Displaying publications 1 - 20 of 80 in total

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  1. Islam MK, Stanslas J
    Pharmacol Ther, 2021 11;227:107870.
    PMID: 33895183 DOI: 10.1016/j.pharmthera.2021.107870
    Cancer immunotherapy is an option to enhance physiological defence mechanism to fight cancer, where natural substances (e.g., antigen/antibody) or small synthetic molecule can be utilized to improve and restore the immune system to stop or slacken the development of malignant cells, stop metastasis and/or help the immune response with synthetic monoclonal antibodies (mAbs) and tumour-agnostic therapy to eliminate cancer cells. Interaction between the programmed cell death ligand 1 (PD-L1) and its receptor (programmed cell death protein 1, PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) linked signalling pathways have been identified as perilous towards the body's immune mechanism in regulating the progression of cancer. It is known that certain cancers use these pathways to evade the body's defence mechanism. The immune system is capable of responding to cancer by stalling these trails with specific synthetic antibodies or immune checkpoint inhibitors, which can ultimately either stop or slow cancer cell development. Recent findings and data suggested that using such inhibitors invigorated a new approach to cancer treatment. These inhibitors usually activate the immune system to identify and eliminate cancer cells rather than attacking tumour cells directly. PD-1/PD-L1 inhibitors have already been substantiated for their efficacy in over twenty variations of cancer through different clinical trials. Studies on molecular interaction with existing PD-1/PD-L1 inhibitors that are mainly dominated by antibodies are constantly generating new ideas to develop novel inhibitors. This review has summarised information on reported and/or patented small molecules and peptides for their ability to interact with the PD-1/PD-L1 as a potential anticancer strategy.
  2. Ramachandran V, Ismail P, Stanslas J, Shamsudin N
    PMID: 19243623 DOI: 10.1186/1475-2840-8-11
    The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.
  3. Labrooy C, Abdullah TL, Stanslas J
    Data Brief, 2018 Dec;21:1678-1685.
    PMID: 30505900 DOI: 10.1016/j.dib.2018.10.097
    This study compared morphological and molecular data for identification of Kaempferia species. Each species was deposited in Institute of Bioscience (IBS), Universiti Putra Malaysia (UPM) as voucher specimens and ITS sequences of each species deposited in NCBI (https://www.ncbi.nlm.nih.gov/) as GenBank accessions. DNA was extracted using a modified CTAB method and PCR amplification was completed using Internal Transcribed Spacer (ITS4 and ITS5) markers. PCR amplification of products were viewed under gel electrophoresis. Sequencing was performed and sequence characteristics of ITS rDNA in Kaempferia is shown. Qualitative and qualitative scoring of morphological characters and measuring techniques for Kaempferia species are included. In addition, a brief review of molecular markers used in phylogenetic studies of Zingiberaceae is included in this dataset.
  4. Lye, Munn-Sann, Aishah-Farhana Shahbudin, Tey, Yin-Yee, Tor, Yin-Sim, Ling, King-Hwa, Normala Ibrahim, et al.
    Neuroscience Research Notes, 2019;2(3):20-28.
    MyJurnal
    Major depressive disorder (MDD) compromises the individual’s capacity for self-care and productivity. Single nucleotide polymorphisms (SNP) of a number of genes have been associated with MDD. The zinc transporter-3 protein, encoded by the ZnT3 (SLC30A3) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of MDD. We hypothesise that variation in SLC30A3 (rs11126936)SNP increases risk of MDD. We recruited 300 MDD cases and 300 controls, matched in theratio of 1:1 by age, gender and ethnicity. PCR-restriction fragment length polymorphism analysis was used in DNA genotyping, validated by sequencing 10%of samples. Deviation from the Hardy-Weinberg equilibrium was tested using the chi-square test. Conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income.Genotypes G/G and G/T showed two times greater odds of developing MDD compared to variant genotype T/T (OR=1.983, 95% CI=1.031-3.815; p=0.040 and OR=2.232, 95% CI=1.100-4.533; p=0.026 respectively). Carriers of genotypes G/G and G/T of the SNP rs11126936 in SLC30A3are associated with increased risk of MDD.
  5. Labrooy C, Abdullah TL, Stanslas J
    Trop Life Sci Res, 2020 Apr;31(1):123-139.
    PMID: 32963715 DOI: 10.21315/tlsr2020.31.1.8
