Meta-analysis of functional expression and mutational analysis of c-Met in various cancers.

Comprehensive genomic profiling is expected to revolutionize cancer therapy. c-Met signaling is responsible for tumorigenesis in various cancers. In this prospective, we present the prevalence of c-Met mutations and copy number alterations across various solid tumors. We used major databases like cBioportal, PubMed, and COSMIC for c-Met mutation and amplification data collection from various cancers. Our result shows complete details about c-Met mutation and its clinical data of various cancers. Hotspot mutation of human c-Met protein reveals that repeatedly and most mutated regions and these hotspots may be a diagnostic tool for cancer confirmation. Amino acid and nucleotide changes and their prevalence were reported in a number of individual cancers. However, we collectively present the amino acid and nucleotide changes in various cancers in this review. Our collection of data for c-Met mutation and its distribution in different cancer tissue is showing that the missense mutation is the major one in all type of cancers. Copy number variation data showing amplification and deletion of human c-Met from various tumor types, lung and central nervous system tumors showing high amplification comparatively other types.

Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats.

BACKGROUND: Elevated blood ammonia leads to hyperammonaemia that affects vital central nervous system (CNS) functions. Fisetin, a naturally occurring flavonoid, exhibits therapeutic benefits, such as anti-cancer, anti-diabetic, anti-oxidant, anti-angiogenic, neuroprotective and neurotrophic effects. METHODS: In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis. RESULTS: Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points. CONCLUSIONS: Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated.