Showing papers by "Shinae Kizaka-Kondoh published in 2004"
TL;DR: It is concluded that the NO donor NOC18 induces Hif-1α synthesis under conditions of NO formation during normoxia and that hydroxylation of HIF-1 α is not regulated by NOC 18.
204 citations
TL;DR: In this paper, the authors used T84 human colon cancer cells to define the pathway by which increases in cAMP induce c-IAP2 expression and found that cAMP-dependent suppression of apoptosis was blocked by treatment with inhibitors of ERK1/2 and p38 MAPK.
106 citations
TL;DR: It is concluded that muscarinic acetylcholine signals activate HIF-1 by both stabilization and synthesis of Hif-1α and by inducing the transcriptional activity of HIF -1α.
61 citations
TL;DR: Results indicate the possibility that transmembrane Trx-related protein (TMX) can modify certain molecules with its oxidoreductase activity and be involved in the redox regulation in the ER.
44 citations
TL;DR: Tumor hypoxia in a solid tumor mass has long been recognized as a cause of resistance to current cancer therapies, and has also been suggested to be a potent driving force towards malignancy, so it is proposed that rodent malignant ascites is an appropriate platform for testing hypoxIA-targeted drugs.
Abstract: Tumor hypoxia in a solid tumor mass has long been recognized as a cause of resistance to current cancer therapies, and has also been suggested to be a potent driving force towards malignancy. Recent progress in the understanding of the molecular mechanism of the tumor response to hypoxia has increased attention on targeting hypoxia for cancer therapy. We have generated a hypoxia-targeting fusion protein, TOP3, which is composed of a protein transduction domain (PTD) of HIV TAT, an oxygen-dependent degradation domain (ODD) of HIF-1 alpha, and procaspase-3. Here, we examine the effects of TOP3 in a rat ascites model. First, we clarified that the fluid in ascites from MM1 cells, which are derivatives of AH130 rat ascites hepatoma cells, was highly hypoxic. In vitro, MM1 cells retained protein degradation machinery through the ODD domain, and TOP3 effectively impaired MM1 cell growth in culture under hypoxic conditions by inducing apoptosis. Intraperitoneal administration of TOP3 prolonged the life span of rats bearing a significant amount of malignant ascites, and 60% of the treated animals were cured without recurrence of ascites. Thus, TOP3 had a dramatic effect on malignant ascites and, hence, we propose that rodent malignant ascites is an appropriate platform for testing hypoxia-targeted drugs.
37 citations