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  1. Lee YT, Tan YJ, Oon CE
    Eur. J. Pharmacol., 2018 Sep 05;834:188-196.
    PMID: 30031797 DOI: 10.1016/j.ejphar.2018.07.034
    Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
  2. Tan YJ, Wendy T, Chieng JY
    Med. J. Malaysia, 2019 Feb;74(1):20-24.
    PMID: 30846657
    OBJECTIVE: The aim of this study was to evaluate the demography, and to determine the detection rate of polyps, and detection rate of adenoma at a Malaysian tertiary hospital.

    METHODS: This is a retrospective study of all the patients who had undergone colonoscopy at Gastroenterology endoscopy unit, Serdang Hospital from 1st January 2010 to 31st December 2016. Patients who had a history of colorectal cancer, polyp or inflammatory bowel disease were excluded. Data collected which included patients' demography, indication for colonoscopy, colonoscopy finding, and histopathology results. Data was analysed with SPSS version 16.

    RESULTS: Among the 559 patients who had fulfilled the inclusion criteria (68 males, 44 females), 112 patients were found to have at least one polyp giving the polyp detection rate (PDR) of 20% and 168 polypectomies were performed. The PDR among male patients was higher than that of females (22.5% vs 17.1%, p<0.05). The detection rate of polyp was nearly equal in Malays, Chinese, Indians, and Others. The polyps were more common in those of age 40 years old and above (p<0.05), with the mean age of 63.0±1.5 years. The commonest morphology of polyp in our patients was sessile (58%) and majority was medium size (5-9mm). Otherwise, the polyps were commonly found in the distal colon those that in proximal colon (55.3% vs 38.7%, p<0.05). The adenoma detection rate (ADR) was 19.1% (107/559).

    CONCLUSION: The detection rate of colonic polyp from colonoscopy is 20% in our centre.

