Displaying publications 1 - 20 of 50 in total

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  1. Mai CW, Kang YB, Pichika MR
    Onco Targets Ther, 2013;6:1573-87.
    PMID: 24235843 DOI: 10.2147/OTT.S50838
    Toll-like receptor 4 (TLR-4) is well known for its host innate immunity. Despite the fact that TLR-4 activation confers antitumor responses; emerging evidence suggests that TLR-4 is associated with tumor development and progression. It is now clear that overactivation of TLR-4, through various immune mediators, may cause immune response dysfunction, resulting in tumorigenesis. Different cancers could have different extents of TLR-4 involvement during tumorigenesis or tumor progression. In this review, we focus on infection- and inflammation-related TLR-4 activation in noncancer and cancer cells, as well as on the current evidence about the role of TLR-4 in ten of the most common cancers, viz, head and neck cancer, lung cancer, gastrointestinal cancer, liver cancer, pancreatic cancer, skin cancer, breast cancer, ovarian cancer, cervical cancer, and prostate cancer.
  2. Chung FF, Mai CW, Ng PY, Leong CO
    Curr Cancer Drug Targets, 2016;16(1):71-8.
    PMID: 26563883
    Cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1) is a newly identified monooxygenase enzyme that is expressed specifically in tumor tissues and during fetal life. Particularly, high expression of CYP2W1 was observed in up to 60% of colorectal cancers and its expression correlated with poor survival. CYP2W1 has been shown to metabolize various endogenous substrates including lysophospholipids and several procarcinogens, such as polycyclic aromatic hydrocarbon. The specific substrate for CYP2W1, however, is currently unknown. Due to its tumor-specific expression and its unique catalytic activities in colorectal cancers, CYP2W1 was deemed as an interesting target in colorectal cancer therapy. This review sought to summarize the current understanding of the CYP2W1 biology and biochemistry, its genetic polymorphisms and cancer risk, and its implication as a tumor-specific diagnostic and therapeutic target.
  3. Mai CW, Kang YB, Hamzah AS, Pichika MR
    Food Funct, 2018 Jun 20;9(6):3344-3350.
    PMID: 29808897 DOI: 10.1039/c8fo00136g
    Vanilloid (4-hydroxy-3-methoxyphenyl benzenoid) containing foods are reported to possess many biological activities including anti-inflammatory properties. Homodimerisation of the Toll-like receptor-4 (TLR-4)/Myeloid differentiation factor 2 (MD-2) complex results in life-threatening complications in inflammatory disorders. In this study, we report activity of vanilloids in inhibition of TLR-4/MD-2 homodimersization and their molecular interactions with the receptor. The inhibitory activities of vanilloids were assessed in vitro by determining their antagonistic actions of lipopolysaccharide from Escherichia coli (LPSEc) in activation of TLR-4/MD-2 homodimerisation in TLR-4/MD-2/CD-14 transfected HEK-293 cells. The in vitro anti-inflammatory activity of vanilloids was also determined using RAW 264.7 cells. All the vanilloids were found to be active in the inhibition of TLR-4/MD-2 homodimersiation and nitric oxide production in RAW 264.7 cells. Rigid and flexible molecular docking studies were performed to gain insight into interactions between vanilloids and the binding site of the TLR-4/MD-2 complex.
  4. Mai CW, Chung FF, Leong CO
    Curr Drug Targets, 2017;18(11):1259-1268.
    PMID: 27993111 DOI: 10.2174/1389450117666161216125344
    BACKGROUND: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target.

    CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.

  5. Chong YS, Mai CW, Leong CO, Wong LC
    Cutan Ocul Toxicol, 2018 Mar;37(1):52-60.
    PMID: 28554225 DOI: 10.1080/15569527.2017.1335748
    PURPOSE: Dysfunction of the microRNA (miRNA)-processing enzyme DICER1 and Alu RNA accumulation are linked to the pathogenesis of age-related macular degeneration (AMD). This study determined the optimal dose of lutein (LUT) and zeaxanthin (ZEA) to protect human retinal pigment epithelium (RPE) cells against hydrogen peroxide (H2O2). The effect of the optimal dose of LUT and ZEA as DICER1 and Alu RNA modulators in cultured human RPE cells challenged with H2O2 was investigated.

    MATERIALS AND METHODS: ARPE-19 cells were pre-treated with LUT, ZEA, or both for 24 h before 200 μM H2O2 challenge. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. DICER1 and Alu RNA were quantified by western blotting and real-time polymerase chain reaction, respectively.

