Publications by authors named "Abdul Aziz Mohamed Yusoff"

19 Publications

  • Page 1 of 1

Somatic mitochondrial DNA D-loop mutations in meningioma discovered: A preliminary data.

J Cancer Res Ther 2020 Oct-Dec;16(6):1517-1521

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia; Center for Neuroscience Services and Research, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Background And Objective: Meningiomas are among the most common intracranial tumors of the central nervous system. It is widely accepted that the initiation and progression of meningiomas involve the accumulation of nucleus genetic alterations, but little is known about the implication of mitochondrial genomic alterations during development of these tumors. The human mitochondrial DNA (mtDNA) contains a short hypervariable, noncoding displacement loop control region known as the D-Loop. Alterations in the mtDNA D-loop have been reported to occur in most types of human cancers. The purpose of this study was to assess the mtDNA D-loop mutations in Malaysian meningioma patients.

Materials And Methods: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds.

Results: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions.

Conclusion: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.
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http://dx.doi.org/10.4103/jcrt.JCRT_1132_16DOI Listing
December 2020

Prevalence of mitochondrial DNA common deletion in patients with gliomas and meningiomas: A first report from a Malaysian study group.

J Chin Med Assoc 2020 Sep;83(9):838-844

Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

Background: The 4977-bp common deletion (mtDNA) is a well-established mitochondrial genome alteration that has been described in various types of human cancers. However, to date, no studies on mtDNA in brain tumors have been reported. The present study aimed to determine mtDNA prevalence in common brain tumors, specifically, low- and high-grade gliomas (LGGs and HGGs), and meningiomas in Malaysian cases. Its correlation with clinicopathological parameters was also evaluated.

Methods: A total of 50 patients with pathologically confirmed brain tumors (13 LGGs, 20 HGGs, and 17 meningiomas) were enrolled in this study. mtDNA was detected by using polymerase chain reaction (PCR) technique and later confirmed via Sanger DNA sequencing.

Results: Overall, mtDNA was observed in 16 (32%) patients and it was significantly correlated with the type of tumor group and sex, being more common in the HGG group and in male patients.

Conclusion: The prevalence of mtDNA in Malaysian glioma and meningioma cases has been described for the first time and it was, indeed, comparable with previously published studies. This study provides initial insights into mtDNA in brain tumor and these findings can serve as new data for the global mitochondrial DNA mutations database.
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http://dx.doi.org/10.1097/JCMA.0000000000000401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478208PMC
September 2020

Detection of , and Genes Variants in Malay Premature Babies with Retinopathy of Prematurity.

J Ophthalmic Vis Res 2019 Apr-Jun;14(2):171-178

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

Purpose: To determine the mutational analyses of familial exudative vitreoretinopathy (FEVR)-causing genes in Malay patients with retinopathy of prematurity (ROP) to obtain preliminary data for gene alterations in the Malay community.

Methods: A comparative cross-sectional study involving 86 Malay premature babies (ROP = 41 and non-ROP = 45) was performed from September 2012 to December 2014. Mutation analyses in (FEVR)-causing genes (, , , ) were performed using DNA from premature babies using polymerase chain reaction (PCR) and direct sequencing. Sequencing results were confirmed with PCR-Restriction Fragment Length Polymorphism (RFLP).

Results: We found variants of FZD4, , in this study. One patient from each group showed a non-synonymous alteration in , c.502C>T (p.P168S). A synonymous variant of [c.3357G>A (p.V1119V)] was found in 30 ROP and 28 non-ROP patients. Two variants of , c.765G>T (p.P255P) and c.*39C>T (3'UTR), were also recorded (29 and 21 in ROP, 33 and 26 in non-ROP, respectively). Gestational age and birth weight were found to be significantly associated with ROP ( value < 0.001 and 0.001, respectively).

Conclusion: Analysis of data obtained from the ROP Malay population will enhance our understanding of these FEVR-causing gene variants. The c.3357G>A (p.V1119V) variant of , and c.765G>T (p.P255P) and c.*39C>T variants of could be common polymorphisms in the Malay ethnic group; however, this requires further elucidation. Future studies using larger groups and higher numbers of advanced cases are necessary to evaluate the relationship between FEVR-causing gene variants and the risk of ROP susceptibility in Malaysian infants.
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http://dx.doi.org/10.4103/jovr.jovr_210_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504731PMC
May 2019

A comprehensive overview of mitochondrial DNA 4977-bp deletion in cancer studies.

