Ependymomas are glial tumors derived from differentiated Background: ependymal cells. In contrast to other types of brain tumors, histological grading is not a good prognostic marker for these tumors. In order to determine genomic changes in an anaplastic ependymoma, we analyzed its mutation patterns by next generation sequencing (NGS).Tumor DNA was sequenced using an Ion PI v3 chip on Ion PubMed Abstract | Publisher Full Text | Free Full Text 3. Wesseling P, Capper D: WHO 2016 Classification of gliomas. Neuropathol Appl Neurobiol. 2018; 44(2): 139-150. PubMed Abstract | Publisher Full Text 4. Ostrom QT, Gittleman H, Fulop J, et al.: CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol. 2015; 17 Suppl 4: iv1-iv62. PubMed Abstract | Publisher Full Text | Free Full Text 5. Zamora C, Huisman TA, Izbudak I: Supratentorial Tumors in Pediatric Patients. Neuroimaging Clin N Am. 2017; 27(1): 39-67. PubMed Abstract | Publisher Full Text 6. Kilday JP, Rahman R, Dyer S, et al.: Pediatric ependymoma: biological perspectives. Mol Cancer Res. 2009; 7(6): 765-786. PubMed Abstract | Publisher Full Text 7. Hamilton RL, Pollack IF: The molecular biology of ependymomas. Brain Pathol. 1997; 7(2): 807-822. PubMed Abstract | Publisher Full Text 8. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol. 1999; 21(3): 203-211. PubMed Abstract | Publisher Full Text 9. Spoto GP, Press GA, Hesselink JR, et al.: Intracranial ependymoma and subependymoma: MR manifestations. AJR Am J Roentgenol. 1990; 154(4): 837-845. PubMed Abstract | Publisher Full Text 10. Andrade FG, de Aguiar PH, Matushita H, et al.: Intracranial and spinal ependymoma: series at Faculdade de Medicina, Universidade de São Paulo. Arq Neuropsiquiatr. 2009; 67(3A): 626-632. PubMed Abstract | Publisher Full Text 11. Vera-Bolanos E, Aldape K, Yuan Y, et al.: Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro Oncol. 2015; 17(3): 440-447. PubMed Abstract | Publisher Full Text | Free Full Text 12. Milano MT, Johnson MD, Sul J, et al.: Primary spinal cord glioma: a Surveillance, Epidemiology, and End Results database study. J Neurooncol. 2010; 98(1): 83-92. PubMed Abstract | Publisher Full Text 13. Louis DN, Perry A, Reifenberger G, et al.: The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131(6): 803-820. PubMed Abstract | Publisher Full Text 14. Leeper H, Felicella MM, Walbert T: Recent Advances in the Classification and Treatment of Ependymomas. Curr Treat Options Oncol. 2017; 18(9): 55. PubMed Abstract | Publisher Full Text 15. Hirose Y, Aldape K, Bollen A, et al.: Chromosomal abnormalities subdivide ependymal tumors into clinically relevant groups. Am J Pathol. 2001; 158(3): 1137-1143. PubMed Abstract | Publisher Full Text | Free Full Text 16. Ross GW, ...

Purpose: Several recent studies have documented CTNNB1 and BRAF mutations which are mutually exclusive for adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) tumors. This discovery is helpful in the development of novel targeted therapies in successful clinical trials with BRAF mutations in PCP cases. However, no such targeted therapy is available yet for ACP. Here, we report novel mutations, which are not previously reported, in a case of an adult ACP using NGS analysis. Results: Patient DNA was sequenced using Ion PI v3 chip on Ion Proton. A total of 16 variants were identified in this tumor by NGS analysis, out of which four were missense mutations, seven were synonymous mutations, and five were intronic variants. In CTNNB1 gene a known missense mutation in c.101G>T; in TP53 a known missense mutation in c.215C>G; and two known missense variants in PIK3CA, viz., in c.1173A>G; in exon 7, and in c.3128T>C; in exon 21, were found, respectively. Seven synonymous mutations were detected in this tumor, viz., in IDH1 (rs11554137), in FGFR3 (rs7688609), in PDGFRA (rs1873778), in APC (COSM3760869), in EGFR (rs1050171), in MET (rs35775721), and in RET (rs1800861), respectively. Three known, intronic variants were found in genes, such as PIK3CA, KDR, and JAK3, respectively. Also, a 3'-UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown allele coverage, allele ratio, and p-value, for all these mutations. The p-values and Phred quality score were significantly high for these variants. Conclusion: As reported in previous studies, in ACP tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in ACP tumors. Finding the PIK3CA mutations in the ACP tumors may help develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are in progress with specific PIK3CA inhibitors in advanced stages of many cancers.

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Antibiotic resistance in pathogenic bacteria is emerging as an issue of serious concern in bio-medical research as well as food and health organizations. Metal complexes are currently being employed in medical devices for their inhibition to bacterial adherence and antibacterial activities. The primary aim of this study was to evaluate the antibacterial activities of pure metals, including selenium, germanium and lithium on planktonic cultures and biofilms of three bacterial species: S. aureus SH1000, P aeruginosa PA01 and E. coli. O157:H7. The antagonistic effects of selenium, germanium and lithium on these three bacterial species were examined using zone of inhibition assay. The minimum inhibitory concentrations and minimum bactericidal concentrations of antibiotics (rifampicin, mupirocin and ciprofloxacin) and metals (selenium, germanium and lithium) were measured. The minimum biofilm eradication concentrations (MBEC) of metals were determined against biofilms composed of S. aureus SH1000 and P. aeruginosa PA01. Metal susceptibility tests suggested that biofilms displayed increased resistance over their planktonic state. Differential inhibitory effects were observed for different strains of planktonic and biofilm bacteria in response to different metals and their varying concentrations. Amongst the three metals tested, selenium proved to be the most active against all three species, whereas lithium demonstrated the least inhibitory effects. Scanning electron microscope (SEM) image analysis revealed several detrimental structural changes in bacterial cells exposed to metals compared to those grown in the metal-free culture. In conclusion, the results demonstrate the antibacterial efficacy of pure metals against planktonic and biofilm bacteria paving the way for further similar investigations in search of alternative antibacterial agents.

Molecular pathology and personalized medicine are still being evolved in Saudi Arabia, and genetic testing for the detection of mutations as cancer markers have not been established in the diagnostics laboratories in Saudi Arabia. The aim of the present study was to determine the prevalence of isocitrate dehydrogenase (IDH1 and IDH2) mutations and epidermal growth factor receptor variant (EGFRv)III transcript expression in Saudi Arabian patients with glioma. Out of 117 brain tumors tested by reverse transcription-quantitative PCR for EGFRvIII, 41 cases tested positive. In the glioblastoma (GBM) category, 28/55 tumors were positive, in astrocytoma tumors 5/22, and in oligodendrogliomas 4/13 cases were positive respectively. EGFRvIII transcript was sequenced by capillary electrophoresis to demonstrate the presence of EGFRvIII-specific junction where exons 2-7 were deleted. In the present study 106 tumors were sequenced for IDH1 exon-4 mutations using the capillary sequencing method. The most common substitution missense mutation c.395G>A was found in 16 tumors. In the case of adamantinomatous craniopharyngioma, a novel missense mutation in c.472C>T was detected in IDH2 gene. Using next-generation sequencing (NGS), 74 tumors were sequenced for the IDH1 gene, and a total of 8 missense variants were identified in 36 tumors in a population of Saudi Arabia. The missense mutation (c.395G>A) was detected in 29/36 of tumors. A novel intronic mutation in c.414+9T>A was found in 13 cases in the IDH1 gene. In addition, one case exhibited a novel synonymous mutation in c.369A>G. Eleven tumors were found to have compound mutations in the IDH1 gene. In IDH2 gene, out of a total of 16 variants found in 6 out of 45 tumors, nine were missense, five were synonymous and one was intronic. This is the first report from Saudi Arabian laboratories analyzing glioma tumors for EGFRvIII expression, and the first study from Saudi Arabia to analyze IDH mutations in gliomas using the capillary and NGS methods.