The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole-exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls-independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant-based filter were employed to call somatic gene-copy number variations. Significantly mutated genes were identified with Oncodrive FM and the Youn and Simon’s method. Candidate driver genes were nominated based on Gene Set Enrichment Analysis. The observed mutational spectrum was similar to that reported by the TCGA project. In addition to confirming known genes of OSCC (TP53, CDKNA2, CASP8, PIK3CA, HRAS, FAT1, TP63, CCND1 and FADD) the analysis identified several candidate novel driver events including mutations of NOTCH3, CSMD3, CRB1, CLTCL1, OSMR and TRPM2, amplification of the proto-oncogenes FOSL1, RELA, TRAF6, MDM2, FRS2 and BAG1, and deletion of the recently described tumor suppressor SMARCC1. Analysis also revealed significantly altered pathways not previously implicated in OSCC including Oncostatin-M signalling pathway, AP-1 and C-MYB transcription networks and endocytosis. There was a trend for higher number of mutations, amplifications and driver events in samples with history of shammah exposure particularly those that tested EBV positive, suggesting an interaction between tobacco exposure and EBV. The work provides further evidence for the genetic heterogeneity of oral cancer and suggests shammah-associated OSCC is characterized by extensive amplification of oncogenes.

No abstract

Cathinone, the active principle of khat (Catha edulis), stimulates, excites and produces euphoric feelings in khat users. Locomotor and rearing activities, either individual or in groups, of male Swiss albino mice were decreased significantly compared to the control. Motor coordination tests (rotarod, rope climb and grip tests) have shown decreased motor performance in the mice treated with cathinone compared to the control. The elevated plus maze test has shown significant anxiety in the mice compared to the control. Contents of dopamine and its metabolite, homovanillic acid, were increased in the limbic areas compared to the control group. In contrast, contents of 3,4-dihydroxyphenyl acetic acid were depleted significantly and dose dependently compared to the control group in the limbic areas of mice. In conclusion, natural cathinone has depleted motor coordination, accelerated anxiety in mice and altered the contents of dopamine and its metabolites.

The leaves of khat plant (Catha edulis) are widely consumed by people of East African countries and Arabian Peninsula for their pleasurable and stimulating effects. The consumption of khat is prohibited in the Kingdom of Saudi Arabia but it is being used by the people of Kingdom, especially in the region of Jazan, where it is easily available due to its cultivation in the neighbouring country Yemen. The objective of the study was to evaluate the effect of very low doses of cathinone on the brain lipids. Male Swiss albino mice were divided in 4 groups, one control and 3 experimental and each group having 6 animals. (-) Cathinone, 0.125, 0.25 and 0.5 mg/kg body weight was given intraperitoneal to animals for 10 days, once daily.  Cathinone has elevated the level of triglyceride significantly and dose dependently as compared to control group. On the other hand, the content of ganglioside was depleted significantly and dose dependently in experimental groups as compared to control group. A significantly elevated level of cholesterol was observed with the doses of 0.25 and 0.5 mg/kg and phospholipids with the dose of 0.5 mg/kg of cathinone as compared to control group. No significant change on total lipids was observed in cathinone treated group as compared to control group. The study concludes that very low doses of cathinone were sufficient for the change on the brain lipid contents to provide excitement in khat chewers.