Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tu ...[more]
Project description:The entire double-stranded DNA genome of the Actinobacillus actinomycetemcomitans bacteriophage Aa Phi 23 was sequenced. Linear DNA contained in the phage particles is circularly permuted and terminally redundant. Therefore, the physical map of the phage genome is circular. Its size is 43,033 bp with an overall molar G+C content of 42.5 mol%. Sixty-six potential open reading frames (ORFs) were identified, including an ORF resulting from a translational frameshift. A putative function could be assigned to 23 of them. Twenty-three other ORFs share homologies only with hypothetical proteins present in several bacteria or bacteriophages, and 20 ORFs seem to be specific for phage Aa Phi 23. The organization of the phage genome and several genetic functions share extensive similarities to that of the lambdoid phages. However, Aa Phi 23 encodes a DNA adenine methylase, and the DNA packaging strategy is more closely related to the P22 system. The attachment sites of Aa Phi 23 (attP) and several A. actinomycetemcomitans hosts (attB) are 49 bp long.
Project description:We selectively oxidized the C-23 hydroxyl group in an asiatic acid (AA) derivative and then, for the first time with AA, modification of the C-23 carboxyl group was conducted to synthesize a series of new AA derivatives. The evaluation of their cytotoxic activities against two human cancer cell lines (SKOV-3 and HCT116) using the MTT assay in vitro revealed a distinctive structure activity relationship (SAR) associated with the intramolecular hydrogen bonding of the amide moiety at C-23. According to the established SAR, the cytotoxic activities of four promising compounds were then evaluated against MCF-7, A549, A2780, HepG2 and HL-60 cancer cell lines. Compound 10 had the best cytotoxic activity among all tested derivatives in the HL-60 cell line, giving IC50 = 0.47 ?M, while showing no cytotoxic effect against human normal cells (HUVEC).