Displaying publications 141 - 149 of 149 in total

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  1. Ayipo YO, Mordi MN, Mustapha M, Damodaran T
    Eur J Pharmacol, 2021 Feb 15;893:173837.
    PMID: 33359647 DOI: 10.1016/j.ejphar.2020.173837
    Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.
    Matched MeSH terms: Brain Neoplasms
  2. Lee YQ, Rajadurai P, Abas F, Othman I, Naidu R
    Front Mol Biosci, 2021;8:645856.
    PMID: 33996900 DOI: 10.3389/fmolb.2021.645856
    Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, "Glycolysis" and "Post-translational protein modification." Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies.
    Matched MeSH terms: Brain Neoplasms
  3. Manah Chandra Changmai, Mohammed Faruque Reza, Zamzuri idris, Regunath Kandasamy, Kastury Gohain
    MyJurnal
    Introduction: Intracranial brain tumour like meningiomas and glioblastomas are most prevalent tumour. The metas- tasis to the brain is one of the major issues in the tumours of the central nervous system. The diagnosis of metastatic and primary brain tumour is incomprehensible with standard magnetic resonance imaging (MRI). The magnetic res- onance spectroscopy (MRS) is basically performed in standard clinical setting for diagnosing and tracking the brain tumour. Method: It is a retrospective study containing 53 patients with MRS. The patients with metastatic tumour (n=10), glioblastomas (n=8) and meningiomas (n=20) are included in the study. Single voxel technique is applied in the tumour core to determine the metabolites. The tumour N-acetyl aspartate (NAA), Choline (Cho), Creatine (Cr), Lactate, Alanine and lipids were analysed. The ratios of NAA/Cr, Cho/NAA and Cho/Cr were recorded and com- pared between the three tumours. The metabolites were detected between short echo time (TE) to long echo time (TE) during MRS. Results: There is a sharp fall of NAA peak in metastatic tumour. The resonance of creatine, lactate and alanine is higher in glioblastomas. A high lipid mean value of 3.13(0.17) is seen in metastatic tumour. The ROC curve shows a low NAA/Cr specificity of 46.7%, high sensitivity of 83.3% in Cho/NAA and Cho/Cr ratio. Conclusion: The metabolic profiles of metastatic brain tumour, glioblastomas and meningioma illustrate a divergence in their description that will assist in planning therapeutic and surgical intervention of these tumours.
    Matched MeSH terms: Brain Neoplasms
  4. Mohamed Yusoff AA, Zulfakhar FN, Mohd Khair SZN, Wan Abdullah WS, Abdullah JM, Idris Z
    Brain Tumor Res Treat, 2018 Apr;6(1):31-38.
    PMID: 29717568 DOI: 10.14791/btrt.2018.6.e5
    BACKGROUND: Mitochondria are major cellular sources of reactive oxygen species (ROS) generation which can induce mitochondrial DNA damage and lead to carcinogenesis. The mitochondrial 10398A>G alteration in NADH-dehydrogenase subunit 3 (ND3) can severely impair complex I, a key component of ROS production in the mitochondrial electron transport chain. Alteration in ND3 10398A>G has been reported to be linked with diverse neurodegenerative disorders and cancers. The aim of this study was to find out the association of mitochondrial ND3 10398A>G alteration in brain tumor of Malaysian patients.

    METHODS: Brain tumor tissues and corresponding blood specimens were obtained from 45 patients. The ND3 10398A>G alteration at target codon 114 was detected using the PCR-RFLP analysis and later was confirmed by DNA sequencing.

    RESULTS: Twenty-six (57.8%) patients showed ND3 10398A>G mutation in their tumor specimens, in which 26.9% of these mutations were heterozygous mutations. ND3 10398A>G mutation was not significantly correlated with age, gender, and histological tumor grade, however was found more frequently in intra-axial than in extra-axial tumors (62.5% vs. 46.2%, p<0.01).

    CONCLUSION: For the first time, we have been able to describe the occurrence of ND3 10398A>G mutations in a Malaysian brain tumor population. It can be concluded that mitochondrial ND3 10398A>G alteration is frequently present in brain tumors among Malaysian population and it shows an impact on the intra-axial tumors.

    Matched MeSH terms: Brain Neoplasms
  5. Alias H, Lau SCD, Schuitema I, de Sonneville LMJ
    Front Psychol, 2018;9:703.
    PMID: 29896137 DOI: 10.3389/fpsyg.2018.00703
    Objective: This study aimed to evaluate neuropsychological consequences in survivors of childhood brain tumor. Method: A case-control study was conducted over a period of 4 months in a tertiary referral center in Kuala Lumpur, Malaysia. Fourteen survivors of childhood brain tumor aged 7-18 years, who were off-treatment for at least 1 year and were in remission, and 31 unrelated healthy controls were recruited. The median age at diagnosis was 8.20 years (range: 0.92-12.96 years). The diagnoses of brain tumors were medulloblastoma, germ cell tumor, pineocytoma, pilocystic astrocytoma, suprasellar germinoma, and ependymoma. Eleven survivors received central nervous system irradiation. Seven tasks were selected from the Amsterdam Neuropsychological Tasks program to evaluate alertness (processing speed), and major aspects of executive functioning, such as working memory capacity, inhibition, cognitive flexibility, and sustained attention. Speed, stability and accuracy of responses were the main outcome measures. Results: Survivors of childhood brain tumor showed statistically significant poorer performance on all tasks compared to healthy controls. Both processing speed and accuracy were impaired in the survivors, in particular under more complex task conditions. The survivors demonstrated deficits in alertness, sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Longer duration off treatment appeared to be correlated with poorer alertness, memory capacity, and inhibition. Conclusion: Survivors of childhood brain tumor in our center showed impaired neuropsychological functioning. Development of less toxic treatment protocols is important to prevent late effects of cognitive deficits in survivors of childhood brain tumor.
    Matched MeSH terms: Brain Neoplasms
  6. Hardiany NS, Yo EC, Ngadiono E, Wanandi SI
    Malays J Med Sci, 2019 Nov;26(6):35-45.
    PMID: 31908585 DOI: 10.21315/mjms2019.26.6.4
    Background: Glioblastoma multiforme (GBM) is the most malignant primary brain tumour and there is no definite cure. It has been suggested that there are significant interactions among mesenchymal stem cells (MSCs), their released factors and tumour cells that ultimately determine GBM's growth pattern. This study aims to analyse the expression of molecules involved in GBM cell apoptotic pathways following treatment with the MSC secretome.

    Methods: A conditioned medium of umbilical cord-derived MSCs (UCMSC-CM) was generated by culturing the cells on serum-free αMEM for 24 h. Following this, human GBM T98G cells were treated with UCMSC-CM for 24 h. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was then performed to measure the mRNA expression of survivin, caspase-9, TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DcR1.

    Results: mRNA expression of caspase-9 in CM-treated T98G cells increased 1.6-fold (P = 0.017), whereas mRNA expression of survivin increased 3.5-fold (P = 0.002). On the other hand, TRAIL protein expression was upregulated (1.2-fold), whereas mRNA expression was downregulated (0.4-fold), in CM-treated cells. Moreover, there was an increase in the mRNA expression of both DR4 (3.5-fold) and DcR1 (1,368.5-fold) in CM-treated cells.

    Conclusion: The UCMSC-CM was able to regulate the expression of molecules involved in GBM cell apoptotic pathways. However, the expression of anti-apoptotic molecules was more upregulated than that of pro-apoptotic molecules.

    Matched MeSH terms: Brain Neoplasms
  7. Kong CC, Kandasamy R, Haspani S, Idris Z, Abdullah JM
    Malays J Med Sci, 2018 May;25(3):88-102.
    PMID: 30899190 MyJurnal DOI: 10.21315/mjms2018.25.3.9
    Background: Meningiomas are the most common intracranial tumours; they account for 13%-26% of all the primary intracranial tumours. Skull base meningiomas make up 25% of all meningiomas and are one of the most difficult intracranial tumours to be managed surgically. This is due to the fact that it is difficult to approach the lesions which are also close to vital structures such as cranial nerves and major blood vessels. Despite the abundance of these cases in Malaysia, local data on meningiomas is scarce.

    Methods: This is a retrospective study consisting of 199 patients with meningiomas who have been operated at the Kuala Lumpur General Hospital from January 2010-December 2014. They were categorised into skull base and non-skull base groups. Demography, tumour characteristics, and patient outcomes were analysed. Kaplan-Meier survival curves as well as Cox hazard univariable and multivariable regressions for the possible predictors of survival were analysed.

