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  1. Mohamed Yusoff AA, Mohd Khair SZN, Wan Abdullah WS, Abd Radzak SM, Abdullah JM
    J Cancer Res Ther, 2020 12 22;16(6):1517-1521.
    PMID: 33342822 DOI: 10.4103/jcrt.JCRT_1132_16
    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.

  2. Mohamed Yusoff AA, Zulfakhar FN, Mohd Khair SZN, Wan Abdullah WS, Abdullah JM, Idris Z
    Brain Tumor Res Treat, 2018 Apr;6(1):31-38.
    PMID: 29717568 DOI: 10.14791/btrt.2018.6.e5
    BACKGROUND: Mitochondria are major cellular sources of reactive oxygen species (ROS) generation which can induce mitochondrial DNA damage and lead to carcinogenesis. The mitochondrial 10398A>G alteration in NADH-dehydrogenase subunit 3 (ND3) can severely impair complex I, a key component of ROS production in the mitochondrial electron transport chain. Alteration in ND3 10398A>G has been reported to be linked with diverse neurodegenerative disorders and cancers. The aim of this study was to find out the association of mitochondrial ND3 10398A>G alteration in brain tumor of Malaysian patients.

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

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

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

  3. Alawiah A, Bauk S, Marashdeh MW, Nazura MZ, Abdul-Rashid HA, Yusoff Z, et al.
    Appl Radiat Isot, 2015 Oct;104:197-202.
    PMID: 26188687 DOI: 10.1016/j.apradiso.2015.07.011
    In regard to thermoluminescence (TL) applied to dosimetry, in recent times a number of researchers have explored the role of optical fibers for radiation detection and measurement. Many of the studies have focused on the specific dopant concentration, the type of dopant and the fiber core diameter, all key dependencies in producing significant increase in the sensitivity of such fibers. At doses of less than 1 Gy none of these investigations have addressed the relationship between dose response and TL glow peak behavior of erbium (Er)-doped silica cylindrical fibers (CF). For x-rays obtained at accelerating potentials from 70 to 130 kVp, delivering doses of between 0.1 and 0.7 Gy, present study explores the issue of dose response, special attention being paid to determination of the kinetic parameters and dosimetric peak properties of Er-doped CF. The effect of dose response on the kinetic parameters of the glow peak has been compared against other fiber types, revealing previously misunderstood connections between kinetic parameters and radiation dose. Within the investigated dose range there was an absence of supralinearity of response of the Er-doped silica CF, instead sub-linear response being observed. Detailed examination of glow peak response and kinetic parameters has thus been shown to shed new light of the rarely acknowledged issue of the limitation of TL kinetic model and sub-linear dose response of Er-doped silica CF.
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