Displaying publications 21 - 40 of 53 in total

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  1. Mustafa Z, Shamsuddin HS, Ideris A, Ibrahim R, Jaafar H, Ali AM, et al.
    Biomed Res Int, 2013;2013:248507.
    PMID: 23586025 DOI: 10.1155/2013/248507
    Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer including glioma. Nevertheless, the capability of NDV infection on heterogeneous glioma tissue in a cerebrospinal fluid atmosphere has never been reported. Recently, Rac1 is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV. Rac1 is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression. Rac1 knockdown leads to significant inhibition of viral replication. In this work, we demonstrated that NDV treatment led to significant reduction of tumour tissue viability of freshly isolated heterogeneous human brain tumour slice, known as an ex vivo glioma acute slice (EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation of Rac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue.
    Matched MeSH terms: Glioma/genetics*; Glioma/therapy*
  2. Zainuddin N, Jaafar H, Isa MN, Abdullah JM
    PMID: 16124450
    Frequent loss of heterozygosity (LOH) and mutations of the tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) have been found in sporadic gliomas. The most documented regions of allelic losses include 9p21, 10q23-25 and 17p1 3 whereas PTEN aberrations are preferentially found in glioblastoma multiformes. This research aimed to detect the incidence of allelic losses on chromosomes 10q, 9p, 17p and 13q and mutations on exons 5, 6 and 8 of PTEN in malignant gliomas. Malignant glioma specimens obtained were classified histopathologically according to the WHO criteria. Each tumor was then subjected to polymerase chain reaction (PCR)-LOH analysis using microsatellite markers and single-stranded conformational polymorphism (SSCP) analysis. Twelve of 23 (52%) malignant glioma cases showed allelic losses whereas 7 of 23 (30%) samples showed aberrant band patterns and mutations of PTEN. Four of these cases showed LOH in 10q23 and mutations of PTEN. The data on LOH indicated the involvement of different genes in the genesis of glioma whereas mutations of PTEN indicated the role of PTEN tumor suppressor gene in the progression of glioma in Malay population.
    Matched MeSH terms: Glioma/genetics*; Glioma/epidemiology
  3. Ramli N, Khairy AM, Seow P, Tan LK, Wong JH, Ganesan D, et al.
    Eur Radiol, 2016 Jul;26(7):2019-29.
    PMID: 26560718 DOI: 10.1007/s00330-015-4045-0
    OBJECTIVES: We evaluated the feasibility of using chemical shift gradient-echo (GE) in- and opposed-phase (IOP) imaging to grade glioma.

    METHODS: A phantom study was performed to investigate the correlation of (1)H MRS-visible lipids with the signal loss ratio (SLR) obtained using IOP imaging. A cross-sectional study approved by the institutional review board was carried out in 22 patients with different glioma grades. The patients underwent scanning using IOP imaging and single-voxel spectroscopy (SVS) using 3T MRI. The brain spectra acquisitions from solid and cystic components were obtained and correlated with the SLR for different grades.

    RESULTS: The phantom study showed a positive linear correlation between lipid quantification at 0.9 parts per million (ppm) and 1.3 ppm with SLR (r = 0.79-0.99, p glioma grades using optimal cut-points of 0.064 and 0.086 with classification probabilities for grade II (SII = 1), grade III (SIII = 0.50) and grade IV (SIV = 0.89).

    CONCLUSIONS: The results underscore the lipid quantification differences in grades of glioma and provide a more comprehensive characterization by using SLR in chemical shift GE IOP imaging. SLR in IOP sequence demonstrates good performance in glioma grading.

    KEY POINTS: • Strong correlation was seen between lipid concentration and SLR obtained using IOP • IOP sequence demonstrates significant differences in signal loss within the glioma grades • SLR at solid tumour portions was the best measure for differentiation • This sequence is applicable in a research capacity for glioma staging armamentarium.