    RESULTS: H2O2 increased cell Alu RNA expression and decreased cell viability of ARPE-19, but had no significant impact on the DICER1 protein level. LUT, alone and in combination with ZEA pre-treatment, prior to H2O2 challenge significantly improved cell viability of ARPE-19 and reduced the level of Alu RNA compared to the negative control.

    CONCLUSIONS: These results support the use of LUT alone, and in combination with ZEA, in AMD prevention and treatment. This study is also the first to report LUT modulating effects on Alu RNA.

  6. Tham SY, Loh HS, Mai CW, Fu JY
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654580 DOI: 10.3390/ijms20020372
    Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.
  7. Maniam G, Mai CW, Zulkefeli M, Fu JY
    Nanomedicine (Lond), 2021 02;16(5):373-389.
    PMID: 33543651 DOI: 10.2217/nnm-2020-0374
    Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM's antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.
  8. Mai CW, Shu Y, Cheong SK, Chua CW
    Sheng Li Xue Bao, 2021 Apr 25;73(2):181-196.
    PMID: 33903880
    Organoids are self-organized cellular clusters in three-dimensional culture, which can be derived from a single stem cell, progenitor or cell clusters of different lineages resembling in vivo tissue architecture of an organ. In the recent years, organoids technology has contributed to the revolutionary changes in stem cell and cancer fields. In this review, we have briefly overviewed the emerging landscape of prostate organoid technology (POT) in prostate research. In addition, we have also summarized the potential application of POT in the understanding of prostate stem cell and cancer biology and the discovery of novel therapeutic strategies for prostate cancer. Lastly, we have critically discussed key challenges that lie in the current state of POT and provided a future perspective on the second-generation of POT, which should better recapitulate cellular behaviors and drug responses of prostate cancer patients.
  9. Wu XH, Liew YK, Mai CW, Then YY
    Int J Mol Sci, 2021 Mar 24;22(7).
    PMID: 33805207 DOI: 10.3390/ijms22073341
    Medical devices are indispensable in the healthcare setting, ranging from diagnostic tools to therapeutic instruments, and even supporting equipment. However, these medical devices may be associated with life-threatening complications when exposed to blood. To date, medical device-related infections have been a major drawback causing high mortality. Device-induced hemolysis, albeit often neglected, results in negative impacts, including thrombotic events. Various strategies have been approached to overcome these issues, but the outcomes are yet to be considered as successful. Recently, superhydrophobic materials or coatings have been brought to attention in various fields. Superhydrophobic surfaces are proposed to be ideal blood-compatible biomaterials attributed to their beneficial characteristics. Reports have substantiated the blood repellence of a superhydrophobic surface, which helps to prevent damage on blood cells upon cell-surface interaction, thereby alleviating subsequent complications. The anti-biofouling effect of superhydrophobic surfaces is also desired in medical devices as it resists the adhesion of organic substances, such as blood cells and microorganisms. In this review, we will focus on the discussion about the potential contribution of superhydrophobic surfaces on enhancing the hemocompatibility of blood-contacting medical devices.
  10. Mai CW, Yaeghoobi M, Abd-Rahman N, Kang YB, Pichika MR
    Eur J Med Chem, 2014 Apr 22;77:378-87.
    PMID: 24675137 DOI: 10.1016/j.ejmech.2014.03.002
    In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.
  11. Tiong JJ, Mai CW, Gan PW, Johnson J, Mak VS
    Int J Pharm Pract, 2016 Aug;24(4):302-5.
    PMID: 26777986 DOI: 10.1111/ijpp.12244
    This article serves as an update to the work by Shafie et al. (2012) which previously reviewed the benefits of policies separating prescribing and dispensing in various countries to advocate its implementation in Malaysia. This article seeks to strengthen the argument by highlighting not only the weaknesses of the Malaysian health care system from the historical, professional and economic viewpoints but also the shortcomings of both medical and pharmacy professions in the absence of separation of dispensing. It also provides a detailed insight into the ongoing initiatives taken to consolidate the role of pharmacists in the health care system in the advent of separation of dispensing. Under the two tier system in Malaysia at present, the separation of prescribing and dispensing is implemented only in government hospitals. The absence of this separation in the private practices has led to possible profit-oriented medical and pharmacy practices which hinder safe and cost-effective delivery of health services. The call for separation of dispensing has gained traction over the years despite various hurdles ranging from the formidable resistance from the medical fraternity to the public's scepticism towards the new policy. With historical testament and present evidence pointing towards the merits of a system in which doctors prescribe and pharmacists dispense, the implementation of this health care model is justified.
  12. Wu YS, Lee ZY, Chuah LH, Mai CW, Ngai SC
    Curr Cancer Drug Targets, 2019;19(2):82-100.
    PMID: 29714144 DOI: 10.2174/1568009618666180430130248
    Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC are discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future.
  13. Tiong JJL, Kho HL, Mai CW, Lau HL, Hasan SS
    BMC Med Educ, 2018 Jul 17;18(1):168.
    PMID: 30016945 DOI: 10.1186/s12909-018-1274-3
    BACKGROUND: This study was carried out to gauge the prevalence of academic dishonesty among academics in Malaysian universities. A direct comparison was made between academics of healthcare and non-healthcare courses to note the difference in the level of academic integrity between the two groups. In addition, the predisposing factors and implications of academic dishonesty, as well as the different measures perceived to be effective at curbing this problem were also investigated.