Oncol Rev 2019 Jan 16;13(1):409. Epub 2019 Apr 16.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

Mitochondria are cellular machines essential for energy production. The biogenesis of mitochondria is a highly complex and it depends on the coordination of the nuclear and mitochondrial genome. Mitochondrial DNA (mtDNA) mutations and deletions are suspected to be associated with carcinogenesis. The most described mtDNA deletion in various human cancers is called the 4977-bp common deletion (mDNA) and it has been explored since two decades. In spite of that, its implication in carcinogenesis still unknown and its predictive and prognostic impact remains controversial. This review article provides an overview of some of the cellular and molecular mechanisms underlying mDNA formation and a detailed summary about mDNA reported in various types of cancers. The current knowledges of mDNA as a prognostic and predictive marker are also discussed.
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http://dx.doi.org/10.4081/oncol.2019.409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478002PMC
January 2019

Trkb-IP3 Pathway Mediating Neuroprotection in Rat Hippocampal Neuronal Cell Culture Following Induction of Kainic Acid.

Malays J Med Sci 2018 Nov 28;25(6):28-45. Epub 2018 Dec 28.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Background: Following brain injury, development of hippocampal sclerosis often led to the temporal lobe epilepsy which is sometimes resistant to common anti-epileptic drugs. Cellular and molecular changes underlying epileptogenesis in animal models were studied, however, the underlying mechanisms of kainic acid (KA) mediated neuronal damage in rat hippocampal neuron cell culture alone has not been elucidated yet.

Methods: Embryonic day 18 (E-18) rat hippocampus neurons were cultured with poly-L-lysine coated glass coverslips. Following optimisation, KA (0.5 μM), a chemoconvulsant agent, was administered at three different time-points (30, 60 and 90 min) to induce seizure in rat hippocampal neuronal cell culture. We examined cell viability, neurite outgrowth density and immunoreactivity of the hippocampus neuron culture by measuring brain derived neurotrophic factor (BDNF), γ-amino butyric acid A (GABA) subunit α-1 (GABRA1), tyrosine receptor kinase B (TrkB), and inositol trisphosphate receptor (IPR/IP3) levels.

Results: The results revealed significantly decreased and increased immunoreactivity changes in TrkB (a BDNF receptor) and IPR, respectively, at 60 min time point.

Conclusion: The current findings suggest that TrkB and IP3 could have a neuroprotective role which could be a potential pharmacological target for anti-epilepsy drugs.
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http://dx.doi.org/10.21315/mjms2018.25.6.4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422567PMC
November 2018

Roles of EphA2 Receptor in Angiogenesis Signaling Pathway of Glioblastoma Multiforme.

Malays J Med Sci 2018 Nov 28;25(6):22-27. Epub 2018 Dec 28.

Universiti Teknologi MARA, Shah Alam, 40450 Shah Alam, Selangor, Malaysia.

Glioblastoma multiforme (GBM) is one of the most common primary brain tumours in adults, accounting for almost 65% of all cases. Among solid tumours, GBM is characterised by strong angiogenesis, including the highest degree of vascular proliferation and endothelial cell hyperplasia. Despite numerous improvements in existing treatment approaches, the prognosis of GBM patients remains poor, with a mean survival of only 14.6 months. Growing evidence has shown significant overexpression of the ephrin type-A receptor 2 (EphA2) receptor in various malignancies, including GBM, as well as a correlation to poor prognoses. It is believed that EphA2 receptors play important roles in mediating GBM tumourigenesis, including invasion, metastasis, and angiogenesis. Despite the clinical and pathological importance of tumour-associated vasculature, the underlying mechanism involving EphA2 is poorly known. Here, we have summarised the current knowledge in the field regarding EphA2 receptors' roles in the angiogenesis of GBM.
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http://dx.doi.org/10.21315/mjms2018.25.6.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422564PMC
November 2018

Mitochondrial 10398A>G NADH-Dehydrogenase Subunit 3 of Complex I Is Frequently Altered in Intra-Axial Brain Tumors in Malaysia.

Brain Tumor Res Treat 2018 Apr;6(1):31-38

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia.

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.
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http://dx.doi.org/10.14791/btrt.2018.6.e5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932297PMC
April 2018

The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo () Shoots on Kv1.4 Channel.

Malays J Med Sci 2018 Feb 28;25(1):101-113. Epub 2018 Feb 28.

Center for Neuroscience Services and Research, Universiti Sains Malaysia, Jalan Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating -related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K across the cellular membrane.

Methods: Chemical compounds from bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from . The current were detected by the two-microelectrode voltage clamp, holding potential starting from -80 mV with 20 mV step-up until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control.

Results: All concentration showed statistically significant results with < 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play any significant roles.

Conclusion: 4-hydroxybenzoic acid was found to be able to enhance the inactivation of Kv1.4 by lowering the membrane potential so that the abnormal neuronal firing can be inhibited. With IC50 slightly higher than 10 μM, increasing concentrations (100 μM, 1 mM and 2.5 mM) had shown to exhibit toxicity effects. The best concentration from this study is 10 μM with Hill slope of 0.1799.
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http://dx.doi.org/10.21315/mjms2018.25.1.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862056PMC
February 2018

Detection of somatic mutations in the mitochondrial DNA control region D-loop in brain tumors: The first report in Malaysian patients.

Oncol Lett 2017 Nov 28;14(5):5179-5188. Epub 2017 Aug 28.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan 16150, Malaysia.

Although the role of nuclear-encoded gene alterations has been well documented in brain tumor development, the involvement of the mitochondrial genome in brain tumorigenesis has not yet been fully elucidated and remains controversial. The present study aimed to identify mutations in the mitochondrial DNA (mtDNA) control region D-loop in patients with brain tumors in Malaysia. A mutation analysis was performed in which DNA was extracted from paired tumor tissue and blood samples obtained from 49 patients with brain tumors. The D-loop region DNA was amplified using the PCR technique, and genetic data from DNA sequencing analyses were compared with the published revised Cambridge sequence to identify somatic mutations. Among the 49 brain tumor tissue samples evaluated, 25 cases (51%) had somatic mutations of the mtDNA D-loop, with a total of 48 mutations. Novel mutations that had not previously been identified in the D-loop region (176 A-deletion, 476 C>A, 566 C>A and 16405 A-deletion) were also classified. No significant associations between the D-loop mutation status and the clinicopathological parameters were observed. To the best of our knowledge, the current study presents the first evidence of alterations in the mtDNA D-loop regions in the brain tumors of Malaysian patients. These results may provide an overview and data regarding the incidence of mitochondrial genome alterations in Malaysian patients with brain tumors. In addition to nuclear genome aberrations, these specific mitochondrial genome alterations may also be considered as potential cancer biomarkers for the diagnosis and staging of brain cancers.
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http://dx.doi.org/10.3892/ol.2017.6851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652220PMC
November 2017

The Effect of 4-hydroxybenzaldehyde on the γ-aminobutyric Acid Type A Receptor.

Malays J Med Sci 2017 Mar 14;24(2):94-99. Epub 2017 Apr 14.

Center for Neuroscience Services and Research, Universiti Sains Malaysia, Jalan Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

The αβγ subtype of GABA receptors is the most commonly found GABA receptor subtype in the mammalian cortex and hippocampus. It is expressed heterologously in the Xenopus laevis oocyte as a αβγS/L subtype for application as an in vitro model for the screening of compounds that modulate receptor activities. In fact, 4-hydroxybenzaldehyde (4-HB) has been identified as one of the major components in Dendrocalamus asper bamboo shoots in our previous study, and the current study showed that at 101.7 μM, 4-HB significantly reduced the GABA-induced chloride current of GABA receptors expressed on Xenopus oocytes, indicating a possible GABAergic antagonistic effect at high concentrations.
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http://dx.doi.org/10.21315/mjms2017.24.2.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566067PMC
March 2017

Association of The IDH1 C.395G>A (R132H) Mutation with Histological Type in Malay Brain Tumors

Asian Pac J Cancer Prev 2016 12 1;17(12):5195-5201. Epub 2016 Dec 1.

Department of Neurosciences School of Medical Sciences Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan MALAYSIA. Email:

Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.
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http://dx.doi.org/10.22034/APJCP.2016.17.12.5195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454658PMC
December 2016

Updates on Knowledge, Attitude and Preventive Practices on Tuberculosis among Healthcare Workers.

Malays J Med Sci 2016 Nov 7;23(6):25-34. Epub 2016 Dec 7.

Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran", Avenida Vasco de Quiroga No. 15, Sección 16, Mexico, D.F. 14000.

Ranking as the most communicable disease killer worldwide, tuberculosis, has accounted with a total of 9.6 million new tuberculosis cases with 1.5 million tuberculosis-related deaths reported globally in 2014. Tuberculosis has remain as an occupational hazard for healthcare workers since 1920s and due to several tuberculosis outbreaks in healthcare settings in the early 1990s, the concern about the transmission to both patients and healthcare workers has been raised. Healthcare workers have two to three folds greater the risk of active tuberculosis than the general population. Several studies on knowledge, attitude and practices on tuberculosis among healthcare workers worldwide have revealed that majority of the participated healthcare workers had good knowledge on tuberculosis. Most of the healthcare workers from South India and South Africa also reported to have positive attitude whereas a study in Thailand reported that most of the healthcare providers have negative attitude towards tuberculosis patients. Nevertheless, majority of the healthcare workers have low level of practice on tuberculosis prevention. An improved communication between healthcare workers and the patients as well as their families is the key to better therapeutic outcomes with good knowledge, attitude and preventive practice towards tuberculosis.
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http://dx.doi.org/10.21315/mjms2016.23.6.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181989PMC
November 2016

Mouse model of intracerebellar haemorrhage.

Behav Brain Res 2016 10 17;312:374-84. Epub 2016 Jun 17.

Center for Neuroscience Services and Research(P3Neuro), Universiti Sains Malaysia, Jalan Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kota Bharu, Kelantan,Malaysia; Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Jalan Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kota Bharu, Kelantan, Malaysia. Electronic address:

The present study aimed to investigate the behavior and neuronal morphological changes in the perihaemorrhagic tissue of the mouse intracerebellar haemorrhage experimental model. Adult male Swiss albino mice were stereotactically infused with collagenase type VII (0.4U/μl of saline) unilaterally in to the cerebellum, following anaesthesia. Motor deficits were assessed using open field and composite score for evaluating the mouse model of cerebellar ataxia at 1, 3, 7, 14 and 21 days after collagenase infusion. The animals were sacrificed at the same time interval for evaluation of perihaematomal neuronal degeneration using haematoxylin and eosin staining and Annexin V-FITC/Propidium iodide assay. At the end of the study, it was found that infusion of 0.4U collagenase produces significant locomotor and ataxic deficit in the mice especially within the first week post surgery, and that this gradually improved within three weeks. Neuronal degeneration evident by cytoplasmic shrinkage and nuclear pyknosis was observed at the perihaematomal area after one day; especially at 3 and 7 days post haemorrhage. By 21 days, both the haematoma and degenerating neurons in the perihaematomal area were phagocytosed and the remaining neuronal cells around the scar tissue appeared normal. Moreover, Annexin-V/propidium iodide-positive cells were observed at the perihaematomal area at 3 and 7 days implying that the neurons likely die via apoptosis. It was concluded that a population of potentially salvageable neurons exist in the perihaematomal area after cerebellar haemorrhage throughout a wide time window that could be amenable to treatment.
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http://dx.doi.org/10.1016/j.bbr.2016.06.034DOI Listing
October 2016

Role of mitochondrial DNA mutations in brain tumors: A mini-review.

J Cancer Res Ther 2015 Jul-Sep;11(3):535-44

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Brain tumor is molecularly a heterogeneous group of diseases, and genetic factors seem to play a crucial role in its genesis. Even though multiple alterations in the nuclear-encoded genes such as tumor suppressor and oncogenes are believed to play a key role in brain tumorigenesis, the involvement of the mitochondrial genome to this event remains controversial to date. Mitochondrial DNA (mtDNA) has been suspected to be associated with the carcinogenesis because of its high sensitivity to mutations and inefficient repair mechanisms in comparison to nuclear DNA. Thus, defects in mtDNA could also lead to the development of brain tumor. By virtue of their clonal nature and high copy number, mtDNA mutations may provide a new effective molecular biomarker for the cancer detection. It has been suggested that establishing mtDNA defective pattern might be useful in cancer diagnostics and detection, the prognosis of cancer outcome, and/or the response to certain treatments. This mini-review gives a brief overview on the several aspects of mtDNA, with a particular focus on its role in tumorigenesis and progression of brain tumor. Understanding the role of mitochondria and brain tumor development could potentially translate into therapeutic strategies for patients with these tumors.
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http://dx.doi.org/10.4103/0973-1482.161925DOI Listing
August 2016

Expression profile of genes modulated by Aloe emodin in human U87 glioblastoma cells.

Asian Pac J Cancer Prev 2014 ;15(11):4499-505

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia E-mail :

Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
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http://dx.doi.org/10.7314/apjcp.2014.15.11.4499DOI Listing
March 2015

Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial membrane potential disruption in human U87 malignant glioma cells by aloe emodin.

J Asian Nat Prod Res 2013 Sep 22;15(9):1003-12. Epub 2013 Jul 22.

a Department of Neurosciences , Universiti Sains Malaysia , Kubang Kerian Kelantan 16150 , Malaysia.

