Displaying publications 1 - 20 of 55 in total

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  1. 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ)
    Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, et al.
    Cancer Lett, 2013 Aug 9;336(1):127-39.
    PMID: 23612072 DOI: 10.1016/j.canlet.2013.04.014
    6-Shogaol has been shown to possess many antitumor properties including inhibition of cancer cell growth, inhibition of cancer metastasis, induction of apoptosis in cancer cells and induction of cancer cell differentiation. Despite its prominent antitumor effects, the direct molecular target of 6-shogaol has remained elusive. To identify the direct targets of 6-shogaol, a comprehensive antitumor profile of 6-shogaol (NSC752389) was tested in the NCI-60 cell line in an in vitro screen. The results show that 6-shogaol is COMPARE negative suggesting that it functions via a mechanism of action distinct from existing classes of therapeutic agents. Further analysis using microarray gene profiling and Connectivity Map analysis showed that MCF-7 cells treated with 6-shogaol display gene expression signatures characteristic of peroxisome proliferator activated receptor γ (PPARγ) agonists, suggesting that 6-shogaol may activate the PPARγ signaling pathway for its antitumor effects. Indeed, treatment of MCF-7 and HT29 cells with 6-shogaol induced PPARγ transcriptional activity, suppressed NFκB activity, and induced apoptosis in breast and colon cancer cells in a PPARγ-dependent manner. Furthermore, 6-shogaol is capable of binding to PPARγ with a binding affinity comparable to 15-delta prostaglandin J2, a natural ligand for PPARγ. Together, our findings suggest that the antitumor effects of 6-shogaol are mediated through activation of PPARγ and imply that activation of PPARγ might be beneficial for breast and colon cancer treatment.
  2. A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis
    Al-Khdhairawi AAQ, Krishnan P, Mai CW, Chung FF, Leong CO, Yong KT, et al.
    J Nat Prod, 2017 10 27;80(10):2734-2740.
    PMID: 28926237 DOI: 10.1021/acs.jnatprod.7b00500
    Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (+)-1 and (-)-1 were established via experimental and calculated ECD data. Compound 1 is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound 2 represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-1 displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC50 7.4 μM), while compound 2 showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC50 values of 0.038-0.91 μM).
  3. Fulltext Academic dishonesty among academics in Malaysia: a comparison between healthcare and non-healthcare academics
    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.

  4. Academic integrity of health care educators: requisite for nurturing professionalism
    Tiong JJ, Mai CW, Yong AC
    Med Educ, 2015 Nov;49(11):1060-2.
    PMID: 26494059 DOI: 10.1111/medu.12828
  5. Fulltext Additivity vs Synergism: Investigation of the Additive Interaction of Cinnamon Bark Oil and Meropenem in Combinatory Therapy
    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.
  6. Fulltext Advancing Pharmacy Service using Big Data - Are We Fully Utilising the Big Data's Potential Yet?
    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.
  7. Alstoscholactine and Alstolaxepine, Monoterpenoid Indole Alkaloids with γ-Lactone-Bridged Cycloheptane and Oxepane Moieties from Alstonia scholaris
    Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.
    Org. Lett., 2018 12 21;20(24):8014-8018.
    PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592
    Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
  8. Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins
    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.
  9. Fulltext Challenges and Opportunities of Nanotechnology as Delivery Platform for Tocotrienols in Cancer Therapy
    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.
  10. Co-encapsulation of gemcitabine and tocotrienols in nanovesicles enhanced efficacy in pancreatic cancer
    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.
  11. Comparative efficacy of vanilloids in inhibiting toll-like receptor-4 (TLR-4)/myeloid differentiation factor (MD-2) homodimerisation
    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.
  12. Fulltext Comparison of vegetable oils on the uptake of lutein and zeaxanthin by ARPE-19 cells
    Baek J, Mai CW, Lim WM, Wong LC
    Int J Ophthalmol, 2023;16(1):40-46.
    PMID: 36659939 DOI: 10.18240/ijo.2023.01.06
    AIM: To compare the effect of vegetable oils on the uptake of lutein and zeaxanthin by adult retinal pigment epithelial (ARPE)-19 cells in vitro.

    METHODS: ARPE-19 cells were cultured in Dulbecco's Modified Eagle Medium-F-12 supplemented with 10% foetal bovine serum and 1% penicillin-streptomycin in a humidified 5% CO2 incubator maintained at 37°C. Cells were treated with 247 µmol/L lutein, 49 µmol/L zeaxanthin and 1% (v/v) of either coconut oil, corn oil, peanut oil, olive oil, sunflower oil, soybean oil, castor oil, or linseed oil for 48h. Lutein and zeaxanthin concentration in the cells were quantified by high performance liquid chromatography.

    RESULTS: Among the oils tested, the highest lutein and zeaxanthin uptake was observed with coconut oil while the lowest was observed with linseed oil.

