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Fulltext Prevalence of nocturia among community-dwelling adults: a population-based study in Malaysia

Yow HY, Tiong JJL, Mai CW, van der Werf E, Zainuddin ZM, Toh CC, et al.

BMC Urol, 2021 Jun 29;21(1):95.
PMID: 34187440 DOI: 10.1186/s12894-021-00860-1

BACKGROUND: Nocturia is widely prevalent condition with detrimental effects on quality of life and general health. In Malaysia, there is a lack of up-to-date prevalence study on nocturia. This study aimed to investigate the prevalence of nocturia and awareness pertaining to nocturia among Malaysian adults.
METHODS: A cross-sectional population-based study was conducted among Malaysian adults aged ≥ 18 years old. The data was collected by mixed mode self-administered questionnaire from May 2019 to September 2019. Nocturia was defined as one or more voids at night.
RESULTS: There were a total of 4616 respondents with 74.5% of response rate. The overall prevalence of nocturia among Malaysian adults was found to be 57.3%. In multivariate analysis, respondents aged 31-40 (1.91 [1.52-2.40]) or > 60 years old (2.03 [1.48-2.71]), and those who presented with hypertension (2.84 [2.28-3.53]), diabetes mellitus (1.78 [1.42-2.25]), renal disease (3.58 [1.93-6.63]) or overactive bladder (1.61 [1.10-2.35]) were associated with higher prevalence of nocturia. A significantly lower disease prevalence (p
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.
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.
The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation

Yaw ACK, Chan EWL, Yap JKY, Mai CW

J Cancer Res Clin Oncol, 2020 Sep;146(9):2219-2229.
PMID: 32507974 DOI: 10.1007/s00432-020-03274-y

PURPOSE: Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells.
METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.
RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.
CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.
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.
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.
Fulltext Potential of Superhydrophobic Surface for Blood-Contacting Medical Devices

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.
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.
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
Separation of prescribing and dispensing in Malaysia: the history and challenges

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.
Fulltext Tocotrienols Modulate a Life or Death Decision in Cancers

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.
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.
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.
Novel 2-Benzoyl-6-(2,3-Dimethoxybenzylidene)-Cyclohexenol Confers Selectivity toward Human MLH1 Defective Cancer Cells through Synthetic Lethality

Song DSS, Leong SW, Ng KW, Abas F, Shaari K, Leong CO, et al.

SLAS Discov, 2019 06;24(5):548-562.
PMID: 30897027 DOI: 10.1177/2472555219831405

DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.
Fulltext Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

Sivaramakarthikeyan R, Iniyaval S, Saravanan V, Lim WM, Mai CW, Ramalingan C

ACS Omega, 2020 May 05;5(17):10089-10098.
PMID: 32391496 DOI: 10.1021/acsomega.0c00630

Synthesis of a series of benzimidazole-ornamented pyrazoles, 6a-6j has been obtained from arylhydrazine and aralkyl ketones via a multistep synthetic strategy. Among them, a hybrid-possessing para-nitrophenyl moiety connected to a pyrazole scaffold (6a) exerted the highest anti-inflammatory activity, which is superior to the standard, diclofenac sodium. While executing the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, a hybrid-possessing para-bromophenyl unit integrated at the pyrazole structural motif (6i) exhibited the highest activity among the hybrids examined. Besides, evaluation of anticancer potency of the synthesized hybrids revealed that the one containing a para-fluorophenyl unit tethered at the pyrazole nucleus (6h) showed the highest activity against both the pancreatic cancer cells (SW1990 and AsPCl) investigated. Considerable binding affinity between B-cell lymphoma and the hybrid, 6h has been reflected while performing molecular docking studies (-8.65 kcal/mol). The outcomes of the investigation expose that these hybrids could be used as effective intermediates to construct more potent biological agents.
Fulltext Traditional and Novel Adiposity Indicators and Pancreatic Cancer Risk: Findings from the UK Women's Cohort Study

Shyam S, Greenwood D, Mai CW, Tan SS, Mohd Yusof BN, Moy FM, et al.

Cancers (Basel), 2021 Mar 02;13(5).
PMID: 33801191 DOI: 10.3390/cancers13051036

(1) Background: We studied the association of both conventional (BMI, waist and hip circumference and waist-hip ratio) and novel (UK clothing sizes) obesity indices with pancreatic cancer risk in the UK women's cohort study (UKWCS). (2) Methods: The UKWCS recruited 35,792 women from England, Wales and Scotland from 1995 to 1998. Cancer diagnosis and death information were obtained from the National Health Service (NHS) Central Register. Cox's proportional hazards regression was used to evaluate the association between baseline obesity indicators and pancreatic cancer risk. (3) Results: This analysis included 35,364 participants with a median follow-up of 19.3 years. During the 654,566 person-years follow up, there were 136 incident pancreatic cancer cases. After adjustments for age, smoking, education and physical activity, each centimetre increase in hip circumference (HR: 1.03, 95% CI: 1.01-1.05, p = 0.009) and each size increase in skirt size (HR: 1.12, 95% CI: 1.02-1.23, p = 0.041) at baseline increased pancreatic cancer risk. Baseline BMI became a significant predictor of pancreatic cancer risk (HR: 1.04, 95% CI: 1.00-1.08, p = 0.050) when latent pancreatic cancer cases were removed. Only baseline hip circumference was associated with pancreatic cancer risk (HR: 1.03, 95% CI: 1.00-1.05, p = 0.017) when participants with diabetes at baseline were excluded to control for reverse causality. (4) Conclusion: Hip circumference and skirt size were significant predictors of pancreatic cancer risk in the primary analysis. Thus, hip circumference is useful to assess body shape relationships. Additionally, standard skirt sizes offer an economical and objective alternative to conventional obesity indices for evaluating pancreatic cancer risk in women.
Fulltext Major dietary patterns in the United Kingdom Women's Cohort Study showed no evidence of prospective association with pancreatic cancer risk

Shyam S, Greenwood DC, Mai CW, Tan SS, Yusof BM, Moy FM, et al.

Nutr Res, 2023 Oct;118:41-51.
PMID: 37562156 DOI: 10.1016/j.nutres.2023.07.007

Diet is a modifiable risk factor for pancreatic cancer. We hypothesized that specific dietary patterns would increase/decrease pancreatic cancer risk. We evaluated the association of dietary patterns with pancreatic cancer risk in the UK Women's Cohort Study. Dietary patterns were assessed at enrollment using: (1) self-reported practice of vegan/vegetarian dietary habits, (2) diet quality indices (World Health Organization Healthy Diet Indicator and Mediterranean Diet Score), and (3) principal component analysis-derived dietary patterns. The association of dietary patterns with pancreatic cancer incidence was quantified using Cox regression survival analysis. Over a median follow-up of 19 years of 35,365 respondents, there were 136 incident cases of pancreatic cancer. No association between dietary habits/quality and pancreatic cancer incidence was evident after adjustments (hazard ratio (95% confidence interval): self-reported omnivores vs vegan/vegetarian dietary habit: 1.13 (0.73-1.76); per-unit increase in World Health Organization Healthy Diet Indicator scores: 0.99 (0.91-1.09); per-unit increase in Mediterranean Diet Score: 0.92 (0.83-1.02). Similarly, no association of principal component analysis-derived dietary patterns with pancreatic cancer risk was evident ("prudent:" 1.02 [0.94-1.10]; ``meat-based:'' 1.00 [0.92-1.09]; ``fast-food, sugar-sweetened beverages, and carbohydrate-rich snacks:'' 0.96 [0.86-1.07]; ``cereal and dairy-rich:'' 1.04 [0.94-1.16], and ``low-diversity and lowfat:'' 1.00 [0.89-1.13]). In this prospective cohort of women, several major dietary patterns were of poor quality. There was no evidence of a prospective association between any of the dietary patterns explored and pancreatic cancer incidence.
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.
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.
Fulltext Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival

Nalairndran G, Hassan Abdul Razack A, Mai CW, Fei-Lei Chung F, Chan KK, Hii LW, et al.

J Cell Mol Med, 2020 Oct;24(20):12188-12198.
PMID: 32926495 DOI: 10.1111/jcmm.15876

Prostate cancer (PCa) is the most common malignancy and is the second leading cause of cancer among men globally. Using a kinome-wide lentiviral small-hairpin RNA (shRNA) library screen, we identified phosphoinositide-dependent kinase-1 (PDPK1) as a potential mediator of cell survival in PCa cells. We showed that knock-down of endogenous human PDPK1 induced significant tumour-specific cell death in PCa cells (DU145 and PC3) but not in the normal prostate epithelial cells (RWPE-1). Further analyses revealed that PDPK1 mediates cancer cell survival predominantly via activation of serum/glucocorticoid-regulated kinase 3 (SGK3). Knock-down of endogenous PDPK1 in DU145 and PC3 cells significantly reduced SGK3 phosphorylation while ectopic expression of a constitutively active SGK3 completely abrogated the apoptosis induced by PDPK1. In contrast, no such effect was observed in SGK1 and AKT phosphorylation following PDPK1 knock-down. Importantly, PDPK1 inhibitors (GSK2334470 and BX-795) significantly reduced tumour-specific cell growth and synergized docetaxel sensitivity in PCa cells. In summary, our results demonstrated that PDPK1 mediates PCa cells' survival through SGK3 signalling and suggest that inactivation of this PDPK1-SGK3 axis may potentially serve as a novel therapeutic intervention for future treatment of PCa.

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