Displaying publications 41 - 60 of 95 in total

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  1. New flavan and alkyl alpha,beta-lactones from the stem bark of Horsfieldia superba
    Al-Mekhlafi NA, Shaaria K, Abas F, Jeyaraj EJ, Stanslas J, Khalivulla SI, et al.
    Nat Prod Commun, 2013 Apr;8(4):447-51.
    PMID: 23738449
    In the present study phytochemical investigation of the methanol extract of the stem bark of Horsfieldia superba led to the isolation of twenty compounds (1-20), of which three (1-3) were new. However, compounds 2 and 3 were previously reported as synthetic alpha,beta-lactones. The compounds were characterized as (-)-3,4',7-trihydroxy-3'-methoxyflavan (1), (-)-5,6-dihydro-6-undecyl-2H-pyran-2-one (2), and (-)-5,6-dihydro-6-tridecyl-2H-pyran-2-one (3). Seventeen other known compounds were also isolated and identified as (-)-viridiflorol (4), hexacosanoic acid (5), beta-sitosterol (6), methyl 2,4-dihydroxy-6-methylbenzoate (methylorsellinate) (7), methyl 2,4-dihydroxy-3,6-dimethylbenzoate (8), (-)-4'-hydroxy-7-methoxyflavan (9), (-)-4',7-dihydroxyflavan (10), (-)-4',7-dihydroxy-3'-methoxyflavan (11), (+)-3,4',7-trihydroxyflavan (12), (-)-catechin (13), (-)-epicatechin (14), (-)-7-hydroxy-3',4'-methylenedioxyflavan (15), 2',3,4-trihydroxy-4'-methoxydihydrochalcone (16), 3',4',7-trihydroxyflavone (17), (+)-4'-hydroxy-7-methoxyflavanone (18), hexadecanoic acid (palmitic acid) (19) and 3,4-dihydroxybenzoic acid (20). The structures of the compounds were fully characterized by various physical methods (melting point, optical rotation), spectral (UV, IR, ID and 2D NMR) and mass spectrometric techniques. In vitro assay of compounds 2 and 3 demonstrated moderate cytotoxic activities against human prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cells, while the chloroform and ethyl acetate fractions of H. superba were found to exhibit moderate AChE inhibitory activity (IC50 72 and 60 microg/mL).
  2. Fulltext Assessment of phytochemical content, polyphenolic composition, antioxidant and antibacterial activities of Leguminosae medicinal plants in Peninsular Malaysia
    Chew YL, Chan EW, Tan PL, Lim YY, Stanslas J, Goh JK
    BMC Complement Altern Med, 2011;11:12.
    PMID: 21306653 DOI: 10.1186/1472-6882-11-12
    Many medicinal plants from Leguminosae family can be found easily in Malaysia. These plants have been used as traditional medicines by local ethnic groups, where they are prepared as decoction, pastes for wound infections, and some have been eaten as salad. This paper focused on the assessment of antioxidant potential, antibacterial activity and classes of phytochemicals of nine plants from the Leguminosae family.
  3. Antinociceptive and antiedematogenic activities of andrographolide isolated from Andrographis paniculata in animal models
    Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.
    Biol Res Nurs, 2010 Jan;11(3):293-301.
    PMID: 19689990 DOI: 10.1177/1099800409343311
    The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.
  4. Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects
    Ramachandran V, Ismail P, Stanslas J, Shamsudin N, Moin S, Mohd Jas R
    J Renin Angiotensin Aldosterone Syst, 2008 Dec;9(4):208-14.
    PMID: 19126661 DOI: 10.1177/1470320308097499
    The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been studied in various populations in relation to hypertension (HTN) and type 2 diabetes mellitus (T2DM) with contradictory results. This study sought to determine the association of insertion (I)/D polymorphism of the ACE gene in hypertensive and T2DM subjects in a Malaysian population.
  5. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity
    Jabir RS, Naidu R, Annuar MA, Ho GF, Munisamy M, Stanslas J
    Pharmacogenomics, 2012 Dec;13(16):1979-88.
    PMID: 23215890 DOI: 10.2217/pgs.12.165
    Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
  6. A labdane diterpene glucoside from the rhizomes of Curcuma mangga
    Abas F, Lajis NH, Shaari K, Israf DA, Stanslas J, Yusuf UK, et al.
    J Nat Prod, 2005 Jul;68(7):1090-3.
    PMID: 16038556
    A new labdane diterpene glucoside, curcumanggoside (1), together with nine known compounds, including labda-8(17),12-diene-15,16-dial (2), calcaratarin A (3), zerumin B (4), scopoletin, demethoxycurcumin, bisdemethoxycurcumin, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one, curcumin, and p-hydroxycinnamic acid, have been isolated from the rhizomes of Curcuma mangga. Their structures were determined using a combination of 1D (1H NMR, 13C NMR, DEPT) and 2D (COSY, HSQC, HMBC) NMR techniques. All diarylheptanoids and scopoletin showed significant antioxidant activity. Zerumin B, demethoxycurcumin, bisdemethoxycurcumin, and curcumin also exhibited cytotoxic activity against a panel of five human tumor cell lines.
  7. Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability
    Tan SF, Masoumi HR, Karjiban RA, Stanslas J, Kirby BP, Basri M, et al.
    Ultrason Sonochem, 2016 Mar;29:299-308.
    PMID: 26585010 DOI: 10.1016/j.ultsonch.2015.09.015
    Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy.
  8. Nanoemulsion-based Parenteral Drug Delivery System of Carbamazepine: Preparation, Characterization, Stability Evaluation and Blood-Brain Pharmacokinetics
    Tan SL, Stanslas J, Basri M, Abedi Karjiban RA, Kirby BP, Sani D, et al.
    Curr Drug Deliv, 2015;12(6):795-804.
    PMID: 26324229
    Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.
  9. SRJ09, a promising anticancer drug lead: Elucidation of mechanisms of antiproliferative and apoptogenic effects and assessment of in vivo antitumor efficacy
    Wong CC, Lim SH, Sagineedu SR, Lajis NH, Stanslas J
    Pharmacol Res, 2016 05;107:66-78.
    PMID: 26940565 DOI: 10.1016/j.phrs.2016.02.024
    SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells. The gene expressions were determined using reverse transcriptase PCR (RT-PCR). Pharmacokinetic investigation was carried out by determining SRJ09 levels in plasma of Balb/C mice using HPLC. In vivo antitumor activity was evaluated in athymic mice carrying HCT-116 colon tumor xenografts. SRJ09 displayed improved in vitro activity when compared with AGP by producing rapid cell killing effect in vitro. Its activity was not compromised in MES-SA/Dx5 multidrug resistant (MDR) cells expressing p-glycoprotein. Cells treated with SRJ09 (0.1-10μM) displayed increased p21 protein level, which corresponded with gene expression. Whereas CDK4 protein level and gene expression was suppressed. The treatment did not affect cyclin D1. Changes of these proteins paralleled G1 cell cycle arrest in both cell lines as determined by flow cytometry. Induction of apoptosis by SRJ09 in HCT-116 cells which occurred independent of p53 and bcl-2 was inhibited in the presence of caspase 8 inhibitor, implicating the extrinsic apoptotic pathway. A single dose (100mg/kg, i.p) of SRJ09 produced a plasma concentration range of 12-30.4μM. At 400mg/kg (q4dX3), it significantly retarded growth of tumor xenografts. The antitumor activity of SRJ09 is suggested mediated via the induction of p21 expression and suppression of CDK-4 expression without affecting cyclin D1 to trigger G1 arrest leading to apoptosis.
  10. Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer
    Lim JC, Chan TK, Ng DS, Sagineedu SR, Stanslas J, Wong WS
    Clin Exp Pharmacol Physiol, 2012 Mar;39(3):300-10.
    PMID: 22017767 DOI: 10.1111/j.1440-1681.2011.05633.x
    1. Andrographis paniculata (Burm. f) Nees, commonly known as 'king of bitters', is a herbaceous plant belonging to the Family Acanthaceae. It has been widely used for centuries in Asian countries like China, India, Thailand and Malaysia for the treatment of sore throat, flu and upper respiratory tract infections. 2. Andrographolide, 14-deoxy-11,12-didehydroandrographolide and neoandrographolide are examples of the major labdane diterpenoids isolated from A. paniculata. These bioactive molecules have exhibited varying degrees of anti-inflammatory and anticancer activities in both in vitro and in vivo experimental models of inflammation and cancer. 3. Extensive libraries of andrographolide analogues have been synthesised mainly by modifying the α,β-unsaturated γ-butyrolactone moiety, the two double bonds Δ(8,(17)) and Δ(12,(13)) and the three hydroxyls at C-3 (secondary), C-14 (allylic) and C-19 (primary). Many of these synthetic analogues exhibit superior anticancer activity over the naturally occurring andrographolides. 4. Andrographolide and its derivatives have been shown to have anti-inflammatory effects in experimental models of asthma, stroke and arthritis, as well as in patients with upper respiratory tract infections. Andrographolide reduces the production of cytokines, chemokines, adhesion molecules, nitric oxide and lipid mediators, probably via inhibition of the nuclear factor (NF)-κB signalling pathway. 5. The anticancer mechanisms for andrographolide include inhibition of Janus tyrosine kinases-signal transducers and activators of transcription, phosphatidylinositol 3-kinase and NF-κB signalling pathways, suppression of heat shock protein 90, cyclins and cyclin-dependent kinases, metalloproteinases and growth factors, and the induction of tumour suppressor proteins p53 and p21, leading to inhibition of cancer cell proliferation, survival, metastasis and angiogenesis. 6. Andrographolide drug discovery is a promising strategy for the development of a novel class of anti-inflammatory and anticancer drugs.
  11. Cytotoxic xanthones from Garcinia penangiana Pierre
    Jabit ML, Khalid R, Abas F, Shaari K, Hui LS, Stanslas J, et al.
    Z Naturforsch C J Biosci, 2008 2 16;62(11-12):786-92.
    PMID: 18274278
    Two new xanthones, characterized as 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (1) and penangianaxanthone (2), with three known xanthones, cudratricusxanthone H (3), macluraxanthone C (4) and gerontoxanthone C (5), as well as friedelin and stigmasterol were isolated from the leaves of Garcinia penangiana. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with the literature ones. Significant cytotoxicity against DU-145, MCF-7 and NCI-H460 cancer cell lines was demonstrated by compounds 1-5, with IC50 values ranging from 3.5 to 72.8 microM.
  12. Biological evaluation of curcumin and related diarylheptanoids
    Abas F, Hui LS, Ahmad S, Stanslas J, Israf DA, Shaari K, et al.
    Z Naturforsch C J Biosci, 2006 12 2;61(9-10):625-31.
    PMID: 17137104
    Nine derivatives of three natural diarylheptanoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were prepared. Their antioxidant, free radical scavenging, nitric oxide (NO) inhibitory and cytotoxic activities were evaluated and compared with those of the respective natural compounds. Curcumin (1), demethoxycurcumin (2), demethyldemethoxy-curcumin (C3), diacetyldemethoxycurcumin (AC2) and triacetyldemethylcurcumin (AC5) exhibited higher antioxidant activity than quercetin while products from demethylation of 1 and 2 exhibited higher free radical scavenging activity. Compounds AC2 and AC5 were found to be most active in inhibiting breast cancer cells (MCF-7) proliferation with IC50 values of 6.7 and 3.6 microM, respectively. The activity of AC2 is almost doubled and of AC5 almost tripled as compared to curcumin. Their selectivity towards different cell lines is also more noticeable. Compounds AC2 and AC5 also showed increased activity against a human prostate cancer cell line (DU-145) and non-small lung cancer cell line (NCI-H460) with IC50 values of 20.4, 16.3 and 18.3, 10.7 microM, respectively.
  13. Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway
    Huq AM, Wai LK, Rullah K, Mohd Aluwi MFF, Stanslas J, Jamal JA
    Chem Biol Drug Des, 2019 03;93(3):222-231.
    PMID: 30251480 DOI: 10.1111/cbdd.13404
    Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson-Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was -49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.
  14. Advances and challenges in developing andrographolide and its analogues as cancer therapeutic agents
    Soo HL, Quah SY, Sulaiman I, Sagineedu SR, Lim JCW, Stanslas J
    Drug Discov Today, 2019 09;24(9):1890-1898.
    PMID: 31154065 DOI: 10.1016/j.drudis.2019.05.017
    Andrographolide (AGP), a naturally occurring bioactive compound, has been investigated as a lead compound in cancer drug development. Its multidimensional therapeutic effects have raised interest among medicinal chemists, which has led to extensive structural modification of the compound, resulting in analogues with improved pharmacological and pharmaceutical properties. Nevertheless, the analogues with the improved properties need to be rigorously studied to identify drug-like lead compounds. We scrutinised articles published from 2012 to 2018, to objectively provide opinions on the mechanisms of action of AGP and its analogues, as well as their potential as viable anticancer drugs. Preclinical and clinical data, along with the extensive medicinal chemistry efforts, indicate the compounds are potential anticancer agents with specific value in treating recalcitrant cancers such as pancreatic and lung cancers.
  15. Investigation and Optimization of Hydrogel Microneedles for Transdermal Delivery of Caffeine
    Chandran R, Mohd Tohit ER, Stanslas J, Salim N, Tuan Mahmood TM
    Tissue Eng Part C Methods, 2022 10;28(10):545-556.
    PMID: 35485888 DOI: 10.1089/ten.TEC.2022.0045
    Caffeine is therapeutically effective for treating apnea, cellulite formation, and pain management. It also exhibits neuroprotective and antioxidant activities in different models of Parkinson's disease and Alzheimer's disease. However, caffeine administration in a minimally invasive and sustainable manner through the transdermal route is challenging owing to its hydrophilic nature. Therefore, this study demonstrated a transdermal delivery approach for caffeine by utilizing hydrogel microneedle (MN) as a permeation enhancer. The influence of formulation parameters such as molecular weight (MW) of PMVE/MA (polymethyl vinyl ether/maleic anhydride) copolymer and sodium bicarbonate (NaHCO3) concentration on the swelling kinetics and mechanical integrity of the hydrogel MNs was investigated. In addition, the effect of different MN application methods and needle densities of hydrogel MN on the skin insertion efficiency and penetration depth was also evaluated. The swelling degree at equilibrium percentage (% Seq) recorded for hydrogels fabricated with Gantrez S-97 (MW = 1,500,000 Da) was significantly higher than formulation with Gantrez AN-139 (MW = 1,080,000 Da). Increasing the concentration of NaHCO3 also significantly increased the % Seq. Moreover, a 100% penetration was recorded for both the applicator and combination of applicator and thumb pressure compared with only 11% for thumb pressure alone. The average diameter of micropores created by the applicator method was 62.94 μm, which was significantly lower than the combination of both applicator and thumb pressure MN application (100.53 μm). Based on histological imaging, the penetration depth of hydrogel MN increased as the MN density per array decreased. The hydrogel MN with the optimized formulation and skin insertion parameters was tested for caffeine delivery in an in vitro Franz diffusion cell setup. Approximately 2.9 mg of caffeine was delivered within 24 h, and the drug release profile was best fitted to the Korsmeyer-Peppas model, displaying Super Case II kinetics. In conclusion, a combination of thumb and impact application methods and reduced needle density improved the skin penetration efficiency of hydrogel MNs. The results also show that hydrogel MNs fabricated from 3% w/w NaHCO3 and high MW of copolymer exhibit optimum physical and swelling properties for enhanced transdermal delivery.
  16. Synthesis of small molecules targeting paclitaxel-induced MyD88 expression in triple-negative breast cancer cell lines
    Poh Yen K, Stanslas J, Zhang T, Li H, Wang X, Kok Meng C, et al.
    Bioorg Med Chem, 2021 11 01;49:116442.
    PMID: 34600241 DOI: 10.1016/j.bmc.2021.116442
    Acquired paclitaxel (PTX) chemoresistance in triple-negative breast cancer (TNBC) can be inferred from the overexpression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) proteins and the activation of the TLR4/MyD88 cascading signalling pathway. Finding a new inhibitor that can attenuate the activation of this pathway is a novel strategy for reducing PTX chemoresistance. In this study, a series of small molecule compounds were synthesised and tested in combination with PTX against TNBC cells. The trimethoxy-substituted compound significantly decreased MyD88 overexpression and improved PTX activity in MDA-MB-231TLR4+ cells but not in HCCTLR4- cells. On the contrary, the trifluoromethyl-substituted compound with PTX synergistically improved the growth inhibition in both TNBC subtypes. The fluorescence titrations indicated that both compounds could bind with MD2 with good and comparable binding affinities. This was further supported by docking analysis, in which both compounds fit perfectly well and form some critical binding interactions with MD2, an essential lipid-binding accessory to TLR4 involved in activating the TLR-4/MyD88-dependent pathway.
  17. Fulltext Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians
    Meor Anuar Shuhaili MFR, Samsudin IN, Stanslas J, Hasan S, Thambiah SC
    Int J Endocrinol Metab, 2017 Apr;15(2):e43319.
    PMID: 28848611 DOI: 10.5812/ijem.43319
    CONTEXT: The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians.

    EVIDENCE ACQUISITION: PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles.

    RESULTS: CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group.

    CONCLUSIONS: The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

  18. Adaptive therapy to circumvent drug resistance to tyrosine kinase inhibitors in cancer: is it clinically relevant?
    Faisal Hamdi AI, How SH, Islam MK, Lim JCW, Stanslas J
    Expert Rev Anticancer Ther, 2022 Dec;22(12):1309-1323.
    PMID: 36376248 DOI: 10.1080/14737140.2022.2147671
    INTRODUCTION: Cancer is highly adaptable and is constantly evolving against current targeted therapies such as tyrosine kinase inhibitors. Despite advances in recent decades, the emergence of drug resistance to tyrosine kinase inhibitors constantly hampers therapeutic efficacy of cancer treatment. Continuous therapy versus intermittent clinical regimen has been a debate in drug administration of cancer patients. An ecologically-inspired shift in cancer treatment known as 'adaptive therapy' intends to improve the drug administration of drugs to cancer patients that can delay emergence of drug resistance.

    AREAS COVERED: We discuss improved understanding of the concept of drug resistance, the basis of continuous therapy, intermittent clinical regimens, and adaptive therapy will be reviewed. In addition, we discuss how adaptive therapy provides guidance for future cancer treatment.

    EXPERT OPINION: The current understanding of drug resistance in cancer leads to poor prognosis and limited treatment options in patients. Fighting drug resistance mutants is constantly followed by new forms of resistance. In most reported cases, continuous therapy leads to drug resistance and an intermittent clinical regimen vaguely delays it. However, adaptive therapy, conceptually, exploits multiple parameters that can suppress the growth of drug resistance and provides safe treatment for cancer patients in the future.

  19. The evaluation expression of non-coding RNAs in response to HSV-G47∆ oncolytic virus infection in glioblastoma multiforme cancer stem cells
    Vazifehmand R, Ali DS, Othman Z, Chau DM, Stanslas J, Shafa M, et al.