    METHODS: A cross-sectional study design with mixed qualitative and quantitative approaches was employed and data collection was carried out primarily using self-administered questionnaire.

    RESULTS: Approximately half (52.5%, n = 74) of all respondents (n = 141) reported having personally encountered at least one case of academic dishonesty involving their peers. The results also revealed the significantly higher prevalence of various forms of academic misconduct among healthcare academics compared to their non-healthcare counterparts. Although respondents were generally conscious of the negative implications associated with academic dishonesty, more than half of all cases of misconduct were not reported due to the indifferent attitude among academics. Low levels of self-discipline and integrity were found to be the major factors leading to academic misdeeds and respondents opined that university managements should be more proactive in addressing this issue.

    CONCLUSIONS: The outcome of this study should serve as a clarion call for all relevant stakeholders to start making immediate amends in order to improve the current state of affairs in academia.

  14. See HQ, Chan JN, Ling SJ, Gan SC, Leong CO, Mai CW
    J Pharm Pharm Sci, 2018;21(1):217-221.
    PMID: 29935548 DOI: 10.18433/jpps29869
    Big data is anticipated to have large implications in clinical pharmacy, in view of its potential in enhancing precision medicine and to avoid medication error. However, it is equally debatable since such a powerful tool may also disrupt the need of pharmacist in healthcare industry. In this article, we commented the contribution of Big Data in various aspects of clinical pharmacy including advancing pharmaceutical care service, optimising drug supplies, managing clinical trials, and strengthening pharmacovigilance. The future direction of the usage of Big Data related to clinical pharmacy will be discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
  15. Yang SK, Yusoff K, Mai CW, Lim WM, Yap WS, Lim SE, et al.
    Molecules, 2017 Nov 04;22(11).
    PMID: 29113046 DOI: 10.3390/molecules22111733
    Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.
  16. Mai CW, Kang YB, Nadarajah VD, Hamzah AS, Pichika MR
    Phytother Res, 2018 Jun;32(6):1108-1118.
    PMID: 29464796 DOI: 10.1002/ptr.6051
    In this study, a series of 20 structurally similar vanilloids (Vn) were tested for their antiproliferative effects against 12 human cancer cells: human breast (MCF-7 and MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29 and HCT116), nasopharyngeal (CNE-1 and HK-1), and leukemic (K562 and CEM-SS) cancer cells. Among all the tested vanilloids, Vn16 (6-shogaol) exhibited the most potent cytotoxic effects against human colorectal cancer cells (HT-29). The apoptotic induction effects exhibited by Vn16 on HT-29 cells were confirmed using dual staining fluorescence microscopy and enzyme-linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic-related markers were determined in HT-29. The results suggested that 8 apoptotic markers (caspase 8, BAD, BAX, second mitochondrial-derived activator, caspase 3, survivin, bcl-2, and cIAP-2) were either upregulated or downregulated. These results further support the chemopreventive properties of foods that contain vanilloids.
  17. Hii LW, Chung FF, Soo JS, Tan BS, Mai CW, Leong CO
    Breast Cancer Res Treat, 2020 Feb;179(3):615-629.
    PMID: 31784862 DOI: 10.1007/s10549-019-05504-5
    PURPOSE: Breast cancer stem cells (CSCs) are a small subpopulation of cancer cells that have high capability for self-renewal, differentiation, and tumor initiation. CSCs are resistant to chemotherapy and radiotherapy, and are responsible for cancer recurrence and metastasis.

    METHODS: By utilizing a panel of breast cancer cells and mammospheres culture as cell-based screening platforms, we performed high-throughput chemical library screens to identify agents that are effective against breast CSCs and non-CSCs. The hit molecules were paired with conventional chemotherapy to evaluate the combinatorial treatment effects on breast CSCs and non-CSCs.

    RESULTS: We identified a total of 193 inhibitors that effectively targeting both breast CSCs and non-CSCs. We observed that histone deacetylase inhibitors (HDACi) synergized conventional chemotherapeutic agents (i.e., doxorubicin and cisplatin) in targeting breast CSCs and non-CSCs simultaneously. Further analyses revealed that quisinostat, a potent inhibitor for class I and II HDACs, potentiated doxorubicin-induced cytotoxicity in both breast CSCs and non-CSCs derived from the basal-like (MDA-MB-468 and HCC38), mesenchymal-like (MDA-MB-231), and luminal-like breast cancer (MCF-7). It was also observed that the basal-like breast CSCs and non-CSCs were more sensitive to the co-treatment of quisinostat with doxorubicin compared to that of the luminal-like breast cancer subtype.

    CONCLUSION: In conclusion, this study demonstrates the potential of HDACi as therapeutic options, either as monotherapy or in combination with chemotherapeutics against refractory breast cancer.

  18. Mai CW, Tan JSH, Koay GWL, Lim LYX
    Pharmacy (Basel), 2020 Sep 13;8(3).
    PMID: 32933158 DOI: 10.3390/pharmacy8030170
    Dietary supplementation is increasingly sought after by consumers looking to meet the demands of a modern lifestyle. Effective supplementation requires knowledge of the purpose and proper use of nutritional supplements. Unverified or inadequate guidance on supplementation can propagate misconceptions and increase undue fears of side effects. Community pharmacists are best placed to guide consumers on nutritional supplement use. In this review, a panel comprised of community pharmacists, pharmacy academia, and dietitians (n = 6) convened to provide an experience- and evidence-based guidance on rational drug use, patient education, and integrated and personalized nutrition care in both community and hospital pharmacy settings. A novel framework to guide community pharmacist-led consultations on supplementation is proposed. The four-step CARE (Categorize, Assess, Recommend, Empower) guide was developed to facilitate and optimize outcomes of pharmacist-led nutritional supplement consultation. Telehealth advancements in the form of digital health applications and personalized nutrigenomic DNA testing support Integrative Nutrition Care, and will further promote appropriate supplementation use to improve overall well-being in the community. Practical implementation of the CARE guide is necessary to ascertain its applicability for optimizing outcomes of pharmacist-led consultation and the recommendation of nutritional supplements.
  19. Maniam G, Mai CW, Zulkefeli M, Dufès C, Tan DM, Fu JY
    Front Pharmacol, 2018;9:1358.
    PMID: 30534071 DOI: 10.3389/fphar.2018.01358
    Plant-derived phytonutrients have emerged as health enhancers. Tocotrienols from the vitamin E family gained high attention in recent years due to their multi-targeted biological properties, including lipid-lowering, neuroprotection, anti-inflammatory, antioxidant, and anticancer effects. Despite well-defined mechanism of action as an anti-cancer agent, their clinical use is hampered by poor pharmacokinetic profile and low oral bioavailability. Delivery systems based on nanotechnology were proven to be advantageous in elevating the delivery of tocotrienols to tumor sites for enhanced efficacy. To date, preclinical development of nanocarriers for tocotrienols include niosomes, lipid nanoemulsions, nanostructured lipid carriers (NLCs) and polymeric nanoparticles. Active targeting was explored via the use of transferrin as targeting ligand in niosomes. In vitro, nanocarriers were shown to enhance the anti-proliferative efficacy and cellular uptake of tocotrienols in cancer cells. In vivo, improved bioavailability of tocotrienols were reported with NLCs while marked tumor regression was observed with transferrin-targeted niosomes. In this review, the advantages and limitations of each nanocarriers were critically analyzed. Furthermore, a number of key challenges were identified including scale-up production, biological barriers, and toxicity profiles. To overcome these challenges, three research opportunities were highlighted based on rapid advancements in the field of nanomedicine. This review aims to provide a wholesome perspective for tocotrienol nanoformulations in cancer therapy directed toward effective clinical translation.
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