    Kaempferia parviflora is an ethnomedicinally important plant. Conventional propagation of K. parviflora is hindered by slow growth rate, long dormancy periods and dual use of rhizomes for seeds as well as marketable produce. In our study, we developed a promising dual-phase micropropagation protocol to increase number of plantlets, survivability, biomass and quality plantlets for mass production. Multiple shoot regeneration was found most successful on Murashige and Skoog (MS) media supplemented with 35.52 μM N6-benzyladenine (BA) in terms of highest number of shoots (22.4 ± 1.84), leaves (29.27 ± 1.30), and roots (17.8 ± 1.72) per explant. High survivability was observed with an acclimatisation percentage of 100% in sterile perlite medium. This method was shown to be preferable compared to conventional propagation in terms of propagation time and number of plantlets. Regenerated in vitro plantlets were then successfully induced to form microrhizomes in MS media with an optimal concentration of 6% (w/v) sucrose. Increase in microrhizome biomass (35.7 ± 2.59 g per flask), number of microrhizomes (5.2 ± 0.78), shoots (8.5 ± 1.58) and roots (8.5 ± 1.58) were observed for this treatment. This investigation successfully highlights the manipulation of single factors in short time frame to produce a simple and efficient alternative propagation method for K. parviflora.
  6. Asraa Faris, Hadri Hadi Md Yusof, Shahidee Zainal Abidin, Omar Habib, Cheah, Pike-See, Stanslas, Johnson, et al.
    MyJurnal
    Introduction: One of the commonly used techniques for mutation screening is High Resolution Melting (HRM) analysis. HRM is a post PCR method that relies on the detection of the fluorescent signals acquired due to the release of DNA intercalated dyes upon the melting of dsDNA to ssDNA. The method is simple, inexpensive and does not require post PCR-handling, making it suitable for high throughput screening. Methods: This study aimed to develop and validate HRM technique for the screening of two disease-associated single nucleotide polymorphisms (SNPs) namely BDNF rs6265 and DAT1 rs40184 using a total of 30 gDNA samples. The obtained results were confirmed and validated by sequencing. Results: HRM analysis showed that the predicted genotypes of BDNF rs6265 and DAT1 rs40184 among all the gDNA samples were in 100% concordance with the sequencing results, making it an accurate and sensitive method for the detection of SNPs. Conclusions: The application of HRM can accurately determine the genotype of BDNF rs6265 and DAT1 rs40184 SNPs, making it a promising tool for rapid and high-throughput screening of targeted SNPs in a large population study.
  7. Manikam SD, Manikam ST, Stanslas J
    J Pharm Pharmacol, 2009 Jan;61(1):69-78.
    PMID: 19126299 DOI: 10.1211/jpp/61.01.0010
    The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2).
  8. Hasan S, B Basri H, P Hin L, Stanslas J
    Pak J Med Sci, 2013 May;29(3):859-62.
    PMID: 24353644
    Encephalitis has been included in the causes of optic neuritis, but post encephalitic optic neuritis has been rarely reported. Majority of the cases of optic neuritis are either idiopathic or associated with multiple sclerosis, especially in western countries. This is very important in the Asian population where the incidence and prevalence of multiple sclerosis is not as high as in the Western countries. Although post infectious optic neuritis is more common in children, it can also be found in adults and is usually seen one to three weeks after a symptomatic infective prodrome. Here, we present a case of a 48 year-old-male who developed optic neuritis following viral encephalitis. His first presentation was with severe headache of two weeks duration. Viral encephalitis was diagnosed and treated. The patient presented again three weeks later with right eye pain and other features typical of optic neuritis. Corticosteroid therapy facilitated prompt recovery. Optic neuritis is an uncommon manifestation of encephalitis. It is important that both doctors and patients remain aware of post infectious cause of optic neuritis, which would enable a timely diagnosis and treatment of this reversible cause of vision loss.
  9. Hasan MS, Basri HB, Hin LP, Stanslas J
    Int J Neurosci, 2013 Mar;123(3):143-54.
    PMID: 23110469 DOI: 10.3109/00207454.2012.744308
    Ischemic heart disease and stroke are the two leading causes of death worldwide. Antiplatelet therapy plays the most significant role in the management of these cardiovascular and cerebrovascular occlusive events to prevent recurrent ischemic attack. Clopidogrel, an antiplatelet drug, is widely prescribed either alone or in combination with aspirin as dual antiplatelet therapy for the prevention of vascular occlusive events. The antiplatelet response to clopidogrel varies widely. Hyporesponders and nonresponders are likely to have adverse cardiovascular events during follow-up. Some drugs, such as proton pump inhibitors (omeprazole), calcium channel blockers, selective serotonin reuptake inhibitors (nefazadone), coumarin derivatives (phenprocoumon), benzodiazepines, sulfonylurea, erythromycin, and itraconazole, decrease the antiplatelet effect of clopidogrel when administered concomitantly. Decreased response to clopidogrel is common among Asians due to genetic polymorphisms associated with clopidogrel resistance, and it is nearly 70% in some of the Asian communities. It is necessary to study Asian populations, because there are a large number of Asians throughout the world due to increased migration. Current guidelines do not make genetic testing or platelet response testing mandatory prior to clopidogrel prescription. Therefore, it is important for clinicians treating Asian patients to keep in mind the interindividual variability in response to clopidogrel when prescribing the drug.
