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Background Interactions with the microenvironment, such as bone marrow mesenchymal stromal cells and nurse-like cells, protect chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis. This protection is partially mediated by the chemokine SDF-1α (CXCL12) and its receptor CXCR4 (CD184) present on the chronic lymphocytic leukemia cell surface.Design and Methods Here, we investigated the ability of AMD3100, a CXCR4 antagonist, to sensitize chronic lymphocytic leukemia cells to chemotherapy in a chronic lymphocytic leukemia/mesenchymal stromal cell based or nurse-like cell based microenvironment co-culture model.Results AMD3100 decreased CXCR4 expression signal (n=15, P=0.0078) and inhibited actin polymerization/migration in response to SDF-1α (n=8, P

Cell-surface TGFβ (transforming growth factor β) receptors partition into membrane rafts and the caveolin-positive endocytic compartment by an unknown mechanism. In the present study, we investigated the determinant in the TGFβ type II receptor (TβRII) that is necessary for membrane raft/caveolar targeting. Using subcellular fractionation and immunofluorescence microscopy techniques, we demonstrated that the extracellular domain of TβRII mediates receptor partitioning into raft and caveolin-positive membrane domains. Pharmacological perturbation of glycosylation using tunicamycin or the mutation of Mgat5 [mannosyl(α-1,6)-glycoprotein β-1,6-N-acetylglucosaminyltransferase V] activity interfered with the raft partitioning of TβRII. However, this was not due to the glycosylation state of TβRII, as a non-glycosylated TβRII mutant remained enriched in membrane rafts. This suggested that other cell-surface glycoproteins associate with the extracellular domain of TβRII and direct their partitioning in membrane raft domains. To test this we analysed a GMCSF (granulocyte/macrophage colony-stimulating factor)–TβRII chimaeric receptor, which contains a glycosylated GMCSF extracellular domain fused to the transmembrane and intracellular domains of TβRII. This chimaeric receptor was found to be largely excluded from membrane rafts and caveolin-positive structures. Our results indicate that the extracellular domain of TβRII mediates receptor partitioning into membrane rafts and efficient entrance into caveolin-positive endosomes. [ABSTRACT FROM AUTHOR]

The -alkylidyne complex Mo2Cp2(-SMe)3(-CCH2Ph) (1) reacts with HBF4in acetonitrile to give the unstable bis-nitrile species Mo2Cp2(-SMe)2(-CCH2Ph)(NCCH3)2(BF4) (2). Treatment with either borohydride or chloride converts 2into Mo2Cp2(-SMe)2(-CCH2Ph)(-1:1-BH4) (3) or Mo2Cp2(-SMe)2(-CCH2Ph)(-Cl) (4), respectively. Clean evolution of 4in non-degassed solvent affords the novel -thioalkylidene derivative Mo2(O)(Cl)Cp2(-SMe)(-MeSCCH2Ph)(5). [ABSTRACT FROM AUTHOR]

The electrochemical reduction of isomeric complexes, [Mo2Cp2(μ-SMe)3(μ-η1:η1-HCCPh)]+ (1+) and [Mo2Cp2(μ-SMe)3(μ-η1:η2-C=CHPh)]+ (3+), where the hydrocarbyl bridges in a η1:η1- or a η1:η2 mode, has been studied by cyclic voltammetry and controlled-potential electrolysis in thf–[NBu4][PF6] and CH2Cl2–[NBu4][PF6], in the absence and in the presence of acid. The binding mode of the CC fragment induces different electrochemical behaviour of the complexes in acid-free solutions since 1+ reduces in two diffusion-controlled one-electron steps while the first reduction of 3+ is characterized by slow electron transfer kinetics. Controlled-potential reduction of both 1+ and 3+ produces a mixture of the acetylide [Mo2Cp2(μ-SMe)3(μ-η1:η2-CCPh)] (2) and alkylidyne complexes [Mo2Cp2(μ-SMe)3(μ-η1-CCH2Ph)] (4). In the presence of acid, the electrochemical reduction of 1+ and of 3+ occurs according to ECE processes. The nature of the products formed by controlled-potential reduction of 1+ depends on the nature of the acid and of the solvent. The transient formation of a complex with a μ-alkenyl ligand, either [Mo2Cp2(μ-SMe)3(μ-η1:η2-CH=CHPh)] (7) or an isomer, is suggested by the oxidative electrochemistry of 7 and by its reaction with acids. In thf–[NBu4][PF6] in the presence of an excess of acid (HBF4/Et2O) and of phenylacetylene, electrolysis of 1+ gives rise to catalytic reduction of phenylacetylene to styrene. However, unidentified reactions limit the efficiency of this process. The reduction of 3+ in acidic medium produces the alkyl complex [Mo2Cp2(μ-SMe)3(μ-CH2CH2Ph)] (6) through alkylidyne [Mo2Cp2(μ-SMe)3(μ-η1-CCH2Ph)] (4) and alkylidene [Mo2Cp2(μ-SMe)3(μ-η1-CHCH2Ph)]+ (5+) intermediates. Some ethylbenzene was formed after reduction of 5+ in the presence of acid. These results show an effect of the binding mode of the hydrocarbyl bridge on the mechanism and products of the reduction of the corresponding complexes. [ABSTRACT FROM AUTHOR]