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Koshi Fujikawa

Publications and source records attributed to Koshi Fujikawa.

5 recordsLinked to original sources
PubMed2006

[A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta.

Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) cooperate in migration and survival of endothelial cells by activation of phosphatidylinositol-3 (PI-3) kinase and mitogen activating protein (MAP) kinase pathways. However, Ang1 opposes the effect of VEGF on vascular permeability. We found that Ang1 also blocks VEGF-mediated diffusion of fluoresin isothiocyanate (FITC)-labeled albumin across an endothelial cell monolayer. VEGF-mediated vascular permeability has been attributed, in part, to activation of phospholipase A(2) and subsequent formation of platelet activating factor. However, Ang1 had no effect on VEGF-induced activation of phospholipase A(2) or the release of arachidonic acid. VEGF-mediated permeability was associated with disruption of endothelial cell junctional complexes, dissociation of beta-catenin from VE-cadherin, and accumulation of beta-catenin in the cytosol. In contrast, Ang1 enhanced the interaction of beta-catenin with VE-cadherin and impaired VEGF-mediated dissociation of this complex. Ang1 also blocked VEGF-induced translocation of protein kinase C (PKC) and beta2 to the membrane, but had no effect on activation of PKC alpha. In addition, staurosporine and a PKC beta inhibitor, LY379196, blocked VEGF-mediated dissociation of beta-catenin from VE-cadherin, diffusion of albumin across the endothelial cell monolayer, and translocation of PKC beta isoforms. These data indicate that VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta isoforms and that this pathway is blocked by Ang1.

Albumins↗
PubMed2004

Decrease of Smad4 gene expression in patients with essential thrombocythaemia may cause an escape from suppression of megakaryopoiesis by transforming growth factor-beta1.

Essential thrombocythaemia (ET) is characterized by the abnormal and sustained proliferation of megakaryocytes. The mechanism for this lineage-specific expansion in ET, remains unclear. We have previously reported that transforming growth factor-beta1 (TGF-beta1) is involved in negative feedback regulation of megakaryopoiesis in both healthy volunteers (HV) and patients with idiopathic thrombocytopenic purpura (ITP). The present study found that megakaryocyte colony-forming units (CFU-MK) of ET patients were less sensitive to TGF-beta1 than those of HV. The expression of Smad4 (Sma- and Mad-related protein-4) in CFU-MK of ET patients was reduced in comparison with that of HV. Finally, to confirm that the impaired TGF-beta1 sensitivity was caused by reduced expression of Smad4, we examined Smad4-transfected CFU-MK from ET patients in the presence of TGF-beta1, and verified that the transfectants were indeed as susceptible as CFU-MK from HV to TGF-beta1. Thus it was surmised that one of the mechanisms for impaired sensitivity of CFU-MK to TGF-beta1 is the reduced expression of Smad4.

Adult↗
PubMed2002

NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation during hypoxia.

Vascular endothelial growth factor (VEGF) and angiopoietins regulate endothelial cell survival and migration and are essential for angiogenesis. Considerable progress has been made towards understanding hypoxia-mediated regulation of VEGF and its receptors. In contrast, little is known about the regulation of angiopoietins and their receptors in hypoxic cells. Using RT-PCR, RNAase protection assay, and Western blotting, we found that Tie1 and Tie2 mRNA and protein levels increased in response to hypoxia in human umbilical vein endothelial cells. Previously, we have shown that NERF2, a member of Ets family of transcription factors that is specifically expressed in endothelial cells, binds to the promoter region of Tie2 and transactivates Tie2 expression. In this study, we show that expression of NERF2 was increased under hypoxia and that this increase temporally correlated with the increase in Tie2 expression. Hypoxia-induced expression of NERF2 and Tie2 was blocked by angiopoietin-2, a competitive inhibitor of angiopoietin-1, and by recombinant soluble extracellular domain of Tie2 but not by VEGF-neutralizing antibodies. In addition, angiopoietin-1 directly induced expression of NERF2 in quiescent cells. These novel findings suggest that angiopoietin-1 regulates expression of NERF2 and its own receptor in hypoxic cells.

Angiopoietin-1↗