  10. Ooi CT, Syahida A, Stanslas J, Maziah M
    World J Microbiol Biotechnol, 2013 Mar;29(3):421-30.
    PMID: 23090845 DOI: 10.1007/s11274-012-1194-z
    This article presents the abilities and efficiencies of five different strains of Agrobacterium rhizogenes (strain ATCC 31798, ATCC 43057, AR12, A4 and A13) to induce hairy roots on Solanum mammosum through genetic transformation. There is significant difference in the transformation efficiency (average number of days of hairy root induction) and transformation frequency for all strains of A. rhizogenes (P < 0.05). Both A. rhizogenes strain AR12 and A13 were able to induce hairy root at 6 days of co-cultivation, which were the fastest among those tested. However, the transformation frequencies of all five strains were below 30 %, with A. rhizogenes strain A4 and A13 showing the highest, which were 21.41 ± 10.60 % and 21.43 ± 8.13 % respectively. Subsequently, the cultures for five different hairy root lines generated by five different strains of bacteria were established. However, different hairy root lines showed different growth index under the same culture condition, with the hairy root lines induced by A. rhizogenes strain ATCC 31798 exhibited largest increase in fresh biomass at 45 days of culture under 16 h light/8 h dark photoperiod in half-strength MS medium. The slowest growing hairy root line, which was previously induced by A. rhizogenes strain A13, when cultured in optimized half-strength MS medium containing 1.5 times the standard amount of ammonium nitrate and potassium nitrate and 5 % (w/v) sucrose, had exhibited improvement in growth index, that is, the fresh biomass was almost double as compared to its initial growth in unmodified half-strength MS medium.
  11. Maulidiani, Shaari K, Paetz C, Stanslas J, Abas F, Lajis NH
    Nat Prod Commun, 2009 Aug;4(8):1031-6.
    PMID: 19768978
    Phytochemical investigation on Globba pendula resulted in the isolation of a new naturally occurring 16-oxo-(8)17-12-labdadien-15,11-olide 1 and benzofuran-2-carboxaldehyde 2. Other known compounds including isoandrographolide, indirubin, vanillin, vanillic acid, 2(3H)-benzoxazolone, as well as beta-sitosteryl-beta-D-glucopyranoside, beta-sitosterol, and 7alpha-hydroxysitosterol were also isolated. The structures were established based on spectroscopic data and comparison with the literature. Furthermore, the compound isoandrographolide has demonstrated strong cytotoxic properties towards a panel of cancer cell lines (MCF-7, PC-3, and H-460) with the IC50 values of 7.9, 8.7, and 9.0 microM, respectively.
  12. Quah SY, Tan MS, Teh YH, Stanslas J
    Pharmacol Ther, 2016 06;162:35-57.
    PMID: 27016467 DOI: 10.1016/j.pharmthera.2016.03.010
    Oncogenic rat sarcoma (Ras) is linked to the most fatal cancers such as those of the pancreas, colon, and lung. Decades of research to discover an efficacious drug that can block oncogenic Ras signaling have yielded disappointing results; thus, Ras was considered "undruggable" until recently. Inhibitors that directly target Ras by binding to previously undiscovered pockets have been recently identified. Some of these molecules are either isolated from natural products or derived from natural compounds. In this review, we described the potential of these compounds and other inhibitors of Ras signaling in drugging Ras. We highlighted the modes of action of these compounds in suppressing signaling pathways activated by oncogenic Ras, such as mitogen-activated protein kinase (MAPK) signaling and the phosphoinositide-3-kinase (PI3K) pathways. The anti-Ras strategy of these compounds can be categorized into four main types: inhibition of Ras-effector interaction, interference of Ras membrane association, prevention of Ras-guanosine triphosphate (GTP) formation, and downregulation of Ras proteins. Another promising strategy that must be validated experimentally is enhancement of the intrinsic Ras-guanosine triphosphatase (GTPase) activity by small chemical entities. Among the inhibitors of Ras signaling that were reported thus far, salirasib and TLN-4601 have been tested for their clinical efficacy. Although both compounds passed phase I trials, they failed in their respective phase II trials. Therefore, new compounds of natural origin with relevant clinical activity against Ras-driven malignancies are urgently needed. Apart from salirasib and TLN-4601, some other compounds with a proven inhibitory effect on Ras signaling include derivatives of salirasib, sulindac, polyamine, andrographolide, lipstatin, levoglucosenone, rasfonin, and quercetin.
