Displaying publications 1 - 20 of 53 in total

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  1. Fulltext A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas
    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*
  2. Absence of Ras, c-myc and Epidermal Growth Factor Receptor (EGFR) Mutations in Human Gliomas and its Clinical Factors Associated with Pathological Grading After Six Years of Diagnosis in North East Malaysian Patients
    Ghazali MM, Mohd Zan MS, Yusof AA, Abdullah JM, Jaffar H, Ariff AR, et al.
    Malays J Med Sci, 2005 Jul;12(2):27-33.
    PMID: 22605955 MyJurnal
    Neoplastic transformation appears to be a multi-step process in which the normal controls of cell proliferation and cell-cell interaction are lost, thus transforming normal cells into cancer. The tumorigenic process involves the interplay between oncogenes and tumour suppressor genes. In this study, we have selected the ras family, c-myc and epidermal growth factor receptor (EGFR) genes to detect whether their abnormalities are associated with the expression and progression of glioma cases in Malay patients. We have used the polymerase chain reaction-single stranded conformation polymorphism followed by direct sequencing for the study. For the ras gene family, we screened the point mutations in codons 12 and 61 of the H-, K-, and N-ras gene; for EGFR and c-myc, we analyzed only the exon 1 in glioma samples. In mutational screening analyses of the ras family, c-myc and EGFR gene, there was no mobility shift observed in any tumour analyzed. All patterns of single stranded conformation polymorphism (SSCP) band observed in tumour samples were normal compared to those in normal samples. The DNA sequencing results in all high-grade tumours showed that all base sequences were normal. All 48 patients survived after five years of treatment. In simple logistic regression analysis, variables which were found to be significant were hemiplegia (p=0.047) and response radiotherapy (p=0.003). Hemiplegics were 25 times more likely to have high pathological grade compared to those without. Patients with vascular involvement were 5.5 times more likely to have higher pathological grade. However, these findings were not significant in multivariate analysis. Patients who had radiotherapy were nearly 14 times more likely to have higher pathological grade. Multivariate analysis revealed that patients with hemiplegia were more likely to have higher pathological grade (p= 0.008). Those with higher pathological grading were 80 times more likely to have radiotherapy (p=0.004).
    Matched MeSH terms: Glioma
  3. Fulltext Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells' Extracellular Vesicles
    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
  4. Fulltext Anti-Cancer Properties of Heterotrigona itama sp. Honey Via Induction of Apoptosis in Malignant Glioma Cells
    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
  5. Fulltext Association of ERCC1 C8092A and ERCC2 Lys751Gln polymorphisms with the risk of glioma: a meta-analysis
    Xin Y, Hao S, Lu J, Wang Q, Zhang L
    PLoS One, 2014;9(4):e95966.
    PMID: 24763305 DOI: 10.1371/journal.pone.0095966
    To comprehensively evaluate the association of ERCC1 C8092A and ERCC2 Lys751Gln polymorphisms with the risk of glioma.
    Matched MeSH terms: Glioma/ethnology; Glioma/genetics*
  6. Fulltext Association of angiogenic cells in the tumour microenvironment and the circulating matured endothelial cells in astrocytic glioma
    Das, Priscilla, Naing, Nyi Nyi, Nadiah Wan-Arfah, Noorjan, KON, Yee, Cheng Kueh, Rasalingam, Kantha
    International Medical Journal Malaysia, 2018;17(2):3-10.
    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. Association of loss of heterozygosity and PTEN gene abnormalities with paraclinical, clinical modalities and survival time of glioma patients in Malaysia
    Abdullah JM, Farizan A, Asmarina K, Zainuddin N, Ghazali MM, Jaafar H, et al.
    Asian J Surg, 2006 Oct;29(4):274-82.
    PMID: 17098662
    The pattern of allelic loss of heterozygosity (LOH) and PTEN mutations appear to be associated with the progression of gliomas leading to a decrement in the survival rate of patients. This present study was carried out to determine the LOH and PTEN mutational status in glioma patients and its association with patients' survival.
    Matched MeSH terms: Glioma/diagnosis; Glioma/genetics*; Glioma/mortality*; Glioma/pathology
  8. Fulltext Association of tumor angiogenic cells (cd133+/vegfa+) and circulating cancer stem cells (cd133+/vegfr2-) in astrocytic glioma patients
    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. Automated Brain Tumor Detection Using Machine Learning: A Bibliometric Review
    Hossain R, Ibrahim RB, Hashim HB
    World Neurosurg, 2023 Jul;175:57-68.
    PMID: 37019303 DOI: 10.1016/j.wneu.2023.03.115
    To develop a research overview of brain tumor classification using machine learning, we conducted a systematic review with a bibliometric analysis. Our systematic review and bibliometric analysis included 1747 studies of automated brain tumor detection using machine learning reported in the previous 5 years (2019-2023) from 679 different sources and authored by 6632 investigators. Bibliographic data were collected from the Scopus database, and a comprehensive bibliometric analysis was conducted using Biblioshiny and the R platform. The most productive and collaborative institutes, reports, journals, and countries were determined using citation analysis. In addition, various collaboration metrics were determined at the institute, country, and author level. Lotka's law was tested using the authors' performance. Analysis showed that the authors' publication trends followed Lotka's inverse square law. An annual publication analysis showed that 36.46% of the studies had been reported in 2022, with steady growth from previous years. Most of the cited authors had focused on multiclass classification and novel convolutional neural network models that are efficient for small training sets. A keyword analysis showed that "deep learning," "magnetic resonance imaging," "nuclear magnetic resonance imaging," and "glioma" appeared most often, proving that of the several brain tumor types, most studies had focused on glioma. India, China, and the United States were among the highest collaborative countries in terms of both authors and institutes. The University of Toronto and Harvard Medical School had the highest number of affiliations with 132 and 87 publications, respectively.
    Matched MeSH terms: Glioma*
  10. Fulltext Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas
    Chelliah SS, Paul EAL, Kamarudin MNA, Parhar I
    Molecules, 2021 Feb 22;26(4).
    PMID: 33671796 DOI: 10.3390/molecules26041169
    Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient's response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.
    Matched MeSH terms: Glioma/diagnosis; Glioma/therapy*
  11. Fulltext Cold allodynia as the presenting symptom in a case of acquired neuromyotonia (Isaacs syndrome) with multiple autoantibodies
    Goh KJ, Abdullah S, Wong WF, Yeap SS, Shahrizaila N, Tan CT
    Neurology Asia, 2014;19(4):409-412.
    MyJurnal
    We report a patient who presented with severe cold-induced allodynia and hyperhidrosis, and found to have acquired neuromyotonia (Isaacs syndrome) with high voltage-gated potassium channel (VGKC) antibody titre,positive contactin-associated protein 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) antibodies. The patient also had positive anti-dsDNA and acetylcholine receptor (AChR) antibodies without clinical features of SLE or myasthenia gravis, suggesting a strong underlying autoimmune tendency. CT thorax showed no thymoma. Her symptoms improved with intravenous immunoglobulin infusion but recurred despite maintenance oral corticosteroids and carbamazepine. She has since been on regular IVIG infusions. Cold allodynia is an unusual presentation in acquired neuromyotonia.
    Matched MeSH terms: Glioma
  12. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)
    Jim HS, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Chornokur G, et al.
    J Genet Genome Res, 2015 09 15;2(2).
    PMID: 26807442
    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10-4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.
    Matched MeSH terms: Glioma
  13. Critical role of HOX transcript antisense intergenic RNA (HOTAIR) in gliomas
    Angelopoulou E, Paudel YN, Piperi C
    J Mol Med (Berl), 2020 11;98(11):1525-1546.
    PMID: 32978667 DOI: 10.1007/s00109-020-01984-x
    Despite extensive research, gliomas are associated with high morbidity and mortality, mainly attributed to the rapid growth rate, excessive invasiveness, and molecular heterogeneity, as well as regenerative potential of cancer stem cells. Therefore, elucidation of the underlying molecular mechanisms and the identification of potential molecular diagnostic and prognostic biomarkers are of paramount importance. HOX transcript antisense intergenic RNA (HOTAIR) is a well-studied long noncoding RNA, playing an emerging role in tumorigenesis of several human cancers. A growing amount of preclinical and clinical evidence highlights the pro-oncogenic role of HOTAIR in gliomas, mainly attributed to the enhancement of proliferation and migration, as well as inhibition of apoptosis. In vitro and in vivo studies demonstrate that HOTAIR modulates the activity of specific transcription factors, such as MXI1, E2F1, ATF5, and ASCL1, and regulates the expression of cell cycle-associated genes along with related signaling pathways, like the Wnt/β-catenin axis. Moreover, it can interact with specific miRNAs, including miR-326, miR-141, miR-148b-3p, miR-15b, and miR-126-5p. Of importance, HOTAIR has been demonstrated to enhance angiogenesis and affect the permeability of the blood-tumor barrier, thus modulating the efficacy of chemotherapeutic agents. Herein, we provide evidence on the functional role of HOTAIR in gliomas and discuss the benefits of its targeting as a novel approach toward glioma treatment.
    Matched MeSH terms: Glioma/genetics*; Glioma/metabolism; Glioma/pathology; Glioma/therapy
  14. Demographic study of brain tumour in a neurosurgical department in Terengganu, Malaysia
    Othman AK, Udin N, Shab MS, Hamzah NA, Mat Azmi IS, Naing NN
    Med J Malaysia, 2020 11;75(6):705-709.
    PMID: 33219181
    INTRODUCTION: Brain tumour (BT) is a tremendous burden on patients, families as well as the surrounding communities, especially the healthcare services. It can be classified into either a benign slow growing tumour (non-cancerous) and malignant tumour (cancerous). The purpose of this study was to determine the incidence and pattern of brain tumour admitted to the Neurosurgery Department in Hospital Sultanah Nurzahirah (HSNZ), Terengganu, Malaysia.

    METHODS: This is a retrospective study of incidence and pattern of BT admitted to the Neurosurgery Department in HSNZ. Data was collected from the yearly census of BT registered from 2013 to 2018.

    RESULTS: A total number of 386 new cases of primary BT were registered. The number of cases of BT was found to be lowest among children (0 to 10 years old) with only 4.4% but at peak among elderly aged between 51 to 60 years old (26.2%). As for gender, males constituted about 44.5% (n=172) whereas females accounted for 55.5% (n= 214) of the cases. In total, meningioma was found to have the highest incidence (27.2%) followed by metastases brain tumour (18.1%) and glioma (17.4%).

    CONCLUSIONS: This study has shown that the incidence of BT was led by meningioma which had a high prevalence among the elderly population, followed by metastasis BT and gliomas.

    Matched MeSH terms: Glioma
  15. Fulltext Development of a 3D Tumor Spheroid Model from the Patient's Glioblastoma Cells and Its Study by Metabolic Fluorescence Lifetime Imaging
    Yuzhakova DV, Lukina MM, Sachkova DA, Yusubalieva GM, Baklaushev VP, Mozherov AM, et al.
    Sovrem Tekhnologii Med, 2023;15(2):28-38.
    PMID: 37389023 DOI: 10.17691/stm2023.15.2.03
    Patient-specific in vitro tumor models are a promising platform for studying the mechanisms of oncogenesis and personalized selection of drugs. In case of glial brain tumors, development and use of such models is particularly relevant as the effectiveness of such tumor treatment remains extremely unsatisfactory. The aim of the study was to develop a model of a 3D tumor glioblastoma spheroid based on a patient's surgical material and to study its metabolic characteristics by means of fluorescence lifetime imaging microscopy of metabolic coenzymes.

    MATERIALS AND METHODS: The study was conducted with tumor samples from patients diagnosed with glioblastoma (Grade IV). To create spheroids, primary cultures were isolated from tumor tissue samples; the said cultures were characterized morphologically and immunocytochemically, and then planted into round-bottom ultra low-adhesion plates. The number of cells for planting was chosen empirically. The characteristics of the growth of cell cultures were compared with spheroids from glioblastomas of patients with U373 MG stable line of human glioblastoma. Visualization of autofluorescence of metabolic coenzymes of nicotinamide adenine dinucleotide (phosphate) NAD(P)H and flavin adenine dinucleotide (FAD) in spheroids was performed by means of an LSM 880 laser scanning microscope (Carl Zeiss, Germany) with a FLIM module (Becker & Hickl GmbH, Germany). The autofluorescence decay parameters were studied under normoxic and hypoxic conditions (3.5% О2).

    RESULTS: An original protocol for 3D glioblastoma spheroids cultivation was developed. Primary glial cultures from surgical material of patients were obtained and characterized. The isolated glioblastoma cells had a spindle-shaped morphology with numerous processes and a pronounced granularity of cytoplasm. All cultures expressed glial fibrillary acidic protein (GFAP). The optimal seeding dose of 2000 cells per well was specified; its application results in formation of spheroids with a dense structure and stable growth during 7 days. The FLIM method helped to establish that spheroid cells from the patient material had a generally similar metabolism to spheroids from the stable line, however, they demonstrated more pronounced metabolic heterogeneity. Cultivation of spheroids under hypoxic conditions revealed a transition to a more glycolytic type of metabolism, which is expressed in an increase in the contribution of the free form of NAD(P)H to fluorescence decay.

    CONCLUSION: The developed model of tumor spheroids from patients' glioblastomas in combination with the FLIM can serve as a tool to study characteristics of tumor metabolism and develop predictive tests to evaluate the effectiveness of antitumor therapy.

    Matched MeSH terms: Glioma*
  16. Diagnostic Accuracy of Cytology Smear and Frozen Section in Glioma
    Mat Zin AA, Zulkarnain S
    Asian Pac J Cancer Prev, 2019 Feb 26;20(2):321-325.
    PMID: 30803189
    Glioma is the commonest primary intracranial tumour and it has been the most predominant tumour in many studies.
    It accounts for 24.7% of all primary brain tumour and 74.6% of malignant brain tumour. Intraoperative diagnosis
    plays a crucial role in determining the patient management. Frozen section has been the established technique in
    providing rapid and accurate intraoperative diagnosis. However due to some disadvantages like ice crystal artefact,
    high expenditure and requirement of skilled technician, there is increase usage of cytology smear either replacing or
    supplementing frozen section technique. The aim of this review is to determine the diagnostic accuracy of cytology
    smear and frozen section in glioma and to see whether there is significant difference between those techniques. The
    overall diagnostic accuracy for frozen section in glioma ranging from 78.4% to 95% while for cytology smear, the
    diagnostic accuracy ranging from 50% to 100%. Based on certain literatures, no statistically difference was observed
    in diagnostic accuracy of cytology smear and frozen section. Thus, cytology smear provides an alternative method in
    establishing intraoperative diagnosis. Both cytology smear and frozen section are complimentary to each other. It is
    recommended to use both techniques to improve the diagnostic accuracy in addition with adequate knowledge, clinical
    history, neuroimaging and intraoperative findings.
    Matched MeSH terms: Glioma/diagnosis*
  17. Fulltext Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers
    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*
  18. Fulltext Emerging Pathogenic and Prognostic Significance of Paired Box 3 (PAX3) Protein in Adult Gliomas
    Angelopoulou E, Paudel YN, Piperi C
    Transl Oncol, 2019 Jul 25;12(10):1357-1363.
    PMID: 31352198 DOI: 10.1016/j.tranon.2019.07.001
    Gliomas present the most common type of brain tumors in adults, characterized by high morbidity and mortality. In search of potential molecular targets, members of paired box (PAX) family have been found expressed in neural crest cells, regulating their proliferation, apoptosis, migration and differentiation. Recently, PAX3 overexpression has been implicated in glioma tumorigenesis by enhancing proliferation, increasing invasiveness and inducing resistance to apoptosis of glioma cells, while maintaining brain glioma stem cells (BGSCs) stemness. Although the oncogenic potential of PAX3 in gliomas is still under investigation, experimental evidence suggests that PAX3 function is mainly mediated through the canonical and non-canonical Wnt signaling pathway as well as through its interaction with GFAP and p53 proteins. In addition, PAX3 may contribute to the chemoresistance of glioma cells and modulates the effectiveness of novel experimental therapies. Further evidence indicates that PAX3 may represent a novel diagnostic and prognostic biomarker for gliomas, facilitating personalized treatment. This review addresses the emerging role of PAX3 in glioma diagnosis, prognosis and treatment, aiming to shed more light on the underlying molecular mechanisms that could lead to more effective treatment approaches.
    Matched MeSH terms: Glioma
  19. Fulltext Emerging therapeutic potential of anti-psychotic drugs in the management of human glioma: A comprehensive review
    Kamarudin MNA, Parhar I
    Oncotarget, 2019 Jun 11;10(39):3952-3977.
    PMID: 31231472 DOI: 10.18632/oncotarget.26994
    Despite numerous advancements in the last decade, human gliomas such as astrocytoma and glioblastoma multiforme have the worst prognoses among all cancers. Anti-psychotic drugs are commonly prescribed to treat mental disorders among cancer patients, and growing empirical evidence has revealed their antitumor, anti-metastatic, anti-angiogenic, anti-proliferative, chemo-preventive, and neo-adjuvant efficacies in various in vitro, in vivo, and clinical glioma models. Anti-psychotic drugs have drawn the attention of physicians and researchers owing to their beneficial effects in the prevention and treatment of gliomas. This review highlights data on the therapeutic potential of various anti-psychotic drugs as anti-proliferative, chemopreventive, and anti-angiogenic agents in various glioma models via the modulation of upstream and downstream molecular targets involved in apoptosis, autophagy, oxidative stress, inflammation, and the cell cycle in in vitro and in vivo preclinical and clinical stages among glioma patients. The ability of anti-psychotic drugs to modulate various signaling pathways and multidrug resistance-conferring proteins that enhance the efficacy of chemotherapeutic drugs with low side-effects exemplifies their great potential as neo-adjuvants and potential chemotherapeutics in single or multimodal treatment approach. Moreover, anti-psychotic drugs confer the ability to induce glioma into oligodendrocyte-like cells and neuronal-like phenotype cells with reversal of epigenetic alterations through inhibition of histone deacetylase further rationalize their use in glioma treatment. The improved understanding of anti-psychotic drugs as potential chemotherapeutic drugs or as neo-adjuvants will provide better information for their use globally as affordable, well-tolerated, and effective anticancer agents for human glioma.
    Matched MeSH terms: Glioma
  20. Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial membrane potential disruption in human U87 malignant glioma cells by aloe emodin
    Ismail S, Haris K, Abdul Ghani AR, Abdullah JM, Johan MF, Mohamed Yusoff AA
    J Asian Nat Prod Res, 2013 Sep;15(9):1003-12.
    PMID: 23869465 DOI: 10.1080/10286020.2013.818982
    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.
    Matched MeSH terms: Glioma
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