Novel Gut Microbiota Modulator, Which Markedly Increases Akkermansia muciniphila Occupancy, Ameliorates Experimental Colitis in Rats.

Background: Since gut microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD), antibiotics or probiotics may be attractive options for the treatment of IBD. Akkermansia muciniphila is expected as a next-generation probiotic for IBD, and OPS-2071 is a novel quinolone with potent antibacterial activity against Clostridioides difficile.

Aims: The aim of this study is to assess the potential of OPS-2071 as a gut microbiota modulator for IBD.

Molecular basis for G2 arrest induced by 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine and consequences of checkpoint abrogation.

2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC) is a nucleoside analogue with a novel mechanism of action that is currently being evaluated in clinical trials. Incorporation of CNDAC triphosphate into DNA and extension during replication leads to single-strand breaks directly caused by beta-elimination. These breaks, or the lesions that arise from further processing, cause cells to arrest in G2.

Cellular and biochemical mechanisms of the resistance of human cancer cells to a new anticancer ribo-nucleoside, TAS-106.

We have established variants of DLD-1 human colon carcinoma and HT-1080 human fibrosarcoma cells resistant to the new anticancer ribo-nucleosides, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)-cytosine (ECyd, TAS-106) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd). Both variants were shown to have decreased (3- to 24-fold decrease) uridine-cytidine kinase (UCK) activity, and exhibited cross-resistance to EUrd and TAS-106. Based on the IC(50) values determined by chemosensitivity testing, a 41- to 1102-fold resistance to TAS-106 was observed in the resistant cells.