Nucleos(t)ide analogs for hepatitis B virus infection differentially regulate the growth factor signaling in hepatocytes.

Background: Recent clinical studies have suggested that the risk of developing HCC might be lower in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate than in patients receiving entecavir, although there is no difference in biochemical and virological remission between the 2 drugs.

Methods: The effects of nucleoside analogs (NsAs; lamivudine and entecavir) or nucleotide analogs (NtAs; adefovir disoproxil, tenofovir disoproxil fumarate, and tenofovir alafenamide) on cell growth and the expression of growth signaling molecules in hepatoma cell lines and PXB cells were investigated in vitro. The tumor inhibitory effects of NsAs or NtAs were evaluated using a mouse xenograft model, and protein phosphorylation profiles were investigated.

Cyclo-glycylproline attenuates hydrogen peroxide-induced cellular damage mediated by the MDM2-p53 pathway in human neural stem cells.

Cyclo-glycylproline (cGP), a cyclic dipeptide containing a condensation bond between glycine and proline, is produced by the cyclization of the N-terminal tripeptide of insulin-like growth factor-1. Previous studies have shown that cGP administration exerts a neuroprotective effect and enhances the regenerative ability in rats with ischemic brain injury. The efficacy of cGP is medicated by regulating the bioavailability of insulin-like growth factor-1 (IGF-1), however, the molecular mechanisms underlying the neuroprotective effects of cGP on brain damage remains to be elucidated.

Phosprof: pathway analysis database of drug response based on phosphorylation activity measurements.

Unlabelled: Protein phosphorylation plays a fundamental role in many cellular processes. Proteins are phosphorylated by kinases, which have been studied as drug targets for the treatment of various diseases, particularly cancer. Because kinases have multiple roles in interconnected molecular pathways, their specific regulation is required to enhance beneficial and reduce adversarial effects of drugs.

Assessing the activation/inhibition of tyrosine kinase-related pathways with a newly developed platform.

The phosphorylation of cellular proteins plays a crucial role in the transduction of various signals from outside the cell into the nucleus. The signals are transduced by phosphorylation chain reactions within multiple pathways; however, determining which pathways are responsible for each defined signal has proven challenging. To estimate the activity of each pathway, we developed a phosphorylation array platform comprising a protein array with 1200 proteins belonging to 376 signalling pathways and an analytical method to estimate pathway activity based on the phosphorylation levels of proteins.

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib: Real-world evidence and assessment via protein phosphorylation array.

The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC.