Antiangiogenic and antitumor activity of IDN 5390, a new taxane derivative.

Purpose: We previously reported that paclitaxel, a microtubule-stabilizing drug, inhibited angiogenesis, mainly by inhibiting endothelial cell motility (D. Belotti et al., Clin.

Characterization and properties of dominant-negative mutants of the ras-specific guanine nucleotide exchange factor CDC25(Mm).

Ras proteins are small GTPases playing a pivotal role in cell proliferation and differentiation. Their activation depends on the competing action of GTPase activating proteins and guanine nucleotide exchange factors (GEF). The properties of two dominant-negative mutants within the catalytic domains of the ras-specific GEF, CDC25(Mm), are described.

BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity.

Matrix metalloproteinases (MMPs) have been implicated in tumor cell invasion, metastasis, and angiogenesis. BAY 12-9566, a novel, non-peptidic biphenyl MMP inhibitor, has shown preclinical activity on a broad range of tumor models and is currently in clinical development. The purpose of this study was to investigate the antiangiogenic activity of BAY 12-9566.

Mesothelial cells induce the motility of human ovarian carcinoma cells.

The dissemination of ovarian carcinoma cells within the abdominal cavity involves interaction of tumor cells with the peritoneal mesothelium. The aim of our study was to investigate whether mesothelial cells might directly affect the spreading of this tumor by inducing motility and invasiveness of human ovarian carcinoma cells. Serum-free supernatants of cultured human mesothelial cells [conditioned medium (CM)] induced chemotaxis and invasiveness of the human ovarian carcinoma cell lines SK-OV-3, OVCAR-5 and A2780 in a Boyden chamber.

Paclitaxel (Taxol(R)) inhibits motility of paclitaxel-resistant human ovarian carcinoma cells.

The effect of paclitaxel on the adhesive and motility properties of human ovarian carcinoma cell lines was investigated. Paclitaxel significantly inhibited the motility of OVCAR 5, SK-OV-3, and HOC-1OTC ovarian carcinoma cell lines (IC50 = 2.1 x 10(-8), 2 x 10(-9), and 1.

Receptors, signal transduction, and spectrum of action of monocyte chemotactic protein-1 and related chemokines.

Chemokines are a bipartite family of chemotactic proteins that bear the structural hallmark of four cysteine residues, the first two of which are in tandem. The spectrum of action of C-C chemokines, monocyte chemotactic protein-1 (MCP-1), MCP-2, and MCP-3, in particular, encompasses, in addition to monocytes, other leukocyte populations. Evidence is presented that MCP-1, MCP-2, and MCP-3 are active on natural killer cells.

Activation of phospholipase D by interleukin-8 in human neutrophils.

Interleukin 8 (IL-8), a member of the C-X-C branch of the chemokine superfamily, stimulated the breakdown of 1-O-[3H]alkyl-2-acyl-sn-glycero-3-phosphocholine ([3H]EAPC) and the formation of 1-O-[3H]alkyl-2-acyl-phosphatidic acid ([3H]-EAPA) in human polymorphonuclear leukocytes (PMN) in the presence of cytochalasin B. In addition, the mass of diradyl-PA was increased with similar kinetics. In the presence of ethanol, 1-O-[3H]alkyl-2-acyl-phosphatidylethanol ([3H]EAPEt) was formed at the expense of [3H]EAPA formation, indicating the activation of phospholipase D by the cytokine.

Receptors and transduction pathways for monocyte chemotactic protein-2 and monocyte chemotactic protein-3. Similarities and differences with MCP-1.

MCP-2 and MCP-3 are recently identified members of the Cys-Cys chemokine family with high sequence similarity with MCP-1 (62% and 71%, respectively). The present study was aimed at defining receptor usage and signal transduction pathways of MCP-2 and MCP-3 in human monocytes in comparison with MCP-1. MCP-2 and MCP-3 induced migration of monocytes with a typical bell-shaped curve and maximal response at 10 and 50 ng/ml, respectively.

Synergism between platelet activating factor and C-C chemokines for arachidonate release in human monocytes.

Monocyte Chemotactic Protein(MCP)-1 and other members of the C-C branch of the chemokine superfamily (RANTES, MIP1 alpha/LD78, and MCP-3) induced, at chemotactic concentrations, the release of [3H]arachidonic acid in prelabeled human monocytes. Arachidonate release was potentiated (2 to 4 fold) in the presence of platelet activating factor (PAF). PAF effect was blocked by a specific receptor antagonist, WEB 2187, and was not present when inactive analogs, PAF inactive enantiomer, or lysoPAF were used.