    J Neurovirol, 2022 Dec;28(4-6):566-582.
    PMID: 35951174 DOI: 10.1007/s13365-022-01089-w
    Glioblastoma multiforme is the most aggressive astrocytes brain tumor. Glioblastoma cancer stem cells and hypoxia conditions are well-known major obstacles in treatment. Studies have revealed that non-coding RNAs serve a critical role in glioblastoma progression, invasion, and resistance to chemo-radiotherapy. The present study examined the expression levels of microRNAs (in normoxic condition) and long non-coding RNAs (in normoxic and hypoxic conditions) in glioblastoma stem cells treated with the HSV-G47∆. The expression levels of 43 miRNAs and 8 lncRNAs isolated from U251-GBM-CSCs were analyzed using a miRCURY LNA custom PCR array and a quantitative PCR assay, respectively. The data revealed that out of 43 miRNAs that only were checked in normoxic condition, the only 8 miRNAs, including miR-7-1, miR-let-7b, miR-130a, miR-137, miR-200b, miR-221, miR-222, and miR-874, were markedly upregulated. The expression levels of lncRNAs, including LEF1 antisense RNA 1 (LEF1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein coding RNA 470 (LINC00470), tumor suppressor candidate 7 (TUSC7), HOX transcript antisense RNA (HOTAIR), nuclear paraspeckle assembly transcript 1 (NEAT1), and X inactive specific transcript (XIST), were markedly downregulated in the hypoxic microenvironment, and H19-imprinted maternally expressed transcript (H19) was not observed to be dysregulated in this environment. Under normoxic conditions, LEF1-AS1, MALAT1, LINC00470, H19, HOTAIR, NEAT1, and XIST were downregulated and TUSC7 was not targeted by HSV-G47∆. Overall, the present data shows HSVG47Δ treatment deregulates non-coding RNA expression in GBM-CSC tumor microenvironments.
  20. Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder
    Badamasi IM, Lye MS, Ibrahim N, Abdul Razaq NA, Ling KH, Stanslas J
    Pharmacogenomics J, 2021 Aug;21(4):498-509.
    PMID: 33731884 DOI: 10.1038/s41397-021-00228-6
    The polymorphisms of the 5HTR1A and 5HTR2A receptor genes (rs6295C/G and rs6311G/A) have been evaluated for association with SSRI treatment outcome in various populations with different results. The present study was carried out to determine the association between genotypes of HTR1A-rs6295 and HTR2A-rs6311 with SSRI treatment outcome among the ethnic Malay patients diagnosed with first-episode major depressive disorder (MDD). The patients were recruited from four tertiary hospitals in the Klang Valley region of Malaysia. Predefined efficacy phenotypes based on 25% (partial early response) and 50% (clinical efficacy response) reduction in Montgomery Asberg Depression Rating Scale-self Rated score (MADRS-S) were adopted for assessment of treatment efficacy in this study. Self-reporting for adverse effects (AE) was documented using the Patient Rated Inventory of Side Effect (PRISE) after treatment with SSRI for up to 6 weeks. Adjusted binary logistic regression between genotypes of the polymorphism obtained using sequencing technique with the treatment outcome phenotypes was performed. The 142 patients recruited were made up of 96 females (67.6%) and 46 males (32.4%). Clinical efficacy and Partial early response phenotypes were not significantly associated with genotypes of HTR1A and HTR2A polymorphism. The GG genotype of HTR2A polymorphism has decreased odds for dizziness (CNS) and increased odds for poor concentration. The GA genotype increases the odd for excessive sweating, diarrhoea, constipation and blurred vision. The CC genotype of HTR1A-rs6295 decreases the odd for nausea/vomiting and increases the odd for anxiety. Thus, some genotypes of HTR1A and HTR2A polymorphism were associated with SSRI treatment outcomes in ethnic Malay MDD patients.
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