  13. Wahyuni FS, Shaari K, Stanslas J, Lajis NH, Hamidi D
    Pharmacogn Mag, 2016 Jan;12(Suppl 1):S52-6.
    PMID: 27041859 DOI: 10.4103/0973-1296.176115
    To isolate compounds from the roots of Garcinia cowa and to evaluated their cytotoxic activity against breast (MCF-7), prostate (DU-145), and lung (H-460) cell lines.
  14. Tan MS, Teh YH, Ho KL, Stanslas J
    Protein J, 2020 02;39(1):54-61.
    PMID: 31620959 DOI: 10.1007/s10930-019-09872-1
    Being an important regulator of cell growth and survival, a point mutation at glycine-12 residue of Kras4B to valine (V), renders Kras4BG12V oncogenic. Kras4B recombinant protein is used as a bait to fish its potential ligands in the attempt of drugging this oncoprotein and to validate its pharmacologically relevant ligand in protein-ligand interaction studies. Nevertheless, synthesis of Kras4B recombinant protein is challenging as it was reported being susceptible to aggregation into inclusion bodies in the bacterial host, resulting in a poor yield of recombinant protein. Here, we describe a novel method to produce native Kras4BG12V protein by using pET SUMO protein expression system as a solution to the formation of inclusion bodies. Kras4BG12V oncogene was cloned into pET SUMO vector, followed by a 12 h chemically induced protein expression in Escherichia coli at 20 °C. Native Kras4BG12V protein was produced in a series of protein purification steps involving immobilised nickel ion-affinity column chromatography, SUMO fusion protein and polyhistidine tag removal, and size exclusion column chromatography. The identity of the purified Kras4BG12V protein was validated by immunoblot analysis. The purified protein exhibited self-dimerising, indicating that the purified protein structurally resembles Kras4B. Its physical interaction with 4,6-dichloro-2-methyl-3-aminoethyl-indole (DCAI), a known binder of Kras4B, confirms the identity of the purified protein as Kras4BG12V. The native Kras4BG12V protein was successfully purified in a substantial amount by using the pET SUMO protein expression system.
  15. Wong MS, Sidik SM, Mahmud R, Stanslas J
    Clin Exp Pharmacol Physiol, 2013 May;40(5):307-19.
    PMID: 23534409 DOI: 10.1111/1440-1681.12083
    Tumour invasion and metastasis have been recognized as major causal factors in the morbidity and mortality among cancer patients. Many advances in the knowledge of cancer metastasis have yielded an impressive array of attractive drug targets, including enzymes, receptors and multiple signalling pathways. The present review summarizes the molecular pathogenesis of metastasis and the identification of novel molecular targets used in the discovery of antimetastatic agents. Several promising targets have been highlighted, including receptor tyrosine kinases, effector molecules involved in angiogenesis, matrix metalloproteinases (MMPs), urokinase plasminogen activator, adhesion molecules and their receptors, signalling pathways (e.g. phosphatidylinositol 3-kinase, phospholipase Cγ1, mitogen-activated protein kinases, c-Src kinase, c-Met kinases and heat shock protein. The discovery and development of potential novel therapeutics for each of the targets are also discussed in this review. Among these, the most promising agents that have shown remarkable clinical outcome are anti-angiogenic agents (e.g. bevacizumab). Newer agents, such as c-Met kinase inhibitors, are still undergoing preclinical studies and are yet to have their clinical efficacy proven. Some therapeutics, such as first-generation MMP inhibitors (MMPIs; e.g. marimastat) and more selective versions of them (e.g. prinomastat, tanomastat), have undergone clinical trials. Unfortunately, these drugs produced serious adverse effects that led to the premature termination of their development. In the future, third-generation MMPIs and inhibitors of signalling pathways and adhesion molecules could form valuable novel classes of drugs in the anticancer armamentarium to combat metastasis.
  16. Hasan MS, Basri HB, Hin LP, Stanslas J
    Surg Neurol Int, 2011;2:177.
    PMID: 22276232 DOI: 10.4103/2152-7806.90698
    BACKGROUND: Neurocysticercosis is the most common parasitic infestation of the central nervous system and an important cause of acquired epilepsy. Although endemic in developing countries, with an increased immigration from the endemic regions, it is also seen progressively in other parts of the world. Hence, there is an increased need for awareness of neurocysticercosis in the non-endemic areas.

