Claude Nicolau | Tufts University (original) (raw)

Papers by Claude Nicolau

Clinical Cancer Research, Nov 30, 2016

Purpose: Tumor hypoxia activates hypoxia-inducible factors (Hifs), which induce a range of malign... more Purpose: Tumor hypoxia activates hypoxia-inducible factors (Hifs), which induce a range of malignant changes including vascular abnormalities. Here, we determine whether inhibition of the hypoxic tumor response through myo-inositol trispyrophosphate (ITPP), a compound with antihypoxic properties, is able to cause prolonged vascular normalization that can be exploited to improve standard-of-care treatment. Experimental Design: We tested ITPP on two syngeneic orthotopic mouse models of lethal colorectal cancer liver metastasis. Tumors were monitored by MRI and analyzed for the hypoxic response and their malignant potential. A Hif activator and in vitro assays were used to define the working mode of ITPP. Hypoxic response and vasculature were re-evaluated 4 weeks after treatment. Finally, we determined survival following ITPP monotherapy, FOLFOX monotherapy, FOLFOX plus Vegf antibody, and FOLFOX plus ITPP, both overlapping and sequential. Results: ITPP reduced tumor load, efficiently inhibited the hypoxic response, and improved survival. These effects were lost when mice were pretreated with a Hif activator. Its immediate effects on the hypoxic response, including an apparent normalization of tumor vasculature, persisted for at least 4 weeks after treatment cessation. Compared with FOLFOX alone, Vegf antibody combined with FOL-FOX prolonged survival by <30%, whereas ITPP combined with FOLFOX extended survival by >140%, regardless of whether FOLFOX was given in overlap or after ITPP exposure. Conclusions: Our findings reveal a truly antihypoxic mechanism for ITPP and demonstrate the capacity of this nontoxic compound to potentiate the efficacy of existing anticancer treatment in a way amenable to clinical translation. Clin Cancer Res; 22(23); 5887-97. Ó2016 AACR.

Biochemical and Biophysical Research Communications, Jun 1, 1977

... IN NORMAL HUMAN LYMPHOCYTES Sheena M. Johnson' and Claude Nicolau+ Division of Immunolog... more ... IN NORMAL HUMAN LYMPHOCYTES Sheena M. Johnson' and Claude Nicolau+ Division of Immunological Medicine Clinical Research Centre Watford Road Harrow, UK +Institut flir Strahlenchemie im MaxPlanck Institut fur Kohlenforschung D4330 M1lheim ad Ruhr West ...

FEBS Letters, Jul 8, 1996

In vivo targeted gene transfer by non-viral vectors is subjected to anatomical constraints depend... more In vivo targeted gene transfer by non-viral vectors is subjected to anatomical constraints depending on the route of administration. Transfection efficiency and gene expression in vivo using non-viral vectors is also relatively low. We report that in vivo electropermeabilization of the liver tissue of rats in the presence of genes encoding luciferase or ~-galactosidase resulted in the strong expression of these genetic markers in rat liver cells. About 31)-40% of the rat liver cells electroporated expressed the ~galactosidase genetic marker 48 h after electroporation. The marker expression was also detected at least 21 days after transfection at about 5% of the level 48 h after electroporation. The results indicate that gene transfer by electroporatinn in vivo may avoid anatomical constraints and low transfection efficiency.

FEBS Letters, Feb 6, 1995

Proceedings in life sciences, 1977

1. Cooperative State Transitions in Biomembranes: Spectroscopic Analyses.- 2. Domain Formation in... more 1. Cooperative State Transitions in Biomembranes: Spectroscopic Analyses.- 2. Domain Formation in Lipid Bilayers and Biological Membranes.- 3. Recent Studies of Lipid-Lipid and Lipid-Protein Interactions by Physical and Chemical Methods.- 4. Modulation of Plasma Membrane Architecture in Animal Cells.- 5. Protein-Lipid Interactions: Freeze-Fracture and Spin Label Studies.- 6. Shape and Solubilization of a Membrane Protein: Rhodopsin.- 7. Biological and Biochemical Changes in the Plasma Membrane of RNA Tumor Virus-Transformed Cells.- 8. Lipid Organization in Biological Membranes.- 9. Density-Dependent Growth Control and Lipid Mobilities in Normal and Tumor-Transformed Cell Membranes.- 10. Coupling Between ATP Hydrolysis and Sodium and Potassium Transport.- 11. Modulation of Some Membrane Enzymes Studied in Variant Cells.- 12. Vasopressin-sensitive Adenylate Cyclase from the Mammalian Kidney: Mechanisms of Activation.- 13. The Molecular Architecture of a Reconstituted Calcium Pump.