    CONCLUSION: ARPE-19 uptake of lutein and zeaxanthin are found to be dependent on the type of oils.

  13. Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles
    Yeong KY, Tan SC, Mai CW, Leong CO, Chung FF, Lee YK, et al.
    Chem Biol Drug Des, 2018 01;91(1):213-219.
    PMID: 28719017 DOI: 10.1111/cbdd.13072
    Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results.
  14. Fulltext Cudraflavone C Induces Tumor-Specific Apoptosis in Colorectal Cancer Cells through Inhibition of the Phosphoinositide 3-Kinase (PI3K)-AKT Pathway
    Soo HC, Chung FF, Lim KH, Yap VA, Bradshaw TD, Hii LW, et al.
    PLoS One, 2017;12(1):e0170551.
    PMID: 28107519 DOI: 10.1371/journal.pone.0170551
    Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway. Gene expression profiling by microarray analyses revealed that tumor suppressor genes EGR1, HUWE1 and SMG1 were significantly up-regulated while oncogenes such as MYB1, CCNB1 and GPX2 were down-regulated following treatment with Cud C. Further analyses using Connectivity Map revealed that Cud C induced a gene signature highly similar to that of protein synthesis inhibitors and phosphoinositide 3-kinase (PI3K)-AKT inhibitors, suggesting that Cud C might inhibit PI3K-AKT signaling. A luminescent cell free PI3K lipid kinase assay revealed that Cud C significantly inhibited p110β/p85α PI3K activity, followed by p120γ, p110δ/p85α, and p110α/p85α PI3K activities. The inhibition by Cud C on p110β/p85α PI3K activity was comparable to LY-294002, a known PI3K inhibitor. Cud C also inhibited phosphorylation of AKT independent of NFκB activity in CRC cells, while ectopic expression of myristoylated AKT completely abrogated the anti-proliferative effects, and apoptosis induced by Cud C in CRC. These findings demonstrate that Cud C induces tumor-selective cytotoxicity by targeting the PI3K-AKT pathway. These findings provide novel insights into the mechanism of action of Cud C, and indicate that Cud C further development of Cud C derivatives as potential therapeutic agents is warranted.
  15. Cytochrome P450 2W1 (CYP2W1) in Colorectal Cancers
    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.
  16. Drug-like dietary vanilloids induce anticancer activity through proliferation inhibition and regulation of bcl-related apoptotic proteins
    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. Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics
    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.
  18. Fulltext Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma
    Pua LJW, Mai CW, Chung FF, Khoo AS, Leong CO, Lim WM, et al.
    Int J Mol Sci, 2022 Jan 20;23(3).
    PMID: 35163030 DOI: 10.3390/ijms23031108
    c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) family members integrate signals that affect proliferation, differentiation, survival, and migration in a cell context- and cell type-specific way. JNK and p38 MAPK activities are found upregulated in nasopharyngeal carcinoma (NPC). Studies have shown that activation of JNK and p38 MAPK signaling can promote NPC oncogenesis by mechanisms within the cancer cells and interactions with the tumor microenvironment. They regulate multiple transcription activities and contribute to tumor-promoting processes, ranging from cell proliferation to apoptosis, inflammation, metastasis, and angiogenesis. Current literature suggests that JNK and p38 MAPK activation may exert pro-tumorigenic functions in NPC, though the underlying mechanisms are not well documented and have yet to be fully explored. Here, we aim to provide a narrative review of JNK and p38 MAPK pathways in human cancers with a primary focus on NPC. We also discuss the potential therapeutic agents that could be used to target JNK and p38 MAPK signaling in NPC, along with perspectives for future works. We aim to inspire future studies further delineating JNK and p38 MAPK signaling in NPC oncogenesis which might offer important insights for better strategies in diagnosis, prognosis, and treatment decision-making in NPC patients.
  19. Gene expression profiling of giant fibroadenomas of the breast
    Yin Lee JP, Thomas AJ, Lum SK, Shamsudin NH, Hii LW, Mai CW, et al.
    Surg Oncol, 2021 Jun;37:101536.
    PMID: 33677364 DOI: 10.1016/j.suronc.2021.101536
    INTRODUCTION: Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers.

    METHODS: mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas.

    RESULTS: A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy.

    CONCLUSION: Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.

  20. Goniolanceolatins A-H, Cytotoxic Bis-styryllactones from Goniothalamus lanceolatus
    Bihud NV, Rasol NE, Imran S, Awang K, Ahmad FB, Mai CW, et al.
    J Nat Prod, 2019 09 27;82(9):2430-2442.
    PMID: 31433181 DOI: 10.1021/acs.jnatprod.8b01067
    Eight new bis-styryllactones, goniolanceolatins A-H (1-8), possessing a rare α,β-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH2Cl2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC50 values ranging from 2.3 to 4.2 μM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.
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