    CASE DESCRIPTION: The case described here is of a 13-year-old girl who presented with refractory seizures. She had been on antiepileptic medication and had also received anti-parasitic treatment for neurocysticercosis. Surgical intervention was recommended because the seizures were resistant to treatment and also because the diagnosis could not be clearly established. Following surgery, the seizures have been under control and the patient has been doing well.

    CONCLUSION: Neurocysticercosis can be a potential cause of refractory seizure even in non-endemic countries. Some cases may be difficult to diagnose. Clinical presentation of seizure and brain imaging should be given priority over blood investigations for diagnosing neurocysticercosis and advanced neurosurgical intervention can be considered in suitable cases for better outcome.

  17. Sulaiman I, Lim JC, Soo HL, Stanslas J
    Pulm Pharmacol Ther, 2016 Oct;40:52-68.
    PMID: 27453494 DOI: 10.1016/j.pupt.2016.07.005
    Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs. New drug candidates with their putative targets that have shown promising results in the preclinical and/or clinical trials are summarised. Examples of these interventions include restoration of Th1/Th2 balance by the use of newly developed immunomodulators such as toll-like receptor-9 activators (CYT003-QbG10 and QAX-935). Clinical trials revealed the safety and effectiveness of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists such as OC0000459, BI-671800 and ARRY-502 in the restoration of Th1/Th2 balance. Regulation of cytokine activity by the use of newly developed biologics such as benralizumab, reslizumab, mepolizumab, lebrikizumab, tralokinumab, dupilumab and brodalumab are at the stage of clinical development. Transcription factors are potential targets for asthma therapy, for example SB010, a GATA-3 DNAzyme is at its early stage of clinical trial. Other candidates such as inhibitors of Rho kinases (Fasudil and Y-27632), phosphodiesterase inhibitors (GSK256066, CHF 6001, roflumilast, RPL 554) and proteinase of activated receptor-2 (ENMD-1068) are also discussed. Preclinical results of blockade of calcium sensing receptor by the use of calcilytics such as calcitriol abrogates cardinal signs of asthma. Nevertheless, successful translation of promising preclinical data into clinically viable interventions remains a major challenge to the development of novel anti-asthmatics.
  18. Jabir RS, Ho GF, Annuar MABA, Stanslas J
    Biomarkers, 2018 Mar;23(2):142-146.
    PMID: 28554261 DOI: 10.1080/1354750X.2017.1334152
    CONTEXT: Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin.

    OBJECTIVE: To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians).

    MATERIALS AND METHODS: One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established.

    RESULTS: There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash.

    CONCLUSIONS: This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

  19. Saik AY, Lim YY, Stanslas J, Choo WS
    Biotechnol Lett, 2017 Feb;39(2):297-304.
    PMID: 27812823 DOI: 10.1007/s10529-016-2246-5
    OBJECTIVES: To investigate the lipase-catalyzed acylation of quercetin with oleic acid using Candida antarctica lipase B.

    RESULTS: Three acylated analogues were produced: quercetin 4'-oleate (C33H42O8), quercetin 3',4'-dioleate (C51H74O9) and quercetin 7,3',4'-trioleate (C69H106O10). Their identities were confirmed with UPLC-ESI-MS and (1)H NMR analyses. The effects of temperature, duration and molar ratio of substrates on the bioconversion yields varied across conditions. The regioselectivity of the acylated quercetin analogues was affected by the molar ratio of substrates. TLC showed the acylated analogues had higher lipophilicity (152% increase) compared to quercetin. Partition coefficient (log P) of quercetin 4'-oleate was higher than those of quercetin and oleic acid. Quercetin 4'-oleate was also stable over 28 days of storage.

    CONCLUSIONS: Quercetin oleate esters with enhanced lipophilicity can be produced via lipase-catalyzed reaction using C. antarctica lipase B to be used in topical applications.

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