Comparison of imatinib, dasatinib, nilotinib and INNO-406 in imatinib-resistant cell lines.

We compared the growth-inhibitory effects and inhibition profile of the SRC family kinases (SFKs) of imatinib, dasatinib, nilotinib and INNO-406. Dasatinib exhibited the strongest potency against BCR-ABL with little selectivity over SFKs. Nilotinib exhibited a weaker affinity than the other inhibitors, but was highly specific for ABL and may be useful for the treatment of P-glycoprotein overexpressing leukemic cells.

Curcumin prevents the development of dextran sulfate Sodium (DSS)-induced experimental colitis.

Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (turmeric). We evaluated the effects of curcumin on the development of dextran sulfate sodium (DSS)-induced experimental colitis. BALB/c mice were fed a chow containing either 3.

The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice.

To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis.

INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity.

Central nervous system (CNS) relapse accompanying the prolonged administration of imatinib mesylate has recently become apparent as an impediment to the therapy of Philadelphia chromosome-positive (Ph+) leukemia. CNS relapse may be explained by limited penetration of imatinib mesylate into the cerebrospinal fluid because of the presence of P-glycoprotein at the blood-brain barrier. To overcome imatinib mesylate-resistance mechanisms such as bcr-abl amplification, mutations within the ABL kinase domain, and activation of Lyn, we developed a dual BCR-ABL/Lyn inhibitor, INNO-406 (formerly NS-187), which is 25 to 55 times more potent than imatinib mesylate in vitro and at least 10 times more potent in vivo.

Immunohistochemical study of chymase-positive mast cells in inflammatory bowel disease.

Mast cell-derived chymase promotes inflammatory responses and tissue fibrosis. Although previous studies have reported changes in the number of mucosal mast cells in inflammatory bowel disease (IBD), the behaviour of chymase immunopositive mast cells has not been studied. In this study, we immunohistochemically investigated chymase immunopositive mast cells in the inflamed mucosa of IBD patients.

Interleukin-17 augments tumor necrosis factor-alpha-induced granulocyte and granulocyte/macrophage colony-stimulating factor release from human colonic myofibroblasts.

Background: Interleukin (IL)-17 is a newly identified T-cell-specific cytokine. In this study, we investigated the effects of IL-17 on colony-stimulating factor (CSF) release in human colonic subepithelial myofibroblasts (SEMFs).

Methods: CSF release and mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting, respectively.

Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts.

Background & Aims: Interleukin (IL)-22, a member of the IL-10 subfamily, is a recently identified T-cell-derived cytokine. We investigated IL-22 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and analyzed its biologic activities in human colonic subepithelial myofibroblasts (SEMFs).

Methods: Mucosal IL-22 expression was evaluated by immunohistochemical procedures.

Development of dextran sulfate sodium-induced colitis is aggravated in mice genetically deficient for complement C5.

The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease (IBD), we evaluated the development of dextran sulfate sodium (DSS)-induced colitis in genetically complement C5-deficient mice. We used DBA2/J mice, which are genetically deficient in complement C5.

Leukocytapheresis therapy modulates circulating t cell subsets in patients with ulcerative colitis.

The aim of this study was to elucidate the molecular mechanisms responsible for the therapeutic effects of leukocytapheresis (LCAP). We investigated the alterations in circulating T cell subsets after LCAP therapy in ulcerative colitis (UC) patients. Eighteen patients with UC were enrolled.

[A case of advanced gastric cancer with pulmonary carcinomatous lymphangiosis responding remarkably to combination chemotherapy of docetaxel (TXT) and TS-1].

A 51-old-female patient was admitted because of dyspnea. This case was diagnosed inoperable advanced gastric cancer and pulmonary carcinomatous lymphangiosis. She was treated by combination of docetaxel (TXT) and TS-1.

Suppression of inflammatory cytokine secretion by granulocyte/monocyte adsorptive apheresis in active ulcerative colitis.

To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis.