Displaying publications 1 - 20 of 69 in total

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  1. Ahmad Hidayat AF, Chan CK, Mohamad J, Abdul Kadir H
    Biomed Pharmacother, 2018 Aug;104:806-816.
    PMID: 29860114 DOI: 10.1016/j.biopha.2018.05.073
    Dioscorea bulbifera, also known as air potato, has been cultivated as food crop mainly in tropical countries in Asia and Australia. The tubers are edible and have often been used in Traditional Chinese Medicine (TCM) and Ayurvedic medicine to treat cancer, diabetes, thyroid disease, and inflammation. This study aimed to investigate the effects of D. bulbifera on HCT116 human colorectal carcinoma cells and to unravel the plausible mechanisms underlying its apoptotic effects. The ethanol crude and fractions (hexane, ethyl acetate and water) of D. bulbifera were subjected to cell viability MTT assay against various cancer cell lines. The lowest IC50 of the extract and fractions on selected cancer cells were selected for further apoptosis assay and western blot analysis. HCT116 cancer cells were treated with D. bulbifera and stained with Annexin/PI or Hoechst 33342/PI for preliminary confirmation of apoptosis. The dissipation of mitochondria membrane potential (MMP) was determined by flow cytometry. The protein expressions of apoptosis-related proteins such as Bcl-2 family, caspases, Fas, PARP, ERK1/2 and JNK were detected by western blot analysis. Moreover, the HCT116 cells were treated with UO126 and SP600125 inhibitors to verify the involvement of ERK1/2 and JNK protein expressions in inducing apoptotic cell death. Based on the result, D. bulbifera ethyl acetate fraction (DBEAF) exhibited the most compelling cytotoxicity on HCT116 cells with an IC50 of 37.91 ± 1.30 µg/mL. The induction of apoptosis was confirmed by phosphatidylserine externalization and chromatin condensation. Depolarization of MMP further conferred the induction of apoptosis was through the regulation of Bcl-2 family proteins. Activation of caspase cascades (caspase-3, -9, -8 and -10) was elicited followed by the observation of cleaved PARP accumulation in DBEAF-treated cells. Furthermore, death receptor, Fas was activated upon exposure to DBEAF. Collective apoptotic evidences suggested the involvement of intrinsic and extrinsic pathways by DBEAF in HCT116 cells. Interestingly, the attenuation of ERK1/2 phosphorylation accompanied by the activation of JNK was detected in DBEAF-treated cells. In conclusion, the findings revealed that DBEAF induced apoptosis through intrinsic and extrinsic pathways involving ERK1/2 and JNK.
  2. Allotey P, Reidpath DD, Yasin S, Chan CK, de-Graft Aikins A
    Lancet, 2011 Feb 5;377(9764):450-1.
    PMID: 21074257 DOI: 10.1016/S0140-6736(10)61856-9
  3. Chan C, Ng W, Merican A
    Malays Orthop J, 2013 Jul;7(2):41-4.
    PMID: 25722826 MyJurnal DOI: 10.5704/MOJ.1307.012
    Non-union is a well recognized complication of femoral neck fractures. The decision whether to attempt fracture fixation or to resort to hip replacement is particularly difficult in patients in the borderline age group in whom complex attempts at gaining union may fail and later present a difficult revision. On the other hand the patient may be young enough that arthroplasty best be avoided . Besides, presence of ipsilateral femoral shaft fracture with delayed union in addition to the femoral neck non-union will pose major problems at operation. We share our experience in treating a femoral neck fracture non-union with ipsilateral femoral shaft delayed union in the shaft and in the distal femur in a fifty years old patient. The fracture was treated with an angle blade plate and supracondylar nail supplemented with a free vascularised fibular bone grafting and autologous cancellous graft. There was radiological union at fourth month. At sixth months, the patient was free of pain and able to walk without support. Thus, we would like to suggest that vascularised fibula bone grafting with supracondylar nailing is a viable option for this pattern of fracture.
  4. Chan CK, Goh BH, Kamarudin MN, Kadir HA
    Molecules, 2012 May 31;17(6):6633-57.
    PMID: 22728359 DOI: 10.3390/molecules17066633
    The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS) externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm) was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.
  5. Chan CK, Cameron LD
    J Behav Med, 2012 Jun;35(3):347-63.
    PMID: 21695405 DOI: 10.1007/s10865-011-9360-6
    Self-regulation theory and research suggests that different types of mental imagery can promote goal-directed behaviors. The present study was designed to compare the efficacy of approach imagery (attainment of desired goal states) and process imagery (steps for enacting behavior) in promoting physical activity among inactive individuals. A randomized controlled trial was conducted with 182 inactive adults who received one of four interventions for generating mental images related to physical activity over a 4-week period, with Approach Imagery (approach versus neutral) and Process Imagery (process versus no process) as the intervention strategies. Participants received imagery training and practiced daily. Repeated measures ANOVAs revealed that Approach Imagery: (1) increased approach motivations for physical activity at Week 4; (2) induced greater intentions post-session, which subsequently induced more action planning at Week 4; (3) enhanced action planning when combined with process images at post-session and Week 1; and (4) facilitated more physical activity at Week 4 via action planning. These findings suggest that inducing approach orientation via mental imagery may be a convenient and low-cost technique to promote physical activity among inactive individuals.
  6. Chan CK, Lee HY, Choi WC, Cho JY, Lee SH
    Eur Spine J, 2011 Jul;20 Suppl 2:S217-21.
    PMID: 20938789 DOI: 10.1007/s00586-010-1585-5
    Sciatica-like leg pain can be the main presenting symptom in patients with cervical cord compression. It is a false localizing presentation, which may lead to missed or delayed diagnosis, resulting in the wrong plan of management, especially in the presence of concurrent lumbar lesions. Medical history, physical findings and the results of imaging studies were reviewed in two cases of cervical cord compressions, which presented with sciatica-like leg pain. There was multi-level cervical spondylosis with cord compression in the first patient and the second patient had two levels of cervical disc herniation with cord compression. In both cases, there were co-existing lumbar lesions, which could be responsible for the presentation of the leg pain. Cervical blocks were diagnostic in identifying the level responsible for the leg pain and it was confirmed so after cervical decompressive surgery in both cases, which brought significant pain relief. Funicular leg pain is a rare presentation of cervical cord compression. It is a referred pain due to the irritation of the ascending spinothalamic tract. Cervical blocks were successful in identifying the cause of funicular pain in our cases and this may pave the way for further studies to establish the role of cervical blocks as a diagnostic tool for funicular pain caused by cord compression.
  7. Chan CK, Saw A, Kwan MK, Karina R
    J Orthop Surg (Hong Kong), 2009 Apr;17(1):19-22.
    PMID: 19398787
    To compare infection rates associated with 2 dressing solutions for metal-skin interfaces.
  8. Chan CK, Chan G, Awang K, Abdul Kadir H
    Molecules, 2016 Mar 21;21(3):385.
    PMID: 27007366 DOI: 10.3390/molecules21030385
    Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death in HCT116 cells. The anticancer activity of DET was evaluated by a MTT assay. Morphological and biochemical changes were detected by Hoescht 33342/PI and Annexin V/PI staining. The results revealed that DET and isodeoxyelephantopin (isoDET) could be isolated from the ethyl acetate fraction of E. scaber leaves via a bioassay-guided approach. DET induced significant dose- and time-dependent growth inhibition of HCT116 cells. Characteristics of apoptosis including nuclear morphological changes and externalization of phosphatidylserine were observed. DET also significantly resulted in the activation of caspase-3 and PARP cleavage. Additionally, DET induced cell cycle arrest at the S phase along with dose-dependent upregulation of p21 and phosphorylated p53 protein expression. DET dose-dependently downregulated cyclin D1, A2, B1, E2, CDK4 and CDK2 protein expression. In conclusion, our data showed that DET induced apoptosis and cell cycle arrest in HCT116 colorectal carcinoma, suggesting that DET has potential as an anticancer agent for colorectal carcinoma.
  9. Chan CK, Supriady H, Goh BH, Kadir HA
    J Ethnopharmacol, 2015 Jun 20;168:291-304.
    PMID: 25861953 DOI: 10.1016/j.jep.2015.03.072
    Elephantopus scaber also known as Elephant's foot (Asteraceae family) has a plethora of traditional applications including dysuria, diarrhea, dysentery, leukemia and cancer. This study aimed to investigate the apoptosis inducing effects of E. scaber and the underlying mechanisms in HCT116 colorectal cell line.
  10. Chan CK, Singh J, Rasid BK, Devaraj T
    Med J Malaysia, 1994 Jun;49(2):122-31.
    PMID: 8090090
    2,124 cases of cancer diagnosed and/or treated in Penang between 1987-1990 were reported to the National Cancer Registry of Malaysia by hospitals in Penang. 1,762 met the criteria for Penang incident cases first diagnosed between 1987-1990, and were the subjects on which all subsequent analyses were based. 85 per cent of case notifications were from Mount Miriam Hospital. Among males, all-site cancer incidence rates (age-standardised) were highest among Chinese, and lowest among Malays. Among females, the Indian female incidence rate was highest, higher than that of any other ethnic-gender sub-group. Site-specific cancer rates varied according to ethnicity and gender, but overall the four most frequent cancers reported from Penang were breast, lung, cervix and nasopharynx cancers. It needs to be emphasised that all these results are highly tentative since they are based on notified cancer occurrences and hence are very uncertain proxies for true cancer incidence. Based on incidence rates from the Singapore Cancer Registry (1978-1982), the expected number of incident cases in 1989 for Penang (Malays, Chinese and Indians combined) was 1,561. The number notified to the National Cancer Registry was 496. This underlines the tentative nature of this analysis of the returns for 1987-1990 from Penang.
  11. Chan CK, Mohamed RM, Azlina AA, Azhar MM
    Malays Orthop J, 2016 Nov;10(3):42-45.
    PMID: 28553448 MyJurnal DOI: 10.5704/MOJ.1611.004
    Multicentric disappearing bone disease, or Gorham disease, is a rare entity. A middle age woman, presented to us with left sided antalgic gait and severe bony deformity of her left knee. Radiograph revealed massive bone defect of the medial condyle of the left tibia with subluxation of the knee joint. She was scheduled for knee replacement in six months. However, she developed another lesion over the right hip that typically mimicked the disease progression of disappearing bone disease. The right femoral head vanished progressively within three months without significant history of infection or trauma. Subsequent bone biopsy of the right femoral head and left tibia condyle confirmed the diagnosis. Total knee replacement was carried out for her left knee. She remained pain free on her left knee. A year later, after confirming by sequential radiographs that the osteolysis had stopped, total right hip replacement was performed. Five years later, she remained pain free and both the arthroplasties were stable.
  12. Chan CK, Tan LT, Andy SN, Kamarudin MNA, Goh BH, Kadir HA
    Front Pharmacol, 2017;8:397.
    PMID: 28680404 DOI: 10.3389/fphar.2017.00397
    Elephantopus scaber L. (family: Asteraceae) has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF) on the release of pro-inflammatory mediators in lipopolysaccharide (LPS)-induced microglia cells (BV-2). Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.
  13. Chan CK, Low JS, Lim KS, Low SK, Tan CT, Ng CC
    Neurol Sci, 2020 Mar;41(3):591-598.
    PMID: 31720899 DOI: 10.1007/s10072-019-04122-9
    INTRODUCTION: Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.

    METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.

    RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.

    CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.

  14. Chan CK, Lam TY, Mohanavel L, Ghani JA, Anuar ASK, Lee CJ, et al.
    Am J Infect Control, 2022 Dec;50(12):1374-1380.
    PMID: 35292298 DOI: 10.1016/j.ajic.2022.02.033
    BACKGROUND: Medical students' white coats were found to harbor harmful organisms. This could be due to non-compliance to white coat hygiene measures. Therefore, we aim to develop and validate a questionnaire to assess the of knowledge, attitude, and practice (LAUNDERKAP) of white coat use among medical students in Malaysia.

    METHODS: This study was conducted in 4 local medical schools. LAUNDERKAP was developed via literature review and had 3 domains: attitude, knowledge, practice. An expert panel assessed the content validity and clarity of wording. LAUNDERKAP was then piloted among 32 medical students. To test construct validity and internal consistency, 362 medical students were approached. Construct validity was assessed using exploratory factor analysis. Internal consistency was evaluated using Cronbach alpha for attitude and practice, while Kuder-Richardson 20 (KR-20) was used for knowledge.

    RESULTS: A total of 319 of 362 students responded. Exploratory factor analysis extracted 1 factor each for attitude and knowledge respectively, and 3 factors for practice. Cronbach alpha for attitude was 0.843 while KR-20 for knowledge was 0.457. Cronbach alpha for practice ranged from 0.375 to 0.689. The final LAUNDERKAP contained 32-items (13 attitude, 9 knowledge, 10 practice).

    CONCLUSIONS: LAUNDERKAP had adequate psychometric properties and can be used to assess KAP of medical students towards white coat use.

  15. Chan CK, Lim KS, Low SK, Tan CT, Ng CC
    Epilepsy Res, 2023 Jan;189:107070.
    PMID: 36584483 DOI: 10.1016/j.eplepsyres.2022.107070
    Epilepsy is a complex neurological disease that can be caused by both genetic and environmental factors. Many studies have been conducted to investigate the genetic risk variants and molecular mechanisms of epilepsy. Disruption of excitation-inhibition balance (E/I balance) is one of the widely accepted disease mechanisms of epilepsy. The maintenance of E/I balance is an intricate process that is governed by multiple proteins. Using whole exome sequencing (WES), we identified a novel GABRA1 c.448G>A (p.E150K) variant and ERBB4 c.1972A>T (p.I658F, rs190654033) variant in a Malaysian Chinese family with genetic generalized epilepsy (GGE). The GGE may be triggered by dysregulation of E/I balance mechanism. Segregation of the variants in the family was verified by Sanger sequencing. All family members with GGE inherited both variants. However, family members who carried only one of the variants did not show any symptoms of GGE. Both the GABRA1 and ERBB4 variants were predicted damaging by MutationTaster and CADD, and protein structure analysis showed that the variants had resulted in the formation of additional hydrogen bonds in the mutant proteins. GABRA1 variant could reduce the efficiency of GABAA receptors, and constitutively active ERBB4 receptors caused by the ERBB4 variant promote internalization of GABAA receptors. The interaction between the two variants may cause a greater disruption in E/I balance, which is more likely to induce a seizure. Nevertheless, this disease model was derived from a single small family, further studies are still needed to confirm the verifiability of the purported disease model.
  16. Chan CK
    New Solut, 2002;12(2):109-19.
    PMID: 17208760
    On June 27, 2001, the World Health Organization conducted hearings in Geneva for a Special Report on Genomics & Health. Initially intended as a document to address the ethical, legal, and social implications of the gathering genomics resolution (ELSI), the terms of reference of the report were significantly modified to give primary emphasis to a scientific and technological assessment of the implications of genomics for human health. The Citizens' Health Initiative, one of two NGOs invited to make submissions at these consultations, suggested that no less important than the scientific and technical assessment was a perspective which gave due attention to the social context and political economy of scientific/technological development and its deployment. The article below touches upon neglected health priorities of poor countries, intellectual property rights and patents, risk management, insurance and discrimination, and predictive (prenatal) testing, reproductive choice, and eugenics.
  17. Chan CK, Lam TY, Mohanavel L, Ghani JA, Anuar ASK, Lee CJ, et al.
    Am J Infect Control, 2024 Jan;52(1):35-40.
    PMID: 37423404 DOI: 10.1016/j.ajic.2023.06.022
    BACKGROUND: Recent studies found white coats to be reservoirs for bacteria and medical students did not conform to proper hygiene measures when using these white coats. We investigated the knowledge, attitude, and practice (KAP) of medical students toward white coat use in clinical settings (LAUNDERKAP).

    METHODS: A validated, online-based survey was disseminated to 670 students from four Malaysian medical schools via random sampling. Scores were classified into good, moderate, or poor knowledge and practice, and positive, neutral, or negative attitude. Mann-Whitney U and Kruskal-Wallis tests were used to analyze the relationship between demographic variables and knowledge, attitude, and practice scores.

    RESULTS: A total of 492/670 students responded (response rate: 73.4%). A majority showed negative attitudes (n = 246, 50%), poor knowledge (n = 294, 59.8%), and moderate practice (n = 239, 48.6%). Senior and clinical year students had more negative attitudes. Male students had higher knowledge, while students from private medical schools and preclinical years had better practice. There was a significant relationship between attitude and practice (r = 0.224, P 

  18. Chen CD, Lee HL, Chan CK, Ang CL, Azahari AH, Lau KW, et al.
    Trop Biomed, 2009 Dec;26(3):360-5.
    PMID: 20237452
    The bioefficacy of nine commercial formulations of temephos against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae were evaluated in the laboratory. WHO larval bioassay with operational dosage of temephos at 1 mg/L was performed. The larval mortality was recorded every 5 minutes until complete mortality was achieved. All formulations of temephos exhibited various toxicity level against Ae. aegypti, Ae. albopictus and Cx. quinquefasciatus. Generally, larvae of Cx. quinquefasciatus was susceptible to all formulations of temephos, followed by Ae. aegypti and Ae. albopictus.
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