    Results: 97.5% of the patients (n = 194) had WHO grade I meningioma and only five patients had WHO grade II meningioma. There was a female predominance (n = 134; 67.3%), with a male-to-female ratio of 1:2. Some 27.1 % patients had skull base meningiomas. Patients with skull base meningiomas had poorer outcomes and discharge conditions (n = 23; 42.6% P < 0.01), in addition to higher risk of incomplete resections (n = 34; 63% P < 0.01). Multivariate cox hazard regressions showed that the skull base meningioma group had four times the risk of death of the non-skull base group.

    Conclusions: Symptomatic meningiomas can be curative if the tumour is completely removed. Our study has revealed that skull base meningiomas which were operated locally had higher rates of incomplete resection and poorer surgical outcomes as compared to the non-skull base group. Patients with skull base meningiomas had four times the risk of death vis-à-vis non-skull base ones. More local studies are needed to look into skull base meningiomas for the improvement of its surgical outcomes.

    Matched MeSH terms: Brain Neoplasms
  8. Zainuddin N, Jaafart H, Isa MN, Abdullah JM
    Neurol Res, 2004 Jan;26(1):88-92.
    PMID: 14977064
    Recent advances in neuro-oncology have revealed different pathways of molecular oncogenesis in malignant gliomas including loss of heterozygosity on chromosomal regions harboring tumor suppressor genes. In the present study, we performed polymerase chain reaction-loss of heterozygosity (PCR-LOH) analysis using microsatellite markers to identify loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in the Malays with malignant gliomas. Of 12 cases with allelic losses, seven (58.3%) cases showed LOH on chromosome 10q, three (25.0%) cases showed LOH on chromosome 9p, four (33.3%) cases showed LOH on chromosome 17p and two (16.7%) cases showed LOH on chromosome 13q. The cases include five (41.7%) cases of glioblastoma multiforme, three (25.0%) cases of anaplastic astrocytoma, three (25.0%) cases of anaplastic oligodendroglioma and one (8.3%) case of anaplastic ependymoma. Four cases showed loss of heterozygosity on more than one locus. Our findings showed that loss of heterozygosity on specific chromosomal regions contributes to the molecular pathway of glioma progression in Malay population. In addition, these data provide useful evidence of molecular genetic alterations of malignant glioma in South East Asian patients, particularly in the East Coast of Malaysia.
    Matched MeSH terms: Brain Neoplasms/genetics*
  9. Khan MS, Majid AM, Iqbal MA, Majid AS, Al-Mansoub M, Haque RS
    Eur J Pharm Sci, 2016 Oct 10;93:304-18.
    PMID: 27552907 DOI: 10.1016/j.ejps.2016.08.032
    Glioblastoma multiforme is a highly malignant, heterogenic, and drug resistant tumor. The blood-brain barrier (BBB), systemic cytotoxicity, and limited specificity are the main obstacles in designing brain tumor drugs. In this study a computational approach was used to design brain tumor drugs that could downregulate VEGF and IL17A in glioblastoma multiforme type four. Computational screening tools were used to evaluate potential candidates for antiangiogenic activity, target binding, BBB permeability, and ADME physicochemical properties. Additionally, in vitro cytotoxicity, migration, invasion, tube formation, apoptosis, ROS and ELISA assays were conducted for molecule 6 that was deemed most likely to succeed. The efflux ratio of membrane permeability and calculated docking scores of permeability to glycoproteins (P-gps) were used to determine the BBB permeability of the molecules. The results showed BBB permeation for molecule 6, with the predicted efficiency of 0.55kcal/mol and binding affinity of -37kj/mol corresponding to an experimental efflux ratio of 0.625 and predicted -15kj/mol of binding affinity for P-gps. Molecule 6 significantly affected the angiogenesis pathways by 2-fold downregulation of IL17A and VEGF through inactivation of active sites of HSP90 (predicted binding: -37kj/mol, predicted efficiency: 0.55kcal/mol) and p23 (predicted binding: 12kj/mol, predicted efficiency: 0.17kcal/mol) chaperon proteins. Additionally, molecule 6 activated the 17.38% relative fold of ROS level at 18.3μg/mL and upregulated the caspase which lead the potential synergistic apoptosis through the antiangiogenic activity of molecule 6 and thereby the highly efficacious anticancer upshot. The results indicate that the binding of the molecules to the therapeutic target is not essential to produce a lethal effect on cancer cells of the brain and that antiangiogenic efficiency is much more important.
    Matched MeSH terms: Brain Neoplasms/metabolism*
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