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Fulltext Molecular genetic analysis of a supratentorial haemangioblastoma in a non-Von Hippel Lindau patient

Zamzuri I, Ghazali MM, Zainuddin N, Sulong S, Samarendra SM, Yusoff AAM, et al.

Med J Malaysia, 2005 Aug;60(3):360-3.
PMID: 16379193

We describe a rare tumor site in a 46 year old man who presented with a two week history of headache. Physical examination revealed bilateral papilloedema with no other localizing signs. Computed Tomographic Scan as well as Magnetic Resonance Imaging of the brain revealed a lesion with a dura tail located adjacent to the falx cerebri of the right frontal lobe. This lesion was not invading the inner table of the skull base. A tumor blush was seen on angiogram. There were no abnormalities on CT scan of the abdomen and fundoscopy was normal. Intraoperatively a vascular tumor not attached to the dura was noted and removed totally. Histopathological examination was typical of a hemangioblastoma. Analysis revealed no mutations of the VHL gene in 5 regions, exon 5-8 of the p53 gene, exon 1-2 of the p16 gene and exon 5,6 and 8 of the PTEN gene. This is the first case report of a supratentorial hemangioblastoma in a non-Von Hippel Lindau patient with genetic evidence.
Fulltext A comprehensive overview of mitochondrial DNA 4977-bp deletion in cancer studies

Yusoff AAM, Abdullah WSW, Khair SZNM, Radzak SMA

Oncol Rev, 2019 Jan 14;13(1):409.
PMID: 31044027 DOI: 10.4081/oncol.2019.409

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 (mDNA4977) 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 mDNA4977 formation and a detailed summary about mDNA4977 reported in various types of cancers. The current knowledges of mDNA4977 as a prognostic and predictive marker are also discussed.
Fulltext Roles of EphA2 Receptor in Angiogenesis Signaling Pathway of Glioblastoma Multiforme

Baharuddin WNA, Yusoff AAM, Abdullah JM, Osman ZF, Ahmad F

Malays J Med Sci, 2018 Nov;25(6):22-27.
PMID: 30914876 DOI: 10.21315/mjms2018.25.6.3

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

Chong PN, Sangu M, Huat TJ, Reza F, Begum T, Yusoff AAM, et al.

Malays J Med Sci, 2018 Nov;25(6):28-45.
PMID: 30914877 MyJurnal DOI: 10.21315/mjms2018.25.6.4

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 (GABAA) subunit α-1 (GABRA1), tyrosine receptor kinase B (TrkB), and inositol trisphosphate receptor (IP3R/IP3) levels.
Results: The results revealed significantly decreased and increased immunoreactivity changes in TrkB (a BDNF receptor) and IP3R, 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.
Fulltext The Effect of 4-hydroxybenzaldehyde on the γ-aminobutyric Acid Type A Receptor

Zhang J, Mohamad H, Wong JH, Bilal M, Ismail AHB, Lloyd AJ, et al.

Malays J Med Sci, 2017 Mar;24(2):94-99.
PMID: 28894409 DOI: 10.21315/mjms2017.24.2.12

The α1β2γ2 subtype of GABAA receptors is the most commonly found GABAA receptor subtype in the mammalian cortex and hippocampus. It is expressed heterologously in the Xenopus laevis oocyte as a α1β2γ2S/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 GABAA receptors expressed on Xenopus oocytes, indicating a possible GABAergic antagonistic effect at high concentrations.