Academic Press eBooks, 1981

ABSTRACT

Biochemical and Biophysical Research Communications, Jun 1, 2007

Annals of Surgery, Nov 1, 2017

Cancer Letters, Nov 1, 2007

FEBS Letters, Nov 26, 1990

International Journal of Cancer, Nov 25, 2013

Bioorganic & Medicinal Chemistry Letters, Mar 1, 2005

Nine inositol tripyrophosphate (ITPP) salts have been synthesized. Their ability to act as allost... more Nine inositol tripyrophosphate (ITPP) salts have been synthesized. Their ability to act as allosteric effectors of haemoglobin (Hb) has been measured in vitro with free Hb and whole blood. All the synthesized compounds bound to free Hb and were also able to cross, to a certain extent, the plasma membrane of the red blood cells (RBCs) in whole blood samples, lowering the affinity of Hb for oxygen. The oxy-haemoglobin dissociation curves were significantly shifted towards higher values of oxygen partial pressures, both for free Hb and for intracellular Hb in whole blood.

Current studies in hematology and blood transfusion, Apr 16, 2015

Experimental Cell Research, Apr 1, 1978

Biochimica Et Biophysica Acta - Biomembranes, Jun 1, 1979

Nanosecond decays of the fluorescence anisotropy, r, were studied for the emission of 1,6-dipheny... more Nanosecond decays of the fluorescence anisotropy, r, were studied for the emission of 1,6-diphenyl-l,3,5-hexatriene (DPH) embedded in a series of mixed multilamellar liposomes containing egg yolk phosphatidylcholine, phosphatidylethanolamine and cholesterol in varying molar ratios, as well as in membranes of intact cells and in virus envelopes. The relative contributions of the fast and the infinitely slow decaying component to the steady-state value, F, of the fluorescence anisotropy were very similar for artifical and biological membranes. Angles, 0, of the cone, by which the motion of the fluorescent molecule is limited, were calculated from the intensity of the infinitely slow decaying anisotropy component and compared with steady-state fluorescence anisotropies and with 'microviscosities', <~}. An increase in {~) from 1.5 to 5.2 P in our systems was accompanied by a decrease in 0 from 49 ° to 30 ° while the decrease in the mean motional relaxation times, el, of the label molecule was not more than 1 ns and due mainly to changes in the potential, by which the diffusion of DPH in the membrane is restricted. From these observations we conclude that differences in the steady-state fluorescence anisotropy and in 'microviscosities' of cholesterol-containing membranes (F> 0.15) represent changes in the degree of static orientational constraint rather than changes in diffusion rates of the label.

Elsevier eBooks, 1986

Publisher Summary This chapter reviews the biochemical and physiological effects of the incorpora... more Publisher Summary This chapter reviews the biochemical and physiological effects of the incorporation of allosteric effectors of hemoglobin in red blood cells. The amount of O2 that can be released in a particular organ depends on the critical O2 partial pressure characteristic for the organ and on the architecture of the microvasculature. This O2 release capacity is controlled by the microcirculation and molecular parameters of the intracellular Hb. The O2 release capacity can be enhanced by an increase in the co-operability of the Hb molecule; and/or by right shifting of the entire O2-binding curve toward higher O2 partial pressures. An abnormally high affinity of hemoglobin for oxygen shifts the O2-binding curve to the left and the P50 (O2 partial pressure at which 50% saturation of hemoglobin occurs) decreases causing a lower oxygen release to the tissues. In human RBC, the right-shift is controlled by several allosteric mechanisms, such as Bohr effect, 2, 3-bis-phosphoglycerate (DPG), and CO2-binding.

Pergamon Press eBooks, 1987

(partial) Some unique applications of erythrocytes as carrier systems, H O Alpar & W J Irwin ... more (partial) Some unique applications of erythrocytes as carrier systems, H O Alpar & W J Irwin In vitro drug release from human carrier erythrocytes, H C Eichler et al. Desferrioxamine loading of red cells for transfusion, A Zanella et al. Rheological approach to human red blood cell carriers desferrioxamine encapsulation, M Jrade et al. Optimisation of desferrioxamine loading in red blood cells, C Hurel et al. Transfusion of thalassemic patients with desferrioxamine loaded standard red blood cell units, G Fiorelli et al. Approach to the optimisation of inositol hexaphosphate entrapment into human red blood cells, M C Villereal et al. The nature and kinetics of red cell membrane changes during the osmotic pulse method of incorporating xenobiotics into viable red blood cells, R Franco et al. Isolated heart as a model to study the effects of the decrease in oxygen hemoglobin affinity, J F Baron et al. P50 shifts and tissue oxygen pressure, R Woodson et al. Arginase-loaded erythrocyte carriers: their fusion to host cells with viral fusogenic proteins and subcellular localization of arginase, C A Kruse et al. Encapsulation of rhodanese by mouse carrier erythrocytes, J Way et al. Antileishmanial activity of red-cell encapsulated drugs, J D Berman. IHP dramatically reduces Babesia microti and Plasmodium falciparum Parasitemias: observations of fluorescent red cells and fluorescent vacuoles, G M Ihler & P-F Tosi. The use of animal models in the encapsulation of drugs in erythrocytes, D A Lewis & J Desai. Towards cellular drug targeting and controlled release of drugs by magnetic fields, U Sprandel.