    Matched MeSH terms: Glioma/classification; Glioma/pathology
  4. Ward HA, Gayle A, Jakszyn P, Merritt M, Melin B, Freisling H, et al.
    Eur J Cancer Prev, 2018 Jul;27(4):379-383.
    PMID: 27845960 DOI: 10.1097/CEJ.0000000000000331
    Diets high in red or processed meat have been associated positively with some cancers, and several possible underlying mechanisms have been proposed, including iron-related pathways. However, the role of meat intake in adult glioma risk has yielded conflicting findings because of small sample sizes and heterogeneous tumour classifications. The aim of this study was to examine red meat, processed meat and iron intake in relation to glioma risk in the European Prospective Investigation into Cancer and Nutrition study. In this prospective cohort study, 408 751 individuals from nine European countries completed demographic and dietary questionnaires at recruitment. Multivariable Cox proportional hazards models were used to examine intake of red meat, processed meat, total dietary iron and haem iron in relation to incident glioma. During an average follow-up of 14.1 years, 688 incident glioma cases were diagnosed. There was no evidence that any of the meat variables (red, processed meat or subtypes of meat) or iron (total or haem) were associated with glioma; results were unchanged when the first 2 years of follow-up were excluded. This study suggests that there is no association between meat or iron intake and adult glioma. This is the largest prospective analysis of meat and iron in relation to glioma and as such provides a substantial contribution to a limited and inconsistent literature.
    Matched MeSH terms: Glioma/etiology; Glioma/epidemiology*
  5. Ponnampalam SN, Kamaluddin NR, Zakaria Z, Matheneswaran V, Ganesan D, Haspani MS, et al.
    Oncol Rep, 2017 Jan;37(1):10-22.
    PMID: 28004117 DOI: 10.3892/or.2016.5285
    The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.
    Matched MeSH terms: Glioma/blood; Glioma/genetics*; Glioma/pathology*
  6. Das, Priscilla, Naing, Nyi Nyi, Nadiah Wan-Arfah, Noorjan, KON, Yee, Cheng Kueh, Rasalingam, Kantha
    MyJurnal
    Introduction: Astrocytic gliomas are the most common and lethal intracranial brain tumours and rely on angiogenesis for the tumour development. Endothelial progenitor cells (EPCs) contribute to the angiogenesis of glioma tumour. Objectives: The study aimed to investigate the matured circulating endothelial cells population in the peripheral blood mononuclear cells (PBMCs) and its associations with tissue resident angiogenic cells in astrocytic glioma patients. Methods: A total of 22 astrocytic glioma patients were recruited from Hospital Universiti Sains Malaysia. Tumour were sliced and stained with CD133+ and VEGFA+ for angiogenic cells (n=22). The circulating (CD133-/VEGFR2+) matured endothelial cells in PBMCs (n=22) were quantified using FACS. The paired t-test and Pearson correlation test were used for the data analysis. Results: The angiogenic cells in brain tumour tissue were significantly higher compared to adjacent normal brain tissue (median 1.07±0.96% vs. median 0.69±0.68%; Wilcoxon signed rank test Z=-3.100; p=0.002). Positive correlation was found between the angiogenic cells of brain tumour tissue and adjacent normal brain tissue (Spearman’s rho correlation test, r=0.56; p=0.007). Significant positive correlation was found between matured endothelial cells in peripheral circulating systems and angiogenic cells in tumour of astrocytic glioma patients (Pearson correlation test, r=0.60, p=0.003).Conclusion:The findings of the study give support to the possible roles of EPCs in astrocytic glioma patients. Thus targeting tissue resident angiogenic cells and matured circulating endothelial cells by antiangiogenic treatment might be useful to prevent the tumour growth.
    Matched MeSH terms: Glioma
  7. Zulkarnain S, Yunus N, Kandasamy R, Zun AB, Mat Zin AA
    Asian Pac J Cancer Prev, 2020 Oct 01;21(10):3085-3091.
    PMID: 33112571 DOI: 10.31557/APJCP.2020.21.10.3085
    OBJECTIVE: Glioma is the commonest primary malignant brain tumour. Diagnosis is made based on cytology smear, frozen section and histopathological examination. Intraoperative pathological diagnosis using either cytology smear, frozen section or combination of both, plays a crucial role in patient's future management and prognosis. This study aims to determine the accuracy of cytology smear and frozen section in glioma, and to compare the difference between both techniques.

    METHODS: A cross-sectional study was conducted involving 22 cases of glioma diagnosed intraoperatively from January 2013 until August 2019 in Hospital Universiti Sains Malaysia. The selected tissues were processed for cytology smear and frozen section. The remaining tissues were proceeded for paraffin section. The diagnosis was categorized as either low-grade or high-grade glioma based on cellularity, nuclear pleomorphism, mitotic count, microvascular proliferation and necrosis. The sensitivity and specificity of frozen section and cytology smears were determined based on paraffin section being as the gold standard. The accuracy of both techniques was compared using statistical analysis.

    RESULTS: The overall sensitivity and specificity of cytology smear were 100% and 76.9%, respectively. Meanwhile, the sensitivity and specificity of frozen section were 100% and 84.6%. There was no significant difference in diagnostic accuracy between cytology smear and frozen section in glioma (p>0.05).

    CONCLUSION: Cytology smears provides an alternative method for frozen section due to good cellularity and morphology on smear. Cytology smear is rapid, inexpensive, small amount of tissue requirement and less technical demand. This finding may benefit to the hospital or treatment centres where frozen section facility is unavailable.

    Matched MeSH terms: Glioma/epidemiology; Glioma/pathology*; Glioma/surgery
  8. Das, P., Naing, N.N., Wan-Arfah, N., Noorjan, K., Kueh, Y.C., Rasalingam, K.
    JUMMEC, 2019;22(2):31-38.
    MyJurnal
    Background: Astrocytic gliomas are the most common primary brain tumors that developed from glial origin.
    The angiogenic cell population from brain tumor enhances the recruitment of circulating cancer stem cells
    homing towards tumor site.

    Objectives: This study aimed to investigate the tumor angiogenic cell population that stained with CD133+
    and VEGFA+ markers and its association with circulating cancer stem cell (CD133+/VEGFR2-) population in the
    peripheral blood mononuclear cells (PBMCs) of astrocytic glioma patients.

    Methods: A total of 22 astrocytic glioma patients from Hospital Universiti Sains Malaysia who consented to
    the study were included. Tumors (n=22) were sliced and stained with CD133+ and VEGFA+ angiogenic markers
    and counter stained with DAPI. The circulating cancer stem cells (CD133+/VEGFR2-) in PBMCs (n=22) were
    quantified using FACS based on the expression of CD133 and VEGFR2 markers. The paired t-test and Pearson
    correlation were used for the data analysis.

    Results: The percentage of angiogenic cell population was significantly higher in brain tumor compared to
    adjacent normal brain tissue (1.25 ± 0.96% vs. 0.74 ± 0.68%; paired t-test=2.855; df=21, p = 0.009). Positive
    correlation was found between the angiogenic cells of brain tumor tissue and adjacent normal brain tissue
    (Pearson correlation, r = 0.53, p = 0.011). Significant positive correlation was found between angiogenic cells
    in glioma tumor and cancer stem cells in peripheral circulating systems of astrocytic glioma patients (Pearson
    correlation, r = 0.42, p = 0.049).

    Conclusion: Angiogenic cells in the brain tumor resident promote the recruitment of circulating cancer stem cells
    homing to the tumor site and induce the proliferation and growth of the tumor in astrocytic glioma patients.
    Matched MeSH terms: Glioma
  9. Zainuddin N, Jaafar H, Isa MN, Abdullah JM
    Med J Malaysia, 2004 Oct;59(4):468-79.
    PMID: 15779579
    Loss of heterozygosity (LOH) on several loci and mutations on PTEN tumor suppressor gene (10q23.3) occur frequently in sporadic gliomas. We have performed polymerase chain reaction (PCR)-LOH analysis using microsatellite markers and single-stranded conformational polymorphism (SSCP) analysis to determine the incidence of allelic losses on chromosome 10q, 9p, 17p and 13q and mutations of exons 5, 6 and 8 of the PTEN gene in malignant gliomas. Twelve of 23 (52.2%) malignant glioma cases showed allelic losses whereas 7 of 23, (30.4%) samples showed aberrant band patterns and mutations of the PTEN gene. Four of these cases showed LOH on 10q23 and mutations of the PTEN gene. The data on LOH indicated the involvement of different genes in gliomagenesis whereas mutations of the PTEN gene indicated the role of PTEN tumor suppressor gene in the progression of glioma in Malay population.
    Matched MeSH terms: Glioma/genetics*
  10. Seow P, Narayanan V, Hernowo AT, Wong JHD, Ramli N
    Neuroimage Clin, 2018;20:531-536.
    PMID: 30167373 DOI: 10.1016/j.nicl.2018.08.003
    Objectives: This study maps the lipid distributions based on magnetic resonance imaging (MRI) in-and opposed-phase (IOP) sequence and correlates the findings generated from lipid map to histological grading of glioma.

    Methods: Forty histologically proven glioma patients underwent a standard MRI tumour protocol with the addition of IOP sequence. The regions of tumour (solid enhancing, solid non-enhancing, and cystic regions) were delineated using snake model (ITK-SNAP) with reference to structural and diffusion MRI images. The lipid distribution map was constructed based on signal loss ratio (SLR) obtained from the IOP imaging. The mean SLR values of the regions were computed and compared across the different glioma grades.

    Results: The solid enhancing region of glioma had the highest SLR for both Grade II and III. The mean SLR of solid non-enhancing region of tumour demonstrated statistically significant difference between the WHO grades (grades II, III & IV) (mean SLRII = 0.04, mean SLRIII = 0.06, mean SLRIV = 0.08, & p glioma. This technique adds to the surgical diagnostic yield by identifying biopsy targets. It can also be used as an adjunct grading tool for glioma as well as to provide information about lipidomics landscape in glioma development.

    Matched MeSH terms: Glioma/metabolism
  11. Seow P, Wong JHD, Ahmad-Annuar A, Mahajan A, Abdullah NA, Ramli N
    Br J Radiol, 2018 Dec;91(1092):20170930.
    PMID: 29902076 DOI: 10.1259/bjr.20170930
    OBJECTIVE:: The diversity of tumour characteristics among glioma patients, even within same tumour grade, is a big challenge for disease outcome prediction. A possible approach for improved radiological imaging could come from combining information obtained at the molecular level. This review assembles recent evidence highlighting the value of using radiogenomic biomarkers to infer the underlying biology of gliomas and its correlation with imaging features.

    METHODS:: A literature search was done for articles published between 2002 and 2017 on Medline electronic databases. Of 249 titles identified, 38 fulfilled the inclusion criteria, with 14 articles related to quantifiable imaging parameters (heterogeneity, vascularity, diffusion, cell density, infiltrations, perfusion, and metabolite changes) and 24 articles relevant to molecular biomarkers linked to imaging.

    RESULTS:: Genes found to correlate with various imaging phenotypes were EGFR, MGMT, IDH1, VEGF, PDGF, TP53, and Ki-67. EGFR is the most studied gene related to imaging characteristics in the studies reviewed (41.7%), followed by MGMT (20.8%) and IDH1 (16.7%). A summary of the relationship amongst glioma morphology, gene expressions, imaging characteristics, prognosis and therapeutic response are presented.

    CONCLUSION:: The use of radiogenomics can provide insights to understanding tumour biology and the underlying molecular pathways. Certain MRI characteristics that show strong correlations with EGFR, MGMT and IDH1 could be used as imaging biomarkers. Knowing the pathways involved in tumour progression and their associated imaging patterns may assist in diagnosis, prognosis and treatment management, while facilitating personalised medicine.

    ADVANCES IN KNOWLEDGE:: Radiogenomics can offer clinicians better insight into diagnosis, prognosis, and prediction of therapeutic responses of glioma.

    Matched MeSH terms: Glioma/genetics
  12. Lim WC, Marques Da Costa ME, Godefroy K, Jacquet E, Gragert L, Rondof W, et al.
    Front Immunol, 2023;14:1265469.
    PMID: 38318504 DOI: 10.3389/fimmu.2023.1265469
    The human leukocyte antigen (HLA) system is a major factor controlling cancer immunosurveillance and response to immunotherapy, yet its status in pediatric cancers remains fragmentary. We determined high-confidence HLA genotypes in 576 children, adolescents and young adults with recurrent/refractory solid tumors from the MOSCATO-01 and MAPPYACTS trials, using normal and tumor whole exome and RNA sequencing data and benchmarked algorithms. There was no evidence for narrowed HLA allelic diversity but discordant homozygosity and allele frequencies across tumor types and subtypes, such as in embryonal and alveolar rhabdomyosarcoma, neuroblastoma MYCN and 11q subtypes, and high-grade glioma, and several alleles may represent protective or susceptibility factors to specific pediatric solid cancers. There was a paucity of somatic mutations in HLA and antigen processing and presentation (APP) genes in most tumors, except in cases with mismatch repair deficiency or genetic instability. The prevalence of loss-of-heterozygosity (LOH) ranged from 5.9 to 7.7% in HLA class I and 8.0 to 16.7% in HLA class II genes, but was widely increased in osteosarcoma and glioblastoma (~15-25%), and for DRB1-DQA1-DQB1 in Ewing sarcoma (~23-28%) and low-grade glioma (~33-50%). HLA class I and HLA-DR antigen expression was assessed in 194 tumors and 44 patient-derived xenografts (PDXs) by immunochemistry, and class I and APP transcript levels quantified in PDXs by RT-qPCR. We confirmed that HLA class I antigen expression is heterogeneous in advanced pediatric solid tumors, with class I loss commonly associated with the transcriptional downregulation of HLA-B and transporter associated with antigen processing (TAP) genes, whereas class II antigen expression is scarce on tumor cells and occurs on immune infiltrating cells. Patients with tumors expressing sufficient HLA class I and TAP levels such as some glioma, osteosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft-tissue sarcoma cases may more likely benefit from T cell-based approaches, whereas strategies to upregulate HLA expression, to expand the immunopeptidome, and to target TAP-independent epitopes or possibly LOH might provide novel therapeutic opportunities in others. The consequences of HLA class II expression by immune cells remain to be established. Immunogenetic profiling should be implemented in routine to inform immunotherapy trials for precision medicine of pediatric cancers.
    Matched MeSH terms: Glioma*
  13. Abdul Rahman A, Jamal AR, Harun R, Mohd Mokhtar N, Wan Ngah WZ
    PMID: 24980711 DOI: 10.1186/1472-6882-14-213
    Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment.
    Matched MeSH terms: Glioma/drug therapy*; Glioma/pathology
  14. Muthusamy KA, Lian LH, Vairavan N, Chua KH, Waran V
    Genet. Mol. Res., 2012;11(3):2939-45.
    PMID: 22782629
    Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.
    Matched MeSH terms: Glioma/enzymology; Glioma/genetics*
  15. Ng WP, Liew BS, Idris Z, Rosman AK
    Malays J Med Sci, 2017 Mar;24(2):78-86.
    PMID: 28894407 MyJurnal DOI: 10.21315/mjms2017.24.2.10
    BACKGROUND: High grade gliomas (HGGs) are locally invasive brain tumours that carry a dismal prognosis. Although complete resection increases median survival, the difficulty in reliably demonstrating the tumour border intraoperatively is a norm. The Department of Neurosurgery, Hospital Sungai Buloh is the first public hospital in Malaysia to overcome this problem by adopting fluorescence-guided (FG) surgery using 5-aminolevulinic acid (5-ALA).

    METHODS: A total of 74 patients with histologically proven HGGs treated between January 2008 and December 2014, who fulfilled the inclusion criteria, were enrolled. Kaplan-Meier survival estimates and Cox proportional hazard regression were used.

    RESULTS: Significant longer survival time (months) was observed in the FG group compared with the conventional group (12 months versus 8 months, P < 0.020). Even without adjuvant therapy, HGG patients from FG group survived longer than those from the conventional group (8 months versus 3 months, P = 0.006). No significant differences were seen in postoperative Karnofsky performance scale (KPS) between the groups at 6 weeks and 6 months after surgery compared to pre-operative KPS. Cox proportional hazard regression identified four independent predictors of survival: KPS > 80 (P = 0.010), histology (P < 0.001), surgical method (P < 0.001) and adjuvant therapy (P < 0.001).

    CONCLUSION: This study showed a significant clinical benefit for HGG patients in terms of overall survival using FG surgery as it did not result in worsening of post-operative function outcome when compared with the conventional surgical method. We advocate a further multicentered, randomised controlled trial to support these findings before FG surgery can be implemented as a standard surgical adjunct in local practice for the benefit of HGG patients.

    Matched MeSH terms: Glioma
  16. Ngadiono E, Hardiany NS
    Malays J Med Sci, 2019 Jul;26(4):5-16.
    PMID: 31496889 DOI: 10.21315/mjms2019.26.4.2
    A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis despite growing medical advancements. Researchers have been looking for better and more effective treatments targeting the molecular pathways of gliomas due to glioblastomas' ability to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to maintaining the glioma population, which benefits from its ability to self-renew and differentiate. Recent research has reported that through the introduction of umbilical cord mesenchymal stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be downregulated. It has more currently been found out that UCMSC release extracellular vesicles (EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses literature to discuss all possible miRNAs contained within the UCMSC's EVs and to elaborate on their molecular mechanisms in halting gliomas and GSC growth. This review will also include the challenges and limitations, to account for which more in vivo research is suggested. In conclusion, this review highlights how miRNAs contained within UCMSC's EVs are able to downregulate multiple prominent pathways in the survival of gliomas.
    Matched MeSH terms: Glioma
  17. Ahmad F, Seerangan P, Mustafa MZ, Osman ZF, Abdullah JM, Idris Z
    Malays J Med Sci, 2019 Mar;26(2):30-39.
    PMID: 31447606 MyJurnal DOI: 10.21315/mjms2019.26.2.4
    Background: There has been increasing evidence showing that stingless bee honey exhibits anti-oxidant, anti-inflammatory and anti-cancer properties. Pharmacologically-active components in honey such as flavonoids and phenolic constituents are known to contribute to its medicinal benefits. To the best of our knowledge, this is the first study on evaluating anti-cancer effects of locally-produced Malaysian stingless bee honey from Heterotrigona itama sp. on malignant glioma cells.

    Methods: Proliferation and apoptosis studies of U-87 MG cells following stingless bee honey treatment were carried out using MTS assay and acridine orange/propidium iodide dual staining, respectively.

    Results: Results demonstrated time and dose-dependent cytotoxicity using 0.625%, 1.25% and 10% stingless bee honey (P < 0.05). IC50 values were calculated using cells treated with 10% stingless bee honey. It was also observed that 10% stingless bee honey induced nuclear shrinkage, chromatin condensation and nucleus fragmentation, indicating that cellular changes were consistent with the apoptotic characteristics of the cells.

    Conclusion: These data provide a good basis for further evaluation of the medicinal properties of stingless bee honey from Heterotrigona itama sp. This source of honey may serve as a potential therapy for malignant glioma.

    Matched MeSH terms: Glioma
  18. Abdullah JM, Ahmad F, Ahmad KA, Ghazali MM, Jaafar H, Ideris A, et al.
    Neurol Res, 2007 Apr;29(3):239-42.
    PMID: 17509221
    Brain tumorigenesis is a complex process involving multiple genetic alterations. Cyclin D1 and BAX genes are two of the most important regulators in controlling the normal proliferation and apoptosis of cells, respectively. In this study, we analysed the possibilities of involvement of cyclin D1 and BAX genes in the gliomagenesis.
    Matched MeSH terms: Glioma/genetics*
  19. Zhukova N, Rajagopal R, Lam A, Coleman L, Shipman P, Walwyn T, et al.
    Cancer Med, 2019 01;8(1):40-50.
    PMID: 30569607 DOI: 10.1002/cam4.1799
    In pediatric low-grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low-toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow-up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment-limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.
    Matched MeSH terms: Glioma/drug therapy*
  20. Abdul Rahman A, Mokhtar NM, Harun R, Jamal R, Wan Ngah WZ
    J Physiol Biochem, 2019 Nov;75(4):499-517.
    PMID: 31414341 DOI: 10.1007/s13105-019-00699-z
    Gamma-tocotrienol (GTT) and hydroxychavicol (HC) exhibit anticancer activity in glioma cancer cells, where the combination of GTT + HC was shown to be more effective than single agent. The aim of this study was to determine the effect of GTT + HC by measuring the cell cycle progression, migration, invasion, and colony formation of glioma cancer cells and elucidating the changes in gene expression mitigated by GTT + HC that are critical to the chemoprevention of glioma cell lines 1321N1 (grade II), SW1783 (grade III), and LN18 (grade IV) using high-throughput RNA sequencing (RNA-seq). Results of gene expression levels and alternative splicing transcripts were validated by qPCR. Exposure of glioma cancer cells to GTT + HC for 24 h promotes cell cycle arrest at G2M and S phases and inhibits cell migration, invasion, and colony formation of glioma cancer cells. The differential gene expression induced by GTT + HC clustered into response to endoplasmic reticulum (ER) stress, cell cycle regulations, apoptosis, cell migration/invasion, cell growth, and DNA repair. Subnetwork analysis of genes altered by GTT + HC revealed central genes, ATF4 and XBP1. The modulation of EIF2AK3, EDN1, and FOXM1 were unique to 1321N1, while CSF1, KLF4, and FGF2 were unique to SW1783. PLK2 and EIF3A gene expressions were only altered in LN18. Moreover, GTT + HC treatment dynamically altered transcripts and alternative splicing expression. GTT + HC showed therapeutic potential against glioma cancer as evident by the inhibition of cell cycle progression, migration, invasion, and colony formation of glioma cancer cells, as well as the changes in gene expression profiles with key targets in ER unfolded protein response pathway, apoptosis, cell cycle, and migration/invasion.
    Matched MeSH terms: Glioma/drug therapy*
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