Aloe emodin, one of the active compounds found in Aloe vera leaves, plays an important role in the regulation of cell growth and death. It has been reported to promote the anti-cancer effects in various cancer cells by inducing apoptosis. However, the mechanism of inducing apoptosis by this agent is poorly understood in glioma cells. This research is to investigate the apoptosis and cell cycle arrest inducing by aloe emodin on U87 human malignant glioma cells. Aloe emodin showed a time- and dose-dependent inhibition of U87 cells proliferation and decreased the percentage of viable U87 cells via the induction of apoptosis. Characteristic morphological changes, such as the formation of apoptotic bodies, were observed with confocal microscope by Annexin V-FITC/PI staining, supporting our viability study and flow cytometry analysis results. Our data also demonstrated that aloe emodin arrested the cell cycle in the S phase and promoted the loss of mitochondrial membrane potential in U87 cells that indicated the early event of the mitochondria-induced apoptotic pathway.
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http://dx.doi.org/10.1080/10286020.2013.818982DOI Listing
September 2013

De-novo mutations and genetic variation in the SCN1A gene in Malaysian patients with generalized epilepsy with febrile seizures plus (GEFS+).

Epilepsy Res 2012 Dec 1;102(3):210-5. Epub 2012 Sep 1.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Generalized epilepsy with febrile seizures plus (GEFS+) comprises a group of clinically and genetically heterogeneous epilepsy syndrome. Here, we provide the first report of clinical presentation and mutational analysis of SCN1A gene in 36 Malaysian GEFS+ patients. Mutational analysis of SCN1A gene revealed twenty seven sequence variants (missense mutation and silent polymorphism also intronic polymorphism), as well as 2 novel de-novo mutations were found in our patients at coding regions, c.5197A>G (N1733D) and c.4748A>G (H1583R). Our findings provide potential genetic insights into the pathogenesis of GEFS+ in Malaysian populations concerning the SCN1A gene mutations.
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http://dx.doi.org/10.1016/j.eplepsyres.2012.08.004DOI Listing
December 2012

What We Know about the Molecular Genetics of Central Nervous System (CNS) Tumours in Malaysia.

Malays J Med Sci 2004 Jan;11(1):37-43

Human Genome Center, Department of Neurosciences.

The new millennium has been regarded as a genomic era. A lot of researchers and pathologists are beginning to understand the scientific basis of molecular genetics and relates with the progression of the diseases. Central nervous system (CNS) tumours are among the most rapidly fatal of all cancers. It has been proposed that the progression of malignant tumours may result from multi-step of genetic alterations, including activation of oncogenes, inactivation of tumour suppressor genes and also the presence of certain molecular marker such as telomerase activity. In this paper, we review some recent data from the literature, including our own studies, on the molecular genetics analysis in CNS tumours. Our studies have shown that two types of tumour suppressor genes, p53 and PTEN were involved in the development of these tumours but not in p16 gene among the patients from Hospital Universiti Sains Malaysia (HUSM). Telomerase activity also has been detected in various types of CNS tumours. Thus, it is important to assemble all data which related to this study and may provide as a vital information in a new approach to neuro-oncology studies in Malaysia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438149PMC
January 2004

Molecular genetic analysis of anaplastic pleomorphic xanthoastrocytoma.

Asian J Surg 2003 Apr;26(2):120-5

Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

A case of pleomorphic xanthoastrocytoma in a 10-year-old Malay boy is reported. The patient presented with headache and epilepsy. On computed tomography, a ring-enhancing low-density lesion was observed in the left fronto-temporal area. During surgery, a cystic tumour containing serous fluid was found and almost totally removed. Histologically, the tumour exhibited marked pleomorphism of oval and spindle-shaped cells intermixed with uni- and multinucleated giant cells, and xanthomatous cells with foamy cytoplasm. The tumour displayed pericellular reticulin and periodic acid-Schiff positive granules. Focally, six mitotic characters per 10 high-power fields were seen, and necrosis was confined only to the inner lining of the cyst. Mutational analysis showed that a frameshift mutation (a 4-bp deletion) in the p53 gene had occurred in codons 273 and 274 of exon 8. No mutation was detected in the p16 gene. No allelic loss and/or loss of heterozygosity were observed on chromosome 10 using microsatellite marker D105532. The patient was treated with postoperative radiotherapy because of histological anaplasia and the presence of residual tumour. The patient showed marked neurological recovery after a follow-up period of 2 years.
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http://dx.doi.org/10.1016/S1015-9584(09)60233-5DOI Listing
April 2003