conserved Zn2+-binding residues such as H54, H56, D58, H59, H131 and H191, important for catalysis, similar with the subclass B3 of MBL. Built 3-D Bleg1_2437 structure exhibited an αββα sandwich layer similar to the well-conserved global topology of MBL superfamily. Other features include a ceiling and floor in the model which are important for accommodation and orientation of β-lactam antibiotics docked to the protein model showed interactions at varying degrees with residues in the binding pocket of Bleg1_2437. Hydrolysis activity towards several β-lactam antibiotics was proven through an in vitro assay using purified recombinant Bleg1_2437 protein. These findings highlight the presence of a clinically important and evolutionary divergent antibiotics-degrading enzyme within the pools of uncharacterized HPs.
  18. Chung FF, Tan PF, Raja VJ, Tan BS, Lim KH, Kam TS, et al.
    Sci Rep, 2017 02 15;7:42504.
    PMID: 28198434 DOI: 10.1038/srep42504
    Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization.
  19. Tan SH
    Health Soc Care Community, 2017 03;25(2):447-457.
    PMID: 26833929 DOI: 10.1111/hsc.12325
    Disability in a child not only affects the child but also presents socioeconomic and psychological impacts to the child's family. This study aims to describe the service needs of caregivers of children with disabilities in the state of Penang, Malaysia, and to determine the child and family characteristics predisposing to having more caregiver needs. A cross-sectional survey was conducted between February and June 2013 among caregivers of children aged 0-12 years with disabilities registered with the Penang Department of Social Welfare. Caregivers completed a self-administered mailed questionnaire containing a 20-item Caregiver Needs Scale (CNS). Each item in the CNS was rated on a 5-point Likert scale ranging from 'help not at all needed' to 'help extremely needed'. A total of 273 surveys were available for analysis (response rate 34.0%). The CNS contained four domains. The 'Help getting Information and Services for child' domain had the highest mean score (3.61, 95% CI: 3.46, 3.77) followed by 'Help with Finances' (3.29, 95% CI: 3.13, 3.45) and 'Help Coping with child' (3.11, 95% CI: 2.97, 3.25), while the 'Help getting Childcare' domain had the lowest mean score (2.30, 95% CI: 2.13, 2.47). Multivariate regression analysis identified caregivers of younger children and with more severe disability as having more caregiver needs in all domains. Besides that, caregivers of children with learning disability needed more help getting information and help with coping. Caregivers of children with learning and multiple disabilities needed more help getting childcare compared to children with other disability. Caregivers of Indian ethnicity, who had less than a tertiary education and who themselves had medical problems needed more help with finances. The findings on caregiver needs in this study can help inform planning of family support services for children with disabilities in Penang, Malaysia.
  20. Tan SH, Habibullah MS, Tan SK, Choon SW
    J Environ Manage, 2017 Dec 01;203(Pt 1):603-611.
    PMID: 28285804 DOI: 10.1016/j.jenvman.2017.02.029
    This study investigates the impact of the aggregate and individual dimensions of environmental performance (EP) on financial performance (FP), based on a dataset covering the travel and tourism industry (airlines, casinos, hotels, and restaurants) across different economic regions over the period 2003-2014. The results reveal that EP positively affects the FP in the hotel industry when aggregate EP is used. When individual dimensions of EP are considered, resource reduction is found to positively (negatively) affect the performance in the hotel (airline) industry, while product innovation positively affects the performance in the restaurant industry. Hence, the trade-off effect seems to be dominant in the airline industry, and the 'heterogeneous resources and reputation-building' hypothesis is evident in both the hotel and restaurant industries. In addition, in general, the findings support the positive moderating effect of slack resources on the relationship between the individual dimensions of EP and FP in the travel and tourism industry, and, hence, are supportive of the slack resources hypothesis. These effects, however, vary depending on the travel and tourism industry under investigation.
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