  3. Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

  4. Tan YJ, Yeo CI, Halcovitch NR, Jotani MM, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2017 Apr 01;73(Pt 4):493-499.
    PMID: 28435705 DOI: 10.1107/S205698901700353X
    The title compound, (C6H11)3PS (systematic name: tri-cyclo-hexyl-λ(5)-phosphane-thione), is a triclinic (P-1, Z' = 1) polymorph of the previously reported ortho-rhom-bic form (Pnma, Z' = 1/2) [Kerr et al. (1977 ▸). Can. J. Chem. 55, 3081-3085; Reibenspies et al. (1996 ▸). Z. Kristallogr. 211, 400]. While conformational differences exist between the non-symmetric mol-ecule in the triclinic polymorph, cf. the mirror-symmetric mol-ecule in the ortho-rhom-bic form, these differences are not chemically significant. The major feature of the mol-ecular packing in the triclinic polymorph is the formation of linear chains along the a axis sustained by methine-C-H⋯S(thione) inter-actions. The chains pack with no directional inter-actions between them. The analysis of the Hirshfeld surface for both polymorphs indicates a high degree of similarity, being dominated by H⋯H (ca 90%) and S⋯H/H⋯S contacts.
  5. Tan YJ, Yeo CI, Halcovitch NR, Jotani MM, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2017 May 01;73(Pt 5):720-725.
    PMID: 28529784 DOI: 10.1107/S2056989017005382
    The title trinuclear compound, [Cu3(C5H8NS2)Cl2(C6H15P)3], has the di-thio-carbamate ligand symmetrically chelating one Cu(I) atom and each of the S atoms bridging to another Cu(I) atom. Both chloride ligands are bridging, one being μ3- and the other μ2-bridging. Each Et3P ligand occupies a terminal position. Two of the Cu(I) atoms exist within Cl2PS donor sets and the third is based on a ClPS2 donor set, with each coordination geometry based on a distorted tetra-hedron. The constituents defining the core of the mol-ecule, i.e. Cu3Cl2S2, occupy seven corners of a distorted cube. In the crystal, linear supra-molecular chains along the c axis are formed via phosphane-methyl-ene-C-H⋯Cl and pyrrolidine-methyl-ene-C-H⋯π(chelate) inter-actions, and these chains pack without directional inter-actions between them. An analysis of the Hirshfeld surface points to the predominance of H atoms at the surface, i.e. contributing 86.6% to the surface, and also highlights the presence of C-H⋯π(chelate) inter-actions.
  6. Tan YJ, Tan YS, Yeo CI, Chew J, Tiekink ERT
    J. Inorg. Biochem., 2019 Mar;192:107-118.
    PMID: 30640150 DOI: 10.1016/j.jinorgbio.2018.12.017
    Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl3PAg(S2CNRR')}2 for R = R' = Et (1), CH2CH2 (2), CH2CH2OH (3) and R = Me, R' = CH2CH2OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ2-bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS3 donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log10 CFU/mL against S. aureus (MRSA).
  7. Xu Y, Victorio CBL, Meng T, Jia Q, Tan YJ, Chua KB
    Virol Sin, 2019 Jun;34(3):262-269.
    PMID: 31016480 DOI: 10.1007/s12250-019-00116-1
    Our previous work has shown that Saffold virus (SAFV) induced several rodent and primate cell lines to undergo apoptosis (Xu et al. in Emerg Microb Infect 3:1-8, 2014), but the essential viral proteins of SAFV involved in apoptotic activity lack study. In this study, we individually transfected the viral proteins of SAFV into HEp-2 and Vero cells to assess their ability to induce apoptosis, and found that the 2B and 3C proteins are proapoptotic. Further investigation indicated the transmembrane domain of the 2B protein is essential for the apoptotic activity and tetramer formation of the 2B protein. Our research provides clues for the possible mechanisms of apoptosis induced by SAFV in different cell lines. It also opens up new directions to study viral proteins (the 2B, 3C protein), and sets the stage for future exploration of any possible link between SAFV, inclusive of its related uncultivable genotypes, and multiple sclerosis.
  8. Er JL, Goh PN, Lee CY, Tan YJ, Hii LW, Mai CW, et al.
    Apoptosis, 2018 Jun;23(5-6):343-355.
    PMID: 29740790 DOI: 10.1007/s10495-018-1459-6
    Pancreatic adenocarcinoma (PDAC) is a highly aggressive cancer with a high chance of recurrence, limited treatment options, and poor prognosis. A recent study has classified pancreatic cancers into four molecular subtypes: (1) squamous, (2) immunogenic, (3) pancreatic progenitor and (4) aberrantly differentiated endocrine exocrine. Among all the subtypes, the squamous subtype has the worst prognosis. This study aims to utilize large scale genomic datasets and computational systems biology to identify potential drugs targeting the squamous subtype of PDAC through combination therapy. Using the transcriptomic data available from the International Cancer Genome Consortium, Cancer Cell Line Encyclopedia and Connectivity Map, we identified 26 small molecules that could target the squamous subtype of PDAC. Among them include inhibitors targeting the SRC proto-oncogene (SRC) and the mitogen-activated protein kinase kinase 1/2 (MEK1/2). Further analyses demonstrated that the SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib) synergized gemcitabine sensitivity specifically in the squamous subtype of PDAC cells (SW1990 and BxPC3), but not in the PDAC progenitor cells (AsPC1). Further analysis revealed that the synergistic effects are dependent on SRC or MEK1/2 activities, as overexpression of SRC or MEK1/2 completely abrogated the synergistic effects SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib). In contrast, no significant toxicity was observed in the MRC5 human lung fibroblast and ARPE-19 human retinal pigment epithelial cells. Together, our findings suggest that combinations of SRC or MEK inhibitors with gemcitabine possess synergistic effects on the squamous subtype of PDAC cells and warrant further investigation.
  9. Lock C, Kwok J, Kumar S, Ahmad-Annuar A, Narayanan V, Ng ASL, et al.
    PMID: 30687707 DOI: 10.3389/fmed.2018.00357
    Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.
  10. Zhang YZ, Xiong CL, Lin XD, Zhou DJ, Jiang RJ, Xiao QY, et al.
    Infect. Genet. Evol., 2009 Jan;9(1):87-96.
    PMID: 19041424 DOI: 10.1016/j.meegid.2008.10.014
    There have been three major rabies epidemics in China since the 1950s. To gain more insights into the molecular epidemiology of rabies viruses (RVs) for the third (the current) epidemic, we isolated RV from dogs and humans in major endemic areas, and characterized these isolates genetically by sequencing the entire glycoprotein (G) gene and the G-L non-coding region. These sequences were also compared phylogenetically with RVs isolated in China during previous epidemics and those around the world. Comparison of the entire G genes among the Chinese isolates revealed up to 21.8% divergence at the nucleotide level and 17.8% at the amino acid level. The available Chinese isolates could be divided into two distinct clades, each of which could be further divided into six lineages. Viruses in clade I include most of the Chinese viruses as well as viruses from southeast Asian countries including Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. The viruses in the other clade were found infrequently in China, but are closely related to viruses distributed worldwide among terrestrial animals. Interestingly, most of the viruses isolated during the past 10 years belong to lineage A viruses within clade I whereas most of the viruses isolated before 1996 belong to other lineages within clades I and II. Our results indicated that lineages A viruses have been predominant during the past 10 years and thus are largely responsible for the third and the current epidemic in China. Our results also suggested that the Chinese RV isolates in clade I share a common recent ancestor with those circulating in southeast Asia.
  11. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
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