Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor.

The emergence of acquired resistance is a major concern associated with molecularly targeted kinase inhibitors. The C797S mutation in the epidermal growth factor receptor (EGFR) confers resistance to osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI). We report that the derivatization of the marine alkaloid topoisomerase inhibitor lamellarin N provides a structurally new class of EGFR-TKIs.

IMU1003, an atrarate derivative, inhibits Wnt/β-catenin signaling.

Aberrant activation of the canonical Wnt/β-catenin signaling pathway triggers tumorigenesis in various tissues. This study identified an atrarate compound, IMU14, derived from filamentous fungi as an inhibitor of Wnt/β-catenin signaling in phenotypic chemical inhibitor screening of the zebrafish eyeless phenotype. Its derivatization resulted in synthesis of IMU1003 with enhanced Wnt inhibitory activity.

Clotrimazole inhibits the Wnt/β-catenin pathway by activating two eIF2α kinases: The heme-regulated translational inhibitor and the double-stranded RNA-induced protein kinase.

The Wnt/β-catenin signaling pathway controls cell proliferation and differentiation, and therefore, when this pathway is excessively activated, it causes tumorigenesis. Our chemical suppressor screening in zebrafish embryos identified antifungal azoles including clotrimazole, miconazole, and itraconazole, as Wnt/β-catenin signaling inhibitors. Here we show the mechanism underlying the Wnt/β-catenin pathway inhibition by antifungal azoles.

DNA damage-induced modulation of GLUT3 expression is mediated through p53-independent extracellular signal-regulated kinase signaling in HeLa cells.

Many cancer cells exhibit increased rates of uptake and metabolism of glucose compared with normal cells. Glucose uptake in mammalian cells is mediated by the glucose transporter (GLUT) family. Here, we report that DNA-damaging anticancer agents such as Adriamycin and etoposide suppressed the expression of GLUT3, but not GLUT1, in HeLa cells and a tumorigenic HeLa cell hybrid.

The intrinsic structure of glucose transporter isoforms Glut1 and Glut3 regulates their differential distribution to detergent-resistant membrane domains in nonpolarized mammalian cells.

The hexose transporter family, which mediates facilitated uptake in mammalian cells, consists of more than 10 members containing 12 membrane-spanning segments with a single N-glycosylation site. We previously demonstrated that glucose transporter 1 is organized into a raft-like detergent-resistant membrane domain but that glucose transporter 3 distributes to fluid membrane domains in nonpolarized mammalian cells. In this study, we further examined the structural basis responsible for the distribution by using a series of chimeric constructs.

Differential localization of glucose transporter isoforms in non-polarized mammalian cells: distribution of GLUT1 but not GLUT3 to detergent-resistant membrane domains.

The hexose transporter family, which mediates a facilitated uptake in mammalian cells, consists of more than 10 members containing 12 membrane-spanning segments with a single N-glycosylation site. However, it remains unknown how these isoforms are functionally organized in the membrane domains. In this report, we describe a differential distribution of the glucose transporter isoforms GLUT1 and GLUT3 to detergent-resistant membrane domains (DRMs) in non-polarized mammalian cells.

[Postoperative radiotherapy with the electron beam in breast cancer].

The usefulness of postoperative radiotherapy for breast cancer was investigated in 152 patients. A dose of 50 Gy was given to the axillar, supraclavicular and internal mammary lymphnode areas using a 12 MeV electron and to the chest wall using a 6 MeV electron. The five and 10-year survival rates were 79.