Echo is a good, not perfect, measure of cardiac output in critically ill surgical patients.

Background: Compared with a pulmonary artery catheter (PAC), transthoracic echocardiography (TTE) has been shown to have good agreement in cardiac output (CO) measurement in nonsurgical populations. Our hypothesis is that the feasibility and accuracy of CO measured by TTE (CO-TTE), relative to CO measured by PAC thermodilution (CO-PAC), is different in surgical intensive care unit patients (SP) and nonsurgical patients (NSP).

Methods: Surgical patients with PAC for hemodynamic monitoring and NSP undergoing right heart catheterization were prospectively enrolled.

Microcavity arrays as an in vitro model system of the bone marrow niche for hematopoietic stem cells.

In previous studies human mesenchymal stromal cells (MSCs) maintained the "stemness" of human hematopoietic progenitor cells (HPCs) through direct cell-cell contact in two-dimensional co-culture systems. We establish a three-dimensional (3D) co-culture system based on a custom-made chip, the 3(D)-KITChip, as an in vitro model system of the human hematopoietic stem cell niche. This array of up to 625 microcavities, with 300 μm size in each orientation, was inserted into a microfluidic bioreactor.

Investigation of the interactions between the EphB2 receptor and SNEW peptide variants.

EphB2 interacts with cell surface-bound ephrin ligands to relay bidirectional signals. Overexpression of the EphB2 receptor protein has been linked to different types of cancer. The SNEW (SNEWIQPRLPQH) peptide binds with high selectivity and moderate affinity to EphB2, inhibiting Eph-ephrin interactions by competing with ephrin ligands for the EphB2 high-affinity pocket.

Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: effect of dimerisation on phosphatase inhibition.

CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity.

Modification of a promiscuous inhibitor shifts the inhibition from γ-secretase to FLT-3.

The inhibition of FLT-3 activity is an interesting target for the treatment of acute myeloid leukemia (AML). The serendipitous identification of FLT-3 inhibitors from a CK1/γ-secretase programme provided compounds with dual inhibitory activity. We analyzed the structure-activity relationship of these inhibitors and derivatized them to arrive at compounds with reduced impact on γ-secretase activity and enhanced FLT-3 inhibition.

5-Substituted [1]pyrindine derivatives with antiproliferative activity.

We report herein the synthesis of 5-substituted [1]pyrindine derivatives and the evaluation of their antiproliferative properties on HeLa cells, a cervical carcinoma tumor cell line, and on the melanoma A2058 cell line. The most efficient compounds display cytotoxicity against tumor cells in the micromolar range but have interestingly no effect against the normal human fibroblasts CRL-2796. Generally, these pyrindines are active on both tumor cell lines.

Development of novel thiazolopyrimidines as CDC25B phosphatase inhibitors.

The development of CDC25 phosphatase inhibitors is an interesting approach toward new antitumor agents, as CDC25 play key roles in cell-cycle regulation and are overexpressed in numerous cancers. We previously reported a novel compound belonging to the thiazolopyrimidine family that inhibits CDC25 activity with an IC(50) value of 13 microM and displays cytotoxic properties against HeLa cells. Structural modifications were subsequently conducted on this new pharmacophore which led to a library of 45 thiazolopyrimidines.

Novel naphthoquinone and quinolinedione inhibitors of CDC25 phosphatase activity with antiproliferative properties.

CDC25 phosphatases are considered as attractive targets for anti-cancer therapy. To date, quinone derivatives are among the most potent inhibitors of CDC25 phosphatase activity. We present in this paper the synthesis and the biological evaluation of new quinolinedione and naphthoquinone derivatives, containing carboxylic or malonic acids groups introduced to mimic the role of the phosphate moieties of Cyclin-Dependent Kinase complexes.

Receptor-based virtual ligand screening for the identification of novel CDC25 phosphatase inhibitors.

CDC25 phosphatases play critical roles in cell cycle regulation and are attractive targets for anticancer therapies. Several small non-peptide molecules are known to inhibit CDC25, but many of them appear to form a covalent bond with the enzyme or act through oxidation of the thiolate group of the catalytic cysteine. Structure-based virtual ligand screening computations were performed with FRED, Surflex, and LigandFit, a compound collection of over 310,000 druglike molecules and the crystal structure of CDC25B in order to identify novel classes of ligands.